Vera Therapeutics Inc - Ordinary Shares - Class A Stock

Great. Good afternoon, everybody. Thanks for sticking around for our last fireside today. We're really pleased to have Vera with us. I'm going to let Marshall make some introductory comments, and then we'll jump into Q&A. Over to you, Marshall. Thanks.

Matthew, thanks for having us and me at your conference. Great to have an interview with you today. I'm Marshall Fordyce, I'm the Founder and CEO of Vera Therapeutics. Great day for us today and for patients. Today, we shared the final efficacy analysis from our pivotal Phase III trial, showing outstanding efficacy by eGFR and by kidney composite endpoint.

It was an important update for the field and for Vera as well as an indication of how launch is going. So we shared that so far, about 10 weeks into our first commercial launch, we have over 350 patient start forms or roughly prescriptions as an early indication of demand.

So 2 important updates for the company, great activity happening now and in the coming time, here we are in September. The data that we toplined today are being submitted or have been submitted both for presentation and publication. It would be great if we could get that done at the next month's major kidney conference, which is called ASN, where we would hope to have an opportunity to present these data in a more fulsome way to the academic world.

And in conjunction with that, We, of course, are pursuing an sBLA in Q4 to target full approval with these top line data and more for mid-2027. So a fantastic moment for us as a company, have to dive into detail about both the clinical results that we shared today as well as the commercial progress early on in our first launch in the disease, IgA nephropathy with TRUTAKNA.

Wonderful. Yes. No, I mean, really exciting updates for today. So maybe first, can we put the clinical data into context? What does what you share mean to patients? How should people think about progression of the kinds of patients that you put into the study and how you've changed that progression.

Sure. I mean we ran a global randomized double-blind placebo-controlled trial in the typical patient who is at high risk of disease progression. So to put it into context, think about who are these patients and what do they experience on current standard of care. They're 40 years old. Their eGFR is on average 60, which means that they've already lost roughly 40% of their kidney function by 40 years old. And if you follow the placebo arm, they're losing up to 5 -- 5 to 10 mls per year in our trial.

So these are patients who are 40 on their way to dialysis by the age of 50. So that puts you into the context of what disease situation are we trying to alter. What we've shared is data from the final efficacy analysis. So we've ended the randomized phase. And what we've shared is that the eGFR difference, meaning the kidney function difference between TRUTAKNA and placebo is 5 mls per minute per year.

So that's significant. That means that over a 2-year period, 104 weeks, which is the extent of the data we looked at, if you're on placebo, you're losing 10% of your kidney function, right? So that's a bad situation. We essentially have normalized the eGFR for patients on TRUTAKNA. The eGFR slope for those patients over that 104-week period was minus 0.6. So just under 1. People without disease lose about 1 ml per minute per year. So this is, on average, what a patient -- what a person without disease experiences.

It's also what international guidelines are trying to target for patients to reverse these bad outcomes for patients. So that was -- we shared the primary endpoint, the confirmatory endpoint that we agreed with FDA, which is at 1 year at 52 weeks. And we also looked at the totality of the data where lots of patients went out up to 2 years, and that's the 2-year eGFR slope comparison. So at 5.0 as a treatment delta is the largest number we've seene in the field.

Moreover, we shared clinical outcome data. So what happens to those patients on placebo? Well, in our trial, 8 of those patients met hard tragic clinical outcomes. They required dialysis, transplant or they died, 8 of them on placebo. On TRUTAKNA none met that outcome. If you add another criteria, which is a significant reduction in eGFR of greater than 30%, so that plus the hard clinical outcomes, we call that the composite kidney endpoint, we showed a hazard ratio of 0.24.

The inverse of that, we also call the risk reduction was 76%. That's a massive risk reduction that really is the best we've seen in any IgAN trial, and you can look even broader at other kidney trials, that's a very big effect size for a new medicine. on these data, we plan to continue to lead the field and set a new standard of care for patients. Today, TRUTAKNA is now available to patients in the United States through accelerated approval. And I think these data will be incredibly important for patients, for providers and for payers as we advance our effort to change standard of care.

And obviously, you showed some stuff on the commercial side, and I want to get to that, but maybe just a couple of other questions on the profile, right. Obviously, there's another therapy with a similar mechanism filed. Otsuka has their drug on the market. Can you talk a little bit about the breadth of the data of the competitors and how you think you compare?

Sure. So first, I think it's really important when you look at a disease area that has a standard of care with a lot of hope that we can raise the bar. It's great that there are multiple players in that space. That increases the share of voice for changing standard of care. So we actually think that's very helpful for patients and for Vera's potential to really penetrate that market.

That mechanism is an APRIL-only mechanism as opposed to dual BAFF and APRIL. From an efficacy perspective, we see our delta between active and placebo at slope for 2 years is 5.0. -- theirs is 4.5. And we've also seen no data yet on the composite kidney endpoint that I'm describing. So we look forward to seeing that. We're really the first among the B-cell modulators to share that.

Safety looks strong for TRUTAKNA. And we also have the first auto-injector on the market. So this is a very simple device that is simple to use on a weekly basis. I have it here in my hand. No button push needed. It simply is an injection once per week, and it takes just a few seconds. That's what's being asked to patients today as we're out in the field. And this is something that I think we really see a lot of acceptance from both patients and physicians.

And then I think the last thing, maybe just comment, right? You've obviously -- you have a dual mechanism, APRIL and BAFF. There are other B-cell modulators in this class that have chosen one of the mechanism. I mean, any differences you think you're seeing from that in the clinical data so far?

Well, I think the clinical data need to mature further, and we just happen to be the first BAFF APRIL on the market today. And I think I would be looking at long-term kidney outcomes that we've shown today and also eGFR delta as being the most important to patients, providers and payers. So I think it remains to be seen how that plays out across the field. But look, this is a really important new step for patients, for the field and setting a new standard of care.

Great. So why don't we talk about commercial? You obviously gave some updates, but maybe before we get there, can we talk a little bit about market size, how you think about the market size and what sort of standard of care for patients is now and what that tells you about patients that are being treated versus how you might expand that market?

Sure. I mean this is a very serious unmet need, as I characterized by the patients who we enrolled in this trial. We would estimate this to be in the U.S. alone, roughly 160,000 patients are biopsy-confirmed IgAN patients. We think that, that's likely an underestimate. By the time they come on to treatment or into a trial, they tend to be pretty advanced with a eGFR of 60 and already 40 years old.

So we hope to see that shift. But that's a large number of patients. The market size is likely very large in the $10 billion to $20 billion range when you look at the value that's being delivered for that number of patients. Not all of them will be considered at risk for rapid progression, but the label that TRUTAKNA has is broad. It's for any patient at risk of disease progression.

Today, most nephrologists define that by those on maximally tolerated standard of care, an ACE or an ARB, most often an SGLT2 inhibitor. For us in Phase III, it was about 60%. And then with that background, they're still producing over a gram of protein in their urine. That is characterizing the patients who have the placebo eGFR trajectory and the hard clinical outcomes that we've reported in a relatively short amount of time in a low number of patients.

So really, that is the market. Already, we're seeing from Otsuka, one of the strongest, maybe the strongest renal drug launch that we've ever seen in history. They've guided to a $380 million sales number in 2026 in their first full year of launch. That's a good indicator that this is likely a very large market.

What we shared this morning is that we have over 350 patient start forms in the first 10 weeks. That tracks very nicely and demonstrates early signs of a growing and large market. We think this will continue to grow as others come to market, and this is a great thing for patients and for the field of nephrology.

We see already feedback from the field telling us about our data. That means that we've really been out there. We have good relationships with the physicians in this space. And there's a lot of excitement for a new medicine that can actually stop kidney function decline and change hard outcomes for patients. That will be really important data for our launch.

Can you characterize -- I mean, you characterized a little bit the 350 start forms, but how should people think about that relative to Otsuka's initial trajectory? And anything you can share in terms of payers or how people should think about what you need to do on the payer side?

Sure. We have fantastic commercial leadership within Vera. We hit the ground running. Patient start forms were generated immediately. Drug was in channel within 3 weeks. We have made good progress. It would be a mistake to say it was linear for the 10 weeks. Of course, it's taken time to get going. And we hope to accelerate that. You can make a model, but we know that we're generating that market every single day in the field. Vera is entirely focused on that execution. So that feels really good to see that growth.

On the payer side, we see an objective for us would be to have similar access to other drugs in the market. We think that is the right way to ensure that physicians keep prescribing decision is in their hands and more so than in the payers' hands. So our objective is really parity, and that's an important feature of what we'd like to do in this market.

Great. And maybe just talk about in the context of what you need to do to resource this launch? Can you give people a sense of how big the commercial infrastructure build is and how that impacts your path to profitability?

Sure. We have resourced the launch. It was really important for us to hit the ground running. We have the right-sized sales force. We have 82 reps. We think that is appropriate for the U.S. area. We're targeting about 6,000 practicing nephrologists. We have additional resources to take up the tail of the remaining thousands in the U.S. for prescribing IgAN clinicians.

But for those 6,000, 82 reps really has the right contact. We already have early telemetry from our launch that, that feels rightsized in terms of our ability to touch decile 8, 9, 10 physicians. even multiple times within the first 10 weeks of launch feels great for where we are. There's other resourcing to be done on the marketing side, and we'll see that evolve this year.

Last year at ASN, we had the #1 share of voice among the IgAN developers, and that was from third-party data. So we feel really good about how we've been out in the community leading the conversation about B-cell modulation with TRUTAKNA and dual BAFF APRIL. We've presented really field-leading data. We're recognized as the leaders by the physicians out there. We continue to do that. We did it today and coming up at ASN next month, we'll continue to target that.

And any changes you think you need to make? Obviously, there's a third competitor potentially coming on market later this year. Presumably, you've already resourced for that. But any other changes or how do you think that changes the market dynamic?

Yes, it doesn't change our resourcing plan. I think, again, it's a positive that we'll have another entrant that's talking about dual BAFF APRIL inhibition. We think that's a positive for Vera. And we welcome the added voice for B-cell modulation. It remains to be seen what that profile looks like. We do think that eGFR data and renal composite endpoint data is going to be important out there.

And I think we'll have that for a long time before we see that from competitors. And I think that will be an important differentiator in the near term at least and sets a high bar for others to try to reach.

Great. As we sort of think about additional updates from you, obviously, at your next quarter, you'll report sort of the initial launch number. But I mean, other metrics that investors should be focused on that you'll be talking about more?

Sure. Revenue. We'll be talking about revenue in November. So Q3 update, roughly November is our time for our earnings call. That will be key. We'll continue to provide quarterly updates on patient start forms, so we give the market an indication of demand. We won't be very granular beyond that, frankly. I think it's important to expect a quarterly cadence for these updates.

And that will be an exciting moment for us to continue to start to put points on the board and show this launch trajectory. Happiness for us is seeing growth for TRUTAKNA and seeing growth for the other B-cell modulators. We firmly believe this is a $10 billion to $20 billion market, and it's all about giving access to patients who really need it and otherwise face really grave outcomes.

So that's really where we are focused. Near term, we're going to see a lot of expansion. So with the profile that TRUTAKNA now has, the efficacy that we highlighted today with the safety that is also consistent with what we've shown before, which is very tolerable. And finally, the form factor of the auto-injector, we're looking at global expansion. So we'll be filing in Europe in the near term.

We'll be filing in Japan. And we're also starting to show data outside of IgA nephropathy. So we're hoping by the end of this year, we'll have the opportunity to present data in IgAN patients who would not have qualified for our Phase III trial. That includes patients who are adolescents who are -- have lost kidney function due to IgAN and have a transplant are now worried about maintaining their transplant, patients with concomitant vasculitis, patients with lower proteinuria that would qualify them for ORIGIN 3. These are important questions for physicians. They're thrilled we're studying it, and we're going to be able to provide some clinical data.

Already today, our label for accelerated approval is broad and would capture much of that population, but provide that clinical data, I think, is useful for the field and continues to demonstrate our leadership in the IgAN space. We'll also start to show data in adjacent autoantibody-driven kidney disease, starting with membranous nephropathy, and we hope we'll have that opportunity by the end of the year.

Maybe just touching on that, can you talk a little bit more about PIONEER, that study, the kinds of patients you've enrolled there? You talked about membranous nephropathy, but I think you also enrolled FSGS and MCD patients, if I remember right. So what's that study? How should people think about those market opportunities and the path for those indications?

Sure. So look, I think the big idea that Vera got invested in 6 years ago when we began developing atacicept is that you can treat autoimmune disease in a way that doesn't immunosuppress a patient the way that high-dose steroids or B-cell depletion does. And that big idea is now increasingly supported by the available clinical data in our Phase II and Phase III trial. That's not just mechanism. It's not just BAFF APRIL. It's also what molecule are you using. We're using the native TACI receptor and a fusion protein.

And what dose did you select? We're selecting the 150-milligram weekly dose. So with that as the totality of our approach to dual BAFF APRIL inhibition, that gives us a profile that has a safety and efficacy profile that we now can take in other areas. In the PIONEER study, as I mentioned, there are sort of 2 buckets. There's the IgAN population that we didn't study in Phase III.

An important one, of course, is concomitant vasculitis, which is a question we often get from physicians, but also autoantibody-driven kidney disease. And as I mentioned, membranous nephropathy, and there is a portion of FSGS or minimal change disease that is autoantibody driven. We actually don't know the portion. There are some studies that put that into the 15% to 20% of FSGS patients, but it could be higher. We will find out.

And that's just the beginning of what the expansion opportunity looks like for TRUTAKNA. If you leave the nephrology space and go into the rheumatology, neurology and dermatology spaces, suddenly, you have a much broader population that could benefit from a medicine with this type of profile among indications that there's strong validation for, whether it's a study in China or elsewhere, could include Sjogren's disease, myasthenia gravis and a variety of other diseases that we think this kind of profile could be highly competitive in.

So we're thrilled about sort of the ability to expand. Near term, our commercial execution in the U.S. in this large double-digit billion dollar market is the near-term priority, but we are expanding quickly into other areas. The pathway in adjacent indications, we haven't shared yet, but we will in the near future.

Okay. And from a data perspective, it sounds like people should expect to see at a minimum the other populations you haven't studied in IgAN and maybe a little bit of some of these additional populations towards the end of the year. Is that the right...

Yes.

Okay. You talked about other geographies. Maybe just talk a little bit about your plans from a commercial perspective for them.

Sure. So it begins with clinical regulatory progress. So with the data set that we've now disclosed and finalized in the U.S., we're taking that to Europe, Japan and elsewhere. And those are really the first steps. We've done the basics we need to do to start to expand into Europe. And these are stage appropriate steps for global expansion. But for now, that's -- it begins with the clinical regulatory progress. We've run our global studies in the U.S., Europe, Japan, China, really in multiple geographies.

Great. Maybe just, I guess, a couple of other things. Maybe just remind people patent profile here, how long you have? Obviously, you're very beginning of your launch, but just how people should think about your ability if you can expand into a bunch of other diseases.

Sure. Well, TRUTAKNA is a biologic. So we do begin with a 12-year regulatory exclusivity in the U.S. But we have awarded patents through 2042 when it comes to formulation process methods of use. So we don't anticipate a biosimilar entrant on that basis into the mid- to late 2040s.

And then any other -- obviously, and we've talked about this a little bit, right? There are different frequencies of dosing, right? -- have you thought about other frequencies that you might explore beyond the weekly that you currently are -- your current presentation?

Yes. Well, in the last 10 weeks of our launch, we've had over 12,000 interactions with health care providers around TRUTAKNA. And we never hear that dosing frequency is an issue, given what I've demonstrated here in 8 seconds, this is not a burden for patients, so it doesn't come up currently.

On the other hand, we do think that providing additional options for patients in the future could be beneficial. So we're doing 2 things. We're running a monthly dosing study that we began last year. It's a study in IgAN patients at 3 different doses, and we'll be evaluating that data later this year.

So that has the opportunity to give us a line extension for monthly dosing. And then we in-licensed a molecule from Stanford in January of 2025 what we call VT109, which is a different construct for BAFF APRIL inhibition. It's still preclinical, but has the characteristics that could look at a longer dosing interval.

We'd like to continue to gather data on those. But I would tell you that currently, the auto-injector weekly small volume, 8 seconds a week is a pretty acceptable profile in today's market and delivers really practice-changing efficacy and very tolerable safety background. So we think we're in a very good position with respect to dosing interval today.

Great. Great. Maybe 2 final things on my mind. As you think about the data package that you have now and the label that support, anything that would change as you go for full approval from accelerated approval? And anything important in that from a payer perspective, from an ability to market perspective, from a demand perspective that you think is important to highlight?

Yes. Look, all of those things are important. So the more mature data set that we're toplining today that we hope to put out into the nephrology field later this year in the presentation publication, getting that reviewed by FDA, seeing if that is appropriate for the label, that would be our expectation in a final approval and in a label, incredibly important and informative to prescribing physicians and the patients who may take that medicine.

So that is important. It's important for continued effort to change standard of care. So yes, critical updates although important that we have it out there in the public today and important that we will have it in a peer-reviewed setting in the near term. So yes, incredibly important. I would also say that guideline committees are going to probably be meeting and changing guidelines are important. That's all going to be driven by what is the benefit and what is the risk. And we think today's data update is really important for that.

And then I guess final question just around cash runway, how you think about your -- how you're financed as a company. Maybe just sort of comment on where you stand there and your ability to finance the launch.

Sure. Well, it's great. We're generating revenue today. We have $500 million in cash. We have a facility with Oxford for an additional $425 million. So access to close to $1 billion to continue in this current mode. The launch curve is looking good, and we're going to continue to draw dots on that curve, and we got a lot of options at this point.

So we feel good from a resourcing perspective. As you asked, wouldn't change anything in terms of what we're doing in terms of our launch. We hit the ground running. I don't expect to really change that a whole lot given what we see today.

Awesome. Great. Marshall, thanks for being here. Appreciate it.

Thanks for the opportunity, Matthew.

Good afternoon, and welcome to the Vera Therapeutics Investor Call and Webcast. [Operator Instructions] As a reminder, this call is being recorded, and a replay will be made available on the Vera website following the conclusion of the event.

I'd now like to turn the call over to Sean Grant, Chief Financial Officer at Vera Therapeutics. Please go ahead, Sean.

Good afternoon, everyone, and thank you for joining us. Earlier today, Vera Therapeutics announced that the U.S. Food and Drug Administration has granted accelerated approval to TRUTAKNA for adults with IgA nephropathy. A copy of the press release we'll reference today is available in the Investor and Media Relations section of our website.

Before we begin, I'd like to remind you all that today's call contains forward-looking statements within the safe harbor provisions of the Private Securities Litigation Act of 1995. These statements contain comments about TRUTAKNA's clinical profile, our expected commercial launch, our confirmatory trial and expected data and our pipeline. These statements are subject to risks and uncertainties and are not guarantees of future performance and represent only our views as of today, and we specifically disclaim any obligation to update them.

With that, it's my pleasure to turn the call over to our Founder and Chief Executive Officer, Dr. Marshall Fordyce. Marshall?

Thank you, Sean, and good afternoon, everyone. Earlier today, the FDA granted accelerated approval to TRUTAKNA, atacicept-vymj, the first and only BAFF and APRIL inhibitor indicated to reduce proteinuria in adult patients with primary IgA nephropathy at risk for disease progression. For the patients we serve, for the nephrology community and for everyone at Vera, this is a significant milestone.

First, we're extremely grateful to the patients and families who trusted us by joining the ORIGIN program, to the investigators and study teams who held the highest standards of clinical science, to the FDA for its rigorous and timely review and to the IgAN Foundation and the broader patient community who have worked alongside us for years, thank you. This approval is yours as much as it is ours. IgA nephropathy is a B-cell mediated disorder with kidney pathology. B-cells are activated by 2 cytokines, BAFF and APRIL that fuel the production of the antigen and autoantibodies that lead to the formation of immune complexes that subsequently damage the kidney. Until now, we have lacked a therapy that can comprehensively address the key upstream drivers of IgAN pathophysiology. TRUTAKNA does exactly that. It targets both BAFF and APRIL. This is why we believe TRUTAKNA is positioned to become a transformational therapy in IgAN.

With that, I want you to hear about the clinical experience from our Chief Medical Officer and Resident Nephrologist, Dr. Robert Brenner. Rob?

Thank you, Marshall. It's a pleasure to review the clinical data that supported the FDA approval of TRUTAKNA, a therapy for IgA nephropathy with disease-modifying potential. As Marshall mentioned, IgA nephropathy is a B-cell mediated disease that leads to progressive and irreversible kidney damage. 2 cytokines, BAFF and APRIL, play a central role in activating B cells, which then produce the antigens and antibodies that ultimately form the pathogenic immune complexes responsible for kidney injury. TRUTAKNA was rationally designed as a native human TACI-Fc fusion protein. By comprehensively inhibiting both BAFF and APRIL, TRUTAKNA targets the underlying immune drivers of IgA nephropathy. This approach reduces the formation of pathogenic IgA-containing immune complexes and addresses the disease process at its source with disease-modifying potential.

