Lexicon Pharmaceuticals, Inc. Stock

Welcome to the Lexicon Pharmaceuticals Third Quarter 2026 Financial Results Conference Call.

[Operator Instructions]

As a reminder, this call is being recorded today, November 5, 2026. I will now turn the call over to Lisa DeFrancesco, SVP, Investor Relations and Corporate Communications for Lexicon. Please go ahead, Lisa.

Thank you, operator. Good morning, and welcome to our third quarter 2026 earnings call.

Joining me today are Dr. Mike Exton, Lexicon's Chief Executive Officer and Director; Dr. Craig Granowitz, Senior Vice President and Chief Medical Officer; and Scott Coiante, Senior Vice President and Chief Financial Officer.

This morning, Lexicon issued a press release announcing our financial results for the third quarter of 2026, which is available on our website at www.lexpharma.com and through our SEC filings.

A webcast of this call, along with the slide presentation, is also available on our website. During this call, we will review the information provided in the release, provide a corporate update, and use the remainder of the time to answer your questions.

Before we begin, let me remind you that we will be making forward-looking statements, including statements relating to the safety, efficacy, clinical development, regulatory status, and therapeutic and commercial potential of sotagliflozin, pilvapadin, LX9851, and our other drug programs as well as our business generally.

This call may contain forward-looking statements relating to our growth and future operating results, discovery and development of our drug candidates, strategic alliances and intellectual property as well as other matters that are not historical facts or information.

Various risks may cause our actual results to differ materially from those expressed or implied in such forward-looking statements, and we refer you to our most recent annual report on Form 10-K and other SEC filings for detailed information describing such risks.

I would now like to turn the call over to Mike Exton. Mike?

Thank you, Lisa. Good day, everyone, and thanks for joining us. As we approach the end of 2026, a year of tremendous focus and strategic evolution for Lexicon, I want to highlight the significant progress we've made across the business.

First and foremost, in HCM, we completed patient enrollment in our Phase III SONATA-HCM study.

The baseline characteristics reflect the broad spectrum of patients being treated for HCM today, which we believe positions the study to evaluate SOTA across both nonobstructive HCM, where significant unmet need remains, and obstructive HCM, where many patients continue to experience symptoms despite available treatment options.

Importantly, the baseline CCQ score of 59 reflects a highly symptomatic patient population with substantial room for symptomatic improvement.

We're very pleased with the overall enrollment profile of SONATA-HCM and look forward to reporting top-line results in the first quarter of 2027.

Now moving to Zynquista. We continue to make strong progress towards the resubmission of our NDA in type 1 diabetes, supported by new prospective safety data from the investigator-initiated STENO-1 study.

We are extremely pleased with the STENO-01 safety data, with rates of DKA that were low and comparable to the standard of care as well as the background rate among T1D patients in Denmark.

It's worth remembering why this matters. Insulin remains the only glucose-lowering therapy for people with type 1 diabetes. And even with today's pumps and sensors, only about 1 in 5 adults reaches the A1c goal of 7%.

And while much of our recent focus has understandably been on providing the additional safety data requested by the FDA, we don't want to lose sight of the strong efficacy results demonstrated in our Phase III inTandem program.

Those results are equally important to evaluating the overall profile of Zynquista. And taken together, we believe the inTandem efficacy results and the new STENO-1 safety data provide a compelling benefit-risk profile for Zynquista and a strong foundation for our NDA resubmission.

We are now preparing that resubmission. And because STENO-1 is an investigator-initiated study and was not designed for regulatory purposes, significant work has been required to analyze the format and prepare the data for submission and review.

What remains is bringing this academic data set up to agreed-upon regulatory submission standards. We are completing that work in parallel with ongoing discussions with FDA with the goal of submitting the highest quality package possible and maximizing the probability of a successful review.

While this process is taking longer than we originally anticipated, we expect to complete the resubmission in the first quarter of 2027.

We've been unwavering in our commitment to people living with type 1 diabetes and to making sotagliflozin available as a new treatment option.

I'm incredibly proud of the work our team has done to get us to this point and grateful to the STENO-1 investigators for their collaboration in helping us pursue an innovative regulatory path forward.

Now in heart failure, our licensee, Viatris, continues to expand the global regulatory footprint for sotagliflozin with regulatory submissions across a growing number of markets outside the U.S. and Europe.

To date, Viatris has obtained regulatory approvals in the United Arab Emirates and Bahrain and submitted applications in more than a dozen additional countries, including Saudi Arabia, Canada and Australia.

Turning to LX9851, our first-in-class ACSL5 inhibitor for obesity, the Phase I study being conducted by our licensee, Novo Nordisk, is progressing nicely.

During the third quarter, we received our third $10 million milestone payment of the year from Novo, with the potential to receive additional milestone payments as the program advances.

We're very pleased with the progress of this promising compound and excited to see Novo continue to move the program forward. And finally, turning to pelabapenib.

Our conviction in the potential of this agent and its novel AAK1 inhibition mechanism continues to grow. Last quarter, I mentioned that we have exciting work underway exploring its potential in additional high-value indications.

And today, I'm pleased to share some of that work, particularly in obesity and weight management. In preclinical studies, pelabapenib has produced a significant reduction in body weight, both as a monotherapy and in combination with semaglutide.

While this work remains early, we are encouraged by what we've seen and believe it points to an intriguing new opportunity for this program. We look forward to sharing more on this and additional preclinical programs with pelidapenib.

Lastly and importantly, we've remained steadfast in our commitment to operational excellence and disciplined investment as we advance our programs and prepare for the opportunities ahead.

To that end, we recently appointed Rachel Martans as Chief Commercial Officer and added new leaders in marketing and market access to advance our pre-commercial planning in HCM and T1D.

I'm extremely pleased with the caliber of talent that we have and continue to attract at Lexicon, which I believe speaks to the strength of our programs and the opportunities ahead of us.

Now, before I turn the call over to Craig, I'd like to return to HCM and spend a few minutes on why we believe this represents such a compelling opportunity for Lexicon and why sotagliflozin may be uniquely positioned to address the significant unmet need across the disease.

HCM is a genetic disease characterized by adverse cardiac remodeling, including myocardial hypertrophy, diastolic dysfunction, and fibrosis.

Importantly, this underlying biology is the fundamental pathology across both non-obstructive and obstructive HCM. And while today, much of the innovation in HCM is centered on cardiac myosin inhibitors, which target the contraction mechanism of the heart.

Sotagliflozin takes a fundamentally different approach. Through its dual SGLT1 and SGLT2 inhibition, we believe sotagliflozin may influence the metabolic and other biological processes that contribute to diastolic dysfunction in HCM.

That distinction is important because the underlying abnormalities in cardiac structure, function, and metabolism extend across both forms of HCM.

And we believe this gives SOTA the potential to deliver meaningful benefits in both obstructive and nonobstructive disease, something SONATA-HCM is specifically designed to evaluate.

Now the HCM market is a large and rapidly growing opportunity for a novel agent like SOTA. Awareness and treatment of HCM is accelerating in the U.S. and around the world, but patients continue to experience significant symptom burden that impacts their lives.

Today, in the U.S., more than 800,000 patients have been diagnosed with either obstructive or nonobstructive disease, but there are many more remaining undiagnosed currently.

In NHCM, in particular, a treatment gap remains with no disease-specific therapies currently approved despite a patient population growing quickly with rising levels of obesity and diabetes.

There's strong support for an option that is simple, safe, and easy to use for busy and growing cardiology practices. We believe sotagliflozin's once-daily oral profile, together with its differentiated mechanism and potential applicability across both obstructive and nonobstructive HCM, could provide an attractive option for physicians and patients.

With that, Craig Granowitz, our Chief Medical Officer, will provide additional color on our pipeline. Craig?

Thank you, Mike, and good morning, everyone. As Mike mentioned, SONATA-HCM is the ongoing Phase III study for patients with symptomatic HCM, the top-line results of which are expected in the first quarter of next year.

SONATA-HCM was designed to evaluate SOTA in a broad HCM population reflective of real-world clinical practice. With the baseline characteristics of the study now available, we are very pleased that the final study population met that objective.

Importantly, the demographic and clinical characteristics of both the non-obstructive and obstructive HCM cohorts are generally consistent with those reported in previous clinical studies of other agents in those respective patient populations.

The overall study population had a mean baseline KCCQ score of 59. The primary efficacy endpoint of the pivotal study is improvement in symptoms compared to placebo as measured by the change in baseline KCCQ at week 26.

In total, SONATA-HCM enrolled 542 patients, with 440 classified as nonobstructive at baseline and 102 as obstructive. The trial also includes patients on stable background therapies, including cardiac myosin inhibitors.

The scientific evidence for sotagliflozin continues to accumulate, strengthening the rationale for its effectiveness and mechanisms in HCM and providing important insights into the potential differentiation of dual SGLT1 and SGLT2 inhibition.

In a preclinical murine model of HCM, SOTA improved baseline measures of cardiac structure and function, including diastolic function, hypertrophy, and fibrosis.

Separate research has also demonstrated SOTA's inhibition of platelet activation and thrombus formation, which were greater than those observed with the SGLT2 inhibitor empagliflozin, highlighting the importance of the SGLT1 effects in impacting thrombotic events.

New investigator-led research being presented at the upcoming AHA meeting this weekend includes work in living human HCM heart tissue, where SGLT1 inhibition directly reduced myocardial work, with SOTA showing greater potency at higher afterloads compared to empagliflozin.

A separate study in healthy adults treated with EPA or soda found a significant reduction in thrombus formation from baseline with soda, while the reduction with EPA did not reach significance.

We believe that body of evidence will continue to grow.

The investigator-initiated SOTA cross study being conducted at the University of Pennsylvania is evaluating SOTA in patients with nonobstructive HCM, including its effects on cardiac function, exercise performance, and quality of life, with completion now expected in 2027.

We believe these findings provide increased scientific and clinical support for the differences between the dual SGLT1/2 inhibitor SOA and SGLT2 inhibitors.

Additionally, the HCM-specific data reinforce our excitement as we approach the expected SONATA-HCM top-line readout in the first quarter of 2027.

Moving to Synquista. To expand upon what Mike highlighted earlier, the inTandem program demonstrated important benefits for people with type 1 diabetes, including a reduction in HbA1c of about 0.4 percentage points, roughly 3 hours per day of time in range, fewer hypoglycemic events, reduced body weight and lower blood pressure.

The FDA requested additional prospective data characterizing the risk of DKA as a precondition for resubmission of the NDA. We have subsequently worked with the agency on a path forward using data from the STENO-1 trial.

The FDA agreed that STENO-1 could provide the prospective data needed to assess DKA rates in a large sotagliflozin-treated population, provided the study achieved sufficient patient exposure comparable to the approximate 200 patient-years of SOTA treatment in the inTandem clinical program.

Indeed, we have now met the criteria outlined by the FDA, including the required level of patient exposure, and have received the STENO data needed to support our resubmission.

The inTandem efficacy results, together with the new STENO safety data, give us increased confidence in the overall profile of Zynquista as we prepare to resubmit our NDA.

Looking at the STENO data in more detail, we are encouraged by the safety results observed in the trial. As shown on this slide, the rate of DKA amongst patients receiving sotagliflozin was approximately 1 DKA event per 100 patient-years of SOTA exposure.

This was comparable both to the standard of care group in the STENA-1 trial and the historic rates in Denmark in people with type 1 diabetes. The rate of DKA is well below that of the rates observed in the SOTA arms of the inTandem studies.

Importantly, as of the end of August 2026, which we are using as the cutoff date being used to support the FDA resubmission, the study included 496 patients randomized to soda and 708 patients receiving the standard of care, which provides the level of patient exposure agreed with the FDA.

As Mike mentioned, significant work is ongoing with STENO in conjunction with alignment from the FDA on analysis parameters to properly prepare the data for FDA submission and review.

While the administrative process is taking longer than initially projected, we remain confident in the robustness of the data set, and we are encouraged by our progress towards resubmission, which we now expect will occur in the first quarter of 2027.

Turning now to pelazapiden, the selective AAK1 inhibitor. We continue to explore the program's potential beyond its established development path in neuropathic pain.

We have been investigating the potential application of pelvapidin in additional indications based on its ability to affect biological pathways involved in several processes, including nerve transmission involved in gastrointestinal motility.

The results shown here provide encouraging early evidence of that potential in obesity and weight management.

In this preclinical study, 10 milligrams per kilogram of pelvapidin reduced body weight by 14% after 28 days of treatment. When pelvapiden was combined with semaglutide, the mice experienced a reduction of 31% in body weight, greater than the 25% body weight reduction observed for semaglutide alone.

Although these are early findings, these results suggest that pelvapidin may have activity as a stand-alone agent and may also provide incremental benefit when combined with the GLP-1 therapy.

We believe that this potential is particularly interesting as the obesity treatment landscape continues to evolve and the need remains for differentiated mechanisms and combination approaches.

We are continuing to evaluate these findings and advance additional work needed to better define the opportunity, and we look forward to providing further updates as this program progresses. I'll now turn it over to Scott to discuss our financial results.

Thank you, Craig, and good morning. I'll begin with a review of our financial results for the quarter.

Total revenues were $11.3 million for the quarter ended September 30, 2026, compared to $14.2 million for the corresponding period in 2025.

Revenues for the third quarter of 2026 included $10 million in milestone revenue recognized from the Novo Nordisk licensing agreement and net sales of INPEFA of $1.2 million.

Revenues for the third quarter of 2025 included $13.2 million of licensing revenue from the Novo agreement and net sales of INPEFA of $1.0 million.

Research and development expenses for the third quarter of 2026 were $16.2 million compared to $18.8 million in the corresponding period of 2025, reflecting lower external clinical trial expenses as a result of the completion of our PROGRESS Phase IIb clinical trial in 2025, partially offset by higher SENATA-HCM Phase III clinical trial expenses in 2026.

Selling, general and administrative expenses for the third quarter of 2026 were $9.5 million compared to $7.6 million in the corresponding period of 2025, reflecting increased employee benefit costs and increased pre-commercialization expenses.

Net loss for the third quarter of 2026 was $14.0 million or $0.03 per share compared to a net loss of $12.8 million or $0.04 per share in the corresponding period in 2025.

Net loss for the third quarters of 2026 and 2025 includes noncash stock-based compensation expense of $3.4 million for each of these periods. As of September 30, 2026, Lexicon had $183.2 million in cash, cash equivalents, and short-term investments, compared to $125.2 million in cash, cash equivalents, short-term investments, and restricted cash as of December 31, 2025.

As previously noted, third quarter revenue included the third $10 million milestone payment received this year from Novo Nordisk following the achievement of a Phase I development milestone for LX9851.

We continue to maintain our operating expense guidance for 2026 of between $100 million and $110 million, with R&D expected to be between $63 million and $68 million and SG&A expected to be between $37 million and $42 million, which includes targeted investments in pre-commercial activities.

We remain incredibly pleased with our financial accomplishments thus far in 2026. As we prepare for several important milestones across our portfolio, we remain focused on maintaining the financial flexibility needed to support execution and advance our key strategic priorities while continuing to evaluate opportunities to unlock additional value across the portfolio.

I will now turn it back to Mike for closing remarks.

Thanks, Scott. Now stepping back, we believe Lexicon is entering a potentially transformational 12-month period, supported by multiple opportunities across our cardiometabolic portfolio.

For Sotagliflozin in HCM, we are approaching the pivotal Phase III SONATA-HCM top-line data readout expected in the first quarter of 2027, while continuing our pre-commercial planning and readiness activities.

In type 1 diabetes, we're working towards the resubmission of the Zynquista NDA, supported by additional safety data from STENo-1, with resubmission expected in the first quarter of 2027.

Beyond these near-term priorities, the Phase I program for LX9851 continues to advance with the potential to create additional development milestone opportunities.

And with pelavaptin, we have a Phase III-ready pain program as well as an emerging opportunity in obesity that we are actively investigating.

Taken together, these programs provide multiple potential paths of value creation.

We believe our progress reflects the strength of our science, the breadth of our portfolio, and most importantly, the commitment to creating new opportunities for people living with serious cardiometabolic diseases to live longer, healthier lives.

Thank you again for joining today. We now look forward to taking your questions. Operator, back to you.

I show our next question in the queue comes from the line of Steve Seedhouse from Cantor.

Sorry about that interruption, Steve. Not sure what happened, but please go ahead and ask your question. Terrific. I wanted to ask a couple of questions on the SONATA baseline demographics.

First, just on the -- I think it could be accurately characterized as a bit of an overrepresentation of nonobstructive HCM in SONATA, certainly there are more patients, but maybe even more than sort of like the prevalence or overall demographic of the disease would suggest.

So what do you think is maybe driving that, just in terms of patient motivation or physician motivation to enroll nonobstructive? And then I wanted to also clarify the percent on background CMI, which you indicated is 9%; is that among the obstructive patients? Or is that overall?

So essentially roughly half of the obstructive patients?

Yes. Thanks, Steve. I appreciate the question. So let me take the first one, and Craig perhaps can take the second one.

I think there was a strong representation of nonobstructive, which, as you know, represents what is happening in clinical practice, perhaps a little stronger than what might be within the clinic.

But we have to remind ourselves that these clinical trials are often being conducted by these large academic centers. And these academic centers are where there are available treatments for obstructive HCM.

And so I think the need in nonobstructive, together with the availability of an approved treatment in obstructive disease, means that likely was a contributor to the preponderance of nonobstructive patients in the trial.

Yes. Steve, it's a great question. I think that leads into your second question: if you look at the percentage of patients that are on a myosin inhibitor, it's actually the same percentage of patients on a CCB.

And again, I think that would be quite different than if you looked at the overall population of the number of patients being treated in the United States on a calcium channel blocker versus those on a CMI; the percent in the CCB would be much higher than that, again, in the general population.

