Scholar Rock Holding Corp. Stock

Good morning, ladies and gentlemen, and welcome to Scholar Rock's Third Quarter 2026 Conference Call. [Operator Instructions] This call is being recorded on Tuesday, November 10, 2026.

I would now like to turn the conference over to Scholar Rock. Please go ahead.

Good morning. I'm Laura Ekas, Vice President, Investor Relations at Scholar Rock. With me today are David Hallal, Chairman and Chief Executive Officer; Keith Woods, Chief Operating Officer; Akshay Vaishnaw, President of R&D; and Vikas Sinha, Chief Financial Officer.

During today's call, David will provide introductory remarks and a business overview. Keith will discuss the U.S. launch of ISEMBYLD and global commercial readiness. Akshay will review our regulatory and R&D progress, and Vikas will provide a financial update. We will then open the call for questions.

Before we begin, I'd like to remind you that during this call, we will be making various statements about Scholar Rock's expectations, plans and prospects that constitute forward-looking statements for the purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995. Any forward-looking statements represent our views only as of today and should not be relied upon as representing our views as of any future date. I encourage you to go to the Investors and Media section of our website for our most up-to-date SEC statements and filings.

With that, I'd like to turn the call over to David. David?

Thank you, Laura, and good morning. Thanks to everyone for joining our third quarter earnings call. Today, Scholar Rock is operating from a position of great strength, and we are executing with focus, discipline and urgency.

In mid-September, we received FDA approval well ahead of our PDUFA date for ISEMBYLD, the world's first and only muscle-targeted therapy for children and adults living with SMA. And following approval, we immediately commenced our U.S. launch.

In early October, we resubmitted our apitegromab MAA in Europe for the treatment of children and adults with SMA. The application, which now includes our alternate fill/finish facility has been validated, and we expect a CHMP opinion in the first half of 2027.

In early November, we submitted our apitegromab JNDA in Japan, 2 months ahead of our guidance. The application was accepted under priority review and pending approval, we anticipate a launch in Japan near year-end 2027.

In Q3, we also commenced dosing in our Phase II FORGE study, evaluating apitegromab in people living with FSHD.

And finally, this morning, we announced we have entered into a definitive agreement to monetize our priority review voucher for $205 million, which will further strengthen our financial position to fund our ambitious global commercial and R&D growth initiatives.

With this, let me turn to our U.S. approval and launch of ISEMBYLD. ISEMBYLD is a highly innovative myostatin inhibitor and the world's first and only muscle-targeted therapy approved for patients with SMA. Over the past decade, while SMN-targeted therapies have brought needed innovation to the SMA community by improving motor neuron health, significant unmet need remains.

Muscle is the principal organ clinically affected by SMA and has been unaddressed. To underscore this point, gaining muscle strength was the #1 need amongst SMA patients in a 2026 Cure SMA survey. In addition, more than 3/4 of neurologists recognize that the future of treatment for patients with SMA is an approach that targets both the motor neuron and the muscle.

Now with ISEMBYLD, Scholar Rock is ushering in the next phase of needed innovation for the SMA community. Importantly, the FDA-approved label provides a substantial opportunity to serve patients. ISEMBYLD is indicated for all patients with SMA, 2 years of age and older, who are receiving an SMN2-targeted treatment. Our U.S. label is underpinned by the compelling clinical benefits ISEMBYLD can bring to children and adults with SMA.

For patients receiving an SMN2-targeted treatment in our global randomized double-blind, placebo-controlled Phase III SAPPHIRE study, ISEMBYLD changed the progression of SMA from a loss of motor function to a gain of motor function. At the recommended dose, ISEMBYLD delivered a robust, clinically meaningful 2.2-point improvement in motor function compared with patients receiving an SMN2-targeted therapy alone as measured by the gold standard Hammersmith Functional Motor Scale.

With this strong foundation in place, our experienced Scholar Rock commercial team is now doing what we know well and what we do well: launching a highly innovative first-in-class rare disease therapy with the potential to dramatically improve the lives of patients.

Immediately following the approval of ISEMBYLD, our team swiftly and successfully executed initial launch activities, and we are very pleased with our progress in these earliest weeks. Our launch metrics reinforce our expectations and confidence in our opportunity to serve the estimated 6,600 patients with SMA in the U.S. who are currently receiving an SMN2-targeted therapy.

Shortly, Keith will discuss 4 strategic imperatives with regards to our early U.S. launch dynamics: awareness, education, demand and access. I'd like to take a few moments now to touch upon demand and access.

In terms of demand for ISEMBYLD through the end of October, we are seeing a strong number of patients enrolling in Scholar Rock Supports in these early weeks since approval. We are very encouraged by the broad-based demand as reflected by both the consistent volume of patients enrolling into the program and by the wide range of prescribers and patients.

In the first 6 weeks of launch, enrollments are balanced across all geographies nationwide. More than 1/3 of the top 140 SMA treatment centers have enrolled initial patients and a significant number of enrollments are coming from centers outside of the top 140. The mix of patients enrolling in Scholar Rock Supports is just as diverse. Importantly, ISEMBYLD treatment-naive patients outnumber those who are starting to transition from our clinical trials and EAP program. Children are the largest enrolled group of patients, but a substantial number of adults have also enrolled.

Patients reflect the full range of disease trajectories, including improving, plateaued and declining motor function, and consistent with SMN 2 prescribing patterns, patients are balanced across Evrysdi, Spinraza and high-dose Spinraza background therapy, including some who had previously received Zolgensma.

Thus far, the pace of demand as measured by patients enrolling in Scholar Rock Supports has been very steady and consistent on a weekly basis, and we expect this trend to continue as we aim to serve an increasing number of new patients over time. As we expected, strong demand is outpacing reimbursement and access at this stage.

While I am very encouraged by early patient-by-patient approvals across insurance types and sites of care, initial delays and denials are common for any first-in-class rare disease launch. Given the timing of when patient enrollments have been received, combined with the anticipated 60 to 90 days or longer from prescription to infusion in this very early stage of launch, we anticipate the majority of the patients who enrolled through October will begin infusions in 2027.

We expect steady progress on payer approvals over time and remain confident that it is a matter of when and not if eligible SMA patients will receive ISEMBYLD therapy. We are building an access engine that will ultimately support broad and reliable access to ISEMBYLD. Our initial performance across these early indicators reinforce our expectations and confidence in our opportunity to serve a steady and consistent number of new patients for quarters and years to come. Keith will share much more detail on our early U.S. launch progress in just a few moments.

Turning now to our global regulatory and pipeline priorities. We are very pleased with the meaningful progress we've made in recent weeks towards serving children and adults living with SMA in both Europe and Japan. Akshay will discuss these important regulatory advancements and progress across our world-leading anti-myostatin pipeline later in the call.

And finally, turning to the financials. We reported $0.6 million in ISEMBYLD revenue in the third quarter, reflecting initial inventory shipped to our specialty network. We ended the quarter with $413.6 million in cash, cash equivalents and marketable securities. Now with the sale of our priority review voucher, that will bring in an additional $205 million. Scholar Rock has the financial strength and flexibility to support our key priorities without the need for an equity offering at this time.

In closing, we have never been better positioned to deliver on the opportunity ahead as we work with urgency to improve the lives of patients living with SMA and other rare and severe neuromuscular diseases.

With that, I'll turn the call over to Keith to discuss the U.S. launch of ISEMBYLD and our apitegromab commercial readiness globally. Keith?

Thanks, David, and good morning, everyone. ISEMBYLD is positioned to define a new standard of care for the estimated 6,600 patients living with SMA in the U.S. who are receiving an SMN2-targeted therapy. As I've shared previously, the vast majority of patients continue to experience persistent and progressive muscle atrophy that limits both function and independence despite receiving an SMN-targeted treatment. Now with the FDA approval of ISEMBYLD, we are ushering in the next phase of needed innovation with this first-ever muscle-targeted therapy.

In the 13 business days between the approval of ISEMBYLD on Friday, September 11 and the end of the third quarter, we executed flawlessly on our key priorities. Immediately following approval, Scholar Rock Supports began working with physicians and families to conduct insurance verifications for initial patients.

Within 1 week of approval, ISEMBYLD vials were labeled, packaged and shipped to our specialty network. And we filed the J-code application, which will give us an ISEMBYLD-specific J-code on April 1, which is the shortest time line possible. We are very pleased with the progress in these earliest weeks. Our launch metrics reinforce our expectations and confidence in our opportunity to serve the broad SMA community.

Let me now provide some important additional detail on our launch as it relates to awareness, education, demand and access. Patient and caregiver awareness and engagement is meeting our high expectations. For example, in the days immediately following approval, we had nearly 1,000 patients and caregivers register for ISEMBYLD educational webinars hosted by Cure SMA and MDA. And through our efforts with our Life Takes Muscle campaign, we had more than 10,000 opt-ins from patients, caregivers and HCPs to receive notification of the ISEMBYLD approval.

In terms of prescriber education, following the ISEMBYLD approval, our highly experienced U.S. team began engaging with the SMA treatment centers, their physicians and care teams on the compelling clinical benefits of ISEMBYLD. Reach to the SMA treatment centers is already deep and wide. Through the end of October, so in just the first 6 weeks of our launch, our team has engaged with 95% of the top 140 SMA treatment centers. This is a tremendous achievement, given that, in my experience, it would typically take at least 4 months to reach this proportion of your target audience.

In terms of demand, as David said, we are seeing consistent volume and breadth of prescribers and patients. Specifically, in just the first 6 weeks of launch, enrollments are balanced across all geographies nationwide. More than 1/3 of the top 140 SMA treatment centers have enrolled patients and a significant number of enrollments are coming from centers outside of the top 140. The mix of patients enrolling is just as diverse. Importantly, ISEMBYLD treatment-naive patients outnumbered those who are starting to transition from our clinical trials and our EAP program. Children make up the largest enrolled group of patients, but a substantial proportion of adults have enrolled as well.

Patients reflect the full range of disease trajectory, including improving, plateaued and declining motor function. Additionally, consistent with SMN2 prescribing patterns, patients are balanced across Evrysdi, Spinraza and high-dose Spinraza background therapy, including some who have previously received Zolgensma. Collectively, these early patterns, including the steady and consistent pace of demand, reinforce the breadth of the ISEMBYLD opportunity and our confidence in the potential for sustained long-term growth.

Turning now to access. As we expected, strong demand is outpacing reimbursement and access at this stage. Specifically, in these early days of launch, the time from prescription to infusion can be more than 60 to 90 days on average due to a number of factors, including the need to use an unspecified J-code for ISEMBYLD until April 1; payer policies that have not yet been established; the time required for prior authorizations and appealing denials; and finally, the requirement for hospital formulary approvals, which takes time.

Since approval, our team has been engaging with payers to discuss the value proposition of ISEMBYLD. Through the end of October, we have reached payers responsible for more than 90% of covered lives in the United States. We are encouraged by the productive payer discussions to date, and we are very pleased by the early published policies that align with the ISEMBYLD label, including 2 of the top payers in the United States, Anthem and Centene, that together represent 47 million covered lives.

Importantly, we are seeing ISEMBYLD payer approvals on a patient-by-patient basis from commercial and government plans that have yet to issue policies. These approvals so far are independent of patient age, time on SMN-targeted therapy, geographic location and infusion site of care, whether hospital, independent infusion center or at the patient's home.

We are also grateful that Cure SMA sent a community-wide ISEMBYLD access letter to U.S. payers, Medicaid officials in all 50 states and all state governors, urging timely broad access to the first and only muscle-targeted therapy for children and adults with SMA.

As we continue to work through reimbursement and access, we are pleased that as of the end of October, 98% of patients with ISEMBYLD prescriptions are coming through Scholar Rock Supports, our world-class patient support program. This enables us to assist the patient in navigating a clear path from prescription to payer approval and initial infusion and to provide ongoing treatment support.

Given the timing of when patient enrollments have been received, combined with the anticipated 60 to 90 days or longer from prescription to infusion, in this very early stage of launch, we anticipate the majority of patients who are enrolled through October will begin infusions in 2027.

We expect steady progress on payer approvals and remain confident that while initial delays and denials are common for any first-in-class rare disease launch, it is a matter of when and not if eligible SMA patients will receive ISEMBYLD therapy.

Our initial performance across these early indicators reinforce our expectations and confidence in our opportunity to serve a steady and consistent number of new patients for quarters and years to come.

I would now like to turn to our launch readiness in Europe and Japan. Starting with Europe, we continue to advance our launch preparations with an initial focus on Germany. We are executing our U.S. playbook, deepening relationships with key treatment centers, prescribers and advocates, and we're preparing to rapidly advance reimbursement submissions upon approval. We look forward to a CHMP opinion in the first half of 2027 and a launch in Germany later in 2027, followed by other key countries over time.

In Japan, in line with our JNDA submission to PMDA, we are now building out our Scholar Rock team, establishing in-country operations and advancing our commercial readiness activities as we prepare for a potential launch near the end of 2027.

In closing, we are now beginning to deliver ISEMBYLD to SMA patients across the United States. and we look forward to expanding our 50-country operating platform so that we can serve the estimated 35,000 people living with SMA globally who are currently receiving an SMN-targeted therapy. We are working with urgency, one patient, one caregiver and one family at a time to deliver on our ambition that every patient who can benefit from ISEMBYLD should have access to ISEMBYLD.

And with that, I'll turn the call over to Akshay for a closer look at our R&D initiatives. Akshay?

Thank you, Keith, and good morning, everybody. With ISEMBYLD now approved in the U.S., our R&D team is focused on 3 priorities. First, securing regulatory approvals to enable apitegromab treatment to be available for children and adults with SMA in up to 50 countries globally. Second, executing a life cycle program for apitegromab, which includes clinical development of the subcutaneous formulation, access for the youngest of SMA patients and developing it in new neuromuscular indications. And finally, our third priority is progressing SRK-439, the next program from our world-leading anti-myostatin platform.

Let me turn first to global regulatory progress. In Europe, in alignment with the EMA, we're very pleased to have resubmitted the apitegromab MAA in early October, just weeks following the withdrawal of our original application. Importantly, the expeditious resubmission of the MAA includes the alternate fill/finish facility that supported the approval of ISEMBYLD in the U.S. in place of Catalent Indiana. The MAA has now been validated and the review is ongoing. We continue to engage with the EMA and anticipate a CHMP opinion in the first half of 2027 with an initial launch in Germany following European approval.

We're also pleased to announce today that we submitted the apitegromab JNDA for the treatment of children and adults with SMA in Japan. Based on constructive discussions with the PMDA, they agreed that the existing apitegromab data package, including the Phase III SAPPHIRE study are sufficient to support our filing in Japan. We received orphan drug designation for apitegromab in SMA. And notably, our application was accepted under priority review for which the PMDA has typically targeted an approximately 9-month review cycle. With the 60- to 90-day process to secure pricing and reimbursement following approval, we anticipate a potential launch in Japan near year-end 2027.

Turning now to our pipeline. We're pleased to now be serving initial patients with ISEMBYLD in the U.S. However, our commitment to continued innovation for the SMA community has never been stronger. To this end, we're advancing our high-concentration subcutaneous apitegromab program. This program is designed to provide optionality for the SMA community as a small volume self- or caregiver-administered anti-myostatin antibody. Following the September FDA approval of ISEMBYLD, we're now initiating engagements with regulators, and we plan to provide an update on the development path forward following alignment with FDA and EMA.

In terms of reaching the youngest of SMA patients, we continue to have robust enrollment in our Phase II OPAL study. This study is evaluating apitegromab in infants and toddlers with SMA under the age of 2 who have been treated with an SMN1-targeted gene therapy or who are receiving ongoing treatment with an SMN2-targeted therapy. This study is important because it is anticipated to expand the impact of apitegromab to the full spectrum of patients. Notably, the rate at which this study is enrolling underscores the significant unmet need and the potential for apitegromab in the youngest of SMA patients.

Turning now to our next indication for apitegromab, facioscapulohumeral muscular dystrophy, or FSHD. FSHD is one of the most prevalent inherited muscular dystrophies with approximately 20% of patients becoming wheelchair-dependent. There are no approved therapies for FSHD. In September, we were delighted to announce that apitegromab was granted fast track and orphan drug designations in FSHD by the FDA. In September, we also announced the commencement of participant dosing in our Phase II FORGE study, a randomized double-blind, placebo-controlled trial, which is expected to enroll 60 patients. Enrollment is progressing well and dosing is ongoing.

Lastly, we continue to progress the next generation of our anti-myostatin platform with SRK-439, our high potency, high-affinity subcutaneously administered myostatin inhibitor. We're excited about this program and dosing in our Phase I healthy volunteer study is progressing very well. We expect to have top line data by year-end and intend to share those with you in early 2027.

In closing, we've accomplished what the industry pursued for nearly 30 years, bringing the first approved myostatin inhibitor to patients. Now we're working with urgency as we leverage our world-leading platform. Our ambition is to extend apitegromab access to all patients with SMA across our planned 50-country operating platform whilst also extending this breakthrough to patients with additional rare and devastating neuromuscular diseases.

With that, I'll now turn the call over to Vikas to provide an update on our financials. Vikas?

Thank you, Akshay. We are very pleased with the U.S. launch of ISEMBYLD following its FDA approval in September. We remain in a very strong financial position as we continue to invest with discipline.

For the third quarter, total revenue was $0.6 million, reflecting initial ISEMBYLD inventory shipments to our specialty network. As we shared previously, we expect to keep inventory at our specialty network to a minimum.

Looking forward, as Keith mentioned, in these early days of launch, the time from prescription to infusion can be more than 60 to 90 days on average, leading to steady and consistent growth in revenues over time.

As it relates to cost of goods for the third quarter, the cost of inventory manufactured was expensed prior to FDA approval. Total operating expenses for the third quarter were $106.6 million, which included $17.9 million in noncash stock-based compensation. Excluding stock-based compensation, operating expenses were $88.7 million. We are pleased that with continued investments associated with our anticipated global launches, we remained disciplined in managing our overall spend.

Turning to our balance sheet. We ended the third quarter with cash, cash equivalents and marketable securities of $413.6 million. In November, we entered into a definitive agreement to sell our priority review voucher for $205 million, which will add significant nondilutive capital to our balance sheet. The cash is expected to be received upon the closing of the transaction.

With the approval of ISEMBYLD, we also now have access to an additional $150 million under our existing debt facility. The strength of our balance sheet reflects the disciplined execution of our plan and provides the financial flexibility to fund our strategic priorities without the need to access the capital markets at this time.

We continue to operate with financial discipline and our prioritized investments remain focused on 4 areas; first, supporting the successful launch of ISEMBYLD in the U.S.; second, advancing launch readiness in Europe and Japan as we build the foundation for our planned global 50-country operating platform; third, strengthening our supply chain to support our expanding pipeline and our anticipated growing global commercial demand for ISEMBYLD over time; and fourth, advancing our highly innovative clinical programs.

With that, I'll turn the call back to David. David?

Thanks, Vikas. Scholar Rock is operating from a position of strength, executing with focus, discipline and urgency as we transition to a commercial-stage company and continue building our foundation to become a global biotech powerhouse.

Our U.S. launch of ISEMBYLD is off to a very encouraging start. And as we look at the growing global SMA market, we are working to deliver on our ambition that every patient who can benefit from ISEMBYLD should have access to ISEMBYLD.

I continue to be very grateful to our patients and families, the investigators and treating physicians who have partnered with us, Cure SMA and the advocacy community and my colleagues at Scholar Rock for what we've accomplished to date. Together, we brought the first muscle-targeted therapy to the SMA community. And now in the earliest stages of the global launch beginning in the U.S., we are just getting started.

With that, we'll now open the line for questions. Operator?

[Operator Instructions] And our first question will come from the line of Eric Schmidt of Cantor.

It sounds like the patient demand is very substantial, but you're obviously working through some of the payer hurdles that you expected to encounter. Just maybe quickly on the demand side, has the bone fracture warning been any issue at all for you? And then on the payer side, you mentioned the wins at Anthem and Centene, congrats on those. Anything specific about the coverage that you could provide on those wins?

Thanks, Eric. I'll start. Regarding fractures, no. There's been no impact on demand or prescribing patterns. And we see this really as in line with some of the work that you and others in the community have done in holding some sessions with KOLs or treating physicians. So it has had no impact.

As it relates to the payers, Keith and I are certainly gratified that Anthem, Centene -- I mean, this is tremendous progress to have published policies in line with our label this early in launch. It's an extraordinary accomplishment. For more color on that across the wider range of payers, I'll turn it over to Keith.

Yes. Thanks for the question, Eric. And I just gave 2 examples of published policies. There's actually more that are out there that are aligned with our label already. I called these out because, I mean, Anthem is the #2 payer in the entire U.S., and Centene is also one of the largest payers in the U.S. But as I stated in the prepared remarks, our team has been already able to meet with the payers that cover 90% of covered lives. So trust me, we are out there and are very encouraged by the discussions that we're having. I can tell you that we anticipate additional policies to be aligned with our broad label to be published over the next 6 months.

But you asked, can we give you some color around those policies? They're truly aligned with the label. There's not an age restriction to them. There's not a type restriction to them. There's nothing about ambulatory status in there. It really allows for a policy that can allow access to a broad range of SMA patients.

And I would just close by saying all of that is underpinned by the strength of the data that the Phase III SAPPHIRE data study had reflected, which is a great basis for these relationships and collaborations with payers.

And our next question comes from the line of Kripa Devarakonda of Truist Securities.

This is Alex on for Kripa. Congrats on all the progress. This is great. We're all excited about the launch. For us, the 60 to 90 days from script to infusion, do you expect that, that will continue up until you get the J-code in April? Or could that be trimmed down as more payers establish policies?

Yes. I mean, first of all, I think I'd just like to make a comment before handing it over to Keith. I think the one thing -- we are super excited with the sort of early observations related to the launch. I think the one thing we're heartened by is not only our team's experience in reimbursement and access, but as you might imagine, the 6,600 patients in the U.S. currently on an SMN2-targeted therapy, they and their physicians have already been down this road before.

That's why they're on an SMN2-targeted therapy. They understand that, certainly, initially at approval, these are very sort of common steps to take. But why Keith and I wanted to reiterate on today's call, it is a matter of when and not if these patients on label are able to access ISEMBYLD therapy, the first and only muscle-targeted therapy that's been approved by the FDA.

As it relates to sort of the movement from 60 to 90 or longer to a more shorter steady state, I'll hand it over to Keith for his comments. Keith?

Yes, Alex, thanks for the question. I guess, first of all, we're really pleased with the effort of the team to get the application in for the J-code for ISEMBYLD so that we have really the shortest possible wait time until we have the official J-code on April 1, 2027. You asked, is it going to take until then before some of these time lines start to condense? The answer is there are several factors that lead into that, sometimes greater than 60 or 90 days. The J-code is just one of the contributing factors.

As we get more payer policies established, that will help us to decrease the level of denials that we have. It's not going to take away the prior auths. So there's still going to be that step. It is a timely process, okay? And they will have to go through prior auths just like they do with SMN-targeted therapies. But also, I would call out to you that formulary status in a lot of these 140 treatment centers, it doesn't happen overnight.

I'll give you an example. We have some hospitals in the top 140 that have already had P&T committee meetings and included ISEMBYLD onto their formulary, and they are now waiting to have it officially entered into their treatment ordering system so that the product can be ordered. We have other hospitals that they couldn't -- they didn't put ISEMBYLD on their P&T committee until after the first of the year.

So there are several elements that lead to this. But to give you the long answer, the long answer, a little shorter is yes. This time will condense over a period of time, and we will get this down to a more manageable. But the 60 to 90 days, not only is this not outside of industry norm, it's accustomed to what I've seen in previous launches.

And our next question will come from the line of Cory Kasimov of Evercore.

This is [ Adi ] on for Cory. Could you maybe share what share of your enrolling patients are coming from outside of the EAP and ONYX extension population? And how should we think of these different populations going on the commercial drug?

Yes. I mean I'll just quickly comment on that. I think Keith and I addressed it. We do have more treatment-naive patients to ISEMBYLD enrolling in Scholar Rock Supports than the patients that are beginning to transition from both our EAP and ONYX in aggregate. And we think that, that's reflective of the very broad interest from both prescribers who are going to be new to ISEMBYLD and also patients that are going to be new to ISEMBYLD.

And then with those enrollment forms coming in, the patients are of a diverse background by age, by SMN2-targeted therapy, by disease trajectory. And we're just gratified that -- our ambition is to make sure, across the U.S., the 6,600 patients with SMA that are currently on an SMN2-targeted therapy, that we reach a very high proportion of those patients over time. And I think our early observations have certainly suggested that we are on that track.

Yes. I mean what I would add is I am very encouraged by the fact that the treatment-naive patients outnumber those of EAP. I can tell you that, as a commercial leader, I'd be disappointed if I was sitting here reporting to you that the main patients that we're getting in or that we're transitioning are clinical trial patients and EAP patients. So I'm pleased with that result.

With that being said, we are in the process of transitioning over the EAP patients. But just as they enroll, they go through the same process as every other patient that we've just walked through. You still have those hurdles to overcome with J-codes and they're part of insurance companies that have not yet established policies. They could be being treated somewhere with the hospital where the hospital formulary comes into play. So they are going to still experience that same type of delay.

For our ONYX patients, they're completing closeout visits with their physicians to conclude that study and then they'll begin enrolling into our program. So I would expect you're going to see enrollments from EAP and ONYX patients over the next couple of quarters to come.

But what I do want to call out is I want you to look at the retention rate that we have had with approximately 98% of our TOPAZ and SAPPHIRE patients rolling over into that open-label study, some of them for up to 7 years. And now here we are, 7 years later, and 93% of them remain on therapy. So I feel quite confident that we'll have strong rollover and retention over the next couple of quarters.

Our next question will be coming from the line of Tess Romero of JPMorgan.

We appreciate the early color here. As you move ahead with the ISEMBYLD launch, what is your latest thinking on the specific metrics that you will be providing consistently here to us beyond revenues? And relatedly, can you share a view of what you might be able to provide on this topic at our [ small ] conference in January?

Thanks, Tess. I think as Keith and I outlined today, we think it is important to kind of share the progress that we are making across the top 140 SMA treatment centers in the country. As we noted today, we're gratified in just the first 6 weeks of launch that more than 1/3 of those are already enrolling initial patients. And I think it's important to note, they're just initial patients as they get started themselves with the process. So we think there's tremendous amounts of growth, both in getting deeper in those first more than 1/3 of 140 top -- more than 1/3 of the 140 top SMA centers. There's more patients to serve there over time. And then, of course, we have a wide range of the other centers that we believe it's just a matter of time.

So I think that, that penetration into those centers is very, very important. And then as Keith noted today, very important to highlight the covered lives from the payer perspective, and we were certainly gratified to see what we saw from both Centene and Anthem. And of course, we'll have much more color on revenues. As we noted, patient infusions only began in October following the near mid-September launch, and that will be an important metric, I think, for many to focus on as we believe we serve a steady and increasing number of patients for quarters and years to come.

And our next question will be coming from the line of Tazeen Ahmad of Bank of America.

A couple of questions. So based on the type of patients that you've been starting to enroll, I know it's early in the launch, as we try to think about what the average cost per patient is going to be, given the weight-based dosing, you're getting mostly children you said, but you also have adults coming online, can you give us some color on how to think about that? And then based on your language on your prepared remarks about these patients mostly being able to get on drug from October through the rest of the year in 2027, is it logical to think that you might have more of a bolus of sales in the first 2 quarters of 2027?

Yes. I'll start maybe on the second part of that question, and then I'll hand it over to Keith. We actually think that the reflective demand of a very steady pace of new patient enrollments into the system across a broad range of centers, prescribing physicians and patients, we actually see this as sort of steady as she goes, consistently adding new patients quarter-on-quarter, year-on-year and just a very healthy growth story.

And I would say that those comments, I think what we just wanted to reflect, right, is that Scholar Rock Supports has been very busy. As Keith noted, they started on insurance verification shortly after the approval. But we just wanted to manage that if one does the math with the 60 to 90 days, and we think the enrollments that are in-house at Scholar Rock Supports, those patients are going to receive the ISEMBYLD that they want and they deserve, but that you have these sort of typical speed bumps, no stop signs, but speed bumps along the way that can result in initial infusions for more patients being in 2027 than with 6, 8 weeks to go. I'm not even counting the holidays from November 10 through the end of the year. We just expect more of those patients to get initial infusion in '27 versus '26.

Regarding the dynamics of weights and what we're seeing patients that are both younger in age, but also the adult patient population, I'll let Keith comment on that. Keith?

Yes. I guess just to go back on one thing, Tazeen, the question of bolus, I'd actually be more concerned if there was a bolus and then the level of enrollments let up. But as David stated, it's been consistent and steady on a week-over-week basis. And we track these things not just on a weekly basis, but on a daily basis here. So I actually find it much more encouraging, the fact that we continue this nice pace of enrollments.

As far as the type of patients that we've enrolled, we did share that there's more peds than there are adults. That is also the case in the Cure SMA database, which is the largest database in the U.S. for SMA patients. And that is the database that we use to set the price of what a typical patient would cost when we did the launch call. So we are closely monitoring where our weight distributions come out as these patients enroll. Obviously, that's something that is involved in the enrollment form. But right now, just as you have in the Cure SMA database, much more peds than there are adults in the database. And as we've said, same here.

Our next question will be coming from the line of Michael Yee of UBS.

Congrats on all your progress. Maybe just 2 questions. One on early demand. Maybe, David, you guys have said some very strong demand, but not necessarily quantifying it. Would you say that you have hundreds of patients that have gotten into the access program or hundreds of patients that have filled out start forms? Maybe you could just sort of quantify the early demand for us, that would be super helpful as we build out our early models. And then second question is on subcu. I don't think there was a question asked on that. Do you think you could just do a PK bridging study? Or would you need some sort of -- at least sort of an open-label efficacy study, somewhat similar to how [ LEQEMBI ] had to do that?

Yes. Thanks very much, Michael, and looking forward to being with you shortly at your conference. As it relates to enrollment forms, as we noted, we're not quantifying that, but we did try to provide some perspectives for you all that -- and we thought one important thing was we had more enrollments in Scholar Rock Supports from treatment-naive patients, so those patients that have not yet had the opportunity to benefit from the first and only muscle-targeted therapy approved for patients with SMA, as opposed to those patients that are now beginning to transition from both EAP and clinical trial or ONYX patients. And so that's the extent of sort of providing you guys some perspective, but I think that, that may be very, very helpful for you.

As it relates to the journey for the subcu high-concentration program, I'll hand it over to Akshay.

Yes. Thanks, David. So you're absolutely right, Mike. subcu bridging via PK/PD is a legitimate route to seek approval of a new route like the IV to subcu transition. We obviously are going to make the case robustly with the FDA and other regulators with that as the centerpiece. We have to complete the dialogue before we report back on the final path ahead. But certainly, that should be a key piece of it.

Our next question will be coming from the line of Ritu Baral of TD Cowen.

I wanted to ask just a little bit more about current trends in, I guess, the vanguard of patients interested in ISEMBYLD. How is average weight stacking up against your expectations and also sort of predominant function? You mentioned they were mostly children. But right now, are you seeing patients on the upswing or more stable patients? And then just a quick follow-up on those non-center of excellence sites beyond 140 that are already prescribing. How would you characterize those sites? And would they -- either the patients or the sites need any special support from the hub to onboard those patients?

That's great. Great question, Ritu. I think as Keith was noting, we're pleased that while the larger group of enrollments are coming from pediatric patients, there's a substantial proportion coming from adults. I think it's early to call on sort of weights and dose, but we stand firm with the work that Keith did with Cure SMA, by far the largest database in the U.S., on sort of what the typical patient will ultimately be.

And then we did try to provide a little bit of color on the diversity of patients coming into Scholar Rock Supports by a number of different characteristics, and I'll hand it over to Keith to make those comments.

Yes. I think that we're very pleased by the diversity of patients that are enrolling into the program. And there's -- really can't paint a patient with a single brush because I can tell you that the age range is quite a variety from the peds to -- we've had enrollments from 60-plus year olds out of community neurologists in rural areas. So there's quite a diversity of the types of patients that we're getting, and they're really -- whether they are still improving on their SMN-targeted therapy or whether they plateaued or whether they're declining, we've seen each different type enroll into the program. So really encouraged about that.

As far as additional work from the hub, one patient is just an individualized patient because they can even be at the same treatment center, but they have different insurance which make them eligible for a different location on where they can be infused. They might live very close to the key center, but they also might live 2 hours away. So they want to look for an alternative infusion center. So this is truly a patient-by-patient basis. That's why we offer Scholar Rock Supports because we offer that white glove service, not just to help you get enrolled, but to help you all the way through the treatment journey.

And our next question will come from the line of Allison Bratzel of Piper Sandler.

Just thinking about ex U.S. launches coming up in 2027, could you just talk to launch preparations and expected trends there? And just how you would expect the geographic patient mix to evolve just given there are more patients on SMN-targeted therapies ex U.S.?

Keith, do you want to talk about launch prep in Europe and Japan? And actually, maybe I'll just start on the mix. Like, as I think you all know, when you look at by almost any metric, patients on SMN-targeted therapies and/or reported revenues from the 3 companies that are commercializing those therapies, there's probably a bit more than 1/3 of revenues in the U.S. and nearly 2/3 of revenues outside of the U.S.

Given some of the pricing dynamics and the difference in pricing, there tends to be even a higher proportion than the nearly 2/3 of revenues outside of the U.S. of those patients on treatment. And that's why this journey that we are taking to reach patients in upwards to 50 countries around the world is so important. We take our mission very seriously. This is the first and only muscle-targeted therapy for patients with SMA, and we want to reach those patients no matter where they are.

As it relates to the launch preparations in Europe and Japan, I'll hand it over to Keith for his thoughts.

Yes. Allison, thanks for the question, Ally. And I guess, first of all, as we've stated, after the EMA approval, after our rapid resubmission, the first country that we can proactively launch in is Germany. I can tell you that, that team is already built out. We have several members of the team that are actually over here with us in Cambridge this week, along with -- we have a visiting KOL from Germany here this week.

So we are already working on disease education awareness. We are establishing relationships with those key centers. And in Germany, we are permitted to and do have an early access program over there that is currently enrolling patients. So we're really operating on the U.S. playbook when it comes to Germany. We've already been building out reimbursement dossiers for other countries in Europe that we will begin to pursue immediately after approval because we cannot actively promote in those countries until we successfully get reimbursement.

With that being said, it also means we're being responsible in how we source these countries, and that would revolve around -- mostly around medical affairs in the countries as opposed to any type of promotional effort until we can be very confident and very close to securing reimbursement.

Additionally, before I go to Japan, I'd just like you to know that there are other countries over in Eastern Europe outside of the United States that we are able to work with based on a U.S. approval and a U.S. label and a U.S. pack. And we have a team that is working on the international partner markets. So we are turning over every stone so that we can get to the 35,000 people that are living with SMA and on an SMN-targeted therapy.

And lastly, Japan, the team is in the process of being built out. We've got about 5 employees there right now. Our general manager is hired and the great work from Akshay's team with regulatory has us on pace to where we'll be launching in 2027. And as you know, Japan is really a key market for SMA. I say that because, number one, after you get your approval from PMDA, you set price within 60 to 90 days and then everybody is insured. We won't have to go through these policies. Everybody is insured. It's also because this is a rare disease and it falls into the intrinsic category, it's a very low out-of-pocket expense. And so we look forward to continuing our work with the key opinion leaders in Japan and preparing for a launch in late 2027.

And then I'll just comment. So the way I look at it, U.S. will obviously be a major cylinder firing for a long time. With the mid-September approval, 330 million population country, reimbursement is essentially open season. In Europe, the first market, let's just say, second half of the year becomes Germany, 80 million population country. And then toward the very end of '27, if all goes well with the review under priority review in Japan, we pull in another 120 million population country. So very, very important to have this sequence laid out for us for both the U.S. and ex U.S. growth that we expect to be delivering for many quarters and years to come.

And our next question will be coming from the line of Gary Nachman of Canaccord Genuity.

Congrats on all the progress. So anything different you're seeing in the SMN portion of the market with increasing use of high-dose Spinraza or potential safety concerns with Zolgensma that might impact you in any way down the road on how ISEMBYLD is used, whether good or bad? And there was such a buildup for ISEMBYLD's approval, is there still a lot more to be done in education and awareness of the importance of muscle function for these patients in the U.S.? Or is it really more just blocking and tackling on the initiation and access that you've been talking about? So I'm curious how you would characterize just the level of awareness at this point for the importance of using something like ISEMBYLD?

Yes, Gary, I'll just comment, 93% of patients in that 2026 Cure SMA survey said muscle strength is a need. It was by far the #1 need across the population of SMA patients, combined with 3/4 of neurologists saying the ideal way to treat SMA now is by focusing on both the motor neuron and the muscle. And Keith, I think, provided a lot of awareness metrics that suggest there's a tailwind there for us and then it becomes blocking and tackling, which we think is largely all manageable, both with our experience and the experience of the SMA community. So we're pretty excited about that.

And then just quickly on the dynamics, as Keith and I said that the balance across SMN2-targeted therapies is quite nice with consistent -- with the prescribing patterns. We see HD Spinraza as a net-net positive for us because anything that can bring needed innovation to motor neuron health is just helpful for us in terms of being able to address the principal organ clinically affected in the disease, which is the muscle.

And then finally, I think it's early to tell on Zolgensma. We tend to be extremely neutral with whatever physician and patients' preference is on motor neuron health. And then, of course, ISEMBYLD represents the first and only option for addressing the muscle component of the disease. So we'll keep you apprised, but we're very gratified by these early observations.

And our next question will come from Phoebe Tan of Jefferies.

I just had a couple on the patient population. So are your patients currently leaning towards sort of a more similar enrollment to what we saw in Phase III for non-ambulatory SMA patients in 12 to -- or 2 to 12-year olds? And additionally, how many additional patients do you expect to unlock with the subcu formulation and the Phase II OPAL study for the 2-year-olds and younger?

Thanks, Phoebe. We'll be seeing you soon. I'll just quickly say, we see the enrollments in Scholar Rock Supports representing label more than the Phase III trial, and we're gratified by that. It's really -- the volume and the breadth has been very encouraging. Keith can comment on what the subcu might offer somewhere down the line, but we sure are, again, encouraged by what the ISEMBYLD that is approved, the IV version every 28 days, is going to be able to offer to the community. Keith?

Yes. I guess I'd first say that, as we've said, the breadth of the patient type that we are enrolling is so much broader than what we really see in the Phase III. So there, I already referenced a patient that was greater than 60 at a community neurologist. That's not the only person of age that's been enrolled in the program. So no, we're not seeing just the 2 to 12, and I wouldn't even say that 2 to 12 is dominating the enrollment.

As far as ambulatory to non-ambulatory in the study, we studied non-ambulatory. That's not in our label, and we are seeing these enrollments that are much more consistent to what we see in label.

Now to subcu. I think that the need -- the unmet medical need in SMA that exists today and the fact that we are the first and only muscle-targeted therapy, for the majority of people that are suffering with SMA, they are going to want to utilize ISEMBYLD IV Q4 weeks because of the difference that it can make and the fact that right now, they have limited function, which can also limit their independence.

When we have a subcu program available, do I think that could -- do I think we'd have switchovers? Yes. And is it possible that we would actually see additional patients? My answer is yes. And I say that because you can see where Evrysdi has expanded the market because they're an oral therapy. And although they did not hit stat sig on the Hammersmith scale, they're still the largest selling SMN-targeted therapy that exists, and that's partially because of convenience. And the subcu that we're able to deliver that could be potentially administered at home by a health care -- by a caregiver, that could open up a convenience that we think could even grow the adult population for ISEMBYLD.

Overall, just a complete plan around life cycle management that we think gives us plenty of legs of growth for many years to come. Maybe one more final question?

Sure. Our next question will come from the line of Basma Radwan of Leerink Partners.

Congrats on the progress. I know it's early, but any commentary you could provide to us about the prior auth approval rates? And in case of denial, what is the key contributor to the denial? Is it the patient criteria not being similar to the clinical trial population or something else? And how long does it take for the appeal process really to complete?

It's a great question, Basma. There's a lot of kinetics between enrollment form to ultimate infusion. I think you're highlighting that. Keith and I see right now, probably the #1 reason why there might be a denial is because ISEMBYLD is not in the system, and there's not a medical policy, and they need to like kind of figure out patient by patient how to deal with that. I think that's actually kind of gratifying to us and why we see this as a matter of when and not if those patients on label in the program are going to receive coverage and reimbursement for ISEMBYLD. Keith?

Yes. I would just call out on the prior auth. Remember, this is not exclusive to ISEMBYLD because we're new. Your SMN-targeted therapies, if you look at the Cure SMA data, 98% of the time, there is a prior auth that is required for them to go on therapies that have been out and available for as much as 10 year -- for as many as 10 years now. So it's not something that I think that's going to go away. I think it's something that you're going to see improvement over time as there's a better understanding of what is being required from each of the various insurance companies from a prior auth and the ease and the ability to fill this out.

Remember, though, this SMA community has not only been familiar with prior auths, and I'm talking about the health care professionals, but also the patients and the caregivers, right? They're familiar with having to deal with prior auths. They're familiar with having to deal with denials. And they also are familiar, still to this day, no matter how long they've been on an SMN-targeted therapy, about being reauthorized every 6 to 12 months. So this is a community that is very persistent from both the health care side and the patient side.

And I guess what I would end with is we're facing the dynamics that are quite typical in a launch, and we will work through this, and we've got a great resource to do so in the SMA community, but also in my Scholar Rock teammates because this team has been built on people that work and have worked in rare disease for many years, and you know that you have to fight for each and every patient to get through the system and ultimately be able to benefit from product.

And then maybe in closing, there just hasn't been anything on the access side that has been unanticipated on our side. It's sort of steady as she goes. And again, we're very encouraged by these early metrics and early observations here in the launch. So we'll keep everybody apprised.

Thank you all for your questions. We'll hand it back to the operator.

And this concludes today's program. Thank you for participating. You may now disconnect.

Good morning, ladies and gentlemen, and welcome to Scholar Rock's call to discuss the U.S. approval of ISEMBYLD. [Operator Instructions] This call is being recorded today on Monday, September 14, 2026. I would now like to turn the conference over to Scholar Rock team. Please go ahead.

Good morning. I'm Laurie Ekas, Vice President, Investor Relations at Scholar Rock. With me today are David Hallal, Chairman and Chief Executive Officer; Akshay Vaishnaw, President of R&D; Keith Woods, Chief Operating Officer; and Vikas Sinha, Chief Financial Officer.

Before we begin, I'd like to remind you that during this call, we will be making various statements about Scholar Rock's expectations, plans and prospects that constitute forward-looking statements for the purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995. Any forward-looking statements represent our views only as of today and should not be relied upon as representing our views as of any future date. I encourage you to go to the Investors & Media section of our website for our most up-to-date SEC statements and filings.

With that, I'd like to turn the call over to David. David?

Thank you, Laura, and good morning. Thank you all for joining us for what is an extraordinary day for the SMA community.

On Friday, we reached a defining milestone, the FDA approval of ISEMBYLD, our novel, highly innovative myostatin inhibitor that is now the world's first and only muscle-targeted therapy for children and adults living with SMA.

Over the past decade, SMN targeted therapy that have brought needed innovation to the SMA community by improving motor neuron health. Yet significant unmet need remained as treatment for muscle, the principal organ clinically affected by SMA had gone unaddressed.

With the FDA approval of ISEMBYLD, we are now ushering in the next phase of innovation in SMA treatment, bringing the first and only therapy designed to directly target muscle to the SMA community, and creating new possibilities for patients and families.

I would note three important points with respect to this landmark FDA approval. First, ISEMBYLD as indicated for all patients with SMA, 2 years of age and older who are currently receiving an SMN2-targeted treatment. This broad label enables us to serve a significant population within the SMA community and advances our ambition that any patient who can benefit from ISEMBYLD should have access to ISEMBYLD.

Second, the label reflects the compelling clinical benefits that ISEMBYLD can bring to children and adults with SMA. For patients receiving a chronic SMN2-targeted treatment in our global randomized, double-blind, placebo-controlled Phase III SAPPHIRE study, ISEMBYLD changed the progression of SMA from a loss of motor function to a gain of motor function, specifically at the recommended dose of 10 milligrams per kilogram, ISEMBYLD delivered a robust, clinically meaningful 2-point improvement in motor function compared with patients receiving an SMN2 targeted treatment alone as measured by the gold standard Hammersmith Functional Motor Scale. Akshay will provide much more detail on the ISEMBYLD label and clinical data shortly.

And finally, we are thrilled that our U.S. launch of ISEMBYLD is now underway. Our highly experienced U.S. team has worked with urgency on extensive disease education and awareness initiatives that have advanced the understanding of SMA as a disease of both the motor neuron and the muscle supported by a broad label, compelling efficacy and a well-characterized safety profile, we are exceptionally well positioned for a successful U.S. launch.

We are poised to redefine the standard of care for people living with SMA as we begin to serve a steady and consistent number of new patients through the initial phase of the launch and for many years to come.

Scholar Rock is operating from a position of strength as we enter a new chapter as a commercial organization. From a financial perspective, we exited the second quarter with $492 million in cash, cash equivalents and marketable securities.

Also, with access to an additional $150 million from our debt facility, a priority review voucher that we intend to monetize and revenues that will now commence and grow, we are well positioned to fund our growth initiatives. They include the ISEMBYLD launch in the U.S., our global expansion to reach patients in Europe, Japan and up to 50 countries around the world and advance our robust clinical pipeline and innovative platform.

With this strong balance sheet, we do not intend to raise cash through an equity offering at this time.

Looking forward, now that our U.S. launch has commenced, our opportunity with ISEMBYLD and SMA alone represents many years of sustainable growth as we begin to serve the estimated 35,000 people with SMA globally who are receiving an SMN-targeted treatment. We are on our way to becoming the next global biotech powerhouse supported by bold science, innovative therapies, fully integrated global capabilities and exceptional talent.

Before I turn the call over to Akshay, to further discuss the approval of ISEMBYLD, I want to express my gratitude to the FDA for their constructive and collaborative engagement throughout the review process which helped bring us to this important moment. With that, I'll turn the call over to Akshay. Akshay?

Thank you, David. I'm delighted to be sharing news of the ISEMBYLD FDA approval with all of you today. This is a momentous milestone for Scholar Rock. After nearly 30 years of failed efforts across the industry to drug myostatin, today, we're the first company to successfully develop and secure FDA approval for a myostatin inhibitor. With that, let me share details of the comprehensive clinical program that supported the ISEMBYLD approval and the resulting FDA-issued label.

SMA is a rare, severe neuromuscular disease resulting in irreversible loss of motor neurons and progressive muscle wasting leading to motor function decline. Patients experience muscle wasting that impacts all aspects of mobility and daily life, including basic functions like breathing, eating, dressing, self-care and walking. Affected children often require significant support, and for many, independent living in adulthood can be very challenging.

Despite progress over the last decade with SMN-targeted treatments, SMA remains a devastating disease for too many children, adults and their families.

The motor unit has two key components: motor neuron and muscle. Given that motor function depends not only on neuronal signaling, but also on muscle responsiveness, approaches that target muscle from the start have been urgently needed. With that, let me share details of the comprehensive clinical program that supported the ISEMBYLD approval and the resulting FDA issued label.

We developed a rigorous program to study apitegromab, now known as ISEMBYLD in children and adults living with SMA. This program includes our global, randomized, double-blind, placebo-controlled Phase III SAPPHIRE study. In the positive SAPPHIRE study, we definitively demonstrated that in SMA patients on chronic background SMN2-targeted treatment ISEMBYLD showed a gain in motor function while placebo was associated with a loss in motor function.

The SAPPHIRE study also demonstrated that ISEMBYLD had a well-characterized safety profile. Turning now to the label, ISEMBYLD is indicated for the treatment of SMA in adult adults and children over 2 years who are currently receiving an SMN2-targeted treatment. The recommended dose is 10-milligram per kilogram IV, administered every 4 weeks. At this dose, ISEMBYLD led to a robust, clinically meaningful improvement in motor function. Specifically, compared to patients on an SMN2-targeted treatment alone, ISEMBYLD demonstrated a 2.2 point improvement at 1 year with a nominal p-value of 0.0121 as measured by the Gold standard Hammersmith Functional Motor scale.

Importantly, 34.2% of patients receiving ISEMBYLD showed a 3-point or greater increase in the Hammersmith scale compared to 13.5% of patients on placebo at 1 year. ISEMBYLD-treated patients were more than twice as likely as placebo-treated patients to demonstrate a clinically meaningful improvement, 34.2% versus 13.5%. Indeed, they're almost 3x as likely as placebo-treated patients to reach this level of motor function improvement.