The ORIGIN 3 trial is an ongoing global multicenter, randomized, double-blind, placebo-controlled Phase III trial in adult patients with IgA nephropathy. Participants were randomized one-to-one to receive either TRUTAKNA or placebo. The primary endpoint of the prespecified 36-week interim analysis evaluated the change in 24-hour urine-protein-to-creatinine-ratio compared with placebo in the first 203 participants who received at least 1 dose of study drug. At 36 weeks, patients treated with TRUTAKNA achieved a 46% reduction in UPCR from baseline and demonstrated a statistically significant and clinically meaningful 42% reduction compared with placebo. The reduction in proteinuria consistently favored TRUTAKNA across all prespecified subgroups, including age, sex, race, geographic region, baseline proteinuria, baseline eGFR and baseline use concomitant SGLT2 inhibitors.

TRUTAKNA-treated patients also showed meaningful improvements in other key markers of IgA nephropathy disease activity. These included a 68% reduction in galactose-deficient IgA1 and resolution of hematuria in 81% of patients who had hematuria at baseline. TRUTAKNA was generally well tolerated. The most common adverse events were infections occurring in 32% of TRUTAKNA-treated patients compared with 28% in the placebo group, and injection site reactions occurring at 30% versus 5%, respectively. Most adverse events in the TRUTAKNA group were mild to moderate in severity and resolved without requiring treatment interruption or discontinuation. Notably, there were no serious severe or opportunistic infections observed in TRUTAKNA-treated patients and no cases of hypogammaglobulinemia were reported.

In addition, antidrug antibodies had no clinically meaningful impact on the pharmacokinetics, pharmacodynamics, safety or efficacy of TRUTAKNA over the 36-week treatment period. Taken together, these results demonstrate the potential of TRUTAKNA to address the underlying biology of IgA nephropathy, while delivering clinically meaningful improvements in key disease measures with a favorable tolerability profile. These findings were summarized and published in the New England Journal of Medicine in November of 2025. And now the full prescribing information for TRUTAKNA, including important safety information, is available online at www.trutaknahcp.com.

With that, let me hand over to Matt Skelton, our Chief Commercial Officer, to cover the commercial opportunity. Matt?

Thanks, Rob, and good afternoon. We are thrilled to bring TRUTAKNA to the IgAN community. We believe TRUTAKNA is a highly desirable treatment for IgAN patients. In addition to what Rob said about the clinical profile, TRUTAKNA is delivered through a small 1 ml once-weekly autoinjector self-administered at home. There are approximately 160,000 IgAN patients in the United States who are diagnosed with IgAN, and that number is likely to grow as awareness and diagnosis improves. Importantly, because these are young patients, this is roughly a 75% commercially insured population, a favorable payer mix relative to most markets. We are targeting about 6,000 nephrologists, the prescribers who care for the great majority of these patients.

Our team has decades of experience commercializing innovative therapies. Our leadership has successfully launched multiple blockbusters and renal therapies. Our field force of 82 representatives is fully hired, trained and in territory. They've spent the last few months on disease state education and account relationships and they are ready to promote TRUTAKNA today. The demand signal is strong. In independent market research, nephrologists ranked TRUTAKNA as the most desired IgAN agent in the development pipeline. We've also watched the first wave of B-cell modulators validate this category ahead of us. As a fast follower entering with a differentiated profile and the ease of an autoinjector, the momentum works in our favor.

We have been thoughtful about access to TRUTAKNA. The value of TRUTAKNA reflects its ability to address a significant unmet need that continues to exist for patients living with IgAN and the innovation demonstrated in the extensive ORIGIN clinical program. To start, we expect most IgAN patients are commercially insured. Eligible commercially insured patients may pay as little as $0 out-of-pocket through our TRUTAKNA TRU SUPPORT co-pay assist program, our support program for patients who are prescribed TRUTAKNA. It is designed to assist health care providers that patients navigate the fulfillment process. TRU SUPPORT offers insurance coverage information, financial assistance options for eligible patients and educational resources designed to facilitate a seamless treatment experience. Dedicated team members are available to provide ongoing assistance and access support every step of the way.

TRUTAKNA's wholesale acquisition cost on a per carton basis, where each carton represents 4 doses or a 28-day supply is $32,700. This annualizes to $425,000 per year. We've conducted extensive pre-approval engagements across the major payers to support broad and timely access at launch. Our objective is to ensure that all eligible patients have access to TRUTAKNA, and that we have the appropriate programs in place to support that goal. It is a privilege to be able to deliver a breakthrough therapy like TRUTAKNA to patients living with IgAN.

With that, let me hand it back to Marshall.

Thank you, Matt. We come to this launch from a position of strength. We've assembled a commercial team with a proven track record of successful product launches. Vera is in a strong financial position with approximately $597 million in cash and marketable securities at the end of Q1, with access to an additional $425 million through our Oxford facility. Our commercial organization is built, trained and ready. We led the way in the clinical development of an IgAN therapy. And today, we build on that leadership position as we launch TRUTAKNA. Our confirmatory ORIGIN 3 endpoint estimated glomerular filtration rate, or eGFR, is expected in the third quarter of this year, potentially supporting our path to full approval. That is the kidney function data, we believe will further distinguish TRUTAKNA.

With that, operator, let's open the line for questions.

[Operator Instructions] So our first question comes from Anupam Rama at JPMorgan.

A big congrats on the approval. Just a quick question for me. When I look at the label for TRUTAKNA relative to, say, Cemiplimab, one thing that sticks out for TRUTAKNA is that you guys don't have any neutralizing antibodies noted in the label. Just wondering if and how you might be able to lean into this commercially or not?

Thank you for the question. Anupam, I'll have, Matt Skelton, our Chief Commercial Officer, answer that.

Anupam, yes, thanks for the question. I think it's a differentiating factor for us in addition to the clean label we received. We feel really good about the profile we have. We think we're differentiated on an efficacy and a safety standpoint, our small volume autoinjector all of these things are going to lead to us being competitive in the marketplace.

Our next question comes from Gavin Clark-Gartner at Evercore.

Congrats on the approval. Nice to see. Maybe you could just lay out the launch metrics that you're presenting to -- or planning to report from the [indiscernible].

Yes. Thanks for the question, Gavin. Matt?

Yes, happy to take that. Gavin, I think the main one we're going to be looking at in the early days are patient start forms. That, I think, is going to be the indicator of demand. And we're going to work hard to make sure that we have a high percentage of pull-through of those patient start forms. But that's going to be our main metric and what we'll look at in the early days.

And not to get too tactical here, but are you planning to present some of those metrics on the August earnings or maybe wait more towards Q3 and November?

I'm happy to just say Q3, Gavin.

Our next question comes from Ritu Baral at Cowen.

Congratulations. Also looking at your label, which is delightfully broad, how are you going to target the appropriate patient or the most amenable patient, I guess, to TRUTAKNA? As we think about that 160,000 diagnosed versus the 82 reps. Does the commercial messaging, I guess, wrap around a type of patient, a certain proteinuria level, are you going by sort of Phase III entry criteria, Matt? How should we think about who you're targeting first out of the gates?

And then as you think about that 130 -- I'm sorry, 160,000 diagnosis rate in the U.S., one of our KOLs recently said at least in the U.K., the diagnosis rate for IgAN was like 10% or 15%. Do you anticipate that this number is already growing? Have you seen that?

Matt, happy you take that question.

Yes, happy to take that. As far as the number growing, I think usually, you see in markets when better treatments become available, markets tend to grow. So we are hoping that's the case. And I've heard that from the key opinion community as well. But as far as a type of patient we're looking for, we look at the broader market. There's tens of thousands of patients on supportive care therapy that can use a disease-modifying agent like TRUTAKNA. So we want to meet nephrologists where they are. As you indicated, we're really pleased with the broad indication. And I think this gives us a lot of addressable patients to target right out of the gates.

Our next question comes from Pete Stavropoulos at Cantor Fitzgerald.

Genuine congrats on the approval. It's great to see you bring this over the goal line. Can you just talk about the commercialization and sales team in place, sort of their background and experience? And what gives you confidence that it's rightsized and that they can enable a successful launch?

Great. Matt?

Yes. Pete, yes, we feel great about the sales force that we were able to attract. Over 80% have nephrology experience, 90% have rare disease experience. This is a seasoned group of pros that we feel really good about and their ability to compete in the marketplace. And importantly, this is a lot of times a relationship business. They have the access with key nephrologists across the country. So we've got the right people out there.

As far as the number, we did a lot of work early on to figure out what the optimal number was for the opportunity, and we think we've landed on that. That was reflected in the recruiting process with the sales reps. These folks like large territories and opportunity, and we were able to attract them based on the number of reps we had. Did a lot of claims work for the opportunity. So again, I'm super confident in that number that we're starting out with it. We're not starting out with a toe in the water, Pete, and thinking that we're going to see how it goes and then add to it. This is the number we feel really good about.

Yes. Great question, Pete, and I'll just add that Vera, at this stage, with this type of leadership and commercial preparation has been built on years of preparation from clinical to medical engagement now to commercialization. The launch meeting that we've recently held was the most cohesive that many of us have ever seen in our career. And it's not just the number that we're confident and that's based on a very quantitative view of what the market looks like to us. So we're not interested in adding additional numbers. This is the right number for our approach and also the quality of the individuals and leadership that we put in the field, we're very pleased with. So this is a very good starting place.

Yes. And Pete, as I had said in my remarks, they're out selling today. So the sense of urgency is there, and we're going to take advantage of the opportunity.

Our next question comes from Paul Choi at Goldman Sachs.

Let me add my congratulations as well. Just curious what your latest market survey work suggests on physician preference of targeting both or dual APRIL/BAFF targeting versus just APRIL? And in terms of physicians prescribing TRUTAKNA or other B-cell modulators here. What is your sense as to how many physicians are just sort of waiting for sort of final eGFR results before starting to write a script, which could really unlock the opportunity here?

Great. Good question, Paul. I'm going to have Rob Brenner, our CMO, answer that.

Thanks, Marshall. I think if we would turn the clock back 2 years ago, I think there was a narrative that maybe blocking BAFF and APRIL might not be advantageous. The data may not be supportive. And now as we look through with care at the accelerated approval label for atacicept, I think we can put that narrative into kind of historical bed. The profile of atacicept now approved of TRUTAKNA, is precisely what I think the medical community has been looking for as a treatment option for patients with IgA nephropathy at risk for disease progression. So as we see it, the feedback we've received has been consistently favorable for an inhibitor that is designed to reduce both BAFF and APRIL. And in many ways, it represents an unprecedented opportunity for the prescription for patients with this disease.

Our next question comes from Vamil Divan at Guggenheim.

Congratulations as well on the news. So I have 2 follow-up questions, if I could, on questions that were previously asked or comments from before. So you mentioned, I think, in your market research that the physicians you've spoken to see atacicept as the most desired product. I'm curious if maybe you can share a little bit more on what specifically it is about that. We get a lot of questions from investors on sort of how this will be differentiated from products on the market, products coming? Is there 1 or 2 or 3 sort of metrics that really stand out most in that market research from with the doctors?

And then my second question was just more -- again, another question we get from investors a lot is around obviously, a great label you have here, nice broad label. Any updates you can provide on extension strategies around the monthly dosing, which you've talked about before? I don't know, is there any update you can provide at this time on that?

Yes. Matt, do you want to answer the...

I'm happy to take that. Yes. So regarding the market research, what I had referred to in my comments upfront was from a third-party source Spherix data. So that was not our own market research that had said that. So details of that, I don't have. But that, again, I think, adds to the validity of it that it was from a third party. But I've also spoken to, I think, the profile and differentiation. We think we have robust efficacy and safety profile, a very patient-friendly offered in a once-weekly autoinjector and small volume. All of that packages into a real nice opportunity and something that we think is differentiated in the marketplace.

Yes. And Vamil, good question. We do have additional studies ongoing. There haven't been significant updates that we're sharing today, but there is good progress that we're excited about across the full program. Today, we'll focus on the TRUTAKNA launch.

Our next question comes from Rami Katkhuda at LifeSci Capital.

I wanted to pass along my congratulations as well. I guess, how long do you expect it will take to get TRUTAKNA broadly available in channel? And are there any remaining gating factors? And then more broadly, do you expect there to be a bolus of patients ready for treatment? Or how should we be thinking about the sales ramp for your new product here?

Matt?

Yes. Rami, we expect to have drug in channel in 3 to 4 weeks. As a company and getting its first product on the market, there are some things we had to wait for, for the approval. So that was a little limiting factor. But 3 to 4 weeks, we are confident in. And then, as far as a bolus of patients ready to go, that's not our expectation. We don't think we saw that with the first B-cell modulator on the market. So I would hope for a nice, steady demand curve.

Our next question comes from Farzin Haque at Jefferies.

Congrats on the approval. So what are some of the learnings from Otsuka's launch that you can leverage for peer discussions and market uptake? And also interested in what will be your messaging to the payers for formulary positioning with the higher pricing in place?

Yes. Yes. We have our own plans and strategy in place that we're going to go after the market. I think what is encouraging from us from the Otsuka experience is that there's been good uptake. And I think they have set the table well for another B-cell modulator and one that I think is differentiated. So that's helpful for us and I think creates a nice opportunity for us to hit the market running.

I know you had a second part of that question.

Yes, like basically formulary positioning with the higher pricing?

We've done a lot of homework with payers, a lot of pre-approval information exchanges. We feel good about the price we're entering the market in. And yes, I wouldn't necessarily call that a premium.

Our next question comes from Ryan Deschner at Raymond James.

A big congratulations on the approval here. My question is, do you have any additional resolution on the time line for submission of full approval later this quarter or on the initial PIONEER readout in IgAN patients?

Ryan, thanks for the question. I'll have Rob answer that one.

Yes. I don't think any change. We've shared that we have pulled forward the time of the final analysis of ORIGIN 3 to Q3 of this year. We are on track to read out still in accordance with that time line, and that sets us up for a potential filing for full approval in Q4. So people are hard at work at those activities in parallel with celebrating this launch and making success.

PIONEER, we had initial disclosure data at the past European Renal Association meeting. I think you'd expect that we'll have more to say in terms of data release at ASN this year.

Our next question comes from Sadia Rahman at Wells Fargo.

Congrats on the approval. Just -- so I wanted to get your expectations for the cadence of PSFs here. Should we expect something similar to what Otsuka has been reporting with its launch in IgAN? Or do you think with Otsuka already having an established nephrology presence in the U.S., marketing another drug, did that help their launch? And could it take more time to see that kind of traction with TRUTAKNA?

Okay. Matt?

Yes. I said earlier, I think that they've kind of set the table for us, and we have seen that B-cell modulators are being accepted in the nephrology community. But at this time, we're not really giving guidance on how we think those PSFs will ramp up. Yes, I think it would be premature to do that.

Our next question comes from Arthur He at H.C. Wainwright.

I just want to congratulations again. So 2 questions and 1 for Rob. Do you guys have any follow-up data on the ADA incidents after 36 weeks? And for Matt, what's a reasonable gross to net we should look at assuming for the early launch trajectory?

Great. Rob?

Yes, the information that's included in the prescribing information on ADAs reflects all of the data points that were available to time of the interim look. So it reflects more than just a 36-week exposure. And I think it's important that this is the first B-cell modulator that has no evidence of any drug antibodies having an impact on pharmacokinetics, pharmacodynamics, efficacy or safety. So that's I think it's great for patience. And certainly, when we do the final analysis for safety and efficacy and file for full approval, that we'll have additional information that we'll be able to share in the updated prescribing information.

Great. Matt?

On gross to net, that's something we haven't given guidance on. It's something we are certainly going to keep our eyes on and try to protect as high as a percentage as possible. But we haven't really put that out there yet as far as expectations.

[Operator Instructions] Dina Ramadane at Bank of America.

Congrats on the approval. Just wanted to ask if you had any general thoughts on [indiscernible] final eGFR results, I believe we saw them last week. Do you view it as kind of just a net positive tailwind for the class? Does it impact maybe how your sales reps will present TRUTAKNA's data package to physicians and ability to kind of highlight the long-term Phase II eGFR data?

Yes. Thanks for the question. Rob?

Yes. Thanks, Dina. I do think our focus is to be to tell the comprehensive story about atacicept now aligned with the prescribing information. We did see that Otsuka put out written comments about their final results. We don't have any numbers. So I'm not really confident that I'm in a position to talk about what may or may not be those results until we see them. And I guess is that won't happen until we get to ASN. In the meantime, we've got a great story to tell about TRUTAKNA, and that's what we're going to do. And I don't think any news that comes from Otsuka is going to change our focus and our confidence in how this launch is going to go.

So this concludes today's question-and-answer session and investor webcast. We thank you for joining us, and you may now disconnect.

Hi, everyone. Thank you for joining us today at the Vera fireside chat. I'm covering analyst, Ritu Baral from TD Cowen at the TD Cowen Healthcare Conference. And joining us from Vera, this is a very incomplete list. We have CEO, Marshall Fordyce. We have our CFO and our new Chief Commercial Officer as well. Welcome, Matt. Welcome, Sean.

So ongoing FDA review. Obviously, you guys have submitted the atacicept application. It has been accepted and you have your July 7 PDUFA with priority review. The data package seems awfully straightforward. What's left to discuss as like review issues for your mid-cycle. I mean we've talked about the label and stuff like that, that seems like a labeling thing. So what are points of potential FDA focus?

Great. Great to be here, too. Thanks so much. PDUFA date is July 7. We're in the midst of prior review, which we're very pleased about the progress, and we can just reflect to you from our internal work with FDA that it's straightforward. Everything that you would expect at this stage of FDA review is happening and we expect to meet that PDUFA date and be ready. There aren't any major themes that are coming up. I think it's reasonable to say that label and negotiations happen later in the cycle. And I think there's quite a lot of learning that we can already take from the field to date, but we're very confident that we're going to get to the July 7 PDUFA date, and we're going to be ready commercially beforehand.

So speaking of the label, a lot of investor discussion has been, can you incorporate the 2-year placebo-controlled eGFR data from the Phase II into the clinical data section of the label. And then there were interesting developments within the Otsuka label for VOYXACT, which was recently approved, and this idea that they had no proteinuria restriction for their IgAN indication. Are those review issues to discuss? Or is that a last 6 weeks labeling issue?

Yes. Again, I think when we get into specific label negotiations, that's later in the cycle, I agree with you, the most -- one of the most interesting things from Otsuka sibeprenlimab label is that the indication statement is broader than the first wave of IgAN therapeutics. There was no proteinuria threshold that defined a high-risk patient. And in fact, the indication statement calls for all patients at risk, and it doesn't provide a proteinuria threshold. So that immediately broadens the patient population who could benefit from that drug. We expect something very similar in our label. But of course, that won't be final until we have a label.

Does that mean that the definition or the understanding of what defines an at-risk IgAN patient is evolving past UPCR?

Absolutely. So...

So what would it encompass?

So there are patients with low proteinuria, proteinuria below a gram, below 0.5 gram who, despite having that proteinuria profile are still having rapid GFR loss. Those patients exist. And there is, of course, an important correlation between proteinuria and GFR outcome, but it doesn't define on a patient-per-patient basis what the risk is.

Is that a large proportion of IgAN patients?

It's a significant group. So we're extremely excited that the overall GFR profile is transformative for atacicept having a slope of minus 0.6 at 2 years. is a result that's never been seen before, to your first question, that's what's published in both our Phase II manuscript and referenced in our Phase III New England Journal Medicine manuscript. And that really, in our view, is what's the most important thing. If you are a patient or a family member, and you've got IgAN, what's going to define your future health and whether you have kidney function or not before the age of 50 is your GFR. And that really has certainly shifted in the conversation. I think most nephrologists would reflect that new reality. We've never had medicines that stop GFR decline in this disease. And so of course, you have a historical focus on proteinuria, but GFR is what defines efficacy in this new class of medicines that we're now leading.

So some check NDA check off the box questions. How is the CMC module? How is your supply chain, potential inspections progressing? And are there any sort of CMC risks to the approval time line that could trigger a 3-month delay?

Yes, great question. I could just continue to reflect confidence that we don't expect any delays with respect to CMC inspection, CMC issues, we're very close to July 7 from Vera's perspective.

Have you send whether your manufacturers are already GMP certified or whether there are inspections that need to be done?

Yes. We have shared and we're not giving specific timing on inspections and the results at this stage. But again, we're well into the process. There haven't been issues. Our supply chain, both for drug substance, drug product, the auto-injector that we're expecting to bring to market on July 7, those vendors that are in our supply chain, all have commercial products that have been on the market.