So I think in discussions we had with the PIs and our steering committee, they thought that the numbers and the distribution of obstructive versus non-obstructive was not surprising to them.

We had shared with the steering committee, while the trial was running, the numbers as they were evolving, and they strongly urged us not to cap enrollment of one subgroup or another.

When you look at the number of patients that are on a myosin inhibitor, the total number is 49 out of the 542. And just to put that in perspective, there are 50 patients on a calcium channel blocker, which again is not that different from the CCP usage, if you look across SONATA to the trials that were done with both AbbVie and MAVa.

If you look at the distribution, it's about 12% of the patients, and again, let me define, because it's an important point, is the use of CMIs: every single person who was on a CMI had obstructive disease before they were on the CMI.

Because remember, the inclusion criteria of the study is that they're on a stable dose of any underlying therapy for, I believe, a period of 6 months prior to enrollment in the trial.

So all of those patients had a gradient, presumably greater than 50, when they were put on the CMI. To me, the interesting thing is that you have the selection of patients that, at the entry to SONATA, have an outflow tract obstruction or not an outflow tract obstruction, but all of them remain highly symptomatic.

So I'm sorry, that was a really long answer. Please pull it apart if there are other concerns. Go ahead, Mike.

I was going to say that was great. If you have anything to add, please feel free.

I have a follow-up question, unrelated. I wanted to also ask about the -- I mean, there's some interesting data on the pelvapiden weight loss.

First, what's the mechanism behind that, do you think? And then, given that both pelvapidin itself and the mechanism broadly have been studied in humans before, was there any weight loss from any of the clinical studies?

I recall there were some tolerability issues, I think, at the highest dose in the pain Phase II program. So do you think there's an adequate therapeutic index here in humans for obesity or weight loss indications?

Yes. Great question, Steve. And again, I think this goes back to the perspective that Mike raised during the prepared comments that we've continued to explore what we think is a really interesting mechanism of action of AAK1.

There are really sort of 2 domains of activity of AAK1 that I think can largely be looked at. The first is around cell surface receptor recycling, which we believe is the mechanism, both in neuropathic pain and probably in obesity, and I'll come back to that in a second.

The other issue is that there is an issue related to the Notch pathway and triggering cell replication.

And there are some other indications that we'll probably be reporting on next year related to that pathway and shifting the balance of Notch and Numb around cellular replication versus differentiation.

But getting back to your question specifically on the weight loss data, we did see weight loss in the knockout mice returning to the original phenotype.

We believe that the mechanism is probably the same mechanism that we've also talked about: there was a slight increase in both blood pressure and heart rate in the neuropathic pain program that we've disclosed.

And that's probably related to the balance of sympathetic versus parasympathetic tone, both in the cardiovascular system related to blood pressure and heart rate. And in the counterpoint in obesity, you're actually increasing the vagal tone, which actually slows down gastric emptying.

So we believe that the mechanism of the weight loss that we see in the animal models is probably related to that increase in the ratio of vagal versus sympathetic tone in the GI tract.

Now in the human clinical program, we did go back and look at our PROGRESS study results, and we did see a reduction in body weight in both the 10-milligram and 20-milligram arms. It was greater in the 20 than the 10.

Again, to your point, we had a concern that it could be both a bit of nausea and vomiting as well as actual weight loss. But in the 10-milligram dose arm, as you recall, the percentage of patients that finished the treatment period was the same as placebo.

So we are seeing a couple of kilograms of weight loss. And again, you're only talking about 8 weeks of treatment, only 6 weeks at dose.

So we do think even though the trial was not designed that way, this was not an obesity enriched population, nor were there any parameters to control weight loss or other parameters that you would put in a formal obesity trial; we did see a reduction in weight loss in the PROGRESS study.

No, I just wanted to add on to Craig's points here to just remind folks that the important thing with the data we're presenting on pelabapenib is that, while they are preclinical data, potentially, this allows us to move pretty rapidly into a proof-of-concept Phase II study in obesity and some of these other indications.

And it's been our intent, as we await some of the critical readouts that we have coming up over the coming months, that we build a package of data across a number of indications with AAK1 that really demonstrate the overall value of the mechanism.

And we can think then strategically about how we take that forward as we evaluate some of the other important catalysts that we've got going on.

Our next question will be coming from the line of Joe Pantginis of H.C. Wainwright.

I'm sorry if any of this was covered in the beginning. I didn't hear anything for quite some time on the call.

Craig, I was hoping for a little bit of profiling for SOTA in HCM because the field is really expanding quite quickly with the CMIs. Aficamten has the potential to be approved in both non-obstructive and obstructive, as well as the upcoming PDUFA for exercise capacity. So, where do you think SOTA fits?

Additionally, Edgewise confirmed today, with regard to their FDA discussions, that they're looking for less or no echoes at all as part of their platform or pivotal pathway.

So curious about just your quick comments, or what you have for the profiling of soda about where it may fit, number one? And then number two, obviously, you are deep in the filing preparation for T1D.

So just curious what you feel is outstanding to get to the completion of the NDA.

Yes. Thanks, Joe. Maybe I'll take the first point again, and Craig can take the second one.

So look, I think in HCM, this is a large market, and there's going to be plenty of room for multiple pathways, multiple mechanisms to treat the disease.

Clearly, it's not going to be a one-size-fits-all relating to the treatment of HCM. Now, where soda potentially fits within that paradigm, we will be somewhat dependent on how the data reads out, obviously.

But what we can say is that SOTA has not only potential efficacy advantages, they're pending, of course, but having a once-daily oral medicine that with a known safety record immediately avails itself to broad potential, both from a patient base, but perhaps more importantly from a prescriber base, where a large number of prescribers can potentially use this medicine.

So whether that comes as the first choice after beta blockers or it's used in combination with a sarcomeric agent, we will be dependent on data, and we'll see as the space evolves.

But I think having a one and only medicine where we can play our own game, if you like, and let the sarcomeric agents battle against themselves for various risks and benefits is going to be the way that we'll play the game. Craig?

Yes, Joe, I'm happy to come back if there are any further clarifications on the question on the positioning of SOTA versus the CMIs or potentially other sarcomeric agents.

I'll answer the questions on T1D. As I think I mentioned in the prepared remarks, we only crossed the threshold with STENO at the end of August. That's why we had in the slide that cut date.

Obviously, the study is continuing to enroll patients; at least in the standard-of-care arm, the MFI arm is fully enrolled, but the exposure continues to accumulate on SOTA during that study.

And we expect the FDA, in fact, has already told us that over the course of the review, they'd like updates on the data. And we wanted to make sure that the DKA rate on the sot arm was also stable before we submitted the package.

I've been trying to come up with analogs of how to sort of frame this compared to a company-sponsored trial because, remember, this was an investigator-initiated trial that was set up in a manner that was never designed to do the level of oversight and intensive monitoring that you would see as we see in SONATA or any of the other regulatory labeling studies.

So we've really been spending a lot of time. And in fact, we've provided significant additional resources to STENO to help them clean the database.

And it really is a matter of trying to get all of the values and assure ourselves that there is accuracy in all of the data reporting, not to the standard of an academic publication, but to the standard of a potential FDA review, which, as you know, are 2 very different standards.

So we feel quite confident in the rates of DKA that we're reporting. The issue is that FDA is going to also potentially want to look at other parameters to assure themselves of the quality control and oversight and a lot of the other administrative aspects that would be required for FDA filing, things like financial disclosures, just a whole host of issues related to database quality.

You have issues with GDPR in terms of getting data from a European study to a U.S. study that was never designed that way. We had to go back, for example, and get changes to the informed consent so that the data could be sent out.

I mean, this has been a whole host of issues that we've been working through with SEO. Now we do feel that these are in hand, but it's just taken time. It's a very large data set. It's close to 2,000 patients, and we just want to make sure that we're going to put in the highest quality submission.

Our next question will be coming from the line of Gasmin Rahimi of Piper Sandler.

Thank you so much for all the great updates. So, really exciting new data from pelvapan showing weight loss. I would love to understand that you have a great partner with Novo that's working on LX9851.

Have you had the opportunity to share some of these pelovapan data with them? Would love to hear your thoughts on that.

And then also, a second question is in regard to HCM. With such a large distribution of patients with non-obstructive disease, is there a statistical hierarchy that allows you to hit statistical separation in KCCQ and non-obstructive as a sole subgroup?

That would be super helpful. And I appreciate your color. And then one last follow-up as well.

Yes, Great. Let me take the first and Craig the second. Look, we're actually in touch with Novo pretty regularly, as you can imagine, not only on LX9851, but there are a lot of things that are common across our portfolios.

And we have had the chance to discuss this with a couple of people within Novo, not the broader team. There's certainly interest there, as you can imagine, and we'll continue to engage with them and other people as we build on this and other data.

As you can imagine, the chart that we presented to you here is just one piece of data from that series of studies. There's a lot of other interesting data behind that, and it is quite robust.

And it really, I think, shows the value of the mechanism of AAK1. And as Craig mentioned, we'll continue to build on that. In fact, we've got other data we'll continue to share when the time is right to show you that this is a really interesting and important mechanism. Craig?

Yes, it's a great question on the distribution of patients.

And in fact, we spent a lot of time internally with our steering committee with some very well-regarded external academic statistical input, many of the names, I think you would know for sure, and then also a regulatory input on the population.

And the strong consensus across everyone is to maintain the primary endpoint as is with the overall study population. We've looked at a number of different scenarios related to trying to pull out separately the nonobstructive group from the obstructive group.

I think, in the long and short of it, we've decided, with a lot of input, to keep the primary endpoint as is. I think in the SAP, there are still some issues around the hierarchy in which are secondary endpoints that we're looking at as we continue to do some modeling on the data.

And again, we want to finalize the SAP soon. But like many other companies, they don't finalize their SAP till right before the database closes. So we certainly have some time, but we feel quite confident that the primary endpoint of this trial is robust.

I think the fact that we have significantly overenrolled the trial, as well as the fact that the therapy has been well tolerated during treatment, gives us a high degree of confidence in the power to detect the endpoint in the study with about a 4- to 5-point difference in KCCQ score.

So we feel really good about that. We also feel really good about the way the treatment is running and the completion rates of patients. And again, the trial is still ongoing.

So I don't want to say too much, but we feel quite good about the statistics of the trial so far. Yes, that really represents our belief in SOTA in HCM and the unmet need that exists across both obstructive and nonobstructive disease.

Having the overall KCCQ delta as the primary endpoint in both obstructive and nonobstructive is important because, as we see here, there are still folks on existing treatments that are highly symptomatic.

The need in obstructive disease is significant, as it is in nonobstructive disease. So it's important, based on the underlying biology and the market need, that we really can address both obstructive and nonobstructive disease.

Our next question will be coming from the line of Yigal Nochomovitz of Citigroup.

So I just had a few more sort of nitty-gritty questions on SONATA. I think, Craig, you just mentioned that you have some flexibility on the secondary endpoints in terms of the hierarchy there.

So what factors govern the decision on shifting around secondaries in terms of maximizing the evidence set? And then, regarding background diuretic therapy, that's an interesting one in terms of how that could impact the outcome.

You can imagine, obviously, on the SOTA arm, you might see less need for that, whereas you may see more of that on the control arm, but that could also impact outcomes.

So how do you reconcile that in terms of normalizing for that possible difference in the background diuretic therapy to make sure you get a clean readout?

Yes, I'll answer the first question again on the secondary endpoints. And again, the primary endpoint of KCCQ in the overall population is going to stay the key secondary of New York Heart in the overall population is going to stay there.

Right now, we are going to continue the hierarchy as planned down the overall study population, versus looking at the nonobstructive versus the obstructive in that hierarchy as you go down the overall parameters.

And there are a number of echo parameters and enzyme parameters as secondary or exploratory endpoints.

I think those are really far more of interest to the academic publication than to the regulatory file and certainly, the PIs of the study, and we have an eye towards getting the highest possible per publication.

So those are the kinds of things that we're talking about in the hierarchy. But from a regulatory standpoint and from a claim standpoint, I don't think those are really going to change appreciably.

Moving on to the diuretic issue. There are very few patients in the study that are on diuretics. In fact, it doesn't even really come up, as you could see in the baseline characteristics that we've shared and that Dr. Day shared at the Boston HCM meeting about a week or 2 ago.

The largest group of patients on underlying therapy is beta blockers; here, about 80% of patients are on a beta blocker.

And as was previously mentioned, I'm sorry for being repetitive, the next most commonly used agents that are acting on the cardiovascular system are calcium channel blockers and CMIs that are similar, both at about 10% of the patients.

So the diuretic use really isn't a significant issue. I mean, there, you're talking about patients with severe heart failure. And then you're looking at the overall pills for patients with either HFrEF or HFpEF, but there really is not much use of diuretics in this population.

The next question is coming from the line of Andrew Tsai of Jeffries.

At the IHCM conference, when you guys shared the Phase III baseline patient population for SONATA in HCM, we noticed that the obstructive subgroup had a lower baseline KCCQ score compared to the 2 other CMI trials, suggesting a more severe symptom burden at baseline.

And I think for nonobstructive baseline, the KCCQ was maybe in line, if not lower. So the net of this is the question is: is this a favorable or unfavorable dynamic for sotagliflozin to show a positive benefit in Phase III on KCCQ?

Yes. Great question, Andrew. Again, the other trials that have been published out there: some have baseline KCCQ, some don't.

But certainly, as you point out, the baseline KCCQ for Sonata is 55 in the obstructive group versus what was reported for SEQUOIA at about 75.

You can also see that the EF of the patients in SONATA at 67 or 68 is significantly lower than that in SEQUOIA and EXPLORER because they set, as you recall, a threshold for enrollment that's much higher for left ventricular function.

And that group of patients is really a more hyperdynamic group of patients just based on the entry criteria of the selection.

It is interesting in that group, though, that the BNPs are about the same and the outflow tract obstruction is actually somewhat larger, as you would expect in SEQUOIA and EXPLORER because the threshold is set at 50 as opposed to 30 in SONATA.

So, based on the feedback we had from our steering committee, they were really pleased with the number of women that actually were enrolled in the trial, which is important and meaningful.

The fact that you do have patients on a CMI still who are symptomatic with obstructive disease means they really feel that this group of patients is important.

And I would argue that the lower baseline KCCQ is really helpful for trying to show a larger delta in KCCQ because we know the lower the baseline KCCQ, generally the greater the change in KCCQ with treatment.

Agreed. Yes. And then secondly, for the top line release in Q1, how much data can we expect you to share? Can you give us a teaser on what kind of efficacy and safety data? And then what would you be saving otherwise for a medical conference?

I think what we would certainly plan to release is the top line of the primary and secondary endpoints. I mean, those are going to be the key.

I think when a lot of these analyses by these subgroups, we're probably not going to be releasing because a lot of that will require full analysis, particularly when you look at the impact of those that have sarcomeric mutations versus not the effects on outcome by underlying medication use that will probably not be released.

And we'll release something probably on the top line of safety-related effects in the trial, the major safety effects. So I think those are really going to be the critical issues that are going to be released at top line.

And our next question will be coming from the line of Rona Roberitz of Leerink Partners.

This is Frank on for Rona. My question relates to the SONATA-HCM trial with 440 nonobstructive patients and 102 obstructive patients.

Curious what level of consistency across the 2 groups would you need to support a broad HCM label if the overall result is positive, but the obstructive group, for example, is inconclusive; would that limit the indication?

Yes, it's a great question. And normally, what is done, and we have experience with this, is what we did with heart failure when we had both HFrEF and HFpEF in a single population. And what we had discussed and agreed with the FDA is to really look at an interaction p-value in that.

I think all of these things will become a review issue as part of the overall package that we submit to the FDA. I think as long as they are directionally the same, that's been our experience with the agency that they would probably grant the broad label.

That's certainly the spirit in which we went down to the FDA when we initially submitted this trial for review and comment.

That concludes the Q&A session. I would now like to turn the call over to Mike Exton, CEO, for closing remarks. Please go ahead.

So thanks, everyone, and apologies for the technical glitches here on the presentation. But nevertheless, hopefully, you've seen this great progress that the company has made in Q3 to date.

And we've got a lot more coming up over the next 6 to 12 months that we believe are quite transformational for the company across a number of late-stage and earlier catalysts.

So really look forward to sharing more with you in the coming weeks and months. Thanks very much, and have a great day.

Thank you for joining today's program. You may now disconnect.

Welcome to Citi's Biopharma Back-to-school Summit for 2026. We're very pleased to be introducing our next company, Lexicon Pharmaceuticals. We have Mike Exton, CEO. Welcome. Craig Granowitz, CMO, and Scott Coiante, the CFO. Welcome, all of you. Thank you so much. I'm Yigal Nochomovitz, cover the company for a long time. Well, since before COVID, I think.

Anyway, -- so maybe, Mike, do you want to just start us off with the quick kind of overview of where things are with sotagliflozin. And of course, you have a very important Phase III readout coming up in a critical area of cardiology. So why don't you start there?

Yes. No. Great. Thanks, Yigal. And perhaps before diving into SOTA, I can give you a little bit of where we're at as a company over the last couple of years. Really, we focused on driving our R&D programs on establishing financial flexibility and completing a number of partnerships that have gotten us to, I think, a really good state, particularly with SOTA, but across the board. And now we're on the precipice of a very important data readout in HCM, hypertrophic cardiomyopathy with SOTA.

We expect data in Q1 of next year. And really, that is the North Star for the company. And as we sort of execute that -- all of the data into the trial, in parallel to that, we start to think around what the commercial opportunity is for us in this pretty important space. And we recently just promoted Rachel Martens in our company to Chief Commercial Officer. Rachel has been leading our BD&L and partnership strategy and was the driver behind our partnership with Novo Nordisk. And really pleased to have her in that position. She ran the insulin businesses for Sanofi and has worked in biotech.