To support the long-term safety, tolerability and clinical benefit of ISEMBYLD, a total of 246 SMA patients have been studied in our clinical program, and we have over 900 patient years of data. The safety and tolerability of ISEMBYLD in children and adults with SMA is highlighted in this table. Underscoring that safety profile, a total of 99% of patients from the Phase II TOPAZ study and the Phase III SAPPHIRE study entered the ONYX long-term extension study and 93% of those participants currently remain in the study, some for more than 7 years. Taken together, these data demonstrate that ISEMBYLD, first and only muscle-targeted therapy for SMA can deliver compelling benefits for children and adults with this disease.

The FDA approval of ISEMBYLD is an enormous milestone for the SMA community and for Scholar Rock. And before I hand the call over to Keith, I do want to take a moment to thank the patients families and the clinical colleagues around the world whose support and commitment enabled ISEMBYLD to be developed. I'd also like to recognize the Scholar Rock team, and in particular, my R&D colleagues and manufacturing colleagues who pursued a bold scientific vision with unwavering focus and determination, accomplishing something that has eluded the field for decades. My sincere congratulations to our team. At this point, I'll turn the call over to Keith to discuss our U.S. launch. Keith?

Thanks, Akshay. I am very pleased to report that we commenced the launch of ISEMBYLD immediately upon Friday's approval, we are thrilled to be serving the SMA community with this innovative first-ever muscle-targeted therapy and now defining a new standard of care for patients living with SMA.

As I've shared with you in the past, the vast majority of patients continue to experience persistent and progressive muscle atrophy that limits both function and independence, despite receiving an SMN-targeted treatment. To this end, neurologists recognize that the future of treatment for patients with SMA is an approach that targets both the motor neuron and the muscle.

Now with the FDA approval of ISEMBYLD, we are ushering in the next phase of innovation where neurologists can do just that.

For patients receiving chronic SMN2-targeted treatment as demonstrated in the Phase III SAPPHIRE trial, ISEMBYLD can change the progression of SMA from a loss of motor function to a gain of motor function bringing life-transforming benefits to patients. Our Scholar Rock team is now executing on what we know well and what we do well. Our exceptionally talented and experienced field team is ready to deliver ISEMBYLD.

Over these past months, the team has been hard at work, building and deepening relationships with the SMA community. Specifically, we continue to engage across the approximately 140 SMA treatment centers 200 prescribing physicians and their multidisciplinary care teams throughout the U.S. And now that ISEMBYLD is approved, we can execute on our plans, highlighting the compelling clinical benefits that ISEMBYLD can bring to the estimated 6,600 patients with SMA in the United States who are receiving an SMN2-targeted treatment. In terms of the launch, we expect a steady and consistent pace of ISEMBYLD patient starts as we work to serve a gradually increasing number of children and adults living with SMA.

As we begin the launch of ISEMBYLD, establishing a seamless high-touch experience for patients and caregivers is a top priority. We have now launched our world-class patient support program, Scholar Rock Supports. The goal of this program is to provide robust dedicated long-term support for each and every patient and family throughout the ISEMBYLD treatment journey.

Our Scholar Rock Supports program offers personalized comprehensive services to patients and caregivers, including disease and treatment education, insurance navigation infusion day logistics, caregiver support and financial assistance for eligible patients.

We expect that approximately 50% of ISEMBYLD patients will be insured by government payers and the remainder to be covered by commercial payers, and we are working collaboratively with them to establish broad and reliable access to ISEMBYLD with coverage that is consistent with our label.

I would now like to provide information regarding the price of ISEMBYLD. When establishing the price for ISEMBYLD, we considered several key factors, including the rarity of SMA the severity of SMA and the compelling clinical benefits of ISEMBYLD. First is the extreme rarity of SMA. As I mentioned earlier, there are only an estimated 6,600 patients in the United States who are receiving an SMN2-targeted treatment.

Second is the severity of SMA, which is a devastating and progressive disease and despite the use of chronic SMN-targeted treatments over time, patients can plateau and decline leading to ongoing motor function loss.

And lastly is the compelling clinical benefits that ISEMBYLD brings to patients, as demonstrated in the positive Phase III SAPPHIRE study, ISEMBYLD change the progression of SMA from a loss of motor function to a gain of motor function, specifically compared to patients on an SMN2-targeted treatment alone. ISEMBYLD demonstrated a greater than 2-point improvement in motor function at 1 year and were nearly 3x as likely to reach a 3-point or greater increase in motor function.

Based on the rarity and the severity of SMA and the compelling clinical benefits of ISEMBYLD, we expect the annual net cost in the U.S. for a typical patient to be approximately $310,000. This typical patient annual net cost takes into account the weight-based dosing in the ISEMBYLD label and the typical patient age and weight based on demographic data from Cure SMA, the single largest U.S. SMA registry. This typical annual net cost also takes into account expected compliance and mandatory government discounts.

Of course, this annual net cost will vary based on the individual's weight and specific insurance coverage. The Wholesale Acquisition Cost, or WAC, of a single-use 150-milligram 3 ml vial is $11,659.

While our team is in the field with health care providers, and Scholar Rock Supports is enrolling initial patients and caregivers. I'd like to provide an update on the commercial availability of ISEMBYLD. Vials have been on site at our third-party provider and are now being packaged and labeled ISEMBYLD will be available for infusion within days. Patients can receive their ISEMBYLD infusions at centers of excellence, freestanding infusion centers or in the patient's home through our home infusion network of more than 10,000 affiliated nurses nationwide.

ISEMBYLD will be available through our specialty distributor and through our expanded specialty pharmacy network that is specifically designed to provide optionality for patients, caregivers, providers and payers.

Importantly, patients can access ISEMBYLD through that same specialty pharmacy where they currently receive their SMN2-targeted treatment. In closing, we are very excited to be launching ISEMBYLD across the United States as we now begin to serve one patient, one caregiver and one family at a time. It is our ambition that every patient who can benefit from ISEMBYLD should have access to ISEMBYLD.

And with that, I will turn it over to Vikas to provide a financial update.

Thank you, Keith. We are very proud of Friday's landmark approval of ISEMBYLD, and we are pleased that the U.S. launch is now underway. From a financial and operating perspective, we are in a very strong position. We exited June 2026 with $492 million in cash, cash equivalents and marketable securities.

Looking forward, we have multiple nondilutive options available to us to continue to strengthen our balance sheet. First, with this approval, we now have an additional $150 million available to us under our debt facility. Second, we are very pleased to have received the priority review voucher from the FDA, which we intend to monetize.

And third, as a commercial stage company, we will begin to recognize revenue from ISEMBYLD sales in the United States.

We are well positioned to fund our ISEMBYLD launch in the U.S., our global expansion to reach patients in Europe, Japan and up to 50 countries around the world and advance our robust clinical pipeline and innovative platform.

With this strong balance sheet, we do not intend to raise cash through an equity offering at this time.

I would like to now provide additional details on the financials related to the U.S. launch of ISEMBYLD. As it relates to cost of goods, the current cost of inventory manufactured prior to FDA approval has already been expensed. For a period of time, cost of goods sold will primarily reflect expenses related to packaging, labeling and other overhead costs, and we then expect COGS to ramp up to a steady state over time beyond 2027.

Turning to the inventory at distributors. While the first quarter of sales will reflect some level of inventory in the channel, we plan to keep levels at a minimum.

We continue to operate with a tight financial plan and our prioritized investments remain focused on our ISEMBYLD launch in the U.S., launch readiness in Europe and Japan, strengthening our supply chain to support our expanding pipeline and our anticipated growing global commercial demand for ISEMBYLD over time and advancing our highly innovative clinical programs.

With that, I would like to turn the call back to David. David?

Thanks, Vikas. Friday's FDA approval of ISEMBYLD, the world's first and only muscle-targeted therapy for children and adults with SMA is a defining moment for the SMA community. This achievement reflects years of rigorous science, disciplined execution, and the perseverance of a Scholar Rock team that never lost sight of the patients and families we aim to serve.

I would like to express my gratitude to our team, our clinical investigators and our patient advocacy partners, including Cure SMA.

Most importantly, I would like to thank the 246 patients and their families who participated in our SMA clinical trials. Their trust, dedication and determination made this milestone possible and continue to inspire our team as we begin to serve the SMA community with this important first-in-class muscle targeted therapy. We are incredibly proud of this milestone, but this is not the finish line. It is only the beginning. As we now enter the next phase of innovation for the SMA community, we do so with a bold ambition, to redefine what is possible for people living with SMA around the world beginning today with children and adults in the United States.

With that, we'll now open the line for questions. Operator?

[Operator Instructions] Our first question coming from the line of Eric Schmidt with Cantor Fitzgerald.

Congrats on the landmark approval and the broad ISEMBYLD label. Maybe for Keith, can you provide a little bit more detail on some of the assumptions behind the average age, weight compliance and discounts that direct you to that $310,000 per year price point?

And then a follow-up in terms of the ISEMBYLD label, obviously, the safety looks clean overall. But I'm hoping the team might address the language regarding fracture risk. Where is that coming from?

Thanks very much, Eric. We'll go to Keith first, and then Akshay will address the other item in the label regarding fractures. Keith?

Yes. Thanks, David. Eric, thanks for the question. I guess the first thing that I want to acknowledge is we're very gratified that the agency, the FDA recognized the important benefit that ISEMBYLD can bring to all adults and children 2 years of age and older with SMA, and that's reflected in this very broad label.

As I mentioned in the prepared remarks, in any time we're go to price a drug, we always consider the extreme rarity and the severity, along with the compelling clinical benefit that ISEMBYLD demonstrated in our Phase III SAPPHIRE study.

I mean I want to first remind you that the wholesale acquisition cost of a vial of ISEMBYLD is $11,659. Now as we took a look at the single largest SMA database that exists in the United States, the Cure SMA registry, we found that a typical patient is expected to weight in the 35 to 45-kilogram range and would be infused with approximately 3 vials every 4 weeks. We've also assumed that a compliance rate of 85% to 90% being dosed every 4 weeks, you could have where patients will miss 1 to maybe 2 doses per year.

In addition, we factored in the mandatory government discounts I mentioned before that the payer mix is roughly 50% commercial and 50% government pay, but we also have patients that will be treated in 340B facilities.

So when you factor in all of these things, compliance and the mandatory discounts, the typical patient weight of 35 to 45 kilograms, we're going to be at a net annual cost for a typical patient to be $310,000 and -- but I do want to close with reminding you that this price is going to vary on a patient-by-patient basis based on that patient's weight and their insurance coverage.

Thanks, Thanks, Keith. Akshay?

Yes. I appreciate the question on the safety, Eric. So a couple of things. First of all, we're very proud of our well-characterized safety profile for apitegromab based on several facts and 99% of patients from the Phase II and Phase III rolled into the ONYX long-term safety extension study. 93% of them are still on that study today, some out over 7 years, and all of that generated 900 patient years of safety data, which leads to the conclusion that the drug is well tolerated.

As for the specifics of the fracture question, the literature rates for annualized incidence rates for fracture in this patient population range from 4% to 14% and indeed, the cumulative lifetime prevalence is up to 40%. So our numbers are well within the annual incidence rate in actual fact. And I think we have to be mindful of the potential for the tyranny of small numbers here with twice as many patients being on apitegromab in the Phase III as on placebo. And obviously, that can skew the amount of safety information you collect for both those groups.

And just to illustrate the issue, no patients from the placebo arm who rolled on to active in the ONYX safety extension study had a fracture at year 1 versus if we look back at the SAPPHIRE Phase III study in eight patients on active had a fracture at year 1. So the fact that the placebo patients going on to active drug apitegromab at 1 year having none shows you how these numbers can wobble around.

And most important to me as a drug developer, I'd say when patients did have a fracture, number one, events were all classified as not related. So from their practice, the investigators appreciate background issues like osteoporosis and falls that were associated with the fracture events. They've seen them before many times. And b, all patients on study who had a fracture, stayed on drug and the fractures resolved. Now I think that says something very important as well.

And finally, I'll close by saying that not a single patient was withdrawn from drug after a fracture or came off study, and that's across the entirety of the clinical development program and the expanded access use program. So I think that's saying something very important as well, and we're very comfortable with the go-ahead safety profile. Thank you.

Our next question in queue coming from the line of Michael Yee with UBS.

Congrats on the approval. It's been a long time coming, and it's been a great journey. Two questions. One, just on thinking about the commercial launch. I know that you said you want to keep inventory low and some things like that. But can you just talk about what type of metrics? What type of data points you will provide? And what type of leading indicators you can be able to talk about over the first 1 or 2 quarters? And how we should be thinking about numbers of patients you think you can go after. I would think there's some bolus or other factors, but maybe you could talk about that over the next 1, 2, 3 quarters?

And then just one detailed question about the fractures. I appreciate the comments you mentioned, but the label talks about specifically proximal type impact in mouse models. And so I just wanted to understand whether the fractures that you saw in the clinical data sets were proximal or distal and that might be helpful, too.

Thanks very much, Mike. We're going to go to Keith on the launch dynamics and metrics and then back to Akshay on the proximity, Keith?

Yes. Thanks, David. Mike, thanks for the question. As we've had additional time to prepare for this launch, we've really built one of the best in the industry, rare disease teams in several different aspects, whether it's the team that's out in the field or whether it's the business analytics team that's here in-house, I can tell you that internally, we already have scorecards that are ready to go, and we have a number of metrics that we will be looking at here internally.

At this time, here we are on day 3. We haven't really made a decision on what type of metrics that we will commit to on earnings calls. Obviously, you know that we'll be reporting revenue, which will be the true north.

It might not be the true north in quarter 1 because as you've heard me discuss before, that when a patient gets prescribed a brand-new therapy in rare disease, that usually leads to prior authorization and many times followed by a denial. So the revenue in quarter 1, I just want to say we'll have consistent and steady growth.

Over time, we'll determine what other metrics that we will be bringing out obviously covered lives and how well we're doing on getting policies that are developed, which are in the public domain anyway. I think, will be a major factor as well as how well our coverage is doing for our team to where these 6,600 patients in the U.S. are currently being treated.

Thanks very much, Keith. Akshay?

Yes, Mike. So in terms of the animal data, the nonclinical profile. Obviously, those are very exaggerated doses and the proximal fractures you mentioned in the clinical situation in the program, there are distal fractures. And in fact, the range of fractures seen in the program is completely within the range that practitioners see in the day-to-day in their practice with these patients.

So as I said, 40% cumulative lifetime incidence of fractures, which is very sad for these patients. But of course, they have all these background concomitant factors like poor nutrition, osteoporosis, falls and hopefully, as the standards of care continue to improve, those will diminish. But the factures were distal so not related to the preclinical profile.

Yes, Mike, we saw your note from yesterday. And in fact, as you indicated as a question in SAPPHIRE, the three femur fractures were all distal.

[Operator Instructions] And our next question in the queue coming from the line of Kripa from Truist Securities.

Congratulations on the approval. I echo Mike's long-term coming -- long time coming, but great journey. So I do just want to go back to the launch trajectory. When we think about it, what are the gating factors that we should be looking at?

And in terms of payer coverage and formularies, how quickly do you expect top commercial health plans and the state Medicaid programs to establish formal policies. Are you expecting any kind of prior auth hurdles at all?

Thanks very much, Kripa, and it's been great to be on this journey with you. As I think Keith and I have noted with nearly all patients with SMA claiming that their #1 need is more motor function and more muscle strength. And 3/4 of neurologists indicating that the optimal way to treat patients with SMA is by both addressing motor neuron health as well as the muscle, the principal organ clinically affected in the disease.

We certainly are expecting some nice demand features in the launch. But I think you adequately and appropriately focus a bit on the reimbursement and access side, which I think Keith has great confidence in over time, but those dynamics initially at launch, are worth him walking through. So I'll hand it over to Keith to comment on that. Keith?

Yes. Thanks, David. Kripa, I guess the first thing is, I agree with David. And I think we've shared that in the extra time that we've had and been able to be out there, it does seem like the demand to utilize apitegromab has grown from a physician and patient perspective.

I think I just saw a survey that came out last week that showed 15 neurologists that were surveyed that 62% of them. They believe 62% of their current patients are good candidates for apitegromab and 3/4 of those physicians said that they could see themselves prescribing it within the first 3 to 6 months. So I do think that the demand is going to be there.

With that being said, our market access team has already been meeting with not only the commercial payers but also government payers and working with Medicaid so that we could discuss what a potential policy could look like. And our goal is to have these policies that will be in line with the label. And as you know, we've got a very broad label here. So look forward to the ongoing discussions with the various payers, both private and public.

With that being said, it typically takes a period of time for policies to get drafted and ultimately published. So what I do expect in this first 6 months that we will be without a J-code. Now the good news is the timing of our approval. We are now only going to sit quarter 4 of this year and quarter 1 of next year with an unspecified J-code. But with Scholar Rock Supports, we will be able to work through that period with an unspecified J-code. But it will take time to get these policies up and in place.

And I think the last thing I'll say is I've given you the statistic before, but in the last launch that I participated in, even 6 months post launch, the average time from prescription to actual infusion was still slightly over 60 days and that's where I'm going to ask that we'd be a little bit patient here in these first couple of quarters as the policies get published as the J-code comes on board as hospital formularies put apitegromab on formulary and then you'll see that time shorten from prescription to infusion. Ideally, we'll get that down into the 10- to 14-day period.

Our Next question in queue coming from the line of Cory Kasimov with Evercore ISI.

Let me add my congrats on this approval. My question, I want to go back to the safety front and kind of a follow-up here by asking, did the FDA require any sort of post-marketing requirements or commitments specifically on whether it's bone or reproductive safety? Or is it sufficient that you kind of ongoing submit data from your ongoing open-label extension ONYX study on that front?

Yes, great question, Cory. Akshay?

Yes. And the answer is relatively straightforward. So there are no post-marketing safety commitments. With respect to the fractures on the reproductive side that you mentioned. And then there will be standard safety updates that obviously, we'll be providing to the FDA.

Our next question in queue coming from the line of Geoff Meacham with Citi Group. Congrats on the approval.

This is Jarwei on for Geoff. Maybe just a quick question on the number of patients and percentage of them. Just can you give us a sense of what percentage of eligible patients reside at centers that are ready to prescribe and fuse ISEMBYLD immediately versus ones that center that maybe require a little bit more work and reach from your FTEs.

And then maybe thinking about preparation, how are you preparing for demand is initial uptake exceeds expectations? Just given you mentioned that you guys plan on keeping inventory in the channels as low as possible.

Thanks, Jarwei. And as I think Keith and I have been noting for some time, a little bit of the extra time has been really helpful for Keith's team, which has really been able to work very closely with the SMA community, the centers of excellence, the KOLs also reach even deeper into the SMA community to understand care pathways and such. So Keith can comment on all of those questions. Keith?

Yes. Thanks a lot. I guess the first thing that I want to call out here that's a definite advantage for us in a rare disease launch is that these patients are known because as our label states, they are already on an SMN2-targeted therapy. So it's not about us being out there having to find the patients and have them diagnosed. They are already known.

The second thing that I would say is the 6,600 patients that are on an SMN2-targeted therapy around the U.S. They really are predominantly in those either 140 centers or they're consulted by somebody at those SMA expert centers. But the 2,600 neurologists that currently prescribe for them is the group that we are actively covering. So I do feel good about the coverage that we're going to have in a timely manner because we have been establishing not just these relationships, but as David alluded to, it's even on a patient-by-patient basis on how they want us to participate enrolling that patient in Scholar Rock Supports will allow us to help with a number of different things, but that would also include infusion logistics, okay?

Your second question is what if we get over demand into the system? I've got to tell you that I've got, I think, the best U.S. General Manager in the business in -- Rebecca McLeod. Rebecca also led the world-class VYVGART launch with me at argenx with myasthenia gravis. And as you know, our demand had increased greatly there.

Now she's only even more experienced after having done this with CIDP and subQ. The team has already built contingency and backup plans in the event that we do have this demand will be able to cover it at Scholar Rock Supports, and we will be able to cover it at our external hub. So I really like the contingency plans that we've built, and I hope that we get to put them into action.

Our next question in queue coming from the line of Tessa Romero with JPMorgan.

Congratulations to you and the entire team at Scholar Rock and to patients and their families. Just to double click here on a prior question. As you think about ramp, is there a specific target or target you can tell us you would like to achieve, hopefully, on new patient starts, payer coverage as you move ahead, that may help guide us on how you're thinking about the trajectory here? And then I have a quick follow-up.

Okay. Thanks, Tess. Keith?

Yes. I guess, first of all, we were not getting granular on numbers on what patient trajectory is and what we expect in the numbers. Obviously, this is something that, as I mentioned before, we will be monitoring on a daily basis, whether they come in through our Scholar Rock Supports programs or if they come in through one of the specialty pharmacies that are in our network, we will be receiving real-time data on this.

I do see in the future, Tess, where we would be able to provide you a percent of covered lives at some point. And ultimately, I expect like you see with most rare diseases, we're going to get that number up into the mid- to high 80s of percent of covered lives.

If I look at the SMN2-targeted therapies right now, as you've heard me say before, it almost always requires a prior auth now. And then when prescribed, 50% of them are denied. And then out of those that are denied, they go through the appeal process and you almost get 90%. It's about 87.5% of patients that get prescribed in SMN2-targeted therapy wind up being able to receive it. We see that we will be able to get into a similar range over time.

And then, Tess, before your follow-up, I would just add that as I think both Keith and I noted earlier, we have great confidence in a steady and consistent addition of new patients quarter-on-quarter, year-on-year for many years to come, starting here in the U.S. and eventually launching in Europe, Japan and up to 50 countries around the world. We think that it is that opportunity over the long run that we see positioning Scholar Rock for sustainable growth for many years to come.

We think demand will front run access for sure. We're a little less concerned about ramp and much more confident in sort of where we're heading in a very steady and consistent way. quarter-on-quarter, year-on-year for many years to come. Your follow-up question?

Great. Great. And anything about your market research work that you would flag in terms of who you expect will be the earliest adopters?

Yes. Yes, it's a great question. I mean -- and that's the benefit of having such a broad label is one could see both from a patient and family perspective as well as a physician and health care team perspective, a variety of different approaches, some may want those patients that have plateaued and are beginning to decline. Others may want earlier is better before muscle atrophy sets in, and one could really look to make sure that they get in front of any plateau or decline. And we -- I think we've seen in surveys a number of physicians, Keith, who indicate that all patients on an ongoing chronic SMN2-therapy are appropriate for treatment and they would want to be discussing the first and only muscle targeted treatment now approved by the FDA with all of their patients.

So I think it's very much like the label, it provides a lot of optionality for who's first. But I think more importantly, we have great confidence that essentially anybody within label who can benefit from ISEMBYLD should have access to ISEMBYLD. And I think Keith has established along with Rebecca, a sensational team prepared to do just that.

Yes. I mean the only thing that I would add is that obviously, we have the ONYX patients that are on our extension trial as well as our EAP patients, these will be the first patients that we'll be enrolling into the Scholar Rock Support program and that we will then be transitioning them over to commercial drug.

What I do find is sites, physicians that have had experience with apitegromab either through the clinical trial or through EAP. They are already the ones that are -- have additional patients in mind that they would like to add to the drug.

As we move forward with all of the other additional sites, we've got some that have patients that they have already identified and are ready to prescribe. And then I think we have others that it's going to be a situation where probably the toughest patient that we will get will be their first one, because I feel confident that after they have their first patient on apitegromab, and they get to instead of reading the primary endpoint and secondary endpoints from a study, they're hearing from the patient, their real-world experience and their quality of life and what's taking place in their life because of being able to now be on the first and only muscle targeted therapy. I think that's what's going to help influence and expand.

So it's going to be -- the last thing I'll say is Look, this is one of the tightest patient communities that I've ever worked in. And so I think the word is going to spread amongst the patients as it has already. So I think that will help be a driver for us.

Our next question in queue coming from the line of Evan Seigerman with BMO Capital Markets.

Congrats on the approval. So with FDA approval in hand, kind of what are the gating factors for a potential European approval? And do you expect that the inspections that were done for this facility should suffice whatever the European regulators need and their processes.

Excellent question. Akshay?

Yes. So we've had an excellent dialogue throughout the MAA review with the CHMP, up to including the recent advice that we should withdraw. We'll be refiling promptly. We believe, with the second fill-finish facility. They're well aware of that. They're very supportive of that. We're just working out the time lines around that. And in fact, as soon as we get the green light, we're ready to refile.

So we feel like we're in a great spot and everything done with the second fill-finish facility in terms of inspection, et cetera, by the FDA will support the ultimate CHMP approval.

And so while we haven't necessarily provided guidance on when we're resubmitting and when we would expect or how long we would expect the review largely with the alternative filler to take. What we have indicated to you is well the European regulators have kind of gotten back from high holiday season, they'll be getting back together. We should be learning in the coming period of time, a little bit more about that timeline, and then we will certainly update you all on those timelines.

Our next question in queue coming from the line of Ally Bratzel with Piper Sandler.

A big congrats from me as well. Just a follow-up question to some of the prior discussion. Could you characterize awareness of apitegromab among patients and caregivers? And just to what extent do you expect prescribing will be patient driven by patients seeking out treatment versus prescriber driven?

And then just one quick follow-up on fractures. Just do you expect that fracture warning language to affect patient selection or treatment discussions in patients with low bone density, prior fractures or contractures?

Yes, Keith, we certainly know this is an incredibly important day for the SMA community. And we, as a company, have been engaging with patients and families for quite some time. We know how engaged they are and how active they are in their care plans with their physicians. I'll have Keith comment specifically on your question. Keith?

Yes. I mean, Ally, since we do know that these patients are already on an SMN2-targeted therapy, their awareness in the community is quite high. And so the fact that this exists already. I would tell you that patient awareness is probably at one of the higher levels that I've seen in a rare disease launch.

I also think that physicians are aware of the product and very soon that it is now going to be available. I think last year, when you had two CRLs for this community in SMA back-to-back 2 days in a row, it even made that drive and desire for this more, and it certainly felt like that over the last 12 months.

As far as will the decision be driven by the patient or by the physician, look, at the end of the day, the physician is always the one that's in charge on prescribing for the patient. But let's not lose the importance that in this industry, we know that when a patient goes in and asks for a medication. It's the majority of the time provided that the safety profile is compelling. There's less hesitation from a physician to be able to utilize that.

We do have a program that's called Life Takes Muscle that we've had patients that have been enrolling in this program for now better than a year, and we are able to make them aware that the product is now approved. So we're going to look at this from all sides, direct to patients and obviously, our work with the health care professionals.

Yes. And then, Ally, I'll just comment on the second part of your question. As Akshay, I think, laid out in a lot of detail. The fact that 99% of all study participants rolled into our long-term extension ONYX study, 93% remain actively receiving apitegromab in that study, some for now more than 7 years. Not a single patient in all of our clinical trials or early access experience has ever discontinued due to fractures, the fact that the incidence rate was well within that, that's been reported in the literature between 4% and 14%, that there is no increase in fractures with more exposure to apitegromab.

And I think as Akshay laid out very nicely. Even in the label where the placebo rate was 2% those patients then rolled into ONYX those placebo patients. And in their first year of receiving apitegromab, there were 0 patients and 0 incidents of fractures, which also sort of highlight as he noted, sort of sometimes the law of small numbers.

So look, I'm glad it's in the label. I think everybody should have the awareness and we're aligned with that. But I think that this is an experienced medical community and patient community that will be able to understand the compelling clinical benefits of ISEMBYLD. And as Akshay noted, the well-characterized safety profile over a 7-, 8-year development program. So we're really looking forward and are happy we're out there now to bring apitagramab or ISEMBYLD to the broader SMA community.

And I'd just add that there is no contraindication and there's no expectation of any kind of DEXA scan to start treatment.

Our next question, the queue coming from the line of Gary Nachman with Canaccord Genuity.

My congrats as well on the approval on broad label. So within the patient support program, how much co-pay support will you be providing, especially until the reimbursement improves? How do you think that will impact the gross to net for the first few quarters of the launch on a relative basis when thinking about the $310,000 average annual net cost? So that's first.

And then secondly, just describe a bit more, Keith, just how the infusion network is set up, how robust it is? And if you think the monthly infusions could be a hurdle for certain patient groups, any of the patient groups whether it's by age or geography or ambulatory status. That will be important.

Yes. Thanks very much, Gary. I'll hand it over to Keith. But I think when Keith was kind of as he noted, the typical patient at that price really was using -- understanding weight-based dosing, leveraging the largest database of its size, but also kind of thinking about like what percentage of infusions will be delivered to patients in a given year. And obviously, with a 50% payer mix of government payers, understanding that there are some mandatory government discounts.

So I think that was all reflected in there. And Keith, I think you even assume that of any underinsured or uninsured patients in the patient assistance program. So I don't think anything is off. I think that was really within the framework of what Keith had shared earlier. Keith, do you want to comment a bit on the infusion network?

Yes. Yes. First of all, I think that just on the first topic, I think that David's nailed that, and I really don't expect a GTN to be impacted by the outstanding assistance programs that we are going to be able to offer eligible patients through Scholar Rock Supports.

It's going to be different types of programs that are eligible for them. And it will be based on that individual's need on which of the programs that they can take us up on it.

As far as the infusion network, look, I think that this is not only going to be driven by patient preference but also by the facility's preference. I can tell you that in real-world practice, I've heard where they have a desire -- our EAP, for example. They do give the first couple of infusions, typically at their center. And then if a patient chooses to be treated elsewhere, it's coordinated. And approximately 50% of our EAP patients right now are, in fact, on home infusion. So we have been putting our network to the test a bit.

As far as from a Scholar Rock point of view, we're agnostic. We're going to help them be treated wherever they would like to receive their infusion. So some people don't want somebody coming in their house or their insurance might not allow them to have home health care. In that event, if they want, we will help them find an infusion center that is more convenient to their house, whether it's a freestanding infusion center or outpatient at a hospital, whatever is going to work best with them.

And so -- at the end of the day, a lot of products are given a lot more frequently than every 4 weeks, IV. And for devastating illnesses and severe unmet medical need that exists like it does here with I really don't think it is that substantial of a burden to basically take 13 hours out of a year to have this product infused.

And we definitely think that's been borne out in all of the persistency rates for patients for all these years of the development program with 93% of patients remain on treatment over that period of time.

Our next question in queue coming from the line of Ritu Baral with TD Cowen.

A great day for SMA patients. A question on the EAP patients that you guys have mentioned a few times. Could you help us EAP patients that you have, what their conversion rate may be, whether there's a bridging program or not in place?

And then there was a comment, I want to make sure I understand this, there was a comment on how -- where a patient is treated may be a factor in the launch curve. I wanted to just drill down a little further on the meaning of that. Is that a statement on sort of like the 140 SMA centers and tiering of these centers or experience of the treating clinicians? If you could elaborate? What the where means, if you know what you mean.

Yes. Thanks so much, Ritu. Keith?

Yes. I would say, first, on the EAP patients and a conversion rate. Ritu, I don't have privy until approval of actually each of those patients and what their actual insurance coverage is. So right now, it would be difficult for me to actually say, "Hey, we expect this level of a conversion rate in the program." These are going to be the first patients that are enrolling into Scholar Rock Supports, and they will be ones that we will be working on converting them just as quick as we possibly can.

As far as a bridging program for them, it's not necessary at this point. And the reason being is because we can still keep them on clinical supply instead of commercial supply because we use the clinical supply at EAP and we're going to allow them to continue to get infused on the EAP program until we successfully converted them over to commercial.

And then the one thing you mentioned on the launch curve, I just -- on where a patient gets treated as to how does that affect our potential launch curve. I would say the biggest impact is going to be when they're going to be getting that first couple of infusions, within the hospital. And I say that to you because most hospitals don't allow you to do a formulary process prior to a launch. So the formulary process will begin now to make the drug available within the hospital. And in some of these larger teaching institutions, this can be a couple few months delay for when they actually would have the product in-house to be available.

And that's something that could -- the demand could be there, ready to utilize it, but they have to be able to purchase the product at the hospital in that situation.

Understood. And how many U.S. EAP patients are there?

We've never really given that number publicly, on the exact number of EAP patients. But I will tell you that we're pleased with the EAP program. You know that we stopped enrollment of that on the Friday night before the September 22 CRL because we thought we were getting approved. But we continue to the adherence to product and the EAP has been tremendous and gives us great confidence.

As far as building anything into a model, I think they're going to be spread out through the next quarter or 2 quarters because we will be going through prior auths, appeal processes, peer-to-peers. And so it will be staggered as when they come on to actual commercial product. Thanks, Ritu.

Now last question in the queue coming from the line of Basma Radwan with Leerink Partners.

Congratulations on the approval. Just a follow-up on one prior question based on your market research, do you expect any difference in the level of adoption between patients who are on Evrysdi versus patients who are on SPINRAZA, given that there is increased treatment burden with the monthly injections?

And also one follow-up question on the dose, given that the 10 mg per kg dose, is a dose being recommended. Do you think, at some point, physicians may be able to escalate to 20 mg for the CD patients? Or that's not the case right now.

Thanks, Basma, why don't we take that second part first, Akshay, just on the...

Yes. No, just very quickly on that. The data very clearly showed that 10 is the optimal lowest, safest effective dose, and there will be no need to go up to 20.

Keith?

Yes. And then I think on the first part, you know from where we stand, we really believe as an organization that a patient, their best opportunity and what we will be making a new standard of care is when you're actively treating the motor neuron and actively treating the muscle.

From our point of view, we're really agnostic whether on Evrysdi or SPINRAZA or quite frankly, high dose SPINRAZA, if it's good for them, and then we can help by targeting the muscle directly, that's where we would aim to be.

Do I think that it expands the potential marketplace it's quite possible because at the end of the day, these patients have never been able to directly treat muscle. And so I do think that whether they're on evrizdy or whether they're on nusinersen I just don't think that, that will be the key factor into why they decide whether they -- whether ISEMBYLD it is going to be the right choice for them.

Yes. And I think, Basma, just make a closing remark on the call. I think that over these last 10 years where the SMN-targeted therapies have brought needed innovation to the SMA community, it's with the understanding of how important SMN protein increase is for motor neuron health.

And I think now we're ushering in the next phase of innovation. And I think there's a greater appreciation that the body's natural negative regulator for muscle growth is probably not something that is particularly helpful for patients with SMA. And so now we have the first and only muscle-targeted therapy ever approved by the FDA for patients with SMA. And so we're excited that patients can now benefit from both increased SMN protein production as well as safe and effective inhibition of myostatin which, as I noted, is the body's natural negative regulator of muscle growth.

So we're super excited to be ushering in this next phase of innovation and look forward to keeping everybody apprised as our launch progresses. Thank you very much.

Thank you. Ladies and gentlemen, this concludes today's conference call. Thank you for your participation, and you may now disconnect.

It's great to be here with you. Maybe just for those on the webcast that are maybe not as familiar with the story, just give us a quick like 2 minute, and we'll get right into some of the Q&A.

Yes. So quickly, we're at an exciting moment in time for the company, 15 years since we founded the organization and now really 3 weeks away from our PDUFA date with the FDA for a monoclonal antibody, apitegromab, which is the first and only myostatin inhibitor that's ever been proven to deliver statistically significant and clinically meaningful benefits in a Phase III trial despite the fact that nearly all major pharma and biotech companies have tried to drug myostatin since it was discovered at Johns Hopkins in 1997 as the body's natural negative regulator for growing muscle. So obviously, if one could harness the potential of safely inhibiting myostatin and effectively inhibiting myostatin, you could restore and deliver muscle growth, muscle strength for a whole host of diseases. And we, of course, are focused on a set of muscular atrophies and muscular dystrophies.

The first, of course, is spinal muscular atrophy, where 35,000 patients globally are receiving at least one SMN targeted therapy. And in our 7-year development program where we took no shortcuts, our Phase III trial was 188 patients, and we delivered a statistically meaningful benefit in the highest bar, the Hammersmith Motor Function Scale for returning motor function improvement in those patients. And so on file with the FDA and ready to launch. Geoff, we'll talk about that with our time together this morning. The action date for the FDA is September 30. Looking to resubmit our MAA in Europe because we've recently withdrawn, all tied to the compliance issues at our third-party fill/finish manufacturing facility.

And then, of course, we are really excited to announce that we have an agreement with PMDA to file our JNDA by the end of this year, needing no additional clinical trials in a local Japanese population. And this really advances our ambition to reach these 35,000 patients and upwards to 50 countries around the world as Vikas and I and the team have done at other companies. And so we're super excited about that and look forward to digging in with Geoff this morning.

Yes. So let's talk about the Catalent facility and kind of the background there. So that is -- now you're talking about proceeding the BLA, right, through the alternative facility. What -- maybe what gives you the confidence that you're -- there's no remaining kind of hurdles. Just give us kind of an update on the manufacturing.

Absolutely. Look, Geoff is appropriately so asking probably the question on everyone's mind, which is if we had a PDUFA date last year of September 22, 2025, all signs read positive for an approval. We were discussing the label essentially a day or two before our PDUFA date. And then we received a CRL for the sole approvability issue being a general site inspection at our third-party fill/finish facility, Catalent, Indiana owned by Novo Nordisk. And that same facility now has just had another plant inspection in April of 2026. That was a reinspection that was supposed to clear the facility. Why are we confident that being back on file with the FDA with an action date in just 20 days, why are we confident that we're heading toward an approval? And that's -- it really dates back to the following.

At the same time that we were working with Novo Nordisk and the FDA for them to remediate their facility and improve their GMP practices, we were also standing up an alternate fill/finish facility that was in good standing with both U.S. and European regulators. We actually announced on November 14, which was our third quarter earnings call of 2025 that we were under a contract with an alternate fill/finish facility and that we had secured commercial manufacturing at that facility in the first half of 2026. So we did that very, very quickly. We rolled out tech transfer in breakneck speed. And on December -- early December, first week in December, we actually requested a Type C meeting with the FDA to talk about the progress at our alternate or second fill/finish facility.

That led to a March 3 Type C meeting where really what was on the table was the progress that we had made at this second fill/finish facility. And Geoff, it was during that Type C meeting with all the leaders of the FDA, OMQ and OPQ, who oversee facilities and product quality that they said, look, this is an important drug for an important patient population. Our suggestion is that we actually have a horse race, resubmit your BLA with both Catalent, Indiana, and your alternate fill/finish facility, whichever one enables approval fastest stays in the BLA, whichever one would not, you remove from the BLA with no time line hit, no major amendment, and away we go. So that was March 3 of this year.

On March 31 of this year, we announced that we had resubmitted our BLA just the day before and that we had resubmitted it under -- within complete alignment with the FDA with both fill/finish facilities. Now look, when we heard inspector showed up at Catalent, Indiana on April 13, so just like a couple of weeks after we resubmitted our BLA, you might imagine with all the attention that Novo Nordisk was putting on remediating this plant, we thought that would have obviously been the fastest path to an approval. We would have dropped our alternate site and then we would have resubmitted that alternate site as an sBLA after approval. We now all know that inspection from April 13 to April 24 didn't go so well. The Form 483 had multiple observations that all read like the poor inspection in 2025. There was definitely improvements at the plant, but not enough to get the FDA through downgrading that facility. And so it kind of started to read for us like the most expeditious path was going to be this alternate facility. Importantly, we have now vialed more commercial apitegromab at the second facility than we ever did at Catalent, Indiana. And vials from this second facility are now awaiting labeling and packaging in our third-party provider on the day of approval. And so we are in a very good position from a launch perspective.

Now specifically to Geoff's question, was it a poor inspection and we removed Catalent, Indiana, and we're kind of flying blind on the second facility -- the answer to that question is no. In fact, what gives us great confidence is that we're in ongoing dialogue with the FDA. Based upon the OAI classification of the April reinspection, we actually said to the FDA, we think it's time to remove Catalent, Indiana. The FDA said, "Wait a minute, let us just complete our review of your alternate facility, and then we'll actually walk you through the process to remove Catalent, Indiana. And of course, in early August, we did announce by press release that we had removed Catalent, Indiana from the BLA under FDA guidance. And that was following their review. I don't want to say that the FDA is ever completely done, but they definitely had a checkpoint in the way. So Things are reading positive from both the CMC review and then the clinical review. There just isn't very much to do since the label was essentially finalized during the last cycle, and we remain very confident that we're going to be receiving an approval here in September.

Let me do one more, and then I'll hand over to you for a few. So just when you talk about the alternate facility, is the capacity similar? Talk about the ability to scale and maybe the early stages of the launch.

It's an important point. This is not a boutique or opaque fill/finish facility. It's a substantial facility with a track record globally. They've had European positive inspections as well as U.S. regulator positive inspections over the long run and recently. One of the things, Geoff, that we thought was important when we identified this facility was that they would have multiple lines that were actually ideal where they had lines that were qualified for a vial configuration. Now why was that important? That was important for speed because if you change anything about your packaging, that would definitely not enable us to add a second vial as quickly as we did. So we validated multiple lines with our engineering and PPQ runs. We've scaled up manufacturing there, which, of course, again, it is fill/finish. So it's -- they're taking our drug substance and they're vialing it. Their work has been extraordinary so far. As I noted, they're in good standing with U.S. and European regulators. They're on file with a number of Japanese applications as well.

And over the long run, Vikas and I will always look for redundancy in our supply chain. But for now, we feel really good with this fill/finish facility. One other important note I would like to make, when we disclosed that we had removed Catalent, Indiana from our BLA, it was only as a commercial supplier of the drug, their data remains in our BLA. The -- we continue to use the drug. No one's ever claimed the apitegromab that's been vialed there is not a high-quality product. In fact, that's the product that we continue to dose our long-term clinical trial patients now for upwards to 7-plus years. So technically, some of the Catalent data is in our BLA. They are just removed as a commercial supplier of apitegromab for now.

Great. Yes. Thank you so much for giving us an overview of some of what's been going on behind the scenes. You touched upon that the labeling was pretty much completed during the last cycle review back in 2025. So maybe help remind us some of who are listening about some of the discussions that had happened and maybe expectations for ambulatory versus non-ambulatory or maybe a broad label that could happen?

Yes. These are excellent questions. And I guess I would first start because we've worked -- while we've been disappointed with the delay of first and only muscle-directed muscle-targeted treatment for SMA, we have been very grateful to the FDA for their collaboration during these past few months since the CRL. And so it would be maybe inappropriate for me to comment specifically on the label. But what I have said in the past is we were pleased with where the label was at the last exchange that we had with FDA, which was September 18, 2025. So that was just 2 business days before the PDUFA date. We had historically seen that the FDA as it relates to SMA has usually seen SMA as a single disease rather than a disease where they're chopping it up by age group, copy numbers, subtypes or ambulatory status. Like if you just look at the other drugs that they have approved, they've generally not done that.

Obviously, the gene therapy was in a very young patient population. So our feeling is that, obviously, the under 2-year-old population will not be on label because we just hadn't studied that in our clinical trials. It was really 2 and older. We do believe that very much in our label discussions, we were very much talking about SMA more broadly and the benefits of SAPPHIRE that our Phase III SAPPHIRE trial were able to demonstrate. And so we were pleased -- just to give you guys a sense of the exchange, when you submit a BLA, you submit with your draft label. I'm on record of saying we were never -- even in the first red line from the FDA, we were never in a different stratosphere from the FDA on what the label should look like. We were always kind of seeing things very similarly.

And so it was very collaborative in the last cycle. They sent us the latest red line on -- it was like 10:00 a.m. on Thursday, September 18, and why we thought we were going to get approved in that cycle. Remember, this is before Catalent, Indiana was classified as OAI and before they got a warning letter. So here we are in deep label discussions. They sent us the label the morning of September 18. They wanted it the morning of September 19, which was Friday. The PDUFA was Monday, the 22nd. We sent back comments to that. We had sand paper out. We definitely didn't have major -- we didn't have major tools, chainsaws, out at all. We were sandpapering some of their comments. We sent it back in the evening of September 18.

What they asked for in this cycle and this rereview of the application is for us to go back to the label we sent to them on the evening of the 18th. That was the starting point for this cycle. So that's why we were -- I've also -- I'm also on record of saying even if they took none of our comments that we sent back on the 18th, we were in a win scenario for the SMA community. We were in a spot where we would have been able to serve a meaningful proportion of the SMA community that could benefit from apitegromab therapy. And hopefully, we'll be able to share in a lot of detail the label in just a few weeks.

Awesome. That's great to hear. So maybe let's then shift to what could happen after apitegromab launches, and we're all very interested in hearing what the branded name will be. Maybe just as the initial patients start to flow through, maybe tell us about your expectations for age 2 years above or what adult status, ambulatory status, background SMN-targeted therapy, maybe prior treatment history. Just trying to get a sense of where you're thinking of the flow of patients coming in and what they may look like.

It's an excellent question. So where do we think the demand comes from? Is it the younger patients who perhaps doctor's ambition is to provide as much normal musculature before atrophy sets in? Is it adult patients who maybe have missed some of the benefits of the SMN-targeted therapies because they had a lot of motor neuron deterioration even in 2016 when SPINRAZA was first approved, when the first drug was approved? And it's a little bit of all. It really depends on the patient, the family and the doctors, and maybe I can walk you through that. So as a reminder, we took patients that on average had been on either SPINRAZA or Evrysdi for about 5 years in our Phase III trial. Those patients were randomized to either receive nothing at all, placebo or apitegromab.

And what we demonstrated in that trial is that those patients that were on Evrysdi and SPINRAZA over the 12-month treatment period, actually were losing motor function. And that's actually pretty consistent with some of the long-term data that even those companies have shared of their registration trials that patients do better initially when they get more SMN protein, they gain motor function, they plateau and then they can actually start actually losing motor function again. And what we demonstrated in the SAPPHIRE trial was patients went from a loss of motor function to a gain of motor function. And in fact, what we believe will be the recommended dose, the 10-milligram per kilogram dose, there was a 2.2-point difference in the Hammersmith Motor Function Scale, which is the gold standard and highest bar to hit even Evrysdi did not hit that prospectively in their Phase III trial, and we had a statistically significant benefit there.

And then we had a 3.8x greater likelihood of a 3-point improvement or more when patients on SPINRAZA and Evrysdi were randomized to apitegromab versus not. And this is, again, a pretty broad patient population. So the TOPAZ study, we did have children as early as 2 years old in that study. They've done exceptionally well. So what we're hearing is the following: 90% to 95% of patients claim today with SMA that their #1 need is muscle strength and more motor function. So nearly the entire community is saying we need more muscle. 75% of neurologists are now saying that we believe the best way to treat SMA patients is by treating both the motor neuron with SMN protein and the muscle by eliminating myostatin because it's those two things that actually make up the motor unit, which actually is what provides patients motor function. And why would anyone want to have the body's natural negative regulator for muscle growth floating around their body if they had SMA? So we think the dynamics are really solid for demand for the drug at approval.

We'll get into, I'm sure, reimbursement and access here as well. But I think what I -- the way I would answer your question is I think it depends on the patient, their patient demand for the drug and the physician as to whether or not there will be more children or more adults. I think it will be a pretty balanced mix across the board, dependent upon the physician, the patient and the family. But we just know there is very strong support to access apitegromab once it is approved because each and every patient feels like they can benefit from more motor function driven by muscle strength and muscle growth.

Just to follow up on that. What are the strategies, I guess, to maybe maximize awareness? How would you characterize kind of among the experts and the SMN community, the awareness for apitegromab today? But then do you need to get in guidelines? Do you need to have pre-discussions on reimbursement with payers? Like what types of things can you do prior to formal approval to kind of help manage that?

Great question, Geoff. It's in fact, one of the benefits of the delay we've had over this past year is we did build a U.S. commercial organization and U.S. medical organization that was ready to launch last September. Fairly small, didn't really burn us from an expense perspective. In fact, Geoff, to your point on awareness, it's actually been quite helpful to map out the patient journey at all the SMN. There's 140 SMA treatment centers in the U.S. It actually helped us to educate the community that the innovation around motor neuron health has been incredible from SPINRAZA, Evrysdi, Zolgensma, incredible. But that the principal organ clinically affected for patients with SMA is the muscle. It's actually in the disease. And so that education that motor function is a sum of motor unit strength, not just motor neuron, not just muscle, but the combination of those two has really been helpful. And so we've seen surveys done in 2025 versus 2026 that show last year at this time, about 1/4 of KOLs said they would call all of their patients and offer them apitegromab at approval. That number a year later, that percentage has jumped to like 42%, 43%.

So just with the awareness factor, and I think patients thought apitegromab was coming last September. I think that delay has created even more interest in accessing the therapy. And that's why we think the landscape is pretty strong from the outset on demand. Obviously, as a once-monthly infusion, we'll have to be thoughtful about pricing reimbursement and access to treatment, which always can be a little bit of a bumpy road when you're introducing a new drug. And certainly, we can speak about that as well. But I think the demand dynamics and the awareness of this therapy. And I think the patient advocacy groups like Cure SMA have been wonderful about getting the message out that this is the first and only muscle-targeted therapy to likely be approved by regulators and available for patients here in 2026.