Understood. And the review team leveling up a little bit, has that stayed intact since the preNDA meeting?

Yes.

Okay. All right. Those are the check off the box. Now we get to the interesting stuff. Pricing and commercial strategy. How do you plan on positioning atacicept to the market, especially against sibe, especially against potential, look, VOYXACT now approved from Otsuka and potential competition from pove.

Sure. I'll start with a few comments then I'd love to introduce Matt Skelton, our Chief Commercial Officer, to TheStreet here. Look, this is a large unmet need. We've been sharing that for some time. So lots of patients. I think the majority of the opportunity is in the United States. The majority of the opportunity is young people. So commercial pay, we estimate over 70% commercial pay. That's a pretty interesting perspective on what the opportunity looks like.

And then, of course, there is now a track record of premium pricing, including VOYXACT's most recent price. So it's not hard to get to a very significant market opportunity when you look overall at the IgAN market. And today, we even see early signs of demand. So you can look at what demand has looked like in the IgAN population for what we might call the first wave of IgAN products, TARPEYO, FILSPARI. And then what does the VOYXACT launch look like in the first few months?

And Matt, maybe you could highlight some of what we've seen about that demand.

How does that look?

Yes. Hi, everybody. We're super encouraged with the early days of the launch. So Otsuka reported 500 patient start forms in the first 11 weeks of launch, which I think is a really encouraging sign of adoption by nephrologists of B cell modulators. What's good for B cell modulators is going to be good for us, right? And so I think being a fast follower having the PDUFA in July and getting out there is the market is going to be ready, that much more ready for us to come out. So really good early signs. I think you also saw that they guided to $163 million in sales for this year, which if they meet that, which I think based on 500 patient start forms in the first 11 weeks, is a pretty conservative estimate. That's going to exceed all the other earlier IgAN launches, FILSPARI, TARPEYO.

Have you been hearing anything on the real-world patient experience with the prefilled syringe and what patient response has been to that?

Not much, just anecdotal, but the prefilled syringes is quite big. It kind of fits in your hand but not quite big. And it's a high volume, it's 2 ml. We think we have a more elegant solution in an auto-injector. And you mentioned from a competitive standpoint, what are we going out with, I think it's the whole package and the whole profile. But an important part of that offering is, I think, we have a much more patient-friendly offering and a once-weekly low-volume auto-injector.

Are you currently laying an inventory ahead of the PDUFA?

Yes, inventory is not going to be an issue.

Okay. And it's not going to show up on -- okay.

How are you going to approach patient identification, assuming approval, July 7. It is going to be sort of the middle of the summer, which can be weird for a launch, but how are you approaching patient identification, prescriber education, given the complexity of IgAN diagnosis and management but also the unmet need.

Yes. A few things. So our sales force is fully hired. They will be trained and in territory 3 months before the launch.

This is the 82%.

Correct. correct. They're all on board, ready to go, and they will be out there, having those disease state education discussions with physicians, making appointments, doing all the things you can do prelaunch, everything short of -- you can't talk about the drug, right? But I think those are all really important things to get ready. And as far as patient identification, again, back to something I said earlier, is that's why I'm glad that Otsuka is out there talking about IgAN.

Cause you can target, like you can see where the -- who's writing those scripts and target those patients...

Oh, yes. So as far as targeting a physician, yes. So it's not 100% straightforward, but we're going to target about half of the nephrologists in the U.S.

6,000, right?

Right around 6,000, right? And for IgAN, there's only been an ICD-10 code since October of '23. So in the world of cutting, that's still fairly new. So we certainly have that data to say, hey, let's look at the claims data to see who was using the code. And then through other ways we triangulate around, it kind of looks and seems like it's an IgAN patient under the care of this doctor and that was included in our targeting.

Is there an ideal patient subpopulation you think you can -- that's a low-hanging fruit, how would you define them?

Yes. Really good question. And usually, when you launch a drug in this -- you want to paint a picture of this is the patient to start using this drug. We haven't got to that point yet where I want to be that prescriptive because it's changed a little because I think what you had with the earlier IgAN drugs, you had a proteinuria threshold to which they treated, right, when they had to be over a level to start the drug. That's not the case in the VOYXACT label that I don't think it's going to be the case in ours. But it's kind of where the physician head is. So we want to meet the nephrologist where they are today, and that will probably tend to be a little higher risk patient as they view it, and we'll start there. The key is we want physicians to start using the drug.

So are you -- given the fact that you may not have proteinuria restrictions on the indication label. Are you prioritizing that expanded IgAN population in the PIONEER study so that you can sort of generate that data in the expanded population so that you can use it as close to launch or on launch as possible?

Yes. I think it's -- I'm glad we're doing that study, and we're the only ones that are studying that. So I think when physicians have those questions, we'll be able to provide answers that we're actually doing the work.

I would highlight this is a large prevalent pool. And if you look at the patient starts that we're hearing from those that are out there in the market, that's still just scratching the surface. There are 160,000 prevalent patients more or less in the United States alone. We estimate roughly half of those patients are in this rapid progression pool. So if you're thinking about 80,000 patients on average, 35 years old who are going to be on dialysis by 50, that's a highly motivated group and physicians who are caring for them want a solution for that. To have a solution atacicept that stops GFR decline in those patients. I think you can even be conservative on your penetration into that pool of roughly 80,000 and say you don't need to be overly specific on your targeting. That's a lot of patients who need a profile that we think we're going to have a launch.

But remind me when we're going to get the PIONEER data that expanded IgAN?

We've guided to the first half. So roughly the cadence in the nephrology community is the American Society of Nephrology is a fall meeting in October, November. And the other meeting is the European meeting, which is in June. So we do expect to share some data we've guided for PIONEER to the first half.

And then you would have that upon launch?

It would be out there at least in the presentation for.

Got it. What launch metrics do you plan on providing post approval?

Yes. I think we're going to be conservative about that initially. We're not going to give specific guidance, but we'll certainly give us a sense of demand as we come out of the gate. And I will be as transparent as we can and set reasonable expectations around how quickly we're going to change standard of care here.

Yes. We'll track patient start forms. And I think that's traditionally been if you look at others in the IgAN space have reported those and still report those. So I think we'll -- that's something we'll keep a close eye on and probably report.

How are you approaching market access and reimbursement, especially in light of the high pricing of competition and the value that ataci brings to the table.

Sure. I'll take that. We have had a very experienced value and access team out in the field since -- gosh, 8 months ago. So they've been out great relationships in the space, know all the payers. That's the first step, right? They've been out there. We have conducted now over 20 -- what are called PIE presentations, preapproval information exchanges with large payers, educating them on the space, what's coming. So we've been doing all of that type of homework and end market preparation as you should. We've seen now 9 policies on VOYXACT that have come out, payer policies. They are not restrictive. They're 2 label. And we feel really good about those and think that will probably follow when we hit the market.

Are you seeing any step edits within that?

The only step through as we're seeing our ACEi/ARB which I don't even see as an issue.

And again, what you're hearing is there acceptance or pushback of combination therapy for IgAN patients to layer on IgAN, not just ACEi and ARBs.

A couple of like branded therapies?

Yes.

Great question. I haven't heard anything specific to that yet. I think it's still early days.

Positive or negative, okay.

Yes

Okay. How should we think about the mechanics of gross to net. Are you planning like a specialty distributor, who's going to take like a little off the top and then the Medicare Medicaid discount contributing to that. What should we be modeling going forward?

Sure. Marshall said this earlier, a good thing about the space from a commercial perspective is it's almost 75% commercial pay. That helps gross to net, right?

You don't have that 231, the automatic 231.

Exactly. Yes. Well, it's a smaller percentage of the business, yes. Our distribution model is through specialty pharmacy. So as you said, there's a little admin fee there. But that's something that we are going to keep our eye on is gross to net and control what we can control. And so we'll see how the market reacts as far as any rebating or discounting but that would not be our intention out of the gates.

What are your current plans for like a patient hub and wraparound services, support services, whether insurance, whether it's compliance, et cetera?

Yes. So our specialists and distribution in building out the hub have been with us now almost 6 months. The hub is in full development.

Is it your hub? Or is it the specialty pharmacist hub, specialty pharmacies hub?

That's part of it, but we're working with someone else and we'll do the hub for us. Right, one that they're very -- the physicians are very familiar with CoverMyMeds right? So high level of familiarity. So we realize going into this space that it needs to be white glove treatment, and we need to make sure that every patient in an office intends to get on drug, gets on drug. So that's something we've paid a lot of attention to and dedicated significant resources to.

What are your expectations for peak share in the U.S. and the key drivers that you anticipate will aid in achieving that?

I think it's too early to give a number there, Ritu. Again, I think...

What's reasonable do you think?

Yes. I think it depends. We've been pretty consistent, we think the B-cell modulator class is a step into the future from what has existed so far. We would consider Otsuka's product to be so modulator, although we're still interested to see what the 2-year GFR data show. So we haven't seen that yet. That's going to be an important data point.

And then there's our data. And then anyone else who comes along, we'll wait to see randomized controlled trial data and 2-year GFR data is going to be really important. So in our view, efficacy by GFR is really a major driver. We've set a high bar for safety, which is placebo-like safety without a significant imbalance which...

Do you expect that to be a differentiator with some of the other mechanisms? I know it's a topic of discussion with pove. It's been a topic of the posters with [ GFR high bar ], how do you see that shaking up? And what do doctors seem to care about?

Yes. I think ultimately, doctors and FDA, what makes it into the label really depends on controlled trial data. So we wouldn't spend a lot of time on safety signals in an open-label trial until seeing whether that's balanced by placebo or not in a meaningful population. That's how Vera has conducted its Phase II and Phase III program. We did dose findings, we have a clear understanding of dose and safety. And I think we'll wait to see data from others.

But the bar is these are young patients. They want the efficacy of GFR stability, and they don't want to lose their kidney function and end up on dialysis. And they'd like that without a safety liability. That's a really strong way to have an offering and a self-administered autoinjector, small volume. And that's the offering we've got. And I just think it's too early. Of course, everyone is going to want to predict the future, I get it. But we don't think that assuming our data is going to be replicated by other drugs, other mechanisms, other doses, is a very clear way to predict the future.

What about ex U.S. regulatory? How are you thinking about Europe? How are you thinking about MFN and population sizes.

Yes. I'll say what we're acting on and what we're thinking about, and I think thinking goes with MFN. Clinical regulatory-wise, Vera has conducted its atacicept program in a global fashion. So in both Phase II and Phase III, we have clinical regulatory presence in Europe, in Japan and other ex U.S. countries. And we've made full progress and regulatory discussions across the board. There are differences between regions in terms of how much experience or buy in there is with proteinuria as an accelerated approval endpoint. And so GFR is more important ex U.S. as kind of a general comment I would make.

So you might wait for that, eGFR data?

There's no waiting at Vera, but we don't have to wait. The timing is working out that we continue to make clinical regulatory progress. And we continue to have full optionality. And with MFN, I think we're watching to see how that continues to settle in and being at a point of optionality at this point is a strong place for us to be.

As IgAN one of those kidney diseases that's like has a curiously outsized prevalence in Japan?

Yes, there is a higher prevalence of IgAN in Japan and other Asian countries, China for example.

Like East Asian countries.

On average, I think there's an estimate of 3 million to 5 million patients with IgAN in China for example. And there's a debate is that more disease detection, is it higher diagnosis because of a different health care system and more frequent screening. So for example, in South Korea, there are aggressive screening programs by proteinuria in schools, and they pick it up more. So I think if you look at in schools -- yes, and schools and young people looking at proteinuria. So there are health care system differences that could account for that. And there's speculation as to overall other immunogenic differences, but the fact is it's higher per capita.

Another major focus of investor conversations is your monthly dose or your monthly development of the monthly dosing. Can you talk us through the status of that study and the time lines? And what you hope PD efficacy will look like? What's acceptable and essentially means equivalents?

Yes. I think we can't be overly specific. I can say that we started our monthly dosing study at 3 different doses last year versus placebo. It's not unhealthy volunteers, it was in IgAN patients...

It was started a year ago, right? A year ago...

So that trial has enrolled, and we are looking at a variety of endpoints. And what's important is that we're looking at PK/PD and aligned with FDA and what endpoints are going to be important to bring that forward all the way to the market. So we haven't been specific. We want to look at the data. We want to align with FDA. And I think the most meaningful data point for TheStreet is that, what does that offering look like for patients as a new component of Vera's IgAn strategy? And at the same time, the lion's share of our focus is, of course, on our go-to-market product.

Have you commented on the formulation and concentration of that monthly because I think what we're focused on is like would this have to be an entirely new NDA because the formulation differences would be so different. Obviously, that would be like another patent thing, which I want to ask about. But -- or could it be if the formulation was the same an sNDA with a quick path to the market.

Yes. All those are good questions. We haven't given specificity on dose volume concentration. There certainly are formulations that allow you to concentrate greater than the 150 mg per ml rough standard that we see in the biologics space. And so all of those are under consideration and internally.

When do you sit with FDA to map the cell?

Yes, haven't been specific, but we're looking at data this year. When we look at data, we're going to be carrying that to FDA when we have a view.

Got it. And in our last few minutes, could you review for us the IP portfolio around ataci and IgAN. Also FSGS, I don't think we're going to get time to go into FSGS component of PIONEER, but we're expecting that, too. But IP around those uses and ongoing strategy, IP portfolio strategy.

Sure. So those paying close attention have seen that we've played a pretty standard playbook with IP. This is a biologic, there is the regulatory exclusivity of plus 12 years in the U.S. and 10 years in Europe. That said, we've taken all of the steps required to protect this franchise. Right now, that data is 2047. And so if you think about what it takes to make atacicept as a...

And these are -- use patents.

Yes, this is going to be IP based on process based on formulations improvements, methods of use. So there's a suite of patents that are important in protecting us through 2047, and that's been a development only in the last couple of years within the Vera team. And beyond that, of course, there are -- there's know-how and trade secrets that aren't patented that are really important and actually producing the product. This is really standard. We've seen this play out before in biologics, and that's the approach there has taken. So I think when we consider biosimilar entry to the market, that's further into the future, and I think we've taken all the steps you would expect for a company like ours to protect a very valuable product.

And I think that leaves us 90 seconds for your VT-109, your newest...

Yes. So another part of the extended franchise is the molecule we licensed from Stanford about 1.5 years ago, making good progress. It's still pre-commercial -- preclinical, an interesting molecule that's another BAFF/APRIL inhibitor with a different mechanism, BCMA.

Where would that fit?

It would potentially enable longer dosing intervals than even monthly. So going to quarterly or a few times a year, and that's the promise of another program in the future. So our strategy is to bring a very strong data package efficacy, safety, patient experience with the first autoinjector BAFF/APRIL inhibitor to market and then build on additional extension so that we have additional offerings.

So monthly and even less frequent dosing. I come from -- originally from the Gilead world where one pill once a day was a really big deal in HIV, and now it's 2 injections a year. That's an incredible development for patients, for really public health and how we treat people. So it's amazing to be in this position now creating a new category and being the leader in that category, the recognized leader coming out of 2025 and having really the first BAFF/APRIL on the market within a few months. We're ready to launch, and it's a really exciting time.

Great. Well, thank you, guys. We are at time. Thank you for the insights.

Thanks, Ritu.

Welcome, everyone, to the 44th Annual JPMorgan Healthcare Conference. My name is Anupam Rama. I am one of the senior biotech analysts here at JPMorgan. I'm joined by my squad, [ Rati Pinhe, ] Priyanka Grover and Joy So. Our next presenting company is Vera Therapeutics and presenting on behalf of the company, we have CEO, Marshall Fordyce. Marshall?

Great. Thank you so much, Anupam. Good afternoon, everyone. Welcome. Thanks for the opportunity to present to you today. I'm Dr. Marshall Fordyce. I'm the Founder and CEO of Vera Therapeutics. Our mission is to lead a paradigm shift to a more targeted way of modulating the immune system and free patients from the burdens of their disease. Today, I'm very pleased to present at the outset of 2026, our outlook as we approach the commercial launch of our lead product candidate, atacicept.

Before I get started, I want to remind you that my remarks contain forward-looking statements under the safe harbor act. As such, we'll present this disclaimer regarding at-risk statements.

Vera was founded here in San Francisco in 2016 and we in-licensed atacicept in 2020. Atacicept is the first-in-class dual BAFF April inhibitor, a mechanism that holds promise to control autoimmune disease activity while avoiding the challenges of immune suppression. Based on positive Phase III results last year, Vera submitted a BLA to the U.S. FDA and it was just last week awarded priority review with a PDUFA date of July 7, 2026.

Atacicept is on track for commercialization in IgAN this July. And it's also under investigation in a Phase II trial in adjacent autoimmune kidney diseases, primary membranous nephropathy, autoantibody-driven FSGS and MCD. Vera has two other molecules in our pipeline, a Phase II asset called MAU868, a monoclonal antibody against BK virus, which is a leading cause of kidney transplant failure. And a preclinical asset, VT-109, that we licensed from Stanford last year, a novel fusion protein with the potential for immune modulation with much less frequent dosing intervals on the order of 2 to 4 per year. Vera maintains ownership of each of these molecules in all indications in all geographies.

There's management team brings deep leadership experience and a track record of success in clinical development and blockbuster commercialization. We are the leading innovators in nephrology through rigorous clinical science, patient-centric development and engagement with the physician community. We have a strong cash position with pro forma cash of $779 million with 71.3 million shares outstanding. In addition, we have access to $425 million in non-dilutive capital through our Oxford financing facility. I want to give you the big idea first. Atacicept's mechanism of action of dual BAFF April inhibition has broad therapeutic potential for many autoimmune diseases, which are substantially driven by abnormal or overactive B-cell function.

The two known circulating cytokines, BAFF and April are both important for the survival and maturation of the B-cell lineage. Elevations of both BAFF and APRIL are found in patients with IgA Nephropathy, lupus and certain other autoimmune diseases that I'll highlight later in my presentation and both play a key role in disease pathogenesis driving anti - autoantibody production and damage to the body. Atacicept is a biologic fusion protein that makes use of the true unaltered TACI Receptor and has picomolar binding to both BAFF and APRIL in binding assays as expected from TACI's natural role in B-cell biology.

IgAN or IgA Nephropathy is our lead indication. It is the most common primary glomerular disease worldwide with an incidence of 2.5 per 100,000 people. This is a disease of young people with approximately half of all diagnosed patients reaching kidney failure or death within 10 years, meaning before their 50th birthday. Current treatment guidelines for nephrologists recommend reducing the rate of kidney function decline as measured by estimated glomerular filtration rate or eGFR, which is calculated from a blood test that you would get when you see your doctor, serum creatinine, a new therapy that could stabilize kidney function decline and potentially avoid dialysis or transplant, at 50 years old or beyond would be completely novel and transformative for these patients.

IgAN patients currently face a very challenging life ahead. if their kidney function decline leads to NCH kidney disease or ESKD, the need for dialysis or kidney transplant dramatically alters their lives and those of their families with mortality over 5 years similar to stage IV colorectal cancer. Through rigorous clinical science, we have aimed to demonstrate that the inhibition of immune complex formation in IgAN through dual BAFF APRIL inhibition offers the potential for these patients to avoid kidney failure over their lifetime. IgAN is a disease of the immune system in which BAFF and APRIL levels are elevated driving circulating immune complexes causing a cascade of downstream damage to the kidney through inflammation, fibrosis and loss of organ function.

Atacicept, as I mentioned, takes the unaltered TACI Receptor that binds both BAFF and APRIL. And in patients with IgAN, this mechanism holds the promise of targeting the disease at its source. And so as we conceive of what this target in this way to drug the target could imply for clinical outcomes, we imagine that at the right dose, we should be able to demonstrate 4 measures of clinical effect, reduction of immune complexes in the blood as measured by Gd-IgA1 in the upper left. Resolution of inflammation in the kidney as measured by hematuria or blood in the urine. In the upper right, reduction of protein in the urine, a sign of glomerular dysfunction, the filters in the kidney or letting protein through abnormally. And finally, in the lower right, the most important stabilization of eGFR stopping kidney function decline.

In Vera's Phase IIb study for which we have reported 2-year follow-up, we have shown just that. Halting kidney function decline is completely novel in IgAN and the implications for young patients facing dialysis are profound. Subsequently, in Phase III, we designed and are conducting a multinational, randomized, double-blind, placebo-controlled trial comparing atacicept 150 milligrams to placebo with a primary endpoint of proteinuria at 9 months and a secondary endpoint of eGFR at 2 years in alignment with the U.S. FDA.