And we're going to form a very small but very mighty commercial team with -- we now have a Head of Marketing and on the precipice of bringing in a market access person who are really going to do all the prelaunch preparation in HCM because that is our #1 commercial opportunity. Beyond that, of course, we're very soon to resubmit sotagliflozin for T1D.

In addition to that, we have pilavapadin, which is a Phase III ready program in DPNP and of course, our program with Novo Nordisk, which is in Phase I, LX9851 for obesity. So a lot of things over the next 6 months where if you think at the end of Q1 of next year, we could be in a situation where we have data from SONATA in HCM, a potential launch in T1D have started a Phase III program in DPNP and Novo starting the Phase II program in weight management for LX9851. So really important time for the company. Lots of things happening, but with a clear focus for us in HCM.

Okay. So let's start with SONATA-HCM as the study is called. Now the primary endpoint is something called this KCCQ measurement. Maybe, Craig, you could just review exactly what that is so people understand.

And you're looking for what I understand is like a 4- to 5-point improvement there. But you've also over-enrolled -- you've exceeded your target. So kind of just frame like how should we think about having an over-enrolled in terms of probabilities of success? And overall, even without the overenrollment, how do you think about hitting on that target?

Yes. Thank you, Yigal. Important questions you're asking. The primary endpoint that has been identified by health authorities is improvement in feeling and function. Since we have a long history with the molecules, sotagliflozin and heart failure and not only have improvement in symptoms in heart failure, but also improvement in cardiac mortality and reduction in heart failure events. And outside the U.S., our partner has gotten approval also for use to reduce stroke and MI with the agent.

FDA and we agreed and have -- before we started the study that the primary endpoint would be in this KCCQ score. And the secondary endpoint would be in the New York Heart Association score, change in those scores, placebo controlled and adjusted. And that is consistent with HCM. The regulatory hurdle is to improve patient functionality and feeling. There are no long-term outcome studies.

The CMIs that have been approved do not have long-term outcomes associated with that agent. In part, they needed a dual endpoint because these are unproven agents that have never been on the market. And I think there was a concern that KCCQ score alone would not be enough, and that's why they have a co-primary endpoint, particularly outside the U.S. for a physical function benefit of peak VO2.

In our trial design, and I hope as we go to market, we've really tried to take a very broad and pragmatic approach and really thinking about being first and only in mechanism and complementary in use no matter what the agent. And the trial design really takes those criteria into account. We have the broadest range of ejection fraction included.

We have the broadest range of baseline medications, including CMIs in the trial and not requiring all of the physical testing like peak VO2 or exercise testing, it also allowed more centers to enroll more patients more rapidly. So that was the philosophy behind the trial. And I think the result of that is we enrolled the trial quickly at relatively modest cost compared to some of these other trials. And as you've already pointed out, we actually overenrolled the study.

Maybe if I just add on to that, Yigal, because you mentioned a 4- or 5-point delta versus placebo. And the study was certainly powered for that and having an overenrollment improves that powering, obviously. But what our expectation for success is, has really been set by the marketplace. So a delta placebo adjusted of 3 points that's statistically significant.

We think given the benefit risk profile of SOTA would be a home run for us commercially. And anything above and beyond that is obviously upside for us. So we think we have a great chance of this being a very important part of the armamentarium in HCM.

Okay. So let's just dig a little deeper in terms of the components. So you're obviously enrolling the obstructive and the nonobstructive groups. So -- now the argument you've made many times is the mechanism is general to the cardiac energetics as opposed to being sort of a mechanical MOA where you may see a benefit more in one subset versus the other.

So without directly answering the question, maybe go into a little more detail there as to how to think about the nonobstructive versus the obstructive. And then also just when you present the data, how are we going to see it? Are we going to see the groups? Are we going to see everything together? Just frame that part of it for us.

Yigal, you're doing such a good job answering the question. I just want you to continue. But the trial is designed for the combined group together to be analyzed as one. So all of the 500-plus patients as one primary group. As we've mentioned, the trial is stratified based on baseline obstructive or nonobstructive. But as you've already pointed out so elegantly, the mechanism really is going to be independent of the underlying mechanism.

I think there's an expectation in the field, which may or may not be borne out, that the obstructive group is less heterogeneous than the nonobstructive group. The nonobstructive group seems to probably be an amalgamation of different diseases. Certainly, the sarcomeric mutations is going to be a more severe and a relatively more pure form of the disease.

It might be more prevalent having these identified underlying genetic mutations primarily in the energy molecules, the energy proteins of the muscle cell, but not uniquely dependent on them. And I think particularly in the nonobstructive group, perhaps one of the reasons why the CMIs have not been as effective on a relative basis is that the disease itself is more heterogeneous. And one of the advantages, we believe, with SOTA is its breadth of mechanism.

So you're not only getting a number of benefits on the cardiac cell itself with the SGLT1 and as you've already pointed out, you're looking at calcium flux, sodium flux, inflammatory markers, energetics. There's a broad range of activities that have been demonstrated for SOTA and only SOTA because there's only SGLT1 receptors on the heart, not SGLT2 receptors. But you're also getting all of the benefits of SGLT2 inhibition on improving the cardiorenal function, which remember, we're enrolling only patients with symptomatic disease. So they all have elements of congestion and SGLT2 inhibitors are very good at reducing congestion.

So as I said before, I think the idea is to be first and only in mechanism and complementary in use that we believe that if the profile that Mike laid out bears out that we would be very high in the use categorization of agents, but at the same time, it's not going to be necessarily exclusive because we have enrolled patients on a CMI in the trial.

Can you speak to the relative split on the populations? Or you can't get into that yet in terms of the percent that are HCM versus non-HCM and the percent that are on CMIs or just based on the general guidelines and knowing the marketplace, what would be expected there?

Well, again, we designed the trial pragmatically. And I think with very strong encouragement from our steering committee, we did not cap at a hard number one or the other. I think we enrolled more nonobstructive patients than obstructive. We've been public on that. We have not provided numbers because we haven't finished cleaning all the baseline demographics yet. And we will be presenting that data at an upcoming medical meeting probably in the early part of 2027.

But I think we went where the need is. So I think where the centers are right now is there's a greater need and more patients available for clinical trials with nonobstructive disease. So again, we try to model what would be what most people see more closely in clinical practice than having a very rigid clinical trial.

And to the second part of your question around CMIs, we haven't said the exact number, and we don't know the exact number yet, but it's relatively small, but significant enough that you can take some data and some questions and some understanding from that.

So we've got a cohort and really, this will be the only trial that has a cohort of patients on both a CMI and SOTA. So it's going to be really fascinating data to see how the 2 work in tandem. But the other take-home from that very point is that patients on a CMI still have the propensity to be symptomatic, which sort of underscores this original point you made, Yigal, that the underlying disease truly becomes the energetics of the disease and diastolic dysfunction.

And despite improving the obstruction, these patients still remain symptomatic. So there's something much more at play here than just the obstruction. And so we'll see that from this data.

Yes. I mean I think to Mike's point, some of the artificialness of how people think about the disease is a reflection of the trial designs that were done. And if you think about obstruction, it's a continuum. And I think there's this belief just -- and again, it's totally understandable that by running obstructive trials and nonobstructive trials that's like these 2 different things.

When you think about a patient, a lot of the issue around obstruction or nonobstruction is how much effort did the person do with their Valsalva. I mean there's a lot of very qualitative factors. We faced a similar issue when we studied HFrEF and HFpEF together in a population. So by being able to study the entire continuum in this case of outflow tract obstruction and looking at results across the continuum as opposed to this artificial line, I think it's going to be far more informative to the medical and the investor audience about the effectiveness of sotagliflozin in this indication.

Plus you also -- I just thought about it, plus you also get -- I know it's -- I don't think it's stratified by CMI use, right?

No.

But nonetheless, you're going to get some data on CMI plus SOTA versus CMI plus placebo that you can put interestingly and analyze. Even though that's not stratified, it's not -- that's not the main thrust of the study, but that's -- there's some very interesting data there potentially.

Yes. And so to that point, presumably, every patient that was on a CMI when they were placed on the CMI because they just need to be on a stable dose. So that means they've been on the CMI 6 months because that was the entry criteria. So they were all on [indiscernible] because [indiscernible] wasn't commercially available in that time frame. We didn't stratify or hold them accountable to a certain baseline outflow tract obstruction.

So I can tell you there's going to be continuum of outflow tract obstructions, some of which would be considered classically obstructive and some would be at the baseline nonobstructive.

So to Mike's point, there is not a great correlation between obstruction and symptoms, and we have all of those flavors in the trial.

Yes. It's always dangerous when you try to take -- create 2 categorical variables out of what's a continuous variable.

We'd love to do it, but you're right, it is fraught with danger and misinterpretation.

Yes. Okay. By the way, so we should talk to you about some of the secondary endpoints, please. What are the ones that are most important in the study?

Well, I think the ones -- and you saw some of that data presented at ESC from the Afi study from ACACIA. But there's really beyond the New York Heart, which is basically the provider assessment of patient functionality. So sort of the mirror image, the patient with KCCQ is rating themselves.

New York Heart is the health care provider sort of making an external assessment of the patients. But in general, they're very highly correlated over time. There's really a lot of parameters. I would put them in the function and feeling. So those are the primary and secondary endpoint. And then there's a lot of secondary endpoints, the enzymes and then really looking at a lot of the echo parameters.

And I think the echo parameters are really important. And I think to me, one of the key takeaways from ESC is that a lot of the benefits, I would say, and the speaker on the podium said, these benefits are modest and reversible. And so that to me is an important element, not just looking at the enzymes because I think the enzymes are not very reflective, at least with CMIs on benefit because the biggest benefit is on cardiac enzymes, but there's no correlation of that to anything.

I think looking at things like left atrial volume is going to be really important because that's a real reflection of left ventricular function. The left -- the less functional the left ventricle is, the more you generally get a large left atrium. We're going to look at left wall thickness. We're going to look at the speed of the contraction. So there's a lot of echo parameters that are going to be looked at as either secondary or exploratory endpoints.

Okay. And I imagine if you hit presumably on the first -- on the primary endpoint that you would expect to see the secondary endpoints track accordingly if the patients are reflecting a better feeling, better quality of life, right?

I have a high degree of confidence in that, Yigal, because, again, we've got this massive database of heart failure outcome studies. And like in HFpEF, the primary endpoint of the trial we've talked about that SOTA-P-CARDIA was left ventricular wall thickness, and that was the primary endpoint was achieved. And KCCQ score was beneficial in 6-minute walk and a number of other parameters. So I have a high degree of confidence just based on our prior experience in heart failure that you're going to see benefit across a range of these parameters.

Okay. Did you want to say anything else about ACACIA read-through or any other comments there in terms of thinking about your study?

I just think they're complementary mechanisms. And the fact is we're going to have patients on a CMI in our trial. I think that's going to give people comfort around relative safety and tolerability of that in a way, to Mike's point, that you're probably not going to see otherwise because it's in a placebo-controlled large multicenter trial.

Okay. Now you mentioned the promotion to Chief Commercial Officer of one of your BD people. So what have you -- what are you learning or have learned recently in terms of the marketplace that will help you with launching the drug?

Yes. We’ll likely be more elaborate as we get into Q3 earnings to talk about some of the specific research. But I think just listening into some of these conversations with KOLs and payers is clearly in nonobstructive HCM, there's a huge opportunity and the profile of SOTA as presented is in layman's terms, a no-brainer, given the lack of other options, given the relative low bar that's been set for us to be successful there.

What has been interesting is that there's still quite a lot of enthusiasm in obstructive HCM as well for various reasons. One, because despite alleviating obstruction, there's still a high degree of symptomology. Of course, dependent on how the drug functions in obstructive HCM the safety and the tolerability of the drug still lends itself either as an add-on to a CMI in those particular cases or even in first-line use because of the ease of use of that particular drug. So it's been very encouraging so far, and we'll present a lot more specific information on that at earnings.

Okay. And just one thing. So the data is 1Q '27, but given you now know you're done with the enrollment, right, do you have -- is there -- can you be a little more granular with the timing in 1Q? Or are you still just going to keep it open to in 1Q? Or do you have a sense as to where in the quarter we might get the data?

That's a good question. Look, I think it's probably still a little bit early. The closing a trial, it actually involves a lot of work. So you've got to get all the data in. You've got to make sure it's clean. Clearly, you do the analysis, et cetera. I think we'll be more confident to give sort of more specific guidance at the start of next year.

Okay. All right. Fair enough. All right. Let's make sure we talk about some other things. We still have to talk about SOTA, but in a different area. So type 1, where we -- I remember being at that AdCom many, many years ago. But so things have progressed a long time -- a long way since then. So tell us what we're waiting for. I know there's this very important natural history study, which is being conducted over in Denmark, I believe. So tell us what the significance of that is the STENO-1, why that's so important. And then just sort of thinking about what the FDA wants to see and the resubmission path.

Yes. Maybe let me start and Craig can dive into some of the details. So the FDA in the history of SOTA with -- in T1D has really asked for a couple of things the whole time. And this time around, we feel very confident, in fact, having very good engagement with the FDA that we can deliver that. And those 2 things are we want a new prospective study, not a retrospective look at the data, cutting it in a different way. And we need to see from that study a certain amount of exposure on SOTA and to see a DKA level that's acceptable. And until now, we've -- as a company, we've never really known what those expectations are.

What we have now is we have that prospective study, STENO-1 that you're saying is running in Denmark. We have agreement from the FDA that, that study is sufficient and will gather sufficient exposure, which they've given us the exact number. And in fact, we achieved that exposure at the end of August. So the data is done. Data is done. Now we just are in the throes of preparing it and getting ready to submit. And we have a DKA level that is less than what we saw in the inTandem program.

So it's -- all of those 3 aspects have been fulfilled. We're in constant engagement with the FDA to prepare this resubmission. And they are the things that are different this time around. And so we are highly confident that we can finally bring this drug to patients with T1D.

So that sounds like there's some new information there, the fact that you've got -- you've reached that exposure target at the end of August.

Right.

Okay.

Put up the press just for you.

Thank you. So then in terms of the DKA rates, are you -- is the point that -- those rates now are more in line with what would be expected in the T1D population? Or are they more -- because the STENO-1 trial, it's not just SOTA, right? It's a whole bunch of things, if I'm not mistaken. So how does it -- how are those DKA rates comparing to all those other cohorts that are being studied because I think it wasn't it like 2,000 patients or something. It's a big.

Yes. So you're exactly right, Yigal, is it's a 2,000-patient study, and it's a treatment algorithm study. And what that means is patients were randomized by study site, either have a standard of care treatment, which was optimized lipids, optimized A1C and then continue with the standard of care or an enhanced treatment regimen that the added treatment would be according to their baseline demographics.

And the 3 options were either a SOTA group, a semaglutide group or a finerenone group. And as patients went through in that enhanced treatment group, the clinicians could add other medications onto that within that mix depending upon their clinical judgment and the background patient characteristics. But there's a period of time when they're on one of those three.

So you've got 1,000 patients that are in this enhanced treatment group and a significant fraction of that 1,000 is on SOTA. And that speaks to Mike's point, it was just a matter of fully enrolling that 1,000 patient cohort, the percentage of those patients that are on SOTA and then the accumulated exposure that met the threshold that we agreed with the FDA, which is roughly the total SOTA exposure in the inTandem registration program.

The comparisons then we can make are we can make a DKA comparison of the SOTA group in STENO-1 compared to the standard of care group in STENO-1 and the rate achieved with DKA in the SOTA group in STENO-1 compared to the historic rate achieved or realized with sotagliflozin in inTandem.

The primary metric that FDA said was comparing yourself to inTandem because in their communications with us, some of which I think was in the end of review meeting that has been made public is they accepted the efficacy. The only thing they wanted to get was a risk benefit, right? And they said, if you get a prospective group of patients where that DKA rate is lower than that in inTandem, then the risk benefit will be favorable and the drug approvable. But just to be sure, we want to have both the rate compared to inTandem, but also the rate compared to the standard of care, and I think we publicly disclosed this at earnings that the rate that we've observed is similar to that of the standard of care in the STENO trial.

So you have sort of achieved, if I'm not mistaken, sort of a higher bar than even what the FDA was stipulating a little bit maybe.

I think it's just supportive. I think it's supportive from -- we've certainly achieved the expectation that FDA has given us, and we've got a number of different angles that support the same conclusion.

Yes.

Yes. Okay. And so now just very quickly, what's the -- what are the gating factors now to get this -- I mean, this just happened in a few days ago, the exposure target. So when you -- when is the submission timeline, I mean, all that?

So there's been a -- more than a 9-month process we've been working with STENO and the FDA on this. And we've had repeated meetings with the FDA.

We've had ongoing almost daily dialogue with STENO. We're at the point now of collecting all the data in the database that they use, all of the relevant metrics that FDA wanted to see. STENO is in the process of cleaning that data adequately for us to then take that database, put the final analyses together and submit to the FDA.

So that is the ongoing process literally as we speak, is that they are collecting the data, cleaning it to make sure that it is accurate, providing us all of that raw data in a database. And we've already covered all of the issues around patient privacy and all these other things, which again is a long process knowing the data privacy laws between the U.S. and Europe. And then we're in the process now of putting that in the final format for submission of what FDA wants.

So at this point, you're not quite ready to give a time line on that.

No, we've said Q4, so it's going to be this year.

And again, as we march forward over the coming months, we may be able to provide a bit more granularity at earnings.

Okay. Very good. So then let's just switch over then to the DPNP program. So there, you had some very, very strong data in the Phase II and you determined a dose. You've been talking about a partner, but just I guess, just update us there because the emphasis on that seems to a little bit deprioritized perhaps.

No, absolutely, Yigal. I think a number of things have transpired in the earlier part of this year that means we have -- we continue to progress that particular asset, but HCM has risen to the top of our focus, both from our resourcing as well as our sort of investor engagement, et cetera, and where the sort of nearer stage opportunity, large opportunity is.