Maybe be helpful just to talk through like maybe your market research on the different modalities in SMA. And initially, obviously, you started off with just SPINRAZA and then you've layered on multiple therapies. So how has the sort of from mono to doublets? Is that still -- is that still reasonable going forward? You probably won't have a triplet type of approach. But I don't know, maybe that's not a crazy scenario.

Yes. I mean we're sort of breaking down the treatment of SMA in three eras. There's the pre-2016 era, which was really one of a disease of high mortality, early mortality. When you would go to a patient meeting, you would hear all the ventilators in the background. There was just nothing to address motor neuron or muscle health. One of the only therapies patients had was like physical therapy and then supportive care like vent support. Then the needed innovation was ushered in by SPINRAZA first and then, of course, followed by Zolgensma and Evrysdi. And again, all focused on SMN protein production to try to preserve whatever motor neuron function one could have. And at the same time, as patients have been living longer, they now want to live better. They really want to be able to do more. They want more self-care. And they view that as being driven by, again, muscle strength and motor function, which is why more than 90% are saying that is their #1 need, and that's consistently coming out of Cure SMA surveys.

And so I think what we've done well, Geoff, is to differentiate that we are a completely different modality that is not in competition with the SMN-targeted therapies, but we are truly addressing the other half of the motor unit, which is the muscle. And again, the way we designed our clinical trial showed that if you did nothing at all, this is what your outcome will be from a motor function perspective. And then if you take your background SMN-targeted therapy and apitegromab is also administered to patients, you have, again, an improvement in motor function.

And by the way, in our long-term data from our Phase II trial, we see that patients plateau, but never really are giving up their gains that they had. And we think that is just such an important element of the outcome. I think it's also why, by the way, we're at 95% compliance, 250 patients in our Phase II, Phase III clinical trials. Those patients remain on therapy upwards to 7 years later. And so back to your point, Geoff, I think like where we come from is no matter what the physician and patient want for SMN protein production is fine for us. That's actually great for us. We just think they're only going to have one choice to address the muscle component of the disease, and that is going to be apitegromab. And so we get super excited about that.

One other element I just want to underscore to Geoff's point about how much more the patients want. Even though there is no well-controlled clinical trials using more than one of these SMN-targeted therapies at the same time, about 1/3 of patients in the U.S. are either sequentially or concurrently getting two or more of these treatments. They might be getting Zolgensma as a onetime gene therapy and then followed up with Evrysdi and SPINRAZA. Some are getting two or more of these therapies, all because physicians and patients do want more motor function. And we think that bodes well for us. As to whether or not there'll be triplet therapy for some of these folks on two therapies or not, I don't know. But I do know that, that is certainly underscoring the need for more innovation. And so what we see, right, first era was no innovation. Last 10 years have been the era of SMN-targeted therapies ushered in the massive era of innovation for patients with SMA. Now 2026 and beyond ushers in the muscle-targeted era of innovation for the SMA community, and we're excited to be really at the forefront of bringing that forward.

Great. So maybe now let's pivot over to the payer side of things. I know you kind of touched on some of the challenges and maybe some of the bumps in the road that can be part of launching a rare disease without a J-code implemented immediately. So maybe talk a little bit about expectations for the initial launch, maybe some of the authorization criteria that patients and physicians may have to go through, and maybe what your expectations are for some of the greater friction points in the first 6 months to the year.

Yes. Thank you for raising it because we do think this is a sophisticated community with great levels of persistence in everything in their life. They've obviously all already had experience with payers to obtain their SMN-targeted therapy. And yet we do expect with any new rare disease therapy, there will be some speed bumps along the way. We think that -- while we think demand will be high and while we have actually developed a patient assistance program known as Scholar Rock Supports, every patient and family will be assigned a Scholar Rock sort of care coordinator to help usher them through the reimbursement process. There are a number of things that we think could delay access to treatment. I don't think it will be a stop sign, but I think it may delay in the form of a speed bump.

One, as you noted, is a miscellaneous J-code. This is a once monthly or every 4-week infusion, and we'll have a miscellaneous J-code. Let's assume we get approved in September, it would at least be Q4 and Q1 that we have a miscellaneous J-code and then starting next April, we would have a drug-specific J-code. That really does help with reimbursement and timely reimbursement. You mentioned medical policies. Let's assume from your earlier question that our label is more broad than our Phase III clinical trial enrollment criteria. We do know, and you all know this from all the companies that you cover, oftentimes an initial medical policy may be more narrow than even the FDA label. That could prevent initially some patients gaining access to treatment. But again, we think that is -- that's a matter of when and not if because it's a very difficult thing for payers to stand by.

We do think with 140 SMA treatment centers of excellence, some of those centers are going to have formulary status issues that they'll need to walk themselves through. And they'll also have to think about the logistics of integrating a once 28-day infusion into their practice. Do the patients get it at the hospital? Do they get it at the physician office? Do they get the medicine at an infusion center? And frankly, as we've also mentioned, we've -- we've got a 10,000 nurse home infusion network, and we'd like patients to be able to get it at home if that's at all possible. So I do think like we will see a high conversion rate and a short amount of conversion time, probably a year after approval, but we will definitely have to be playing a little bit of whack-a-mole in the first year along with the SMA community to make sure that every patient who can benefit from apitegromab will have access to apitegromab.

I just have a few minutes left, but I wanted to ask about the global opportunity. Maybe give us a status update on European, Japanese or OUS filings?

So in August, we announced three things related to our global regulatory update. The first is that under FDA guidance, as I've already mentioned, we removed Catalent, Indiana from our BLA and the PDUFA date remains September 30 because there was some concern that removing that might have created a delay in a PDUFA action date. That was not the case. That's number one. Number two, based on the fact, see, we never had the equivalent of a CRL in Europe. So as a result, we had received the benefit from European regulators of multiple clock stops waiting for the inspection outcome of Catalent Indiana, which was the only fill/finish facility in our MAA. And then when it came down in April, of this year -- I'm sorry, of August of this year, just last month, everyone was on vacation in Europe. There was really nothing they could do about adding the second vialer. And so it was their advice to us to withdraw the MAA. That would be the way to remove Catalent, Indiana and add the second vialer and resubmit the MAA.

We are ready to resubmit whenever they tell us to. As you guys know, in Europe, there's a specific day each month to resubmit. We're just waiting to get a go-ahead on is that this month, is that next month? And hopefully, that will be an expeditious review. But I really have no guidance on time line yet. But once they get back from vacation and give us that guidance, we'll be letting the world know probably in the form of we've now resubmitted our MAA. So there's a little bit of a pushback in Europe. We have built the team in Germany. They are ready to go. But what we announced also last month, Geoff, with a little bit of a pushback in Europe is we think it more than makes up for a little bit of a delay in Europe is the acceleration in Japan. Because if we -- if PMDA said we had to do a Japanese clinical trial, that would have been multiple years in the making. But they looked at the merits of our global clinical trial program, the importance of apitegromab for the SMA community. And they agreed that we could file our JNDA by the end of this year. And again, we'll be able to advise when we submit, when it's accepted and what we think the review time line will be. But as you know, as a 120 million population country, that more than makes up for a little bit of delay in Europe, where we would have only initially launched in Germany an 80 million population country. So we're super gratified for that.

As I think all of you know, there are no other muscle-targeted therapies even in clinical development in SMA. So our ambition to reach patients in 50 countries around the world, Europe, U.S. and Japan gets us to close to 30. We think we're well on our way to doing that without any meaningful competition over the next 5 to 10 years. We think this is really our market to develop and grow and protect with a significant moat for many years to come.

With that, David, Vikas, thank you very much.

Great to be here with you, Geoff. Thank you.

Good morning, ladies and gentlemen, and welcome to Scholar Rock's Second Quarter 2026 Conference Call. [Operator Instructions] This call is being recorded on Thursday, August 6, 2026.

I would now like to turn the conference over to Scholar Rock. Please go ahead.

Good morning. I'm Laura Ekas, Vice President of Investor Relations at Scholar Rock. With me today are David Hallal, Board Chair and Chief Executive Officer; Akshay Vaishnaw, President of R&D; Keith Woods, Chief Operating Officer; and Vikas Sinha, Chief Financial Officer.

During today's call, David will provide introductory remarks and a business update. Akshay will review our R&D progress. Keith will provide an update on our commercial readiness activities and Vikas will provide a financial update. We will then open the call for questions.

Before we begin, I'd like to remind you that during this call, we will be making various statements about Scholar Rock's expectations, plans and prospects that constitute forward-looking statements for the purposes of safe harbor provisions under the Private Securities Litigation Reform Act of 1995. Any forward-looking statements represent our views only as of today and should not be relied upon as representing our views as of any future date. I encourage you to go to the Investors and Media section of our website for our most up-to-date SEC statements and filings.

With that, I'd like to turn the call over to David. David?

Thank you, Laura, and good morning. Thanks to everyone for joining our second quarter earnings call. Today, Scholar Rock is operating from a position of strength as we enter a defining period for our company and for the SMA community. Across the business, we are executing with focus, discipline and urgency as we drive towards the U.S. launch of apitegromab this quarter, advance our apitegromab MAA in Europe to approval and prepare for launch in Germany, build momentum across our world-leading anti-myostatin platform and maintain the financial strength to support our ambitions. Most importantly, we are on the threshold of bringing the world's first muscle-targeted therapy to children and adults living with SMA as we advance apitegromab through the final stages of the FDA regulatory process.

Let me now provide additional detail on the ongoing review of our apitegromab BLA in the U.S. As a reminder, the sole approvability issue for apitegromab noted in the complete response letter that we received on our priority review PDUFA date last September was related to observations identified at a routine general site inspection of the Catalent Indiana fill/finish facility owned and operated by Novo Nordisk. Since our constructive and collaborative Type A meeting in November, the cadence of activities has reflected the shared understanding between us and the agency of the high unmet need in the SMA community and a shared sense of urgency to bring apitegromab to children and adults with SMA as rapidly as possible.

We are grateful for the agency's sustained level of engagement and for our ongoing dialogue, including our March 3 Type C meeting, where we discussed the accelerated progress that we had made at our second fill/finish facility and the agreed-upon data package to facilitate the FDA review of the second fill/finish facility. In alignment with FDA guidance from this discussion, we submitted the apitegromab BLA on March 30 with 2 fill/finish facilities, both Catalent Indiana and our second fill/finish facility. Our BLA was accepted in April with a PDUFA date of September 30.

Agency review of our application is progressing well. Importantly, we have significant optionality with 2 independent paths to approval, either through Catalent Indiana or through our second fill/finish facility or both, whichever is determined to be the most rapid. As it relates to Catalent Indiana, the FDA inspection classification following the April 2026 general site inspection is pending. We continue to be very pleased by the progress made at our second fill/finish facility. Importantly, the data package for the FDA's review of the second facility has been submitted and the review is progressing, underscoring our operational excellence at our second site. We now have more vials available from this facility than we do from Catalent Indiana.

Notably, vials from both Catalent Indiana and our second facility are now on site at our third-party provider awaiting packaging and labeling upon approval. As we near the final step in the U.S. regulatory process, we are well aware that patients are awaiting the world's first muscle-targeted therapy for this devastating disease.

Turning now to our commercial readiness in the U.S. Our team continues to advance our launch preparations across all key functions, ensuring we are prepared to support patients, caregivers and prescribers from day 1. Our team is ready to launch apitegromab at any time prior to and including our September 30 PDUFA date. Keith will discuss our commercial preparations in greater detail shortly.

In addition to the U.S., we continue to look forward to serving children and adults living with SMA in Europe. I would now like to provide an update on where we stand in the European regulatory process. The apitegromab MAA includes only Catalent Indiana fill/finish facility and the EMA is awaiting the FDA inspection classification for that facility. In parallel, we are engaging with European regulators with regards to potential inclusion of our second fill/finish facility in the apitegromab application. Importantly, this facility has had recent successful site inspections by the FDA and the EMA. We are grateful for the EMA's continued level of engagement, and we look forward to providing updated guidance on the potential timing of a CHMP opinion upon alignment with the European regulators.

Turning to our launch preparations in Europe. We are executing our commercial playbook, building momentum with launch readiness activities and engaging with the SMA community. We are planning for an initial launch in Germany with additional countries and regions to follow as we build out our planned 50-country operating platform. We know it is not a matter of if but when apitegromab will be approved for children and adults with SMA in both the U.S. and Europe, and we continue to work with urgency to reach the 35,000 people with SMA around the world who have received an SMN-targeted therapy.

Turning now to our world-leading anti-myostatin pipeline. We continue to make meaningful progress with our key clinical programs. We have robust enrollment in our Phase II OPAL study evaluating apitegromab in infants and toddlers with SMA. We initiated our randomized Phase II FORGE study in patients with FSHD. We are ready to engage with U.S. and European regulators on the development path of our high concentration subcutaneous formulation of apitegromab, which we will do once we have regulatory approvals. And enrollment and dosing is proceeding very well in our Phase I healthy volunteer study for SRK-439, our novel high-potency anti-myostatin antibody. Akshay will discuss these programs in greater detail shortly.

Turning now to the balance sheet. We were very pleased to have ended the second quarter of 2026 with $492 million in cash, cash equivalents and marketable securities. This cash balance includes net proceeds of $63 million from our ATM program during the second quarter. Vikas will provide more detail later in the call.

In June, we had the opportunity to be with the SMA physician and patient community at the Cure SMA Annual Meeting in Orlando. I was able to sit down with several SMA treating physicians and with a number of patients and their families. And during our time with them, we've heard some very moving stories about the impact apitegromab has had on children and adults who are participating in our ONYX and EAP programs. Our team at Scholar Rock is so inspired by these patients and by their families, and we look forward to ushering in the next phase of innovation for this community.

With that, I'll now turn the call over to Akshay for a closer look at our R&D initiatives. Akshay?

Thank you, David, and good morning, everybody. As David shared, we are very pleased that the apitegromab BLA continues to progress through FDA review with 2 independent paths to approval, and we remain on track for a decision by the September 30 PDUFA date. The FDA inspection classification for Catalent Indiana is pending. We had anticipated the classification in late July within 90 days following inspection completion based on the agency's guidelines. We remain engaged with the FDA, and we'll provide updates as appropriate.

As it relates to the second fill/finish facility, we're very pleased to report that all necessary data have now been submitted to FDA and the agency's review of those data is progressing well. We're gratified by the agency's continued support since the CRL last September from the constructive and collaborative in-person Type A meeting in November to the early March Type C meeting. Throughout, the agency has appreciated the high unmet need in the SMA community, and we look forward to the final steps in the process.

Turning now to Europe. We're pleased with the EMA's review of the apitegromab marketing authorization application and with their continued level of engagement. As we have previously noted, approval in Europe is dependent on FDA clearance of the Catalent Indiana facility, which is currently the sole fill/finish site included in our MAA. The EMA continues to await the FDA's inspection classification for this facility. Additionally, we're engaging with the EMA regarding the process to include our second fill/finish facility in our apitegromab application. Importantly, this facility is in good standing with European regulators. We will provide an update on timing upon alignment with the EMA.

Turning to our pipeline. Let me start with the Phase II OPAL trial. We continue to have robust enrollment in the study, which is evaluating apitegromab in infants and toddlers with SMA under the age of 2. As a reminder, this trial is enrolling participants who have been treated with an SMN1-targeted gene therapy or who are receiving ongoing treatment with an SMN2-targeted treatment. This study is important because it is anticipated to expand the impact of apitegromab to the full spectrum of patients, including those treated with Zolgensma. Notably, the rate at which the study is enrolling underscores the significant unmet need and the potential for apitegromab in the youngest of SME patients.

Turning now to our next indication for apitegromab, facioscapulohumeral muscular dystrophy or FSHD. FSHD is a rare devastating neuromuscular disease. It is one of the most prevalent inherited muscular dystrophies, and there are no approved therapies to date. We've prioritized FSHD as the next indication for apitegromab for 3 key reasons: first, the significant unmet need since approximately 20% of patients become wheelchair dependent. Second, the compelling preclinical data from the gold standard FLExDUX4 mouse model that provides mechanistic rationale for apitegromab in FSHD. And finally, data from randomized studies in FSHD, which suggests muscle mass can increase and has the capacity to show functional benefit.

For example, in studies of either rigorous physical therapy or treatment with anabolic agents, patients with FSHD demonstrated increases in lean mass and muscle function. These data suggest that apitegromab as a monotherapy may have the potential to bring important benefit to FSHD patients. We're very pleased to announce today that we've initiated our Phase II study called FORGE, which is a randomized, double-blind, placebo-controlled trial with a sample size of 60 patients. We're also advancing 2 additional therapeutic programs in our world-leading anti-myostatin pipeline, a high concentration subcutaneous formulation of apitegromab and SRK-439. In our subcutaneous apitegromab program, we showed some very exciting data in January from the Phase I study, which demonstrated that subcutaneous apitegromab appears to have favorable bioavailability and the pharmacodynamic profile comparable to IV administration. Additional development activities are ongoing, and we continue to plan for engagement with U.S. and European regulators later this year following approval of apitegromab.

Turning now to SRK-439, our high potency, high-affinity subcutaneously administered myostatin inhibitor. We're very excited about this program and dosing in our Phase I healthy volunteer study is progressing well. We expect to have top-line data from the study later this year.

In closing, we're executing with urgency to bring apitegromab to children and adults with SMA, whilst in parallel working to maximize our impact for patients with our world-leading anti-myostatin pipeline across a range of rare, devastating neuromuscular diseases.

I'll now turn the call over to Keith to discuss our commercial launch preparations. Keith?

Thanks, Akshay, and good morning, everyone. As David noted, with the potential FDA approval of apitegromab for children and adults with SMA by September 30, our U.S. commercial organization is launch-ready across all key functions, and we are prepared to support patients, caregivers and prescribers from day 1. Given the significant unmet need in SMA, we have moved with urgency to build our commercial operations to ensure that patients who can benefit from apitegromab will have broad and reliable access to apitegromab.

In the U.S., despite approximately 78% of children and adults living with SMA receiving an SMN-targeted therapy, 95% of patients continue to experience persistent and progressive muscle atrophy that limits both function and independence. As further evidence of the unmet medical need, data shared with us by Cure SMA show that an estimated 1/3 of people living with SMA in the U.S. have received 2 or more SMN-targeted treatments, either sequentially or in combination. This data again underscores the significant opportunity we have with apitegromab, the world's first muscle-targeted therapy for children and adults with SMA.

Since our last earnings call, our U.S. field team continues to broaden their reach, focusing on disease education and awareness around the unmet medical need while also reinforcing a broader understanding of SMA as a disease that consists of both the motor neuron and the muscle, the principal organ impacted by the disease. We are also expanding our reach and frequency across approximately 140 SMA treatment centers, 2,600 prescribing physicians and their multidisciplinary care teams. Through these engagements, our field team is establishing case flows on a center-by-center basis to ensure that upon approval, we are well positioned to support the SMA treatment centers once apitegromab treatment decision has been made.

This past quarter, we have also strengthened our Scholar Rock Supports patient services program. The Scholar Rock Supports team is fully trained and prepared to provide comprehensive individualized support to patients and caregivers at launch. Eligible patients and their families will be able to access this program to understand insurance coverage, identify available financial and co-pay assistance and navigate treatment logistics.

Turning now to patient engagement. Our connections with the SMA community remains strong. This past June, we had a significant presence at the Cure SMA Annual Meeting in Orlando. Scholar Rock served as a presenting sponsor of the meeting and throughout the week, our teams engaged with health care professionals and members of the SMA patient community. I was very pleased that the Scholar Rock Symposium for health care professionals entitled Expert Perspective on the Evolving Management of Spinal Muscular Atrophy was one of the most attended expert sessions during the meeting.

Equally, our patient symposium, Muscle, there's more to the story in SMA was attended by hundreds of SMA patients, caregivers and families. And during this session, we sought their perspective on needs and priorities for people living with SMA. Every interaction we had during this meeting reinforces our determination and further strengthens our commitment to serve patients and families.

Turning to U.S. reimbursement. Our market access team continues to advance discussions with national and key regional payers as well as Medicare and Medicaid with the goal of achieving broad reimbursement for eligible patients after approval. Given the significant scope of our efforts and progress we've made in the past several months, we are ready and well positioned to successfully support apitegromab in the U.S. immediately upon FDA approval.

Turning now to Europe. We are advancing our launch preparations with a particular focus on Germany as we work with the EMA on the next steps for our application. Our team in Germany is using this additional time to execute the same launch readiness playbook that we have successfully deployed in the U.S. over the last several months. This includes broadening and deepening of relationships with key SMA treatment centers and potential prescribers. In parallel, we are engaging with SMA advocates across Europe, participating in educational programs at various congresses and symposia hosted by patient advocacy organizations.

As it relates to reimbursement and patient access, following European Commission approval of apitegromab, we will be prepared to rapidly advance reimbursement submissions in Germany and other key markets. In addition, we are advancing our distributor relationships to extend the commercial reach of apitegromab across multiple additional countries.

In closing, we are fully prepared for a successful U.S. launch immediately upon FDA approval, while advancing our launch preparations in Europe and working to establish our 50-country operating platform with the ambition of reaching the estimated 35,000 patients living with SMA worldwide who have received an SMN-targeted therapy. We are ready to usher in the next phase of innovation for children and adults with SMA, one patient, caregiver and family at a time.

With that, I'll turn the call over to Vikas for a review of our financial performance. Vikas?

Thank you, Keith. As we have shared previously, our financial objectives for 2026 remain focused on supporting our commercial build to deliver a strong apitegromab launch, funding R&D activities to advance our pipeline and expand our leadership in the myostatin and muscle space and continuing to evaluate opportunities to strengthen our balance sheet in a way that supports long-term shareholder value.

Consistent with these priorities, I'd like to briefly review our second quarter financial results. For the second quarter, we reported $108.9 million in operating expenses, which included $19.7 million in noncash stock-based compensation. Excluding stock-based compensation, operating expenses were $89.2 million. As we continue preparing for the anticipated launch of apitegromab, we have strategically increased our commercial investments while keeping our overall operating expenses at the levels generally consistent with the second quarter of 2025. This disciplined approach to capital allocation has enabled us to advance launch readiness while continuing to invest in our key R&D programs and strengthening our global supply chain.

Turning to our balance sheet. We ended the second quarter with $492 million in cash, cash equivalents and marketable securities. During the quarter, we further strengthened our cash position with $63 million in net proceeds from our ATM program. Looking ahead, our FDA approval of apitegromab, we will have an option to draw down an additional $150 million from our existing debt facility, and we plan to monetize a priority review voucher to further strengthen our balance sheet.

We continue to operate with a disciplined financial plan and our investment priorities remain focused on our apitegromab commercial launch readiness in the U.S. and Europe, strengthening our supply chain to support our expanding pipeline and anticipated global commercial demand for apitegromab over time and advancing our highly innovative clinical programs that Akshay discussed earlier in the call.

With that, I'll turn the call back to David. David?

Thanks, Vikas. As we look ahead, Scholar Rock is entering one of the most important chapters in our history from a position of strength. With 55 days until our PDUFA date, we have the team, the financial foundation and the operational readiness to execute with confidence. Across the organization, our teams are prepared, energized and focused on what comes next, bringing forward the world's first muscle-targeted therapy for children and adults with SMA. We are moving into these final 55 days with urgency, discipline and a deep sense of responsibility to the SMA community. We know what is at stake. We know what is possible, and we are ready to deliver.

As we close, we are mindful that August is SMA Awareness Month. This is an important opportunity to recognize the strength and resilience of the individuals living with SMA, their families and the advocacy organizations that work tirelessly on their behalf. We are grateful to the patients, caregivers, health care professionals and advocates whose partnership continues to advance awareness, earlier diagnosis and access to care. This month reinforces our commitment to the SMA community and our focus on delivering meaningful innovation that can make a lasting difference for people living with this rare and devastating disease. We look forward to updating you on our continued progress.

And with that, we'll now open the line for questions. Operator?

[Operator Instructions] The first question will be coming from the line of Eric Schmidt of Cantor.

Appreciate all the updates. My question is on apitegromab's second fill/finish provider. How confident are you that this facility alone independent of Catalent can support approval by the PDUFA? And can you share any kind of anecdotes from your FDA interactions to support that they're making progress in the review of the package you submitted?

Thanks very much, Eric. Yes, as we noted, really dating back to that March 3 Type C meeting, we were really gratified as we were updating the FDA on the rapid and meaningful progress we were making in our second facility that really together, we agreed that resubmitting our BLA with 2 fill/finish facilities and actually having a plan to enable an apitegromab approval with the fastest path, whether or not at the Catalent Indiana, the second fill-finish facility or both, we were gratified that there was a complete alignment between us and the agency that that was the best approach.

As we've noted on the call, the team here at Scholar Rock and the second facility, we're really proud of their efforts to now have more vials of apitegromab ready for launch from this facility than we do from Catalent Indiana. And frankly, than we did from Catalent Indiana at the time of our last PDUFA date, I think, underscores how well we are working together. The review, I think, as both Akshay and I noted, is progressing well. The FDA has all of the data that we agreed upon during our Type C meeting that was going to enable the review and eventual approval from that second facility. So we're pleased with that. And as we're noting, we're corresponding with the FDA on that.

I would also note a couple of other facts that I think are important here. That second facility has had successful recent site inspections by FDA and EMA. None of the approvals from this facility in the last 12 months have required a PAI or a PLI. And I think underscoring the performance of that facility during that time, the site underwent multiple routine GMP general site inspections by EMA and FDA. So we feel really good about the position that we are in. And then I might close by saying we contemplated the, well, what if we remove one of the facilities from the application? Could it impact our time line at all?

And that was contemplated and discussed between us and the agency. And based upon our discussions with the agency dating back to those March discussions, we do not expect that removing a facility from the application would have any impact on our ongoing review time line at all. So Keith and team are ready to launch at any time between now and up to our September 30 PDUFA date. I'm certainly gratified by Scholar Rock's technical operations and quality team. They have stood up this second fill/finish facility faster than almost any example we can find in the industry. And they now have more apitegromab vials that will be commercially available from this second facility, and they are at our labeling and packaging site awaiting approval. We're super excited. So we'll continue to keep you all updated over these last 55 days, but we feel like we're in a really good position.

And the next question is coming from the line of Kripa Devarakonda of Truist Securities.

Congratulations on all the progress. I have a follow-up question on Eric's question regarding the second site. David, you just mentioned that you can drop one of the sites at any time and it won't delay. But I was wondering if Catalent remains classified as OAI, is there a deadline or a date for administratively withdrawing that site, so it doesn't trigger any delay for your PDUFA?

It's a great question, Kripa. We are in correspondence with the agency. They are -- we're both well aware that the inspection classification is still pending from the April reinspection. As Akshay noted, it's now drifted a bit beyond the 90-day guidance period, but it is only a guidance period from the FDA that they would classify an inspection.

And look, we're very direct with one another about when we would reach that step, should we need to reach that step in your example that you provided, let's just say the inspection classification reveals that there's no change to the current OAI classification. We've discussed with the agency, it would be a relatively simple step to notify them that on their signal that we are removing that site and the review would progress with that second facility. So -- and again, with our alignment with the FDA, we would expect no impact to the ongoing time line. So that's where we are. I think Akshay and I are both heartened by the fact that we have ongoing open correspondence with the FDA and the review is progressing well.

Our next question is coming from the line of Tessa Romero of JPMorgan.

So just to double-click here on some of these earlier comments, what are the specific items procedurally from now to September 30 that still need to be kicked off to allow for an approval? I think Akshay used the words final steps. And just to set the record straight, is there any reason to believe that the FDA will not be able to complete this review by September 30?

Yes. I'll just hand it over to Akshay, but just to underscore that last question. There really is no reason to believe that the work that's been done at the second facility and where we believe the FDA is in terms of reviewing the application, which, as you recall, right, our resubmitted BLA really only included the new information from the second facility and the updated safety database. There's no reason to believe the FDA can't get their work done in these next 55 days. Akshay?

Yes. I would just reconfirm that. So starting last November when we had a face-to-face meeting with the FDA with all relevant parties and in March, the FDA guided that Catalent is the lead site in the MAA, but the second site would be welcome because it gives them greater ability to help us get this drug approved in a compliant manner to patients in a high unmet need setting. at the March juncture, we said we're ready to submit a second fill/finish site. They welcome that.

We talked through the process of how to get to submission and then the finish line with the PDUFA date, and we are exactly on track with all of that. Their review of the second fill/finish site is progressing well. And as David said, we see no reason why we can't get to the PDUFA date with this drug approved before or at that time. And so it certainly feels on track. And we're very grateful to the agency's guidance and the expeditious manner in which they've been working with us and the true engagement and partnership.

Our next question is coming from the line of Michael Yee of UBS.

This is Madeline on for Michael. Congrats on all the progress and thank you for the updates today. We were just wondering, do you have any color or any feedback from the FDA on that later-than-expected reclassification of the Catalent site, given the decision was sort of expected by the end of July, if you just have any feedback you could pass along.

Yes. The only thing that we would note is, obviously, the inspection report is public as on the 483 observations in that inspection report. We are well aware that Novo Nordisk provided a pretty robust response as they had the option to do within 15 days of that inspection. So there was a lot there for the FDA to review. And I would just note that that guidance period is a guidance period. We're aware that sometimes the FDA does take a bit more time than that 90-day period. And as we noted, we're awaiting that. I'm sure our friends at Novo Nordisk are awaiting that inspection classification.

While in parallel, the EMA is awaiting that classification, we're also engaging with our European regulators on the inclusion of our second fill/finish facility. So there really is nothing more to it other than the fact that it does happen. The 90 days are not a statutory requirement. The FDA literally has provided that as guidance. There's probably a lot there that the FDA is reviewing. And we await like everybody else the pending inspection classification. But I'd bring it back to this, both in U.S. and Europe, we're continuing to move forward with this meaningful progress that we've made with our second fill/finish facility, really wanted to make sure that we had a belt and suspenders approach to serving children and adults living with SMA and their families. And we feel like we're in a position of strength as we move forward. And we await like everybody else, that inspection classification.

The next question is coming from the line of Cory Kasimov of Evercore.

I guess I'll shift gears a little bit here and I want to ask about your national and regional payer discussions. And curious how they're framing apitegromab in step edit terms. Are you seeing any payers signal that they'll impose time limits or require a rereview of benefit after a shorter initial authorization?

Thanks, Cory. I'm going to hand that over to Keith for his comments. I would just note as a headline as Keith is prepared to answer that we do believe this robust clinical development program that we've been running for 7-plus years. And again, the fact that we met the highest bar, which was the Hammersmith motor function scale in SMA with a stat sig result from our pivotal SAPPHIRE trial, the robustness of that data sets up very, very well. As you know, and I'll just underscore for everybody listening in.

I know you know it quite well, Cory, patients were randomized who are on ongoing SMN targeted therapy to receive either placebo or apitegromab. So they were on these ongoing therapies. And again, to hit that highest bar of the Hammersmith Motor Function Scale in SMA at stat sig with 0.019 p-value, we feel with a very low number of patients, we think sets up very, very well for those national and regional payer discussions. Keith?

Yes. Thanks, David. Look, as I stated in the prepared remarks, the team has been working and really extending not only our reach with these various payers, whether it's the commercial payers or government payers, but also the quality of the meetings by bringing in members from our medical team to discuss the robust clinical data package from our apitegromab studies and ultimately with the goal of making apitegromab available for the broadest possible audience of children and adults living with SMA.

So as I've stated before, the real goal with these meetings is to be able to create policies as rapid as possible and policies that we believe will align more with the potential label, the FDA label and less with an inclusion/exclusion criteria from our SAPPHIRE study. With all that being said, if you take a look at the data on treatment for SMA, so I'm talking about the 3 SMN-targeted therapies that are available, almost 100% of them have a prior authorization. So I fully expect that you'll see that apitegromab will have a prior authorization even when we have favorable policies that are constructed.

Next question comes from the line of Amy Li of Jefferies.

Congrats on the progress. I just wanted to put a finer point on the second fill/finish facility. You mentioned that you submitted data that the FDA requested the Type C, which sounds encouraging. But could you give us a sense of what was included in that data package? Are stability runs and release testing for this facility fully complete and you would consider the facility launch ready? And do you expect any additional clearance from the FDA?

Thanks, Amy. Yes, I mean what was inclusive and what we agreed upon was obviously the data that we generated from engineering runs, PPQ runs, the FDA has the full package in hand where we know their review of that is progressing well. We're in correspondence with them on that. Everything is straightforward and perfunctory. And there is, I guess -- just to underscore the question, there is no more testing that is required for the product that has been vialed at that facility at all. And again, as noted, that product is at our third-party labeling and packaging facility awaiting approval to support the launch. And of course, in a belt and suspenders approach, we have vials from Catalent Indiana at the packaging facility as well. So we're in a really good position.

We're gratified to have reached an agreement with the FDA in March at the Type C meeting on what was required. I would note that what was required was delivered to the FDA in a very timely fashion because you don't only agree on what is submitted, but when it would be submitted within your framework of your PDUFA date, and we felt like we delivered that in a very, very, very timely fashion. And we're looking forward to these next 55 days to get through the final step and eventually launch apitegromab. So thank you very much for your question.

Our next question is coming from the line of Gary Nachman of Canaccord.

So as you've been preparing for a while now with the commercial team, any other initiatives you need to put in place between now and approval? Or is it just really waiting for the final label? And what's the low-hanging fruit to go after with SMA patients where there could be a fair amount of pent-up demand for apitegromab? And how long do you think it will take to get those patients on board?

Yes, I'll start and Keith will get in. But I think the -- as I mentioned during the call, Gary, we spend a lot of time with the community, patients, their families, the advocacy groups, the health care providers. And our ambition is that any patient living with SMA that can benefit from apitegromab should have access to apitegromab. And so we really do look at this holistically across the 35,000 patients globally that have received an SMN targeted therapy, and we believe that we can really offer meaningful benefits to them. So we do think about it very holistically. Keith can share with you some of the dynamics at launch, but I think our general view is it could vary patient by patient, family by family, physician by physician in terms of their thinking about commencing treatment. Keith?

Yes. Thanks, David. I guess, first of all, what else is there to do? The point I want to make really clear is we are ready if we were to get the call tomorrow. The team is kind of chomping at the bit to really get out there and launch this product. With that being said, there's always additional work that we can do. One of the main things that's taking place that I mentioned is really working with the various centers, so that we can be prepared with these treatment centers on a case-by-case basis to work through the process of enrolling patients into our Scholar Rock Supports program. We cannot begin to do any of this until after we have FDA approval. So we are doing a lot of dry run work here, so that we can have a seamless and flawless execution as we take patients from being prescribed the product to ultimately being able to receive the product.

Where do you think some pent-up demand is? I've shared before on previous calls. We do have an early access program. Those will be the first patients that we will be focused on, converting from early access product over to commercial product. That being said, we don't have full line of sight into what insurance coverage these early access patients have. So we're going to have to be going through that process and enrolling them in our program. The next will be our open-label extension patients, our ONYX patients. I want to remind you that they will have to go to a closeout visit of that study before they can even convert over to commercial drug, but we will begin to work them through the process of our Scholar Rock Supports program.

So when you ask how long will it take, it will take time, mostly because you're going to see a prior auth with all of our patients that are going to be prescribed apitegromab. The majority of them, you are most likely going to receive a denial for various reasons, whether it's a J-code or a policy not created or for some other reason. That will then send us into an appeal process, which can sometimes take some time. So I think that there will be certain patients that will have coverage that will allow them to go on sooner rather than others. But -- what I've typically seen in other launches is during this first 6 months of launch, while we will be without a J-code, the time -- the average time from prescription to a patient actually being able to get infused is greater than 60 days.

Next question is coming from the line of Marc Frahm of TD Cowen.

Maybe just -- I mean it seems like the medical review is kind of done on both sides of the Atlantic. So maybe you can speak to kind of the labeling discussions? And do you expect a largely identical label? Or do you think there are maybe important differences between the U.S. and European label? And then I'll have a follow-up.

Yes. No, it's an important question. As you know, Akshay and I both addressed that we felt like we were in a really good spot at the end of the last review period with the FDA, and we're going to be picking it up or we picked it up in the BLA right where we last left off and then the comparisons between the 2, Akshay can comment.

Yes. I would just say we are very happy and comfortable with the way the dialogue has gone through the medical review. And obviously, it's not for us to comment on the final label, but we are certainly grateful for the engagement and very constructive conversations. So we look forward to getting this drug approved in U.S. and Europe. And I think we'll be comfortable with how to get it to the right patients.

Yes. And Marc, I think due to the great work by Akshay and the entire team, I think at the end of the day, we ask ourselves, are we going to have an opportunity to serve a meaningful number of patients living with SMA in the U.S. and Europe. And again, eventually, our ambition is to reach patients in 50 countries around the world. And I think that Akshay has put us in a really good -- and the entire team, Jing and the entire team has put us in a really good position to be able to do that. But Akshay is right. until we have final USPIs and SMTCs, I think we'll comment on that when it's the right time. And hopefully, that time is coming in the coming days.

Okay. That's helpful. And then just on the CMC side, EMA clearly seems to be essentially deferring to the FDA on the Catalent Indiana facility. Do you expect them to ultimately act kind of similarly with the second facility? Or is there something about the -- either that facility itself or the flexibility that the FDA has kind of granted you in terms of CMC requirements there that might lead the EMA to kind of be more proactive itself in making a decision?

It's a very thoughtful question, Marc. Akshay?

Yes. I mean, in our prepared remarks, we emphasized that the second fill/finish facility is in very good standing with regulators, and we're delighted that that's in progress with the FDA. Now with respect to the EMA, obviously, any approval for apitegromab that involves the second facility will help. And we are right now heavily engaged with the CHMP to work on the progress of the MA to completion and how we incorporate the second fill/finish facility, if necessary.

Next question is coming from the line of Kalpit Patel of Wolfe Research.

One for Europe. If the FDA maintains the OAI classification for Catalent, can you walk us through your potential time line to get the second fill/finish facility into the MAA and your thoughts on the earliest projected time line for European approval?

Yes. No, thank you very much. And as we noted during the call, while EMA and we await the classification decision from the FDA in parallel, we're having the dialogue. The EMA is very well aware of where we are with the second fill/finish facility. Akshay?

Yes. And as that dialogue is ongoing, I don't want to second guess what the final advice will be vis-a-vis necessity or the mechanism by which we incorporate the second fill/finish facility. But suffice it to say that the engagement and flexibility that both FDA and CHMP have shown us is very gratifying to us. They appreciate the unmet need, and they're working with us. So we will be guided by them. That's an ongoing conversation. And hopefully, soon in due course, we will update every.

I think just as a capper, I think what Akshay and I really gratified, just as we've experienced with the FDA, we're just gratified by the receptivity and the dialogue with EMA. But again, we'll await the specific approach pending the inspection classification and of course, in parallel, our discussions on the second facility.

Our next question is coming from the line of Etzer Darout of Barclays.

This is Luke on for Etzer. For FSHD, on the clinical trial side, I know you guys mentioned that you're looking to focus in slightly less severe patients and you're listing the participation reporting is 1.5 to 3 on a Ricci scale on a 0 to 5 scale. I just want to verify that you're using a modified scale there because I think the Ricci scale is 0 to 10. And could you give some color as to what percentage of the FSHD population falls within that scale range?

Yes. We're using the same Ricci scaling system or scoring system that Roche folks are used. And I think I just want to confirm what you said that we're indeed focusing on patients with the Ricci score of 1.5 to 3 because once you get beyond a score of 3, we know from an FSHD database we have access to, and I don't know whether Roche had it or not, but we know that by MRI, many muscle groups, including the quads, which was the primary endpoint, begin to show significant fat infiltration and fibrosis. So focusing on patients with the higher scores, I think, is a tough ask. And so you need some muscle preserve so that the anti-myostatin can act on it to boost muscle mass and hopefully function too.

Also, in terms of functionality, you'll note that their inclusion criteria included 10-meter walk between 4 to 12 seconds. So the upper bound 12, whilst we've stipulated that the upper bound or our 10-meter walk is less than 5. So we're certainly in that mild-to-moderate group of patients whilst they were in the moderate to severe.

As to the exact numbers of patients, this is the common muscular dystrophy or there's at least a very significant 5-digit number of patients around the world to help. And I think we're comfortable that we will help many, many patients should this drug ultimately be approved in that space. So I'm not concerned about that. And of course, as we know in all these rare diseases, as soon as the therapeutic appears, the rate of diagnosis improves and the rate of access to therapies improves and patients start getting put on therapy earlier and earlier in the course of their disease. So we're looking forward as we announced today to getting momentum going now in the study. The study is initiated, and we're excited to do this study where we have wonderful mouse data and where we think there's a robust rationale with our drug.

Next question is coming from the line of Basma Radwan of Leerink Partners.

Could you please share your perspective on Regeneron recent updates regarding the Eylea high-dose prefilled syringe? Specifically, management indicated that it plans to add a third plant on the regulatory package to enhance the likelihood of approval. How do you interpret that decision given that the situation is very similar to yours with regard to Catalent's involvement? Do you think it suggests that Catalent problems may be still outstanding? That's it for us.

Well, we know -- first of all, I don't -- I can't really comment on Regeneron other than to say I think we have a very different situation because our second fill/finish facility is different than their second fill/finish facility in this case, from our understanding. So that would just be a bright line. The similarity is that we both have Catalent Indiana in our applications. So I really can't comment on their commentary beyond the fact that I would note that our second fill/finish facility is in good standing with the FDA and EMA. They've had several general site inspections by FDA and EMA in 2025 and 2026. Their last 12 months of approvals for products there, and they have like nearly 3 dozen or more commercially available products from that facility.

But in the last 12 months, all approvals from that fill/finish facility, the PLI/PAIs have been waived by the agency. So I would just comment that, yes, as we've noted, the Catalent Indiana inspection classification is still pending. So that could be one thing that what you're referring to means. But they're very different situations in that we have a different second fill/finish facility.

And the last question will be coming from Geoff Meacham of Citigroup.

David, in line with your belts and suspenders comment, does the second facility provide a fully independent approval path? Or are there any elements of the filing that are still dependent on Catalent Indiana? And then second question, maybe for Akshay, what regulatory work will be required to get subcutaneous apitegromab into the next sort of pivotal development? I just wanted to maybe go over that.

Akshay, do you want to take?

Yes. Thanks, Goeff. So on the first question, the second fill/finish facility provides a fully independent path and the details of that were discussed in that March meeting we mentioned in the prepared remarks. So we feel good about that. And I think that sort of speaks to David's belts and suspenders comments. So that's great. And vis-a-vis the subcutaneous apitegromab, just to refresh folks in January, we shared data showing the wonderful sort of PK/PD profile of subcu apitegromab, which makes all this feasible. And we have prepared a briefing document that we will be ready to send very soon after the approval of apitegromab, so that we can engage with regulators and begin that next important phase of development to bring a subcu option for patients.

Now that involves a dialogue with the FDA because for different drugs, different paths have been adopted. There's one view of the world that says there can be a PK/PD path matching the PK/PD criteria with IV, the level of myostatin suppression and saturation and so forth. And the other extreme is you need to do more substantive development work. You mentioned pivotal. We are now finalizing the briefing doors to present the path forward that we think is reasonable, but we obviously need to engage with regulators to get their guidance. But as soon as we've done that, we will then provide an update in due course as to the path forward because that will ultimately influence the time line of getting subcu patients.

Thank you. And this does conclude today's program. Thank you so much for joining. You may now disconnect.

We can get started. We have David Hallal from Scholar Rock here with us. Thank you so much for joining us.

Maybe to start, if you could provide us an overview of your company for those who may not be familiar, including the updates that we'll see within the next year.

Great. Thanks, Tommy. It's great to be here once again at the 47th Goldman Sachs Healthcare Conference. David Hallal, Chairman and CEO of Scholar Rock, which is a Cambridge-based biotech company that has been focused on myostatin biology, and we're very proud that we are the world leaders in myostatin biology. This is obviously a target that was identified in 1997.

The first anti-myostatin inhibitor went into the clinic in 2004, 2005. And really, over the period of these last 20-some years, there have been multiple myostatin inhibitors that have failed in clinical development. We stand alone with our unique technology platform and approach to myostatin biology as the first and only company that has successfully developed a myostatin inhibition program through mid- and late-stage development with a successful Phase III trial with our lead asset, which is apitegromab for children and adults living with SMA.

As Tommy has asked, what does the next 12, 18 months look like for our company? We're super excited having hit a statistically significant and clinically meaningful benefit in motor function with the highest gold standard measure of the Hammersmith Motor Function Scale in SMA for children and adults living with SMA to now be on file with both the FDA and the European Medicines Agency with action dates this year in 2026. So we're looking forward to launching apitegromab into the spinal muscular atrophy space in 2026 in both the U.S. and in Europe. And then eventually, as many of us have done at prior organizations, we'll look to commercialize apitegromab in up to 50 countries around the world so that we can meet patients with SMA wherever they may be.

Beyond apitegromab in SMA, we're also very excited about some additional programs that we have ongoing. We are going to be commencing just after the middle of this year, a trial with apitegromab for patients with FSHD, which we can talk about. It's a Phase II trial, randomized, double-blind, placebo-controlled. And we are also making sure that no patients with SMA are left behind. So we do have an ongoing Phase II trial, our OPAL study, which is for those patients that are under the age of 2, so the youngest of patients living with SMA.

And then to advance our technology platform forward, we can also catch up on the progress that we're making with a subcutaneous version of apitegromab as well as SRK-439, which is in and of itself, a different molecular entity. It's a high potency, high affinity, low-frequency, low-volume subcutaneous injection. And that program is in healthy volunteers today, and we'll be reading out that healthy volunteer study toward the end of 2026.

Okay. Great overview. And as we start with the SMA market, so multiple treatments, multiple modalities. As you think of your positioning as an add-on to improve muscle strength, who are the early adopters in terms of phenotype and combination therapy? And who do you think it will take some more time to reach?

Yes. It's a great question. And maybe where I'll start, Tommy, is that really before 2016, SMA, which is a devastating disorder, really was in very, very high need for innovation. And so over the last decade, what we've seen is the initial phase of innovation was ushered in for the treatment of patients with SMA, all focused on motor neuron health. And so these programs are SPINRAZA from Biogen, Evrysdi from Roche, Zolgensma from Novartis.

And really, what we've seen over the last 10 years is that patients are living longer and having greater motor function from the focus on stimulating SMN protein, either SMN protein 1 or SMN protein 2. Obviously, SMN means survival motor neuron protein. And so these are necessary to protect the motor neuron from death. And what we have seen from this last decade is that patients indeed are doing a little bit better. So patients are living longer, but they really are claiming almost all of them that their #1 need is more motor function and more muscle strength.

And so important to note that the motor unit, which is responsible for motor function is not just comprised of the motor neuron, but it's comprised of the motor neuron and the muscle. The muscle is the principal organ that is clinically affected in SMA. And over these last 10 years, where we've seen needed innovation around motor neuron health, there has not been anything to address the muscle component of this disease.

And so we were super gratified with our Phase III SAPPHIRE study to show for the first time that patients that were on these SMN-targeted therapies, if you will, were randomized to either receive placebo or apitegromab. And in our Phase III trial, what we were able to show is substantial improvement, stat sig in motor function using the Hammersmith Motor Function Scale and also nearly a 4x greater likelihood of patients having a 3-point improvement on this motor function scale when they received apitegromab as opposed to the SMN-targeted therapies alone.

So the way that we look at this is definitely not like an add-on therapy, but for the first time, we can start to treat the entire disease of SMA with these wonderful sort of SMN-targeted therapies focusing on motor neuron survival and motor neuron health, but then also addressing the muscle component of this disease.

And so coming back to your question, when we look at the market, we really think every patient is going to be eligible for treatment because muscle is the principal organ clinically affected by this disease. And whether those patients are as we've seen with SMN-targeted therapies alone, those patients tend to do better in the first 1 to 2 years, but then they plateau.

And then we've actually seen in the long-term extension trials of those therapies or even in our Phase III trial, where the average patient was on those therapies for 5 or 6 years, there's usually a return to the progressing form of SMA where those patients start to lose motor function again. And so what we were able to show in our Phase III trial as opposed to a loss of motor function, there was now a gain of motor function when those patients were randomized to receive apitegromab.

So we feel like now with patients who have been on our therapy from our Phase II trials for upwards to 7 years, that whether or not patients are improving on SMN-targeted therapies, whether or not they have plateaued or whether or not they have returned to the progressing form of the disease, they are all candidates for treatment, and we will be really discussing with the patient community and the physician community, the importance of not only wanting as much SMN protein as you possibly can get from those highly innovative SMN-targeted therapies, but every patient with SMA should also want any myostatin, which is the body's natural negative regulator for muscle growth. So you would want to eliminate that in any patient with SMA. And we think it's quite a compelling case as to why there's a very, very broad group of patients that are going to be applicable and targets for apitegromab therapy.