In this consort diagram at the 36-week interim analysis presented last year, retention on atacicept was high at 93% versus 87% on placebo. The baseline characteristics include enrolled subjects that were similar both in Phase IIb as well as Phase III. And these are patients who are at high risk of disease progression, and we're on current optimized background chronic kidney disease treatment. Baseline characteristics reflect a relevant and diverse population. Mean age was 40 years old, mean eGFR of 65 mean proteinuria of 1.7. This pivotal Phase III trial met its primary endpoint at 36 weeks, achieving a statistically and clinically significant reduction in proteinuria with a 42% placebo-adjusted delta.

Importantly, in Phase III, this treatment effects on proteinuria reduction was robust across all prespecified subgroups according to demographics, baseline kidney disease by both proteinuria and eGFR as well as background treatment. Secondary endpoints were also consistent with what we showed in Phase II. We've reported secondary endpoints, Gd-IgA1, the measure of immune complexes and hematuria, the measure of active kidney inflammation. These results are similar to those in Phase II. Per FDA's recommendation, we have not reported eGFR results, but of course, these are part of our BLA submission. But the registrational trial is still ongoing, and I'll highlight that we plan to share these eGFR results when available estimated in early 2027.

Importantly, the clinical safety profile of atacicept was similar to placebo. Atacicept was well tolerated and IgAN patients with no reported deaths, a low rate of serious adverse events of 0.5% and a low rate of adverse events leading to discontinuation. There was no evidence of opportunistic infections, no significant imbalance of infectious adverse events, either serious or mild was seen in the active arm. Some increased rate of injection site reactions was observed on atacicept, but these were mostly mild or moderate in severity. And recall that our experience in Phase IIb has shown over 90% retention of patients self-administering weekly atacicept for over 2 years.

These results were presented at the 2025 kidney meeting, ASN in Houston last November at the opening plenary session and simultaneously published in the New England Journal of Medicine. With our cumulative clinical data in both Phase IIb and Phase III, Vera is preparing for commercialization this year with a winning profile. With the longest term efficacy data from a randomized controlled trial in the B cell modulator class with a rapid and sustained response seen consistently across our 2 global trials and across all subgroups, with the differentiated safety profile and a desirable patient-centric features of delivery, Vera is well positioned to address a significant unmet need for IgAN patients in the United States this year.

Atacicept has product characteristics similar to other blockbuster biologic drugs. We have presented atacicept for review by FDA as an at-home, self-administered 1 ml auto-injector using a 27-gauge needle, a rapid injection time with once-weekly frequency. Recent third-party surveys indicate that nephrologists view atacicept as one of the most desirable IgAN agents in the development pipeline. There is strong interest in B-cell modulators for IgAN with most participants willing to prescribe them for high-risk patients as well as patients earlier in the treatment paradigm.

It's a highly dynamic category-creating moment for new therapies in IgAN. How many patients are there. In the United States alone, we estimate that the U.S. population of IgAN -- diagnosed IgAN patients is roughly 160,000 patients with roughly half that number in the highest risk category matching our pivotal trial study population. Vera is also studying atacicept's potential benefit in moderate and low-risk patients in the ongoing PIONEER trial with results expected this year. There are 6 cohorts in the PIONEER trial, which includes not only moderate and low-risk patients, but also patients who are adolescents, patients who have ongoing or recurrent IgAN after kidney transplant and the like, which serves a very important data gap for these patients with a high unmet need.

New practice guidelines are recognizing the potential opportunity to stop disease progression and specifically call to initiate treatment at lower proteinuria thresholds currently at 0.5 grams per day, which falls into that moderate risk category. The treatment targets described in guidelines speak directly to the treatment effects we have shown with atacicept including prevention of immune complex formation, reduction of inflammation, reducing proteinuria and most importantly, stopping eGFR loss to a rate of less than 1 ml per year. Over the past 5 years or so, 5 new drugs have been approved for IgAN, each with premium pricing annualized on this slide.

The IgAN market has many hallmarks of an attractive commercial opportunity. And atacicept is well positioned to meet this substantial unmet need. There is a large and growing market with a favorable payer mix and a significant opportunity to deliver a differentiated product. The key measure of efficacy recognized by FDA, nephrologists and of most concern to patients, is their overall kidney function GFR where atacicept has long-term data supporting a return to normal eGFR slope. Moreover, with the clinical profile that has emerged in our developing program, atacicept represents a paradigm shift in how we might treat a much broader array of immune diseases which represents an even bigger opportunity beyond kidney disease alone, and I'll touch on that before I close.

Therapeutic potential in other autoimmune diseases depends on a mechanistic match in which BAFF and APRIL are elevated and apparent key drivers of disease and we see an opportunity to expand into a double-digit billion dollar market as we build our pipeline. We identify here at least 12 distinct indications for which there is significant unmet medical need. A strong mechanistic fit, significant clinical validation, attractive regulatory pathway and opportunity to differentiate from the emerging standard of care. Among these indications, we estimate about 1.2 million addressable patients between nephrology and non-nephrology diseases in the U.S. alone.

In closing, Vera is poised for a transformative year in 2026 as we gather momentum towards our U.S. commercial launch. Priority review is currently underway with a PDUFA date of July 7. Our Phase III trial is ongoing with a 2-year confirmatory GFR result expected in 2027 with full approval projected to 2028. In addition, our EXTEND and PIONEER clinical trials studying atacicept in additional IGN cohorts in adjacent autoimmune kidney diseases are enrolling very well, and we'll be sharing clinical data results at a nephrology conference later this year. I want to thank you for your time and interest, and we'd be happy to answer questions. Thank you very much.

Thank you, Marshall. As always, I'll ask the first couple of questions. And then if there are questions in the audience, just raise your hand and I'll call on you.

Marshall, I want to start out with a question that I've been getting a lot here in the last week or so, which is just if you could comment on the IP estate for atacicept.

Sure. atacicept is a biologic product. We in-licensed this from Merck KGA in 2020, and it was a Phase III-ready program at that time. formulation and process since we've brought it in-house over the last 5 years has had substantial improvements. We have full control of the supply chain, and that's generated not only new IP but also trade secrets and know-how. So it's a very well protected molecule. Most recently, there's been some public updates on the way that we've built our picket fence around this asset, including methods of use that get us to 2041.

Our target is to get to 2047 and beyond, and this is a very standard playbook for a molecule like this. Yes.

And then as you have a PDUFA now, right? So like what is going to be kind of your key medical education market prep work here in the first half as we look to PDUFA action date.

Yes. I like the surprise in the voice. We're not surprised. We expected this.

That was a good surprise. Good surprise.

We've been preparing for a long time, and it's been great to have our Chief Operating Officer, DJ Johnson, who joined us from Global Blood and previously from Gilead. He oversees the overall commercial organization, CMC and certain G&A activities. We have Matt Skelton, our EVP of Commercial and leading the U.S. launch. They're really building on work that has been going on at Vera for 4 years. We believe that when you have the right target molecule data, you need to communicate about that data. We've been very active out there. So disease state awareness. This is a category-creating launch. We've taken that seriously now for years. We invested heavily in our ability to communicate to the nephrology community with a focus on the United States.

And we're very pleased at the end of 2025 to see the slide I showed you, which is a very good awareness of atacicept. It's data and ensuring that there's a broad understanding of this disease, its mechanism and the data that we have coming forward. So there's a lot of work that has been done and that will continue to be done as we prepare for launch. But the team is fully in place. This is a commercial company. We have all of our sales leadership in place, and sales force is being hired in the very near future.

Questions from the audience? What's going to be the size and scope of your sales force as you look to a launch here. And when could we get an update on what that structure looks like?

Yes. Happy to share it right now. We're hiring 82 sales reps. We envision a very strong coverage and the right sizing of that sales force. There are about 11,000 nephrologists in the United States will target a bit more than half of those. This is a size and structure that makes a lot of sense to our experienced leadership. Matt overseeing the U.S. commercial launch has chosen to have good span of control. We have a West -- Western U.S. sales leader and an Eastern U.S. sales leader who I've been in the field with were fantastic. They've hired their regional managers and the next step is hiring and sales training. So some of it's about size and structure. A lot of it is about the quality of people.

And competitively, there's going to be a bunch of updates in the space, right? You're going to have Vertex's initial proteinuria data, Otsuka eGFR data. How do you think about that in the context of what you've shown with atacicept already?

Yes. I think we've set the context. We've set the bar that one needs to meet. And that really -- when we think about new products, we used to say efficacy is king. The most important thing is that GFR stability, if you're a 35-year-old with a diagnosis like this, you want to take a drug that's going to work over the long term. We've shown 2-year data that gets a 35-year old to 37, that's not enough. We're interested in decades of durability. So we like that we're a dual BAFF April inhibition. We like that we are the native TACI Receptor. We like that we have the longest-term data out there in the field. And it's our view that it would be very challenging given the unknown pathophysiology.

Once you get the fibrosis and you show up with the GFR of 60, you can't reverse that. You need an antifibrotic for that. So the best another program can do in our view is to match it, and that sets a really high bar. I will also say that it's good to not be alone. We're not the only ones raising awareness about this unmet need about the importance of modulating B cells in a safe manner with a good therapeutic window. And so it helps us that we're not alone in that. And we welcome the chorus of interest in helping these patients.

Questions from the audience? Marshall, if I could just push a little bit on what you just said, right? So agree with you. This is a eGFR game. I agree with you. These patients are young. They're going to be on these products chronically, right? So if you have to think about it, what is the minimum eGFR delta between 2 products, right? Because this is a chronic disease and even 0.5 ml will cumulatively add. So what is that minimal delta that you think is clinically meaningful as you think about these patients chronically?

I love that question. So first, those of us who are lucky enough not to have a chronic kidney disease lose 1% or 1 ml per minute per year. So that's normal. In Phase II, we showed a minus 0.6 slope, which we would round to 1, so that's why we were excited. You have to think about what does the disease do? If you're at high risk, you're losing 5 to 10 mls per minute per year. You're losing up to 10% of their kidney function every year, which puts you on dialysis by 50. So I think that's important to keep in mind.

Look, we're standing on the shoulders of giants. We're not the first drug to market. Others who brought drugs to market have been able to improve that slope from losing 10% to losing a bit less. And that's fantastic. You are actually saving months to years of kidney function and keeping someone off dialysis. So what's clinically meaningful in this disease has already been shown, which is great. we'd like to really transform what that target is and normalize it. And that's what's so exciting about the data set that we pulled forward. So you can make these inferences and extend out. But you need to do the data. And I think that's where Vera has been very strong and rigorous in its clinical science.

We know that others have moved quickly from initial proof-of-concept in open-label trials to registrational trials without doing careful dose finding. We think that incurs meaningful risk with respect to safety and getting the right therapeutic window. And I think it's hard to know what the effect size is until you've done a proper fully powered Phase III trial. That's not only controlled but randomized and double-blinded and run for the full duration.

Questions from the audience? Maybe, Marshall, you could give us an update on your monthly formulation of atacicept, which I know you're working on. When could we learn more about what that profile looks like.

Sure. It could be later this year. We're running a dose range finding study, and I would put this in the category of creating new options in the Vera pipeline for the future. I do think that dosing frequency eventually in a market can become an important option for patients. So we've known that and invested in potential monthly. That ongoing study should yield data for us around midyear. And then we'll be looking at that data and determining the path forward in concert with regulatory authorities. So that's the plan. That's roughly the timing. And then VT-109, again, as I mentioned, has the opportunity to do even less frequent dosing. That's important in the leadership position that we have to continue to create options for patients.

What would you say to those people who say, Vera has to have a monthly atacicept formulation out there ahead of or around if Vertex comes to market?

Yes. I guess I would say that the data doesn't that view, the data that we have in hand, a 2-year data in open-label atacicept weekly with a prefilled syringe. 90% retention is a home run number. You got to pay attention to that if you think the patients aren't going to take it. I do think that prescribing and maintaining on a drug does depend also on the data set that you have forward. So that's not just the frequency but also the overall data set is important as well. So we do have this thesis. We're now seeing it come out in our own long-term data and retention, and we also see it in third-party surveys where this is not going to be a meaningful hurdle for us as we seek to bring this to patients.

A question from the audience? Yes, go ahead.

The KDIGO guidelines, last time they were updated, there were no approved therapies. Can you talk any changes you'd expect to happen now that we have approved therapies coming to market?

Sure. Good question. What influences how these patients are managed among nephrologists. There is an international guideline, so distinct from other areas, subspecialties of medicine. There's the KDIGO guidelines, it's not U.S. specific, which is a little unusual relative to other fields. They were updated recently, as I reviewed on the slide, and they really indicate the data set that I'm describing to you. So these are a bit anticipatory, but as you'd expect, they don't include any non-approved drugs. We would expect an update in these guidelines sometime after our approval.

So second half of this year is our general estimate of when that will happen, but there isn't a clear date coming from KDIGO I'd also point out that not all nephrologist go to that as the singular source, sources like UpToDate and other guidance documents that physicians use are also important and sometimes are updated faster.

I have one more question, but additional questions from the audience. Final chance? Then final one for me. As we think about the ORIGIN Extend and PIONEER updates in 2026. For extend, any chance we may get that ahead of PDUFA as part of a more medical education on durability and things like that. And then kind of the size and scope of what we should think about Pioneer?

Absolutely. I would just speak for our Chief Medical Officer in saying, at this stage, making sure that our fresh clinical data is presented at conferences is important. In the U.S., it's ERA, which is in the fourth quarter. In Europe, there is -- there tends to be a late May, early June meeting called ERA which precedes our PDUFA date. So that is a possible target for some new data from our additional trials.

And I think you meant ASN in the U.S.

I did. I might have switched them ASN in the U.S. fourth quarter, ERA and Glasgow in June.

Yes. All right. Thank you, Marshall.

Good. Thanks so much for the opportunity.

The CEO, Marshall Fordyce, welcome. Thank you. And special guest, Robert Brenner, CMO. Thank you very much as well for joining us up here.

So a lot to talk about. You're late stage, of course, in IgAN. But maybe just set the stage and tell us where you are, tell us about the recent data, of course, at ASN and what the time lines are for getting to market.

Great. Yigal, great to see you, and thanks for your great science-based coverage in the space. We need it today. I'm Marshall Fordyce. I'm the Founder and CEO of Vera. I am a physician by background. We're incredibly excited to bring Vera to the stage. We have now read out Phase III data that are both positive and very compelling in a new category creating area of kidney medicine in glomerulonephritis, specifically IgA nephropathy. We had Phase III data that was shared at the opening plenary session of the ASN or American Society of Nephrology, the biggest kidney meeting of the year last month. We had concomitant publication in the New England Journal of Medicine, and we submitted our BLA filing on November 7. So the timing of the review of that in the cardiorenal division is 2 months plus 6 months. So we have breakthrough designation. We expect to hear about a PDUFA date in early January, which would time a potential PDUFA date in July.

This is a very serious unmet need that we have been approaching with atacicept, our lead product candidate. The patient population in IgA nephropathy, also called IgAN is about 160,000 biopsy confirmed cases in the United States. All of them are at risk for progression to end-stage kidney disease. End stage kidney disease means your kidneys don't work and you need to be hooked up to a machine for dialysis or you need a transplant and the 5-year mortality of people with ESKD is on par with cancer. Is a terrible outcome for patients and in IgAN patients happens early. It happens on average at the age of 35 years old, and you can look at the baseline characteristics of our late-stage trials and others.

Vera is in a position to be the leader in this space. We have the longest efficacy data. We have 2-year kidney function data by estimated GFR, which is now published in both Jason and the New England Journal medicine from our 2-year extension study in Phase II. We are the only program to be approaching an auto-injector at launch next year. So a small volume auto-injector. And there have been other programs that have approached trying to solve this problem, but none have had the efficacy, placebo-like safety and patient convenience profile that we're coming to market with.

So it's an incredibly exciting time for Vera and really for patients with glomerular disease. And I'm happy to have our Chief Medical Officer, Dr. Rob Brenner, who's been a multi-decade nephrologist, I think has built the best nephrology talent within the industry within Vera, and we're excited to have the groundswell of interest in atacicept that we've created.

I love to hear your perspectives on the data and what it means for patients?

Yes. It's a very exciting time in nephrology and in particular, for those who care for patients with glomerular disease. The development cascade that's unfolded in IgA nephropathy is truly remarkable. And on the heels of the most recent Kidney Week, the annual meeting of the American Society of Nephrology, there was kind of palpable excitement about where we are as a field. Not just within IgAN but even more broadly, with IgAN exemplifying the kind of progress we can make when we harness the power of new scientific learnings with great new therapeutics and an integrated focused effort by industry, the academic community, the societies and regulators to advance for patients that we collectively serve.

The data we showed at ASN was a follow-on from our Phase II program. In Phase II, we had a 96-week experience where we looked at the impact of atacicept on patients who had a biopsy-proven kidney disease and showed that for the very first time in the history of drug development in nephrology that patients with this biopsy-proven kidney disease could have a GFR profile, a measure of their kidney function. That's the same as a healthy 40-year-old. It was a remarkable achievement. And we piggybacked upon that with our Phase III experience, which we've now shared where we looked at proteinuria. We looked at resolution of hematuria, a marker of inflammation, and we looked at a reduction in the autoantigen, which drives the immune complex formation of this disease and showed that we had a huge impact. That was done at the same time with a safety profile where atacicept looks similar to placebo. This is a drug that is modulating the immune system by acting on B cells, but we don't see any evidence of opportunistic infection.

We don't see an imbalance of infections overall between active and placebo, and we see a profile that looks very similar to patients who are getting the injection of placebo and not the drug commensurate with the potential for it to be a chronic therapy. So we integrate the safety profile, the efficacy profile and that is underpinned by a very palatable presentation, which is a small 1 mL volume administered in an auto-injector at home by patients once a week. We think the future has never looked brighter for patients with IgA nephropathy.

Tell us -- love to talk about all those things, the efficacy, the safety, but start with the safety. So what is it about the drug that is -- because when you talk about B-cell suppression curves and you think about Rituxan and other things like that, you start to worry about the things you highlighted, what's different?

It's a great question, Yigal. And I think the first thing is to recognize that for decades, both within nephrology but in medicine, the tools we've had at our disposal to treat patients who have autoimmunity or who are inflamed are blunt instruments. Whether we're thinking about corticosteroids or B-cell depleting agents, they're kind of a one size fits all. B-cell modulation as exemplified for the first time by atacicept is a new category of drugs. And we recognize that B cells are the target cell of interest in a disease that is characterized by immune complex formation. Why is it the B cell is so important? Because both the autoantigen and the auto antibody that come together to form pathogenic immune complex are derived by B cells and plasma cells. So we want to intervene just on that 1 cell.

Is there a way to do that gently. And the answer is that there are 2 cytokines that fuel the activity of B cells. One is called BAFF, the other is called April. And nature has created a receptor called TACI, which binds both BAFF and April, these 2 cytokines with picomolar binding affinity. And in the era of modern biotechnology, we can create a rationally designed therapeutic agent. We can take that binding affinity from the extracellular binding domain of that receptor, fuse it to an activated Fc. And now we've got a soluble receptor with a 35-day half-life that reduces the circulating levels of BAFF and April and decreases the activity of B cells, just like walking over to that wall and turning down the thermostat.

We can do that without creating an environment where there's frank immunosuppression or patients who are at risk for opportunistic infections. That's what's novel, combination of amazing efficacy unimpacted by the overhang of a safety profile and adverse experiences that lead to the ability to only treat on a transient basis and in those patients who are treated to have to manage them differently. It's a new era for autoimmunity and it's absolutely a new paradigm for patients with IgA-mediated disease.

Yes, I'd like to add a little to that, which is an example during the time of COVID-19 with a highly virulent airborne virus, patients who, for their underlying illness took high-dose steroids or Rituxan were at higher risk of severe COVID and death. So we have now significant experience with that medically. We ran our Phase II trial of atacicept 150 weekly in the time of COVID and saw no difference in the rates of COVID positivity or severity. This is a really different profile than when you think of other immunomodulatory agents where you might see an imbalance of an opportune infection like zoster. So this is really a truly different type of safety profile than what we've seen with other immune-directed therapies.

And then, of course, on efficacy, just to keep it really simple. If I'm an IgAN patient and I walk into the clinic and the physician says, you're losing whatever x units of GFR per year, and now they have this drug, which is about to be on the market in short order, what will -- how will they present the efficacy picture. We'll just talk about it as a patient would understand what the benefit would be in terms of slowing the GFR decline or saying to them you don't need to worry about ESRD or X years or you stay on the drug. It's just out of -- it's not a risk that you need to be concerned about.

Yes, I think you summarized it. So let me provide a little bit more. Patients are identified as having IgA nephropathy because they have a kidney biopsy. That means they presented to the health care system. They've identified as having one or more of 3 findings. They can have blood in their urine, protein in their urine or their measure of kidney function or GFR can be below normal. At some point, they'll make it to a nephrologist. And the nephrologist, the only way I can find out exactly what's causing your problem is to get a sample of the kidney tissue from a biopsy. So they'll go to the biopsy suite, and a few days later, the diagnosis will come back, you have IgA nephropathy.