Nevertheless, one of the things that we said when we were at that time engaging with potential partners as well as publicly is this mechanism, AAK1 has a lot of promise well beyond DPNP. And so to maximize the value of any partnership, we wanted to ensure that they saw that value they could realize well beyond just neuropathic pain. And we don't have the data ready for prime time yet.

But this year, later this year, we will present data, preclinical data admittedly. But again, with pilavapadin, the lead asset for -- that we use in DPNP that shows really remarkable results in a number of new indications. And so we want to bundle all of that up as we look to progress pilavapadin generally and for DPNP specifically.

Okay. So any -- you want to give any teasers there in terms of what other indications?

No. Nice try. You'll hear it first, along with everyone else.

Okay. Fair enough. All right.

But I think it's fair to say these are broadly also aligned with where we are as a company in the cardiometabolic space in areas of high interest.

And I ask this, I gather or maybe I'm interpreting that some of the partners were saying like we'd be interested in X, Y and Z and then you did some of these preclinical experiments to get a little clue or it wasn't like that?

No. We -- look, we -- and Craig really instigated this early last year, I'd say that we have, as you know, through Genome5000, a pretty significant database of lots of different studies or preclinical studies across lots of indications for many, many mechanisms. And we went back and did a huge review of that. And so we kick-started that work before we were really getting serious with the conversations with partners.

Now those conversations with partners and some of this preclinical work were ongoing in parallel. But certainly, those conversations helped reinforce the idea that really let's make sure we capture the full value that this mechanism potentially brings well beyond what is a significant opportunity in DPNP, but we want to make sure that we're not missing any value by leaving potential high-value indications on the table.

I think the other element, and again, I really thank you, Mike and Scott for this is that raising other source of capital, we were able to do the capital raise, the deal with Novo, we took some of the pressure off of having to do a deal to finance in part finance the company.

So we thought that there's a much better value proposition of trying to get additional data and really validating AAK1 as a pathway. Just like we validated sotagliflozin as a pathway, we validated 9851 as a pathway, as we've shared with you, not only in obesity, but also in MASH and potentially in looking at the lipids and cardiac plaque to maximize the value proposition. These are really interesting pathways where we're first and in many cases, only. And I think doing the additional work to have a disproportionate impact on value is what has been afforded with being able to find other ways to finance the company.

Okay. That's a perfectly sensible way to go.

So then last one, so the Novo partnership. I remember at the R&D Day in New York many years ago, you showcased the initial mouse data there, which looked pretty interesting. So ACSL5, obesity is obviously super competitive space and dominated by the heavyweights. So no pun intended. So tell us why ACSL5 -- and what do you sort of expect Novo to do with this drug?

Again, maybe I'll speak generally, Craig, you can speak about ACSL5. But this was really one of the first things we did in my tenure as we looked to focus the company and focus our resources. We knew that we had in LX9851 a very powerful, as you mentioned, the results are pretty incredible on weight loss either as monotherapy or combination on top of semaglutide.

But yet we had a number of other things that were sort of later stage where we wanted to focus our resources and this would be best served in one of the heavyweights' hands. And we had discussions with a number of companies and Novo really rose to the top because of a few things.

Of course, the financial aspect, and this was a very lucrative deal for a preclinical asset, I think. But really, they were very enthusiastic about the mechanism. Craig can talk about that in a second. But then the other very compelling part of Novo taking this on is that, as you know, all of our medicines are once-a-day orally dosed. And we had the feeling -- knew that this would move to an oral-based therapy program, like many cardiometabolic diseases where you use different mechanisms of action, pills in combination. And that's indeed where Novo thinks they're going. And they're putting this right at the top of their mission-critical status and are moving at a speed of knots.

Yes. The ACSL5 mechanism is very important. Early gate in triglyceride metabolism, both biosynthesis and degradation. And that's why it's expressed in the organs where triglycerides are most actively managed and packaged in the body, which is in the gut and in the liver. Now triglycerides are really important in a number of major diseases.

It's the major energy source for the body is triglyceride and how the body moves triglyceride from the gut to the liver to the muscles and the other tissues is via these particles, lipoprotein particles that are primarily triglyceride. So having a mechanism that impacts triglyceride metabolism has massive benefit potentially in obesity, in MASH, which again is the mismanaging of lipids, primarily triglyceride in the liver. And then also in plaque because as you've seen with all these LDL and HDL and Lp(a), these are all packaging addresses of these lipoproteins that go through the bloodstream.

And if they're not packaged correctly, they get deposited in the bloodstream, which leads to development of plaque and cardiac arrest and in stroke. So I think that's why Novo has been so interested while the primary focus is on obesity, there are these other potential benefits. And just to put a point on what Mike said, they only highlight a few of their early-stage assets. Every time now, this is one of the assets that they highlight in their public statements, in their corporate deck. So we're really pleased with having them as a partner.

Okay. Great. One more just because we are asking everyone about AI very quickly. If anyone wanted to throw in their two cents on where you -- how are you using AI internally?

Yes. So at the moment, we're evaluating AI for what I think could be a pretty transformational program for the company. And it's interesting. We've never talked about this, but it's not necessarily material yet to the company. But as you can imagine, the Genome5000 database is a huge data set across both structured and nonstructured data that was collected over the span of a decade or so.

And researching and extracting information from that database is very complex. It was set up 30 years ago. And we are now looking to how do we overlay an AI engine over the top of that, where we can make search queries automatic to enable not only work on our sort of current core programs, but if partners are interested in oncology, for example, we don't even really touch the oncology space of Genome5000, we have the potential to interrogate that database in a very automated, fast and systemic way -- systematic way, I should say.

And just to remind everyone, that was something that was started, I think, in like 1995 or something like that.

Yes. Your memory is good.

That was -- where you basically serially knocked out every gene in the mouse and tried to interrogate the phenotype, yes. Is that what it was?

5000 genes.

Right. Okay. So that was...

Across 60 or 70 different sort of therapeutic trials, preclinical trials across oncology, metabolism, cardiovascular disease, immunology, et cetera. And all of the targets that Craig and I have discussed today came out of that program. All of our medicines are internal. We haven't in-licensed anything. It shows you the power of that Genome5000. But really, given the sort of dating on it, there's untapped potential that we're not necessarily taking advantage of completely, and we think AI will provide us the tool to do that.

Okay. Very interesting. Okay. Well, we'll have to wrap it up there, but thank you all very, very much.

We appreciate you. Thank You.

Welcome to the Lexicon Pharmaceuticals Second Quarter 2026 Financial Results Conference Call. [Operator Instructions] As a reminder, this call is being recorded today, August 6, 2026.

I will now turn the call over to Lisa DeFrancesco, SVP, Investor Relations and Corporate Communications for Lexicon. Please go ahead, Lisa.

Thank you, Therese. Good morning, and welcome to our Second Quarter 2026 Earnings Call. Joining me today are Dr. Mike Exton, Lexicon's Chief Executive Officer and Director; Dr. Craig Granowitz, Senior Vice President and Chief Medical Officer; and Scott Coiante, Senior Vice President and Chief Financial Officer.

This morning, Lexicon issued a press release announcing our financial results for the second quarter of 2026, which is available on our website at www.lexpharma.com and through our SEC filings. A webcast of this call, along with the slide presentation is also available on our website.

During this call, we will review the information provided in our release, provide a corporate update and then use the remainder of our time to answer your questions.

Before we begin, let me remind you that we will be making forward-looking statements, including statements relating to the safety, efficacy, clinical development, regulatory status and therapeutic and commercial potential of sotagliflozin, pilavapadin, LX9851 and our other drug programs as well as our business generally. This call may also contain forward-looking statements relating to our growth and future operating results, discovery and development of our drug candidates, strategic alliances and intellectual property as well as other matters that are not historical facts or information. Various risks may cause our actual results to differ materially from those expressed or implied in such forward-looking statements, and we refer you to the most recent annual report on Form 10-K and other SEC filings for detailed information describing such risks.

I would now like to turn the call over to Mike Exton. Mike?

Yes. Thank you, Lisa, and good day, everyone. Thanks for joining us. Look, I want to begin by focusing on our most recent and major accomplishment, the completion of enrollment in SONATA-HCM, our Phase III study of sotagliflozin in hypertrophic cardiomyopathy or HCM. This study is the largest Phase III study to date in both obstructive and nonobstructive HCM. This marks an important milestone for patients living with the symptoms of HCM as SOTA would be a completely novel and complementary treatment for their disease as compared to all approved treatments currently available and other agents in development.

We're thrilled with the outcome of our enrollment efforts, which resulted in the study being significantly over-enrolled. I couldn't be more pleased with the accomplishment of this critical milestone, and we eagerly await the top line data, which we expect to announce in Q1 of next year.

In addition to the completion of enrollment in SONATA, we've also made other important progress across our portfolio. I'll start by providing an update on Zynquista, where we are at an important and exciting moment for the program.

If you recall, the FDA asked for 3 things to support a resubmission of our new drug application: a prospective study, adequate patient exposure and DKA rates below those observed in our previous clinical trials.

I'll ask Craig to take over here.

The FDA has previously confirmed that STENO1, an open-label investigator-initiated study of sotagliflozin being conducted by the STENO Diabetes Center in Denmark may serve as that prospective study. STENO1 is on the verge of achieving the exposure levels previously identified by FDA as necessary to support a resubmission and the DKA rates observed to date in the study in patients treated with SOTA are similar to patients on the standard of care in the trial and below those observed in our earlier trials. As a result, we believe that each of the FDA's criteria for resubmission of the NDA will soon be satisfied.

We expect that STENO1 will achieve adequate exposure levels by the end of August and following, we will quickly move to finalize the administrative aspects of patient level data collection and transfer from Denmark.

We currently anticipate that we will complete a resubmission of our NDA during the fourth quarter of this year. While this is a slight delay from our previous time line, we cannot be more pleased with the data we've received to date. This is a huge step forward for Zynquista, for Lexicon and for patients with type 1 diabetes who for many years have pleaded for another option besides insulin to manage their blood sugar.

Furthermore, in heart failure, our licensee Viatris has also continued to submit regulatory applications for sotagliflozin across an increasing number of markets outside the U.S. and Europe. To date, Viatris has obtained regulatory approval in the United Arab Emirates and in Bahrain and has submitted applications for regulatory approval in more than a dozen other countries, including Saudi Arabia, Canada and Australia.

Viatris anticipates regulatory decisions in Australia and Canada and additional regulatory submissions in other markets this year.

Turning to 9851, a first-in-class ACSL5 inhibitor for obesity, a Phase I study is underway and being conducted by our licensee, Novo Nordisk. We have previously received 2 $10 million milestone payments under our license agreement with Novo and have the potential to receive a third $10 million milestone payment later this year. We are excited to see the continued progress on this promising compound.

Finally, turning to pilavapadin. Our belief in the potential of this agent and its novel AAK1 inhibition mechanism of action only continues to grow. We have exciting work underway exploring its utility in other potentially high-value indications, and we look forward to sharing data from these preclinical studies as early as later this year.

Yes. Sorry about that, everyone. Thanks, Craig, for taking that on. But really, I couldn't be more pleased with where we're at, both for HCM and importantly, for Zynquista. This is a really important milestone for us in this program. As many of you know, we've been working with the FDA very constructively and are now on the precipice of having all the requirements needed to move forward with the NDA.

So with that, I'll ask Craig to continue and give you the pipeline update.

Thank you, Mike, and good morning, everyone. I'll start with sotagliflozin, our novel oral SGLT1 and SGLT2 inhibitor, which is in late-stage development in both HCM and type 1 diabetes. I'd like to begin by discussing the underlying pathology of HCM and why we at Lexicon believe that sotagliflozin is uniquely positioned to address the tremendous unmet need in this space.

Hypertrophic cardiomyopathy, or HCM, is a genetic disease characterized by adverse cardiac remodeling associated with myocardial hypertrophy, diastolic dysfunction and fibrosis. This fundamental biology is present across both non-obstructive and obstructive HCM, which I'll refer to as nHCM and oHCM independent of underlying anatomy.

It is important to note that even in oHCM, symptoms and progression are not explained by left ventricular outflow tract obstruction alone. It is noteworthy that in oHCM, patients in which the outflow tract obstruction has been eliminated through surgery or other means, patients may still remain symptomatic due to the underlying disease process.

Diastolic dysfunction is the underlying disease process observed in both nHCM and oHCM. This dysfunction is characterized by an abnormally thick and stiff left ventricle and impaired diastolic relaxation. These metabolic and anatomical changes negatively impact cardiac function.

Both types of HCM are characterized by a thick and left ventricle associated with fibrosis, which results in a less pliable and improperly functioning left ventricle. These changes in cardiac structure and function result in the physical manifestations of shortness of breath and exercise intolerance that often impact patient quality of life.

SOTA's unique dual SGLT1 and SGLT2 inhibition directly addresses the underlying diastolic dysfunction that characterizes HCM. By improving how the heart uses energy and other mechanisms, we believe that SOTA has the potential to demonstrate similar benefits in both nHCM and oHCM.

SGLT1 is expressed by cardiac myocytes and the level of expression is increased in cardiac diseases such as HCM and other cardiomyopathies. And as a reminder, SGLT2 is not routinely expressed in the myocardium.

By inhibiting SGLT1, SOTA improves cardiac cell function in the heart through mechanisms such as enhanced calcium flux, improved energy utilization, reduced inflammatory and fibrosis markers and reduced epicardial fat. In addition to the cardiac benefits of SGLT1 inhibition, SGLT2 inhibition also has a positive effect on the cardiorenal dysfunction that is a hallmark of all patients with heart failure. As a result, SOTA is the only agent that works both inside and outside the heart to reduce the symptoms of HCM.

As Mike highlighted earlier, we are excited to have completed enrollment in the SONATA-HCM trial, which is evaluating the effects on symptoms, function and other patient-reported outcomes as well as safety in patients with symptomatic HCM. We are pleased that the trial was significantly overenrolled and as such, should positively impact the overall study powering.

The study included a substantial majority of patients with nHCM, providing a robust opportunity to evaluate SOTA in a patient group for whom effective treatment options remain limited as well as a meaningful cohort of patients with oHCM.

As a reminder, the primary efficacy endpoint is improvement in symptoms as measured by the change from baseline to week 26 in the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score or KCCQ CSS for the overall patient population. Patients with symptomatic HCM on a stable dose of guideline-directed HCM therapy, including cardiac myosin inhibitors were permitted to enroll in the trial.

Our objective was to conduct a pragmatic study where the enrolled patients truly reflect the treatment paradigm for this disease. We believe that the final study population will enable a thorough assessment of SOTA's potential across the spectrum of symptomatic HCM, and we look forward to sharing top line results in the first quarter of 2027.

Moving to Zynquista. I'd like to elaborate a bit on where we are in the resubmission process for our new drug application. By the end of August, we expect that the STENO1 study will have achieved the number of patient years of sotagliflozin exposure that FDA had previously identified as being necessary to support refiling.

The DKA rates observed in the STENO trial amongst patients treated with SOTA remain similar to those observed in the standard of care group in the study and well below that observed in our previous inTandem studies.

Based on our previous discussions with FDA, we believe that these levels of exposure and DKA rates support a resubmission of the NDA. We have been providing these data along with additional information from the study to the FDA on an ongoing basis, excluding and most recently as this week.

Concurrent with our FDA discussions, we have been in continuous dialogue with the STENO group to ensure the appropriate collection and formatting of the necessary data fields and analysis parameters for NDA resubmission, which we believe could occur at the end of October 2026 based on our current estimates.

Turning to our earlier-stage pipeline, LX9851, a first-in-class non-incretin oral small molecule inhibitor of ACSL5 is currently in Phase I development by our licensee, Novo Nordisk. We could not be more pleased with the continued collaboration with Novo on this promising compound, and we look forward to future results.

I'll now turn it over to Scott to provide an update on the company's financials.

Thank you, Craig, and good morning, everyone. I'll begin with a review of our financial results for the quarter. Total revenues were $0.7 million for the quarter ended June 30, 2026, compared to $28.9 million for the corresponding period in 2025. Revenues for the second quarter of 2026 represented net sales of INPEFA, and revenues for the second quarter of 2025 included $27.5 million in licensing revenue recognized from the Novo Nordisk licensing agreement in addition to net sales of INPEFA.

Research and development expenses for the second quarter of 2026 were $17.4 million compared to $15.7 million in the corresponding period of 2025, reflecting higher external costs in 2026 related to our ongoing SONATA-HCM Phase III clinical trial.

Selling, general and administrative expenses for the second quarter of 2026 were $9.8 million compared to $9.4 million in the corresponding period of 2025. Net loss for the second quarter of 2026 was $31.8 million, or $0.07 per share compared to net income of $3.3 million or $0.01 per share in the corresponding period in 2025.

Net loss for the second quarter of 2026 and net income for the second quarter of 2025 included noncash stock-based compensation expense of $3.3 million and $3.2 million, respectively. Net loss for the second quarter of 2026 also includes a loss on the early extinguishment of debt of $4.3 million, or $0.01 per share resulting from the early repayment of the company's term loans with Oxford Finance. The company replaced its debt facility in May of this year, which I will expand on momentarily.

As of June 30, 2026, Lexicon had $190.6 million in cash, cash equivalents and short-term investments as compared to $125.2 million of cash, cash equivalents, short-term investments and restricted cash as of December 31, 2025.

As previously noted, we have taken steps to improve our balance sheet and enhance our financial flexibility. And in May of this year, announced a $100 million debt facility with Hercules Capital. Under the terms of this agreement, an initial $55 million tranche was funded at closing and was utilized to repay our previous loan facility with Oxford Finance.

A second $20 million tranche is available for draw Lexicon's option, subject to the achievement of certain clinical, regulatory and financial milestones and specified timing requirements.