Interesting. And you have had some announcements on the regulatory side around manufacturing, especially the Catalent, Indiana facility. What are the next updates here and the impact to commercial supply as you look to a potential launch?

Yes. Tommy raises a very good point. We had a look at our Phase III study and presented it in Q4 2024, which was, again, for the first time after 20 or more years of efforts to effectively target and block myostatin apitegromab and Scholar Rock was the first and only effort to be successful. Based upon the strength of our Phase III study, the FDA granted us a priority review when we had submitted our application in 2025 with an action date of September 22, 2025.

We, of course, had a very successful review with the FDA, except for the knit of our fill/finish facility, which was Catalent, Indiana, owned and operated by Novo Nordisk. So the FDA had a general site inspection at Catalent, Indiana in the summer of 2025. During that inspection, they cited observations associated with GMP compliance. And as a result, as many of you know, a facility that is listed in any one's biologics license application needs to be in good standing and good compliance with the FDA for that drug to be approved. This ended up being the sole approvability issue and why we received a CRL after hours on September 22, 2025.

Nonetheless, we've worked very closely with Novo Nordisk. We've actually worked very closely with a second fill/finish facility, and we've been in ongoing dialogue with the FDA really since September of 2025 to get back on file with the FDA. So we have resubmitted our BLA. That BLA has been accepted, and we have a new action date of September 30, 2026.

Importantly, what's an improvement over this BLA than our initial BLA is that we now include 2 fill/finish facilities in the BLA. So we have 2 independent paths to an approval. That is Catalent Indiana, should that be reclassified from its OAI classification, which means official action indicated and is unlikely that a drug would -- a new drug would get approved under that classification. So it would have to be downgraded to a VAI only through an inspection, which we'll get to in a second.

Or the second independent path to an approval is our second fill/finish facility, which has already filed all of the apitegromab that we need for launch in the U.S. and Europe. It's also all of the apitegromab that has generated the data for review of the FDA to approve our application with that second fill/finish. And of course, there's a third potential outcome, which is we may get approved with both fill/finish facilities in the application.

And frankly, the time lines are now overlapping with one another. So the FDA did have another general site reinspection of Catalent, Indiana in April of this year. So just about 6 weeks ago. They did cite more observations at that facility, actually 8. And now the FDA has about a 90-day guidance period to make a determination as to whether or not Catalent in the inter remains in OAI or whether or not that gets downgraded to a VAI. And that 90-day guidance period takes us into late July.

At the same time, the second fill/finish facility, as I noted, has now filed all of the apitegromab that we need for launch. That is going to be available also in July to support the launch. And so what we're expecting now is the FDA to be making a determination on both fill/finish facilities. And that's why we stand ready to receive an approval and launch this drug at any time between now and up to and through September 30 and we're really excited to finally get on with the launch and serve the SMA community that is desperately waiting for the first muscle-targeted therapy to be approved by the FDA.

And understanding that you probably can't get into that much detail here, but to the extent that you can say what you're aiming for in the language for the label, maybe in terms of SMA type, age, ambulation, combination therapy, et cetera?

Yes, it's a great question. And in fact, the nice thing, if there is such a thing about receiving a CRL is, first and foremost, you know exactly what the approvability issue is. And as we noted on September 23, after receiving our CRL is the FDA made it very clear that the only approvability issue was the status of compliance at our fill/finish facility. What that meant, obviously, and we had a very successful review up until we received the CRL was that the FDA was very comfortable with the clinical package, both safety and efficacy.

And in fact, they indicated that when we do resubmit, just go back to the same label that we had sent them at the tail end of the review period, and that actually was like within 24 to 48 hours of our PDUFA, we had a good sense as to which way the label was going to turn out. And we were -- as we noted, we were pleased with where we were. There was never -- during the review, there was never a significant gap between where the review division was at the FDA and where we were in terms of what we thought would be appropriate use of the drug in patients with SMA.

To get to your point specifically, we -- the FDA has tended with the other approved treatments to be more -- see SMA as a single disease as opposed to one where they're looking at ambulatory status or copy numbers or age. They've generally taken a broader view. And so while I won't comment on the specifics of the label, we feel like we're well aligned with the FDA when we do have an approval where we will be able to address a wide range of patients living with the disease where there is biologic plausibility that by inhibiting and fully eliminating myostatin patients have the best chance for an improvement in motor function.

So we don't see any major restrictions. Obviously, we did not study -- now we are, but we did not study apitegromab in SMA patients under the age of 2. So we wouldn't expect to be able to, at launch, treat infants and toddlers. But we do believe at the age of 2 and above, those are going to be a population of patients that we're able to serve given the strength of our clinical data. And I'm looking at my Chief Operating Officer here, Keith Woods. We think that in the U.S., there is going to be a wide range of patients to serve with apitegromab. So we're sort of pleased where we were in September of last year, and we expect that as the starting point to finalize the discussions with the ongoing BLA.

And you also have an infant study. When could that expansion happen?

That's exactly right. So the OPAL study is really our obligation more than maybe a commercial opportunity. It's really our obligation of the SMA community to make sure that we understand the youngest patients living with SMA, what the role of apitegromab is. And so that study is ongoing. We would expect after approval and when we generate data, the PK/PD data, the safety data is all going to be very important for the FDA to consider maybe broadening the label to those patients who are under the age of 2.

Okay. And then maybe if you could speak to what you see as critical really to execute on the launch. And as you think of aspects such as in-clinic versus at-home infusion, access reimbursement, noting that this is a Medicaid representative population. Maybe you could just speak to kind of those metrics or points that you're really looking to execute on.

Yes. Maybe I'll start first with sort of demand generation, and then we'll get to access and reimbursement. So as I noted earlier, given the wide range of patients that we studied in our 188-patient randomized, double-blind, placebo-controlled Phase III trial, the SAPPHIRE study, we actually see a wide range of patients that are going to be appropriate for therapy.

As I noted, as long as the patients are on an SMN targeted therapy, no matter whether or not they are having an improvement in motor function, they're plateaued on motor function or they have a decline in motor function, we believe that the opportunity to completely inhibit myostatin again, the body's natural negative regulator for muscle growth can improve the outcome for those patients. And so I also noted some cure SMA, which is a phenomenal patient advocacy group, has done plenty of surveys of the SMA community and 95% of patients continue to report that their #1 need today is muscle strength and improvements in motor function. And so we do anticipate that there is going to be significant interest from the patient community and the family community.

At the same time, we've also seen that approximately 3/4 of all neurologists and neuromuscular specialists also are acknowledging that while there's been great innovation with motor neuron health with the SMN-targeted therapies, that this is a disease that requires treatment of both the motor neuron and the muscle. So you got 95% of the patient community saying, we really want something to address the muscle. You have about 3/4 of the physician community saying, yes, it seems like the best way to treat patients is by addressing both the motor neuron and the muscle. And we think that, that setup is quite nice for us in terms of demand generation of the community wanting to access apitegromab at approval.

So let's pivot now to access and reimbursement. Maybe just to level set everybody here, apitegromab is an IV therapy. It is approximately a 1- to 2-hour infusion and it's delivered monthly, technically every 28 days. And so on average, patients would have to dedicate probably 1 to 2 hours a month to receive the infusion. And we recognize that it's important to provide patients and families with options on how they're going to receive those infusions. So as Keith has acknowledged on some of our prior earnings calls, we've established a 10,000 infusion nurse network around the country. So wherever patients are, we can deliver this medicine to them potentially in their home. We also recognize a lot of KOLs are going to want to commence treatment at their sites and then maybe look for something a little bit closer to home, but we want to provide that optionality to patients.

I think what's important also to note is we've now had patients on apitegromab for upwards to 7 years. The combination of our Phase II and Phase III clinical trials has resulted in more than 90% of patients that remain on open-label apitegromab in our open-label extension study, otherwise known as the ONYX study. And so we do believe that we're set up for -- given the strong value proposition of apitegromab for a program that will, we think, deliver very, very high compliance for patients.

Now let's actually take the payer side of this. You mentioned that it's a Medicaid dominant population. We do see that the market in the U.S. is probably 50% commercial, 50% government that will be either Medicaid or Medicare. We do know as an infusion product, we will initially have a miscellaneous J-code, so not a drug-specific J-code at least for 6 to 9 months. That can usually result in like automatic denials or deferrals and delay reimbursement. We also recognize a lot of the SMA expert treatment centers, maybe hospitals where there might be formulary status that's needed.

And then we also recognize like a lot of payers, especially Tommy, to your earlier question, if the label might be broader than the Phase III clinical trial population, payers are going to have to also take a little bit of time to establish their medical policies for apitegromab. So all of that results in, we think, not a matter of if, but when reimbursement happens. And as we've typically seen with many new infusion drugs at launch, there can be delays, there can be denials, there can be appeals.

In our own experience, and Keith has had maybe more than anybody else, that it can be upwards to 60 days from an intended enrollment form, start form or prescription to funded supply that can happen at launch. And then eventually, over the first 9, 12, 15 months, we'll get to steady state of a more rapid prescription to reimbursement coverage and infusion.

So we, as a company, have established a white glove service known as Scholar Rock support. So we'll be able to enroll every individual patient and family in our reimbursement and access program. We also have an in-field reimbursement team, and in-field sort of coordinator of care with every patient and every family. And so we want to make sure that we can work very, very closely with physicians and the patient community and helping them through this process.

So over time, we are super optimistic about the opportunity to serve patients, but we do know upfront, and this is just to manage everyone's expectation, given the amount of time that it might take from prescription to funded access and infusion, it may be a steady launch, not necessarily like a pent-up hockey stick at launch, we think the demand will be there, but it will take a little bit of time for access. Overall, though, we see this as a massive opportunity to serve patients and a massive opportunity for growth through the end of this decade and well through the next in the U.S. and Europe and up to 50 countries around the world.

Okay. That's very helpful. And is there anything else that you would want investors to understand about this asset before we pivot to the rest of the pipeline?

The only thing I would want investors to understand, and I've said this a lot, we've talked a lot about getting through the final steps in the regulatory process, again, largely through our third-party manufacturer who is doing fill/finish. We've talked about things like, as you said, access and reimbursement. We've talked a lot about launch curves. But the only thing I would want everybody to understand is there's somewhere around 7,000 patients in the U.S. that are likely going to be appropriate candidates for treatment and then another 28,000 outside of the U.S. that are going to be appropriate candidates for treatment.

So approximately 35,000 patients globally across all of the SMN targeted therapies. This is a $5 billion market today, and it continues to grow. More innovation is coming around the motor neuron health sort of therapeutic options, but we are the only ones to address the muscle component. And that's why we are quite confident that this is a very, very large opportunity to serve patients and a very, very large opportunity to grow our business for many, many years to come.

So what I'd like everybody to think about over time is I know we're thinking about the first 6 to 12 months of launch. The more important thing is massive opportunity for strong, steady growth through the end of this decade and well into the next. And every single year, we'll be bringing new countries on board. There'll be new launches, new patients on board. And that's why we think we are one of the strongest global growth stories on the horizon in biotech right now, and we're super excited about it.

Okay. Great. So in FSHD, we've seen a lot of recent activity from the DUX4 targeting agents. You have a different approach. As you look to starting your Phase II study, what are the key endpoints here? And what does success look like? And overall, could you maybe frame your positioning in this market?

Yes. Great question, Tommy. So we believe, as I presented at at the JPM conference in January that there is a host of genetic and acquired myopathies and neuropathies that may be of particular interest for us with our platform with apitegromab and eventually with subcu apitegromab and 439. In other words, we believe we sort of have a platform and pipeline that we can develop for this product alone. And while we are really excited about more and more correctors being developed, as you mentioned, those that are targeting DUX4 and FSHD, we believe that the muscle component remains a high unmet need in many diseases beyond SMA.

And so we've been exploring. We've done some preclinical work in DMD. We've now done preclinical work in FSHD, and there's more to come. So we see a series of potential rare and neuromuscular diseases that we can apply our expertise to. What we've announced is as of earlier this year is that FSHD would be the first disease outside of SMA that we would target. [indiscernible] clinical data looked very robust.

So we [indiscernible] Flex DUX4 mouse model. We applied our antibody to those mice. And what we saw is an improvement in muscle mass, muscle force and exercise endurance. And actually, it provides a strong preclinical rationale, very much like what we saw in SMA. So that was important.

What we also saw when we looked at FSHD is that there's actually some clinical work by looking at rigorous exercise programs and/or the use of anabolic agents like HGH and testosterone that show that by targeting the muscle alone, there was improvements in lean muscle volume as well as functional measures. And so we said, we actually think that as a monotherapy, we can actually throw off a proof of concept. And yet all of that should also apply should there be great success in the corrector therapies addressing DUX4, it could be used potentially monotherapy or in combination with those corrector therapies.

FSHD, 30,000 patients diagnosed in the U.S. and Europe. Usual onset of disease is sort of adolescents to early adulthood. It's a devastating disease in which about 1/5 of patients end up in a wheelchair or needing an assisted device. And again, the other thing that we're pretty attracted by an FSHD is it tends to be a disease where you have -- because of DUX4, you have patchy dysfunctional muscle, but you have patchy normal musculature, which also may be the reason why targeting the muscle alone can show a benefit.

So coming to the FORGE Phase II study, 60 patients, double-blind, randomized placebo-controlled. The primary endpoint will be lean muscle volume at 12 months, but we will look at some functional measures as well. I think the regulatory endpoint that some are using today is a combination of lower and upper extremity of functional outcomes like QMT, quantitative muscle testing. We'll be looking at that as well in our study. And we'll look forward to start enrolling patients. We're looking at more of the moderate form of the disease. So there is enough normal musculature, whereas a monotherapy, we can show a benefit. And we're looking forward to enrolling the study and sharing some results sometime in '27 or early '28.

Okay. Great. And maybe just as a last question and overall strategy question. As you look on the forward future for the company, maybe rare versus prevalent diseases and wholly owned versus partnerships, how are you thinking about those aspects?

Yes. Tommy raises a very good point. Our very compelling Phase II EMBRACE study was just published yesterday in nature, and it's received a lot of press. And this was a study that we did in over 100 patients that were randomized to receive either tirzepatide or apitegromab with tirzepatide. And what we showed was a lean mass preservation that was quite striking with a p-value of 0.001.

And so the question has been like in the world of cardiometabolic, obesity, longevity, how as world leaders in myostatin biology and muscle health, how do you see yourselves applying your platform moving forward? I think what we've said is that we think what we know well and do well is rare neuromuscular, these serious diseases that impact both children and adults, and we want to apply our resources there.

But we've also said that one thing we could see ourselves doing because we have some fusion protein technology in-house is that we could see some kind of a unimolecular approach to our myostatin inhibition platform and GLP-1s, GLP-1 RAs and we just had an abstract at ADA this past week kind of unveiling that. We think there could be a partnership in the future where leaders in the cardiometabolic space, combined with us, leaders in the myostatin space, maybe could work on something together, but we think the appropriate approach might be a fusion protein as opposed to a stand-alone asset.

So for now, we want to take what we know well and do well and apply it to a broad range of rare neuromuscular disorders that can then fit into this 50-country operating platform that we will build to initially serve patients with SMA, hopefully then serve patients with other rare neuromuscular disorders like FSHD, DMD or beyond. We'll provide you updates on that progress and then continue to build out sort of our rare disease platform for many years to come.

Okay. Great. Well, thank you very much for joining us, and we look forward to watching the progress.

Thank you. Thanks, Tom. Thanks, everybody, for tuning in.

[Audio Gap] here at the Bank of America Healthcare Conference. We're kicking off our very first session of the very first day. It's my pleasure to have with me Scholar Rock as our first presenting company, sitting up here on stage with me is David Hallal, who is, of course, Chief Executive Officer and Chairman. David, good morning. Thanks for making the trip over from the East Coast.

So maybe let's just do a quick overview of the company. Just give us a little bit of an overview of the focus of what you're trying to do and how you might be differentiated from other companies trying to do at least similar indications?

Thanks, Tazeen. Yes, we're super proud at Scholar Rock to have succeeded where 20, 30 years of failure preceded us. And that is that in 1987 when myostatin was discovered, it was certainly something that just about every biotech or pharma company mostly the big pharma companies have tried to target and block because what myostatin is, of course, is the body's natural negative regulator of growing muscles. So the thought was if one could safely and effectively inhibit myostatin, one could then release muscle growth in the body that could be applied to a set of diseases and certainly, we're focused on rare neuromuscular.

So we had an idea when we started the company at Scholar Rock, which was if we could do it slightly differently, we may be able to really harness this value off of our platform. And that is mature myostatin looks like other things in the body. When you look to inhibit that, you actually have off-target effects. We focus on pro and latent myostatin. So we actually inhibit it in a chemical form that's very, very unique. And so we were gratified in late '24 to have the first ever Phase III clinical trial success with statistically significant clinically meaningful benefit in patients, children and adults with spinal muscular atrophy. And now we are poised to launch the first myostatin inhibitor in the history of our industry.

And why that differentiates Scholar Rock is there really is no meaningful competition in front of us, even most recently, other big pharmas had failed to target myostatin successfully. And so what that really positions us to do is starting with spinal muscular atrophy and then a set of other rare and devastating neuromuscular disorders, we can play out this unique capability that we have as the world leaders in myostatin biology to hopefully address a set of devastating disorders that affect children and adults, again, as I noted starting with spinal muscular atrophy. What that means for us really is an opportunity to establish ourselves as a leader in serving patients with rare disease with our core focus being what we know well and do well, which today, it is inhibiting myostatin.

Yes. So maybe let's dig a little deeper. You mentioned that other bigger companies have tried to go down this path and have had some roadblocks. So what do you think, in particular, differentiates your program that's allowed you to get to the stage where you're basically now just trying to complete a resubmission?

Right. Thank you, Tazeen. So ultimately differentiates us is this idea that we had that myostatin, unfortunately, is homologous to other proteins in the body and when all of these efforts to target either mature myostatin or the myostatin receptor, the trap programs have just led to suboptimal efficacy and/or safety and they've resulted in terminations of clinical programs, most recently the one from Roche in SMA and FSHD.

So from our standpoint, we had this very unique way of approaching both pro and latent myostatin that gave us exquisite selectivity. And as a result, we think we had a molecule that we could move into any patients. And today, we'll get into this, we're even treating now toddlers and infants with our drug. So it's exquisitely selective and very, very safe. And so that's one. It's starting with a molecule that truly is differentiated off of our platform.

I think secondarily, we chose well. We chose the right indication. We actually did a robust Phase I, Phase II, Phase III clinical trial program. We were informed every step of the way on the right dose, the right interval, the right patient population to study in our pivotal trial. And as a result, I think it has set us up to demonstrate this incredible opportunity to transform the lives of children and adults living with spinal muscular atrophy and then sets up with a series of genetic and acquired myopathies and neuropathies that gives us a set of different diseases to apply our success in SMA to over the years to come.

Okay. We'll talk about the resubmission in a second, but since we're on the topic of the drug itself, it's also differentiated in the sense that you're not trying to have patients swap out of whatever other drug that they might be taking. So maybe talk to us about the benefits of that, both for the patient and commercially speaking.

I'm really thankful, you mentioned that Tazeen because I often hear that while there have been innovations brought to the SMA community over the last decade. And these are very, very important therapies that have brought massive innovation to a community that desperately needed it. But all of those new therapies focused on motor neuron survival and motor neuron health. And certainly, Biogen ushered that in and Ionis with SPINRAZA.

So over the last 10 years, we've seen this innovation come in. But really, spinal muscular atrophy, the principal organ affected by the disease is the muscle. And so when one is trying to improve the lives of patients living with spinal muscular atrophy, two things have to happen. One, one needs motor neuron health, but the other is they need muscle health. And so one entire side of the motor unit, which is comprised of the motor neuron in the muscle, there has been no innovation. So our idea was if we could address the muscle component associated with this disease, we can make a meaningful difference for patients.

And so I think one thing is really clear in our Phase III SAPPHIRE trial really underscored this. If you're treating a patient child or adult with SMA, 2 things you should want to do. One is you should want as much SMN protein as possible to address motor neuron health and you should probably try to eliminate myostatin, which is the body's natural negative regulator for muscle growth. If you can do those 2 things, biologically, plausibly, you can provide the best outcome for patients from the perspective of motor function. And we're really excited to be -- we think now just a few months away any time now from ushering in the next wave of innovation for patients living with spinal muscular atrophy, which, of course, is the first and only muscle-targeted therapy that has been successful in a Phase III trial, and that's apitegromab.

Yes. Okay. So now let's go back to the business at hands, which is the resubmission process, right? How are you feeling about that? Where are you in that process? You've talked about this now at length on multiple earnings calls, but we're here now. And is it your expectation that by year end, you will have a commercially available drug?

First of all, I want to thank you for your patience, Tazeen, because I think you initiated coverage like right before some of all of this began with our fill/finish facility and ultimately, the delay that we have had. So maybe just walking back the audience to where we were. We had this incredible Phase III data that we presented in Q4 of 2024. We submitted our BLA in January of '25, and the FDA, given the high level of innovation of the first-ever muscle-targeted therapy that was studied for patients living with SMA granted us a priority review with an action date of September 22, 2025. So we were poised to launch the drug in Q4 of last year.

And then, of course, we disclosed on August 6 that there was a general site inspection at our fill-finish facility Catalent Indiana, which is owned and operated now by Novo Nordisk. And this is a plant that has had some dust-ups before on inspections that were impacting other therapies, including around the time of the pandemic, spike backs from Moderna. And so we had thought and hoped that their Novo Nordisk's response to those observations would get us through to the other side by September 22, that was not the case. So we received a CRL solely based upon the state of compliance at our fill-finish facility.

That then followed an official action indicated classification of the facility in a warning letter, which usually can lead to a prolonged path to remediation of that plan. So all of that happened in Q4. At the same time, we had a really productive, constructive and collaborative in-person Type A meeting with the FDA in November of 2025. And recall where we were at that time. It was the longest federal government shutdown in the history of this country and yet we were granted an in-person meeting with the FDA. So all the leaders of the FDA were there. Novo Nordisk came in, the leaders from Cure SMA were there as well.

One thing that came out of that meeting is that we believe there was a shared understanding of the unmet need that still existed for the SMA community despite the level of innovation targeting the motor neuron and that there was a shared sense of urgency to try to get this resolved for apitegromab. And so they've been working the FDA with Novo Nordisk pretty aggressively, which has led to a reinspection of the facility just recently. But at the same time, we looked ourselves in the eyes. We look at the SMA community, and we said we've got to be better on this application than we were on the last one. And we should actually have an alternative to Catalent Indiana. And so we worked very, very hard on a second fill-finish facility.

And so really in close collaboration with the FDA from November of '25, which was our Type A meeting to our Type C meeting in March '26 we aligned with the FDA that we should resubmit our BLA with not only Catalent Indiana, but also a second fill-finish facility, one that we have, I think, beat speed records to stand up that facility, and we are going to have commercial drug that will be releasable as early as early Q3 from that second fill-finish facility. So we were very pleased last week on our Q1 call, to let you all know that our BLA has now been accepted by the FDA with not only Catalent Indiana, but 2 fill-finish facilities.

The reinspection has taken place now at Catalent Indiana and the FDA by their own guidelines has 90 days to evaluate that inspection and determine if they can reclassify that facility. But within that same 90 days, we're going to have drug ready to go from the second fill-finish facility. And overall, we were granted a Class II resubmission with an action date of September 30. So what we have been guiding is that we see with either or both of these facilities, a path to approval by Q3, and we're very, very excited about that. And I can assure everybody that we will have plenty of apitegromab launch supply for Keith and team should one or either one or both of those facilities be approved within our application.

Okay. Thanks for all that color. So there's a lot of moving parts between now and September. And so questions that we tend to get are, are there experiences where FDA can -- or you can point to where FDA has had a similar scenario where there was the potential of 1 or 2 facilities that they would need to look at in order to get to an approval date.

There's a few, if I may, that are also within this window of what's been happening with us. So you guys may have noticed beyond EYLEA HD and EYLEA HD prefilled syringe. Regeneron had a cancer therapy in October, that they actually had 2 fill-finish facilities as part of their application, Catalent Indiana. And I think they had one through their relationship with Sanofi. And when it became very clear in October of '25 that Catalent Indiana was not going to be reclassified in time, they dropped Catalent Indiana without any timeline hit and they were approved with the other facility.

And so within the contours of our Type C meeting in March of '25 with FDA, we did talk about that, that this can, in essence, be a horse race. What helps us get approved the fastest because of this high unmet need for the SMA community and the shared sense of urgency for apitegromab to be launched for children and adults living with SMA. And should one look like it was outpacing the other we could actually move on to an SBLA, but let's get this drug approved. Now what has happened is this 90-day window post reinspection and how fast we've been moving at the second fill-finish facility, these lines are starting to overlap with one another. And so we'll just remain in close contact with the FDA on this progress.

And look, I would love nothing more than something fast and with both. But at this point, our commitment is to the SMA community, and we'll take either one at this moment in time. So we can get to the children and adults that desperately want this innovative therapy apitegromab to be added to their current treatment regimen.

Okay. And then just to clarify one thing you said, if within that 90 days, FDA does come back for whatever reason they might have additional questions, do you believe that the time remaining would allow for that second facility to meet their standards and get approved by your September PDUFA.

It's an excellent, excellent point. We believe because the FDA -- so I noted last Thursday, but I haven't noted here and I think it's important to say this to our audience is that all of the apitegromab that is required for review and approval from the second fill-finish facility has been vialed. So it's like there isn't really anything in front of us. The data the FDA will have from the product that has been vialed and like I said, the drug is already to be released upon approval as early as several months before the September 30th PDUFA date.

So you start to see a lot of July. There's a July with a commercial drug that's available from the second fill-finish. There's a July, mid- to end of July that is that back end of the 90-day window for the FDA to deliberate on whether or not to reclassify the facility. And so all of those things may be aligned. But let's just say the FDA woke up and said, we want a clear Catalent Indiana. We would move the second fill-finish facility into an SBLA, and we would launch with Catalent Indiana.

And vice versa, we're not going to give up on Catalent Indiana, if they say, look, you made meaningful improvement, but a warning letter is serious business. We want to keep you here for a little bit of time, see how you -- we may not require another inspection but see how you work through your remaining issues if that were to be the case, then there definitely would be the case where you could see Catalent Indiana becoming an SBLA and us approving with a second fill-finish facility. So again, we're hopeful that it's both, but let's see how the days progress. And I want to be publicly thankful to the FDA because they really have been extremely flexible with us in terms of understanding the different paths to approval as quickly as possible.

Okay. Great. So understanding that the most important thing is to get the drug available for patients as soon as possible. Longer term, do you have a preference for which facility you think would be your primary facility?

I do. And it's largely business model related. So our second fill-finish facility, which I should know is a U.S.-based facility. It's in great standing with all regulators. They have a long-term and recent positive inspection history. And in fact, some of their most recent therapies that have been approved, the FDA waived the PLI, which is actually interesting as well. And as I noted, they have about 3 dozen approved products. And that is their business model. As you may know, but I think it's worth describing, Catalent Indiana was owned by Catalent, which is now owned by Novo Holdings. This is a little confusing, but let me clarify that.

But when Novo Nordisk needed more fill-finish capacity after Catalent was acquired by Novo Holdings, Novo Holdings then sold 3 fill-finish facilities to Novo Nordisk. And they are now part of the internal operations of Novo Nordisk, which really has no interest in being a third-party CDMO. So we know and we have known that they're going to exit the CDMO business, so we would be migrating our operations from there anyway. And so I think overall, our ambition would be long term to have both because having redundancy is always a good thing from a supply chain perspective, but it is that second fill-finish that looks like the long-term supplier, and we'll be thoughtful about this incredible commercial demand that I expect from Keith, and how much redundancy we do want to have in the supply chain over time. Hopefully, that's helpful.

Yes, that is. Part of the reason I ask is because I wanted to understand the role that the Indiana facility is going to play for your European application.

Tazeen is raising a really important point that hopefully I can clarify for our audience here in Las Vegas as well as tuning in remotely. So unlike the FDA and EMA, we have not had any delay and/or the equivalent of a CRL, okay. We're still on file with EMA. And in fact, the European regulators have been really flexible also, and we like the state of where we are with our MAA in Europe. But the difference is because we haven't had a rejection, our application includes Catalent Indiana only today.

Now they're obviously because they have a mutual recognition program with the FDA. They're waiting for that facility to be cleared, and then we would imagine we get on the agenda for CHMP and then we're approved and we launched in Europe, starting in Germany in the second half of this year. That is our guidance. We remain firm on that guidance. EMA is well aware of the second facility. The second facility is in very good standing with EMA. We're talking to them about the same elegance of what we have with FDA and wanting to make sure that we have that same level of optionality.

But today, the MAA only has Catalent Indiana in the application, and we are discussing with the European regulators, the nature of the fill-finish facility, all the good work that's been done, the agreement with the FDA and how that could work to provide us that same belt and suspenders approach to an approval in Europe that we currently have in the U.S.

Okay. So now let's talk about the commercial opportunity. So we know Keith Woods from his previous life. So as you mentioned, you've set up a good team to do the launch. But maybe walk us through what you think the initial uptake is going to look like. So included in that would be questions around negotiating with payers, presumably, you've already had some early discussions about that and maybe talk about range of pricing if you could.

Sure. So one of the things, I think, Keith and I would say and have said is we would not have wanted a delay for even 24 hours. Given our own time that we've taken to be with the community, be with patients, be with families, be with parents, be with the patient advocacy groups. They were clamoring for this therapy given the strength of our Phase III data. But if one were to kind of make lemonade out of this, how when we brought Keith in at the end of April, and of course, he's done incredible work with us at Alexion, and of course, his best work yet was at Argenx.

He really didn't have time to make all of the I think, execution and planning decisions that he would have liked to have made before September 22 of '25. So how do you use that extra time to actually make sure you got the team, you have the plan and you have everything in place to support every one of the stakeholders from a patient, healthcare provider and payer perspective. So we've been using that time wisely. And I think as a result, Keith has spent a lot of time on the access programs, has spent a lot of time on the -- getting beyond just national payers into regional payers and making sure that they understand what apitegromab can offer to them.

And as a result, I think we're more well positioned for the commercial launch today in these next weeks and months than we were back then. What do we expect? Sometimes when something is ready for an approval, like we were all thinking the review was reading positive for an approval in September of 2025 and it doesn't get approved. The demand for it just increases. And I think what we've seen is almost 100% of the SMA community, I think, Keith, as you quoted, 95% of SMA patients say their #1 need is more muscle strength and motor function tied to their irreversible muscular atrophy that they're currently facing and muscle wasting. So almost all patients want to address their muscle component of their disease.

And nearly 3/4 of all neurologists acknowledge that dual modality is the way to go for the SMA community, treat the motor neuron as well as treat the muscle. That's a really nice setup for demand. And then I think as you aptly state, Tazeen, there is that payer side. And there's usually like a little bit of time before you get to that steady state of conversion time and conversion rate. Will they want to limit an approval for reimbursement to the Phase III criteria or the label that we have. And we believe it's not a matter of if, it's when the payers are paying according to the label that the FDA grants us. But there's a miscellaneous J-code. There are formularies to work with. There are infusion schedules. This is an every 4-week infusion, as you all know, where 95% of our patients that have been in our long-term extension trial remain on treatment. We think that says a lot about the value proposition.

But I think the demand will be there. I think the -- I'll get to pricing in a second. I think it will take a little bit of time before we get to sort of that steady state of conversion time and conversion rate that makes this a little bit more predictable. But one thing is for sure. The SMA community does not take no for an answer. They've been through this before when they've been waiting for their SMN targeted therapy. And I think we're going to, between physicians and patients and payers, and of course, with Scholar Rock support, which is our access program that we've set up to walk every individual patient through the reimbursement process, we think the setup is quite well for us.

And then finally, regarding pricing. I've been asked about this quite a bit. And while it's a little premature to talk about the specific price, what I would say is we always think about a couple of things. One, the rarity of SMA. So there's only a few thousand patients in the U.S. living with SMA that received an SMN targeted therapy, about 7,000 of those and another 28,000 around the world. That's number one. Number two, the severity of the disease without our therapy. So despite this high level of innovation of these SMN targeted therapies, patients eventually plateau and start to progress or revert to the progressive form of SMA, where they're losing motor function year-on-year. We saw that in our Phase III trial. We see that in their long-term extension routes.

And yet with apitagramab, what we saw was a move from a loss of motor function to a return of a gain of motor function for the entire population of patients and nearly a 4x greater likelihood of patients having a 3-point improvement in the highest bar that you could have, which is the Hammersmith motor function scale in SMA. So we think the value proposition is there. So I think we can price proudly. I think we'll be reimbursed at that price. I think it's very much reflective of the value that we're going to be providing. And I do think the community and the patient size is not so large that the budget impact will be significantly great. So demand will front run the access side, but I think overall, we're really excited about the long-term prospects to serve these 35,000 patients globally for many years to come.

So what do you think the level of awareness is among patients? Because this is a small community, but a very educated community. Obviously, you don't start detailing until you get approved. But interested on where you are, should we expect a bolus of demand upon approval?

So demand is probably going to be measured in the enrollment in Scholar Rock support, which is going to be some combination of -- and it has to happen this way, right? The patient has to want the therapy and the physician has got to want to prescribe the therapy and then they enroll in Scholar Rock support. So that will be that first indicator. Keith is still determining exactly what launch metrics he might share. Obviously, revenue at the end of the day is what you all care about. And look, I think demand will front run revenue. That's just the way it is usually with these rare disease launches, especially when it's an IV infusion, and it's a miscellaneous J-code.

But I do think that there will be -- the awareness is high, as I was mentioning. And I really can't wait to have a trade name or a brand name for the drug because, unfortunately, the SMA community cannot say apitegromab. Actually, half the people at Scholar Rock cannot say apitegromab. Nobody knows how to pronounce it. So what they say is they just want Scholar Rock. They call our drug Scholar Rock. They can't wait for Scholar Rock to be approved, and I think that's really cute. The adults call it the juice, which is altogether a different thing. And -- but I think the awareness of this therapy is quite high. I think the delay is actually even heightened the awareness, and the leadership at Cure SMA has kept us front and center, will again have a very, very strong presence at the Cure SMA Annual Conference in Orlando in June, will be as well represented as any company.

And Keith, as you know, and [ Vitas ], we just had a great presence at SMA Europe also as we get ready to launch outside of the U.S. It is there for sure. And we think we're just the right team and the right company and it's the right product. And this is something that I think the SMA community is very much looking forward to.

Okay. We'll keep saying apitegromab and so people can get...

Yes. You and I are going to keep saying apitegromab.

Of course, it's going to take a little bit of time to record actual revenue, but looking at other rare disease launches as a comp new patient start forms, whatever information you're going to be providing in the early portion. I think people are wanting to know. It sounds like from what you're saying that the demand is going to be there, that you will see the translation pretty quickly from approval to doctors wanting to get their patients on it. I don't want to put words in your mouth, but am I interpreting that correctly?

I think there's reasonable demand on day 1. I think it is just the combination of sort of like conversion rate and conversion time from the payer side, and we'll be patient because it's going to be a matter of when and not if. The product gets reimbursed, and I think the setup is quite nice for us. But I would just advise folks to not get crazy about what the revenue curve looks like because these things take time to do it right. And I think that we're well set up to do with the right way over time for the community.

Okay. And last question really quickly, cash needs, balance sheet strength.

So we were very thankful in our call last week to announce that our cash balance was $480 million at the close of Q1, that was fortified by a pull down on our debt facility of $100 million in Q1 as well as leveraging our ATM program for another $98 million. I think the combination of the $480 million, the clarity now on an accepted BLA with 2 fill-finish facilities the ability to pull down another $150 million off the debt facility at approval.

And of course, we do have a priority review voucher, which we intend to monetize at approval as well sets us up very, very well, not only -- and I know we didn't get to the pipeline, but not only to support the commercial launch for apitegromab in the U.S. and Europe, but also to keep fueling the pipeline that Akshay is we're focused on with FSHD with the OPL study in infants and toddlers with subcu apitegromab and with SRK-439, which is our highly innovative high potency, low volume, high-affinity myostatin inhibitor, which is in Phase I, and we'll have some data on that later this year also. So we want to continue to build what we believe is a very special rare disease company. Our super power is myostatin biology. We think we're well positioned for growth through the end of this decade and well into the next. And I look forward to working with Tazeen and the Bank of America team and keeping you all apprised on our progress.

Okay. With that, we're out of time. Thank you, David.

Thanks, Tazeen.

Thanks, everybody.

Good morning, ladies and gentlemen, and welcome to Scholar Rock's First Quarter 2026 Conference Call. [Operator Instructions] This call is being recorded on Thursday, May 7, 2026.

I would now like to turn the conference over to Scholar Rock. Please go ahead.

Good morning. I am Laura Ekas, Vice President of Investor Relations at Scholar Rock. With me today are David Hallal, Chairman and Chief Executive Officer; Akshay Vaishnaw, President of R&D; Keith Woods, Chief Operating Officer; and Vikas Sinha, Chief Financial Officer.

During today's call, David will provide introductory remarks and a business update. Akshay will review our R&D progress. Keith will provide an update on our commercial readiness activities, and Vikas will provide a financial update. We will then open the call for questions.

Before we begin, I'd like to remind you that during this call, we will be making various statements about Scholar Rock's expectations, plans and prospects that constitute forward-looking statements for the purposes of the Safe Harbor provisions under the Private Securities Litigation Reform Act of 1995. Any forward-looking statements represent our views only as of today and should not be relied upon as representing our views as of any future date. I encourage you to go to the Investors and Media section of our website for our most up-to-date SEC statements and filings.

With that, I'd like to turn the call over to David. David?

Thank you, Laura, and good morning. Thanks to everyone for joining our first quarter earnings call. Scholar Rock is positioned for a pivotal year ahead. To that end, today, I am very pleased to announce that the FDA has accepted for review our biologics license application for apitegromab for the treatment of children and adults living with SMA. The agency has assigned a PDUFA action date of September 30.

Importantly, the accepted BLA includes 2 fill-finish facilities, Catalent Indiana and a second U.S.-based facility, providing Scholar Rock with 2 independent paths to apitegromab approval. As a reminder, the sole approvability issue for apitegromab noted in the complete response letter last September was related to observations identified during a routine general site inspection of the Catalent Indiana fill-finish facility, which is owned and operated by Novo Nordisk.

Since our in-person Type A meeting with the FDA in Q4, we have continued to work constructively and collaboratively with the agency, and we have made steady and rapid progress.

During the first quarter, we made meaningful advancements at Catalent, Indiana and our second fill-finish facility. And with our ongoing open communication with the agency, we resubmitted our apitegromab BLA in late March in complete alignment with the FDA to include both facilities.

This approach underscores the shared understanding between the FDA and Scholar Rock of the unmet need in the SMA community and the shared urgency to bring apitegromab to children and adults in the U.S. as quickly as possible.

I would like to now provide an update on the status of each of these 2 sites. As it relates to Catalent Indiana, we are pleased that following acceptance of our BLA, the FDA completed an unannounced reinspection of the facility.

This timing was in line with our expectations as the FDA had noted following multiple engagements with Novo in Q1 that they would conduct an unannounced inspection following routine manufacturing activities, which resumed in late February. We are pleased that the inspection was completed in early Q2 and in accordance with FDA guidelines, the agency has up to 90 days to classify the facility.

As it relates to the second fill-finish facility, we continue to be pleased with our ongoing meaningful progress. Importantly, the entirety of the apitegromab drug product required for FDA review and potential approval has been filed.

From a commercial supply standpoint, we are well positioned as we expect to have ample commercial apitegromab available from the second facility in early Q3, well ahead of the September PDUFA date. We remain committed to the SMA community, and we are grateful that significant progress continues to be made at a rapid pace.

Our U.S. commercial team continues to advance the critical activities and capabilities required to deliver a seamless launch and support patients from day 1. Importantly, the team stands ready to launch apitegromab immediately upon approval at any time prior to, and including the September 30 PDUFA date.

In addition to the U.S., we continue to look forward to serving children and adults with SMA in Europe. The review of our MAA is progressing very well, and we expect a CHMP opinion near midyear. We are building momentum with launch readiness activities, and we continue to anticipate a launch in the second half of the year, beginning with Germany.

We know it is not a matter of if, but when apitegromab will be approved for children and adults with SMA, and Keith will discuss the continued progress we are making with commercial preparations and our disease awareness initiatives shortly.

We continue to advance our world-leading anti-myostatin pipeline with enrollment in our Phase II OPAL study evaluating apitegromab in infants and toddlers with SMA, the anticipated initiation of our randomized Phase II study in patients with FSHD and progress with subcutaneous apitegromab and a novel high potency anti-myostatin antibody, SRK-439 currently in Phase I. Akshay will discuss these programs in greater detail shortly.

Turning now to the balance sheet. We are pleased to have ended the first quarter of 2026 with $480 million in cash, cash equivalents and marketable securities. This cash balance includes the drawdown of an additional $100 million from our debt facility, which we took in March. Our cash balance also reflects net cash proceeds of $98 million from our ATM program during the quarter. Vikas will provide more details later in the call.

We are building on a solid foundation for our company's growth, which we believe will be steady and consistent through the end of this decade and well into the next as we prepare to serve up to 35,000 children and adults living with SMA around the world who have received at least one SMN targeted therapy. Beginning with SMA, we are excited to be shaping the future of treatment for patients living with rare and devastating neuromuscular diseases.

And with that, I'll now turn the call over to Akshay. Akshay?

Thanks, David, and good morning, everybody. We're very pleased with advancements in our world-leading anti-myostatin pipeline during the first quarter.

Turning first to apitegromab for children and adults with SMA. We're delighted to share that the FDA has accepted the apitegromab BLA. As a reminder, the BLA was resubmitted in alignment with the agency to include both Catalent Indiana and a second U.S.-based fill-finish facility. The approach provides Scholar Rock with 2 independent path to apitegromab approval by the PDUFA action date of September 30.

We're gratified by the agency's continued support since the CRL last September from the constructive and collaborative in-person Type A meeting in November to the early March Type C meeting and the current acceptance of the BLA. Throughout, the agency has appreciated the high unmet need in the SMA community, and we now look forward to the final steps in the U.S. regulatory process.

Reflecting the agency's vigorous efforts, we were pleased most recently with the timing of the FDA's unannounced reinspection of Catalent Indiana. For FDA guidelines, the agency now has up to 90 days to classify the status of the facility.

I'd now like to turn to our second fill-finish facility, where we continue to make meaningful progress. As David noted, the apitegromab drug product required for FDA data review and potential approval has been filed, and we expect to have ample commercial apitegromab from the facility in early Q3 ahead of the September PDUFA date.

Based on the significant progress at both facilities, we anticipate approval of apitegromab for children and adults with SMA, which could be supported by either or both facilities by the end of the third quarter.

Turning now to Europe. Our MAA for apitegromab for the treatment of children and adults with SMA continues to progress well through EMA review. As evidence of the progress, we have planned to be with the EMA recently for an oral explanation meeting. However, because we and the EMA were able to align prior to the scheduled meeting, we mutually agreed that the oral explanation was no longer necessary.

As we highlighted previously, approval in Europe also requires FDA clearance for the Catalent Indiana facility. Based on our discussions with EMA, they're aware of the progress at Catalent Indiana and are comfortable with the review time line that accounts for the FDA's classification as site. We continue to be very pleased with how the review is progressing, and we anticipate a CHMP opinion in the middle of the year.

Turning to our pipeline. Let me start with the Phase II OPAL trial. We continue to enroll and dose patients in this study, which is evaluating apitegromab in infants and toddlers under the age of 2. As a reminder, this trial is enrolling participants who have been treated with an SMN1-targeted gene therapy, or who are receiving ongoing treatment with an SMN2-targeted therapy.

This study is important because it is anticipated to expand the impact of apitegromab to the full spectrum of patients, including those treated with Zolgensma. In addition, we believe early intervention with apitegromab could support muscle during a critical early development phase, potentially improving motor outcomes in the youngest of patients with SMA.

Turning now to our next indication for apitegromab, facioscapulohumeral muscular dystrophy or FSHD. FSHD is a rare, devastating neuromuscular disease with significant unmet need. More than 30,000 patients are diagnosed in the U.S. and Europe alone, and there are no approved therapies. We prioritized FSHD as the next indication for apitegromab for 3 key reasons: First, the significant unmet need; second, the compelling preclinical data from the gold standard FLExDUX4 mouse model that provides mechanistic rationale for apitegromab in FSHD.

And finally, as shown on Slide 11, data from randomized studies in FSHD, which suggests muscle mass can increase and has the capacity to show functional benefit. For example, in studies of either rigorous physical therapy or treatment with anabolic agents, patients with FSHD demonstrated increases in lean mass and muscle function. These data suggest that apitegromab as a monotherapy may have the potential to bring important benefit to FSHD patients.

We're very pleased with the progress of activities to support the initiation of our Phase II study called FORGE in the middle of this year. Enrollment will commence soon in this randomized, double-blind, placebo-controlled trial, which has a sample size of 60 patients. We're also advancing 2 additional programs in our world-leading anti-myostatin pipeline, a subcutaneous formulation of apitegromab and SRK-439.

In our subcutaneous apitegromab program, we showed some very exciting data from a Phase I study in January, which demonstrated that subcu apitegromab appears to have favorable bioavailability and a pharmacodynamic profile comparable to IV administration.

Additional development activities are ongoing, and we continue to plan for engagements with U.S. and European regulators later this year following approval of apitegromab.

Turning now to SRK-439, our high potency, high affinity subcutaneously administered myostatin inhibitor, which we discovered by leveraging our world-leading expertise. We're very excited about this program and dosing in our Phase I healthy volunteer study is progressing well. We expect to have top line data from this study later this year.

In closing, we're executing with urgency to bring apitegromab to children and adults with SMA, whilst in parallel working to maximize our impact for patients with apitegromab and our world-leading anti-myostatin pipeline across a range of rare devastating neuromuscular diseases.

With that, I'll now turn the call over to Keith to discuss our commercial launch preparations. Keith?

Thanks, Akshay, and good morning, everyone. With the BLA accepted by the FDA, our team continues to operate with urgency as we prepare for the launch of apitegromab immediately upon approval, which may be granted at any time through September 30, 2026.

Nearly a decade after the introduction of SMN-targeted therapies, muscle strength and motor function remain the top unmet need with 95% of patients continuing to experience persistent and progressive muscle atrophy. That limits function and independence. As further evidence of the unmet medical need, data shared with us by Cure SMA show that an estimated 1/3 of people living with SMA in the U.S. have received 2 or more SMN-targeted treatments, either sequentially or in combination. This data again underscores the significant opportunity we have with apitegromab, the world's first muscle-targeted therapy.

Our U.S. customer-facing team continues to make significant progress in the field with disease education, awareness around the unmet medical need and reinforcing a broader understanding of SMA as a disease which consists of both the motor neuron and the muscle, the principal organ impacted by the disease.

In the U.S., we have achieved significant reach across the approximately 140 SMA treatment centers, 2,600 prescribing physicians and their multidisciplinary care teams. Through these engagements, our field team is working to establish case flows on a center-by-center basis to ensure we are well positioned to support the SMA treatment centers once a treatment decision is made.

This includes preparations to launch our patient services program, Scholar Rock Supports. This program is designed to provide comprehensive and individualized support to patients, caregivers and providers.

In the first quarter, we had a meaningful presence at the Muscular Dystrophy Association meeting in March. During this meeting, our team further engaged with health care professionals. As one example, we hosted a very well-attended industry forum called going beyond the motor neuron to the muscle, expanding the focus of SMA care.

We also remain highly focused on patients and community activation. We are building on our disease awareness campaign called Life Takes Muscle, and we continue to have numerous in-person patient and patient advocacy group engagements.

Turning to U.S. reimbursement. Our market access team is advancing discussions with national and key regional payers as well as Medicare and Medicaid. With this extra time, we've been able to go deeper and broader across the range of payers. We are ready and well positioned for a successful launch of apitegromab in the U.S. immediately upon approval.

Scholar Rock is also making significant progress in Europe. We have established our European headquarters in Switzerland. Also in Germany, where we expect to launch apitegromab upon EMA approval, our local leadership is on board. We have hired our medical and commercial field teams, and we are actively enrolling patients in our compassionate use program. We are making meaningful progress with reimbursement planning to enable rapid patient access.

In the broader region, we are advancing reimbursement dossiers in multiple countries, strengthening our distributor relationships and building our EMEA infrastructure to support future commercialization.

Additionally, we had a significant presence at the SMA Europe meeting in March in Budapest. Among other high-impact activities, we hosted an SMA disease education workshop and a health care professional symposium, where the attendance reflected a high interest in further understanding SMA and the unmet needs in this disease.