At that point, physicians who are educated in this disease will know that, while historically, we have thought of this as a slowly progressive disease and one that doesn't rise to the top of our focus because it progresses slowly. It turns out that based on more recent data from the United Kingdom, we see that patients' lifetime risk of needing dialysis or a transplant is extremely high, and it's particularly high if they don't achieve an annual rate of loss of kidney function of only 1%. Anything above that because they're identified young, means their lifetime risk for going on dialysis or needing a kidney graft is very high. So now we can start to look at their kidney function over time with a simple blood test.

And doctors are used to either looking at the automated lab printouts or to actually take out a piece of graft paper and plotting their creatinine over time and saying, this is the rate that you're losing. We now have a drug like atacicept in the future when it's fully approved based on GFR that has the potential to say we can now attenuate the rate of loss of GFR. And based on our Phase II experience, that impact was obvious. It was unprecedented. So that's the narrative. That's the conversation. I don't think patients really care as much about, hey, how much protein do I have in my urine or how much microscopic blood do I have in my urine.

What patients want to know is, am I going to need to go on that machine? Do I need to find a donor for a kidney transplant? Or am I going to go onto dialysis or how am I going to stay alive with kidney failure. The hope is with drugs like atacicept that we're going to have an ability to change the outcome for patients. And when we talk to the IgAN Foundation, the patient societies, I think what they see in atacicept and other drugs like it is the opportunity to have hope that they can live with their disease chronically and not have the overhang of the potential for renal replacement therapy as a future of their health care.

Have you sort of modeled or characterized the data in terms of the reduced risk of ESRD. Have you -- is it presentable that way or modelable that way? Or are there long-term studies that will give you that answer more concretely?

Yes, to all of the above. So Vera is taking a lead in capturing long-term data for patients who are treated with atacicept. Our Phase II program went out for a long period of time. And a year ago, we initiated what we call ORIGIN Extend, which is a long-term open-label program that someone can move into after they complete any one of our previous trials, and we will keep them on study drug until the drug is approved in the region in which they reside. This will create ample opportunity for us to do long-term assessment of the impact of the drug.

In addition, the community in general is very attuned to the lifetime risk of kidney failure in patients with IgA nephropathy. And so it's a straightforward exercise to think about if you can really change the trajectory of their eGFR slope decline to one that is losing, let's say, in the neighborhood of 5 to 8 ml per minute per year to one where they're only losing, let's say, 1 ml per minute per year over 10 years, that impact is extraordinary. And you don't have to be a sophisticated mathematician to understand that the difference between losing, let's say, 50 mls per minute over 5 to 10 years versus 5 mls per minute over that amount of time is enough to keep you off the machine.

Of course, it's a competitive space, which is a good thing because there's a lot of interest, so there are other drugs out there. How do you think about your drug with respect to the players that are already on the market that have different mechanisms. Just kind of talk about how nephrologists are seeing potential implementation as a potentially foundational therapy, disease-modifying potentially foundational therapy.

Yes. Happy to start here. So there are 5 drugs approved in this space in IGA nephropathy, only one of them has had an approach that targets the B cell signal. So there's an April only approach that was just approved last week. And when we look at the comparison, I think consistent with what Rob said, we have the only ones with 2-year GFR data. So I think that will be interesting to see if even the currently approved drug that targets April only has an ability to stabilize GFR over long term. We've seen some neutralizing antidrug antibodies in that program that has an effect on efficacy that's in the label. So that was notable. But what's important about that label is that it's for patients at risk of progression in kidney disease, and that hasn't been seen before.

So really, 2 updates really in the last few days have been one, that's a significantly broader label for the first program in the B cell modulator space into the pricing is at a relative premium to 3 out of the other 4 drugs. So I think there's a broad recognition that an ability to target B cells and extend time off end stage kidney disease is extremely. So very helpful. I agree with you Yigal. This is a great time for patients because there are multiple programs coming to market and very promising profiles as the second B-cell modulator on track to get to market, the first with the dual BAFF/April inhibition mechanism, the first with an auto-injector, these are really important differentiating factors for us. We think this is going to be great for patients.

So let's switch a little to some of the commercial. So obviously, you've been planning for this for many, many years, planning for success. Well, a few things. So talk just about the commercial strategy, who you're hiring all the basic sort of blocking and tackling there. Are you -- and you say are you going to launch with the auto-injector? Or that's going to be kind of like fast right soon after the launch, just talk a little more detail there. And then some questions on -- just on the regulatory. We saw with another company, they had -- their AdCom was canceled for FSGS. Do you expect an AdCom or not. What's the pulse from cardiorenal.

Great. Happy to go backwards here. So we don't expect an advisory committee. We are expecting to launch with an auto-injector. We have high confidence in that given all of our work as well as our interaction with FDA. So we are a breakthrough designation program, and so we do have frequent contact with FDA around those topics. Commercially, we're ahead of the curve in terms of ready to launch in the U.S. We've had a core of commercial leadership at the company now for multiple years preparing for this. More than a year ago, we brought in significant commercial leadership. DJ Johnson is our Chief Operating Officer, former Chief Commercial Officer at Global Blood; Matt Skelton, who has launched renal drugs at Amgen with Rob previously and then was at Seagen before leading our U.S. commercial effort.

He's really built each of the verticals, commercial operations, marketing, value and access and more recently with our Phase III readout, we have national sales leadership in place and regional leadership in place for sales as well. We've sized and structured our sales force. They're going to be in their seats in the new year. And it's an incredibly exciting time at this point with the type of profile we have and the groundswell that we've created around awareness of the disease state, the urgency to treat, the promise of atacicept as the first BAFF/April inhibitor and with the type of profile that we've been sharing in the peer-reviewed publication space and at ASN this year, there's a lot of awareness, a lot of excitement for this drug.

What about guidelines? Is that -- how is that going?

Yes. The guideline process in nephrology is led by an organization called KDIGO, and the guidelines get updated as new drugs come to market. We're still evolving the pace with which that occurs in clinical nephrology, but there is a broad recognition amongst leadership in the academic community and the guideline authors about what new drugs are poised to come over the course of the next few months. And I think there's a very strong motivation on the part of those authors to try and have the guidelines that come from KDIGO to be as relevant and as timely as possible as quickly as possible after those new drugs are approved.

So we look forward to participating in those -- in that process. And I think the future will have physicians to be able to have a resource both from KDIGO and then from other sources that will help contextualize the development of the new drugs, so they can figure out how to implement that into the day-to-day care practice that they have.

And once you have good synergy there? Because I mean, if I just do the math, like you're going to get approved in, I guess, July or potentially, and then KDIGO, they're doing the update in the fall period, no. So won't you benefit from that -- having that inclusion certainly after the launch?

We will. And I know the motivation on the part of leadership at KDIGO is to tailor key updates to when they are impactful new approvals to drive a reassessment of how to provide guidance.

Okay. So IgAN is the tip of the spear, but there's more. So maybe we can expand a little bit on some of the other nephrotic diseases where there's applicability of this tool, BAFF/April mechanism and where you are in development with those?

Yigal, I would go broader than that and say this is really a novel paradigm for treating autoimmune disease generally, which we would say currently sits with steroids and other immunosuppressive approaches the safety profile that we've been spending time describing really could be applied well beyond nephrology. But Vera's corporate strategy is to begin with IgAN and move to additional adjacent glomerular diseases like membranous nephropathy, FSGS, minimal change disease that are driven by autoantibodies, but atacicept has experience reducing autoantibodies in a variety of diseases even outside of renal disease. So Rob can speak to our current trials ongoing within renal, but the potential certainly is much broader. If you take a survey of autoimmune disease where there is evidence of elevated BAFF or April or both, there's quite a broad set.

If you look at clinical regulatory pathways and assess feasibility, there are quite a lot of approaches and then where we see the emerging profile that we now have in a reproducible both Phase II and Phase III that really gives us broad optionality. And we don't like to say we can boil the ocean here. We would probably define and haven't fully disclosed each one of these, but we've defined about 11 different indications outside of nephrology where the atacicept 150 weekly profile is likely to generate very significant improvement in clinical outcomes, and we're bullish about that. But the corporate strategy is to build first in renal and make sure that we are the leader in that space and then expand from there. Rob, maybe you want to speak to just the PIONEER study.

Yes. In October of last year, we had a Research and Development Day where we came forward and shared with the community, our plans to move beyond the ORIGIN program to secure registration for atacicept in this disease. And the first thing that we realized was on the underpinnings of this incredible Phase II data package that it made sense for us as a -- from a corporate decision-making process to pull forward our spend, to learn about the use of atacicept in sort of all comers with IgA mediated disease and not only to look at patients who would meet Phase II, Phase III enrollment criteria.

That program is called PIONEER and there are 6 cohorts of broader IgA nephropathy that are captured in that. Patients with very low proteinuria, patients with very high proteinuria, lower GFR, pediatric patients, patients who have concomitant vasculitis along with their kidney involvement and the unfortunate patient who's had a kidney transplant and now has recurrent IgA nephropathy. All of those patients would have been excluded from traditional registrational activities prior to first approval. So Vera is the only sponsor that said, let's go ahead and study those patients now.

Can I just ask to clarify, is that -- does that -- what you say there, is that beyond the 160,000 biopsy proven or within it?

It's to get to probably 50% of that 160,000 would be excluded because of who we studied to date. So it's to get to that full 160 if you will. But we know that the same investigators who are caring for patients with IgA mediated disease are caring for other forms of autoimmune kidney disease. Among those are membranous nephropathy particularly those patients who have an auto antibody to an antigen in the kidney called PLA2R, so they have anti-PLA2R antibodies. In addition, there are patients who have forms of focal segmental glomerulosclerosis, or FSGS, along with minimal change disease who have an auto antibody to another glomerular antigen called nephrin. They have antinephrine antibodies.

The thesis is that atacicept by reducing the production of antibodies will reduce the production of the auto antibodies to these kidney-specific antigens and could be a game-changing intervention in patients with membranous, FSGS and minimal change disease. Those patients are also included in other cohorts within the PIONEER protocol umbrella, and we're studying them now. And amongst those, we're particularly keen on membranous nephropathy and think that that's a really great opportunity for future registrational work with the drug.

And the reasoning behind that is because of competitive reasons? Or you believe there's a higher probability of success? Or is there something about membranous nephropathy that presents an easier path forward?

We can identify those patients. There's a big unmet medical need. We have an assay that's available to measure the antibodies that are binding to the kidney antigen. We've got proof of principle not just for other sponsors work but because we're conducting our own Phase II experiment, and we think there's a path forward for registration. So for all those reasons, we like membranous nephropathy, a lot as an area where atacicept has the potential to be an unlock for clinical benefit.

So you're going to read this out. When is it reading out by the way?

So we started enrolling patients this year, and our plan is to start to share data publicly as we get to the next series of academic congresses in the first half of 2026.

So we'll see the results across this broader set and then you'll determine -- I mean you have a favorite, it sounds like, but you'll look at the data and determine which one or one or more of those would go into Phase III?

Yes. I would say we're able to do a lot of that work in parallel. And what I would hope to do is come forward and say, here are some results that we've learned. And when the time is right, we'll be able to articulate what our plan is for the next series of development activities.

Okay. Tell us a little bit -- there's more in the pipeline, right? You have a few other assets. So can you maybe enumerate some of those?

We do. So the first thing I will say before we get even to the new assets is one of the other things that we initiated this year was a dose range finding study, looking at 3 different potential monthly doses of atacicept compared to weekly administration with 150 milligrams. And we expect to have early data from that monthly program also in 2026. And if we find a dose that we think is the right dose to carry forward for label investigation activities, we'll be able to articulate what the plan is to secure label claims for monthly dosing. That was also part of our activity at the end of last year, which we announced at JPMorgan of this year, which was the acquisition of VT-109 from Stanford.

So atacicept is an Fc fusion protein that utilizes the extracellular binding domain of the TACI receptor. But there's another receptor on the surface of B cells and plasma cells that binds BAFF and APRIL, and it's called BCMA. And through our work with Stanford, we've now gained access to a molecule that has been engineered to have very high affinity for both BAFF and APRIL. And from the get-go, the Vera team has been focused on trying to deliver against a target product profile that would have a very differentiated profile versus what we have with atacicept or other drugs that are currently in development by other sponsors. The next catalyst for that program is filing of an IND, and we look forward to that as the next step as we move forward with that molecule.

Is the therapeutic hypothesis different there? Just are they same or just...

Same therapeutic hypothesis, but we're looking at a very different dosing algorithm. And I think it would be phenomenal if we could complement atacicept with a molecule that could be dosed, let's say, once a quarter.

Okay. And then just kind of the usual questions around the cash spend and the time lines to -- I don't know if you probably haven't talked about this yet, like P&L dynamics and things like that.

Yes, we're very well resourced ending the year in the range of $400 million to $500 million and have access to an additional $500 million through our facility with Oxford. So we have roughly $1 billion access as we get into next year for a first launch year. Having provided specific guidance beyond that, but we're well capitalized to launch this drug next year.

And when you think about executing on the launch and being very successful and front footed, what are the key things that you just maybe lessons learned from some of the prior launches you've obviously watched very closely to make sure that you execute most effectively and getting the message exactly right to nephrology community.

Yes. Great question. The Vera team leadership, both within commercial and beyond have held leadership positions in multiple blockbuster drugs so -- in those launches. And so I think we have a lot of cumulative experience going into this launch. Drug launches are dynamic. They're different now than they were even a few years ago. And so this is a very front-footed group, and we're watching all of that and making full use of that information to make a very successful launch next year.

What -- do you have details in terms of like the Medicare versus commercial and the split of the market and how you're going to support all those segments of the payer landscape?

Yes. We know this market very well at this stage. We've been preparing this for some time. I can share some insights, I won't share them all. But these are young patients. So it's about a 75% private commercial pay population. These are patients who are seen by a wide variety of the roughly 8,000 nephrologists in the United States. There aren't deeply established centers of excellence. These are distributed in terms of the caregivers for these patients. There's a lot of detail to this population in this market that we understand. We are working on for some time. We have a very clear strategy to win in the space.

And you would expect that patients that may be on another modality would be available to atacicept, right? I mean just because they're on another mechanism doesn't exclude them in any way.

Yes. I mean this is...

Just so we're clear on that.

What we would say is we would project a future prescription for IgA nephropathy to be grounded on using a B-cell modulator to turn off pathogenic immune complex and have an impact across all the measures that are relevant for this disease. It wouldn't make sense to use a steroid on top of atacicept given the mechanism of action, nor do I think there would be much need for a complement inhibitor. In contrast, I think using drugs that we would say are good for CKD hygiene in general, ACE inhibitors, angiotensin receptor antagonist, SGLT2 inhibitors may be very reasonable to use. And in our own development program, everybody was on an ACE or an ARB and in the Phase III half the patients were on an SGLT2.

Now we also have endothelin receptor antagonist approved and I think that would be fine to use if someone wanted to substitute one of those instead of an ARB or an ACE inhibitor. So if I would project a future prescription, I think it would have a B-cell modulator as the cornerstone therapy and it will be complemented with an ACE, ARB, ERA and/or an SGLT2 inhibitor.

And have you pressure tested those assumptions with payers in terms of dual coverage of both of those mechanisms? That's more than feasible approach?

We certainly share this concept. And they've asked us where do we think the prescription patterns are going to evolve to, and this is very consistent with the narrative that we shared.

Excellent. All right. Well, thank you so much. Appreciate it. Super interesting. Good luck with getting the PDUFA date, which is soon. And we'll pay very close attention.

Thanks so much, Yigal. Thanks for the time.

You're welcome.

Good afternoon, and welcome to the Vera Therapeutics Investor Call and Webcast. [Operator Instructions] As a reminder, this call is being recorded, and a replay will be made available on the Vera website following the conclusion of the event.

I'd now like to turn the call over to Marshall Fordyce, Founder and Chief Executive Officer of Vera Therapeutics. Please go ahead, Marshall.

Thank you, and welcome. I'm Dr. Marshall Fordyce, Founder and CEO of Vera. And on behalf of the entire Vera team, I'm thrilled today to share with you the interim results of the ORIGIN Phase III trial of atacicept for the treatment of adults with IgA Nephropathy. I'm speaking to you from Houston, Texas, where the Annual Meeting of the American Society of Nephrology, or ASN, is hosting its Kidney Week. ASN is the largest association of nephrologists in the world.

Our data were presented this morning by Dr. Richard Lafayette, Professor of Medicine and Nephrology at Stanford, and Director of the Glomerular Disease Center at this morning's opening plenary session with thousands in attendance and standing room only. These pivotal trial results were also published today in the New England Journal of Medicine.

On this call, after my introductory remarks, you will hear from Dr. Richard Lafayette, who will take you through the data. Next, you'll hear from Matt Skelton, our Executive Vice President of Commercial, who will share with you some highlights of how we see the market landscape and the potential of atacicept to make a meaningful difference in the lives of patients with IgAN and beyond. Then you'll hear from our Chief Medical Officer, Dr. Robert Brenner, regarding Vera's expanding pipeline and broad potential in multiple large markets.

Finally, there will be an opportunity for Q&A with this group as well as Dr. Jonathan Barratt, who leads the Renal Research Group at the University of Leicester in the United Kingdom. Doctors Lafayette and Barratt co-chair the Steering Committee for our Phase III ORIGIN study, and I'm extremely grateful to you both for your guidance and collaboration with Vera. Next slide, please.

Before we get started, I want to remind you that my remarks contain forward-looking statements under the Safe Harbor Act. And as such, we present this disclaimer regarding at-risk statements. Next slide, please.

Today marks an important milestone in Vera's history as we progress the development of atacicept, a potential first-in-class mechanism, dual BAFF/APRIL inhibitor to transform treatment of autoimmune diseases. Atacicept is foundational to driving Vera's bold growth trajectory.

Vera's mission is to change standard of care for patients with autoimmune disease from one based on steroids and the depletion of B-cells to a more targeted modulation of the immune system and free patients from the burdens of their disease. Vera is poised for a potential commercial launch of atacicept in 2026 and to pursue development and additional indications in other autoimmune kidney diseases and beyond. Next slide, please.

Vera has rapidly made progress towards its objectives in 2025 and is on track for our near-term catalysts in 2026. Following our Phase III full enrollment and primary endpoint readout earlier this year, we're on track to file our BLA this quarter, enabling potential U.S. commercial launch in mid-2026. Our additional clinical trials of atacicept in the Extend trial and the PIONEER trial in additional IgAN cohorts and in other autoimmune kidney diseases are enrolling well, and we'll be sharing initial clinical trial results in the near future. Next slide.

Vera today is in a strong position financially with pro forma cash of $497 million and 63.9 million shares outstanding. We also have access to an additional $425 million in nondilutive capital through our Oxford facility, which we expect to be sufficient to fund through multiple catalysts, including approval and launch. Next slide, please.

Atacicept's mechanism of dual BAFF/APRIL inhibition has broad therapeutic potential for certain autoimmune diseases, which are substantially driven by abnormal B-cell function. Atacicept inhibits the 2 known cytokines circulating called BAFF and APRIL, which are both important for the survival and maturation of B-cell lineage. Elevation of both BAFF and APRIL are found in patients with IgAN, lupus and other autoimmune diseases and both play a role in disease pathophysiology, driving autoantibody production and damage to the body. Next slide, please.

Patients with IgAN currently face a very challenging path ahead. On average, people with IgAN are young, 35 years old of age. And among those at high risk, rapid kidney function decline leads to end-stage kidney disease or ESKD before 50 years old. ESKD means your kidneys don't function and you need dialysis or a kidney transplant, dramatically altering lives and those of patients' families. The severity of ESKD is often underestimated. And as seen here, mortality over 5 years from this diagnosis is similar to cancer.

Through rigorous clinical science, we at Vera aim to demonstrate that the inhibition of immune complex formation in IgAN through BAFF and APRIL inhibition offers the potential for these patients to avoid kidney failure over their lifetime. I'm proud to represent the Vera team and the progress we've made toward unlocking the pipeline and the product potential of atacicept. It's my great pleasure to share with you the results of our pivotal Phase III trial, and I'd like to introduce Dr. Richard Lafayette, who will take you through the data. Dr. Lafayette?

Good afternoon. It's a great pleasure to be with you. It was great to present the data this morning. And hopefully, I can see my first slide to take you quickly through this presentation. That's just who I am.

And on the next slide, Marshall already gave you a beautiful background that IgA Nephropathy is the most common primary glomerular disease throughout the world, estimated incidents of about 2.5 cases for every 100,000 individuals, but we feel that's underestimated given the need to diagnose this by biopsy and that there's way too often very late presentations where patients go immediately into advanced chronic kidney disease care or dialysis.