A third $25 million tranche is available for draw at Lexicon's option, subject to Hercules consent and specified timing requirements. The loan facility provides for an initial interest-only period of 18 months with the potential for 2 6-month extensions.

We are also reiterating our operating expense guidance for 2026 of between $100 million and $110 million and continue to anticipate R&D to be between $63 million and $68 million and SG&A to be between $37 million and $42 million.

During the second quarter, we initiated targeted investments in precommercial activities focused primarily on medical education and marketing preparation. These investments will also include market access activities as we approach the late-stage development of our assets, which is included in our estimates.

We are incredibly pleased with our financial accomplishments thus far in 2026, including our capital raise in February and the new loan facility with Hercules. We have strengthened our balance sheet and improved our financial flexibility while remaining prudent with our expenses ahead of our important milestones expected in the coming months.

I will now turn it back to Mike for closing remarks.

Yes. Thanks, Scott. Look, this quarter, we're really starting to see the output of the Lead to Succeed strategy, which we put in place 1.5 years ago. We're focused on driving opportunities that have the highest probability of impact where we believe we can truly make a difference and have the greatest chance for success.

Indeed, using Lead to Succeed as our guiding principle, we believe the next 12 months have the potential to be one of the most transformational periods in Lexicon's history. We have significant opportunities ahead of us that could meaningfully expand the reach of SOTA and the impact we can have for patients. First and foremost is our opportunity for SOTA in HCM, where it has the potential to be the first and only medicine indicated to treat patients across the spectrum of disease.

As Craig explained, SOTA's unique mechanism of action, which includes not only SGLT2 but also SGLT1 inhibition, differentiates it as a hemodynamic and metabolic agent and sets it apart from all other agents in HCM. SOTA also offers what we believe will be an ease of adoption for patients and prescribers, supporting its potential as a first-line treatment with broad use.

At the same time, we've reached an instrumental point in the development of Zynquista in type 1 diabetes. Over the last 12 months, we've actively engaged with FDA and received clear feedback on their requirements for submission of our NDA.

In addition to these late-stage opportunities, we're also making progress across our entire portfolio and continuing our commitment to operational excellence. Together, these priorities position Lexicon to drive value and growth while staying focused on areas of meaningful patient impact.

Thanks again for joining today. We now look forward to taking your questions. Operator?

[Operator Instructions] Our first question today is from Yigal with Citigroup.

This is Joohwan Kim on for Yigal. On SONATA, given that there's a substantial majority of nHCM patients with a meaningful oHCM cohort as well, how should we think about that mix in terms of the commercial and regulatory value of the study if overall population is positive? And is directionality across both phenotypes more important in your view than the exact magnitude in each group?

Yes. Thank you for the question. It's Craig Granowitz. I'll start, and I'll turn it over to Mike to answer the commercial element.

From the standpoint of the trial enrollment, this is really where the need is. As I mentioned during the prepared remarks, we're really looking at a pragmatic study that reflects the population that is currently available and in greatest need. And that really is a large number of nonobstructive patients where there really are no options that are available.

With obstructive, there are both surgical and other options as well as medical options available. As I've mentioned in past calls, and I hope I was able to communicate, the trial was powered on the overall population. That was what we had discussed with the FDA that includes both obstructive and nonobstructive, and particularly with the significant over enrollment, this gives us even more confidence in the primary endpoint that we selected in our power to observe that primary endpoint.

And also to reinforce, while there are more nonobstructive patients in the trial, we believe that there's a significant number -- a significant enough number in the -- of the obstructive patients that gives us great confidence that we'll be able to observe and find meaningful results in both the obstructive and nonobstructive groups.

Yes. And from a commercial perspective, we see that there's opportunity across the spectrum of disease, both in obstructive and nonobstructive, obstructive clearly where there are already approved agents, but still a significant number of patients remain symptomatic and nonobstructive where there are currently no approved agents. And this mechanism allows us to work in a space where we are the one and only SGLT inhibitor in HCM. And that provides applicability across the broad spectrum of disease either as a solo treatment for HCM or in combination with the other CMIs.

Got it. And if I could just ask one more question. On LX9851, I was curious how we should think about the bar for continued development coming out of the Phase I. What would constitute a supportive data package for Novo to move the program forward?

Yes. Look, for 9851 in terms of the bar for development, that really is a question now for Novo. What we can say is that we're incredibly pleased with how the partnership has progressed to date. Novo is very enthusiastic about this mechanism and the trial -- Phase I trial is progressing extremely well.

So we have always thought that the combination of different mechanisms of oral medicines will probably be an important player, an important therapeutic option in obesity. And clearly, Novo being the leader of oral weight loss medicines is taking that approach with LX9851 as well. So we're really excited to see the continued development and progress that Novo is making.

Our next question is from Andrew Tsai with Jefferies.

It's Brian Balchin here for Andrew Tsai. Just on type 1 diabetes, you're resubmitting that now in Q4 versus I think it was around mid-'26 before. So is it fair to assume approval could be closer to mid-'27, assuming a Class II resubmission? Can you just talk a little bit about why that's taking longer to accrue data?

Yes. It's a great question. And we've been working very hard with both the FDA and STENO. And I hope I've been effective at communicating over time that STENO is an investigator-initiated trial that was never designed for regulatory purpose. And we've been continuously work with STENO to pull all of the data together. We had a certain regulatory path that we were considering, but just based on the ability of STENO to pull the data together in a timely way in the manner that the FDA wanted, it's just taking them more time.

I think as both Mike and I reinforced, the most important aspects is that the trial has now achieved the exposure required by the FDA for sotagliflozin patients as well as the control group because FDA wanted to see the control group in the study as well and extraordinarily encouraging the rates of DKA that we're seeing. And as a reminder, this is an open-label trial.

So we're getting monthly or even more frequent updates from STENO on the exposure data. The rates of diabetic ketoacidosis in the SOTA-treated group seems to be similar on an exposure basis to that in the standard of care. And that's certainly well below that, which was observed in the inTandem trial.

So to me, it's just a matter of how long is it going to take to pull the details together from STENO in the format and the way that we have agreed with the FDA to submit, not do we have a drug that has met the requirements that FDA set out in the outset of this process of a favorable risk benefit.

And I think the other thing to keep in mind here regarding the timing, we expect and as we outlined, we think that the submission could be as early as the end of October, which with a 6-month review would put us nicely in Q2, but not at the end of Q2. But having said that, this is an unusual review because clearly, the FDA has seen a lot of the information that they'll see in this submission. And the actual data that they'll be reviewing from STENO is not as comprehensive as a normal review. So we will work with them very proactively as we have done in the past to see if there is possibility for a review quicker than the statutory time line.

Our next question is from Roanna Ruiz with Leerink Partners.

A couple from me. I wanted to ask a question about SONATA and if you're able to share the proportion of patients on CMIs? And how you think that might impact the -- both the overall results and informing future prescribing because I noticed that you're talking about majority of patients are nHCM. So what does that mean for the oHCM proportion of patients in the trial?

Yes. Thanks, Roanna. Great question. We haven't broken out and we probably won't until we share the baseline characteristics of the study at an upcoming medical meeting. But I can say that there are a fair number of patients on a CMI. But as you would expect, the availability of CMIs in the trial was rather limited. We included 20 countries in the study. And while the U.S. was the largest -- single largest enrolling country, was certainly not a majority of the patients.

So I think sort of taking that into account and the protocol required patients to be on a stable dose of any of their underlying CMI -- underlying HCM medication for at least 6 months. But I can say that we do have patients in the trial that are on a CMI and both patients that the baseline were considered obstructive by the criteria and nonobstructive by the criteria.

So what I would infer from that is that all of the patients are put on a CMI because they were obstructive at some point. So it is interesting to note, and as we were referencing repeatedly through our prepared comments, that even if you remove the outflow tract obstruction, patients are still symptomatic.

So we have, in a sense, all different options. We have patients who are obstructive and nonobstructive in the trial and patients that are on CMI that are also at the baseline of enrollment in our trial that have either an obstruction by the definition of obstruction in the trial or nonobstructive.

The single unifying characteristic of the trial is they all have a baseline KCCQ score of less than 85. And I think that really is the gold standard today is managing symptomatic relief of these patients.

Super helpful. And a follow-up question. Could you give us your updated thoughts about where you believe SOTA fits into the HCM landscape? We've been following a couple of biotechs that are gearing up to start Phase III trials and could potentially enter after SOTA as well in the market. How do you see prescribers making decisions between these different programs?

Yes. I think overall, the important thing is that this is a complementary mechanism to the currently approved agents and potentially newer agents as well. So this is really the way we've approached it with Lead to Succeed is that we can play in a way our own game and have the potential to be prescribed either as a stand-alone or combination therapy with other agents.

Now there are a few unique attributes to SOTA in this market that really augur well for a first-line treatment option. The first is that it's an oral once-a-day medicine that's extremely well tolerated and very safe. And so that really has the propensity to be prescribed very easily with broad access for patients. And so we would see this naturally as an option that a broad range of prescribing physicians could turn to immediately for symptomatic HCM with the possibility of currently, if they have an obstruction, then looking to add the CMI if they are still symptomatic.

Our next question is from Yasmeen Rahimi from Piper Sandler.

Thank you so much for all the great updates and again, congrats on SONATA. Excited to look forward to the data. Craig, question for you is obviously, the population contains both obstructive and nonobstructive and the study is powered for a KCCQ in both populations. How do you envision between now and the top line data to maybe potentially explore the optionality if there is a path forward if you see statistical separation in one population versus another? Is that something that you guys would evaluate? What work goes into it? And how much flexibility do you have until you lock the database and provide that update? So if you could talk about sort of the statistical protocol, how you're thinking, whether you want to change it or not?

And then the second question is, I'm sorry if it has already been answered, but maybe just the type of data that were generated by the PI for Zynquista as well as in-house to correlate together to make -- to ensure a filing to be near complete and the timing around that? And I'll jump back in the queue.

Yes. Thanks, Yas. Great questions. It's a really good question about the statistical analysis plan. And good clinical practice, normally, you want to finalize your SAP before you close your database. So we have a number of months theoretically that we can do that.

In light of as we're completing enrollment, we are certainly taking a really another good hard look at the SAP. I don't think there's really probably going to be any changes to the primary endpoint. The primary endpoint is the KCCQ score at week 26 in the overall population between placebo and the treated group. And as I said previously and Mike has said, that includes both the obstructive and nonobstructive.

I think depending upon market, how the market unfolds and as other piece of information come into the market over the next several months as this is a dynamic market, there might be some shifting in the order that we do the hierarchy in the statistical plan right now. The key secondary is New York Heart. I think there are potential things that we could think about in the hierarchy of the statistical plan. But I think right now, we're very much aligned internally and with our external Scientific Advisory Board and co-PIs that the primary endpoint of week 26 placebo-adjusted KCCQ score is not going to change.

I think on the -- I hope that answers the first. I'll answer -- move to the second question on STENO. The amount of interaction we've had with STENO is extensive. And as I think I mentioned, we get monthly updates from STENO on patient enrollment, patient enrollment by group, number of cases of DKA. We have the detailed narratives of every single patient that's developed DKA. They've been translated. We've been in continuous dialogue with the PIs of that group.

We've looked at their database. We've looked at their electronic medical records. We've looked at the ability of that electronic medical record, which is in a certain format to be downloaded into SAS, which is the format that FDA database requires for submission. We've looked at the programming of SAS. I mean we have really extensively looked at this from both a data quantity and quality standpoint.

We've agreed on the key variables that FDA wants to see as baseline characteristics, the exposure of DKA. We -- as I said, we have the detailed narratives of the DKA cases. So we feel comfortable that we understand each individual patient that's developed a DKA event, whether or not they are on SOTA or not. So I feel that we've really detailed gone through this in a really extensive fashion.

Let me just pile on that quickly there, Craig. I just want to take a moment to really recognize the scope of this data and the scope of the study as well because what we have been able to collect in collaboration with the FDA is now an exposure on SOTA that really is just a little less than what we saw in the entire inTandem program.

So inTandem program was the largest trial in type 1 diabetes for glycemic control. So this is a significant amount of data, a significant amount of exposure. And as we mentioned in the prepared remarks, what we're seeing in the DKA rates between SOTA and the standard of care is similar, exactly no more than standard of care.

And so this is really compelling data that we've engaged with FDA over a number of months now. And we're at the precipice of being able to really have all that together and submit the NDA. And really, it's a pretty significant moment for this program, which has a history both with Lexicon and the FDA, as you know. So I'm really, really delighted that we've reached this milestone.

[Operator Instructions] I'm showing no other questions at this time. So I would now like to turn it back to Mike Exton, Chief Executive Officer of Lexicon.

Thanks, everyone. Look, thanks for joining us today. This has been a really important call and a really important point for Lexicon as we really execute lead to succeed.

We've got a lot going on over the next 12 months, a lot to execute, but many milestones and potential catalysts ahead of us. And so I really want to thank the Lexicon team for all the effort that they've put in, in particularly progressing these 2 very important late-stage programs for sotagliflozin in type 1 diabetes and HCM and look forward to updating you further as we go throughout the rest of 2026. Thanks a lot, and have a great day.

Thank you for your participation in today's conference. This does conclude the program. You may now disconnect.

Welcome to the Lexicon Pharmaceuticals First Quarter 2026 Financial Results Conference Call. [Operator Instructions] As a reminder, this call is being recorded today, May 7, 2026.

I will now turn the call over to Lisa DeFrancesco, SVP, Investor Relations and Corporate Communications for Lexicon. Please go ahead, Lisa.

Thank you, Tricia. Good morning, and welcome to our first quarter 2026 earnings call. Joining me today are Dr. Mike Exton, Lexicon's Chief Executive Officer and Director; Dr. Craig Granowitz, Senior Vice President and Chief Medical Officer; and Scott Coiante, Senior Vice President and Chief Financial Officer.

This morning, Lexicon issued a press release announcing our financial results for the first quarter of 2026, which is available on our website at www.lexpharma.com and through our SEC filings. A webcast of this call, along with a slide presentation is also available on our website. During this call, we will review the information provided in the release, provide a corporate update and then use the remainder of our time to answer your questions.

Before we begin, let me remind you that we will be making forward-looking statements, including statements related to the safety, efficacy, clinical development, regulatory status and therapeutic and commercial potential of sotagliflozin, pilavapadin, LX9851 and our other drug programs as well as our business generally. These statements may also include characterizations and projections relating to the clinical development, regulatory status and market opportunity for our drug programs and the commercial performance of INPEFA for heart failure.

This call may also contain forward-looking statements relating to our growth and future operating results, discovery and development of our drug candidates, strategic alliances and intellectual property as well as other matters that are not historical facts or information. Various risks may cause our actual results to differ materially from those expressed or implied in such forward-looking statements, and we refer you to our most recent annual report on Form 10-K and our other SEC filings for detailed information describing such risks.

I would now like to turn the call over to Mike Exton, our CEO.

Yes. Thanks, Lisa, and good day, everyone. Thanks for joining us this morning. Look, we began this year with an ambitious set of 2026 objectives, which are to: firstly, advance our late-stage regulatory programs, both of which have major potential milestones midyear; second, expand our internationally through both existing collaborations with Viatris and Novo Nordisk and the new collaboration for pilavapadin; and third, to remain operationally disciplined and focused, which is the foundation to support long-term growth and value creation. And I'm really excited that we've executed on all of these fronts.

Now as I reflect back at where we were last year around this time, it's truly incredible to look at the evolution of Lexicon across the board. Our strong R&D execution has resulted in significant progress across each one of our late-stage programs. And through our focus on operational excellence, including lowering our expenses, executing a successful capital raise earlier this year and establishing a new debt facility, which we just announced this quarter, we've taken the steps to ensure we're financially solid. We're on the precipice of a number of pivotal milestones in the coming months with the potential to completely reshape the future of this company as well as the treatment landscape for the patients we serve. We couldn't be more excited for what's to come.

Now to summarize our year-to-date highlights in a bit more detail. Lexicon is advancing a portfolio of novel targeted therapies in 2 main therapeutic areas, cardiometabolic diseases and chronic pain. We've made meaningful progress across each of these programs. Now starting with sotagliflozin. In hypertrophic cardiomyopathy, or HCM, we are on track to complete enrollment in the SONATA Phase III study midyear. SONATA continues to enroll well, and we're seeing strong execution as we approach enrollment completion.

Type 1 diabetes, we remain on track to resubmit our application for approval of Zynquista with the FDA by midyear, putting us in the position of a potential approval as early as this year. As a reminder, this resubmission will leverage investigator-initiated study data from the STENO1 study, and the data we've seen thus far continue to support a favorable benefit risk profile.

On the global front, our licensee, Viatris has submitted regulatory applications for SOTA in heart failure across an increasing number of markets outside the U.S. and Europe with a launch underway in the United Arab Emirates. With LX9851, a first-in-class ACSL5 inhibitor for obesity, our licensee, Novo Nordisk initiated the Phase I study in March, marking the program's entry into clinical development and triggering a second $10 million milestone payment.

We're incredibly pleased with the progress and applaud the Novo Nordisk team for how swiftly they advanced this novel treatment candidate to the clinic. We're excited to see the continued progress. And within chronic pain, we continue to deepen our understanding of the profile and potential of pilavapadin. We've met our regulatory objectives and remain in discussions with third parties regarding next steps for the program.

Now our initial objective in securing a partner for pilavapadin was really to secure nondilutive capital to support the important late-stage cardiometabolic opportunities in HCM and T1D. While we currently have no plans to fund the Phase III development for this program, the steps taken to strengthen our financial position, including our recent capital raise and refinancing of our loan facility provide us with the financial flexibility to find the right partner and explore structures that reflect the value of this novel asset, which we believe is significant.

Lastly, in addition to the strong progress on our pipeline, the team has continued to deliver on our commitment to operational excellence and strengthening our balance sheet. So lots going on, lots to look forward to.