In closing, we are investing with discipline to build the commercial foundation necessary to support a world-class launch and to achieve our long-term ambition to bring apitegromab to the estimated 35,000 patients living with SMA around the world who have received at least one SMN-targeted therapy. We are ready to usher in the next phase of innovation for children and adults with SMA, one patient, one caregiver and family at a time.

With that, I'll turn the call over to Vikas. Vikas?

Thank you, Keith. As we have shared previously, our financial objectives for 2026 remain focused on supporting our commercial build to deliver a strong apitegromab launch, funding R&D activities to advance our pipeline and expand our leadership in the myostatin and muscle space and continuing to evaluate opportunities to strengthen our balance sheet in a way that supports long-term shareholder value. In keeping with these objectives, I'm pleased to provide our first quarter financial results.

For the first quarter, we reported $102 million in operating expenses, which included $80 million in noncash stock-based compensation. Excluding stock-based compensation, operating expenses were $84 million.

Turning to our balance sheet. We are very pleased to have ended the first quarter with $480 million in cash, cash equivalents and marketable securities. During the quarter, we strengthened our cash position with the drawdown of an additional $100 million from our existing debt facility, which we took in March. We also had net cash proceeds of $98 million from our ATM program during the first quarter.

Looking ahead, upon FDA approval of apitegromab, we will have an option to draw down an additional $150 million from our existing debt facility, and we plan to monetize a priority review voucher to further strengthen our balance sheet.

We continue to operate with a tight financial plan and our prioritized investments remain focused on our apitegromab commercial launch readiness in the U.S. and Europe, strengthening our supply chain to support our expanding pipeline and our anticipated growing global commercial demand for apitegromab over time and advancing our highly innovative clinical programs that Akshay discussed earlier in the call.

With that, I will turn the call back to David. David?

Thanks, Vikash. Scholar Rock is poised for a transformative year in 2026. Our priorities are clear, and we are executing with focus, discipline and urgency as we seek to deliver the world's first muscle-targeted therapy to children and adults living with SMA, while also laying the foundation to realize our ambition to develop life-transforming therapies for patients with additional rare and severe neuromuscular diseases globally. We are ready now more than ever to usher in the next phase of innovation forth SMA community, and we look forward to updating you on our continued progress.

And with that, we'll now open the line for questions. Operator?

[Operator Instructions] And the first question comes from Eric Schmidt with Cantor.

Congrats on all the progress. Maybe just a couple of quick questions on apitegromab approval time lines in the U.S. Team, I know it's not your facility, the Catalent facility, but are you aware of any field notes that were provided to Novo following the reinspection? And then I guess I'm also curious about the statement that you reiterated a couple of times now that approval may come at any time. I know that probably reflects the shared understanding and communication you have with the FDA, but just curious about the intent of that statement.

Thanks, Eric. I'll take both. And look, we were obviously very pleased today to have announced that the FDA accepted the BLA with 2 fill-finish facilities. And to be clear, it was a Class II resubmission with a PDUFA action date of September 30, which is sort of per protocol for manufacturing-related issues. So we anticipated that. And of course, as a reminder, we submitted that BLA in complete alignment with the FDA ahead of the reinspection of Catalent Indiana commencing.

Look, like since that in-person Type A meeting that we had back in November, all the way through the Type C meeting that we had in early March, we have just been really pleased with the high level of engagement from the agency and sort of the consistent pace and progress across this period of time. So look, what I would note about the reinspection is we were pleased with the timing -- we think the FDA has done their job. We believe that Novo has done their job. And per FDA guidelines, it's really now a 90-day period of time for the FDA headquarters to do their work and make a determination on the classification of the facility.

And I think, again, underscoring sort of the 2 paths to approval. I am gratified that our team has made massive amounts of progress with our second fill-finish facility. As noted today, all of the drug that is required for the FDA's review in this BLA at that second facility has been filed. And that product would be available in early Q3. So what you kind of see here, Eric, when we talk about we have to be ready at any time prior to and including September 30, is that let's just do a little bit of math together.

The FDA is now in a 90-day period of time to determine classification of Catalent Indiana. We have product that's going to be available in early Q3 from the second fill finish. That sort of brings you to something that is well advanced from the September 30 PDUFA date. And so we just know that we need to be prepared because many times, Class II resubmissions and action can be taken by the agency well ahead of that PDUFA date. And that's really what we mean about it any time prior to. We'll continue to work with the FDA collaboratively, and we continue to be really excited with their level of engagement, again, as I noted from our Type A meeting right through this moment today. And we'll keep you guys apprised on that progress.

[Operator Instructions] And the next question will come from Mani Foroohar with Leerink Partners.

This is Lili Nsongo on for Mani. Congratulations on the progress. So now that the reinspection has occurred for the Catalent facility, how much risk -- or maybe I should say, how much confidence do you have in a successful non-experimentated classification for the facility? And how should we think about the capacity split between the 2 facilities in, say, the first year of launch?

I didn't get the second part of that question, Lili. On the first part, like as I noted to Eric, we feel like through this process, really since the sole approvability issue with our initial file was the general site inspection that the FDA had at Catalent Indiana. We know that Novo has been working really hard on that site with their initial remediation plan and then subsequently, their follow-up remediation with the FDA. And with a lot of engagement in Q1 with the FDA, as we previously noted, they had an early Q1 meeting that was then followed by a site visit and then subsequently in early Q2, the reinspection.

So I think we just need to respect that the FDA has really worked diligently, which we think is a rapid time line given the situation at Catalent Indiana to reinspect that facility. Based on their work, Novo has done their work, and now we want to be respectful of the time that the FDA will now take to make a classification decision. I think importantly, what Akshay and I were noting today is that we have a lot of drug vials from both facilities. And I think if any one of those 2 were to be the basis of the approval, each is going to have plenty of product to launch with. So I think that's great news.

I think one thing that maybe isn't lost on us is when you take a 90-day time line for up to a 90-day time line for the FDA to reclassify the Catalent Indiana facility. And then you think about an early Q3 timing of having product available commercially from the second fill-finish, there's definitely an opportunity also that our file could be approved with both fill-finish facilities. And I think that, that was one of the things that Akshay and I wanted to communicate as well.

So a lot of optionality here, a lot of good news for patients, a lot of good news for the SMA community. I am really grateful to our internal team at Scholar Rock for doing something pretty remarkable here with our second fill-finish facility, but also grateful to the FDA and Novo for the continued progress at Catalent Indiana, and we will keep you guys apprised at the updates across the board on our application.

Great. The second part of my question was about commercial supply capacity split between the 2 facilities, which you also answered. So thank you.

And the next question will come from Tess Romero with JPMorgan.

I actually wanted to ask a commercial question this morning. Now that Itvisma is fully approved for ages older than 2 years old, how are you thinking about apitegromab being able to be used in combination with that therapy if and when you are approved?

Yes. Thank you, Tess. Keith can address how we're thinking about that opportunity. As you noted today, really important information from Cure SMA -- in general, we are prepared to launch apitegromab at any time between now and up to September 30. And I think the incredible work that Akshay has done with our team and engaging the FDA there's going to be a very significant opportunity to serve patients with SMA. So Keith, do you want to comment on really more than anything else, the dynamics in the marketplace and your preparations for launch?

Sure. Thanks for the question, Tess. I guess what I'd say, first of all, is we believe that regardless of the therapy, but any type of a therapy that an SMA patient can potentially benefit from an SMN-targeted therapy, we're agnostic as to which one the treating physician choose because we think that they go hand-in-hand along with our muscle-targeted therapy with apitegromab.

Now specifically with Itvisma, in our SAPPHIRE study, we did not study patients that were previously on Zolgensma. As Akshay has noted several times, we are studying them in our OPAL study. And we also shared with you that we do have post Zolgensma patients in our EAP program. So there's some experience out there with it. But as far as being able to utilize apitegromab with it, I think it's going to depend upon the label and where the policies come out with the payers.

And our next question will come from Cory Kasimov with Evercore.

I wanted to ask you about the ongoing CHMP review. Coming out of the recent oral explanation, have the questions there have been largely similar to what the FDA has inquired about during its review and now just really boils down to CMC? Or are there other nonmanufacturing items that EU regulators are still trying to get their arms around?

Thanks, Cory. Akshay?

Yes. Thanks. So obviously, we don't get into the back and forth of regulatory reviews, FDA or EMA. The one thing I can say is that, that oral explanation that was scheduled led to a very good dialogue in advance of the meeting, and we were very happy with the pre-meeting alignment, which led to mutual agreement that there was no need for the meeting. And in fact, as a result, we obviously look forward to continued progress with the review and ultimately to launching the drug in Europe for children and adults with SMA.

As to the remaining time line, I commented in the formal remarks that the Catalent Indiana facility continues to support the application, and we look forward to a decision around midyear. But I think overall, the progress has been excellent.

And then just tagging on, Cory, just to tag on to Akshay, and Akshay has mentioned this multiple times. We've been having very good open dialogue with the European regulators about what's been happening here with the FDA and Catalent Indiana. So it's been very collaborative, like everything going on here has been a topic of discussion in Europe, and they've really been very flexible in working with us on timing.

And the next question will come from Michael Yee with UBS.

Two questions, really quick. One is a follow-up, just in terms of the fill-finish facility, the second one. Can you remind me -- previously, I recall there was different stability testing and things that had to be completed, but it sounds like this site had sort of been pulled very much forward and was filed earlier, which was fantastic. And so it's the understanding that either of these sites can support approval by September 30, and that's why there's definitely increased confidence and there's not necessarily such a reliance on the Indiana site. And so I have that correct.

And the second question is regarding a potential approval and indications. I know previously, there has been some discussion around the broadness of the label, type 1 versus type 2 in different age groups, given the primary endpoint was on a certain age group definition. Can you just remind us about your confidence around general broadness of the label and how we should think about that?

Michael, great questions. I'll start on the 2 fill-finish facilities and then Akshay will take up the label. So yes, I mean, I guess at the end of the day, we have an enormous amount of confidence in our BLA as the headline news of what's changed from late last year to this year is really the fact that we have 2 fill-finish facilities in our BLA.

One of those, we expect reclassification within a 90-day window from the closeout of the inspection. And subsequently, in that second fill-finish facility, as you aptly noted, we have made massive amounts of progress in accelerating that where all of the drug that is required for the FDA's review and approval has been filed and that drug would be available commercially in early Q3.

So when you kind of take that 90-day window, the up to 90-day window per FDA guidelines for the Catalent Indiana facility, when you look at that window of commercial apitegromab being available in early Q3 from the second facility, we are very confident in this window that we're talking about within Q3 and up to the September 30 PDUFA. And I think that what I'm most gratified about is we try to live here at Scholar Rock by a deep commitment to the patients and families that are impacted by SMA.

And I'm grateful to the team that we took it upon ourselves to say, okay, let's do better this time than we did last time. Let's not rely on a single fill-finish facility. Let's have multiple paths to get to that point where we can deliver the first ever targeted therapy to patients who are living with this disease and the families that are impacted by this disease, and I think we've been able to do that. And tying -- dovetailing nicely into that is the question that you had on the label and our opportunity to serve a meaningful percentage of the community that is impacted by this disease. And I'll turn it over to Akshay to comment on that. Akshay?

Yes. Thanks. Mike, vis-a-vis the label, of course, it's premature to comment on the exact nature of the label before the regulatory deliberations are finalized here in Europe. What I would say is that, generally speaking, the regulators have taken a very important approach to the labels for SMA products. They look at the enrollment criteria of the pivotal studies, which exactly is the population. They look at the portability of the mechanism across the spectrum of disease, and they look at the unmet need.

And so I feel like they've been very good with those principles to serve the community. We've been working with them. As you know, when we got the CRL, the draft label was completed. The one outstanding issue was the manufacturing issue. And both in U.S. and Europe, all I can say is we've had constructive regulatory dialogue throughout the period last year and this year, and we look forward to launching this product for children and adults with SMA.

And Michael, Akshay and I would just note that as we previously have disclosed that where we were towards the tail end of our last BLA review, we were pleased. And that's where we picked up this new application is exactly where we were at the tail end of the last one on the label, and we look forward to continuing to work with regulators to bring us to the point of approval and delivering apitegromab to the community.

And the next question is going to come from Tazeen Ahmad with Bank of America.

This is Wesley on for Tazeen. Congrats to the team on all the progress really. I had a question on sort of the game plan going forward now that you have a PDUFA date in hand. So are there any sort of new types of discussions you can have with payers or other like commercial bodies now that apitegromab is officially under review? And is there any sort of new, I guess, strategies or ways that Keith and the commercial team are sort of laying out the groundwork for potential approval? Or is it just kind of just chugging along and doing what's been done already?

Well, Wesley, as I think you guys all know Keith very well. You would imagine as disappointed as we were to not launch late last year, we had to look at the opportunity that we had to prepare ourselves to be even better to serve the SMA community. That was our obligation. One such piece of that under Akshay and under Lisa Wyman and team was to make sure that this application was even stronger than the last one, and that's inclusive of now the 2 fill-finish facilities and 2 independent paths to approval.

The other obligation that we made is to be better from a commercial perspective. How do you use that time to make sure that you can meet the moment for the SMA community. And I think your question is a good one now with the September 30 PDUFA, but yet being ready for an approval at any time.

And with that, I'll hand it over to Keith to talk about the things that he has been doing and what this means for him and the team. Keith?

Yes. Thanks, David. And Wesley, thanks for the question. What I can tell you is that joining the company 4 months prior to the PDUFA date, we were scrambling for that PDUFA date. We would have been able to launch successfully, but we have really been able to take advantage of the additional time that we have. Some specific examples that I've shared in the past, first of all, with payers, we are able to meet with the payers and with our medical team to really discuss apitegromab and the data. So those discussions are ongoing. We've just been able to take them to a much broader range of payers and really deepen the discussions that we have with them specifically around this.

Additionally, we built out how our site of care plans will be. I've shared with you before that we now, through our partners, have over 10,000 home infusion nurses available around the U.S. that would be able to provide apitegromab to patients shall they choose to go through home infusion. We've expanded our specialty pharmacy network so that no patient has to go to multiple specialty pharmacies to get their different meds that they may be on for SMA treatment, whether it's their SMN targeted therapy or that apitegromab.

And just we continue to really move forward with patient engagement activities. And that's through our program to really have patients demand better treatment for themselves with light takes muscle.

And so I can tell you this. I want you to know that the team has been working very hard all the way through this delay, but we are clearly ready to launch now. So whatever that time frame that will be between now and September 30, I want you to know that the team will be ready to be out there the next day, and we will have supply in the channel very rapidly after approval.

And the next question will be coming from Marc Frahm with TD Cowen.

A lot has been asked already on the PDUFA and apitegromab itself. Maybe just looking at the subcu version. I mean you mentioned you have that data in hand. And once you get the approval for the IV formulation, you'll look to meet with the FDA to discuss it. Just what are the kind of key issues you think you need answers from the FDA on? And kind of what are the range of time lines for when you think you might be able to kind of launch that product depending upon the outcome of those discussions?

Thanks, Marc. Akshay?

Yes. Thanks, Marc. So I would say there are no issues as such. These things are a matter of just alignment with regulators as to what the optimum path forward to bring another innovation to SMA patients and in this case, it would be subcutaneous apitegromab. The Phase I data were excellent, showing a very good bioavailability and pharmacodynamic overlap between 2 routes of administration. And what we have to do now is to share those data following the approval and align on the path forward in terms of any further development that we needed. So that could be PK/PD data and consideration of any additional safety or efficacy.

However, from a safety perspective, obviously, the exposure is maximized with IV apitegromab. And so with the very large database we have in hand already from the studies we've done, we feel very good about safety via additional routes of administration. And so we just want to get on and have those conversations and finalize the path. Once we've done that, obviously, we'll guide you on the time line, premature to speak to that in advance of those conversations.

Okay. And if I can squeeze in also just on the FORGE trial. Just can you kind of walk through what's different about that trial or maybe the supporting data that apitegromab has been able to generate relative to the efforts that Roche had in FSHD and which ultimately, as of a few weeks ago, they disclosed did not lead to moving into pivotal development.

Yes. 3 or 4 points here. Number one, we're obviously very proud of the innovations that have occurred at Scholar Rock with our leading anti-myostatin pipeline. It still remains apitegromab, the only validated anti-myostatin antibody make it through Phase III and delivered the kind of risk and benefit profile that we saw in the Phase III with the SAPPHIRE study in SMA.

Whilst we await that approval, obviously, many others are interested in this target. Roche and Chugai are world-leading company. It was sad to see that antibody drop out. We've never really seen any Phase I data or the FLExDUX4 mouse model data from the Chugai-Roche antibody. So we don't quite know the nature of those data, and we await to see how strong they were. We know our data apart from the positive Phase III study, of course, we have very nice data in the FLExDUX4 mouse model with an anti-myostatin approach showing increase in muscle mass and talk and additional function.

We know that there are, within FSHD normal fibers that can be boosted by means of an anti-myostatin approach. We know other clinical trials in FSHD that have shown increase in muscle mass and function. So we're very encouraged by our data and our diligence. And finally, we believe the Phase II design is different from the Roche study, specifically the inclusion/exclusion criteria and the severity of the disease that we're enrolling relative to what they enroll, which appears to be quite advanced.

And based on our diligence with the experts, we decided because of input from them to go towards the milder end in terms of the Roche scores with patients with established disease where we felt we could still show benefit. And so we remain confident with our validated asset going into that Phase II study and look forward to kicking off very soon.

And the next question will come from Geoff Meacham with Citigroup.

I had another commercial kind of reimbursement question. Just given the range of options in SMA today, how are you guys thinking about incentivizing switches or maybe deploying a more novel outcomes-based pricing strategy just to help the early stages of the launch? And are the strategies different when you look to the EU and the early launch in Germany versus the U.S. launch?

Thanks, Geoff. I think as Keith noted, a cornerstone of our sort of campaign thus far around the disease itself has been an acknowledgment, and we see that the community gets it, that this disease is -- the hallmark is not only the motor neuron, but the resulting muscle atrophy. And so all of this innovation over the last 10 years has been on motor neuron survival and motor neuron health. And this has been needed innovation for the community. And yet, as Keith noted, nearly all patients are wanting their muscle atrophy to be addressed. And this will be the first and only muscle-targeted therapy that's approved.

So we don't necessarily really think about switches, Keith, right? We really think about no matter what you choose to do for motor neuron health, we applaud. And we're going to deliver something that addresses the organ that is the principal organ affected by this disease is the muscle. And that's what's been left behind over these 10 years of innovation that we're finally able to address. And putting that into practice, I know, Keith, has been the cornerstone of what you guys have been talking about with the community, and I'll let you take it from here.

Yes. No, Geoff, we're really not going to be focused on any type of switches because what we've shared before is that in our own market research with treating physicians, we know that 3/4 of them have already said that they believe dual modality is the future standard of care for treatment in SMA. So that's directly targeting the motor neuron and directly targeting the muscle -- so we believe that, that will be how this is viewed.

And then additionally, from a payer point of view, we did share the data that Cure SMA shared with us in the prepared remarks with roughly 1/3 of patients already receiving more than one SMN targeted therapy. It just continues to drive home the unmet medical need that exists with these SMA patients. But as David just referenced, the principal organ that's impacted in this disease is the muscle, and we look forward to bringing forward the world's first muscle-targeted therapy.

And the next question is going to come from Amy Li with Jefferies Company.

David, congrats on all the progress. Just wanted to get a sense of the next steps and time lines for the Catalent site. Based on feedback from the FDA after the reinspection and the Novo closeout meeting, do you expect a Form 483 related to reinspection? And does the speed of your BLA filing acceptance, which was around 30 days compared to the standard 60 days, indicate any FDA urgency or prioritization?

And then finally, on the second manufacturing side, I just wanted to clarify, are you maintaining it primarily as a hedge against Catalent? Or is there a potential for approval of both sites?

Yes. Thanks, Amy. I'll take that last point first. As we noted when Catalent Indiana was acquired by Novo, we knew that Novo was acquiring that facility really for its own internal purposes, and they would have this transition phase into moving "customers" out because they're not a CDMO. That's not their business model. And so all along, we've recognized that we would want to have and would require to have an additional or more than one fill-finish facilities that are outside of Catalent. So all of that, right, was part of our plan even prior to the Form 483 observations that the FDA had in their general site inspection last year.

So I think it's important to note that we see this second fill-finish facility is absolutely vital for all of our global demand. Now we also see Catalent is important. We have drug vial there. We would anticipate that they would be part of our supply chain. And in due time, they're going to phase -- we would phase them out if they're going to be phasing us out. So more than anything else, we see them both as being important. And yet we do think having 2 independent paths to an approval under this BLA is a very significant enhancement to our BLA in 2026 versus the one that we had last year in 2025.

And we also think timing is really good. You note the FDA's urgency and how they've been working expeditiously with us. We do think that was really anchored by a very constructive in-person Type A meeting in Q4 that Akshay led with our team down there, and we are just grateful that the FDA has continued to show a sense of urgency and understanding the needs of the community. So more than anything else, we see a world in which apitegromab gets approved with one or the other or both, and we think that, that's a wonderful spot to be in. We'll let the FDA do their work on the review of the second fill-finish facility and the data that has been generated by us on that second fill-finish facility with drugs becoming available in early Q3.

And we'll also let the FDA do their work expeditiously and thoroughly on their inspection as well as the inspectors concluded that reinspection recently. So we're excited for what the future brings and more than anything else, I think you guys can see these time lines of the 2 facilities have really come pretty much together. And I think that that's a key takeaway to recognize.

And the next question will come from Gary Nachman with Canaccord.

My congrats as well on all the progress. So David, just to follow-on the last point you were making there. If everything ends up being fine with Catalent with the classification, are you still considering pulling the second fill-finish facility from the BLA to simplify it for the FDA? Or you'll just keep it in there regardless to have that better supply chain, even if it would potentially delay the approval and push it out a little bit?

And then just a follow-up. Someone asked before on pricing, but just, I guess, to ask it a little differently. Is there a strategy that would make more sense of launching first in Germany or in the U.S.? Or regardless, it would just be one global price and you're not anticipating any MFN issues. So pricing isn't really a consideration in terms of how you'll stagger the launches?

Yes. These are great -- really great questions, Gary. I'll just make one comment and then hand it over to Akshay. When Akshay and I hosted a call, late in Q1 on the resubmission of our BLA, we did actually talk about the alignment that we've had with the FDA, the dialogue that we had with the FDA throughout Q1 about the submission with both fill-finish plants and the optionality that, that really provided us. And so Akshay, do you want to comment on that? And like if there is a meaningful difference in time line, the flexibility that we may or may not have here?

Yes. I mean just repeating what you said, I think this has been so important to all the progress that's occurred that there's been very constructive collaborative approach between us and the FDA and indeed with the EMA throughout this whole period. And based on that, we submitted both facilities in the BLA with the full support and alignment. And the most straightforward thing is Catlin Indiana is reclassified, is in compliance, and we can start getting drug out of the pending approval. And the second facility would be withdrawn from the BLA.

However, given all the constructive approach that's occurred with the FDA, we'll be guided by them. And in the long run, we clearly want redundancy in the supply chain. And so we look forward to bringing on an additional finish sites. So I think all the options are open for us and the really great position we're in now to serve patients is that by September 30, we're going to be approved by one or the other facility. But in the long run, of course, we'll have established in supply chain.

Yes. So Gary, let's just say the FDA has up to 90 days, but they make a decision faster than that. and they still need to review some information on the second fill-finish. As Akshay had even described about a month ago, we would certainly have that flexibility of then just moving that second fill-finish to an sBLA, which was always an option that we had considered as well. So lots of flexibility and optionality there, and it was a very good question. On sequencing and pricing, Keith?

Yes. So first of all, Gary, as I mentioned in the prepared remarks, the team is ready to launch here in the U.S., but also the team is built in Germany. And so if you think about -- is there a preference for one before the other? No. We want to get this across the finish line, both in the U.S. and in Europe. You mentioned how does this overall affect pricing. We go out with our list price here in the U.S. We go out with our list price in Germany and in Europe.

Remember, Germany is the only place that we can proactively promote right after EMA approval. And so you're promoting and selling at your list price while you go through the AMNOG process and you go through the reimbursement and establishing that price. So it really wouldn't have an impact. And the bottom line is we're going to be prepared to serve patients in whichever market comes first, and there shouldn't be a substantial impact to our ability to price, negotiate in an overall impact on most favorite nations because we won't be at a point right away that we would even trip the cause of most favorite nations.

And our next question will come from Kripa Devarakonda with Truist.

This is Alex on for Kripa. Congrats on the great news today. We have one about the Roche discontinuation of Emugrobart in FSHD. I wanted to know have you seen any uptick in investigator interest in working with apitegromab for your FSHD trial.

Yes. Thanks for that, Alex. So the whole neuromuscular space is very excited about the apitegromab program after in SMA. You're right, the intensity of interest increases. Obviously, everyone is looking forward to the approval in SMA. But the neurology world looks with anticipation towards what a validated anti-myostatin approach like apitegromab can do not just in FSHD, but in a range of diseases.

And so we're looking forward to the start of the study, which will be very soon now, Phase II study in FSHD and with additional indications to follow where we'll study this drug. But you're absolutely right. There is plenty of interest and very constructive input as we think about triaging through these indications.

Thank you. This does conclude the question-and-answer session and also concludes today's conference call. Thank you for your participation, and you may now disconnect.

Hello, and welcome to Scholar Rock's BLA resubmission Call. [Operator Instructions] Please be advised that today's conference is being recorded. I would now like to turn the conference over to Scholar Rock. Please go ahead.

Good morning. I'm Laura Ekas, Vice President of Investor Relations at Scholar Rock. With me today are David Hallal, Chairman and Chief Executive Officer; Akshay Vaishnaw, President of R&D; Keith Wood, Chief Operating Officer; and Vikas Sinha, Chief Financial Officer. During today's call, David and Akshay will provide remarks. We will then open the call for Q&A with all 4 members of the management team.

Before we begin, I'd like to remind you that during this call, we will be making various statements about Scholar Rock's expectations, plans and prospects that constitute forward-looking statements for the purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995. Any forward-looking statements represent our views only as of today and should not be relied upon as representing our views as of any future date. I encourage you to go to the Investors and Media section of our website for our most up-to-date SEC statements and filings. With that, I'd like to turn the call over to David. David?

Thank you, Laura, and thanks to everyone for joining the call today. I am pleased to announce that we have resubmitted our biologics license application to the FDA for apitegromab for the treatment of children and adults living with spinal muscular atrophy. As a reminder, the sole approvability issue for apitegromab noted in the complete response letter that we received on our priority review PDUFA date was related to observations identified at a routine general site inspection of the Catalent Indiana fill-finish facility, which is owned and operated by Novo Nordisk.

Our BLA resubmission is an important step forward in our mission to deliver apitegromab to the SMA community as quickly as possible. Patients with SMA continue to experience muscle wasting and functional decline despite ongoing chronic treatment with SMN-targeted therapies. Apitegromab has the potential to be the first and only muscle-targeted treatment to improve motor function in SMA by addressing the principal organ clinically affected by the disease. We continue to work urgently to bring this transformative therapy to children and adults in need.

As we have noted, since our constructive and collaborative in-person Type A meeting last quarter, which included Cure SMA and Novo Nordisk, we have been gratified by the agency's shared understanding of the high unmet need in the SMA community and the shared sense of urgency to bring apitegromab through the final step in the U.S. regulatory process. Since that Type A meeting, we have made steady and rapid progress. This has enabled us to resubmit our BLA in complete alignment with the agency to include Catalent Indiana and Scholar Rock's additional fill-finish facility, reflecting the meaningful progress at both fill-finish facilities.

Let me first address the rationale for resubmitting the apitegromab BLA prior to FDA reinspection of Catalent Indiana. This decision was made in alignment with the FDA and reflects the significant progress that has been made by Novo Nordisk at the Indiana facility. As we discussed during our Q4 call, the FDA and Novo had a constructive meeting in early Q1, which was followed by an FDA site visit. During both the Q1 meeting and the site visit, no additional corrective actions were requested by the FDA to Novo's remediation plan.

FDA also stated to Novo that it intends to conduct a site reinspection following routine manufacturing activities, which resumed in late February. Based on this progress, we were pleased to align with the FDA to resubmit our BLA prior to reinspection. We continue to anticipate a reinspection in the coming period. I would like to now turn to the decision to include our second fill-finish facility in the BLA resubmission.

As we discussed on our Q4 earnings call, I continue to be very pleased that progress with our second fill-finish facility is moving quickly to strengthen our supply chain and support future growing demand across our planned global commercial footprint. On March 3, we engaged with the FDA in a positive Type C meeting to discuss our progress towards qualifying this second facility. Based on our accelerated fill-finish time lines for apitegromab commercial supply, we aligned with the FDA to include the second fill-finish facility in our BLA resubmission.

Our approach provides us significant optionality with 2 independent paths to apitegromab's FDA approval. Importantly, it reflects both our confidence in an FDA reinspection of Catalent Indiana in the coming period and our accelerated time lines to release commercial apitegromab from the second fill-finish facility. We anticipate a review period of up to 6 months from the date of resubmission and a PDUFA date in late September.

Akshay will share more details on the BLA resubmission and discuss the flexibility and optionality we have with 2 fill-finish facilities included in the application. We remain committed on behalf of patients, and we are grateful that important progress continues to be made. The sustained cadence of activity over these past few months reflects the efforts by all parties to bring apitegromab to children and adults living with SMA. We expect this momentum to continue. And commercially, we are ready now.

Our team continues to operate with urgency as we prepare for the U.S. launch of apitegromab. Scholar Rock remains focused and disciplined, advancing the critical activities and capabilities required to deliver a seamless launch and support patients from day 1. In addition to the U.S., we look forward to serving children and adults with SMA in Europe. The review of our MAA is progressing very well, and we expect a mid-2026 decision from the European Medicines Agency. We continue to build momentum with launch readiness activities and anticipate a launch in the second half of the year, beginning with Germany.

Akshay will share more details on the continued progress of our apitegromab's MAA shortly. We know it is not a matter of if, but when apitegromab will be approved for children and adults with SMA in the U.S. and Europe. We continue to be emboldened by the commitment we have made to the more than 35,000 patients globally living with SMA who have received an SMN targeted therapy. And with that, I'll now turn the call over to Akshay. Akshay?

Thanks, David, and good morning, everybody. As David noted, we remain focused on bringing apitegromab to children and adults with SMA as rapidly as possible. To that end, I'm delighted that based on alignment with FDA, we have now resubmitted our BLA with Catalent Indiana and a second U.S.-based fill-finish facility. The updates to the BLA for resubmission were limited in scope and primarily composed of a standard safety update from patients enrolled in the ongoing apitegromab clinical studies and the early access program.

The resubmission document also included the draft labeling from our last round of interactions with the FDA. Regarding the path forward, we anticipate an FDA decision on acceptance within 30 days of this filing and up to a 6-month review period. Based on Novo Nordisk's progress, we're confident in Catalent Indiana's readiness for a reinspection.

The steps required are as follows: first, an unannounced FDA reinspection of the Indiana facility will occur in the coming period. Next, following conclusion of that reinspection, any 483 observations will be issued. Parenthetically, I note that it is typical for the FDA to issue a Form 483 following inspections, and this would not necessarily limit FDA's ability to favorably reclassify the status of the Indiana facility. And finally, subsequent to the reinspection, Novo will have 15 business days to respond to any potential observations, following which FDA would review the responses and reclassify Indiana as appropriate.

Whilst the length of the process I've just outlined can vary, we remain encouraged by the rate of progress and the level of FDA engagement. With both Catalent Indiana and the second fill-finish facility included in the BLA resubmission, importantly, we now have significant optionality with 2 independent paths to FDA approval. We've been guided by the agency that whichever fill-finish facility leads to the most rapid approval will remain in the BLA while the other could be removed. If there were a case where one facility was removed, we would subsequently submit an sBLA for the other facility shortly after the apitegromab approval to strengthen our supply chain and support future commercial demand.

Importantly, we anticipate having plenty of commercial apitegromab vialed and released from our second facility a few months prior to an anticipated PDUFA action date. With the collaborative and urgent approach that the FDA has shown since the Type A meeting last November, we anticipate a decision by no later than the end of September 2026.

Turning now to Europe. Our MAA for apitegromab for the treatment of children and adults with SMA continues to progress well through EMA review. As we mentioned during our Q4 call, approval in Europe also requires FDA clearance of the Catalent Indiana facility. Based on our discussions with EMA, they're aware of the progress at Indiana and are comfortable with the review time line that accounts for the FDA's clearance of that site. We continue to be very pleased with how the review is progressing and believe we're on track for a mid-2026 decision in Europe. With that, I'll turn the call back over to David. David?

Thanks, Akshay. In closing, we remain focused on bringing apitegromab to children and adults living with SMA. We are working expeditiously to deliver on our ambition that globally, any patient with SMA who can benefit from apitegromab should have access to apitegromab. This is indeed what we know well and what we do well, and we are confident in the significant opportunity that we have to serve patients with SMA, which provides a strong foundation for growth through the end of this decade and well into the next.

I would like to thank the FDA, Novo Nordisk and our second fill-finish facility for their continued high level of engagement. I'd also like to thank the Scholar Rock team who show up every day with relentless focus. And importantly, I am grateful to Cure SMA and the global SMA community for their continued support. We look forward to updating you on our continued progress. And with that, we'll now open the line for questions. Operator?

[Operator Instructions] Our first question comes from the line of Mani Faroohar with Leerink Partners.

Congrats. Great day for you guys and most importantly, for patients. A quick one on approval time lines. You laid out a path to presume a PDUFA date that assumes kind of a usual 6-month external review process. Given how much you've disclosed and how often we and others have talked about the amount of the review that has already occurred, some label discussions, review of the data packet under prior submission, how should we think about that timing? Is that -- should we think of that as an outside date, midrange of expectations? How should we think about?

Yes. Thanks, Mani. I'll start and then Akshay will jump in. I think we were very clear that we view getting back on file with the anticipated acceptance of our resubmission as being accepted under Class II for the following reasons. The reinspection has not yet happened at Catalent Indiana. And of course, the second fill-finish facility requires new data for the FDA to review.

Importantly, as Akshay laid out, we are going to have commercial drug release from that second facility several months before an anticipated sort of Class II review period of up to 6 months. But that's how Akshay and I are looking at this is up to 6 months. And hopefully, the FDA's engagement really since our highly collaborative in-person Type A meeting last quarter is sort of a predictor that we're going to continue to work very collaboratively and urgently together. Akshay?

Yes. And just on that last point, I think we've been very gratified and grateful to the FDA for that collaboration and how much they have tried to help us with the best path forward. And I'm sure during this review period, they'll do the same. As you said, September is the standard 6 months or so time line. But I'm sure everyone, including us, FDA and all the parties will do their best to get this drug approved into patients as soon as possible. So let's go from there.

And Mani, just to cap it off, you are absolutely right. The resubmission is a lighter document, right? I mean -- and Akshay can comment on really what is in the resubmission. This is really anchored to clearing 1 of these 2 fill-finish facilities more than anything else, Akshay?

Yes. I mean there are these 2 significant options now available to us that the FDA is going to help with during their review. And I'm sure they will work as expeditiously as possible to enable getting this drug to patients based on all the interactions we've had and the quality of the supportive dialogue we've had. So it could happen before September. I'm sure everyone is trying to because all parties appreciate the urgency of getting this drug to SMA patients. But at the same time, we have to let FDA do their work.

That's helpful. And a quick follow-up, which I guess maybe is more of the cost question or a commercial one. As you've had time to engage with the market with this somewhat more protractive than usual review process, given what's the catalyst, how should we think about pricing in terms of where should we think about potential price ranges that you'd launch at? Just I know you can't give us an exact number, but where we should look in terms of precedents, et cetera. And while I know this is certainly not the type of indication that draws a lot of pricing scrutiny, to what extent does the evolution of the U.S. versus OUS pricing discussions, MFN, et cetera, influence how you think about that?

Yes. It's a great question, Mani. I'll start. This is David. First and foremost, as we noted and a big part of wanting to have multiple fill-finish facilities is our anticipated 50-country operating platform so that we can reach the 35,000 patients that have received at least one SMN-targeted therapy. So we want to have -- we really want to have a very robust supply chain. We've also looked and feel like with the things that are happening with MFN, it really -- our global plans are unchanged in any way. We see very little impact to Scholar Rock in the global launch of apitegromab.

As it relates to pricing, it's still a little premature, but I will say that we continue to be anchored by a couple of principles as we think about establishing a price for apitegromab. One is the rarity of the disease in which there's somewhere between 5,000 and 7,000 patients in the U.S. that have received at least one SMN-targeted therapy and about 28,000 outside of the U.S. So it's quite a rare disease.

Secondly is the severity of the disease. And as Akshay and I have noted multiple times, despite the use of ongoing chronic very important SMN-targeted therapies, patients tend to, over time, revert to the progressing form of SMA where there's a loss of motor function. And then lastly, the compelling clinical data that we've been able to deliver through our robust clinical development program over these last 7, 8 years where we were able to show that patients had a return of a gain of motor function as opposed to a loss of motor function. And we think those things combined are very important considerations as we move forward and establish a price. And that again, as I've noted, we see very little impact on MFN to us, and we are really looking forward to reaching patients in upwards of 50 countries around the world over time.

Our next question comes from the line of Tessa Romero with JPMorgan.

Congrats on all the progress here. So first one from us is procedurally, at this Type C meeting, did the FDA align with you on submitting the BLA before the reinspection because your second fill-finish facility was BLA ready? Or was it also because of progress at Catalent? And then second question, just as a matter of housekeeping. The facilities are not cleared in your filing, right? They are just both included.

Yes. So they are both included in the resubmission. And Akshay should take on. I think your question is a really good one. The resubmission, including both fill-finish facilities was on the merit of the progress in each one of the fill-finish facilities. And I think that, that is a really important point, and I'm glad you asked the question. And for a closer look at that, I'll turn it over to Akshay.

Yes, a closer look, but I would also say that we have to respect the process and the FDA always considers each sponsor and each trial in the context of what's contained there, the unmet need, the quality of the data and the progress to date. So in our situation, they looked at the 2 sites we're working with and they guided us to this resubmission, which we're grateful for. Everyone will work hard now to bring one of those to fruition and get this drug to patients. But I'm not going to go into the exact back and forth at the various meetings we've had.

We're just grateful that there have been multiple meetings and that there's been good alignment. And very good guidance to get this drug to patients as efficient as possible. And we do think it was helpful as we noted on our Q4 call and again here today, the interactions that FDA has had with Novo, both in terms of the early Q1 meeting and the site visit, all is helpful for the FDA to assess the progress being made by Novo on their remediation plan.

Our next question comes from the line of Michael Yee with UBS.

This is Kyle Yang for Michael Yee. So just help us understand the scenarios there. So hypothetically, if the Catalent reinspection is not successful, do you expect to still able to get approval with the second facility? So what other boxes do you have to check with the second facility to ensure this can get approved by the potential September PDUFA date? Just help us understand the cadence of events if the reinspection is not successful.

Yes. No, thank you. And I think Akshay and I tried to illuminate in our prepared remarks, the beauty of filing with all the progress that's been made at both fill-finish facilities, the beauty of filing with both really provides us some wonderful flexibility and optionality, and I'll have Akshay make some comments on that.

Yes. I think this filing has been enabled by outstanding work by Novo Nordisk by our second fill-finish facility. Obviously, all our colleagues here at Scholar Rock have been working with those 2 facilities. And everyone in that time frame has worked as expeditiously as possible to make this filing happen. And most of all, it's all happened with complete transparency with FDA and their guidance. So I think we're looking forward, hopefully, to a successful reinspection of the Catalent Indiana facility based on all the progress they've made and they've reported to us and the agency.

We're optimistic about that. Of course, the FDA has to do an unannounced inspection, and we have to let them do that work, but we do feel good about Catalent Indiana and they're on the right track. So that is the first goal to get Catalent Indiana facility back online with the FDA's blessing and get this drug approved within the time frames we've already discussed.

Now the beauty of it is that based on the guidance by the FDA, we've worked hard on a second fill-finish facility. And it's great that the progress we've made to date has also allowed inclusion of that in this resubmission again with the agency's blessing. And I'm not going to sort of outline exactly where we are in that process, but I think most of you are familiar that bringing the second facility involved engineering runs, PPQ runs and all the rest of it. We've made outstanding progress on all of that stuff. There's more work to do and more data to file. But again, we're very pleased that there are 2 significant options here for Scholar Rock and for patients and the agency will be endeavoring to get to the finish line with one or the other or both.

Thank you, Akshay. And again, I would just highlight, as Akshay noted earlier in the call, we think it's really important with those accelerated time lines that we will have commercial apitegromab ready for release from that second facility several months before an anticipated late September action date.

Our next question comes from the line of Amy with Jefferies.

Congrats on the progress. Just quickly on the September PDUFA date and then the 30-day to acceptance, what visibility have you had gotten from the FDA on the reinspection timing? Would you need to get reinspected before the FDA accepts the BLA? Or have you -- or could that happen afterwards? And then, yes, and then I have a quick follow-up on the second facility.

Sure. Yes. No, I think the way to look at it, right, is, first of all, everything that we've described today, as Akshay and I have noted, has been in complete alignment with the FDA through really high-quality interactions with the FDA. So the resubmission of the BLA, which is inclusive of both facilities is based upon the progress of each one of those facilities, recognizing that we are now resubmitting prior to reinspection, which again was agreed upon with the FDA. The way to look at it is that, that reinspection would not need to have happened for the acceptance of our resubmission. But the way to think about it is it would be a review issue as part of our resubmission. The outcome of that inspection would be the key review issue, if you will. And I think that's the right way to look at it.

Okay. And then in terms of the second fill-finish facility, have -- during your Type C meeting with the FDA, have they been able to review some of the initial data from PPQ runs, comparability, bridging data? I know we discussed that you are -- they're allowing kind of an accelerated pathway because you're able to take away some of the data you generated from Catalent. Just wanted to see from a September -- like when this site will be ready, if there will need to be inspections and if that site will kind of fulfill the September PDUFA just in case anything happens to Catalent?

Yes, I'll start and then Akshay can jump in. But yes, the FDA in that Type C meeting is well aware of all of our time lines, all of the progress, everything as Akshay just laid out from tech transfer, engineering runs, PPQ runs, release of product, when all of the data that they would have access to, leveraging data from the other pillar. All of that was obviously discussed and agreed upon with the agency. And then I would just note that if there is a PLI required, it would all be contemplated within the framework of a review time line that we sort of anticipated would provide a late September PDUFA date. Akshay?

Yes. So I think just to add one thing to what David said, which is that the second fill-finish facility is a U.S.-based facility and is in good standing with the FDA. There have been multiple inspections before now. So we have a high degree of confidence in the site, and they're executing on that sort of list of work that David just mentioned. FDA is well aware of where we are on that path and again, in alignment with all parties we've now resubmitted the BLA.

Our next question comes from the line of Tazeen Ahmad with Bank of America.

I have one on the label. Based on discussions that you've had with payers so far, is there a specific language that you think is going to be necessitated in the label in order to allow for broad-based coverage because this is a rare disease, and I'm just trying to understand if there is something outside of simply getting an approval from the FDA that might enhance and make more efficient the process to get covered.

Yes. I'll start and Keith may want to jump in. Tazeen, as we've described it over these past few months, Akshay, myself, the company felt really good about where we last left it with the agency in our label discussions, which were just a few days before the PDUFA. And it's called out in the CRL that is redacted that the FDA released to the public that they would like us to just go back to that label in our resubmission, which we have done. So we felt really good about where we are, but we have been very disciplined not to comment too specifically given the fact that we want the agency to do their work. And when we talk about the label, we want to actually have an approval letter from the FDA.

Nonetheless, I think what you're highlighting is given some precedents of the FDA and the way they've looked at SMA as one disease as opposed to sort of segmenting it out, we generally felt like we were in a good spot to be able to serve a meaningful number of patients with SMA. And I would just say that Keith and his team have used this time very, very well to engage with key national, key regional payers and establish alignment on -- begin to establish alignment on just sort of how would one think about a label that might be broader than that of a Phase III pivotal trial criteria.

And I think that work will continue to be ongoing. But as I've noted, and I'm very thankful to Keith and the team that they are ready to launch now. And I think that's reflective of a lot of work that's been done with the physician and healthcare provider community, the patient community as well as the payer community, we are ready to go.

Keith, anything you would add?

Yes. I guess, Tazeen, the only thing I would add is when you bring the payers into it in our meetings with them, although we do not discuss an indication statement because it wouldn't be appropriate to as we go through the discussions with the FDA. What we have done is talked about example policies that could potentially benefit patients that can benefit from apitegromab can have access. Our goal is to have policies that are put in place that are not aligned with the inclusion/exclusion criteria of our Phase III, but more aligned that would give a broader sense of utilization for the community. And it's been well received in our discussions to this point.

Our next question comes from the line of Marc Frahm with TD Cowen.

Congrats on the update today. Maybe just thinking through the kind of time lines as you've kind of spoken to a bit earlier on the call and certainly in prior venues, there is some hope that certainly, if the inspection goes well, the Catalent Indiana site might be able to support an approval, well a rapid approval on resubmission and well ahead of the PDUFA. Would the secondary fill-finish be ready from a stability and everything else perspective if that would happen? Or would you possibly in the kind of very good scenario with Catalent need to kind of pull the secondary facility and ultimately resubmit it?

And then kind of vice versa, if things go maybe not as well as expected in the inspection, do you think you need that absolute full PDUFA window to have that second facility the product really ready from a stability in all the different follow-up assays that have to happen after these engineering runs? And I have a follow-up.

No. Thanks, Marc. Look, I think for sure, one takeaway from this call is that the time lines have been getting closer together at both facilities, largely due to how much we've accelerated the time lines at our second fill-finish facility as noting that we have now resubmitted our BLA here in Q1, inclusive of that second facility and commercial product being released from that second facility several months before an anticipated late September PDUFA. So all of that bodes well for us.

Obviously, when you're releasing product from that facility, the FDA would have all of the data from that second facility that they would need. And I think that Akshay will cover this once again. I think what's elegant about today's announcement is that with meaningful progress at both fill-finish facilities, it offers tremendous optionality and flexibility for us. And I think it allows us and our partners and of course, the agency, which we're very gratified to them for their ongoing engagement on this. It allows them really the opportunity to continue to work in an expedited fashion to meet the needs of the SMA community. Akshay?

Yes. So Marc, I think both sites have made tremendous progress. The second fill-finish facility, the sequence of engineering run, PPQ run the stability program, the progress that's been made towards those aspects and also the work that is yet to be done on some of those. That's all being discussed internally with our second fill-finish facility with the FDA. And that body of work is well underway. And we feel that within the 6-month time frame, one or both sites will be ready. And so we're very confident with the BLA resubmission that we're enabling this drug as best as we can and then allow the FDA to do this work now and get us to the finish line. By September, hopefully soon it's all possible that both -- either site could work out.

And then, Marc, to your point, right, I mean, if the time lines are a little bit more distant apart, I think Akshay highlighted the -- it's very nice to have some optionality to drop one, move forward with an approval and then shortly thereafter, resubmit an sBLA, which is always contemplated in our planning as well. We think that this announcement today is wonderful news more than anything else for the SMA community, but we have a significant amount of optionality moving forward from here.

Okay. That's all very helpful. And then just if you end up having to go down that path of the secondary facility becoming the primary and kind of sole approval, do these early runs have enough -- are you building enough inventory and capacity through these early runs to fully supply the commercial market? Or is there a scenario where if the launch goes well, if demand is good, that maybe there's a period where you kind of have to meter access to the drug just to build up the kind of supply chain?

Yes, Marc, that's a great question, and I'm happy that you asked it. So we can clearly say that we will have plenty of commercial apitegromab to launch with several months before a late September PDUFA date so that Keith and the commercial team would be unencumbered in meeting the needs of the SMA community at approval. So we're very grateful to all of the parties, including our second fill-finish facility and our internal team that has been accelerating the time lines on a daily basis for us to be able to say that.

So this is not -- certainly not us trying to get cute with an approval, but there'd be limited supply. There will be more than enough supply to meet the needs of the marketplace with commercial apitegromab from the second facility alone. But it is our intention that both facilities, not a matter of if, but when, they are both approved one way or the other through this current resubmission or one gets dropped, we get approved and then an sBLA so that all drug would be in the marketplace at some point in time. But certainly, we're in a good spot from an inventory perspective, and that's been contemplated in all of our time lines with the second fill-finish facility.

Our next question comes from the line of Geoff Meacham with Citigroup.