As already mentioned, this is a of young people in the prime of their lives trying to start families and live their lives. But unfortunately, while this was previously thought to be a relatively benign diagnosis, people like Jon Barratt here and many other registries have really shown that patients are really facing a 50% risk of losing their kidney function or dying within 10 years or slightly longer at diagnosis.

This has led the international guideline organization to suggest we get much more aggressive with these patients, really control their proteinuria. But most importantly, we need to try to achieve disease progression rates in terms of losing kidney function or estimated GFR at a rate of less than 1% or less than 1 ml per minute, per year, which is similar to adults with healthy kidneys. Thus, there's still this great need for a disease-modifying therapy that can truly stabilize kidney function in a safe, well-tolerated manner. Next slide.

Again, as alluded to, we now have more and more evidence that IgA Nephropathy itself is a B-cell-mediated disease that causes kidney pathology. And as you heard these terms back in April, are cytokines that have receptors on B-cell, predominantly TACI and can stimulate B-cells to mature, to survive as plasma cells and be long-lived producers of antibodies.

And in IgA Nephropathy, that leads to the production of galactose-deficient IgA1 and also to autoantibodies against that galactose-deficient IgA1, which together can form immune complexes. It is those immune complexes that we see in kidney biopsy within the kidney that are felt to drive the inflammation as a response to that immune activation in the kidney and lead to hematuria, proteinuria and eventually scarring of the kidney such that they lose their function. Next slide.

Thus as introduced already, atacicept as a rationally designed fusion protein consisting of that TACI protein, which is very potent in binding both APRIL and BAFF with picomolar potency can therefore, stop the B-cell activation in turn reducing galactose-deficient IgA1 and the autoantibodies and immune complex, reducing inflammation, reducing hematuria, proteinuria and protecting the kidney from progressive injury and loss of function. This agent can be given at home in a 1 ml shot weekly in a well-tolerated fashion. Next slide.

And we have history with this agent through its development and in the Phase II study, as you likely know, 3 different doses of atacicept were compared to placebo in a 36-week randomized trial for patients at high-risk progression, adults with biopsy-proven IgA Nephropathy, who had more than 0.75 grams per gram of proteinuria, GFR over 30 and well-controlled blood pressure on maximally tolerated RAAS inhibitors with the primary endpoint being the efficacy in terms of proteinuria reduction, but all patients were offered rollover to atacicept at 150 milligrams each week at home for an additional 60 weeks. Next slide.

And as we would hope that our clinical desire for effective interventions in IgA Nephropathy and the one now endorsed by the 2025 KDIGO guidelines suggest we really have a need to reduce immune complexes here assessed by galactose-deficient IgA1 that we would like to resolve the inflammation, perhaps assessed by glomerular hematuria. We need to reduce proteinuria as that's our most potent predictor of progressive kidney injury and in turn, stabilize eGFR progression rates similar to people without kidney disease.

And in the next slide, you, of course, know that in the Phase IIb program, this was nicely achieved with a safe 2/3 reduction in galactose-deficient IgA1 with resolution of hematuria for those patients at baseline who had blood in the urine of nearly 80%, a reduction in proteinuria exceeding 52% through that 96-week period and change in kidney function of less than 1 ml per minute, per year at 0.6 ml per minute, year slope, again, achieving similar rates of decline as would be seen in healthy patients and done without significant side effect burden compared to the placebo patients. Next slide?

So the Phase III trial design went forward as a similar design to the Phase II study, same worldwide sites as a randomized global placebo-controlled trial comparing placebo to that atacicept 150-milligram subcutaneous weekly given at home and similar population of adults with biopsy-proven IgA Nephropathy on stable RAAS inhibitors and/or SGLT2 inhibitors as in the prior study. They had to have a urine protein greater than 1 gram or greater than 1 gram per gram and eGFR greater than 30, again, with well-controlled blood pressure. And again, primary goal was to look at proteinuria change here at week 36. Next slide.

And 750 patients were screened to have 431 patients randomized, 428 of those were treated. This analysis includes 214 atacicept and 214 placebo patients for the safety analysis, but the prespecified interim analysis occurred when there's 106 atacicept patients and 97 placebo patients reaching week 36, and there was wonderful retention, in fact, better in the atacicept group than in placebo patients. Next slide.

And the demographics of these patients were very similar to the Phase IIb study and similar to global trials of patients at high risk of progression with IgA Nephropathy. These are young patients averaging 40 years, slight male predominance, slight Asian predominance, but excellent mix of racial background, eGFR showing that they've already suffered some decline in their kidney function, averaging 65 ml per minute, substantial proteinuria at baseline at around 1.8 grams per gram, signaling a daily protein discretion well in excess of 2 grams per day.

And these patients had relatively fresh disease diagnosed on average 2.5 years earlier than the study, but with a broad distribution. And the main difference between the IIb study and ORIGIN III is that as per clinical practice, now more than half of the patients are treated with SGLT2 inhibitors along with their RAAS inhibitors, while just a few years ago, only 14% were. Next slide.

And here, you can see, again, the very substantial success in reducing proteinuria that was achieved with atacicept, where there's ongoing interval by interval reduction in proteinuria that has not yet plateaued, reaching 46% at 36 weeks. At that point, there was a 7% reduction among placebo patients. So the modeled net difference between active treatment and placebo becomes 42%, again, highly statistically significant and very clinically meaningful in predicting a benefit to kidney function. Next slide.

Importantly, this benefit in reducing proteinuria was seen in all prespecified subgroups. So whether you're older or younger; male, female; from Asia or otherwise; white or not white, have higher or lower proteinuria; higher or lower GFR or whether or not you were treated with SGLT2 inhibitors, patients still enjoyed that 40% to 50% reduction in proteinuria. Next slide.

And again, biomarkers demonstrate that the galactose-deficient IgA1 was similarly reduced. Here, we've seen about a 68% reduction at 36 week with no change in placebo patients. And again, among patients with blood in the urine at baseline, there was an 80% resolution, 20x greater than what was seen in patients just on their background therapy. Again, eGFR is not disclosed for this data for regulatory recommendations. And so that's a difference that we don't have the confirmation that we had in Phase IIb yet. But as you know, the study continues on awaiting its 2-year GFR data. Next slide.

Again, importantly, adverse events are generally balanced between atacicept and placebo patients. This is the full safety population, so now 428 patients. You can see overall adverse events are similar. In fact, the serious adverse events are numerically lower in patients who were assigned atacicept and received atacicept therapy. Drug discontinuation was also numerically lower in patients receiving atacicept. When we look at infections infestations, there's really no difference in the overall number and all the serious and severe infections occurred among placebo patients.

There's no opportunistic infections and any imbalance in adverse events is really attributable to differences in injection site reactions, which, again, are mild to moderate and did not cause patients to leave the study. No discontinuations. What was called hypersensitivity reactions actually was more common among placebo patients. And again, fortunately, there's no deaths in the study. And there was no hypogammaglobulinemia seen in this study to date. Next slide.

So in sum -- again, IgA Nephropathy is a B-cell disorder causing kidney pathology. BAFF and APRIL are 2 key cytokines that drive B-cells to make autoantibodies to lead to this pathology. Atacicept has been rationally designed as a native human TACI-Fc fusion protein to bind BAFF and APRIL and to modulate B-cell effect, again, with picomolar affinity, once weekly dosing. The Phase IIb study demonstrated reductions in galactose-deficient IgA1 hematuria, proteinuria and wonderful stabilization of kidney function as measured by eGFR.

Now we have the 36 week results from Phase III, again, showing numerically even better proteinuria reduction, reduction in galactose-deficient IgA, resolution of hematuria, proteinuria reduction across all the subgroups of patients and safety at least comparable to placebo without any evidence of serious, severe opportunistic infections and without immunosuppression, again, setting up this intervention, this agent as a very viable option for long-term delivery to our patients who very much need therapy to stabilize their kidney function.

So thank you very much.

Thank you, Dr. Lafayette. Next slide, please. I'll note again that these results were also published online at the New England Journal of Medicine, and I appreciate Dr. Lafayette, your leadership and guidance.

Next slide, please. I'd next like to introduce Matt Skelton, our Executive Vice President of Commercial here at Vera Therapeutics. Matt, thanks so much for your time.

Thanks, Marshall. Hey, I'm pleased to update you on the progress we have made in commercial and our view on the opportunity before us. I want to start off with first with an update on some building out of the team. Vera's sales leadership team is hired. We attracted top talent. Leading the West region is the former national leader of Amgen's nephrology sales force and leading the East is the former East region sales leader for Calliditas, a company in the IgAN space. They have hired their sales management team. And soon, we will build out the sales force, and they will be in territory well before our anticipated approval.

Here's the opportunity before us. There is a large prevalent pool of 160,000 patients in the U.S., of which 90,000 are addressable. This is the Phase III population. We are confident we can compete for meaningful share in this population. And as the data continues to emerge with atacicept, we hope to eventually expand into moderate and lower-risk patients. This is a market with lots of growth potential. Next slide.

Here, these findings are from a third-party survey conducted with 100 nephrologists. We are very pleased to see the strong ranking for atacicept amongst other pipeline assets. I will focus you on the dark blue section of the graph. Here, you see a clear preference for atacicept as the most desired pipeline product in IgAN. With results presented at the plenary session this morning, this high level of anticipation will likely increase. Next slide.

We've been conducting our own market research. The atacicept product profile is compelling to nephrologists. The Phase IIb long-term eGFR data resonates the most, followed by the dual inhibition, MoA and disease-modifying therapy. Another important attribute is the patient-friendly presentation. At-home administration with an auto-injector and a low 1 ml injection volume led to over 90% patient retention in the trials. Next slide.

To further the point, we are a good company with leading injectable biologics. A weekly self-administered low-volume injection with an auto-injector is a very familiar presentation to patients and physicians. Next slide.

Here's the existing market. Innovation in the IgAN space is allowing for premium pricing. FABHALTA is a clear outlier, but remember, it was initially approved for PNH. The strength of our data and the promise of the long-term eGFR data from Phase IIb gives us plenty of headroom when we consider pricing. Next slide.

I'll conclude with this slide. The market and the product are attractive. It is a large and growing market with unmet need. Nephrologists are hungry for innovation. The payer mix is mostly commercial. Remember that patients are usually diagnosed in their 30s. We are excited about the atacicept profile. Nephrologists are excited about the profile. I'm confident we can gain significant market share with these results.

And with that, I will now hand off to Dr. Brenner, Chief Medical Officer at Vera.

Yes. Thank you, Matt. I want to begin echoing Marshall's comments from earlier, and I want to congratulate Dr. Lafayette and Jon for their leadership with the ORIGIN III program. For those people who were fortunate enough to be in the plenary session this morning, I think the energy in the room was palpable. And in many ways, the meeting that's going on in Houston this week is an example of a transition point for clinical nephrology and for us to have greater optimism in the future therapeutic strategies that we'll be able to deploy for the patients that we collectively serve.

As we think about where we're focused with atacicept, we have been absolutely focused with the ORIGIN III program, the data readout this summer and into the fall. And with the program that we began earlier this year called PIONEER, which is allowing us to expand into a really broad population of patients who suffer from IgA-mediated disease. but also to start looking at other forms of autoimmune kidney disease where autoantibodies are binding to not only circulating autoantigens like galactose-deficient IgA1, but they're also binding to glomerular antigens like nephrin and PLA2R.

So the program that we have designed and are executing that includes both ORIGIN, ORIGIN Extend and PIONEER allows Vera to be in a leading position to study all comers with IgA-mediated disease as well as patients who have other forms of autoimmune glomerular disease. That said, we also are very motivated to think about the long-term proposition of impacting other forms of autoimmune disease that exists outside of the discipline of kidney medicine.

And we've talked in the past about our focus on diseases that are cared for -- for patients who are cared for by rheumatologists, hematologists, neurologists, et cetera, where we think the long-term opportunity for B-cell modulation to be transformative for patients is great. But in the near term, our focus is on the IgA opportunity and in the adjacent indications that are defined by autoimmune glomerular disease. Next slide.

So a little bit more about the PIONEER study. This program got underway in the first half of the year. And it begins by looking at the reality that all of the trials that Dr. Lafayette and Dr. Barratt have been involved with have focused on a specific set of inclusion and exclusion criteria for patient enrollment. And as we looked at the relevance of the Phase II data that we read out a year ago, it gave Vera and our academic collaborators motivation to think about studying more of a broad footprint of IgA-mediated disease now and not waiting for years to elapse before we take on this daunting challenge of studying everybody.

So there are a number of cohorts of patients with IgA-mediated disease who would not be eligible for the ORIGIN program, but now have a home in the PIONEER study, where we're able to evaluate the efficacy and the safety of the drug.

Once we're in all of these sites, studying patients with IgA mediated disease, we can appreciate the same clinicians, the same study coordinators are caring for patients with other forms of autoimmune-mediated glomerular disease, namely patients with membranous nephropathy associated with anti-PLA2R antibodies and patients with both focal segmental glomerulosclerosis, and minimal change disease who have anti-nephrin autoantibodies.

And so under the basket of one large umbrella, we're able to study all of these cohorts of patients in one singular program. Enrollment continues. There's been great enthusiasm globally for participation in this trial, and I'm thrilled with the progress that we're making, and we look forward to sharing results from the study as the data set matures. Next slide.

And finally, a little bit about our pipeline. So clearly, our focus is on filing, gaining approval and launching atacicept for patients with IgA-mediated disease, IgA Nephropathy. In addition, now we're well underway to advancing our understanding of the impact of atacicept in patients with membranous nephropathy, FSGS and minimal change disease, where they have documented autoantibodies against glomerular antigens. And we think in the future, there are other opportunities within the autoimmune glomerular disease space where atacicept offers the promise of being an important therapeutic advance.

In addition, within the walls of Vera, we have MAU868, a monoclonal antibody against BK virus that has moved into Phase II clinical studies. And finally, at the beginning of this year, we announced the acquisition of VT-109 through a transaction with Stanford University, which is an alternative form of an Fc fusion protein with a high binding affinity for both BAFF and APRIL and could lend itself to a differentiated profile than what we've seen to date with other B-cell modulators that are under development. In aggregate, we think that this integrated pipeline represents really strong opportunities for value creation in the months and years to come.

And with that, I will turn it back over to the moderator.

[Operator Instructions] So our first question comes from Anupam Rama at JPMorgan.

Congrats on a great session this morning. This morning at the oral plenary, we heard a lot about combination strategies. And given the safety profile of atacicept for both the company and the KOLs on the line, how do you think about combination strategies with the product going forward in IgAN?

Dr. Brenner, why don't you begin and then we'll ask Dr. Barratt to opine.

Yes. So I think many patients as they advance through their journey as a patient come to be seen by a nephrologist after they've been recognized to have 1 or more of 3 things. They have blood in their urine, they have protein in their urine or they have a reduced measure of their GFR or an elevated creatinine. And eventually, they'll make it to a nephrologist and a decision will be made to bring them to the biopsy suite to make a tissue diagnosis.

In advance of that, it's not uncommon for patients to start on either an ACE inhibitor or an angiotensin receptor antagonist and in recent years, to even begin with concomitant SGLT2 inhibition. But the specific prescription for IgA Nephropathy would begin after a biopsy is returned and confirms that, that's what they have. My view is that in the future, when B-cell modulator like atacicept is available, it would be the drug of choice to start treating patients who now have a tissue diagnosis that confirms the disease. But there, in my mind, would not be a reason to discontinue an ACE or an ARB or an SGLT2 if it's already on board.

My personal view is that over time, based on the data that we've seen to date and the data that we'll see after the trial is complete, I think there'll be less use of corticosteroids for this disease. And I think there'll be less use of complement inhibitors in this particular disease. That's my own view, and it may not be the same view that others have. But that's really the way that I think the management of this disease is potentially poised to progress.

Jon, do you want to share your thoughts?

Yes. I mean, as a nephrologist, all I'm interested in is preserving GFR and stopping my patient from developing kidney failure. And if I -- if we replicate the data that was shown in the Phase IIb and we return the rate of loss of kidney function to that seen in a healthy individual, why would I think of a combination therapy if I can achieve it? I can't do any better. I'm not going to get the kidney function better than it is because I can't grow new nephrons. I can preserve the nephrons they have.

So I think it's interesting what Rob said because I think the data that we've seen is already combination therapy in the Phase III because the patients are on the RAAS inhibitor, half of them are on SGLT2 and clearly half of them are on atacicept. So that's already combination therapy.

I would like to see a situation where we have an early diagnosis and we start atacicept and we only come in with CKD treatment if we see a decline in kidney function because the Phase IIb data where there were far fewer patients on SGLT2 inhibitor, they still were able to return their kidney function to the physiological state. So there was no requirement to achieve that result with an SGLT2 inhibitor on board.

So for me, I think we will move to a situation, hopefully, where we have an earlier diagnosis and we treat the disease immediately with disease-modifying therapy. And we add additional therapies if we do not achieve our goal, which is to return loss of kidney function to the healthy population. And so I think the requirement for combination therapies is going to be small if we see the results of the ORIGIN IIb replicated in the Phase III. And that's my hope for patients. Why would I want them to take 5 tablets when I can achieve what I want to achieve with one injection, [ I believe. ]

Our next question comes from Pete Stavropoulos at Cantor Fitzgerald.

Marshall, Rob and Sean, congrats on the data and the publication as well. For Dr. Lafayette and Barratt, when you look at the benefit by subgroup and you sort of hone in on the eGFR greater than less than 60 ml per minute, and you see a much larger effect on proteinuria on those with greater kidney function at baseline. Why would that be the case? What does that sort of suggest to you in terms of what patients benefit? Where would the atacicept fit in the treatment paradigm, and in the backdrop of the updated KDIGO guidelines in terms of target proteinuria levels?

Yes. Thanks. I'll take first stab at that question. Again, when we do subgroup analyses, we're looking for similarity of effects. And when they're overlying error bars, we really reject the notion that there's a meaningful difference in the high GFR or low GFR group. So even though the dots may move slightly in different directions as long as those little whiskers of sort of the range of effect are overriding each other and are way away from 0, then we're pretty confident to say that there's not a meaningful difference in responsiveness among low or high GFR patients. And thus, I wouldn't really hazard speculating on why there might be a differential response because I really don't think it exists. Furthermore, this is formally tested statistically, and there really is no statistical difference between those 2 different lines.

Yes, I think what's very striking, as Richard says, is this effect is consistent across all prespecified subgroups. So there is no patient population that responds less well to atacicept based on age, sex, where they live, what race they are, what their baseline proteinuria, GFR is or whether they're taking an SGLT2 inhibitor. It's very, very clear statistically, there is absolutely no evidence of a differential effect in different patient groups from the ORIGIN III study.

Okay. And just one quick follow-up. We always look at these biomarkers, and we're looking at kidney function stabilization. But just when you speak to the patients that you've treated, sort of how do they feel being on drug before and after? Any changes in physical ailments, mental health effects when they learn the kidney function is stabilized? And any feedback on administration?

That's a really great question. And I wish we had an adequate tool to assess quality of life in IgA Nephropathy. But we don't have an adequate patient-reported outcome tool. We're working on it, but we don't have a validated reliable way of assessing that in any of the clinical trials. It's absolutely something that's important to patients. It's important to us as clinicians. I wish we had a validated tool to test that. But unfortunately, we don't at the moment.

Feedback that you get from the patients?

Yes. So what I'll just add to that, I think it would be nice to have a formal tool and really evaluate it as an investigator taking care of these patients, of course, they're blinded. So I can't really know whether they're on or off therapy.

No, Phase IIb data.

Pardon me?

On the Phase IIb.

Yes. And again, I was an investigator there and do know which patients we're taking. But even there, it's sometimes hard to sort out who's having a good week otherwise, bad week otherwise. What we can say is that looking at the overall adverse event profile, willingness to continue on the study that the fact that there is, again, less discontinuations in the atacicept group means they're feeling at least as well as those taking the placebo patients. But just sort of viewing the patients, I don't see either elation, burst of amazing energy or the reverse.

And I'd just -- I mean, Marshall has been at the patient events. The biggest challenge patients face is effects on their mental health, dealing with the uncertainty of what's going to happen to them. And if we can show from the ORIGIN IIb and it's replicated in the ORIGIN III that we can stabilize your kidney function, that will deal with one of the major impacts on their quality of life, which is that uncertainty of whether they're going to develop kidney failure or not because we can take that out of the equation by stabilizing their kidney function. And that, if you talk to IgA Nephropathy patients, and Richard and I talk to them a heck of a lot, is the major driver for what affects our day-to-day living.

Our next question comes from Gavin Clark-Gartner at Evercore.