And with that, I'll ask Craig Granowitz, our Chief Medical Officer, to provide additional color on these pipeline updates. Craig?

Thank you, Mike, and good morning, everyone. I'll start with sotagliflozin, our novel oral SGLT1 and SGLT2 inhibitor, which is in late-stage development in both HCM and type 1 diabetes. I want to take a moment and remind everyone of the important and unique effects of sotagliflozin's mechanism of action. Sotagliflozin is the only dual inhibitor of both SGLT1 and SGLT2, and I want to emphasize the importance of the SGLT1 effects.

While SGLT2 is expressed primarily in the kidney, SGLT1 is expressed in the kidney, but also in other tissues, particularly the GI tract and the heart as well as the endothelial. Inhibition of SGLT1 in the GI tract is important in postprandial glycemic control in people with T1D. And we believe the inhibition of SGLT1 in the heart has important effects on myocardial health, particularly in disease states like HCM. It is also noteworthy that SGLT1 expression is upregulated in patients with ischemic heart conditions and in patients with hypertrophic cardiomyopathy. Lexicon continues to study and publish the biology of inhibition of the dual effects of both SGLT1 and SGLT2.

As Mike mentioned, we are rapidly approaching 2 important potential catalysts for sotagliflozin, both of which are anticipated around midyear. First, for HCM, we expect enrollment of our global Phase III SONATA trial of sotagliflozin in HCM to be completed by mid-2026. This pivotal study is evaluating approximately 500 patients with HCM, randomized across 130 enrolling sites in 20 countries and includes patients with obstructive and non-obstructive phenotype.

Based on current enrollment trends, we continue to anticipate top line data from this study in the first quarter of 2027. In type 1 diabetes, we remain on track for an NDA submission of Zynquista for glycemic control in adults with type 1 diabetes based on clinical data from the STENO1 investigator-initiated trial. Based on the data from the study thus far and FDA discussions, we believe there is potential for Zynquista to be approved in 2026. On the base of our activities with SONATA-HCM trial and with the STENO study group, we believe that sotagliflozin has the potential to meaningfully advance the treatment landscape for people with HCM and for those with T1D.

With this in mind, let me tell you a bit more about what gives us confidence in sotagliflozin in these 2 indications. As a reminder, SONATA-HCM is a large global registration trial with a primary endpoint of placebo-adjusted improvement in the KCCQ CSS score and is designed to support a regulatory filing and broad label in HCM. The study randomized adults with symptomatic HCM, which includes both obstructive and nonobstructive phenotypes. With its unique dual mechanism of action, we believe sotagliflozin should provide clinically meaningful improvements in both symptoms and function in both the obstructive and nonobstructive disease.

Sotagliflozin is acting through a dual mechanism or a distinct mechanism from CMIs. Patients on a stable dose of CMI who continue to have heart failure symptoms are also enrolling in the study. What makes sotagliflozin different is that it's acting both as a hemodynamic agent and as a metabolic agent to treat HCM. To explain further, through SGLT1 inhibition, sotagliflozin acts as a metabolic agent directly on the heart to improve the heart -- the functioning of the heart muscle.

Additionally, sotagliflozin is acting as a hemodynamic agent by acting on the cardiorenal axis to improve the body's fluid balance and improve outcomes. In total, if you consider its once-daily dosing regimen, established safety profile in clinical studies and post-marketing use and proven CV outcomes in patients with heart failure, we believe that sotagliflozin has the potential to be broadly adopted in the management of HCM with a strong benefit risk profile.

In recent months, we've continued to present additional evidence supporting sotagliflozin's unique potential. In addition to recent data presented on T1D, I'd like to focus on the SOTA-P-CARDIA study of sotagliflozin at the American College of Cardiology Annual Meeting. These analyses provided further evidence of benefit across patient subgroups potentially related to its mechanism of action.

As previously reported, results from SOTA-P-CARDIA demonstrated a placebo-adjusted 19-point improvement in the KCCQ score. These new analyses showed meaningful effects of SOTA on changes in patient functioning as measured by the 6-minute walk test. Additionally, there was an impact on a number of metabolic parameters, including a reduction of epicardial fat in patients treated with sotagliflozin. While not shown in this slide, there was also a reduction in the left atrial volume in those patients treated with sotagliflozin. Collectively, the data from this study demonstrate meaningful benefits on symptoms, function and physiology, which may validate the effectiveness of SOTA in HCM for clinicians.

Turning now to Zynquista in type 1 diabetes. As we have previously discussed, the FDA has confirmed that data from STENO1, third-party funded investigator-initiated study being conducted by the STENO Diabetes Center in Denmark is adequate to support a resubmission for our NDA provided patient exposure and safety data requirements are achieved. Based on the data that we have seen to date, we are optimistic that we are on track for NDA resubmission midyear with potential approval in 2026. There are 3 key points supporting our time lines and potential for Zynquista. First, enrollment is going as expected in the trial. Second, we remain comfortable with the data and safety profile STENO1 has generated to date. And third, we are continuing to work on an ongoing basis with the FDA on the final parameters surrounding the exact formatting and submission dates for the data.

In short, there are a number of items that need to be completed in order to file midyear, but we remain on track. If approved, Zynquista will be the first and only oral adjuvant to insulin therapy ever approved for glycemic control in type 1 diabetes. Our final cardiometabolic program is LX9851, our first-in-class non-incretin oral small molecule inhibitor of ACSL5 in development for obesity and associated metabolic disorders. Global development by our licensee, Novo Nordisk continues to advance and LX9851 is now in the clinic following Novo's initiation of a Phase I study in March. We are pleased by Novo's continued enthusiasm for this candidate and its novel mechanism and how swiftly Novo has advanced this program into clinical development.

Now turning to our chronic pain program. Like sotagliflozin, pilavapadin has a broad pipeline and a pill potential. Pila is a novel investigative therapy targeting AAK1. Beyond DPNP, we believe that there are a number of potential applications for pilavapadin. The AAK1 pathway is central to a number of cellular processes such as synaptic signaling between neurons involved in pain signaling and also spasticity. With this in mind, we are conducting IND-enabling work in multiple additional neuroscience indications.

Last month, we presented 2 additional data sets at the AAN Annual Meeting that further validate the development of pilavapadin in DPNP as well as other neuroscience indications. First, we shared additional efficacy data from the PROGRESS-3 Phase IIb study supporting the selection of pilavapadin 10 milligrams for Phase III development in DPNP.

Following the top line results from the PROGRESS Phase II study last year, we knew we needed to deepen our understanding of these results through additional analyses. The data presented at AAN provided additional validation needed to advance pilavapadin 10 milligrams as well as a deeper understanding of the profile of this novel mechanism. The data we have seen to date give us further confidence that pilavapadin is Phase III ready in DPNP.

Second, we presented preclinical evidence supporting pilavapadin as a novel oral therapy for spasticity, including evaluation in preclinical models of multiple sclerosis and spinal cord injury. The data shared at AAN underscore the opportunity to expand the potential of pilavapadin beyond DPNP, consistent with the pipeline in a pill opportunity that we have discussed.

I'll now turn it over to Scott to provide an update on the company's financials.

Thank you, Craig. I'll begin with a summary of our results for the first quarter of 2026. Total revenues were $21.1 million for the quarter compared to $1.3 million for the corresponding period in 2025. Revenues for the first quarter of 2026 include 2 $10 million milestones recognized from the Novo Nordisk agreement and net sales of INPEFA of $1.1 million.

Research and development expenses for the first quarter of 2026 were $12.8 million compared to $15.3 million in the corresponding period of 2025, reflecting lower external research expense in 2026 due to the completion of our PROGRESS Phase IIb clinical trial and the licensing of LX9851 to Novo Nordisk. Selling, general and administrative expenses for the first quarter of 2026 were $9.2 million compared to $11.6 million in the corresponding period of 2025. The decrease in 2026 reflects reduced marketing efforts and lower personnel costs.

Net loss for the first quarter of 2026 was $1.0 million or less than $0.01 per share compared to a net loss of $25.3 million or $0.07 per share in the corresponding period of 2025. Net loss for the first quarter of 2026 included noncash stock-based compensation expense of $3.1 million. As of March 31, 2026, Lexicon had $199.7 million in cash, cash equivalents, short-term investments and restricted cash as compared to $125.2 million as of December 31, 2025. Total debt as of March 31, 2026, was $49.7 million as compared to $54 million as of December 31, 2025.

I'd like to now highlight a few items from the first quarter. As I mentioned, revenue for the first quarter included 2 $10 million milestones recognized under our Novo Nordisk licensing agreement. Quarter-over-quarter, our operating expenses decreased by $4.8 million, reflecting our continued operational discipline and the strategic repositioning we began implementing in late 2024. We are also reaffirming our full year 2026 outlook for operating expenses.

Earlier this week, we took steps to improve our balance sheet and enhance our financial flexibility. We announced a $100 million debt facility with Hercules Capital. Under the terms of this agreement, an initial tranche of $55 million was funded at closing and was utilized to repay our existing loan facility with Oxford Finance. A second $20 million tranche is available for draw at Lexicon's option, subject to the achievement of certain clinical, regulatory and financial milestones and specified time requirements. A third $25 million tranche is available for draw at Lexicon's option, subject to Hercules consent and specified timing requirements.

The loan facility provides for an initial interest-only period of 18 months with the potential for 2 6-month extensions. We are incredibly pleased with our financial accomplishments thus far in 2026, including the completion of our capital raise in February and our new loan facility with Hercules. We have strengthened our balance sheet and improved our financial flexibility while remaining prudent with our expenses ahead of our important milestones in the back half of this year.

I will now turn it back to Mike for closing remarks.

Yes. Thanks, Scott. Now before we turn to Q&A, I just want to reiterate how -- just how pivotal year 2026 is for Lexicon. To ensure success for the year and to get us to this point where in H2, we will have a number of important things happen for the company, we've done 2 things. We've taken steps, firstly, to strengthen our financial foundation over the last few months. And second, we've executed incredibly well. And as a result, we have many significant milestones just weeks away.

I'm excited for how the opportunities are really shaping up for us, both with our own actions, but also importantly, within the external environment, which is favoring our approach across the board for all of our programs. For HCM, as the field evolves and awareness of both obstructive and now importantly, nonobstructive disease really advance. We are well positioned with a therapy that has the potential for a strong benefit risk profile and ease of use at a time where market awareness will be high and the need will clearly remain significant.

In T1D, we haven't given up. Indeed, our result is strengthened by the ongoing constructive dialogue with the FDA. Indeed, we're close to being able to submit new clinical data that we believe demonstrates a strong benefit risk for Zynquista with people with T1D, supported by high unmet need and strong patient support for approval.

With pilavapadin, we're pursuing the right strategic partner to allow for the greatest potential for this novel asset at a time when the pain therapeutic space and legislative and regulatory environment are increasingly in our favor of new novel non-opioid approaches. And finally, with LX9851, our licensee, Novo Nordisk continues to prioritize the clinical development of the asset. And indeed, just yesterday, highlighted 9851 in their earnings call.

So by next quarter, even in just the next few weeks, we believe we'll be able to share a number of positive developments, and we thank you for your continued attention and support.

And with that, I'll turn it back to you, operator, to guide us through the Q&A.

[Operator Instructions] And your first question comes from the line of Andrew Tsai with Jefferies.

It's Brian here on for Andrew. Just given the ACACIA data in nonobstructive that just hit with aficamten, how does that make you feel about your own SONATA Phase III? And if you can just talk about potential differentiation there as well, please?

Yes. No, thanks, Brian. I appreciate the question. So look, I think first and foremost, it's really an exciting time to be in the field of HCM. I think there's a lot of enthusiasm and a lot of patient need. And what we saw yesterday from the ACACIA study really gives us a lot of confidence that we have an asset where we believe we will have an incredibly strong benefit risk profile. We know the safety of sotagliflozin through many years of study and many thousands of patient exposure.

And if SONATA is positive, we believe that represents a strong benefit risk profile. And really, the opportunity, particularly in nonobstructive is incredibly large. And so we're really buoyed by that, and it gives us confidence in our step moving forward, particularly because with a strong benefit risk profile, together with that simple once-a-day oral dosing, we really see ourselves positioned particularly in nonobstructive as a first-line therapy. It makes a ton of sense where you don't have a REMS, you're a simple, well-known, safe product that provides significant symptom relief that first-line asset can work very well for us.

And importantly, really, these are 2 very different mechanisms. And like many types of cardiometabolic disease, using multiple mechanisms for shots on goal to relieve symptoms and improve outcomes is typically done. So we're incredibly pleased that we have a strong opportunity in non-obstructive and obstructive disease.

Yes. I'll just add, Brian, a couple of other points. Thank you, Mike, for your comments. As Mike mentioned, the mechanisms of action here are not in conflict. In fact, they're probably complementary I think the general feeling in the field is that CMIs are acting primarily as hemodynamic agents. And as I tried to mention in my prepared remarks, SOTA is acting as a hemodynamic agent in a different manner, really acting on the cardiorenal axis and also improving a number of other parameters, some weight loss, increase in hemoglobin, decrease in blood pressure, all of which are beneficial for the heart in any heart failure state.

And in addition, we believe that the SGLT1 effects with SGLT1 receptors upregulated, particularly in the myocardium that acting directly on the heart muscle tissue in a way that is novel and distinct from a CMI is important. As we've mentioned in prior calls, we have not excluded patients on CMIs in this trial. And I can tell you that we are enrolling symptomatic patients on CMIs. Obviously, they're all mavacamten because that was the only product that's been commercially available heretofore.

I also think that the results from ACACIA had, I would say, at least on a median basis, a relatively modest effect on KCCQ score. And if the patients had baseline KCCQ scores similar to what was seen in ODYSSEY, my guess is a number of those patients will still remain symptomatic and will require additional therapy, which is consistent with what we're seeing in our trial enrollment that all the patients that are on CMIs remain symptomatic.

So I think in that regard, as Mike said, the biggest issue in nonobstructive is going to be patient identification because people have not been looking for nonobstructive disease and I think historically have just sort of lumped them into a slightly different variant of HFpEF. And I think that differentiation of a much thicker left ventricular wall has probably not been appreciated to date and having another company out there really talking about the importance of nonobstructive HCM as a separate disease state from HFpEF, I think will be extraordinarily important for the field and for Lexicon.

Your next question comes from the line of Yigal Nochomovitz with Citigroup.

This is Caroline on for Yigal. We're wondering if you can tell us what percent of enrollment in the Phase III SONATA-HCM study has been completed? And how is the split in enrollment trending between obstructive and nonobstructive patients? Is there a risk of too many nonobstructive patients relative to obstructive patients given some obstructive patients are currently being treated with CMI, which you've mentioned before? And what if the enrollment is weighted more towards one group or the other?

Yes. Great questions. I'll answer them in the order that you asked them. We haven't given exact numbers of enrollment, but I can say confidently that we reaffirm the time lines that we have with enrollment middle of this year in terms of last patient first visit of 500 target patients. We've seen, as expected as all the sites come online, the expected and dramatic uptick in enrollment as the sites open and become familiar with the study and its availability.

The distribution of patients, again, I don't want to comment too early before we finalize enrollment. I think as we've said, the need is larger in the nonobstructive group since there is an obstructive therapy available with CAMZYOS during the duration of the trial, but we are enrolling significant numbers of both obstructive and nonobstructive patients in the trial.

[Operator Instructions] And your next question comes from the line of Yasmeen Rahimi with Piper Sandler.

This is Dominic on for Yas. Congrats on the great quarter. We just had a few questions and then kind of going along with some of the conversation about enrollment. At the time of enrollment completion in mid-2026 for SONATA, would you potentially unveil baseline demographics? And then kind of in line with that, do you have any thoughts on how similar SONATA's patient population will look to ACACIA for the recent readout? And we have one more question just on what would be a clinically meaningful difference in KCCQ? And what did you power SONATA for on this endpoint?

Yes. Thanks, Dominic. Let me start up and then Craig can take some of the detailed SONATA questions as well. So we haven't finalized exactly the information that we will release at the time of enrollment, but we're certainly committed and understand that there's interest across a number of parameters. Of course, this split as given by the questions that are coming, the split of obstructive, nonobstructive is of interest and to really get the final baseline dems to compare that to SONATA.

So we will -- we're very cognizant of that, and we will determine over the coming weeks exactly what we will release when. So we haven't sort of finalized, but we will be providing updates because we are cognizant that, that's important for folks to understand.

As it comes to the sort of the SONATA specific questions, I might let you take those, Craig.

Yes. Thanks, Mike. I hope I have your questions correct. I'll answer the one on demographics first. Again, we're still enrolling the trial and ACACIA has not really, to my knowledge, given details on the demographics similar to what was done with ODYSSEY since ODYSSEY is now already published. But I think we're seeing a patient population similar to what has been reported for ODYSSEY. You're really looking at a population in their mid-50s to 60, pretty symptomatic disease, a good distribution by gender, equal distribution of gender.

So we have a population, I think, was very consistent with what we expected, particularly the demographic and the geography that we're enrolling in this trial, which is U.S. and across Europe. So I think in that regard, we've not seen anything unexpected. We haven't looked at detail yet at the KCCQ scores or anything else. But certainly, we know that patients are symptomatic that are coming into the disease.

And broadly similar entry criteria, right?

Yes. Exactly, Mike. Yes. Thank you. Very similar entry criteria to the other trials. Clinically meaningful KCCQ score, I think the field is generally focused on 5, 4 to 5 as a number. I think there may be a rethinking of that in light of some of the more recent study results that have come out. But certainly, historically, that has been seen as an important threshold for clinical meaningfulness. And that's how we powered our trial is based on that range. Again, we haven't given the exact statistical plan that we're using, but we can certainly detect in that range comfortably with a high degree of probability of success.