This is Jarwei on for Geoff. I want to add our congrats on the progress with the regulatory agencies. Maybe just real quick on the EMA for the mid-2026 expectations, the time line, I guess, you previously said that the European agency is comfortable with the current time line as is with progress being made at Catalent. But I guess if things were to shift to the second fill-finish facility, whether it's just delays in FDA with Catalent or maybe a CRL again, could you maybe expand on how that might affect the current expectations for mid-'26?

Yes. And I think it's an important question, and it's one that we and under Akshay's leadership and the team at EMA, this has obviously been very public since our disappointing news late last year, but one that has been out in the open and discussed as we all continue to be very pleased with the progress we're making with our MAA and the ability to eventually serve children and adults living with SMA in Europe as well as the U.S. And Akshay can comment on your question specifically, should we rely on the second fill-finish facility?

Yes. So good question. And the first thing I want to say is that we have to remember tremendous progress made by Nova at the Catalent facility. And so we're looking forward to hopefully a successful reinspection in the coming period, and that will enable all parties to help us get to the finish line, FDA, EMA and everybody. So that's the first thing to say. I think the second thing is, as we've emphasized about the guidance we've had from the FDA, we've also had very good guidance all along and understanding with the CHMP of the EMA during this review process. And I think should it come to a necessity to switch to the second fill-finish facility, I'm sure we'll be able to come to an understanding. But we'll cross that bridge when we come to it, and we'll obviously keep everybody informed. But so far, excellent meeting of minds on all sides. So looking forward to getting this Catalent facility through the reinspection with Novo obviously in the FDA review and then we go from there.

Thanks, Akshay. And I think the questions have been very helpful today because they do illuminate that this resubmission with both fill-finish facilities is evident of meaningful progress that the FDA has seen at both fill-finish facilities, including the progress that Novo has made at the Indiana site.

Our next question comes from the line of Kripa Devarakonda with Truist.

Let me also add my congratulations on the regulatory progress. A couple of questions for me. One, with better visibility into approval time lines, do you expect any incremental cash burn between now and approval? And second one, a competitor made the decision to discontinue their myostatin program in SMA. Would love to get -- Akshay, I would love to get your thoughts on what this means for the anti-myostatins, especially in these rare neuromuscular diseases. And Keith, maybe you can comment on -- does this change your pricing strategy in any way because there's less of competition now?

Yes, Kripa, I'll start, then we talk on the balance sheet and then Keith can kind of come back to any implications with really the final potential competitor discontinuing their SMA program and announcing that just in the last couple of weeks and any implications for us. I would just note that for a long time here in the coming few months, I'll be starting my 10th year at the company. We have just been really excited about the unique way that we're able to inhibit difficult-to-inhibit proteins or growth factors in the body, and we've chosen myostatin as our first meaningful target to inhibit.

As you know, there's been 20, 30 years of failure in the pharmaceutical and biotech space to try to drug effectively this very elusive target. And we think over these last couple of years, it's really borne out that we are the world leaders in myostatin biology with apitegromab, with subcu apitegromab and with SRK-439, we feel like we have quite a unique sort of capability here. And our aim is to not only transform the lives of children and adults living with SMA, but Akshay has very meaningful plans across a range of rare, severe and debilitating neuromuscular disorders that we look forward to keeping you updated on. Related to the cash burn, Vikas, with some visibility, I'll have you comment and then, Keith, you can talk about pricing.

Kripa, your question was with the expenses. Most of the expenses that are already in the numbers are headcount related and that our team is already fully ready to launch as quickly as possible. And the launch costs are right now gated for us to go forward. We'll look at defining the timing of some of them, but it's not going to be really material from where we are. We have a good cash balance, and we have -- the PRV is going to come on the approval and $150 million more that we could get at the time of approval from our lenders. It gives us a very, very good position right now. So small amount might move up and down, but nothing material to worry about.

Yes, Kripa. And then in regard to pricing and what this means for us, as we've shared before, we've been doing a lot of work on price, not only for the U.S. but also outside of U.S. and taking several things into consideration. But the bottom line is our meetings that we've had with payers and actually with governments, it is clearly known that there still exists a substantial unmet medical need in SMA. As David referenced before, the majority of these patients will plateau and then begin to regress. And ultimately, our data being the first and only myostatin to have clinically significant and statistically significant results in a registrational trial allowed us to turn a loss of motor function into a gain of motor function.

And that is not being lost on the payers that we are speaking to and on the government. I guess the last thing that I would mention is just we just believe that the total impact to any single payer or government is probably not very large because we are looking at a rare disease as a whole. So we will continue to do this. And trust me, I really look forward to the launch call, and we'll get really specific on pricing.

And then finally, Kripa, I would just say on behalf of everyone here at Scholar Rock, we do not take this responsibility lightly that we are the only company that has successfully developed a therapy that targets myostatin safely and effectively through Phase III and that we are really poised for many years to come to be the first and only company to launch a muscle-targeted therapy to patients in need. And this responsibility sits with us every single day to do it in a very good stewards of a community that we ourselves look up to every day for strength and ambition and optimism, and we look forward to holding that mantle with a great deal of pride.

Our next question comes from the line of Etzer Darout with Barclays.

This is Luke on for Etzer. So with the time lines here, did FDA give any information or do you have any idea as to which facility may reach that finish line first? And how does selection of a facility in the stage in this way affect your commercialization plans in the future? Do you kind of have like a favorite child in this site? And if it ends up being that Catalent isn't able to -- if they get CRL'd again, I know you mentioned to a previous question that you have enough for the commercial launch for the second fill-finish, but will you need to acquire more capacity from them to maintain a further launch?

Yes. Thank you. I'll address the question. I think as we noted today, we were gratified to be in alignment with the FDA to resubmit our BLA with both Catalent Indiana and our second fill-finish facility. We were able to do that based upon meaningful progress that's taken place at both sites. Novo Nordisk has been working diligently on their remediation plan and their readiness for reinspection in the coming period. And certainly, we think that, that progress was illuminated earlier in this quarter with a Novo FDA meeting as well as a site visit.

At the same time, our team at Scholar Rock has been working diligently with a second fill-finish facility that we chose very carefully that had lines that were validated for our vial configuration that had a clean inspection history with U.S. and international regulators that had dozens of commercially approved products at that facility. And we just thought they were a great match for us in terms of the urgency to meet the needs of the SMA community, and we're also very gratified at that second -- for that second facility's work to help us accelerate the plans to be in a position here in Q1 to be able to resubmit our BLA with both fill-finish facilities.

And I think as Akshay and I noted repeatedly in this call, there's a lot of elegance to having the flexibility and optionality to have these 2 fill-finish facilities in the BLA resubmission. And with alignment of the FDA, there's 2 independent paths to an approval here for apitegromab, which will be the world's first and only muscle-targeted treatment for children and adults living with SMA. So we're in a good spot with multiple paths to approval and plenty of drug. Either way we get there, we would anticipate at some point in time, both facilities will be approved as part of our file, and we will have wonderful redundancy in our supply chain to support not only the U.S. market, but our high ambitions to reach patients in 50 countries around the world. Thank you for your question.

[Operator Instructions] Our next question comes from the line of Evan Seigerman with BMO Capital Markets.

This is Conor MacKay on for Evan. Maybe just 2 quick follow-ups, if we may. First one, what are the remaining gating items, if any, that still need to be completed at the Catalent Indiana site before approval can occur? Or is this really just a matter of waiting for a reinspection at this point? And then maybe on commercial launch readiness as well. We appreciate some of your earlier comments on inventory, but we're wondering if maybe you could share anything else on how you're thinking about building physician awareness or other pre-promotional activities.

Great question. I'll quickly address the first one and then Keith on the second. But I think Akshay laid it out nicely. We expect an unannounced reinspection in the coming period. The FDA did note on their recent site visit to the Indiana facility that they would be coming back for a reinspection following a routine manufacturing activities, which just resumed at the end of last month at that site. So we're expecting an unannounced reinspection in the coming period. We would note that about 3/4 by FDA's own dashboard on their website, about 3/4 of inspections, reinspections have some observations associated with those.

So we would expect that to happen. That doesn't necessarily preclude the facility from being cleared and reclassified. That would happen at the last day or the closeout meeting of a reinspection at the Indiana site. Novo would then have 15 days to respond to the Form 483 observations that may or may not be provided. And then sometime after that, the FDA would make a decision on clearing and reclassifying the facility. So those are the steps that we would expect at this point. And as we said, quite a bit of progress has been made by Novo and the FDA in Q1. So it was a good month from that perspective. Again, in any event, we're very excited to be -- have an established time line here of up to a 6-month review that we would anticipate and hopefully could be faster. And with that, I'll turn it over to Keith because he and his team while making the most of the extra time that we have had, they are ready to launch now. Keith?

Yes. Thanks, David. Conor, all I can tell you is that for all the members of the team, they're seeing this press release this morning and they're texting and because they're so excited to finally be on the clock, they are ready to launch. We continue our disease state education plans that we have been executing on and building relationships with not just the prescribing physicians, but the entire SMA treatment teams. We've grown our specialty pharmacy network since the September 22 PDUFA date. We've grown that so that we will be able to serve all patients regardless of what SMN-targeted therapy they're on from the same specialty pharmacy that they currently use.

We've built out a 10,000 nurse home infusion network, continued work with our payers. We've been able to expand this beyond national to regional and even Medicare and Medicaid. And we've really been testing and retesting our Scholar Rock supports program so that we can take care of these patients when we finally have approval and we're able to enroll them in our program and help transition them from a prescription to a patient on treatment. So trust me when I tell you that the team is ready. We will continue to drive hard, but we'll be ready for launch.

Our next question comes from the line of Kalpit Patel with Wolfe Research.

Gugan on for Kalpit. Congrats on the resubmission. In the event of a successful reinspection, do you anticipate a quicker turnaround than the 6-month time line? And any historical precedent that you can refer investors to in a similar situation for resubmission?

Yes. So the resubmission is in. It's been submitted to the FDA. They've validated that we've resubmitted. And as Akshay noted, we would expect in upwards to the next 30 days, they would likely apply a Class II to this. We want to be careful to say up to 6 months because there are precedents where once the reinspection is done and a facility gets reclassified, it can be earlier than that. We certainly want the FDA to do their work and take the time that they need to do their work. So that's important. But we are -- continue to be really gratified with the FDA's high level of engagement since our highly collaborative in-person Type A meeting last quarter that Akshay presided over.

And we would just be hopeful that in the future, if there is an option to be able to approve this in that 6-month window ahead of an action date, that could happen. But of course, we'll leave that up to the agency, and we're just very grateful that the agency continues to be highly engaged and focused on the needs of the SMA community.

Our next question comes from the line of Andres Maldonado with H.C. Wainwright.

Just a quick question on some of the commentary on the payer dynamics here. I guess, how are you thinking about budget impact discussions where adding apitegromab may force trade-offs within rare disease portfolio? I guess the commentary has been you've had productive conversations with payers, but how should we be thinking about the scenario of how this could potentially slow, I guess, the uptake despite the strong clinical rationale?

Yes, it's a great question. I think Keith and I for a long time have said like we expect demand from the physician and patient community to be quite high. But we do know that there are a lot of precedents where early on for a number of reasons. There can be payer headwinds, again, not a matter of if they'll pay, but when they'll pay. And we would see increasingly higher conversion rates that happen faster over time, but that we would note a number of different factors, things like miscellaneous J-codes, the fact that this is an every 4-week infusion, the fact that the label may be beyond that of the Phase III clinical trial criteria, the establishment of medical policies and things of that nature.

But I think the most important thing you're asking is this is the first of its kind therapy that targets the muscle. For 10 years, we have seen a lot of innovation around motor neuron survival. And I think we and the SMA community are certainly grateful to the 3 therapies that are out there that can focus on motor neuron survival. But as we noted in today's call, the organ that is the principal organ that is clinically affected by this disease is the muscle. And for a long time, this has been noted as a very high need of the SMA community.

And I think what you're saying is, will the payers be supportive of that. And I think at a high level, what Keith and the team is seeing is the payers get it. They've seen the long-term data of patients that are on an SMN-targeted therapy alone. They see that over time, those patients plateau and revert to the progressing form of SMA and that in our clinical trial, what we were able to show is those patients move from a loss of motor function to a gain of motor function. And we think that, that sets up for a very nice foundation of partnership between Scholar Rock, the SMA community and our payers over time, and we're certainly looking forward to that moment in time, Keith, when your team is launching.

Yes, absolutely. But I mean, your point is well taken. It is going to take some time, and that's why we've led to consistent and steady growth over time because ultimately, with these payers, even with SMN-targeted therapies today, 50% of them are first rejected and have to go through an appeal process. But ultimately, about 87% of the time they're prescribed that prescription is, in fact, filled, and we expect that we'll get to a very similar spot with apitegromab post launch, maybe not the first month after launch, but after we get some of those headwinds out of the way that David just referred to, ultimately, the unmet medical need and the benefit that apitegromab provides, we believe, with the SMA community will win out.

Ladies and gentlemen, I'm showing no further questions in the queue. That concludes today's conference call. Thank you for your participation. You may now disconnect.

Good morning, everyone. My name is Etzer Darout, senior biotech analyst at Barclays. It's my pleasure to have Scholar Rock with us this morning. With us on stage, we have David Hallal, Chief Executive Officer and Chairman at Scholar Rock.

David, thank you for joining us this morning. I'm sure most folks are familiar with the Scholar Rock story. But maybe just to help those that are not, maybe just a brief introduction, some introductory remarks would be great.

Thanks, Etzer. So Scholar Rock is a biotech company that this year, will celebrate our 15th anniversary. We were formed with some highly innovative technology out of Tim Springer and Len Zon's lab back in 2012. The focus of this was to develop antibody technology to block otherwise difficult to inhibit growth factors in the body, largely around a family of growth factors and proteins. And through this technology, we've been able to target some prior very difficult to drug targets in the body by biotech and pharma for several decades.

And as Etzer and many of you know, our most prolific success so far has been the inhibition of myostatin, which has led to, after 3 decades of pharma and biotech looking to effectively drug myostatin, the first positive pivotal trial targeting myostatin, in this case, in children and adults living with spinal muscular atrophy. We reported out on that data at the end of 2024 and are now eagerly awaiting an FDA and EMA approval and eventual launch this year. So we're super excited about the position that we are in.

right. No, that's great. And you recently announced a new debt instrument, and one of the questions that we've gotten around that is whether or not you think that this is something that could get you to profitability, again, assuming that everything goes as planned for apitegromab.

Yes. So we announced this $550 million debt instrument last week on our Q4 call, and we're going to be pulling down an additional $100 million by the end of this quarter. And it's important that we fund our operations because, Etzer, as you know, 2026 is set up to be a transformative year for Scholar Rock.

As I noted, we are in the final stages of the regulatory processes in the U.S. and Europe, and we're planning commercial launches in both of those territories this year. We also expect to be building a 50-country operating platform and to fund the build-out of our operations in Asia Pacific and Latin America. And we'll be providing updates on that over time.

In addition to that, we're continuing to advance our pipeline. And we were proud to announce a couple of key Phase II clinical trials that we are undertaking, one to make sure that no patients are left behind with spinal muscular atrophy, so our Phase II OPAL study to study apitegromab with the gene therapy that stimulates SMN1 protein in infants and toddlers under the age of 2. And then in addition to that, we were pleased to announce a Phase II trial that will commence later this year for FSHD to study apitegromab in 60 patients, randomized double-blind, placebo-controlled. And I think we'll talk about that in a little bit.

And so we want to continue to fund the pipeline. And we want to continue to innovate. As I noted, apitegromab has been our first lead asset based on this highly innovative platform that we have to inhibit antibodies, but we have 2 additional opportunities to continue to bring innovation to patients. And that's a subcutaneous version of apitegromab, which we announced some Phase I data just a few months ago, and also our highly innovative SRK-439, which is a high-affinity, high-potency, also subcutaneously administered myostatin inhibitor that is now in a Phase I study. We hope to have data on that later this year.

So there's a lot going on, and yet SMA and FSHD are just the first 2 rare neuromuscular disorders that we think we can apply our very unique platform and great success in targeting myostatin where the industry has failed to. So it comes back to our runway. We want to fund a lot of things. We want to fund our commercial readiness and commercial preparation and eventual commercial launches in the U.S. and Europe. We want to continue to fund our pipeline with these additional Phase II studies. And then we want to continue to invest in all of the clinical regulatory and manufacturing work around subcutaneous apitegromab and SRK-439.

That was why we went out and secured $550 million debt instrument. That is why we're going to pull down $100 million. We did finish the year at a $368 million cash balance. That was before the $100 million that we're going to pull down. And a couple of things about our runway, Etzer, as you know, that are not factored into our runway. We do qualify for a rare pediatric disease priority review voucher, which we would expect to monetize at approval. And we're not able preapproval to have any sales sort of in our calculation for runway as well.

So we'll be thoughtful about continuing to manage dilution while we also think about funding what we believe is the basis for the next great global biotech company, which is Scholar Rock, on the basis of the opportunity to serve patients with SMA.

And obviously, the remediation process with Catalent is something that's top of mind for folks as far as the apitegromab refiling. But I guess one of the things that I wanted to touch on with respect to that is what additional conversations are you having with KOL in the meantime? Because it does kind of offer you a window, if you will, to have more conversations with KOLs around SMA and the SMA community. What has those dialogues have been like?

Thank you, Etzer. It's very perceptive of you. Obviously, for many reasons, our delay to approval based on a sole approvability issue right now for apitegromab is the state of compliance across our fill/finish facility, which is owned by Novo Nordisk. That's Catalent Indiana in Bloomington. And so we were disappointed while we were being reviewed under priority review to essentially get there on the full review and yet received a complete response letter until that plan is remediated. And I'm sure we'll talk about that in a moment.

I would say that this extra time has not benefited most, most certainly patients who are suffering from irreversible muscle loss, muscle wasting and a loss of motor function. And our data certainly underscores that despite the use of every motor neuron surviving drug that might be available today, one needs to address the muscle.

But the one group that has maybe benefited a little bit from the delay has been our Chief Operating Officer, Keith Woods, and our commercial team in that we have only just hired them a few weeks before our original PDUFA and we had trained and deployed the team. But Keith came in, in the end of April, early May from the great work he did at argenx with VYVGART and probably didn't have all the time that he would have liked in planning for the commercial launches in the U.S., Europe and around the world.

And that additional time both in training the team and putting together our patient assistance program, which as we've indicated is going to be called Scholar Rock Supports, our disease education program, Life Takes Muscle Version 2.0, is now launched. The team, both the medical affairs team and many of our other team members, have been working with KOLs. And what we hear from them is that our message resonates, and that is to have optimal motor function in SMA.

We've had this incredible innovation for the last 10 years, and that has been brought to bear by the drugs that stimulate the increase in either SMN1 or SMN2 protein. And that allows the motor neuron to survive a bit more. This is the origin of SMA. But the principal organ that is clinically affected in SMA is the muscle. And there's never been anything that has been able to target the muscle until now with apitegromab.

And so what the KOLs are telling us is there's a great appreciation amongst their patient community and the families that by being able to address the muscle, and we've got about 250 patients from our Phase II, Phase III clinical trial that remain on treatment, that one is seeing a tremendous benefit as opposed to patients plateauing and eventually beginning to lose motor function again on an SMN-targeted therapy alone.

Patients are able to gain function and hold those gains over a longer period of time. And that's certainly exciting the community to now address the muscle component associated with this devastating genetic disease and not just the motor neuron.

Right. One of the questions around sort of the potential resubmission we get on apitegromab for SMA is around the potential timing just the approval. And I guess are there any rare disease drug resubmission analogs that we could maybe use to proxy as to how long would the FDA ultimately take to review the resubmission?

Thank you, Etzer. You're raising a really important point, which is 99% of the conversation is about the timing of a reinspection and resubmission. But I think what you're hitting on is when you get there, there's this whole other thing called the new review time. And within that new review time, even though this is the sole approvability issue, the inspection report probably will be evaluated by the FDA.

And the FDA will make a decision to reclassify the facility, which is downgrading it from the OAI designation, which is official action indicated, to like a VAI or NAI, VAI as voluntary action indicated. And that's really the green light for us and any other application that's being held up at Catalent Indiana.

So what Etzer is raising is what we announced on March 3 is a steady drumbeat of rapid progress from our complete response letter to a Type A meeting on November 12 that we had with the FDA, which, by the way, was an in-person meeting. It included all of the leadership from the relevant groups at the FDA. We brought Cure SMA, Kenneth Hobby, the President of Cure SMA, to that meeting so the patient voice was heard about the impact of a delay.

And interestingly enough, we also brought Novo Nordisk, which to that point hadn't really had a constructive communication pathway with the FDA, even though the bad inspection that happened at that plant was July of '25. So their first audience with the FDA was really November of '25. Since that point, there's now been this extremely rapid progress taking place, where Novo responded to the warning letter right after our Type A meeting to the FDA by mid-December.

Just a few weeks later, the FDA reached out and scheduled an early Q1 meeting with Novo. That meeting went well and the FDA indicated that there were no new asks in the remediation plan. And then since then, there's been a field visit to the site that was also constructive, no new asks. And the FDA indicated that they would return for a formal reinspection since Novo had resumed routine manufacturing activities, which they resumed those at the end of February.

But what Etzer is raising is, let's just say, okay, now we know the near-term horizon suggests there's going to be a reinspection. We have indicated that our base case is that we will resubmit our BLA with some evidence of a positive reinspection. So let's just say that, that happened shortly after a reinspection. The FDA then has 30 days to either call our resubmission a Class 1 resubmission which is a 60-day review or a Class 2 resubmission which is a 6-month review.

And it dates back to the day we file. So 30 days later, if it's a Class 1, we got 30 more days left. 30 days later, if it's a Class 2, we've got 5 more months left.

The best sort of example that I can point to, Etzer, is in the very same plant, in 2023, based on inspection findings, originally EYLEA HD received a complete response letter. They resubmitted. And oftentimes, reflexively at the FDA, these resubmissions get a Class 2 even if there's not a lot to do. So they did get a Class 2 resubmission. But the drug was approved within a 30- to 60-day window after they had resubmitted.

So while we're sort of almost expecting a Class 2, we think the same sort of shared sense of urgency with the FDA that was created at our in-person Type A meeting in November needs to carry through not just through the reinspection of the plant, but all the way through the review period to reclassify the facility and ultimately resulting in what patients are waiting for, which is an approval letter from the review division, the neuro division at the FDA so we can get on with launch.

So I know it's not super clear answer. But we certainly believe that the community ought to be aware that a Class 2 is likely. But we believe beating that timeline by quite a bit is very realistic given some other examples.

Great. And I guess the other question related to that, that we've sort of gotten questions on, and it would be great to hear your thoughts there, is around the timing of approval. And does that have an impact on the priority voucher itself when you think about the anniversary, if you will, of the PDUFA going back to September 22? And is there any difference in having an approval pre or post sort of the anniversary of that PDUFA?

Etzer brings up a good point. There was a lot of focus on our CRL. Hopefully our audience knows the value of a PRV, these priority review vouchers, has been ranging between $150 million to just over $200 million recently. So these are transferable to companies who would really benefit from being able to accelerate one of their own filings. And we've indicated that we would look to monetize this.

The reason why there was a thought that we had to be approved within a year is because Congress needed to renew the program, and the program was expected to expire at the end of September 2026. It just so happened our original PDUFA was September 22, 2025. So there was this thought, is it a year later and then the PRV goes away?

No. What we just needed was Congress to renew the program. And I'm pleased to announce to you all, and many of you may have seen this in some of our trades, Congress did renew the program now into 2029. And so we don't necessarily -- believe me, Etzer, we have a sense of urgency to get done by September for sure because patients need us. But the PRV doesn't necessarily go away if for some reason we were approved on October 1, as an example.

And thank you. While we can all think about where maybe Congress goes slow or can't reach an agreement, thank goodness, they reached an agreement on extending the priority review voucher program into 2029.

Great. And you've guided to potential EMA decision mid-2026. You talked about Germany potentially being the first country there that you would take apitegromab to. Maybe just help us understand the SMA community and Germany access? Anything that you could provide in terms of sort of that market for SMA.

Yes. And again, thankfully, when we were together, Keith, at Alexion, you went and led a major European country. We always talk about how valuable that would be for all of the things you would do on a global scale. And then, of course, Germany was an extremely successful market with myasthenia gravis and VYVGART.

But it's not just Keith success and experience there. Germany typically is the first country in Western Europe to launch after an EMA approval. And that is because access is already established. There will be a longer-term sort of pricing and reimbursement review process, but patients will have access. So we have established leadership in Germany. Some folks that, I don't know, Keith and I tend to fall back on people that we've been in the trenches with and built some amazing companies with, like either Amgen or Alexion or argenx.

So leadership is in place. They're interacting in the community, our medical affairs team with KOLs. We do have an early access program ongoing in Germany. The review, as Etzer noted, is ongoing with EMA, and we would expect a decision near midyear. And so we think we're poised obviously in Europe. It's more of a staged launch, Germany.

And then country by country, we'll go through the reimbursement and access processes in countries like Italy, France, Spain and so on and so forth. But we think we're well positioned not only to launch in the U.S. in 2026 but also in Germany in the second half of this year. And we look forward to keeping you all apprised.

And remember, these will be the first 2 countries across a 50-country operating platform that is our ambition so that we can reach the 35,000 patients with SMA that have received at least one SMN-targeted therapy is our target audience. About 7,000 of those are in the U.S., 28,000 of those are outside of the U.S. And so we think we have a tremendous opportunity to serve patients with the world's first and only muscle-directed treatment. And we think that, that bodes well for the growth of Scholar Rock well through the end of this decade and into the next.

What a tremendous growth engine. And yet that's why we feel indebted to this SMA community to deliver for them. And then we'll continue to work on our rare neuromuscular franchise with what we do best, in inhibiting myostatin over the long run. But it all starts in the U.S. and Germany, and then we'll be providing progress from there.

Great And you're developing a subcutaneous version of apitegromab. What do you expect the path to approval to look like for that formulation?

Yes. Also a very important program. One of the things that I say often is one of the greatest honors, I think, that we have in our company is that we're going to have an opportunity to serve these remarkable patients and families that are impacted by SMA. We have to make a commitment to that because we believe when they start on apitegromab, it's the start of a 5-, 10- or 15-year relationship with that family. And we believe we need to continue to invest in innovation for them.

So the launch of apitegromab again will be with our Q4 week dosing, which has delivered via IV. Important to note that while visits for a Q4 week, every 28-day infusion, are not trivial for the SMA community, more than 90%, about 95% of our patients that enrolled in clinical trials remain on treatment and on time every 4 weeks.

But we've also said to ourselves, let's keep bringing innovation to patients. Let's give them a lot of options. In an IV form, let's give options on any way to access the drug, including through home infusion. And Keith has established a 10,000 infusion nurse network in the U.S. to help patients with that. But what about subcu? We think that would be a great value add.

So in January, what we presented at JPMorgan was 45 healthy volunteers that were broken up in 3 groups. 15 healthy volunteers got 100 mg per kg of apitegromab. But most notably, what we compared was 800 mg -- I'm sorry, not per kg: 100 mg, 800 mg IV and 800 mg subcu. What we saw is beautiful overlapping pharmacodynamic curves between IV and subcu. So we said, this is possible.

We've done some incredible formulation work. We'll select the device. And then what I guided last Tuesday is the clinical regulatory path will be determined by, and I think it's wise to do this, staging the discussions with regulators after we have the final approval for IV apitegromab. And then we'll look forward to updating you all as to whether or not that's a bridging study or some other ask of the FDA.

And we'll keep you apprised of that. But we think we have the right formulation, and we think it's going to be needed innovation for the patient community.

Great. And then for FSHD, you're initiating the Phase II FORGE study. I think you've guided to mid-2026 for that study. Maybe just the rationale for apitegromab in FSHD?

There's been a lot of attention on this, Etzer, as you know. And it's because, okay, if you guys at Scholar Rock have succeeded where every other company has failed, and most recently, companies have failed again trying to target myostatin. So it's one of those things. The novelty isn't if you can effectively drug myostatin, you're going to have a successful therapeutic on your hands.

The novelty is that we have been able to do it in multiple Phase II trials and a pivotal Phase III trial. And we think that's because of the uniqueness of inhibiting pro and latent myostatin, the pro form of the growth factor as opposed to the mature form of the growth factor or the receptor. And so if you can do this and you've had success in SMA, it seems to make sense that there would be a set of genetic or acquired neuropathic diseases or myopathies that you could apply this unique platform to, also why it's important for us to move forward beyond IV apitegromab and the subcu apitegromab and SRK-439.

So I know we're running short on time. We chose FSHD. This is 30,000 patients diagnosed in the U.S. and Europe. Onset of disease is adolescents and early adulthood. It's a bad disease with about 1/5 of patients ending up being wheelchair-dependent. The hallmark is dysfunctional muscle but they still have patches of functional muscle. And that's what we think we can target with apitegromab. And that's how we've designed the trial to focus on moderate patients, to focus with an endpoint of lean mass volume, which is a precursor of functional endpoints, which we will be measuring as well.

As I noted, 60 patients, randomized, double-blind, placebo-controlled. And we think that this is an ideal disease, whether alone or in combination with a corrector down the line, where we can make a meaningful impact on these patients suffering with FSHD.

Two other data points. We don't just think that this is the right disease. We've proven it in our preclinical models where we've developed with a FLExDUX4 mouse model. We've used our antibody and shown significant improvements in muscle mass, muscle force and exercise endurance. And then lastly, very importantly, there's been rigorous clinical programs with physical therapy, which patients cannot do outside of the setting of a clinical trial, where physical therapy and targeting the muscle has had an impact on patients.

And then there have been some studies with anabolic agents like human growth hormone and testosterone that again showed that by targeting the muscle, one can have some benefit. So we think both clinically and preclinically, we have the rationale to advance this. And we're looking forward to providing you updates on the FORGE study in the near future.

Great. So we're up on our time. David, as always, thank you for a great discussion. And we'll be back shortly with our next session.

Thanks, Etzer. Bye-bye.

Ladies and gentlemen, thank you for standing by. Welcome to the Scholar Rock Fourth Quarter 2025 Financial Results and Business Update Call. [Operator Instructions] Please be advised that today's call is being recorded. I would like now to turn the conference over to Scholar Rock. Please go ahead.

Good morning. I'm Laura Egis, Vice President of Investor Relations at Scholar Rock. With me today are David Hallal, Chairman and Chief Executive Officer; Akshay Vaishnaw, President of R&D; Keith Woods, Chief Operating Officer; and Vikas Sinha, Chief Financial Officer. During today's call, David will provide introductory remarks and a business update. Akshay will review our R&D progress. Keith will provide an update on our commercial readiness activities and Vikas will provide a financial update. We will then open the call for questions. .

Before we begin, I'd like to remind you that during this call, we will be making various statements about Scholar Rock's expectations, plans and prospects that constitute forward-looking statements for the purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995. Any forward-looking statements represent our views only as of today and should not be relied upon as representing our views as of any future date.

I encourage you to go to the Investors & Media section of our website for our most up-to-date SEC statements and filings. With that, I'd like to turn the call over to David. David?

Thank you, Laura, and good morning. Thanks to everyone for joining our fourth quarter and full year 2025 earnings call. Scholar Rock is poised for a transformative year in 2026. Our priorities are clear, and we are executing with focus, discipline and urgency. As we seek to deliver the world's first muscle-targeted therapy to children and adults living with SMA while also laying the foundation to realize our ambition to develop life-transforming therapies for patients with additional rare and severe neuromuscular diseases globally.

Our highest priority is to bring a finite math to the SMA community as quickly as possible. We remain relentless on behalf of patients and we are grateful that important progress continues to be made at a steady and rapid pace. Let me briefly summarize the key events that have occurred since our constructive and collaborative in-person Type A meeting in November.

First, a week following our Type A meeting the FDA issued a warning letter to [indiscernible] Indiana. Next, Novo Nortis rapidly responded to the FDA by mid-December. Then following Novo's response, FDA reached out prior to the holidays to schedule an early Q1 meeting. That meeting has since taken place and importantly, at that meeting, the FDA had no additional request to Novo's remediation plan.

And most recently, following the meeting with Novo, we were encouraged that the FDA sent the field team to [ Catalent, ] Indiana. At the conclusion of the visit, the FDA once again did not have any additional request to Novo's remediation plan and state of de novo that it intends to conduct a site reinspection following routine manufacturing activities, which has since resumed in late February.

The cadence of activity since our Type A meeting reflects the shared understanding between us, the FDA and Novo of the high unmet need in the SMA community and a shared sense of urgency to bring apitegromab to children and adults living with SMA as rapidly as possible. We are pleased with FDA's continued level of engagement, and we expect this momentum to continue.

Our team is prepared to resubmit the apitegromab BLA following a successful FDA reinspection of the [ Catalent ] Indiana facility. We are reaffirming our guidance of BLA resubmission and U.S. launch following approvals in 2026. Also, I am pleased that progress with a second fill/finish facility is moving quickly to build redundancy into our supply chain.

Engineering runs at the facility are now underway with additional manufacturing runs to follow we anticipate filing a supplemental BLA for the second filer later this year. As we advance the regulatory process for apitegromab toward approval for patients with SMA in the U.S. Our MAA review continues in Europe, and we expect a decision from the European Medicines Agency in mid-2026.

With anticipated regulatory approvals in the U.S. and Europe this year, I would like to now turn to our Scholar Rock commercial launch preparations. In the U.S., our team is deployed in the field and is educating potential prescribers and payers on the unmet need in SMA and the importance of targeting muscle.

The principal organ affected in SMA while also broadening and deepening relationships with the community. In Europe, we are building momentum with launch readiness activities and engaging with the SMA community. We continue to plan for a launch in the second half of the year, beginning with Germany.

Keith will discuss the substantial progress we are making with commercial preparations and our disease awareness initiatives shortly. We know it is not a matter of if, but when apitegromab will be approved for children and adults with SMA. We are emboldened by the commitment we have made to the more than 35,000 patients globally living with SMA who have received an SMN targeted therapy.

We are working expeditiously to deliver on our ambition that globally any patient with SMA who can benefit apitegromab a clinical map should have access to a ping mab. This is indeed what we know well and what we do well, and we are confident in the significant opportunity that we have to serve patients with SMA. We are ready now more than ever. to usher in the next era of innovation for the SMA community.

I would like to now turn to the progress we are making in advancing our world-leading anti-myostatin pipeline. Enrollment and dosing continued in our Phase II OVAL study, evaluating [indiscernible] in infants and dollars with SMA. Our IND for [indiscernible] and FSHD is cleared, and we are on track to initiate a robust, randomized, placebo-controlled Phase II study later this year.

With regards to our subcutaneous formulation of opium, we shared the promising results of a Phase I study comparing subcu and IV apitegromab in January. We expect to share our clinical and regulatory strategy for the program later this year. And finally, we continue to enroll in those participants in our Phase I study for our highly innovative SRK 439 myostatin inhibitor, we expect to have top line data from this study in the second half of this year.

Akshay will discuss these programs in greater detail shortly. Turning now to our balance sheet. We were pleased to have added -- we are pleased to have ended 2025 with $368 million in cash and cash equivalents. This includes $60.4 million from the exercise of warrants that were set to expire on December 31. We continue to strengthen our financial position to drive our commercial and R&D priorities in this morning, we are pleased to announce that we have secured a new debt facility for up to $550 million, which Vikas will discuss later in the call.

2026 will be a transformative year for Scholar Rock. We are ready to resubmit our BLA for apitegromab at any moment. Our U.S. commercial team is working with urgency to prepare the market for the launch of the world's first and only muscle-targeted therapy for children and adults living with SMA.

Beyond the U.S. the build-out of our 50-country operating platform is underway in Europe with other regions and countries to follow, and our highly innovative world-leading anti-myostatin pipeline with apitegromab and SRK-439 is progressing with strong momentum. The opportunity ahead of us to serve patients with SMA and additional rare and severe neuromuscular diseases is significant.

We remain steadfast in our strategy confident in the determination of our team and energized by the transformative potential of a pinnacle map and our broader pipeline. The road ahead is one of purpose progress and extraordinary possibility. And with that, I'll now turn the call over to Akshay for an R&D update. Akshay?

Thank you, David, and good morning, everybody. As David noted, we remain focused on our apitegromab BLA remission to bring this important therapy to children and adults with SMA as rapidly as possible. Since being joined by CureSMA and Novo and our in-person type meeting with FDA leadership in November, I've been pleased by the ongoing level of engagement and progress made on the offer patients.

We expect this momentum to continue, and our team is prepared to resubmit the ipilimumab BLA following a successful FDA reinfection of the Kaplan Indiana facility. I'd now like to provide an update on the status of our second or [indiscernible] facility, which will strengthen supply continuity and support future commercial demand.

As we shared late last year, we're working with a world-class U.S.-based manufacturing facility that has a proven track record of successful FDA and EMA site infections. Importantly, engineering runs are now underway with additional manufacturing runs planned to Q2, and we continue to expect to submit the supplemental BLA with this facility later in 2026.

Outside of the U.S., our apitegromab MAA is progressing through the review process with the EMA, and we continue to anticipate the decision in the middle of this year. Turning to our pipeline. Let me start with the Phase II OVAL trial, evaluating apitegromab in infants and toddlers under the H2. This trial is enrolling participants to be treated with an SMN1 targeted gene therapy or who are receiving ongoing treatment with an SMN2 type of therapy.

The study is informed of 2 regions in particular. First, it is anticipated to expand the impact of apitegromab the full spectrum of patients currently being treated for SMA as this is the first time we're evaluating the use of apitegromab in organical treat patients in a clinical translation. Second, we believe early intervention with apitegromab could support muscle during the critical early deferment phase, complementing SMN targeted therapy that aim to preserve mecheurons.

By promoting muscle growth when both mothers and muscles are still maturing, apitegromab has a unique opportunity to improve motor outcomes in the youngest patients with SMA to ensure that no patients are left behind. We continue to enroll patients in the study and dosing is ongoing.

Turning now to our next indication for apitegromab [indiscernible] muscular dystrophy or FSHD. FSHD is a rare devastating neuromuscular disease with significant unmet need. More than 30,000 patients are diagnosed in the U.S. and Europe alone, and there are no approved therapies.

Associate caused by disregulation of [ DUX4 ] approaching that can cause muscle damage when inappropriately expressed. Since usually begin in adolescents or early adulthood with muscle weakness in the face and upper party, but FSA can impact any mustered an estimated 20% of patients will become wheels.

We're prioritizing FSHD as the next indication for apitegromab for 3 key reasons. First, there is significant unmet need in this population for a safe and effective there. Second, we have preclinical basins in the dose standard flexes for mass model that provides magnistic rational for apitegromab in SFC. Using this as bundle, we changed that myostatin inhibition to introduce robust increase in muscle mass, significant improvements in muscle force and consistent gains in during after 28 days.

Third, we are a randomized studies in FSHD that suggest muscle mass can increase in hyper capacity to show functional benefit. For example, in study to be the rigorous physical therapy for treatment with anopolicatients Patients with FSHD demonstrated increases in lean map muscle function. These data suggest that the apitegromab as a monotherapy may have the potential to bring important benefit to FSHD patients.

The FSHD IND is clear, and our next step is to conduct a robust randomized double-line placebo-controlled Phase II study that is expected to not 60 patients. The study for -- We're not trying to initiate limit of this year. We also continue to advance 2 additional programs in our world-leading aside satin pipeline, a subcu formulation of apitegromab and as of April 9.

In our patio program, we showed some very exciting data from the Phase I study earlier this year. In that study, healthy vote has received a pilot of the 100 or 80 mg of Q or 800 mg IV. The data demonstrated that 800 mg of Q resulted in an overlapping pharmacodynamic profile with 800 IV.

Accordingly, subcu apitegromab appears that favorable -- appears that favorable by availability with a [indiscernible] profile comparable to IV administration. Additional development activities with apitegromab are underway we're planning engagements with U.S. and European regulators later in the year.

Turning now to SRK 439, which we discovered by leveraging our local leading expertise in talking [indiscernible]. 439 is a subcutaneously administered bypassing inhibitor, finding both pro and latent mistake with high affinity and activity. We recently presented data demonstrating that 49 is 10x more potent than a pine map since we have shown in nonhuman primates that 439 use changes in whole body Lema at doses as low as 0.3 meter kick -- we're very excited about this program and dosing in our Phase I healthy volunteer study is well underway.

We expect to have top line data from the study in the second half of this year. In closing, we're executing with focused urgency to bring opinion to children in adult with SMA, whilst in parallel investing with discipline to advance our world-leading antimonate pipeline. The strength of our data and the sustained momentum of our programs underpins our confidence that we can shape the future of treatment for patients living with rare neuromuscular diseases.

I'll now turn the call over to Keith to discuss our commercial launch preparation. Keith?

Thanks, Akshay, and good morning, everyone. As Dave had noted, our team continues to operate with urgency as we prepare for the launch of apitegromab. Our commercial organization remains focused and disciplined advancing the critical capabilities required to deliver a seamless launch and support patients from day 1.

Nearly a decade after the introduction of SMN targeted therapies, the market continues to grow and now represents nearly $5 billion in global annual sales. However, while SMN targeted therapies have brought much needed innovation, muscle strength and motor function remain the top unmet need with 95% of patients continuing to experience persistent and progressive muscle weakness.

That limits function and independence Additionally, 3/4 of neurologists believe multiple modalities are necessary to optimally treat patients with SMA. This data underscores the significant opportunity we have with port the world's first muscle-targeted therapy. To this end, our U.S. customer-facing team is active in the field.

Focused on disease education programs that reinforce a broader understanding of SMA as a disease of the motor unit consisting of both the motor neuron and the muscle, which is the principal organ impacted by the disease. We continue to engage across approximately 140 SMA treatment centers 2,600 prescribing physicians and their multidisciplinary care teams throughout the U.S., and our SMA disease education efforts remain a core component of our work in the field. In parallel, we are strengthening and advancing the key elements of our commercial capabilities to ensure launch readiness.

We have expanded our specialty pharmacy network to enhance SMA patient and caregiver convenience. SMA patients currently receiving an SMN targeted therapy from a specialty pharmacy will be able to access apitegromab through that same specialty pharmacy. In addition, through our patient access partners we have established a home infusion network of more than 10,000 affiliated nurses nationwide. We are also working to ensure we mitigate reimbursement and access bottlenecks.

This includes preparations to launch our patient services program, which we have named Scholar Rock supports. This program is designed to provide comprehensive and individualized support to patients caregivers and providers. In addition, we remain focused on patient engagement and community activation.

In January, we launched the next phase of our disease awareness campaign called Life takes muscle aligned with our objective to deepen community awareness of the importance of targeting muscle. And finally, we continue to engage with payers advancing discussions with national and key regional payers as well as Medicare and Medicaid.

At U.S. approval and launch, I look forward to discussing our comprehensive SMA patient access support program in more detail. While we make substantial progress in preparing for the launch in the U.S. we are also advancing launch readiness across key European markets in anticipation of a mid 2026 EMA decision.

In Germany, we have established local leadership initiated our compassionate use program and our progressing reimbursement planning to enable rapid access following approval. Across the broader region, we are advancing reimbursement dossiers in multiple countries strengthening our distributor relationship, and we are building out our EMEA infrastructure to support future commercialization.

In closing, we have invested thoughtfully to build the commercial foundation necessary to support a world-class launch, and we believe apitegromab is well positioned to play a central role in the next era of SMA care. Our team is prepared to move quickly upon approval and to deliver on our commitment to the SMA community, one patient, one caregiver and one family at a time. With that, I'll turn the call over to Vikas. Vikas?

Thank you, Keith. Our financial objectives for 2026 remains consistent. We are focused on supporting our commercial base to deliver a strong apitegromab launch funding R&D activities to advance our pipeline and expand our leadership in the myostatin and muscle space. And continuing to evaluate opportunities to strengthen our balance sheet in a way that supports long-term shareholder value.

In keeping with these objectives, I'm pleased to provide our fourth quarter and full year financial results. For the fourth quarter, we reported $91.9 million in operating expenses which included $19.4 million in noncash stock-based compensation. Excluding stock-based compensation, operating expenses were $2.5 million.

For the year ended 2025, we reported $384.6 million in operating expenses, which included $75.6 million in noncash stock-based compensation. Excluding stock-based compensation, operating expenses were $309 million for the year ended 2025. Turning to our balance sheet. We ended 2025 with $368 million in cash and cash equivalents.

During the fourth quarter, we strengthened our cash position, adding $60.4 million from the exercise of warrants that were set to expire on December 31. We continue to strengthen our balance sheet and are pleased to announce today that we secured a new debt facility for up to $550 million which blew our capital.

This debt facility consists of 4 elements: First, upon closing, $100 million was immediately available to us, which we have used to repay our prior $100 million debt facility with [indiscernible] Second, an additional $100 million is available to us this quarter, which we expect to draw down by March 31.

Then following FDA approval of apitegromab we have the option to draw up to $150 million in additional capital. And lastly, we have an option for additional incremental facilities of up to $200 million at the mutual consent of Scholar Rock and [indiscernible] This debt facility provides us with additional flexibility as we transition towards a global commercial space company while investing in our pipeline.

In addition to the $150 million available from the debt facility upon FDA approval of apitegromab we will look to monetize our priority review voucher to further strengthen our balance sheet.

Looking ahead, we continue to operate with a tight financial plan. Our prioritized investments remains focused on apitegromab commercial launch readiness in the U.S. and Europe, strengthening our supply chain to support the pipeline and commercial demand practice and advancing our highly innovative clinical programs that Akshay discussed earlier in the call. With that, I will turn the call back to David. David?

Thanks, Vikas. In closing, we remain focused on bringing apitegromab the world's first and only muscle targeted treatment to improve motor function to children and adults living with SMA as rapidly as possible. We are encouraged by the progress that has been made and by the continued momentum across our regulatory, clinical and commercial priorities.

With a strong foundation, clear strategic priorities, and a world-class team, we are well positioned to make 2026 a transformative year for Scholar Rock as we continue to work with urgency on behalf of children and adults living with SMA. We look forward to updating you on our continued progress throughout the year.

And with that, we'll now open the line for questions. Operator?

[Operator Instructions] And our first question is come from Eric Schmidt with Cantor.

David, just to put a pin in on is Novo now ready for reinspection, open for reinspection? And then assuming the reinspection does go well, what would trigger your resubmission? What do you need to see from that reinspection to be able to push the button on the refiling?

Thanks, Eric. So we are gratified really since our [indiscernible] meeting in November with the shared sense of urgency and high priority that both FDA and Novo has made the remediation of the [indiscernible] Indiana facility. And you got a set from the call, just the drumbeat of progress week after week, month after month.

We like the high engagement we continue to see. And given the constructive meeting in early Q1 and then the following sites is really the gating item. Now just as a reinspection follows these routine manufacturing activities as Novo moves into full-scale production. As far as our trigger we would look for, obviously, a successful reinspection as you noted, and we're assuming that given the progress that has been made, and that would then trigger. We are at the ready to submit our BLA submission very, very quickly.

But it really would be with some level of confidence that it was a successful reinspection.

And our next question will come from Tazeen Ahmad with Bank of America.

Not to belabor the point on timing here, but I know you're confident about the ability of Novo to resolve the issue. But in the event that you do have to revert to your backup facility, you've guided to a supplemental filing in the second half of the year. What would happen to the time lines of that needed to be the primary filing?

Thanks, Tazeen, very much. As I noted on the call, we were gratified in the rapid and steady progress that has been made between FDA and Novo. And we do think apitegromab and the importance of apitegromab for the SMA community as a key driver in this, not the sole driver, but a key driver in this.

I would say that we are pleased with how rapidly we are moving forward with an additional filer. And our assumption is whether or not were to be a supplemental BLA, which is our plan or whether or not we had to fall back. We've always looked at that as an important effort on our part, no matter what because we cannot control everything in this process.

And we don't really believe that, that timing would be altered tremendously in terms of if it were not and SBLA so we thought about it. It is our plan that it will be in SBLA. That's the level of insight information and confidence that we have but nonetheless, we would be prepared to pivot should need be on behalf of children and adults living with SMA.

Thank you. And our next question comes from Tess Romero with JPMorgan.

So first one is, can you elaborate on what it meant that the FDA sent field team. What was the purpose of that? And is that routine? And then the second one, just to loop back on sort of better understanding the next procedural steps post the reinspection and what the time lines could be there. Will you get verbal communication or has written documentation, what you'll see similar to a normal inspection.

Yes. Thanks, Tess. It's a good question because it's Certainly, nothing has been completely ordinary about this process. And I do think what has created some level of extraordinary behavior with kind of a constant drumbeat of progress. I think it was really set off by that in person Type A meeting that we held with FDA and where there really was with her SMA and attendance with Novo in attendance.

There was a share sense of urgency to bring a Cantor to patients. And so while I can't really comment on what was the overall sort of objective, we do think what it shows is for just weeks after a really constructive meeting with Novo in early Q1, where there were no new requests by the FDA of Novo into their remediation plan.