Really great to see the positive reception to the data this morning at the conference. So for Doctors Lafayette and Barratt, I wanted to ask how you think about hypogammaglobulinemia. Do you think this is a harbinger for infections with extended treatment? What about hypogamm that's clinically asymptomatic? And how often do you measure IgG titers?

And then for the Vera team, I believe there were 0 cases of hypogamm in this Phase III. Did you see any cases when looking longer term in the Phase IIb?

Turn it over to Vera first.

First, we have not had cases of hypogammaglobulinemia so far in the program.

Yes. So given that, I think when we are dealing with a therapy that works with B-cell modulation and [ part of paraclete ] is right upfront that we know to expect about a 20%, 30% reduction in IgG. We get a little bit anxious if there's significant hypogammaglobulinemia. But every week that goes by, every program that reports that this class does well without infections, that's the major issue.

So I think in a program where IgG is blinded, we didn't need to know it to safely manage our patients through it, that this is going to be really not a concern and particularly in the atacicept program, where there's no significant hypogammaglobulinemia, I think that physicians and patients will enjoy being able to use this drug without needing to monitor IgG.

Now very clearly, patients who do get fevers ill, acutely ill, we'll be looking at IgGs then. We'll be considering whether or not the drug needs to be put on hold. But right now, there's no indication that, that's really a risk. And again, infections have not at all been associated with the change in IgG.

And I think the other thing which you need to realize is a 30% fall in IgG, if we actually look to absolute levels of IgG, patients don't fall out of the normal range for a healthy population. So their individual level has dropped. But if you look at the absolute level in the context of a healthy person, it's within the normal range.

And so perhaps that's the way we should think about presenting the data in the future rather than a percentage change an absolute level with clear demarcation of where the normal ranges are. But I think when we see those data, patients, even though their levels fall, they still remain within a normal range for the lab, which if I were to check, I would not even think twice about because it's normal for the population. So as Richard said, it's something we need to think about, we need to bear in mind. But practically, it's not been an issue.

Our next question comes from Ritu Baral at Cowen.

Sorry about that. I was on mute. As I look at the biomarkers on Dr. Lafayette's slide is presented today, what's notable is that there's no degradation since the Phase IIb. And as I look at the baselines, everything, maybe except for SGLT2 use is pretty equal.

Dr. Lafayette and Dr. Barratt, based on these biomarkers, is there any reason that the eGFR at 9 months in ORIGIN III should be any different than the eGFR level? I know it wasn't disclosed, but is anything about the SGLT2 or any other aspects of the baseline notable enough that investors shouldn't infer that the eGFR should look like the eGFR response in Phase IIb?

And if I could squeeze one last check off-the-box question in, Marshall, what's left before the NDA filing?

So I think the easy thing to say is no. There's no reason not to suspect the result will be identical, if not better, because it's slightly better resolution of hematuria, better reduction in proteinuria and the SGLT2 inhibitor use certainly should not prevent the stabilization of the GFR. So yes, I'll just say no. There's no reason not to suspect that the data will be at least as good.

For completeness, I completely agree. Yes.

And I can say that the Vera team is very close to filing the BLA, and there really aren't any steps I would name today between us and that moment and the filing is imminent.

Our next question comes from Paul Choi at Goldman Sachs.

Congratulations on the data and the standing room reception and the publication as well. My question for Dr. Barratt and Dr. Lafayette are, as you think about the magnitude of differences between SGLT2 naive and those on background therapy, can you maybe speak a little bit more to how you would contextualize the atacicept data today versus some of the combination data we've seen in terms of the competitive landscape?

And then I guess, for Marshall and team, I want to just ask to clarify on the commercial prep. Are there any particular centers or as you think about the initial target population of physicians who could be prescribers, how should we sort of think about the ramp of penetration and timing there?

Great. Well, maybe we'll begin at a high level with your second question and go to your first question. Second question is Vera is gearing up for U.S. commercial launch mid-2026. As Matt highlighted some of the detail of that, our leadership is fully in place. This is a highly experienced and motivated group.

We have strong opinions and depth of understanding of this potential market, and we're going to pursue it aggressively. This is not the moment where we're going to share thoughts on how we differentiate and how we think about that market. We will come back and have an Analyst Day at some point in first half of next year to provide a bit more color, but this is not the time we would do that.

And I think the SGLT2 story is a red herring. I don't think we need to be concerned. I actually don't think the SGLT2 inhibitors are necessary to return kidney function to a healthy state if you are taking atacicept. The fact of the matter is there are a number of reasons why you might be on an SGLT2 inhibitor. And if that's all you've got available, you will use it. But I would really warn against thinking that SGLT2 inhibitors will modify the effect of a true disease modifier in IgA Nephropathy.

Now of course, if you have diabetes with cardiovascular disease, you absolutely must be on an SGLT2 inhibitor for cardiovascular protection. But that's different to preservation of GFR, which quite clearly at the moment from the Phase IIb data is not necessary to preserve kidney function if you are taking a true disease modifier like atacicept. People are on SGLT2s, as Rob said, we would never advocate stopping them, but we would equally -- I personally would not be advocating starting them if the goal of starting them is to preserve kidney function when I have a drug that is quite capable of doing that by itself.

Yes. And I'll just take that to your remaining question, which is compared to the already approved drugs. I think when we present this Phase III data and see this reduction in proteinuria, again, by itself, it predicts an improvement in the GFR progression rate. But it's really astounding that both in Phase IIb and the expectation here is that it's going to be stable.

And I don't know if you saw the plenary session by Dr. Perkovic this morning, but he really took to task the IgA Nephropathy development that while there is improvements, even with combination therapy of TARPEYO plus sparsentan, you still would not expect normalization of GFR progression to healthy kidney function. So this is really a new class, as Jon said, really true disease-modifying therapy, and it's likely to really be a first choice of educated clinicians.

Our next question comes from Rami Katkhuda at LifeSci Capital.

Just wanted to pass along my congratulations as well for the presentation and publication. I guess first for Doctors Barratt and Lafayette. There's historically been a discussion as to whether patients of the Eastern Asian descent may have more severe disease and may react differentially, I guess, to BAFF/APRIL inhibition. I guess, does the data today put that argument to bed?

And then maybe secondly for the Vera team, when should we expect data from the monthly atacicept dose range finding study? And what could that presentation ultimately look like?

So in terms of the patient population, if you look at the baseline characteristics, these are absolutely typical patient population that I see in my clinic every week. And the sensitivity analysis that we've seen show that irrespective of the GFR, their baseline proteinuria, race, region, sex, they respond as well to atacicept. So for me, I think this population that we recruited is almost identical to the population of patients I look after in my clinic in the U.K. And I'll let Richard comment on how representative this trial population are to the patients he looks after in the United States.

Yes. And again, I'm in Northern California. So we do have a very nice mix. In my practice, we have a slightly greater Hispanic population than is represented in this trial. But fortunately, there's enough patients that we can look and see later if they respond similarly, I suspect that they will. And again, I just want to always be the academic. I think we still will feel that patients of Asian race are at higher risk and higher disease burden. But it's remarkable that these interventions still can have the same impact on those patients. And still, hopefully, when we get to the GFR data, we'll have the similar benefits on GFR progression.

And Rami, thanks for the question on the monthly program. Just to provide a little bit of background. Earlier this year, Vera initiated a monthly dose range finding study, looking at 3 different potential doses of atacicept administered subcutaneously on a monthly interval. Ideally, the way that we'll communicate about this is get to the point where we've been able to review enough of the data that the company has been able to determine what the appropriate monthly dose is and then to provide guidance on what the path to getting that information into the prescribing information will look like with the regulatory authorities.

I'd like to be able to do it all at once. If we're able to do that, we will. If we need to come forward and provide an interim update before I have all of that, we'll do that as well. But I'm hoping to kind of wrap it all up and have one integrated disclosure.

Our next question comes from Ryan Deschner at Raymond James.

Congratulations on the data and the publication. For the KOLs, how big of an impact would a positive readout for PIONEER in the lower proteinuria and lower eGFR IgAN patients have on prescriber decision-making once atacicept is on the market? And when would you expect this impact to sort of occur? And then I have a follow-up.

So again, you're tiny bit garbled, but I think you're asking about how PIONEER can, first off, demonstrate benefits in a lower proteinuria group. And I think our goals will be, again, short term to read out proteinuria with full expectation that there'll be similar proteinuria reduction. And I think just that fact that there's similar proteinuria reduction together with safety in that group as expected, would be enough to convince prescribers that that's a good way to go.

As again, Jon has shown, those patients can still be a very, very substantial risk. But of course, beyond that, we will be gathering GFR data, looking at that in context and really seeing if it's acting similar to the higher-risk patients.

So let me make one comment, Ryan. I think one of the things that the attendees in the opening plenary session heard this morning, first from Vlado and then echoed indirectly by Rich is the fact that I think we're in a period of transition and thinking about how we conceptualize patients and their overall risk of disease progression.

Historically, in an era where the drugs that we had at our disposal were predominantly effective at reducing proteinuria, it made sense to categorize patients based on the amount of protein they had in the urine to think about when you would intervene and when you wouldn't.

But now that we, for the first time, have drugs, at least in Phase II over 96 weeks have had a tremendous impact on GFR rate of loss, and current guidelines are calling for the achievement of a GFR rate of loss of less than 1 ml per minute per year to avoid lifetime risk of ESRD.

I think we can start to pivot in thinking about what we prioritize when we're looking at when to intervene and when not. And what that means is I can foresee a future where someone who has a very modest amount of proteinuria, but in the last 2 years has lost 10 mls per minute of GFR that the prescribing nephrologists is going to be focused on their GFR rate of loss and we'll be thinking about proteinuria as a secondary component of their risk equation.

Yes. Just to echo that, the direction of travel is to treat as early as possible. And as Vlado intimated, you can only treat patients that we have in our clinics. The next challenge that we are addressing is going out to finding these patients earlier, because the average GFR for a new patient presented to a nephrologist in the U.S. is between 40 and 50 mls per minute, which means they are -- by the time they present, they've lost half their nephrons, probably lost almost 3/4.

And we can stabilize that kidney function, but we can never get it better. I'd much rather treat a patient with a GFR of 75 and know that I can treat those patients and they're going to keep that GFR. So the direction of travel is earlier diagnosis and earlier treatment.

And I think if you look at what the FDA have done for full approvals, they don't stipulate proteinuria, they don't stipulate GFR. They say, if you as a nephrologist believe that patient is at risk of progression, you should be thinking of -- you are allowed to use this treatment. And that is very insightful by the FDA. And as a community, we are informing what we believe the risk of progression is. And so that is only going to get lower, and we are going to want to treat -- to treat people earlier.

And a quick follow-up. Can you remind us what the stratifications or which stratifications were employed in ORIGIN III?

So I don't know whether Rob wants to answer that in terms of the clinical trial design.

The GFR proteinuria and yes [indiscernible] geography, sex, region, and it's all in the manuscript.

Our next question comes from Farzin Haque at Jefferies.

So can you give us a sense of what proportion of the patients are getting to below certain UPCR threshold, so below 1 gram, 0.7 gram, or 0.5 gram [indiscernible]

Sorry, I couldn't hear that. Would you mind repeating it?

So what proportion of the patients are getting the proteinuria below a certain threshold like 1 gram or 0.7 gram or 0.5 gram back to 36 week in ORIGIN III?

So the proportion of patients that hit a proteinuria less than 0.5 gram in ORIGIN IIb.

In III -- ORIGIN III.

Yes. So that data has not been subjected to that analysis yet. And I think that will have to be a discussion about whether and when we do it. But hopefully, at some point, probably on the complete data set.

It was not part of the predefined statistical assessment of the interim analysis.

Got it. And then maybe for -- to find out like what is the current FDA feedback on the BLA filing package? Like how are they going to see through this class of drugs differently versus the oral competitors, particularly given that under accelerated approval.

Could you hear?

Farzin, you're going to have to repeat the question more clearly. We can't hear what you're asking.

So for the BLA filing package, like what is the feedback from the FDA? Like are they viewing this class of drugs differently versus the oral competitors?

We can't, at this point, share those conversations. I think we've been quite consistent in our public comments that we have a strong relationship with the Division of Cardiorenal. We're in close communication with them. They view these data set in a similar way that we've been presenting them. They've been presented this morning. And I think I'd just leave our comments at that at this stage, and it's going to be really exciting to see the progress from this point on.

Our next question comes from Arthur He at H.C. Wainwright.

Marshall and team, I just want to extend my congratulations. I think the atacicept score a drug profile every drug developer dream of. And maybe for Dr. Lafayette and Dr. Barratt. Given the strong efficacy wise in the subpopulation, what do you think about the agent just to remove the color of the UPCR at the beginning for the accelerated approval?

And also, it seems like in the ORIGIN III, the patient get a deeper and the fast response compared to the ORIGIN II. So is there any thoughts around that?

So I think in terms of response, you can see data for Gd-IgA1 you can see hematuria. We haven't presented data at the granularity that we have proteinuria yet, but that data will be coming. I think the thing that strikes me is very rarely do you see a Phase III trial replicate almost word for word and data point for data point, the same thing you saw in the Phase II.

And as Richard said, it's at least as good, if not better, for most parameters that we have looked at in a larger population, in a global population, and that can only reinforce the value of targeting BAFF and APRIL in this disease and that this disease is truly -- this drug is truly disease modifying. I think that's what I'd say. I would not look at the nuances yet until we have the full data set. But what we have at the moment is as good and I suggest better than what we saw in the IIb.

Yes. And I would echo that and just because this is a point of discussion about whether or not patients have a demand for some drug in the interim before you see marked proteinuria reduction or hematuria reduction for active anti-inflammatory therapy. And I think the Phase IIb results and these results would suggest that you could be patient without risking loss of kidney function.

And of course, the GFR is that -- if you haven't -- if your GFR has been lost at the same as a healthy person, how can you do better by an early anti-inflammatory intervention because your GFR is as good as if you were a healthy person. So I think that is the proof of the pudding. That's why the GFR data from the Phase IIb over 90-plus weeks is so impressive and compelling.

Yes. I just want to add to my comments here. This is what we hope to deliver to the nephrology community and the patients that we serve. That's what we're doing here in Houston. One of the bedrocks of science is to have a control arm to make use of randomization and double blinded. That's really the innovation in medicine that's transformed what we can offer patients. So one is the gold standard design, and there was consistency in design between Phase II and Phase III. And the other bedrock of science is reproducibility, and we're very proud to present that today in both presentation and manuscript form today.

And if I may, maybe for Matt. I know it's kind of a little bit earlier. So could you give us more color your strategy for early physician education and awareness campaign?

Sure. So we are actively out there now with the disease state education campaign. You can't walk around Houston and ASN here without seeing something about B-cell modulation, BAFF and APRIL as the right targets. So the word is definitely out there, and I would say it is the buzz of Houston. We will strive when we get our sales force out there to continue that messaging around disease state and certainly have the market ready and educated about B-cell modulation before launch.

Our next question comes from Dina Ramadane at Bank of America.

Congrats on the presentation and the publication this morning. I guess a question for Dr. Lafayette or Dr. Barratt. I just wanted to maybe touch upon kind of the evolving drug pipeline and contextualizing atacicept's profile. And it kind of sounds like your view on atacicept is in line with Vera's market research that there's considerable excitement for atacicept over the other pipeline therapies.

And you talked a lot on this call already about your excitement, but can you maybe provide some additional color on why specifically there is excitement for atacicept over other agents, just kind of given that other agents have maybe kind of achieved a similar proteinuria or eGFR benefit in clinical trials? And is it really anchored by that 2-year eGFR benefit from the Phase II or other aspects of the clinical profile we anticipate at launch?

And then just maybe a clarification question to your earlier point of proteinuria kind of being, I guess, the secondary to eGFR. Is it kind of correct in thinking that if you have an agent like atacicept that's stabilizing eGFR, there is maybe kind of a lower unmet need in trying to get patients' proteinuria down to align with the new KDIGO guidelines past that 500 milligram and maybe that's why kind of you foresee maybe no combo therapy in the future and that the BAFF/APRIL will be getting to that first-line treatment option?

So I think it's really simple. If you ask nephrologists what they want, they want a drug that safely and effectively stabilizes kidney function and prevents kidney failure. That's what we want. And therefore, if you look at the available data that has been published and peer reviewed, best quality data we have of a drug that stabilizes kidney function over the longest period of time is the ORIGIN Phase IIb data.

If you ask me, if I know a patient's kidney function is stable, I really don't care what the proteinuria is because it's not translating to loss of GFR. But that's quite theoretical in modern nephrology thinking. But I think what we're seeing is we are going to have to reimagine the relationship between proteinuria and GFR dependent upon the drug that you are taking at a time. And what I don't want to see is if I have a drug that stabilizes kidney function, patient may have persistent proteinuria. I don't want patients filled up with antiproteinuric drugs. They don't need that aren't adding value to kidney function protection.

So for me, we are going to -- when we have the longer-term GFR data, if I'm able to stabilize kidney function, that is the thing I'm interested about with a drug that is safe and patients tolerate. And those are the major goals. And so that is what people will be looking at in the data -- literature. And at the moment, when you look at the data and the published data, the strongest and most compelling data is the ORIGIN IIb that we can achieve this with a single agent.

Our next question comes from Sadia Rahman at Wells Fargo.

Congrats on the results. So my question is on eGFR and the data that competitors are showing relative to your data. So we don't have such long-term eGFR data from the competitor B-cell agents. But in the shorter-term data that we do have, we're seeing some increases in eGFR by like 2 or 3 mls per minute out to about 1 year.

So just wanted to get your thoughts on that. Do you think those differences could represent true benefit? Or could that rise be due to either variability in the data or even a transient benefit that comes with resolving an inflammation. And I think with atacicept, we also see some of that eGFR increase at earlier time points. So I just wanted to get your thoughts on that.

So I don't overinterpret minor increases in GFR. I think the key thing is a lack of loss of kidney function because at the end of the day, you can't grow more nephrons. You have the nephrons you have when you start. We have drugs that have increased GFR detrimentally and have increased proteinuria because they cause hyperfiltration and we don't want to see that, and we don't see that with this drug.

The overwhelming message I would obtain from these data is in a population treated with standard of care therapy, high-risk patients lose 5 mls to 6 mls of GFR per year. So 10% of their kidney function per year. The data from ORIGIN IIb completely negates that loss of kidney function and returns the old kidney function to the healthy population.

I wouldn't overinterpret minor increases in GFR. It's the fact that you are getting no loss that is the most important thing. And that's what I aim for in my patients, not to increase GFR by any amount, but to maintain the GFR and prevent any further loss.

Got it. And can you just clarify whether an improvement in inflammation could lead to some early increase in eGFR?

Well, we do see that in a situation, say, for ANCA vasculitis, where someone could present with a rapidly progressive loss of kidney function, where the disease phenotype is very, very different. IgA Nephropathy is not like that. And remember, GFR, certainly for the steroid therapies, eGFR is based on a serum creatinine, creatinine comes from muscle, changes in muscle metabolism due to steroids would alter serum creatinine GFR.

Again, I wouldn't overinterpret this, and I certainly wouldn't use it to compare one drug against another. The key thing here is the difference between loss of kidney function and maintenance of kidney function and return to the healthy population.

Just to complete the answer, we know from the 1970s when micropuncture studies were done in models of Heymann's nephritis that the reduction in GFR in patients who had acute inflammation in glomeruli was the loss of surface area. So theoretically, if you are able to have big impact acutely on the amount of inflammation in the glomerulus, you might be able to recover some of that. That would be the more mechanistic component of the answer.

Our final question comes from Vamil Divan at Guggenheim.

Congrats also on the data and everything. So 2 questions, if I could. So one, just back on the regulatory side. Marshall, you mentioned the filing is imminent. I'm curious if you'd be willing to comment on whether you expect a priority review or not for this accelerated approval? And is that dependent in any way on getting commission before/after [indiscernible] potentially getting approved later this month?

And then on the commercial side, we now have a couple of comps to look at on the IgAN launches in the last few years. And I'm just wondering how you think about atacicept potential uptake initially relative to what we've seen from TARPEYO and FILSPARI. I think there's certainly going to be much more enthusiasm for the mechanism, but obviously, those [ are ] already out for now.

So you're capturing some of the eligible patients, especially ones with more maybe higher levels of proteinuria and obviously the orals versus the injectables there? So just I know maybe it's still a little bit early and maybe there's more of a question for your commercial event in the end of the first half of next year. But just your thoughts on how we should think about potential uptake initially relative to what we've seen so far?