And I do think that is going to be a real point of discussion in the field of risk benefit with modest improvements in KCCQ, but with potential for safety concerns and monitoring, I think those are going to be important discussions that the field will be having as the field of nonobstructive HCM is further discussed at upcoming medical meetings and probably also with payers and regulatory authorities.

And there are no further questions at this time. I will now turn the call back over to Mike Exton for closing remarks.

Thanks so much, everyone. Thanks for tuning in and listening to our update. As I mentioned, the team has really worked incredibly hard to put us in a strong financial and strategic position and to execute across all of our programs. And we're really looking forward to H2 here in 2026.

I think as you see from our remarks, we've got many things that we've been working on diligently over the last week while are going to come to fruition. And so I really look forward to updating you with a lot more information in the not-too near future. So have a great day and look forward to speaking with you all again soon. Thank you very much.

Ladies and gentlemen, that concludes today's call. Thank you all for joining. You may now disconnect.

Welcome to the Lexicon Pharmaceuticals Fourth Quarter and Full Year 2025 Financial Results Conference Call [Operator Instructions] As a reminder, this call is being recorded today, March 5, 2026. I would now like to turn the call over to Lisa DeFrancesco, SVP, Investor Relations and Corporate Communications for Lexicon. Please go ahead, Lisa.

Thank you, Michelle. Good morning, and welcome to our Q4 and full year 2025 earnings conference call. Joining me today are Dr. Mike Exton, Lexicon's Chief Executive Officer and Director; Dr. Craig Granowitz, Senior Vice President and Chief Medical Officer; and Scott Coiante, Senior Vice President and Chief Financial Officer. This morning, Lexicon issued a press release announcing our financial results for the fourth quarter and full year of 2025, which is available on our website at www.lexpharma.com and through our SEC filings. A webcast of this call, along with a slide presentation is also available on our website.

During this call, we will review the information provided in the release, provide a corporate update and then use the remainder of our time to answer your questions. Before we begin, let me remind you that we will be making forward-looking statements, including statements related to the safety, efficacy, clinical development, regulatory status and therapeutic and commercial potential of sotagliflozin, pilavapadin, LX9851 and our other drug programs as well as our business generally. These statements may include characterizations and projections related to the clinical development, regulatory status and market opportunity for our drug programs and commercial performance of INPEFA for heart failure.

This call may also contain forward-looking statements relating to our growth and future operating results, discovery and development of our drug candidates, strategic alliances and intellectual property as well as other matters that are not historical facts or information. Various risks may cause our actual results to differ materially from those expressed or implied in such forward-looking statements, and we refer you to our most recent annual report on Form 10-K and other SEC filings for detailed information describing such risks. I would now like to turn the call over to Mike Exton. Mike?

Yes. Thanks, Lisa. Good day, everyone. Thanks for joining us today. As I reflect back on this year, my first full year as CEO at Lexicon, I'm enormously proud of all the progress we've made. In addition to all we've accomplished in 2025, we've had a tremendously productive start to this year. So we're excited to give you some updates on our recent progress and discuss the many important milestones ahead of us in 2026.

By way of a high-level overview, Lexicon is advancing 3 very strong novel late-stage programs in the therapeutic areas of cardiometabolic disease and chronic pain. In cardiometabolic, we have sotagliflozin, which is currently in late-stage development in hypertrophic cardiomyopathy. Also planning an NDA submission for sotagliflozin in type 1 diabetes and collaborating with our licensee, Viatris on making sotagliflozin available in patients outside the U.S. and Europe. We also have our novel oral early-stage program in obesity, LX9851, which is being advanced by Novo Nordisk. Within chronic pain, we have pilavapadin, a Phase III-ready drug candidate for diabetic peripheral neuropathic pain.

Each of these programs have key potential catalysts upcoming, which we'll cover shortly. Any one of these programs alone would represent a significant opportunity and scientific achievement to be excited about. But taken together, they comprise a portfolio that we're quite proud of. Now before I jump into the details and next steps for each of these programs, I want to emphasize that in addition to the R&D excellence behind this pipeline, we've also been diligent about driving operational excellence as well as improving our financial position and cost structure to sustainably support our core programs going forward.

So looking ahead, we've set clear goals for what we need to achieve in 2026. The SONATA-HCM Phase III trial of SOTA for obstructive and nonobstructive HCM is enrolling well, and we expect to complete enrollment in the middle of this year. We received feedback from FDA that data from the third-party STENO1 study can support an NDA resubmission for Zynquista for glycemic control in type 1 diabetes, if supported by patient exposure and safety data from the study.

Now based on the data we've seen thus far, we expect to resubmit in 2026 with potential approval later this year. Our partnership strategy continues as we support our existing licensees, Novo Nordisk and Viatris while also exploring new partnerships where appropriate to augment our capabilities, including seeking a partner for Phase III development of pilavapadin. And last but not least, we're financially well positioned following our recent capital raise. We plan to maintain our operational discipline to support long-term growth with diligent expense management and continued focus on deploying capital towards the highest value, highest impact opportunities.

Collectively, this truly demonstrates our lead to succeed strategy in action. Now we entered 2026 with significant momentum, and that has really continued in the first few months of the year. In January and February alone, we announced a successful end of Phase II meeting with pilavapadin in DPNP with no objections raised by the FDA to advancement into Phase III development.

We strengthened our financial position with more than $100 million in additional cash from our recent capital raise as well as the Novo Nordisk milestone payment. We continued enrollment in the ongoing SONATA-HCM Phase III study of sotagliflozin for HCM, surpassing 50% enrollment completion earlier this quarter and progressed our work towards a potential resubmission of our NDA for Zynquista in type 1 diabetes later this year if the STENO1 patient exposure and safety data requirements identified by the FDA are achieved. So as you can see, we're very much up and running and so much more to come. With that, I'll ask Craig to provide a deeper dive on our lead programs. Craig?

Thank you, Mike, and good morning, everyone. As most of you know, our pipeline is focused in 2 primary therapy areas, the first being cardiometabolic disease and the second being chronic pain. I'll start with our cardiometabolic platform and sotagliflozin. As we approach important upcoming milestones for sotagliflozin in both HCM and T1D, it is an opportune time to review sotagliflozin's unique mechanism of action.

As the only dual inhibitor of both SGLT1 and SGLT2, we want to focus on the importance of the SGLT1 effects. While SGLT2 is expressed primarily in the kidney, SGLT1 is expressed in the kidney, but also in other tissues, particularly the GI tract and the heart as well as the endothelium. We believe that inhibition of SGLT1 in the GI tract is important in postprandial glycemic control in patients with T1D. Similarly, we believe that inhibition of SGLT1 in the heart has important effects on myocardial health, particularly in disease states like HCM.

It is also thought that inhibition of SGLT1 and endothelium may be important in reduction of ischemic events like stroke and MI. The graphic on the next slide demonstrates the distribution of SGLT1 and SGLT2 protein expression in human tissues. On the right-hand side of the panel, it is evident that SGLT2 expression occurs primarily in the kidney. SGLT1 but not SGLT2 is expressed in the GI tract and heart. It is also noteworthy that SGLT1 expression in the heart is significantly upregulated in patients with ischemic heart conditions and in patients with hypertrophic cardiomyopathy.

We will continue to discuss these and other factors contributing to the growing body of evidence supporting the potential benefit of SGLT1 inhibition for the treatment of HCM in the coming months. The mechanistic differentiation leads us to the rationale behind our current development efforts for sotagliflozin, a potential first-in-class therapy for HCM and glycemic management in type 1 diabetes. Regarding HCM, interest and awareness of the disease has been growing, particularly with new treatment options becoming available, but this disease remains an area of severe unmet need for both people with obstructive HCM and particularly those with nonobstructive HCM.

Our SONATA-HCM Phase III study includes patients from both populations and top line results are expected in the first quarter of 2027. In type 1 diabetes, Lexicon has been committed to the development of a novel treatment for glycemic control in patients for T1D for many years. The FDA has provided feedback that clinical trial data from STENO1, a third-party funded investigator-initiated study of sotagliflozin may support a resubmission of our NDA for Zynquista in T1D.

Based on the study data we've seen to date, we're preparing to resubmit the NDA and potentially receive regulatory approval in 2026. Elaborating further on the opportunity for HCM, our Phase III SONATA-HCM study is a large global registrational trial with a KCCQ endpoint designed to support a regulatory filing and broad label in HCM. We have completed the initiation of our target 130-plus study sites in approximately 20 countries across the United States, Europe, Israel and Latin America.

I could not be more proud of the team's significant efforts in achieving this goal. SONATA is the only registrational trial currently enrolling patients with both obstructive and nonobstructive HCM. The study is pragmatic in design, allowing for patients currently being treated on a CMI. The enrollment in the study is stratified but not capped. And as Mike mentioned, we have surpassed a 50% enrollment target earlier this quarter and on track to complete enrollment by midyear.

As I mentioned earlier, as a dual inhibitor of SGLT1 and SGLT2, we believe that sotagliflozin could offer distinct advantages for the treatment of obstructive and nonobstructive HCM. Importantly, it is the only drug to our knowledge in clinical development for HCM that works both inside and outside the heart. It acts directly on the myocardium to modify cellular energetics, and we believe it has the potential to be a first-line agent with no REMS in both obstructive and nonobstructive HCM. Additionally, sotagliflozin is already approved for heart failure with no observable -- no observed risk of AFib to date.

This is important given that many patients who have HCM go on to experience major adverse cardiovascular events such as myocardial infarction, stroke or heart failure. Complementing the upcoming clinical results from the SONATA-HCM trial are 2 investigator-initiated trials, the SOTA-P-CARDIA and the SOTA-CROSS studies. SOTA-P-CARDIA, data from which was presented at the American Heart Association meeting last November, evaluated the effects of sotagliflozin in patients with HFpEF without diabetes with a baseline ejection fraction greater than 50%.

Clinically, these patients have a number of symptomatic and anatomical characteristics similar to those with nonobstructive HCM. Data from SOTA-P-CARDIA showed improvements in patient symptoms such as KCCQ score and 6-minute walk test as well as cardiac functions such as left ventricular mass and left atrial filling pressure, findings which support the rationale for sotagliflozin's use in nonobstructive HCM. SOTA-CROSS is a crossover study evaluating sotagliflozin in symptomatic nonobstructive HCM. This is an ongoing 12-week crossover study with a readout expected in 2027, measuring a number of outcomes, including cardiac function, symptoms and biomarkers.

Moving on to the next slide. There is a growing body of evidence that supports sotagliflozin's unique potential for reducing cardiovascular events. This slide highlights recent data presented at the AHA scientific sessions in the HCM Society and an upcoming presentation at the American College of Cardiology's 75th Annual Scientific Sessions that highlights sotagliflozin's impact on cardiac remodeling in HCM, the benefits of sotagliflozin in HFpEF and sotagliflozin's effects on MACE events in patients with type 2 diabetes.

In summary, we are excited to complete enrollment in SONATA-HCM and look forward to upcoming data presentations at ACC and several HCM-related medical meetings in the second half of this year. Now turning to Zynquista, our sotagliflozin program in type 1 diabetes. As we previously announced, we had productive meetings with the FDA in late 2025, during which they confirmed that STENO1, a third-party funded investigator-initiated study of sotagliflozin being conducted by the STENO Diabetes Center in Denmark, appears to be sufficient to support a review of a resubmission of our NDA for Zynquista in T1D.

Based on current STENO1 enrollment estimates and safety data we've received to date, we're planning for an NDA resubmission and potential regulatory approval in 2026. There are approximately 1 million patients with type 1 diabetes in the United States, and there has not been a new therapy approved for over a century to help those patients achieve glycemic control alongside insulin. That is an unacceptable status quo. The outpouring of support for Zynquista from the diabetes community has been remarkable and reinforces what we've always known.

These patients desperately need new treatment options. If approved, Zynquista would be the first and only oral therapy in its class for type 1 diabetes. It's not just a commercial opportunity, though certainly it is, but it's a chance to fundamentally improve how we treat this challenging medical condition. Global development of LX9851 in obesity remains on track, and our progress on this program triggered a $10 million milestone payment in February under our license to Novo Nordisk with potential for another $20 million in additional milestones in 2026.

We have now fully handed off development to Novo Nordisk following the completion of IND-enabling activities, and we are encouraged by the continued enthusiasm for this asset and its novel mechanism. Just this week, the Journal of Endocrine Society highlighted our recent publication on ACSL5 inhibition as a featured article. These preclinical data provide some insights as to the potential of ACSL5 as a target and LX9851 as a drug candidate for obesity and chronic weight management.

In addition to our cardiometabolic programs, Lexicon also has a Phase III-ready non-opioid asset for neuropathic pain, pilavapadin. Pilavapadin is a novel investigative agent targeting AAK1. And like sotagliflozin, pilavapadin has a broad pipeline and a pill potential. Our lead indication for pilavapadin is DPNP, supported by 2 Phase II studies that provide evidence of consistent and clinically meaningful pain reduction. We have accumulated data from more than 600 patients treated with pilavapadin and have demonstrated a well-understood and acceptable safety and tolerability profile.

Beyond DPNP, we believe there are other potential applications for pilavapadin. The AAK1 pathway is central to a number of cellular processes such as synaptic signaling between neurons involved in pain signaling and spasticity. With this in mind, we are conducting IND-enabling work in multiple exciting neuroscience indications. As Mike mentioned, we had a successful end of Phase II meeting with the FDA for pilavapadin in DPNP. During that meeting, FDA raised no objections to the advancement of pilavapadin into Phase III development in that indication.

The Phase III program would include 2 placebo-controlled 12-week 2-arm registrational studies comparing the 10 milligram daily dose of placebo. The primary endpoint of the Phase III study would be placebo-controlled change in average daily pain score from baseline to week 12. The FDA also confirmed that it will not require any additional preclinical or preclinical studies that would be expected to complicate or delay the advancement of this program into Phase III development and potential regulatory submission. With this regulatory alignment in hand, we are continuing our ongoing discussions with potential partners for pilavapadin. I will now turn it over to Scott to provide an update on the company's financials.

Thank you, Craig. We begin this morning with our results for both the fourth quarter and full year of 2025. Total revenues were $5.5 million and $49.8 million for the quarter and year ended December 31, 2025, respectively. Revenues for the fourth quarter of 2025 include $4.3 million of licensing revenue recognized from the Novo Nordisk agreement and net sales of INPEFA of $1.1 million. Revenues for the year ended December 31, 2025, include $45 million of licensing revenue from the Novo Nordisk agreement and $4.6 million of net sales of INPEFA.

Total revenues for the fourth quarter and full year 2024 include the upfront payment of $25 million received upon entering into the Viatris license agreement and net sales of INPEFA of $1.6 million and $6 million, respectively. Research and development expenses for the fourth quarter of 2025 decreased to $11.3 million from $26.7 million in 2024. Full year 2025 research and development expenses decreased to $61.1 million from $84.5 million in 2024, primarily reflecting lower external research expenses from our PROGRESS Phase II clinical trial, partially offset by increased investment in our SONATA Phase III clinical trial.

Selling, general and administrative expenses for the fourth quarter of 2025 decreased to $8.8 million from $32.3 million in 2024. Full year 2025 SG&A expenses decreased to $37.3 million from $143.1 million in 2024. The decrease in 2025 reflects lower costs resulting from the company's strategic repositioning in late 2024 and our significantly reduced marketing and promotional efforts for INPEFA in 2025. Net loss for the fourth quarter of 2025 was $15.5 million or $0.04 per share compared to a net loss of $33.8 million or $0.09 per share in the corresponding period in 2024.

Net loss for the full year 2025 was $50.3 million or $0.14 per share compared to a net loss of $200.4 million or $0.63 per share in the same period in 2024. For the fourth quarters of 2025 and 2024, net loss included noncash stock-based compensation expense of $2.8 million and $1.5 million, respectively. And for the full years of 2025 and 2024, net loss included noncash stock-based compensation expense of $12.5 million and $13.5 million, respectively. As of December 31, 2025, Lexicon had $125.2 million in cash, investments and restricted cash as compared to $238 million in cash and investments as of December 31, 2024.

Subsequent to year-end, Lexicon strengthened its cash position by more than $100 million from net proceeds received from the sale of common and preferred stock and a milestone payment from Novo Nordisk. I'd like to now note a few financial highlights from both the fourth quarter and full year 2025. In addition to the revenue highlights, which I mentioned previously, operating expenses were reduced by $39 million for the fourth quarter of 2025 as compared to the fourth quarter of 2024. We continue to look for ways to reduce costs and streamline our operations. We also meaningfully improved our cost structure for 2025 with operating expenses down $129.5 million for 2025 as compared to '24 reflecting our strategic repositioning in late 2024 and substantially reduced marketing and promotional spend for INPEFA in 2025.

In addition, we also reduced our total debt by approximately $46.3 million in 2025, primarily using the proceeds from the Novo Nordisk upfront payment. Moving ahead to 2026, we expect total operating expenses to be between $100 million and $110 million. R&D expenses are expected to be between $63 million and $68 million and do not include costs associated with Phase III pivotal studies of pilavapadin as our goal would be to move this asset forward with a development partner. SG&A expenses, which include sales and marketing expenses, are expected to range between $37 million and $42 million. I will now turn it back to Mike for closing remarks.

Yes. Thanks, Scott. Now before we turn to Q&A, I just want to say again how excited we are about the year ahead in 2026. Last year was a year of progress and 2026 is a year of potential and possibility with several pivotal milestones ahead. Across our 3 core programs, we have multiple upcoming catalysts that we believe can drive substantial value creation from pilavapadin's partnership opportunities in neuropathic pain to sotagliflozin's multiple shots on goal across HCM, heart failure and type 1 diabetes to LX9851's near-term milestone potential in obesity, we're really firing on all cylinders this year.