We think it just continues to show high priority by the FDA to send a field team out to interact with the site and to indicate that after routine manufacturing activities, which have since recommenced at the facility. They would be in line for a reinspection.

So overall, we just feel good about the drumbeat of progress here, and we're quite pleased. And we would expect, given the sort of rapid and steady pace that we've seen over these last 3 months, that anything else that follows the timing of a reinspection timing of resubmission, that review.

Hopefully, it continues to follow sort of this commitment that has been made to rapidly progress the apitegromab file so that we can deliver this drug to children and adults living with SMA. And we'll certainly keep you apprised on that progress.

And our next question comes from Mani Foroohar with Leerink. Your line is open.

We have Ryan on for Mani. Congrats on the update. Maybe just 1 sticking with the review, kind of based off your latest conversations with the FDA, I'm curious what your expectations are for a turnaround time following BLA submission to eventual approval. Are there any details that still need to be worked out, label, et cetera, with regulators?

And then maybe just as a second one on the pipeline. Can you talk about the strategy for 439. Is this something that you plan to keep in out, look for broader strategic options? Is it best suited in rare neuromuscular diseases or potential broader application?

Thanks, Brian. Regarding the timing, again, just to remind everybody tuning in today, in our CRL that we received last year, the sole approvability issue was the state of compliance at the [indiscernible] Indiana facility. So we're certainly very focused on working with FDA and Novo on that.

As I noted earlier in the call, we would -- and we are planning and we are ready to rapidly resubmit our BLA following successful for reinspection. And again, we would just point to, without really being able to comment on timing, we would just kind of point to the evidence of the progress over these last 3 months and how attentive the FDA has been to remediating this facility and our focus Novo has been to really working with urgency as well, and we'll keep you apprised on that timing.

Regarding the pipeline of 439 auction.

Yes. 439 obviously is a very important and exciting drug. It's a high-potency antimitotic antibody appears to us, at least from the preclinical work to be about tenfold more potent. So could be a very low volume, small volume in frequent administration type drug -- so I think that creates a very interesting and exciting possibilities in the revenue muscular space for us.

And at least at the current time, we think this is some of proprietary asset and we have no intention to partner it. But we'll share further development plan after we get the top line Phase I factor later this year.

And our next question is going to come from Srikripa Devarakonda with Truist.

Timelines wise, not to be to the point, you expect -- you continue to expect inspection, BLA submission, U.S. launch, everything to happen in 2026. For the launch to be in 2020, say, can it still happen with a Class II physician? Or do you diligence suggests that this is most likely going to be a class of submission and in any of your recent conversations with the FDA, was there any hint or indication for a potential CPV for apitegromab?

I didn't get the last part of that Kripa, could you say?

Commissioners prior voucher the National city water.

These are all very good actions, Kripa. And as you might imagine, we've thought about it all, right? And we -- with all of the information that we have and the progress that is made -- we were pleased and confident to reaffirm the guidance that we provided today of 2026 BLA resubmission and U.S. launch upon approval. We would certainly point to sort of this steady FDA prioritization and progress with NOVO over these past weeks and months, and it remains very steady.

And I think like we have thought about Class I versus Class II. And what we've seen actually in our own sort of analysis of this, even when Class II's are sort of granted, oftentimes a decision is taken out before that 6-month time line.

And again, I'm just reminding you that the sole approvability issue for us has been the status of the [ Catalent, ] Indiana facility. And we're pretty -- we are planning for the resubmission to be happening once we have indication that it was a successful reinspection. So we'll keep you apprised at that, but we certainly are very, very comfortable with the guidance that we have provided.

And then regarding like the commissioners sort of -- I would just say that we are just staying in close communication with the FDA on all of our different initiatives and just keeping in the forefront the very high priority that exists with the SMA community in the United States to gain access to the world's first and only muscle targeted treatment, and we look forward to continuing to keep you guys apprised on our regulatory progress there with FDA.

And our next question will come from Michael Ye with UBS.

I'm not going to ask a submission question. Can you talk a little bit about the expectations for the label as it relates to either ambulatory, non ambulatory and with no issues regarding age subgrouping, given that you had what sounds like a very successful review process and only CMC was the understanding part, how should we think about a broad label?

And then a follow-up, assuming approval, maybe for Vikas, can you just remind us, given that your drug is a weight-based drug, how to think about the comparable pricing relative to other drugs and if models should reflect anything philosophically as it relates to the differences in how the drugs are distributed.

Thanks, Michael. Akshay, on the label and then Keith, on the weight-based element of the drug and pricing. Akshay?

Yes, Michael, we were gratified by the progress made do the origination cycle. We have gone to a very advanced stage with the draft label and the FDA have really worked hard to depth. With the capital issue being on the outstanding issue, we anticipate that it would be relatively straightforward to get aligned with the FDA on the final level after our PLA resubmission.

Now all of that in the details ultimately, that's up to the FDA, but we know from the conversation picking up to the September per day. that kind of the guiding principles are what the FDA has shown before in the SMA space, the trial design that supports the approval at info. Now as you note that the totality of our package, we have experience with both non ambulatory and aerator we have experience with children 2 years in older, not experience in patients Lister plan and the inert.

And so I think that these are important guiding factors gamers previously has tended to look at full applicability for nor of the perp hypothesis and the negotiate drug to try and maximize getting these drugs and the turret many patients as possible.

Now those are the kind of gating principle. I think we have to lay off the LAD submission and see where we end up. But we've been pleased so far with how straightforward FD agency pro and then on price, I guess, first of all, it's not really appropriate for us to comment on specifics at this stage.

But I do promise you when we have approval and we have our launch call, we will get very specific about the pricing. But Mike, as you mentioned, because it is weight-based dosing, you are going to see a range.

So it's not going to just be net price for all. But look, when we think about pricing of prima we think about 3 key factors, and it's the rarity and the severity of SMA, it's the progressive nature of the disease.

And in combination with SMN targeted therapies, our data from both Topaz and SAPPHIRE have just demonstrated compelling clinical benefits. So we will get into all of the specifics on pricing on the launch call.

And our next question is going to come from Amy Li with Jefferies.

So looking ahead to launch, what commercial analogs would you point us to as we think about the initial uptake and launch trajectory? And then maybe another one on subcu epi you think approval will require a full clinical study in SMA, a smaller bridging study or primarily human factor studies? And if you could give us a time line to market, that would be awesome.

Thanks very much, Amy, and yes. What I would say is that for sure, we've been pleased in our engagement with the patient community, the caregiver community. As well as, as Keith noted, neurologists appreciation that not only addressing the order neuron component of the disease.

But for the first time, to really be able to address directly the muscle component of the disease, which is -- which is a principal organ that is clinically impacted and affected [ Avitas ] disease. We sense that there is a lot of interest in accessing the drug, and that in and of itself could support like a very nice uptake at launch.

I think what Keith and I have looked at though, is this is a essentially a Q4 week infusion. It will have a miscellaneous J code for some period of time. We know that there are payers, for example, Medicaid that could be a little sluggish at launch. We recognize payers in and of themselves -- it's not a matter of if they reimburse but sometimes it takes time to reimburse.

And so we believe robust demand, but we think that will be met with initially some access speed bumps that could impact our launch curve. But overall, the long-term opportunity that we see for apitegromab in the U.S. and beyond, we feel like is quite significant for us and we're really looking forward to the eventual approval and then Keith and team launching a pedigree to the SMA community.

With respect to your question on subcu and clinical regulatory strategy, I'll hand that over to Akshay.

Yes. Thanks, David. So for subcu period of math, what we have is very interesting and supportive data for the subcu gratis viable, shows excellent by availability and a somatic profile. Now, we know a lot about apitegromab in terms of BNP from our prior work the with administration. We obviously want to leverage that and find a path forward for subcu by saying this is a drug that's well characterized in the studies by different administrations. But if we can mimic the appropriate PKPD, then there's no reason why it could not be equally safe and effective.

Now those are all discussions that we need to have with the FDA, the initial approval of the drug, of course, is very important. But subsequent to that, we hope to get alive with regulators on that approach.

So ultimately, we can't drive the time lines today, but we're hoping the year progresses to engage regulators and formulate our time on time and then discuss the path forward.

And our next question will come from Geoff Meacham with Citi Group.

This is [indiscernible] on for Geoff. Maybe just thinking about the second fill/finish facility. If you guys were to switch over to that one, would it completely derisk the supply chain from the U.S. and launch perspective? And then on the launch, what specific leading indicators of payer and physician readiness are you guys tracking? Maybe you guys can give some color on that, it would be helpful.

Absolutely. I'll start with the second vial arm and Keith, you might a clarification on the second.

Yes. Can you repeat the second question, please?

Yes, sure. What specific leading indicators are you guys paying attention to, to indicate payer and physician readiness that you're tracking?

So second, fill finish. We are really pleased with the progress that we have been making. As I mentioned, tech trends were commenced in Q4. Engineering runs are underway and there are additional manufacturing runs followed here in the very near term. So we're working urgently.

Again, our assumption is this is going to be our second mile or we're going to submit [indiscernible] should we rely on this facility solely, we are confident that we would be derisking as well. our U.S. and EU commercial opportunities. So we wanted to be very thoughtful in selecting the right second partner for fill finish, and we're gratified that we have done that.

And also, as I noted, really pleased with the progress that's being made at a very rapid pace. Keith?

Yes. So first of all, when it comes to the payers, we've been really pleased with the access that our team has been able to get. As I stated in the prepared remarks, to not just the big national payers, but also now regional payers and even some Medicare and Medicaid, while we've had more time. We've been able to have in-depth discussions with them and our medical team has been able to go through the SAPPHIRE clinical data with them.

The bottom line is just as we -- just as what's been shared in a lot of the Cure SMA data and some of our own market research, neurologists and patients, they want more and they need more. And that's why we understand 3/4 of these physicians already believe in multiple modalities to treat this to treat SMA.

And our next question will come from Salvator Carusso with TD Cowen.

This is Salavtore Carusso on behalf of Mark for TD. Just one quick question kind of cross ones and does the status of the MMA review, will that market also be served by the Novocain Indiana facility? And if so, has the taken any action in response to the FDA inspection findings.

Yes. I'll start and then I can hand it over to Akshay. There is a mutual recognition between both FDA and the -- and so this steady and rapid progress we're making with FDA actually serves us very well for the current MAA review with regulators. And so it's very important that we continue to make this progress forward.

As I noted, the continued remediation and eventual successful reinspection will really support our EMA decision near midyear. And then as I noted, if for some reason, we were to rely on the second filer, that would also be very important. But for now, we're very excited with the rapid and steady progress that we've made. Akshay, anything?

Yes, you covered, David, I think the other piece that we've got to close such with the reviewing authorities that fully is important, and we all await those capital side, which we'll obviously to improvement.

And the next question will come from Etzer Darout with Barclays.

Guess a couple for me. Has the FDA requested or could they request additional safety data that could extend review of apitegromab. And then on HSD, just wondered would you be looking at any functional endpoints in the Phase II study that you're planning? And could this be a more appropriate indication for SRK longer term?

Thanks, Acer. Yes, it's a great comment, and we can remind you that BLA resubmission will be a fairly rapid and small resubmission, but there would be an update to sort of our safety database, which was called out in our response letter from the FDA. Akshay can comment on that. and then talk about any sort of functional outcome measures for FSH. Akshay?

Yes. So we're in line with the FDA. Then the unmeet was useful in many regards, including that and which aspect of the safety day space needs to be updated and so that all agreed to. And so we're ready and prepared with the PLA submission. So I don't see any great issues there, but it's a good question.

And all we should always provide the FDA with the late safety understanding backup, which we will do. With respect to the 4 Phase II study in FSHD, the primary endpoint will focus on increasing the postal volume and measure very sensitively by imaging techniques but we will have on statement here, which is to validate or FSHD to understand the functional impact of any potential change in month.

And we look forward, obviously, to those data.

And our next question will come from Evan Seigerman with BMO Capital Markets.

Mark [indiscernible] on for Evan. Thinking about the financials of the business. I know you mentioned the new debt facility secured with approvals in U.S. and Europe coming this year. I just wanted to how are you thinking about expectations for time to profitability and whether you anticipate any additional need for financing ahead of that kind of profitability hinge point?

Thanks, Malcolm. Vikas?

Yes, we have not given a forward-looking guidance at all here, but we will follow most likely the normal rare disease kind of revenue trajectory, which leads you to very similar levels of profitability timeframe of 2 to 3 years from launch. But it also depends on how our pipeline progresses during that time, and we will weigh into profitability versus investing into the future.

But overall, looking at a fundamental principle of creating long-term shareholder value.

And our next question comes from Allison Bratzel with Piper Sandler.

Just drilling down on some of the prior discussion around review timing. I know you talked a lot about FDA sense of urgency on apitegromab, I guess, is there a good precedent for FDA spending less than 6 months to review a Class II resubmission?

And can you just clarify, does your guidance for commercial launch in '26 assume a Class II resubmission and the full 6-month review? And then separately, just on Opal, could you talk to what you're seeing on enrollment trends there? And just what that tells you about the underlying awareness of apitegromab in the SMA community.

Thanks, Allison. Maybe I'll just point out one example. On the Class II not taking the full time. And I think it's important as we have been mentioned occasionally here during this current journey with Regeneron. And in 2023 at the same facility, Regeneron did have a CRL at a resubmission. I believe it was a Class II resubmission and yet it was approved within essentially a sort of a 60-day window.

And so -- but we have more examples than that. I'd just point to that because it's a little bit relevant given the fact that it was a CRL and it was the same facility. And I think it had to do with some assessment of the facility post an inspection. So I would just point your attention to that.

Yes, following up on that loss in train -- what was the second question. Yes, hopefully -- that's right. is going very well. I mean I think the first thing to say actually, if people will go to norm, that's very wide knowledge and appreciation for a muscle-based approach in the patient community and the prescriber community and tea spoken to that.

In fact, it's starting high and patients founders and physicians to await the agreement with this drug. And consistent with that, they see the possibilities throughout the entire patient age range and disease severity range as a community and we've clarified by the very nice progress with that. I'm not going to share details today.

But yes, we're seeing a good clip of enrollment. And as we get later into the year, we'll clarify the sort of mine comes into a site, but exactly when we have data on total extent certainly consistent with more of the drug and its potential very good involvement.

And Ali, I would just add, as Akshay noted in the prepared remarks, we have a deep commitment to the SMA community, and I'm really, really pleased that we are making sure no patients are left behind by opening up this under 2 study. So we're super excited to be doing this work and the youngest of patients with SMA.

And the next question will come from Kalpit Patel with Wolfe Research. This is [indiscernible] on for Kalpit. Previous milestone inhibitors in FSHD increased muscle mass that meaningful functional improvement. Can you give some color on how apitegromab aims to address this historical hurdle and what a clinically meaningful functional improvement might be in the planned Phase II?

Sure. Akshay?

Yes. So I think you're pointing to the drugs that didn't have a very and well-validated machine action and potency and safety profile. So the earlier generations of [indiscernible] didn't have a selectivity of June [indiscernible] our opinion.

More importantly, another one is the -- another point you raised is the Excel example, I suspect, makes a long in the study in FSHD and they're injecting lot in one isolated muscle. Now one can expect that to result in global functional improvement.

But we do know separately that globally applied strategies like intense physical therapy or anabolic occasions that increase muscle mass but just maturate go for and to foster and other similar agents that those kinds of agents clearly showed increase in muscle mass and also increasing functional capacity. So we incorporated content my metric testing into the Phase II to evaluate the change in muscle function, the primary approach or time and point of basis, the docomo change in the muscle volume but we look forward to getting those data, and that's a valuator approach the notation and we'll share with later happen.

Thank you. I am showing no further questions at this time. This will conclude today's conference call. And thank you so much for participating, and you may now disconnect.

Welcome, everyone, to the 44th Annual JPMorgan Healthcare Conference. My name is Tessa Romero, and I'm one of the senior biotech analysts here at JPMorgan. We're very pleased to be kicking off the conference with Scholar Rock. And presenting on behalf of the company, we have Chairman and CEO, David Hallal. David, over to you.

Thank you very much, Tess. It's great to be kicking off the JPMorgan conference early on a Monday morning, and we are super excited for our week here in San Francisco as well as 2026, which will be a transformative year for the company. I want to thank Tess, JPMorgan, everybody here in the room in California East as well as many, many others that are tuning in remotely via webcast.

Scholar Rock is in a position of strength as we enter 2026. We are the world leaders in myostatin biology. And with that capability, we are shaping the future of treatment for patients living with rare neuromuscular disorders. For the past 7, 8 years, we've been focused on developing our highly innovative monoclonal antibody, apitegromab, for children and adults living with SMA. It is the first myostatin inhibitor that has ever delivered a successful pivotal Phase III study, and it's the only muscle-targeted treatment to demonstrate clinically meaningful benefit for patients living with SMA.

Based on the strength of that data, in 2026, we remain on track for a U.S. and European approval with launches to follow. The initial country in Europe will be Germany. There's a large opportunity to serve patients in more than 50 countries around the world, and we are well positioned to meet the patients where they are. We want to make sure that no patients living with SMA are left behind.

Importantly now, we are leveraging that 7 to 8 years of successful drug development experience by delivering the first myostatin inhibitor to be successful in a Phase III trial, and we want to now bring that to more patients living and suffering with neuromuscular disorders. We were pleased to announce this morning that our next indication for apitegromab will be FSHD, and we will begin to dose patients later this year.

We're also excited that in Q4, we commenced dosing of healthy volunteers in our SRK-439 Phase I study with data to follow later this year. I'll speak more about these programs shortly.

And we have a cash balance on our -- at our company to support all of our high-value commercial and R&D initiatives moving forward. We thoughtfully fortified our balance sheet throughout 2025. Apitegromab is poised to usher in the next phase of innovation in SMA. Over these last 7, 8 years, while we've been developing apitegromab, we've been seeing the initial phase of innovation bring needed benefits to the SMA community. SMN-targeted therapies focus on preserving motor neurons, but that is not the entire motor unit, which drives motor function. Importantly, the motor unit consists of both the motor neuron and muscle. And now we are on the doorstep of delivering apitegromab to patients and finally being able to address the principal organ that is affected in SMA, the muscle.

As I noted, we expect our launches in the U.S. and Europe to commence this year, and that will be followed by a series of milestones as we drive this next phase of innovation forward, targeting the muscle for many years to come.

There are now 35,000 patients living with SMA that have received at least 1 SMN-targeted therapy. The global apitegromab opportunity and SMA alone offers the potential for many years of sustainable growth. This growth in patients receiving SMN-targeted therapies is really driven by high diagnosis rates with the disease and accelerated time to treatment. We've seen over the last decade there's been an increasing number of patients receiving SMN-targeted therapies and now apitegromab has the potential to be the world's first and only muscle-targeted treatment for the patients living with SMA.

This opportunity has us positioned to power substantial growth for our company through the end of this decade and well into the next.

As we've noted, the dynamics with SMA are very similar to other rare disease markets. We see our opportunity to serve patients in the U.S., being about 1/3 to 40% of all patients, but a meaningful proportion of patients are outside of the U.S. We see about 1/3 of the opportunity in Europe and 1/3 of the opportunity in Rest of World, including important countries in Asia Pacific and Latin American countries. That's why, as we have in the past, this management team, we are planning to build a 50-country operating platform so that we can serve patients wherever they may be receiving SMN-targeted therapies upon approval of apitegromab.

We are poised for our U.S. and European launches this year, but we will aggressively be moving forward with regulatory and commercial preparation in upwards to these 50 countries around the world.

As I noted, Scholar Rock is shaping the future of treatment for patients living with rare neuromuscular diseases. While we anticipate being able to serve a broad range of patients living with SMA with our initial label, we do want to make sure that no patients are left behind, and we're pleased that we have initiated a Phase II trial focusing on the youngest patients living with SMA, those patients under 2 years of age. As I noted, we're also gratified to be moving apitegromab into a Phase II study for patients living with FSHD. And yet the era has not been there. We are focused on additional neuromuscular diseases for which the proof of concept that we have generated with apitegromab provides great hope for those patients.

We are also pleased to announce and I'll share more data from our subcutaneous formulation of apitegromab because we expect to be building long-term relationships with the patient community, and we want to continue to bring innovation and optionality to them.

And finally, the team at Scholar Rock has done a remarkable job to move SRK-439 into the clinic in Q4 of 2025.

Our priorities at Scholar Rock in 2026 are very clear. With focused execution and financial discipline, we will; one, commercialize apitegromab for children and adults living with SMA beginning in the U.S. and Europe. We're going to expand the impact that we make with apitegromab, our highly innovative monoclonal antibody, by developing apitegromab for the youngest of patients living with SMA as well as bringing it to additional rare, severe and neuromuscular diseases. And we want to continue to advance the world-leading anti-myostatin platform and pipeline that we have built, and that's obviously advancing subcutaneous apitegromab as well as SRK-439.

I'd like to first focus on our important priority of commercializing apitegromab for the treatment of children and adults living with SMA. We believe that this will transform the treatment paradigm for patients with SMA and the medical community that treats them.

As I noted earlier, SMA causes motor neuron loss, leading to muscle atrophy and progressive weakness for the patients. And while SMN-targeted therapies have brought needed innovation to these patients, they really have been remarkable therapies. They slow further degeneration of motor neurons, but they do not target the muscle. Despite the significant advancements of these SMN-targeted therapies, progressive muscle weakness remains the #1 unmet need in the SMA community and apitegromab has been designed to address just that need, to deliver the first muscle-targeted treatment for patients living with this disease.

And we see this underscored in the community. 90% of patients with SMA rate muscle strength and motor function as their top unmet needs, and about 3/4 of all neurologists agree that multiple modalities addressing both the motor neuron and the muscle is necessary to optimally treat patients living with SMA. This is a large opportunity that we have to pursue, and we want to make sure that we can serve patients with the highest level of innovation that is coming from Scholar Rock.

Our Phase III data really underscore our opportunity to serve patients. We specifically designed our Phase III study to take on patients that were receiving chronic ongoing SMN-targeted therapies, and we randomize those patients to either receive apitegromab or placebo. The primary endpoint in this trial was the gold standard Hammersmith Motor Function Scale in SMA. It's the highest bar to hit. And what we saw in our Phase III SAPPHIRE trial was quite remarkable. Patients on ongoing chronic SMN2-targeted therapies had a loss of motor function, while those patients who received apitegromab with their ongoing SMN2-targeted therapies had a gain of motor function. This was a statistically significant and clinically meaningful benefit in a broad range of patients with SMA.

There was additional data that was quite compelling from our Phase III trial. About 1/3 of patients who received apitegromab with their SMN-targeted therapies had a 3-point improvement or greater in the Hammersmith rating scale compared to just 12.5% of those patients on ongoing chronic SMN-targeted therapies alone. We saw a consistent clinical benefit across all patients and a continued encouraging safety profile as 95% of all patients that we have studied with SMA continue to remain in our long-term extension trials. This really underscores the potential of apitegromab to be the first and only muscle-targeted treatment to improve motor function in patients living with SMA.

Now I'd like to turn importantly to the time lines and the progress that we are making for our BLA resubmission and U.S. launch upon approval. As many of you know, we were being reviewed under a priority review at the FDA with an action date for September 22, 2025. What we saw in our complete response letter, which we were both surprised and disappointed, was that we met the high bar of the FDA for clinical efficacy and safety based on the strength of that SAPPHIRE data. But the reason for our CRL solely was the general site inspection, which took place at Catalent, Indiana, our fill/finish facility, which is owned by Novo Nordisk.

Now I'd like to focus on the white boxes on the right-hand side of this slide. After the CRL, we held a constructive and collaborative in-person Type A FDA meeting on November 12. During that meeting, we were joined by Novo Nordisk and Cure SMA. The patient voice was heard. There was a shared understanding of the high medical need for the first muscle-targeted therapy to be delivered to the SMA community and a shared sense of urgency with the FDA to move forward expeditiously so that this product could be approved.

We knew that a couple of steps needed to take place after that Type A meeting. The FDA needed to communicate with Novo Nordisk on their remediation plan. They did that the next week with their warning letter. We then needed Novo Nordisk to respond to that warning letter with an update on their remediation plan, not just from their 483 observations, but also from the warning letter. They did that within 15 business days. Then the FDA and Novo continued to work up until the holidays and through the holidays. And the next step is a meeting between the 2 parties. The FDA has scheduled that meeting for early Q1. This shows the continued sense of urgency amongst the FDA, Novo Nordisk and Scholar Rock to make sure that we can set ourselves up for a successful reinspection, BLA submission and, as I noted, a U.S. launch following the approval by the FDA.

We are pleased with the progress and pleased with the continued efforts of the FDA. This has been on a very rapid pace, and we're happy that this meeting is taking place in early Q1 to discuss the remediation plan.

Now we are planning for success. The U.S. commercial team was recently deployed just before the September PDUFA date. It's a top team that is preparing the marketplace for the eventual approval of apitegromab. The team is focused on engagement, disease education about the importance of the muscle, addressing the muscle component of the disease as well as the motor neuron component. And they're educating a broad SMA stakeholder base, physicians, SMA centers of excellence, all of the SMA treatment centers. We continue to build strong collaborations with Cure SMA and additional advocacy groups because we know that the success at Scholar Rock is going to be built by lasting relationships, one patient at a time, one caregiver at a time and one family at a time.

And look, we expect that there is going to be strong demand for apitegromab upon approval, and we want that demand to be met with simple, reliable and trusted access. Our U.S. commercial team has used this additional time wisely to work with national and regional payers to educate them on the unmet need and the potential benefit of apitegromab so that this opportunity will be well planned for upon approval of apitegromab in the United States.

As Keith has often said, the U.S. will be the playbook that we run for our opportunities globally. And Europe is the market that would follow the U.S. We built strong momentum with apitegromab launch readiness in Europe. We're building a world-class team. We're engaging the SMA community, and we are working on all of the important dossiers that will set up for individual country-by-country reimbursement processes. We believe that this work really leads to a successful launch throughout Europe, which will commence with Germany in the second half of 2026, with other important countries to follow.

Apitegromab and SMA represents a large global opportunity to serve patients. Our estimates show that in 2025, the SMN-targeted therapies that are approved will do about $5 billion in global revenue. This marketplace continues to grow. Apitegromab is positioned to be the first and only muscle-targeted treatment to show clinical benefit in patients with SMA, and we see a $2 billion plus opportunity for apitegromab in SMA alone.

We continue to hear from the community that they are demanding access to this treatment as soon as possible.

I now want to turn to our other priorities for 2026, including developing apitegromab for patients under the age of 2 and additional neuromuscular diseases. We've seen all along the opportunity to build a pipeline and a product strategy with apitegromab given the high innovation that it brings. As I noted earlier, we are very pleased to have commenced our Phase II study, looking at patients under the age of 2 that have received an SMN1-targeted gene therapy. We want to make sure that no patients are left behind, especially the youngest patients with SMA. Patient dosing has commenced, and we will continue to provide you updates on the progress with our OPAL trial throughout 2026.

We were very pleased this morning to announce our next indication for apitegromab, FSHD. FSHD is a rare devastating neuromuscular disorder with significant unmet need. More than 30,000 patients are diagnosed in the U.S. and Europe alone, and there are no approved therapies. This is a disease that has caused from abnormal expression of DUX4, symptoms usually begin in adolescence or early adulthood, and about 1/5 of patients will become wheelchair dependent. Importantly, there's data that really support apitegromab's therapeutic hypothesis in FSHD. Randomized studies of exercise programs suggest muscle has the capacity to show functional benefit. In a study of anabolic agents, human growth hormone and testosterone suggest increase in lean mass and muscle function, as you can see in this bottom panel on the right-hand slide in both lean body mass as well as the muscle function as measured by a 6-minute walk distance test.

We've also done our own preclinical work that provides mechanistic rationale for apitegromab in FSHD. We used the gold standard FLExDUX4 mouse model, and what we showed with apitegromab preclinically is a robust increase in muscle mass, significant improvements in muscle force and consistent gains in endurance just 28 days after administering our antibody.

Our IND is cleared, we can proceed, and we're very excited to commence the FORGE Phase II trial evaluating apitegromab in patients with FSHD. This will be a high-quality Phase II randomized, double-blind, placebo-controlled studying 60 patients, randomized to receive either apitegromab at 10 mg per kg or placebo. We're going to be focusing on mild to moderately severe FSHD patients, and the primary endpoint will be lean muscle volume change at 12 months. We'll look at additional secondary and other endpoints, including, importantly, the functional endpoint of quantitative Myometry testing. This is an important functional measure that's been used in advanced clinical trials for FSHD. Dosing will commence later this year in the FSHD study.

As I noted, the era has not been there. We see a world beyond SMA and FSHD with genetic neuropathic diseases, genetic myopathies and those diseases that are also acquired. And Akshay and team will continue to evaluate how we can maximize our impact with apitegromab across a range of diseases that devastate patients.

I want to now close with advancing our world-leading anti-myostatin pipeline so that we can continue to bring innovation to patients who we will start to serve in 2026.

We showed some very exciting data with our subcutaneous apitegromab, which demonstrated favorable bioavailability with a pharmacodynamic profile compared to IV administration. We dosed healthy volunteers at either 800 milligrams IV or subcu. And what you see here is an overlapping pharmacodynamic profile for both of those modes of administration. This really supports further development, which those activities are ongoing, and discussions with U.S. and European regulators later this year.

We're also super excited about SRK-439. We're leveraging our world-leading expertise to drive continued innovation by targeting myostatin. As you can see in this in vitro assay on the left, SRK-439 is 10x more potent than our highly innovative apitegromab molecule. And as you can see in -- at about 56 days, in nonhuman primates, there was a change in whole body mass, even seen at a very low dose of 0.3 mg per kg with SRK-439. The team was busy at work. Our IND cleared in November. We started to dose healthy volunteers in December, just last month, and we are on track to share top line data across 76 healthy volunteers in the second half of 2026.

I've just got a slide or 2 to close on our financials and our upcoming milestones. We fortified our balance sheet with minimal dilution in 2025. We have a strong cash position as we enter 2026, as Vikas is focused on making sure that we operate with financial discipline, but yet invest in our high-value programs. We have approximately $365 million in cash and equivalents at the close of 2025. This really provides cash runway to support our operations into 2027. And importantly, it's a very conservative estimate because we do not include monetizing the priority -- the rare disease priority review voucher and/or any revenues for our expected launches in 2026. This cash balance allows us to make our strategic investments to support commercial readiness and our launches in the U.S. and Europe as well as thoughtful capital allocation to continue to advance our clinical pipeline.

So I'll just close with our priorities for 2026. Commercialize apitegromab for children and adults with SMA starting in the U.S. and Europe, expand the reach of apitegromab by making sure no patient with SMA is left behind, and also moving apitegromab into additional rare, severe and debilitating neuromuscular disorders, and continuing to advance what we do best, our world-leading anti-myostatin platform and pipeline with subcu apitegromab and SRK-439. We are going to drive value through focused execution and financial discipline, and we are very excited for 2026, a transformative year for Scholar Rock. Thank you.

David, do you want to introduce the rest of your team that you'll have up on stage?

Yes. Thanks, Tess. For Q&A, I'd like to bring up Akshay Vaishnaw, our President of R&D; Keith Woods, our Chief Operating Officer; and Vikas Sinha, our Chief Financial Officer.

Great. Well, thank you so much for the presentation. I thought I would start with a bigger picture commercial question here. What specifically are the key underlying assumptions underpinning your view of a $2 billion plus opportunity in SMA? What are the Rest of World regions that are most interesting to pursue globally?

Yes, I'll start and then Keith can jump in. Look, we are confident in that projection. We really base it on a couple of things. First of all, ushering in the next era of innovation in SMA, being the first and only therapy that addresses the muscle, an important, really the principal organ that is affected in SMA. We look at the 35,000 patients globally that are receiving at least 1 SMN-targeted therapy. We look at the demand from the physician and patient community. We obviously are anticipating our labels starting in the U.S. and then in other regions. We think about pricing and reimbursement in the U.S. and around the world. And we think that these are -- obviously, we're continuing to see 10 years later, Tess, since the first SMN-targeted therapy was approved, continually this market is growing with more and more patients receiving the therapy. And as we noted, 10 years later, these 3 approved therapies are reaching $5 billion in global revenue.

So we see this as a very reasonable and in some ways, a conservative estimate for us as we think about the opportunity that is in front of us. And I would just note for the audience, we've kind of seen this before, our pattern recognition. Many of us have worked on brands where we build a 50-country operating platforms. We did that at Alexion successfully. Keith, after Alexion, did that quite well as the architect of the VYVGART launch at Argenx. And with that, I'll bring Keith in on just sort of looking at those markets, I think, Tess, outside of the U.S. and Europe, the ones that are particularly attractive. Keith?

Yes. I mean, first, what I'd add to what you just said is that the $5 billion marketplace for SMN-targeted therapies that continues to grow. This is a space that you're already seeing from the data that David shared that 9 out of 10 patients are saying that muscle strength is one of their most important needs. And already before even launching a muscle-targeted therapy, we have 3/4 of physicians that are saying multiple modalities are required to treat these patients. It's the unmet medical need that's going to allow us to play in the entire SMN-targeted population eventually.

As far as the key marketplaces, look, we're going to stage -- we're going to stage this. We're managing our expenses as we do so appropriate. But while we do so, we advance, as we said, U.S. and get this across the finish line. We're making great progress with Europe as we speak. We'll then go to Asia Pacific, Japan specifically first, and then we'll be going into LatAm. So the opportunity to accomplish this, I think, is not only quite possible, I expect us to.

Okay. And how much of that $2 billion plus is U.S.?

I'd like not to break that out at this time. But obviously, we do feel good about the strength of our application with the FDA, the progress that we are making. Akshay may want to comment on just the label itself. And of course, as the global market grows, the U.S. market continues to grow with approximately 7,000 patients receiving at least 1 SMN-targeted therapy, in many cases, upwards to 1/4 to 1/3 are receiving more than 1. And so we feel like the U.S. is set up quite nicely for us for a robust launch.

And on the label there, can you give us a little bit of a preview of what the FDA agreed upon? What is the indication statement that we should be thinking about for apitegromab?

Yes. I'm going to bring Akshay, and one of the things Akshay and I are very thoughtful about is making sure we don't get out in front of the FDA, given that we will be resubmitting our BLA. But as Akshay has noted, we've made meaningful progress there. Akshay?

Yes. Prior to the complete response letter, we were delighted with the review of the BLA culminating in very robust discussions around the label and the indication statement, Tess. Obviously, we can't say anything until the drug is approved. We've got to let FDA complete their work. What I would say, a couple of things, I think, are very important as we look at how the FDA has labeled up drugs in the SMA space. One is that they regard SMA as a single disease. They tend not to use the older type 1, type 2, type 3 type nomenclature. They feel the mechanism is applicable to the disease broadly, then they allow the drug to be indicated for SMA as opposed to subpopulations. So I think that's important to note, and we're excited about that.

We're also pleased that, in general, they've reflected the unmet need and the breadth of the population, and they look at the inclusion/exclusion criteria in the pivotal studies. We dose patients older than 2 on background SMN corrects. And previously, they've faithfully stuck to that or build on that for the indication statement. So again, we've got to let the FDA finish their work, but those are some things we have observed about their prior approaches in this space.

Great.

And certainly, I would say, the anti-myostatin mechanism is broadly applicable, we believe, to the entire SMA space.

Okay. I'd love to get into a few manufacturing questions, if I could. So the warning letter was made public on the FDA's website, and it appeared to have multiple parts to it. And in your press release this morning, you also noted that you continue to work closely with the FDA in Catalent, Indiana, to progress remediation activities at the Bloomington fill-and-finish facility to support your BLA submission as rapidly as possible, or resubmission rather. Can you elaborate specifically on what you mean here? What is your understanding of what was specifically in that response to the FDA warning letter?

Yes. Happy to do so. I think importantly, when we had our in-person constructive and collaborative Type A meeting, which Akshay really led our team, which, as I noted, included our Scholar Rock team as well as Cure SMA and Novo Nordisk, we felt like there was an agreement to move with sense of urgency to sort of get on with the things that needed to happen before we could resubmit our BLA. As I noted, it would be a communication to Novo. We got the sense in that meeting it might be by the end of the year. I think that shared sense of urgency really manifested itself by the warning letter coming the next week. I actually think, in some respects, that was very helpful. Because if you need 15 business days to respond to a warning letter, good that it came out the next week after our Type A meeting as opposed to the end of the year.

Importantly, for us and Novo Nordisk, there were really no new issues in the warning letter. They didn't raise anything new. They did highlight some parts of the remediation plan that fell short. Novo Nordisk brought in a sensational group to help them provide what we think was a great response. They've provided the FDA with their progress, not only on remediation from the 483 observations that were seeing in July of 2025, but also the warning letter. They made meaningful progress. And then we were really heartened by the fact that Novo and the FDA were really working up till the end of the year to schedule this meeting that is going to be the precursor to a reinspection. And the fact that, that is scheduled for early Q1 is actually, we think, really underscores the fact that FDA, Novo and Scholar Rock are all working with urgency to eventually serve the SMA community with an approval for apitegromab.

Can you confirm that the Bloomington site was indeed inspection-ready at the end of 2025?

Yes. It's a very good point. What I can confirm for you, again, as Akshay oversaw that meeting, is Novo attended our Type A meeting, and they stated to the FDA, Novo did, that they were reinspection ready by the end of the year. When we saw the warning letter, our question was, is it still going to be by the end of the year? It's a bit irrelevant if the meeting is taking place early in Q1 because we know a reinspection won't happen before that meeting. But I know that Novo Nordisk feels really good about their reinspection readiness here in early 2026, and we're really looking forward to this meeting between FDA and Novo in early Q1.

Okay. Any further granularity on what the dialogue might look like in that meeting?

I think they'll discuss the remediation progress. As I noted, remediation progress will be both the initial 483 observations as well as the additional things that were raised in the warning letter. And then we would be hopeful that they're sort of putting a circle around so what kind of time line would one be on for an unannounced reinspection of the facility, which obviously then unlocks our application. And again, we -- having the insight that we do, we're pleased with the work that Novo has done. We're pleased with the pace that the FDA has been working on given the great work that Akshay led at our Type A meeting. And so we're hopeful that it is really the last key step toward the reinspection that really enables a reclassification of the facility, a BLA resubmission and an approval for apitegromab. And we're quite pleased and remain confident in the guidance that we provided for BLA resubmission and U.S. launch here in 2026.

Okay. And for the second fill-and-finish facility, what are the next steps there? And how much time will you need before you can submit an sBLA for this facility?

Yes. So we -- tech transfer is underway as we announced on November 14. This is another fill/finish facility in the U.S. They've got dozens of approved therapies, recent and long-term successful inspection history with regulators. And they happen to have a line that was available to us that we were able to unlock that is actually perfect for a vial configuration, a commercial line. So we jumped on that and we locked in commercial capacity reservations beginning in Q1. What would happen is engineering runs and PPQ runs here in Q1, Q2. That really helps to provide the data for us to then add them, which we would expect we would add them in an sBLA. So we would expect this to be the second facility that we add, but it could be good if, for some reason, something didn't work out in our favor, good to be moving forward with them with a sense of urgency, and we would expect that to happen in the second half of 2026. But we're working very well with the second fill/finish.

Of course, we have to find another fill/finish anyway because Novo wants to internalize operations at Catalent, Indiana, for their own portfolio. They are not going to be in the business of being a third-party manufacturer. They bought this from Catalent for the use of their own portfolio and their own pipeline.

Can you just talk a little bit about your commercial supply build-out given kind of all these moving parts that we're talking about here? Will you be ready to launch in 2026?

The answer straightaway is yes. So we've said all along, we've had a lot of product that has been manufactured and vialed and is ready to go. And we believe that supports even the high demand that we expect in the U.S. market that will support the launch. And obviously, we'll be manufacturing and filling more apitegromab at any one of our fill/finish facilities over time. But we've got plenty of drug substance. We've got plenty of vialed finished drug and it is just awaiting to be labeled and ready to go upon approval.

Okay. Last question from me. I forgot how short these presentations are. How should we think about OpEx in 2026 and cash burn?

Vikas?

Yes. In terms of OpEx, we have controlled the costs significantly. And as you see, we announced the cash position in Q4. We have really managed it in a good spot, and we'll continue to do that going into 2026. And if we do have a launch in the horizon coming soon, and then we'll discuss to augment that further by a non-dilutive financing that we will bring in, especially in the form of debt.

And Vikas, I would just say we have very little debt on the balance sheet at this moment. Thank you.

Well, I think we're going to have to leave it there. Thank you so much to the entire Scholar Rock team, and thanks for everyone joining us.

Thanks for joining.

Andrew Pucher. I'm a member of the Citi Biopharma Investment Banking team here. Very pleased to be joined this afternoon by David Hallal and Vikas Sinha of Scholar Rock. And so why don't we get into it with a little bit of Q&A around the company, your data, how to think about the path to commercial launch and beyond.

Maybe just opening remarks, I'll open it up for you guys, a little bit on your background and how you got involved and what you saw at Scholar Rock to get you involved in your current executive roles would be good context. And then maybe some opening remarks, David, from you in terms of how investors should think about the positioning of Scholar Rock today.

Great. Thanks, Andrew. It's fantastic for Vikas and I to be here at the Citi Healthcare Conference in Miami. As you know, Andrew, this has been really a transformative sort of 12, 14 months for the company, really starting with the readout of our Phase III trial in October of 2024, where we hit stat sig as the first ever muscle-targeted treatment to be used in children and adults with SMA. And then it's been quite a fun 14 months to get to this point today. Interestingly enough, as you know, in April of this year, -- we did announce that I was going to step into the CEO role in addition to my Chairman role, which I've been holding since July of 2017. But for me, given the opportunity that I see for Scholar Rock, which is to really build one of the next great global biotech powerhouses, much like the pattern recognition of some of us that we built together previously at places like Alexion and argenx and Alnylam.

I thought it was important the day that I took over as CEO was to establish the foundation with a world-class executive team. And so on the same day that I was announced as stepping into the CEO role after 8-plus years as Chairman, we announced my partner, Vikas Sinha, was assuming the role of CFO. My dear friend, Akshay Vaishnaw, who for 19 years, led R&D for Alnylam, had been on the Board with me at Scholar Rock, stepped into the role of President of R&D. And then for the third time, I had an opportunity to hire Keith Woods as our Chief Operating Officer. Keith and I worked together at Amgen in the 1990s, again, at Alexion in 2010 to 2017. And then some of the best work that Keith has done was at argenx, where he was really the architect of the VYVGART launch in MG.

The reason why I was so eager to not only step into the role when Jay Backstrom was resigning and retiring from the role, but to bring in this world-class leadership team as we sort of see the opportunity in front of us. It's to build a dominant force in the rare neuromuscular space, led by our first asset, apitegromab, with this opportunity that we have to serve patients globally with SMA and then to follow that on with a series of clinical development programs for apitegromab and then some other myostatin inhibitors that we have at an earlier stage. And that provides us the opportunity, as I noted, not only to launch an extraordinary drug in the U.S., but much like we've done before Vikas, turn our attention to Europe, Asia Pacific and Latin America and build a 50-country operating platform where we can make sure that we can serve patients in need wherever they reside around the world. And that is really what we have been focused on over these past 7, 8 months.

Vikas?

Thanks, David. Yes, when David invited us to come and join the Scholar Rock management team, it's just like going back to building once again the same way that we built Alexion Pharmaceutical from 0 to a $40 billion company. We are looking at this opportunity as a starting point and building it from here.

And Andrew, I'm going to go all the way back to -- after 11 years at Alexion, why I accepted the role as Board Chairman of Scholar Rock is my own pattern recognition was the following: what was not novel at Alexion was that we were targeting on complement to inhibit. What was novel at Alexion was that after years of pharma and biotech trying to effectively drug complement and being unable to do so, Lenny Bell and the scientists of Alexion had developed the ideal way both safely and effectively to inhibit complement. And that opened the door not only to the first-ever treatment for paroxysmal nocturnal hemoglobinuria, but it gave the company really a pipeline and a product for wherever complement was implicated in disease.

And so when I looked at Scholar Rock, for 20, 30 years, pharma had been focused on trying to drug myostatin and every one of those trials failed. And we saw kind of a unique platform that we had at Scholar Rock to inhibit myostatin more uniquely than any other company had done before in a very novel way. And that is why even in a preclinical stage, I stepped in as Board Chairman because I thought we had the opportunity to do something really special. Now 8, 9 years later, we're the first company to ever have a successful Phase III trial with a myostatin inhibitor. We did choose an indication that we think we can make a meaningful impact for patients and build the financial strength for our company for many years to come, and we're super excited about the future and discussing that in more detail with you over the course of our time together here.

Great. So you guys have clearly put together a world-class team around this to prosecute this opportunity. Maybe before we get to how to think about SMA and apitegromab's positioning in that marketplace, let's talk a little bit more about the approach to myostatin. And to your point, David, there's been a long list of attempts and failures. Just what's the secret sauce? How should investors think about what's differentiated here in terms of your approach to targeting myostatin?

So what I saw back in 2017 was that most companies that were targeting myostatin were doing it 1 of 2 ways, either by developing inhibition strategies to the mature form of myostatin or looking for a trap technology for the receptor. The problem with that is there are many other growth factors in the TGFß superfamily of growth factors that pharmacologically look and act very similarly to myostatin. And therefore, if you were to develop an antibody, for example, or a trap strategy, you are going to have off-target effects. You will inhibit other TGFß superfamily of growth factors, and that leads to either imperfect potency in inhibition and also some safety signals and safety challenges.

And so the secret sauce at Scholar Rock was when one -- myostatin is such a powerful negative regulator of muscle growth that the body itself has a chemical cage around myostatin when it's released from the muscle and that cage is what releases the mature myostatin into the body. What our scientific founders discovered was that it was that chemical cage or the latent form of myostatin that had a more pharmacologically unique chemical structure. And if we were to develop an antibody for that, we would have exquisite selectivity, only inhibit myostatin, not have any of those other off-target effects on things like Activin. In that case, we could, we think, effectively drug this target that has been so elusive for pharma. And we think our 8-year development program has really proven that out.

Yes. So with that selective approach -- let's talk about the SMA opportunity. And how do you -- how should investors think about just the SMA market with the SMN products that we have, 3 of them in the market today. And what's apitegromab's positioning as you think about launching this in the next couple of years?

It's a great question, Andrew. So as you noted, over the last decade, we've seen the introduction of SMN targeted therapies that really focus on upregulating a protein which patients need for motor neuron survival. It's either SMN1 protein, which the gene therapy from Novartis Zolgensma focuses on or SMN2 protein for which Biogen's SPINRAZA or Roche's Evrysdi really target those things. And it's actually brought very meaningful innovation to a community of children, adults and families that desperately needed it. There were very significant mortality rates in the SMA population. And over these last 10 years, these 3 drugs have actually really improved the morbidities and mortality associated with SMA.

At the same time, though, motor function is not just impacted by motor neuron survival. The motor unit is actually the motor neuron and the muscle, the organ of the muscle. Those 2 things together is what provides motor function, which is what patients who are now surviving longer desperately need. And so our hypothesis, which has been proven out now in our Phase II and Phase III trials is that anything that one can do with Zolgensma, SPINRAZA and Evrysdi is going to help patients by upregulating either SMN1 or 2 protein and help with motor neuron survival, but we call this disease spinal muscular atrophy for a reason. Muscles deteriorate. There is irreversible muscle loss in these patients, and there has never been a muscle-targeted treatment to focus on muscle strength.

It is the sum of muscle strength, muscle mass, muscle responsiveness with motor neuron survival that will provide the optimal benefit for motor function, which is what the community is really looking for. So we designed our Phase II and Phase III clinical trials largely to take patients who have been on one of these SMN-targeted therapies. They then receive apitegromab. And what we have now seen over many years in clinical development is a statistically significant, clinically meaningful improvement in motor function when apitegromab is used with an SMN targeted treatment versus an SMN-targeted treatment alone.

In fact, in our Phase III trial where we hit stat sig with a p-value of 0.01, what we actually saw was patients who had been on these SMN-targeted treatments over the long run started to once again progress to motor function loss after being on these therapies for quite some time. And what we were able to show and demonstrate in our Phase III trial a return of motor function improvement or motor function gain rather than the patients on SMN-targeted treatments alone having motor function loss.

Also underscoring the benefit is there was a near 4x greater likelihood in our Phase III trial of patients having the most significant improvement in motor function, which is a 3-point improvement in the Hammersmith motor function score for SMA compared to an SMN-targeted treatment alone. We thought that, that was quite profound. And it is really in that 188-patient placebo-controlled global clinical trial has really been the basis up to this point, a very successful review cycle with the FDA to get to a point where we are on the near doorstep of an approval and bringing this to patients in the U.S. living with SMA.