Vamil, it's Rob. I'm not sure we got all of it, but let me see if I can answer 2 of the components I think came through to us in the room. First, yes, our expectation is that we will be granted priority review given that we have breakthrough designation. And second, as it relates to do we think that the trajectory of the launch success for drugs that have come thus far with accelerated approval in IgA Nephropathy are good forebearers of what we'll experience with atacicept. I think we would not look at any of the examples of drugs that have been launched thus far as a good direct readout of the performance that atacicept will have in the marketplace. I think, we have higher expectations.

So this concludes today's Q&A session. I'll now turn it back over to Marshall for closing remarks.

Thanks, everybody, for joining. A huge congratulations to the Vera team and our important collaborators, Dr. Barratt and Dr. Lafayette and all of the patient volunteers and study teams that made the data possible. And together, we strive to change standard of care and improve outcomes for the patients we hope to serve. Thanks, everyone, for your attention, and let's close the call.

So welcome to the Cantor Global Healthcare Conference. I'm Pete Stavropoulos, a biotech analyst with Cantor. With us, we have Vera Therapeutics, a company I cover, and I'm pleased to introduce Marshall Fordyce and CEO; and Robert Brenner, CMO. Welcome.

Thanks so much, Pete. Great to be here.

Let's start off with a brief intro for those that don't know who you are...

Sure. I'm Marshall Fordyce. I'm the Founder and CEO of Vera Therapeutics based in San Francisco. We are -- I've been a public biotech company now for about 4 years, made great progress with our lead product candidate called atacicept which is an immune modulator for B-cell-driven diseases. We've recently read out our Phase III trial in a major unmet medical need called IgA Nephropathy, and we are now planning to file for a BLA in the fourth quarter this year. So very shortly, we'll file our package and expect to be on the market mid next year. So really exciting time and have been building the commercial profile of the company in the recent years.

And I'm Rob Brenner, Chief Medical Officer. I've been with the company for -- coming up on 2 years. It's been an amazing journey. I'm a nephrologist by training. And I think the kidney community is appreciating that we're on the precipice of a new era in our ability to manage patients with IgA Nephropathy and other forms of autoimmune kidney disease. It's a super exciting time, both for patients, for providers and certainly for all the employees of Vera.

Yes. So when I was in [ move to diligence ] in the IgAN space, I remember -- it was probably around November 2023, I had spoken to a KOL, nephrologist, but not an IgAN KOL but looking at acute kidney injury. And I had asked him about your 36-week data and his perspective on IgAN. And he was a little bit dismissive at that time, meaning like IgAN kicked the ball down the road and not that big of a deal.

And then you had your 72-week data in January. And then I spoke to him again in March after that, and he had a completely different perspective and a different tune. And he was impressed by your eGFR data, 72 weeks. And so first, the exact -- what is the burden of disease? And is it something that you just kicked down the road? That's number one. And then number two, are the more, let's say, of community-based nephrologists becoming more and more aware of IgAN and your drug?

I'd love to start and then Rob, as the nephrologist on the stage talk about this. But this is a large unmet need. I'm a physician as well by background. In the United States alone, there are 160,000 patients with biopsy-proven IgAN, of which at least half have high risk of disease progression. This is a significant unmet need. Diagnosis on average is delayed, but it happens currently at the age of 35 years old.

We now have seen, Pete, in our data and others' data that if you're on placebo with that profile, you're on dialysis before the age of 50. So this is an urgent unmet need. And we're the first and only to show that on atacicept over 2 years, you can stop kidney function decline as measured by GFR. And that data set is not just understood by KOLs, it's understood in the field.

Last week, I was in Florida talking to nephrologists who are not normally on stages, and they're very aware of our Phase II data. So that's an exciting moment for us. Rob, any other thoughts on GFR data?

Yes. It's -- in the history of drug development in kidney disease, we've never been in a situation where we have a population of patients who actually had a kidney biopsy and have been found to have a specific kidney disease where we've been able to intervene with an agent that changes the course of the progression of their kidney function from one that has them on pace, to Marshall's point, of maybe needing dialysis in a decade to one where they could potentially live the remainder of their life without the need for a transplant or to go on dialysis. It's never happened before.

And now we're on the verge of being able to provide a drug or a new class of drugs are able to do that for patients, starting with IgA Nephropathy. And I think it's the magnitude of the evolution in a data package that is now sitting in front of clinicians that they've never seen before that does create this opportunity.

So you just mentioned 160,000 patients in the U.S. But when you look at different companies and when you look at the academic literature, when I go to the academic literature, it's about 112,000 where I put it. But I also see Novartis had about 185,000 patients in the U.S. and Otsuka published a paper, I think, late last year, showing about 200,000. And so what's your perspective on that? Are you being conservative or...

We're generally conservative. We do think that this disease is underdiagnosed. So somewhere in the middle of 160,000, Pete. And as you can do pretty simple math with current pricing, that's a $10 billion to $20 billion market.

So it's a very large opportunity commercially. But more importantly, we're focused on identifying those patients beyond just those who currently have biopsy but also pushing out -- when you bring a transformative new therapy to patients, diagnosis tend to increase because there's a reason to diagnose, and you can do something about the disease. I've seen in prior work in infectious disease. We think that's the situation again here.

So touching on atacicept. It's designed to address the disease from an immunological standpoint. Can you just walk us through the therapeutic hypothesis, which you've proven with your Phase II and Phase III data that we'll get into in a moment. And from a mechanistic standpoint, why the drug has disease-modifying properties as well, not compromising safety.

Sure. do you want to take it?

Yes. So what is IgA Nephropathy? It's a B cell disorder with kidney pathology. So this is a disease that has its hallmark is a formation of an immune complex. There's an autoantigen, which is recognized by an autoantibody. Those immune complexes circulate, they deposit in the kidney where they drive inflammation, fibrosis, nephron loss and kidney failure.

But we know that both components of the immune complex originate in the B cell. So the B cell is the cell that we want to intervene against. How might we do that? It turns out that there are 2 cytokines that act as the energy source for B cells that are fueling the production of immunoglobulins.

And atacicept is an example of a rationally designed biologic agents. It has an extracellular binding domain for both of those 2 cytokines. One is called BAFF, one is called APRIL. And it's got picomolar binding affinity for both of them. It's a soluble receptor that we can administer to patients. They can administer themselves once weekly at home using an auto-injector, low volume. And we can reduce the amount of BAFF and APRIL. And when we do that, we reduce the expression of antibodies. We reduce the generation of the immune complex. We reduce the inflammatory burden in the kidney. We lower proteinuria, a marker of disease, and we can stabilize GFR. So that's the mechanism of the drug, and those are the key readouts that we've seen through the Phase II and now into the Phase III program.

Yes. The hypothesis that we've proven out is target the source of the disease and see everything downstream actually resolved in terms of inflammation, proteinuria and GFR. And that's been very exciting to [ sibe ].

Yes. So you have shared multiple data sets. And key for me is that this consistency there, right, Phase II to Phase III. In fact, you didn't see a degradation of signal. It actually increased. So the first thing to touch on is the patient population that you enrolled, A, were there any differences? And also when you compare to other studies such as [indiscernible]?

Yes. So first, internal consistency within the atacicept program from Phase II to Phase III. In the Phase II and Phase III programs, we enrolled patients who had same age. They were about 40 years old. They have the same amount of kidney function remaining, about a GFR of what we call 60 mls per minute, which means they've lost 40% of their endogenous kidney function at the time they enrolled.

They had the same vintage from the time that they were diagnosed with the disease of a couple of years. They have the same amount of protein in their urine. They had the same ethnic background, and we know that IgA Nephropathy is overexpressed in patients of Asian descent. So that was accounted for.

The one difference in the Vera program between Phase II and Phase III was the amount -- number of patients who are receiving SGLT2 inhibitors on top of an ACE inhibitor or an angiotensin receptor antagonist. In Phase II, it was 15%. In Phase III, it was 50%. What was super interesting is that the presence or absence of an SGLT2 inhibitor had 0 impact on the results that we've observed in the clinical program.

Okay. When you do look at the data, Phase II to Phase III, your Phase III was in line with the protocol versus the ITT. And so just walk us through how you accomplished that. And when it comes to safety outcomes, particularly infections, what were the observations in Phase III?

Yes. The Phase II program studied 3 different doses of atacicept versus placebo. There were 30-odd participants in each cohort and the proteinuria reduction was robust, well north of what the FDA is looking for, which is a 30% reduction compared to placebo.

In the Phase III program in 203 participants randomized to placebo or the commercial dose, which will be 150 milligrams administered as a 1-ml volume once a week by patients at home, we saw a 46% reduction in proteinuria in the active group and overall a 42% placebo-adjusted reduction, well north of the FDA 30% threshold. Those results are as impressive, if not more impressive than what we saw in Phase II.

I think it has to do with the sample size. I think it has to do with the effectiveness of our ability to have people follow the protocol as it's written and not deviate. So I think it's a very good representation of the magnitude of effect that patients will see commercially once the drug is approved.

All right. And at ASN last year, you did present a 96-week data from your Phase II. And can you just discuss those data and what gives you confidence that you're actually going to replicate it in Phase III?

Yes. Great question. The most important thing that we measure in patients with kidney disease is a measure of their function. And what we use is something called glomerular filtration rate or GFR. When people are young and healthy, they've got a GFR of about 100 mls per minute. And when patients need kidney replacement to stay alive with either a transplant or dialysis, they have about 15 mls per minute or less. So only 10% or 15% of their endogenous kidney function.

People, once they reach the age of about 40, lose about 1 ml per minute per year just as part of the normal aging process. So unfortunately, looking around the room, that's what all of us are experiencing today.

The 96-week data that we showed was this long-term experience of patients receiving atacicept at home. They entered with a GFR of about 60. So they're already about 40% reduced from completely normal, but they've got a biopsy-proven kidney disease, and they're losing about 6 mls per minute per year, even when they're on an ACE inhibitor and an SGLT2 inhibitor, maybe even ERA or steroid. So that means they're losing 10% of the remaining kidney function a year. And to Marshall's point, they are on a track to needing dialysis or a transplant within a decade.

What we showed is that over the 96 weeks, over 2 years, they had a GFR slope of minus 0.6 mls per minute. That means at that rate, if they're 40 years old, they're going to live the rest of their life without needing dialysis or a transplant. That's how transformative the data set was, and it's unprecedented, as I said earlier, in the history of kidney drug development.

What do I think for Phase III? Well, we've seen the GFR data for the interim analysis at 36 weeks. We haven't disclosed it publicly because the FDA has asked us not to. The FDA has seen the results. I will tell you the only reason we're not disclosing the results as now is because the FDA has asked us to. There'd be no other reason for us not to disclose it. And my expectation is that the GFR results from the Phase III program, when it completes, will look very comparable to what we saw in Phase II.

And so you are going to show some data at ASN, I'm assuming you are. What should we expect to see and what should we be looking out for that?

Yes. In my view, there are 4 parameters that we look at to provide evidence for true disease modification in IgA Nephropathy. First, we look for a reduction in sort of the burden of immune complex. We can measure the autoantigen. It's a form of IgA called galactose-deficient IgA1. We can measure that. And we showed in Phase II that there was a 2/3 reduction in the Gd-IgA1. So I would hope that we'll be able to disclose the Gd-IgA1 result at ASN.

Next, we look at the burden of inflammation in the kidney and people who have IgA Nephropathy. And there's an easy way to do that. We can use a point-of-care device. We can use urine dipstick for hematuria for blood in the urine. And in the Phase II program, we showed that there was an 80% reduction in hematuria in patients who had blood in their urine at baseline. To me, very clear evidence that we're having an anti-inflammatory effect, and it begins early when you start using the drug.

Then we can measure proteinuria, which is the surrogate endpoint that the FDA uses to grant accelerated approval. And as I said, the threshold is a 30% or larger reduction compared to placebo. And then the fourth component is the GFR. And so we've shown for the Phase II, the quartet of findings that all are improved that indicate true disease modification. We'll show as much of that quartet as we can at ASN, but still to align with FDA expectations of what we disclosed.

Okay. So after you did announce the Phase III data for UPCR competitor program from Otsuka, they also presented at ERA, their Phase III data. So how do the 2 data sets sort of compare, understanding the different studies? Any key differences worth highlighting such as patient population, efficacy outcomes or anything else?

Yes. I think as much as we would like these trials to be identical and the super imposition of one another, they're not. There are some meaningful differences in the study. The high-level take is that the results from atacicept are incredibly encouraging. And I think the superficial results from Otsuka's program are also very encouraging.

I think until we get to the point where we have final results that make it into a label, make it into a peer-reviewed publication, there may be some movement a little bit with each of the data sets. But Vera is incredibly confident that the results that we've demonstrated both in Phase II and Phase III reflect a new era for future management of this disease and the future has never looked brighter for patients with IgA Nephropathy.

Some movement in data sets, what do you mean by that?

If you look at the precedent in this space for data disclosure followed by publication and approval labels, there's not a one-to-one concordance of what the preliminary release data look like compared to what's presented. And so my expectation is what we saw in Vienna may not reflect what is actually written in the label or in a peer-reviewed manuscript. That's my only point.

Okay. So you do have Extend? It's the open-label extension for ORIGIN. Just give us a sense, if you can, if not quantitatively, but qualitatively, how the rollover is going.

It's going great. We've been enrolling that program since the end of last year. It is an opportunity for any participant in our clinical program who's completed a study to have an opportunity to receive atacicept in an extension program until it's approved in the region in which they reside. We feel that we have an obligation to do that for patients. It's also provided an opportunity for us to have some real-world experience with our auto-injector, which we're going to have when we launch. So that's been a nice opportunity. Enrollment is going great. Program is moving forward.

I'd also highlight what we shared last year, which is when treatment with atacicept is interrupted, the disease comes back, and we measure that by the recurrence of the immune complexes and a continued decline in GFR. So this data set is going to be pretty interesting to show not just the continued chronic dosing, but what happens after interruption drug incredibly important for physicians to see what is the risk/benefit profile of taking this drug and what an interruption might be.

You are reenrolling patients from the Phase IIb that have that drug holiday.

Yes.

What's the enthusiasm to come back?

Been high.

Very high. Yes.

Yes. All right. And are any of the patients enrolled in extend? You did mention it either being with the auto-injector. And so is this the majority? Or is this...

It's not the majority, but it's a cohort of the program where we have the ability to provide them with auto-injector, and it's been a smooth transition.

Have you gotten any feedback in terms of the use of the auto-injector from patients or physicians who are treating those patients?

I think it's been an advantage for patients to have this device to use at home the way that other auto-injector biologics are used. A low-volume 1 ml once a week self-administered algorithm is about as successful an approach we've had for any biologic drug in the history of our planet. So we're really confident as we look forward to the future world where we're providing this commercially for patients.

All right. So I guess the next major step for the program is the BLA filing and followed by an approval. Do things sort of remain on track for 4Q? And are there any gating factors? And is there any reason why we should not expect priority review?

Yes, things are going great. We locked our database at the end of May. Team has had their head down, focused on executing. We're in the final stages. There are no major gating activities before we submit. I feel really good about the quality of the application and really grateful for the hard work of all of my colleagues back at Vera, who -- it's been a summer of Vera for a lot of us, and that's what it should be because patients are waiting, and every day counts. So we're really close and fourth quarter is coming pretty soon.

Is there any reason you should not expect a prior review? Did you mention it?

We are planning for it.

No. All right. So how are you thinking about the label? I've had some discussions on whether or not the agency will use FILSPARI and TARPEYO accelerated approval of label as sort of precedents. So restricted to 1.5 grams per gram. Patients restricted to patients who have 1.5 grams per gram. Do you expect that to be the case? Or do you think the agency is actually going to take into account all the data that's been generated to date, including safety and also taking into account the mechanism of action?

Yes. I think the agency is going to look at the data for atacicept with fresh eyes. What may be viewed as regulatory precedent within the IgAN space that's tethered to other mechanisms with other data sets. I don't think may be a great predictor of what's going to happen for Vera and for atacicept.

The quality of the narrative and the dialogue that we have with FDA is really high. I've been doing this for a long time. I have a lot of respect for our review division. We have a great relationship with them. The conversations have been extremely collaborative and productive. And I'm cautiously optimistic that we'll be in a position to have a very competitive label out of a chute.

All right. Looking forward to that. So what are some of the ongoing early efforts, commercialization efforts? It looks like you have experienced leadership in place, including the medical affairs and commercialization. How are you thinking about this? And what are some of the ongoing activities to prepare?

I can tell you that we've been preparing commercially for a good long time. We're focused on the U.S. launch. There are roughly 8,000 nephrologists in the United States. We've got sales leadership now in place after Phase III readout. We have sited the structure in terms of the team. And we've been really engaged with the nephrology community for a very long time.

So early feedback is that Vera and the atacicept data are very well understood by the nephrology community. We have great awareness. And I think that should be expected for a company that is entirely focused on its first launch and can credibly say that we're committed to the nephrology community and bringing new patients -- new therapies to patients. So it's been a major focus for us. We're thrilled by the talent that's attracted to the opportunity that we've been building.

I don't know if I missed or while you're discussing also, I think, sort of in touch with the patient community.

Yes. I mean we've been doing this for a long time. I've been going to the IgAN Foundation meeting every year. We've been deeply engaged with them and I was there in Chicago over the summer. So the PIONEER study, Pete, that you've been tracking with us to go beyond our Phase III protocol and say, what are the other IgAN patients who could benefit from atacicept? Part of the cohorts in PIONEER come directly from my conversations with patients. So we've been deeply engaged with this community. And this is how you transform medicine is to stay super focused on patients.

And I think in every area of medicine, there are advocates at varying forms. And I think the IgAN Foundation and the advocacy community around this disease has been gaining momentum. It's been an incredible effort to see really poised to change medicine in the way that Dr. Brenner has seen and been a part of.

Excellent. So I guess one thing that investors do want to see is if it's feasible to do a monthly dosing. And so I do know you have a study that's ongoing. I believe it was initiated back in May. Are there any updates on this program? And -- or when can we expect some updates?

Yes. We shared last October that we plan to do a [ dose-ranging ] study to identify a preferred dose for monthly. That study is up and running. It's enrolling. And as soon as we feel like we've identified what the right dose is, we'll be able to come back to the market and talk about what the cadence will be to get that information in the label. It's a little early to do that, and I don't want to show too much of my hand to our competitors because it's such a dynamic space.

With that, I would also remind folks that in January, we announced the acquisition of VT-109. We did a license from Stanford. This is a novel fusion protein that we think has the potential for a very differentiated product profile. And so when I think about how we're going to play in this space for decades, how we're going to win, part of it is with atacicept and part of it is to harness the potential in VT-109 and to use those in an integrated way to have a dominant position for an extended period of time.

Yes. So I think both of those programs are exploring longer-dosing interval. But I think it's an interesting thing to focus on when first you begin with, does the drug work well, does it have a transformative outcome for patients efficacy.

Then you've got safety, which looks similar to placebo in both Phase II and Phase III, and then the patient experience. And we'll be on track to be the first and only BAFF/APRIL mechanism of action on the market next year with an at-home, self-administered small volume auto-injector, that's a phenomenal profile between does it work, is it safe? And does it -- is it a convenient thing to take. It's a few seconds once a week. We've had 90% retention over 2 years with that profile, and that's a great position for us to be in.

I guess we have 2 minutes left. Just quickly touch on pipeline and product potential and PIONEER. Where are you with that study?

Yes. Let me speak to this just briefly. From an overall perspective, we are focused on the nephrology community, and that's why we're pursuing IgAN first PIONEER captures additional IgAN populations. We're moving into membranous nephropathy as well as other autoantibody-driven glomerular diseases like FSGS and MCD.

So conceptually, think about Vera as focused on the patient population and the physicians who serve them. We think that's the highest value in terms of what we build in terms of near-term value. But without a question, there are rheumatologic, neurologic, dermatologic indications for BAFF/APRIL inhibitor that has this type of profile. But maybe an update on progress in PIONEER.

Yes, actively enrolling, enormous appetite for the program. And it's super exciting. I love the fact that after our Phase II data, we really leaned in dedicated resource to looking at kind of allcomers with IgA Nephropathy, not just those individuals who meet Phase II, Phase III entry criteria. That hasn't been done before. I think we'll address many questions when we get to commercialization and how phenomenal it is to think about using this drug in patients with other forms of autoimmune-mediated kidney disease. We're really kind of leading with the community in thinking about what future management is going to look like and let's go get some data.

And I assume you're leveraging the same physicians treating [ fraud ] again.

Yes, a lot of synergy, a lot of -- from a -- how are we managing our capital, being good stewards of that capital. It's a very efficient program.

Last question, if we're sitting here a year from now, what would you like to say that you accomplished?

Transforming medicine. We've got to have a new drug on market. We expect to see this very well received and start to open up the pipeline [ a year ]. So it's very exciting for us.

All right. Well, thank you very much for participating in our conference and the fireside chat and looking forward to BLA filing and approval.

Thank you.

Thank you, Pete.