And so as you think about -- and I think the data that you guys have published and presented and made public is quite profound, to your point, of motor function improvement. Maybe paint the picture of relative to the current market of patients that are on SMN-targeted therapies, how should we think about apitegromab's opportunity here in conjunction with patients that are currently on therapy? Maybe just size the market for us.

It's a great question. So in the U.S., there are approximately 7,000 patients who have received at least 1 SMN targeted treatment. And globally, there are about 35,000 patients, inclusive of the 7,000 in the U.S. And that actually Vikas follows very much, the global footprint that we saw in other rare diseases at companies like Alexion. So we would see maybe 1/3 of the opportunity in the U.S., 1/3 of the opportunity in Europe and 1/3 of the opportunity rest of world. And certainly, that seems to be playing out when we look at the sales and the revenues of those other 3 programs.

In aggregate, those other 3 drugs are delivering year-on-year continued growth a decade after the first one was introduced by Biogen, SPINRAZA. And in aggregate, they're doing $5 billion a year in annual revenues, and it continues to grow. For us, we think whatever SMN targeted therapy is used, what the patient community really needs is the first ever muscle-targeted treatment to provide the optimal benefit for motor function improvement. And so that we see this as our opportunity in the U.S. is these 7,000 patients that have received one or more of these SMN-targeted therapies and 35,000 patients globally.

We think that's quite -- it's almost a perfect size. It's a small enough rare disease community where the budget impact is not so great that it will really trip off the system, but it's a really meaningful number of patients that we think provides sustainable revenue growth through the end of this decade and well into the next for Scholar Rock as we grow what we believe is a multibillion-dollar opportunity for apitegromab in SMA alone. And then I'm sure Andrew will talk about our plans to enter the clinic for other rare neuromuscular disorders as we've been able to develop this very strong body of evidence starting in SMA. But together, we see in the U.S., a tremendous opportunity and globally, probably more than $2 billion in annual revenue for apitegromab in SMA alone.

And let's talk about 2 follow-up questions there, David. One is, I think it's important to understand the commercial preparedness and how you plan on executing on that opportunity, not only in the U.S. but globally. Obviously, you and members of your team have very successfully done that in the rare disease space a couple of times before. So where does Scholar Rock stand? And how do you think about -- as you think about the patient opportunity outside of the U.S., in particular, how you tackle that relative to the current competition with SMN targeted therapies?

And then let's talk about really the opportunity to build a global leader beyond -- this is not just an SMA play, right? As you think about neuromuscular more broadly, let's talk about where you think this approach to myostatin and your world-leading expertise in biology there is applicable to really build a pipeline and a pill type of opportunity here.

Thanks, Andrew. I guess, first off, what I would say is I view Biogen, Roche and Novartis as definitely not as competitors. And the reason for that is they focus on a key part of the motor unit, which is motor neuron survival, but there is no doubt that patients and physicians, and we hear this on a daily basis, really do believe that motor function is the sum of motor neuron survival and muscle strength. And there is nothing to address muscle strength in SMA. So we really see what apitegromab is, is like we're kind of like the Switzerland in this marketplace where no matter what one or in many cases, what we see in the U.S. is upwards to 1/3 of patients are receiving more than one of these SMN-targeted treatments at the same time because the patient community is really looking for more. No matter which one or more of those therapies you choose to use, no matter what, the background or foundational treatment really ought to be apitegromab so one can address the muscle component of this disease and address the muscle atrophy. So we feel like we're well positioned where we're really competing with ourselves.

We don't really see any near-term competitors over the next 3 to 5 years. We think most other programs have just not matured or delivered favorable Phase III results. And I think we're still upwards to a year away from even the first proof-of-concept study being done with a muscle-targeted treatment behind us, and then there's years to then plan and enroll a Phase III trial. So we think we're in a really, really good position.

Now commercially, how we're approaching this, and Andrew, as you and others at Citi came to know Vikas and I previously in the multibillion-dollar businesses we've had to build before, those were rare diseases where the the patients had the disease, but they were not yet diagnosed. These were such rare diseases that most doctors didn't even know what they were, never even thought of them, PNH, aHUS. In the case of SMA, these patients are diagnosed. In the case of SMA, these patients have either private or public funding for rare disease therapies because they are already on either Zolgensma, SPINRAZA or Evrysdi. So it means they're residing in a country in which there is support for rare disease therapies. And that probably helps us in terms of the timing of being able to identify and treat these patients. And we think that, that's a quite a nice setup for us.

So the patients are known to us. The patients are known to the medical community. They're now gaining a greater and greater appreciation for how important a safe and potent muscle-targeted therapy will be for their overall sort of outcomes over the long run, and we think we are well positioned to sort of really take advantage of this unique dynamic in the marketplace. We also think -- and I think this is important. I've been asked, how do we feel about apitegromab now being reimbursed in addition to the current SMN-targeted treatment that a patient is on. I think if one looks at many rare diseases, both the patient numbers can be higher and even the price of a single drug could be higher, we think there is plenty of room for the combination of apitegromab with those SMN-targeted therapies where there will be limited budget impact and really optimal sort of outcomes for patients by receiving apitegromab and their current SMN-targeted treatment. So it sets up very, very well for us to kind of follow the market that's been created over these last 10 years.

To come to your next question, so the way I think about the growth at Scholar Rock and Vikas is really helping us build that balance sheet and then build, he will oversee along with Keith Woods, kind of the global build-out very much like we've done at Alexion before. We'll start in the U.S., we'll move to Europe. We'll then add on Japan, other key markets in Asia Pacific and also then Latin America. And these are not massive operational builds. These are generally very tight, small organizations country by country. And we see over the next 10, 15 years, just consistent growth year-on-year as we add new countries and add new patients with SMA on apitegromab over the course of a 10- to 15-year period of time. And so that's -- that will be kind of our very methodical march to building a multibillion-dollar business in SMA alone.

But then you asked another important question, Andrew. We're not going to stop there. We'll announce early in 2026, the next indication with an IND that has been cleared so that we can move into the next rare neuromuscular disorder that we believe we can then follow the same pattern as SMA, really address the needs of the marketplace, do a robust Phase II trial to demonstrate safety and efficacy in that next rare neuromuscular disorder and then follow that into Phase III. And the air will not be thin there. We've talked about FSHD. We've talked about DMD. There's a number of other indications we are assessing right now, and we look forward to sharing more light on that in the near term. But very much like you've seen at argenx more recently, Alexion dating back over the last 20 years, we think that pipeline and a product strategy is a very efficient way to build an extremely valuable company that's really focused on the service of patients with rare diseases.

Great. I'm sure we all look forward to hearing more about that in 2026 as you roll out that next leg of how you're thinking about the pipeline in rare neuromuscular. Maybe to come back to the SMA opportunity. I know you face a lot of questions of what's the state of FDA interactions post CRL. Maybe bring us up to speed on what you're able to share on interactions with the FDA and how to think about time line to potential launch.

First of all, it is refreshing to talk about something not related to the manufacturing. So -- but this is also the thing we're obviously thinking about quite a bit because it's the one thing in the way of bringing a revolutionary new treatment option to children and adults with SMA. To bring us back to the story, we were -- as I noted at the beginning in my opening remarks, we were thrilled after 7-, 8-year development program to have a positive Phase III trial, which we announced in October of 2024.

We then submitted our BLA in January of 2025. And then just before the announcement of Vikas, Akshay and Keith joining me on the executive team, just a few weeks before that in April of 2025, we announced that the FDA had accepted our BLA under priority review, which then provided us an accelerated review period with an action date of September 22. During the course of that, we obviously had all the necessary inspections focused on clinical GCP standards in all of our clinical trial sites, on-site inspections at Scholar Rock, on-site inspections at those clinical trial sites, but then also inspections at our drug substance and drug product manufacturers.

What we announced in our Q2 earnings call on August 6, I believe, was that the FDA, one in doing a PLI inspection at our drug substance manufacturer and then at a general site inspection at our drug product manufacturer issued a Form 483 with multiple observations in those facilities. And I think the thing that obviously was a bit of a concern was that in the drug product manufacturing facility known as Catalent Indiana, now owned by Novo Nordisk, these were repeat observations dating back to prior inspections for when Catalent had owned that facility. We did feel like at that time, between August 6 and September 22, there was enough time for those manufacturing facilities to adequately respond to the Form 483 observations with a robust remediation plan and try to get to be done with as much as possible so that we could be approved on time on September 22.

In fact, we had a great late cycle meeting with the FDA. Everybody was lined up to try to get there by the 22nd of September. Given the tone and the tenor and the nature of the review, we expected when we woke up on Monday, September 22, given what we were doing with the FDA on the 18th and 19th of September, we expected we were getting approved. Unfortunately, we then received a CRL after 5:00, 6:00 or so on the 22nd. And what was outlined in that CRL is that the one remaining issue that led to the CRL was the drug product manufacturer, Catalent Indiana, owned and operated by Novo Nordisk.

In fact, the Form 483 observations at the drug substance facility had been adequately resolved. And look, both facilities had completed a similar percentage of their remediation plan. I think the difference was the historic observations and issues with GMP practices at the drug product manufacturer and the FDA wanted to see more from them. This obviously followed Regeneron getting tripped up with their own time lines because they were at the same facility. So the CRL was issued on September 22. We felt like Novo was really committed to remediating the plant. And then in October, right around Columbus Day weekend, we then learned from Novo Nordisk that the classification of the facility became OAI, official action indicated, which kind of made us feel like we were heading toward a little bit longer of a remediation process than we would have hoped for.

And that obviously was all issued before our Type A meeting. Our Type A meeting we requested shortly after our CRO, and we held that on November 12. And what was important about that Type A meeting, Andrew, it was going to be the first time with Novo being at that meeting with us that they were able to present. They have been sending the FDA updates on their remediation plan, but they were able in person to present their progress on their remediation plan and state to the FDA that they would be reinspection ready by the end of 2025, by the end of December. And we had a very constructive and collaborative in-person meeting with the FDA. They don't do a lot of in-person meetings. We think that underscored their commitment to want to learn about what was happening and sort of hold hands and agree that there was shared urgency to get this very important first and only drug for patients with SMA targeting the muscle to patients as quickly as possible.

We walked out of that Type A meeting feeling like there was going to be more urgency to resolve the remediation plan at the facility. And in fact, we expect the next step would be some level of correspondence that the FDA would have with Novo, and then that would trigger whatever needed to be done before the reinspection. In fact, a week after our Type A meeting, and we just disclosed this yesterday via 8-K, that correspondence came in the form of a warning letter that is not yet even published on the FDA website. That warning letter is pretty consistent with the Form 483 observations.

Novo is committed to responding to that warning letter within 15 days, and that should then lead to the necessary next steps of within a month after responding to that warning letter, we would hope that Novo and the FDA would be working together to then agree on whatever is left to be done and then sort of start to indicate when the reinspection could occur in 2026. And we expect this to all be handled expeditiously by both Novo and the FDA. And we'll continue to work with both parties in a very collaborative fashion because this is the only issue remaining in the way of apitegromab finally being approved for children and adults with SMA. Hopefully, that's helpful.

It is. Yes. Thank you for going back through that. I'm sure there's been no shortage of questions about that over the last couple of months. Maybe to shift gears, I'd love to come back to the pipeline in SRK-439 and maybe put in context how that next-gen anti-myostatin, which is subcu fits into the portfolio and the broader rare neuromuscular opportunity that you outlined for us.

And I should say, Andrew, on November 14 after the Type A meeting, recognizing that a correspondence was likely coming from the FDA to Novo, it would either be an untitled letter or a warning letter, the content of which would likely be the same. We actually shared guidance that we expect to resubmit and launch in the U.S. in 2026, and that guidance remains unchanged. That's what we're expecting. We know that's a wide time window, and we're not ready to narrow that time window just yet until Novo and FDA sort of have a couple of more meetings about kind of where they are with their remediation plan.

Coming back to SRK-439 and our confidence that we will be launching next year, we continue to move forward with our pipeline. As I noted, we'll highlight our next indication for apitegromab in Phase II trial early in 2026. And then we are starting to dose healthy volunteers with SRK-439 this month. This is a really important drug for us. SRK-439 is not a next-gen apitegromab. It's a completely independent molecule. It's a very potent, high affinity, low-frequency subcu presentation of a myostatin inhibitor based off of our very same platform of inhibiting latent myostatin.

When I had become the CEO of the company, it was generally thought that this would be the cardiometabolic or obesity program for Scholar Rock, but I kind of took a step back. And I said, given all of my experience, we're going to build a multibillion-dollar business with apitegromab. It's going to be an SMA in a variety of other rare neuromuscular disorders. Given the power of SRK-439, wouldn't it be great if it was going to be something to help us defend and grow this rare neuromuscular franchise that we are building. And that's why we've just tamped down the brakes in sort of determining that this is going to be something not for rare neuromuscular. I think we want to get through our healthy volunteer studies. It's got its own IP. It's got composition of matter well into the 2040s. By the way, apitegromab has composition of matter well into the 2030s and late 2030s, we feel really good about that. But we think this is going to be a very, very important asset for us. We think the healthy volunteer data, which we'll disclose in 2026, will be important because if you can safely and potently inhibit myostatin, there's going to be a pretty clear read-through that this will be a very effective therapeutic that we'll be able to bring in clinical trials, and we look forward to updating the world on that next year.

Great. So you guys have had a very eventful 2025 and 2024 as well, too. We're looking forward to all the progress that you'll make in '26 with the launch, the next indication, 439. Maybe in closing, and then I'll open it up for questions to the extent there are any here from folks in the room. Anything we haven't covered that you want to cover in closing remarks?

I would like to cover the balance sheet because we took some steps with the CRL. But I think the one thing about the CRL, there was kind of a little bit of strength behind our stock, which is not common with a CRL. But I think there was a lot derisked with the CRL. I've often said like a CRL served us better than a major amendment. If we got a major amendment, there still would have been questions around, have you met the bar for safety and efficacy with the FDA. Was your drug substance manufacturing facility cleared or not cleared? We wouldn't have known that with a major amendment. The CRL actually helped to illuminate we have one issue and it's solvable. And our approval is not a matter of if, but when. But what we wanted to do in the strength of sort of how we were continuing to perform is tighten up the balance sheet so we can continue to build a great company. And I'd love for Vikas to just share those steps that we took, our current cash balance and how we look at being able to finance our operations right through the approval next year and U.S. launch and beyond. Vikas?

Thanks, David, and thanks, Andrew, for hosting us today. We -- in our Q3 call, we talked about $369 million in our balance sheet, which takes us into 2027 in, right? The first role I see as a CFO to play here is how do you control the costs. And with the leadership and the company all behind me, we've [indiscernible] a lot of expenses that we would only release it once the approval comes. So that helps us give us a little time.

And the second one is try to avail as much as we can the anti-dilutive ways. So we are currently looking at expanding our loan facility. So we are currently withdrawn $100 million, add another $100 million into that and try and create at approval another $150 million. What was very intriguing yesterday that the House also passed the extension of PRVs, right? So we should be able to -- that will help us monetize the PRV whenever the approval comes, that adds a good chunk of cash also into the balance sheet. So we feel fairly comfortable right now that the launch will have enough dollars for us to take us through.

Great. Well, thank you both, gentlemen. Really enjoyed the conversation. Maybe I'll open it up with the remaining few minutes we have to the extent that anybody has questions here in the crowd.

On that note, thank you, David and Vikas. Appreciate your time.

Thanks, Andrew.

Good morning, ladies and gentlemen, and welcome to Scholar Rock's Third Quarter 2025 Conference Call. [Operator Instructions] This call is being recorded on Friday, November 14, 2025.

I would now like to turn the conference over to Scholar Rock. Please go ahead.

Good morning. I'm Laura Ekos, Vice President of Investor Relations at Scholar Rock. With me today are David Hallal, Chairman and Chief Executive Officer; Akshay Vaishnaw, President of R&D; Keith Wood, Chief Operating Officer; and Vikas Sinha, Chief Financial Officer.

For those of you participating via conference call, the accompanying slides can be accessed in the Events section on the Investors page of our website. During today's call is outlined on Slide 2, David will provide introductory remarks and a business update. Akshay will review our R&D progress. Keith will provide an update on our commercial readiness activities and Vikas will provide a financial update. We will then open the call for questions.

Before we begin, I'd like to remind you that during this call, we will be making various statements about Scholar Rock's expectations, plans and prospects that constitute forward-looking statements for the purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995. Any forward-looking statements represent our views only as of today and should not be relied upon as representing our views as of any future date. I encourage you to go to the Investors & Media section of our website for our most up-to-date SEC statements and filings. With that, I'd like to turn the call over to David. David?

Thank you, Laura, and good morning. Thanks to everyone for joining our third quarter earnings call today. In April, when I was appointed CEO after 8 years in the Board Chairman role, and on the same day, we brought in Akshay Keep MCOs. We were confident that Scholar Rock positioned to be the next great global biotech powerhouse. We based this on several factors. First, our conviction that the global opportunity with apitegromab in SMA alone offers the potential for many years of sustainable growth that will power our company through the end of this decade and into the next.

Second, as world leaders in myostatin biology, our ability to deliver transformative therapies to patients suffering with additional rare, severe and debilitating neuromuscular disorders. and third, leveraging our innovative platform to advance our novel subcutaneously administered myostatin inhibitor, SRK 439. When we joined Scholar Rock PAUSE -- the most significant milestone ahead was the September 22 PDUFA date for apitogramab in SMA, which had been granted priority review. Our BLA was supported by robust data PAUSE demonstrating apitegromab's efficacy and safety for children and adults living with SMA. Based upon our 188 patient prospective, randomized, double-blind, placebo-controlled PAUSE multinational Phase III trial. This trial showed a statistically significant and clinically meaningful benefit in motor function as measured by the gold standard Hammersmith motor function scale for SMA. While we were disappointed to receive a complete response letter on September 22, we were pleased that the strength of our Phase III data was reflected in the FDA's review of our BLA.

And that the sole approvability issue referenced in the CRL was the status of our third-party fill/finish facility in Bloomington, Indiana, which is owned by Novo Nordisk. We know that it is not a matter of if but when apitegromab will be approved in the U.S. for patients living with SMA. We are emboldened by the commitment we have made to the more than 35,000 patients globally living with SMA who have received an SMN targeted therapy. We are working expeditiously to deliver on our ambition that globally any patient with SMA who can benefit from apitegromab should have access to apitegromab. And now more than ever, we are confident in the significant opportunity that we have ahead of us to serve the SMA community as we work with the termination to bring this important medicine to children and adults with SMA. This is indeed what we know well and what we do well.

I would like to now provide a regulatory update on apitegromab. We had our Type A meeting with the FDA on Wednesday. We are grateful to the agency for their full participation, particularly in the context of a government shutdown. The meeting was in person and included the relevant leaders and decision-makers from the agency, including the neurology division and the Office of compliance. Our team was joined by Kenneth Hobby, President of Cure SMA and representatives from Novo Nordisk. We were encouraged by the meeting -- it was constructive and collaborative. It was clear that there is a shared understanding of the high unmet need for the SMA community and a shared sense of urgency to bring apitegromab to children and adults with this disease. Novo Nordisk detailed the progress they have made in implementing their remediation plan at the Bloomington facility and affirmed that they expect the facility to be ready for reinspection by the end of this year.

We discussed the path forward and await the final minutes of the meeting. We will continue to work closely with the FDA and anticipate resubmitting the BLA and U.S. launch following approval of apitegromab for children and adults with SMA in 2026. I'd like to now turn to adding redundancy to our supply chain. When Novo Nordisk purchased the Bloomington site in December of 2024, they plan to internalize the plant for their own products. In light of that, Scholar Rock implemented a plan to add an additional U.S.-based fill/finish facility. Now with the OAI classification, Scholar Rock has accelerated our time line for an additional biller. We have selected a world-class commercial facility that has a proven track record and has successfully completed recent site inspections, including with the FDA and EMA. As you know, 1 of the bottlenecks to rapidly adding a new vialer is securing commercial capacity. This can be a lengthy process. Importantly, we have secured commercial capacity commencing in the first quarter of 2026, and tech transfer is now underway.

We anticipate submitting an sBLA for this facility later in 2026. In summary, we will continue to work with urgency to bring this important medicine to the SMA community. We look forward to providing clarity on resubmission time lines as soon as we are able. In addition to the large opportunity we have to serve children and adults with SMA, we continue to strategically advance our pipeline. This includes the Phase II OVAL study progressing apitegromab in a second rare debilitating neuromuscular disorder as well as advancing SRK-439 into the clinic. Akshay will provide additional detail on these activities shortly. Importantly, to reach our ambitions, I am pleased to opportunistically strengthened our balance sheet during the third quarter, and we continue to operate with a tight financial plan. which Vikas will discuss later in the call. This plan is aligned to thoughtful strategic investments to drive long-term value creation.

We remain confident in the strength of our strategy, the grid of our team and the transformative potential of apitegromab and our pipeline. The regulatory challenges we face today are temporary, but the opportunities ahead to serve patients are extraordinary.

With that, I'll turn the call over to Akshay to provide more detailed update on our R&D progress. Akshay?

Thank you, David, and good morning, everybody. As David noted, we continue to work with urgency to bring a bit of amount to children and adults with SMA as quickly as possible. SMA is a rare severe neuromuscular disease resulting in irreversible loss of muscular and progressive muscle wasting that diminishes the independence of both children and adults. Apitegromab has the potential to reverse the trajectory of SMA from a loss of motor function to a game of mode.

As demonstrated in the Phase III SAPPHIRE study, underscoring the importance of the potential benefit of this therapeutic. I'd now like to turn to Wednesday's Type A meeting. I was pleased to lead our team at that meeting for Peter. A Baleno, the meeting was in person and included the relevant leaders and decision-makers from the agency, including the neurology division and the Oxotecompliance. Team was joined by Kenneth Hobby, President of Cure SMA and representatives from Novo Nordisk. The meeting was constructive and collaborative. We reviewed the comprehensive data from the item apitegromab development program, including the Phase II TOPAS study, which demonstrated that delayed treatment results in suboptimal motor function outcomes. PAUSE These data underscore the impact of delayed treatment and the urgency to make apitegromab available to the SMA community.

At the time of meeting, it was clear that the CRL we received on September 22 was based solely on the need of the Bloomington facility to be in compliance with CGMP or current good manufacturing practice regulations. During the meeting, never there, there's detail the progress they have made in implementing a robust remediation plan at the Lovington facility. Novo Nordics also shared with the FDA that did expect the facility to be ready for the inspection by the end of the year. We remain in close coordination with Neonode as we await the minutes from the Type A meeting. After Novo's completion of remediation of the Bloomington facility and a site inspection by the FDA we anticipate recommission of the BLA and U.S. launch following approval of apitegromab in 2026. As part of our long-term growth plans to serve patients around the world with apitegromab we're also accelerating time lines to bring a second fill-finish facility online.

This process requires rigorous validation and regulatory approval to ensure the same quality, safety and efficacy of the drug product. Importantly, we have secured commercial capacity commencing in the first quarter of 2026 and anticipate submitting an sBLA for the second facility later in 2026. Outside of the U.S., we continue to expect a decision from the EMA on our apitegromab marketing alteration application, or MAA, near the middle of next year. Further to our commitment to a broad SMA community we announced today that we've initiated dosing in our Phase II OPL trial evaluating apitegromab in intent and probes under the age of 2.

The cloud is enrolling participants have been treated with an SMN1 pilot gene therapy or who are receiving treatment with an approved SMN 2ttherapy. It is designed to investigate 2 different doses of apitegromab for a duration of 48 weeks and will assess PK, PD, efficacy and safety. In the open study, early intervention with apitegromab could support muscle during the critical earning development phase, complementing Mentaterapy that aim to preserve merge neurals. Emerging muscle growth when merchants muscles are still forming a bit of a apitegromab has a unique opportunity to improve motor outcomes in young children with SMA. Beyond SMA, we're on track to initiate clinical development activities for apitegromab in a second neuromuscular disorder by year-end. We plan to provide additional information on the disease and the clinical development strategy in early 2026.

And finally, we continue to advance our world-leading Antimo staffing platform beyond apitegromab. The FDA has cleared the IND for SRK 149, and we're on track to initiate a Phase I study in healthy volunteers before the end of this year. This program is built on the validated approach that delivered apitegromab. Specifically, 149 was designed to be an innovative, subcutaneously administered myostatin inhibitor binding to both pro and latent myostatin with high affinity and selectivity. Based on prepoceldata, 39 has the potential to potently inhibit my staffing and increased muscle mass. We expect to have data from the south portion of the Phase I study in 2026.

In summary, our focus remains on bringing apitegromab to patients in 2 patients and investing with financial discipline to deliver on the promise of our broader pipeline. The strength of our data and the momentum across our programs gives us confidence in the impact we can deliver.

Now at this point, I'll turn the call over to Keith to discuss our commercial launch strategy and planning. Keith?

Thanks, Akshay. The SMA community is demanding more. Even with currently available treatments, they need a treatment that directly addresses progressive muscle wasting. Apitegromab demonstrated that ability in our Phase III SAPPHIRE study, and we will be ready to deliver apitegromab to the SMA community upon approval. This is not a matter of if, but when. Our understanding for the demand of opidagrumab and our confidence in its potential to address the unmet need for children and adults with SMA continues to strengthen. As we look at SMA globally, nearly a decade following the launch of the first SMN targeted therapy, the demand for treatment continues to grow. After the first 3 quarters of 2025, annual revenue for current SMA treatments are trending to approximately $5 billion globally with the continued growth of SMN targeted therapies the need for the world's first muscle-targeted therapy is greater than it has ever been before.

Our small, lean and highly experienced U.S. customer-facing team is active in the field and we are using this additional time to enhance our engagement activities and to strengthen our performance against key prelaunch readiness metrics. As a reminder, we are just under 4 months in to our pre-commercial field deployment, whereas most biotech companies typically benefit from a longer runway prior to approval. Nationwide, there are approximately 140 SMA treatment centers and more than 2,600 SMA prescribing physicians. With this additional time, we are working to both broaden and deepen our engagement with these potential prescribing physicians. However, an SMA patient is not just treated by 1 of these physicians but by a broader cross-specialty SMA treatment team. This team can include physical therapy, homonology, orthopedics and more.

This additional time is enabling us to better understand the patient journey and the roles of the SMA treatment team in each of these 140 treatment centers and how they influence patient care. Additionally, our market access team is expanding their focus beyond that of national payers to also include top regional payers. This builds on our ambition that any patient with SMA who can benefit from apitegromab should have access to apitegromab. Furthermore, our unwavering commitment to the SMA patient community continues by a partnership at a local and national events and to educate on the importance of targeting muscle. We are deepening our collaboration with the accuracy groups, and we are also building lasting relationships, 1 patient, 1 caregiver, 1 family at a time. In Europe, our efforts continue to drive SMA education and awareness, laying the groundwork to ensure we reach patients efficiently across key markets.

Our opportunity to serve patients around the world in SMA is significant. There are an estimated 35,000 people with SMA who have received an SMN targeted therapy and who could be eligible for treatment with apitegromab -- we are making strategic disciplined investments in our launch infrastructure, and we will be ready to execute rapidly once apitegromab is approved.

In short, we are ready the strategy is clear. The team is in place and our commitment to the SMA community has never been stronger.

Now I will turn the call over to Vikas. Vikas?

Thank you, Keith. Our overarching objectives are to fund our R&D activities to expand our leadership in the myostatin and muscle space to support a strong commercial launch and to extend our runway to meet our eventual time lines for apitegromab approval. In line with these objectives, I'm pleased to provide our third quarter financial results and to discuss our approach to managing our cash runway and investment prioritization moving forward.

Turning first to our third quarter results. We ended the third quarter with $369.6 million in cash and cash equivalents. For the quarter, we reported $103 million in operating expenses which includes $18.3 million in noncash stock-based compensation. Excluding stock-based compensation, operating expenses were $85.3 million, which reflects ongoing investments in infrastructure to support apitegromab regulatory approval, commercial readiness and our clinical pipeline. During the third quarter, we strengthened our balance sheet, adding $141.7 million. This cash came from 2 sources. First, we executed our ATM and sold approximately 2.8 million shares, which resulted in net proceeds of $91.7 million.

And second, we drew down $50 million from our existing debt facility. As we await apitegromab approval, we continue to operate with a tight financial plan focused on potful capital allocation to advance our clinical pipeline and strategic investments to support commercial readiness. Accordingly, we have adjusted our go-forward operating plan. We have deferred investments across a number of areas, including new hiring, launch expenses that are gated to approval, certain R&D activities, including a third indication for apitegromab and other discretionary spend.

Now I'll turn to the 6 prioritized investments we are making. The acceleration of a second fill/finish facility for apitegromab SME commercial launch readiness, Onex apitegromab extension study, the Phase II OPL study, the second indication for apitegromab and the commencement of SRK-439's clinical development.

Turning to our balance sheet. Our current cash balance is $369.6 million, which we expect to be augmented by approximately $60 million in cash from the exercise of outstanding common warrants by year-end. With this, we expect our cash to be sufficient to fund operations into 2027. This cash runway has conservative assumptions and does not reflect any upside from potential sales of apitegromab or a priority review voucher. To further strengthen our balance sheet, we intend to expand our credit facility while preserving our nondilutio financing options. We will provide further clarity on this as well as our anticipated operating expenses for 2026 during our fourth quarter earnings call.

Scholar Rock continues to operate from a position of financial strength with a disciplined approach to capital allocation and a clear focus on supporting our strategic priorities.

With that, I'll turn the call back to David. David?

Thanks, Vikas. In closing, Scholar Rock remains focused on near-term execution while building with financial discipline for the future. Our conviction, apitegromab and in our broader strategy is stronger than ever, and we are moving with urgency and purpose to deliver meaningful impact for patients. Our priorities are clear. execute with urgency to bring apitegromab, the world's first and only muscle targeted treatment that improves motor function to children and adults living with SMA as rapidly as possible. Advanced epitogramab development activities in the second rare debilitating neuromuscular disease, and that will be followed by additional indications where we can have a transformative impact for patients. We want to progress SRK 439 into the clinic and continue to invest in our future with discipline to support these high-value initiatives.

Before I close, I want to share my sincere appreciation for Cure SMA and the SMA patient community. Over these past weeks, I have had the opportunity to meet with many individuals and families living with SMA. And the words of support that have been shared with us and with me directly have been tremendously meaningful as we work harder, better and faster to bring this impactful medicine to those who can benefit.

With that, we'll now open the line for questions. Operator?

[Operator Instructions] Our first question comes from the line of Mani Faroohar from Leerink Partners.

Congrats on the progress through what's been obviously a choppy period for everyone in the government. I think a couple of quick questions. I know I'm violating 1 question. One, in terms of thinking about further financing opportunities to top up the tank as necessary, how do you think about debt versus royalty equity? Like how do you think about relative cost of capital and what's the most appropriate use once you get to a launch.

And then another commercial question. In the early days of launch, it is probable that you will be transitioning from 1 facility to another. To what extent does that introduce any operational risk going from products from 1 to so to another? And how can that be addressed ahead of time by you guys now?

Thanks, Monti. Why don't we take the first question first with the cost on the financing options and then I'll come back on the redundancy of supply chain with Phil finish. Vikas?

Yes. Thank you, David. Man, our first objective here is to bridge the financing until the approval. And the first path to go from the lowest cost of capital is to take additional -- extend our loan facility a little bit more. We are in discussions with that. That will be our first opportunity. Royalty probably comes next, and it goes too long, and then we have to take a little bit of equity, that will be the last and the most expensive one, which we are trying to avoid at any cost is trying to get it as more non-dilutive first. Does that answer your question?

Yes. So a follow-up. That would imply that, relatively speaking, we should expect you guys to wind down use ATM much less going forward? Like how does that fit into the strategy?

Yes. Obviously, our first objective is to work with the loan facility and expand upon that. And ATMs are put in place just to take some small augmentation of the capital at an opportunistic view. And we did take it down in the last quarter. Because we are only $50 million loan facility available. We're expanding that loan facility as we discussed. And as soon as we have the new facility in place, will share it with all of you.

And then, Manny, regarding the second vial, a couple of bottlenecks I've shared with you and others in the past. One of the big ones I highlighted in the call was obviously finding a commercial line that is available, that is -- got the ideal configuration for our vial -- and our team under the leadership of Lisa Wyman, our Chief Tech and Quality Officer just did an extraordinary job in accelerating our second Vilar progress to secure commercial capacity in Q1 and commenced tech transfer in lightning speed since that middle of October time line when the OAI hit, we hope that, that was really important. Now to get there and to get there quickly, you want to change as little as possible in your second vial as in your primary vialer, whether or not it's vialconfiguration, analytical testing, like -- so that actually helps you with speed as well.

And those are the things that we'll be focused on. And then the impact in the marketplace really should be almost seamless whether or not we are distributing our apitegromab from the Bloomington facility or the new second vialer, it should really be quite seamless operationally to the marketplace, and we would expect it to be that way.

Our next question comes from the line of Eric Schmidt from Cantor.

Congrats on the progress as well. David and team, for those of us who've kind of been reading the gory play by play around the Catalent facility in Bloomington, and know some of the prior history and all the past issues. How do you -- how do you how to provide confidence that this remediation effort is on good footing and that the inspection will prove positive? And then maybe secondarily, do you expect that to be a Class I or Class II acceptance for the resubmission.

Thanks, Eric. And no doubt, there is a history in the facility. We think the history is really anchored around the quality system, the quality culture and the facility. I think importantly, it largely links back to ownership that did not include sort of the steady hand of Novo Nordisk and their commitment to quality and compliance. And so 1 of the things that I've been saying often, and certainly, the gory details are gory, right? We got the observations, and we notified you all of those observations back on August 6, our last earnings call, which feels like a lifetime away now. And then we've kind of been riding through the CRL and the OAI. But what we have had a front row seat to is the collaboration with Novo, the commitment from the top of the organization, the changes in the staff that they are making. The integration of the Novo quality system into that facility and then the substantial progress that they've been making on a robust remediation plan, which as they noted to the FDA on Wednesday, they feel like there -- the facility is going to be reinspection ready by the end of this year.

We don't think that Novo takes that lightly. We think that they are going through a series of internal exercises to make sure that they are reinspection ready. We would imagine that they'll continue to communicate with the FDA and gather feedback on what might be missing from their remediation plan that they would then need to tweak before any reinspection would take place, but we are surely been pleased with the seriousness and the urgency that from the top of that organization right through that facility, they are taking the remediation plan.

Regarding Class I or Class II, I'll turn that over to Akshay for his thoughts as he was presiding over our team in person in Befesa, Wednesday, and the team just did a fantastic job. Akshay?

Thanks, David. Eric, I just want to reiterate that it was a very constructive and collaborative meeting. And I think the agency, as you might expect, shares, the need for urgency as we all work together to try and get apitegromab to patients. So it's not for us obviously to second gas table to be Class 1 or Class 2. But we were very heartened by the comments they made and the approach they committed to committed to help detect the license patients. So we need to work with Novo to get their work done. Let's wish them the best get to slight reinspected, resubmit the BLA and I'm confident the agency is going to act with earns and commitment to this community of patients we have always shown when it comes to us.

Our next question comes from the line of Tess Romero from JPMorgan.

David and team, thanks so much for the question here. So to be clear, the BLA that you plan to submit in 2026 for pmab will include Catalent as your primary fill finish and you plan to file the SBLA for the additional sale finish facility later in 2026 following the potential approval of the BLA. Why is that the right path versus using an additional fill/finish only?

And then a follow-up is just on the EMA review. How is that going with respect to manufacturing-related items.

Thanks, Jess. Yes. I mean I think given where we are, given the tone and tenor of the meeting that Akshay presided over this week and again, the progress that Novo has been making which really enabled them to communicate to the FDA that they are on track to be reinspection ready by the end of this year. We just think that, that is the absolute right path for us. We would expect that our BLA would be resubmitted with Catalent as our primary filler. And we would expect a second pillar to be added to our file, which was frankly always going to be our plan anyway given the fact that Novo wants that facility for internal purposes. And so that is the path that we are following, obviously, everything that we are doing to accelerate our second vialer is a great insurance policy for us no matter what would happen and I was really gratified by our team's efforts over the course of just the past month with the major progress that they have made to secure commercial capacity at a second boiler and already have tech transfer underway, and of course, we'll be expecting the commencement of our commercial capacity to be leveraged beginning in Q1 of 2026.

Regarding the EMA, I'd love to have Akshay comment on that. Obviously, quality and compliance is important to all regulators, including them.

Indeed. And just to review the status of the MAA, the question and answers, I go back and forth have proceeded well. So the review continues in exactly the time frame you'd expect. And as we guided on the full comment, we expect a decision by the middle of next year.

Now vis-a-vis the Kaplan manufacturing status and the EMA, there is a mutual recognition procedure. And so there is an interdependency. And I think we obviously agree with that. Though I would point out that everything we're doing for the 2026 resubmission, we Novo and all our averages from the 2026 resubmission of our BLA in the U.S. launch following approval by the FDA is in line with supporting our MAA. So there's not much more I can say right now, and obviously, we'll keep you updated. But let's stay, on track and as we proceed we hope that support the proposal.

Our next question comes from the line of Tazeen Ahmad from Bank of America.

Thanks for the detailed update. So can I ask when is the latest that you can have this reinspection for Catalent to be completed and given the green light in order to meet your expectations for a 2026 launch? And then just to play the scenarios for a second. And for whatever reason, the second inspection for Catalent doesn't resolve all issues. How quickly could you pivot to make any application with your second sale finish? And how would that impact your time lines for 2026. Like would you be able to switch that BLA filing to a BLA filing and keep the time line the same as you just mentioned?

Yes. Thanks, Tazeen. It's again, a good question. Getting back to what we're targeting back to Eric's point, there's a history at the facility. It was under prior ownership. They've had a few difficult inspections that have led to Form 483s and in this case, some repeat observations. So I understand and we understand that everybody could share some level of concern and/or skepticism that just getting a reinspection is not the objective. It's a successful reinspection. And we share with Novo Nordisk that is the objective. And to really put their own team through not only the remediation plan, but rigorous exercises to be reinspection ready, and we know that they are doing that. Related to your point about what if it doesn't resolve all issues, I think there's 2 ways to look at this to see there still observations in the facility and -- but yet to those observations warrant or not sort of a reclassification of the facility because that's really what we're playing for, a reclassification from OAI to either VAI or NAI.

And for that, certainly, that is what the objective is. I think regarding your time line, I think a reinspection could technically go pretty well into 2026, and we would still be within a frame of our guidance of resubmitting our BLA and then the U.S. launch upon approval. We're obviously pleased that the tone and tenor of our Type meeting led by Akshay with the FDA with all the key decision makers, all the key groups. I think was constructive. It was collaborative. And there really was a shared understanding of the unmet need and a shared understanding that urgency is necessary to serve a very important patient population. And so we're hoping that all of the steps that would be required that gets us to a reinspection would be done in an expeditious way within the regulatory framework that exists and that Novo will do their part. We don't think that they take lightly indicating to the FDA that they will be reinspection ready by the end of this year.

We don't think that, that's a low bar. We think they're holding themselves. Given the commitment to quality and compliance in the culture of Novo Nordisk, we think they say that with a pretty high hurdle in mind. But back to your question about should like a media right hit that facility. In other words, should the inspection not go well. Then what role would the second Vilar play? Well, everything that we've done to accelerate that second vial would be obviously extremely important for us in terms of should we need to pivot, and it's not an addition of this vial on an SBLA, but it's actually our primary resubmission strategy. There are a number of ways that the FDA, and we expect they've done this in the past. And given the shared urgency would understand some level of potential pathways to expedite adding a second biller as your first bilar in the form of a BLA. And everything that we're doing to expedite this process, we think, will aid us in case the impact of the inspection is not what we all expect it to be, which is a successful reinspection.

And as we continue to work with that second biller, we can provide further guidance to you as we progress from tech transfer, which is now underway directly into the filling lines that we will be executing in Q1 and Q2, and we'll provide those updates over time.

Our next question comes from the line of Kripa Devarakonda from Truist Securities.

Congratulations on all the progress. Thanks for all the details. So in terms of time lines for resubmission of BLA, I feel like we're all asking the same question, but is the plan to wait for the reinspection and for the OAI to be resolved before you submit the BLA and I understand that Novo has said that they're going to be inspection ready by year-end, but could Noble request an inspection and finally, would you be able to address whether Noble hired any outside consultants to help with this process?

Yes. Maybe related to the time lines on resubmission. I think that Akshay can comment on our thinking and recognizing that with the collaboration with the FDA and the shared urgency, it's a little dynamic. We don't have our Type A meeting minutes yet, but Akshay can share at least our go-forward plan with respect to that.

Yes. I mean I think base case Chris safe to say that the reaction will have to account would submit after that. But as David said, it is a dynamic situation, and we'll do everything possible to we submit in a fashion to expedite the approval of this growth, which patients need so badly. And we were hardened by the in support from the agency during our tie -- so a lot is going to happen in the coming weeks and early part of next year, and we look forward to resonate.

Well, for sure, Kripa, given that, again, it's reiterated our PAUSE sole and primary issue is the classification of this facility and their state of compliance. I think it's a safe assumption that we'd like to see that clear. And be ready to go immediately with a resubmission. That's sort of our go-forward plan at this point.

And I think it's worth adding, David, that resubmission is really competitive the initial BLA remission neediest much more contained at around just the safety update and the CMC aspects of the file. So it's very -- we're ready to file that resubmission at very short notice.

Crick, related to the Cnova request of reinspection. I think in a way, they're signaling that they're ready. We would imagine that Novo and the agency still has some wood to chop. Just how do we feel about the remediation plan? Is there anything left before reinspection needs to be done? I would expect that to be happening, okay? That would be an expectation. But in a way, they put themselves on notice with the FDA that they stand ready to be reinspected toward the end of this year. And we think that, that is really, really important. But as you know, this reinspection will not be announced. It would be like your typical unannounced inspection. And so that you can put yourself on notice and communicate with the office of compliance that you're reinspection ready. As they notified at our Type A meeting at the end of this year, but we would expect the FDA to when they do reinspect the facility, it would likely be an unannounced inspection.

And then your final question about like third parties, I think Novo is really looking very broadly, and they have been working with outside experts and helping them through all of these things, including the remediation plan and the progress with the remediation plan, and we have been pleased with the level of quality and urgency that they are applying to this remediation plan, and we're thankful to them for that.

Our next question comes from the line of Ed Sir Dara from Barclays.

Just because investors have sort of been circling this September 2026 date in terms of sort of timing for a potential approval David. Maybe if you could us understand what could -- maybe the PA minutes unveiled to you on the type of resubmission that you have to make, maybe their time lines around the decision once you have filed -- refiled the BLA?

Yes. Thanks, Azur. It's a great question. And again, something that I think Akshay wanted to have some robust conversations with the agency on our Type A meeting, we're obviously not we don't have meeting minutes in hand, and we certainly want to allow the agency to do their work. But Akshay can comment on how we're thinking about the resubmission timing, and again, whether or not it would be Class I or Class II.

Yes, as far as the minutes are concerned, I think it's always good to get the minutes in Haneda wrest that we're conveying to you this morning that they're documented in the minute or the progress that Adnovohas made of commitment that everyone is showing to the 1 of the math, Nova's comment about being ready for reinspection. And everything we just said so far -- so we await those minutes, and we're confident that they'll reflect what we're conveying this morning. Now as far as the recommission is concerned, we've just discussed that with the last question and, of course, we'll need to be as soon as the inflation is done or earlier, if possible. But we'll be guided by the agency to all of that. And we'll also be given on the review time line.

Now the minutes we get won't sell out the nature of the review time lines for the resubmission. That's not their fact if they wait recommission of the BLA before that. 1 thing I can tell you is that David emphasized the term and tenor of the meeting that there was support to active open to get on all parts of an pet agency to get this drug to patients as soon as possible.

Our next question comes from the line of Mark from TD Cowen.

And all the detailed disclosures around this meeting. Maybe in that light, just as you move forward and Nova hopefully is, in fact, in position to be reinspected. Just what do you expect to be able to disclose and kind of on what time line, particularly given that it isn't even your facility directly, but it is a partner. Will you be able to disclose right when it gets inspected not until maybe some 433 are received? Just what are the disclosure plans there?

Thanks, Mark. I think our disclosure plans will really kind of look in the mirror and focus on us and the things that are material to us that we think are important this year. Obviously, the reinspection time line when it happens, the outcome of it is really important. So I think we want to be open to sharing the important information with you. Obviously, the way this would work is inspection takes a week to a couple of weeks. There's generally a closeout meeting. At that closeout meeting there's generally some kind of preliminary assessment when of Form 483. As we've noted in the past, I think, again, it's hard to believe when we first disclosed these Form 483 observations was only last quarter because it feels like for me, it's been a long time.

But as you know, a Form 483 usually travels 75% of the time with any inspection. But of course, we wouldn't expect a Form 483 to result in an OAI most of the times. And I think that's what started all of us. But I think that all along Novo has been approaching this very aggressively. So I think we'll just maintain as we have open lines of communication with you all when we have important information to share, we'll certainly do that. And I think what we've done in the past is even if it wasn't something for us, what we did learn of, let's just say, the classification of the facility as we did just last month in October. We tried to get out in front of that and disclose that and have some dialogue with you all on what that meant. And we'll continue to make a commitment to do the same here as we continue on this journey to an eventual resubmission and U.S. launch upon approval.

Okay. That's helpful. And then maybe just on the idea of waiting for the reinspection to kind of happen in the reclassification before filing. But also in your prior answer is, you noted this would be kind of like an unannounced reinspection once they've communicated that they really are in position to be ready. But kind of a forcing mechanism to that at some level, it could be a submission of a BLA from anyone using this facility. So maybe is there some value of maybe filing ahead to kind of try to force the time line on the inspection -- or is your expectation that there are just so many other products flowing through this facility that that's kind of going to happen on its own without you guys being the forcing.

Well, Mark, a couple of the things you said are really important. One is that we've heard this too, right? I mean the thing that creates urgency are pending applications. And right now, we don't have a pending application. We have a pending resubmission. At the same time, I would note that we were generally pleased with how constructive and collaborative, the in-person Type A meeting was and that there was this shared understanding of the unmet need and shared urgency. So while we're not on file, I would say a lot of the things, and you're absolutely right on your last point, that there are other pending applications at that site, and that can serve us well. We do think our Type A meeting serves as a really good central point of highlighting while we're not on file, there is real urgency here for a community that is desperately wanting to benefit from the world's first and only muscle-directed therapy.

And so we have to continue to work with the agency, be collaborative with them. Find everyone's right footing on what the right thing to do is, and that is really our go-forward plan. And we think we've built sort of a foundation and framework with the agency frankly, all the way through the initial priority review period up until September 22 and even through Wednesday, a really strong foundation for collaboration for us to work together to resolve this issue.

Yes. Thanks, and I just want to reiterate the importance of that collaborative approach. And you mentioned forcing functions as the by resubmitting ahead of the reinspection. I don't know that, that's why we want to be working closely with the FDA and be guided by them now. As we said, it's a dynamic situation then in the bite us. So they support any kind of resolution in a particular time frame in and around the resection. We will, of course -- we are ready and we can resubmit very efficiently -- but it's not about forcefution. We have to collaborate with the FDA.

Our next question comes from the line of Evan Seigerman from BMO Capital Markets.

With the delays for apitegromab. -- can you talk more about what your sales or market research team's efforts are to of patients ahead of the launch. You mentioned efforts to work with centers of excellence to understand the patient journey better, but do you feel you are developing a more robust number of patients which you could target for therapy following approval, potentially leading to a little bit of a faster uptake than people were probably initially expecting.

Yes. It's a great question. Keith was highlighting it earlier in the call, and I'll turn it over to him for further comments on launch prep.

Yes. Thanks for the question. I guess I'd say first of all, when the September 22 date occurred, that was after 2 months of the team being able to spend time out in the field. And now with the extended time, we're getting to not just visit with the physicians, but we're also getting to meet the SMA treatment teams and getting that full feel. And what is that additionally, not just the SMA treatment teams, we're spending more time with patient advocacy events and getting to speak with patients and their families. And I can tell you what we're hearing is that there's a clear understanding of the unmet medical need and the approach of attacking this disease from a dual modality no longer just the motor neuron but also directly targeting the muscle, and this is being well accepted as we get the opportunity to meet with more people in the community. You add to the fact of the safety profile that apitegromab has demonstrated.

And quite frankly, all of our studies, not just our SMA studies, but if you take a look at Embrace, that was also all adults all treated with 10-milligram per kilogram and exceptional safety results. I guess I would end with the fact that at the end of the day, we're offering the world's first muscle-targeted therapy, and in the event, if you have a choice to either be in a situation of having experienced muscle loss or the potential for muscle gain, why wouldn't you want to use a pitot.

This concludes today's conference call. Thank you for participating. You may now disconnect.