Each of these programs addresses serious unmet medical needs and each has the potential to be transformative for patients who desperately need new treatment options. We have the pipeline. We have the team, and we have the momentum, and I'm incredibly excited about what lies ahead. So thanks, and I'll hand it over to the operator, and Craig, Scott and I will take your questions.

[Operator Instructions] Our first question will come from the line of Andrew Tsai with Jefferies.

This is Matt dialing in for Andrew Tsai. Congrats on the progress this quarter. Just a couple of questions for me. How much patient worth of data does open-label [ IST ] STENO1 study have on DKA safety right now for you to be able to guide to a potential approval in 2026? And then what are the exact time lines from submission to approval that you're expecting? Is this going to be a Class I or Class II resubmission here?

Yes. Thanks, Matt. I'll let Craig talk about the data. So we're expecting a 6-month review here. So reemphasizing that the data that we're seeing, we expect a submission this year and as well an approval before the end of 2026. Craig, do you want to talk about the data that we're seeing?

Yes. So again, Matt, I need to be a bit careful because this is in our trial. It's an investigator-initiated study. But as a reminder, this is a large trial. It's 2,000 patients total, 1,000 patients which are on -- is considered the standard of care and then another 1,000, which are randomized based on baseline characteristics to enhanced care, which would include sotagliflozin in a significant percentage of patients, but also the possibility of being on semaglutide and/or Kerendia depending upon baseline patient demographics.

The study has enrolled the majority of the patients. And again, I don't want to overstep Dr. Rossing and the STENO group, but enrollment has proceeded briskly. I think you can see some of their updates on ClinTrials.gov. And the enrollment, as we laid out with the FDA is proceeding to plan. We pre-agreed with FDA on 2 important criteria for resubmission. The first would be the total exposure required.

The second would be a rate of DKA. I can be a bit more expressive about the second criteria because the FDA put that in their end-of-review letter that they were really looking for a rate of diabetic ketoacidosis at or below that achieved with the 400-milligram dose arm in the inTandem program, which in the FDA's parlance was a number needed to harm of about 26, which corresponds to a rate of about 1 case -- I'm sorry, 3.5 cases per 100 patient years. I can tell you that currently, we are tracking in a way both in terms of total exposure and DKA rates that give us a high degree of confidence in where we stand in terms of our submission and approval time lines that both Mike and I highlighted during the call.

Our next question comes from the line of Yigal Nochomovitz with Citigroup.

Okay. I've got a question on the partnerships for the pain program. So you had the end of Phase II meeting. Could you just talk about how much that -- the results from that meeting have accelerated the partnering discussions since then? And is there a clearer line of sight to transacting something this year?

Yes. Thanks, Yigal. So I wouldn't say that they accelerated because we're in constant dialogue with a number of partners that we have been communicating with, but it allowed the conversations to be a little more specific and obviously provide some confidence around the program being able to move into Phase III and take away that sort of regulatory risk, if you like, which has been incredibly well received by partners. So we continue to sort of talk details with them and look forward to providing some more updates in the very near future.

Okay. And also, how much more can you say about what Novo plans to do with 9851 in terms of how it's going to be inserted into the development program, meaning in combo with the GLP-1 or for those perhaps not responding well enough or perhaps even as a maintenance therapy following the course of GLP-1 therapy? What can you say there? Or is that really Novo's call now?

Yes. I don't necessarily want to speak on Novo, but I think I've sort of hypothesized where I think that LX9851 would fit into the treatment paradigm and certainly was some of the background for their enthusiasm. But before I do that, Yigal, let me just reinforce how impressed we've been with the Novo team. And I think we all recognize that perhaps they're sort of losing the battle in injectables and have really pivoted strongly towards oral formulations as being the future and their future in obesity management.

And really, we've had that hypothesis all along that the future of obesity treatment will be in oral combinations of different MOAs, just like it is in most of cardiometabolic disease, whether it be hypertension, hyperlipidemia, et cetera, because it allows you to get synergies by combining different MOAs and orals obviously facilitate that ability to drive combinations. I think they're being very open, and they, therefore, are really doing an incredible amount of work on this program to see whether it's going to be as a stand-alone monotherapy to see whether it's in combination, to see whether it's right at the initiation of treatment, whether it becomes a maintenance therapy.

I think all of those options are on the table for them, and they're really driving very, very hard, which gives us confidence, as we mentioned in the opening remarks around the potential of receiving those 2 further milestones this year, which would really be an accelerated Phase I development. And we're excited about the possibility of clearing that hurdle and then really getting into Phase II and beyond, which would be very material for the company. Craig, do you have any additional thoughts or...

I'll just add from the scientific standpoint, the mechanism is complementary to semaglutide as we've communicated, and I think it's nicely summarized in the Journal of Endocrine Society paper that just came out this week, as we mentioned during the prepared remarks, this mechanism is thought to be really the only agent that is in development acting on what's called the allele break, which is a very different neuroendocrine signal of satiety that we've seen and we've communicated, I think, at prior meetings could act additively both to the amylin mechanism and certainly to the GLP or semaglutide mechanism.

So I think that's really how Novo is thinking about this is that this agent could be acting either alone or in combination with semaglutide or potentially in an additional combination with both an amylin analog and semaglutide analog. But again, we don't want to speak for Novo, our partner.

Our next question is going to come from the line of Joe Pantginis with H.C. Wainwright.

So Mike, I know the intent for pilavapadin is moving forward with an expected partner. But I want to ask the question this way. So based on your -- the larger coffers that you have now and how things are rapidly progressing with the data and your FDA discussions, are you looking towards any sort of flexibility or optionality with regard to even starting the study on your own prior to getting a partner?

Yes. It's a great question, Joe, and it's a great position to be in when you've got a number of opportunities ahead of you. And we're really very much focused on our near-term cardiometabolic opportunities. I think what we see in the opportunity with T1D for SOTA as well as HCM are both incredibly large commercial opportunities for us. And so we're very much focused on driving that forward. We have been continuing to do some work in preparation of what the Phase III program would look like for pilavapadin.

And in fact, that's been a part of the partnering discussions as well as we continue to sort of engage in a very granular time frame of what would be expected moving forward. And even that is changing as we speak. As you know, the recent announcement by Dr. [ Makary ] for one trial possibility is something that is coming into our thought process as well. And we need to consider that as a possibility for pilavapadin as we will be for all programs. So we are doing work in parallel, but we're not going to invest the financial commitment to commencing a Phase III trial for pilavapadin because we really want to invest that cash for both T1D and HCM at the moment. Craig, have you got anything else?

Yes. I think, Mike, you summarized the strategic part really well. I just wanted to reinforce the importance of the patient groups in the legislative dimension as well. And what we've seen in this regard is a tremendous interest from the patient community and really trying to bring that into a legislative position as well. As you know, Joe, a lot has been done in the acute pain setting, particularly in light of the opioid situation.

Patients who are on chronic pain treatment like DPNP are at much higher risk of actually developing opioid addiction. So there's been a really strong interest across the board in the pain community, both on the opioid avoidance side as well as the diabetes community in terms of really trying to put momentum behind this effort from a legislative front.

So we're really trying to approach this from multiple different ways, a regulatory legislative patient access standpoint as well as, as Mike said, we've really now finalized what the development program would be under standard conditions based on the end of Phase II meeting. So we continue to really look at all of these areas as the discussions continue because we don't want to just have the assets sitting there.

Yes. No, exactly. So I think Craig summarized that well. There's a bunch of activity that we're doing to continue the preparation for the program in parallel with the discussions. But our investment of capital is squarely focused at this time on Zynquista and HCM because we see those opportunities coming at us very, very fast.

That's very helpful. And maybe a question for Craig here. When you look at the SOTA profile for HCM, just curious how you believe the CARDIA and CROSS studies on the periphery could potentially impact future sNDAs and/or the marketing potential as you look at the broadening profile for SOTA and HCM.

Yes. Thanks for the question, Joe. We try to approach this in a way that really is -- the sum of the total is far greater than each of the individual parts. And we've really tried to take a pragmatic design approach to SONATA-HCM that would be clear, efficient and rapid that would spare capital in terms of doing a study that would achieve the goals of the FDA and other health authorities, but not add dramatically to the cost or slow enrollment.

And in that regard, we're really looking at SOTA-CROSS, SOTA-CARDIA and a number of other trials that we've been discussing investigator-initiated trials, looking at various imaging, functional patient feel outcomes that would complement the primary endpoint of SONATA-HCM. And we hope that the sum total of all of that will provide more mechanistic understanding of how the SGLT class will complement that of the CMIs and also going to be the first and only in HCM, but also to differentiate the dual mechanism of SOTA and the SGLT1 effects from the SGLT2 inhibitors, which are not being studied and have no data in HCM.

Yes. No. And just allow me to throw a little more color on to that, Joe, because it's a very important element of our portfolio, and we think it's a great opportunity not only for SOTA in patients with HCM, but for Lexicon. So as we noted, we did raise close to $100 million earlier this year. And we're spending a small portion of that this year at the moment as -- sorry, Scott gave in his guidance for the year.

But one of the important elements that we are going to undertake is to have a small field medical team to really bring about what is a ton of evidence now showing the reason to believe of SGLT1 as being a new class of medicine and being -- and having a lot of evidence that indicates it will be a very significant medicine for both obstructive and nonobstructive HCM.

So we're going to employ that field force as we march towards the data in Q1 2027 to not only talk about SONATA, not only talk about SOTA-CROSS and SOTA-P-CARDIA, which are very important elements, but a lot of the mechanistic evidence, one of which we presented today. And I think as we sort of educate the physician community beyond top KOLs, they will really see why SOTA has significant potential in HCM. So it's really an important focus for the company over the next 12 months.

Our next question comes from the line of Yasmeen Rahimi with Piper Sandler.

This is Shannon on for Yas Rahimi. Congrats on the progress. Could you just help us understand your visibility and confidence for getting the additional 50% enrollment for SONATA by mid-2026? And then also, is there -- the cadence of that enrollment, is that the same in both cohorts for nHCM and oHCM?

Yes. Great question. So I'll let Craig have first go at that one.

Yes, Shannon, it's a great question. We have a really nice window right now of enrollment that there are not a lot of competing global trials right now. We have, as I mentioned during the prepared remarks, all 130 sites now open across 20-plus countries. And we're at that, what I would call, steep part of the S-shape enrollment curve. We've sort of gotten over the early parts. We've had a few protocol amendments to make enrollment clarify things where there were open issues and enrollment has really ticked up consistent or ahead of our projections at this point.

And as Mike mentioned, we've crossed the 50% enrollment target much earlier in this quarter, and we see continued uptake in enrollment across all of the regions, the U.S., Europe, and Latin America are all contributing. Your second part of your question regarding enrollment is we have enrolled significant numbers of patients with both obstructive and nonobstructive HCM. What we are seeing, not surprisingly, is that there are some patients, particularly these large academic centers that are being treated currently with the CMIs for obstructive.

So we're seeing even more patient inflow for the nonobstructive cohort than the obstructive cohort. But we believe that we have enough patients in both cohorts to achieve what we set out in the trial. And as we mentioned, the trial is stratified but not capped. So we did stratify the patients based on their baseline characteristics of either being obstructive or nonobstructive, but we have not set a formal cap of a specific number of each group, and that we did discuss and align with FDA before we started the trial.

Yes. Shannon, it's a great point. As all those people know who've run clinical trials, enrollment is never linear in any clinical trial. And we have our target curve and our enrollment curve is right on that target curve, and we continue to enroll strongly such that we have a high degree of confidence that we'll hit that midyear target, which will have then a data readout in Q1 of '27.

Our next question comes from the line of Roanna Ruiz with Leerink Partners.

This is Michael on for Roanna Ruiz at Leerink Partners. I have a question about Phase III design of pilavapadin program. Previously, you mentioned several measures to mitigate the placebo response that you saw previously. Are you able to comment on what the enrollment criteria changes will look like for Phase III? Like for instance, will you require like minimum pain score threshold, things like that?

Yes. Great question, Michael. Thank you for that question. I think the changes that we're going to have, as we mentioned, probably the single largest change we're going to have is actually to expand enrollment that during the year, we did run a renal impairment study and we believe that having a renal impairment study completed with no impact on clearance with GFRs down to 30 significantly increases the enrollment potential for this study because there is a high degree of correlation between neuropathy and nephropathy, both in terms of the enhancement of patients, but also the severity of their neuropathic pain.

So as GFR drops, you tend to see a higher percentage of patients that have neuropathic pain, but also the more severe neuropathic pain. In terms of the other entry criteria, we're really looking at similar pain scores at baseline. I think the only change that we looked at, and we looked at a number of variables that might have affected the placebo rate. On the patient characteristics, the only one that we saw that was meaningful, and again, this is all retrospective looking back at the completed data was the duration of their neuropathy prior to enrollment.

So we might make some minor changes to the enrollment criteria in terms of the duration of their neuropathy of about a year. I believe in the Phase II study was 6 months, but to extend that to approximately 1 year. The other major elements that in talking to our advisers and to the FDA and in discussions with them, we are going to do more regarding the training of patients during the pain score because, again, reinforcing constantly how to use the visual analog scale for pain management, both with the sites and the patients is another element that we think that we can do to have more consistency across patient enrollment in the study sites.

And also, we now have a large number of study sites that have significant experience with us running these trials because we've now run 2 large trials, 2 large Phase II trials. So we think we have a good supply of sites to enroll these studies that will have experience with this drug, and we know have experience with doing DPNP studies.

And I'm showing no further questions at this time. And I would like to hand the conference back over to Mike Exton for closing remarks.

Yes. Thanks so much, operator, and thanks, guys, for your questions. Very much appreciated. Look, as I reflect on 2025, moving into 2026, the company has made a giant leap forward in my opinion. If you think about where we were last year, we needed to really summarize all of the Phase II data for pilavapadin. We needed to find a path forward for Zynquista. We needed to accelerate the enrollment of SOTA in HCM and fast forward to nearly at the end of the first quarter of 2026, and we now have clarity on pilavapadin and partnership.

Discussions are ongoing. We're on the precipice of a resubmission for Zynquista, and we're nearly closing the enrollment of HCM study, SONATA with a readout in '27. So we've got an amazing set of opportunities ahead of us and hopefully, you can see how pumped we are about all of those things coming our way in 2026 and beyond. So we feel very good. We're pushing very hard and look forward to giving you some more updates as the year progresses. So thanks very much, everyone.

This concludes today's conference call. Thank you for participating, and you may now disconnect. Everyone, have a great day.

Good afternoon, everyone. Welcome to the 44th Annual JPMorgan Healthcare Conference. My name is Alex Morrison. I'm an associate on JPM's health care team. Today, it's my pleasure to introduce Lexicon Pharmaceuticals. We'll have CEO, Mike Exton, speak; as well as Craig, Chief Medical Officer; and Scott, Chief Financial Officer, on stage for Q&A.

Great. So thanks so much, Alex, and thanks to JPMorgan for the invitation to present the Lexicon story. So for those of you who are unfamiliar with Lexicon -- let me go back. I'll be making some forward-looking statements. Please refer to the SEC filings for further details.

But Lexicon was founded 30 years ago with a bold ambitious plan at the time around before the human genome was described, before the mouse genome was even described to take 5,000 genes and create knockout mouse lines for all of those genes. Creating those mouse lines, then running them through a battery of tests to see what would be the impact of those genes. And as a result, they identified 200 genes of interest.

And fast forward through the Lexicon story. And we're pleased that over that time, we've had over 80 clinical trials looking at a number of new medicines and has resulted in the approval of 2 medicines in the United States. And -- and the approval and commercialization of INPEFA and taking new novel mechanisms into the clinic. We now have a medicine for non-opioid approach in neuropathic pain and a new non-incretin mechanism in obesity.

The Lexicon approach is to take oral medicines that we dose once daily across a number of different cardiometabolic and pain indications. And what we are trying to do is create a pipeline in a pill using oral medicines dosed once daily that really give a dosing opportunity both for combination therapies as well as having the possibility for monotherapies in areas that are very simple to dose against, and create medicines that have applicability across a number of different indications.

We've proven that with sotagliflozin, where we have indications and research going for heart failure, where we have an approved medicine for hypertrophic cardiomyopathy or HCM, and in type 1 diabetes for the control of glucose in T1D.

We've proven that again in neuropathic pain, where with pilavapadin, we have clinical data for neuropathic pain as well as a number of different other indications for the applicability of pilavapadin. Finally, LX9851, which is a new novel incretin for obesity and related conditions where we also see preclinical evidence in MASH and lipid control.

So we've landed on a focused company in 2 primary therapeutic areas: the first is cardiometabolic disease, and the second is pain. In cardiometabolic disease, we've really landed on a number of areas that are of hot interest to the clinical and investor community at the moment.

The first, INPEFA for heart failure is being commercialized in the U.S. We now have that same molecule in Phase III clinical trials for hypertrophic cardiomyopathy or HCM. And we're engaging the FDA in regulatory discussions around Zynquista for type 1 diabetes.

LX9851, a first-in-class non-incretin mechanism that's complementary to GLP-1s and other incretin-based assets is the first development candidate against ACSL5, and we're investigating that in obesity and related metabolic disorders.

On the other hand, in pain, it's an area of high unmet need where there's been very little developed over the last 2 decades, and we have pilavapadin, a first-in-class inhibitor of AAK1 which is a novel target, completely new target, and Lexicon is the leader of AAK1 biology. And this seems to be highly involved in the development of neuropathic pain. And we now have progressed the program to enter into Phase III clinical trials in 2026.

So last year, we pivoted to really focus on our R&D portfolio. We really set up a bold ambition of developing and progressing the pipeline to be able to really come into 2026 into a commercial-ready company. In HCM, we've initiated all the sites for the Phase III clinical trial, and we've accelerated the enrollment. For T1D, we have aligned with the FDA about resubmitting for type 1 diabetes and sotagliflozin with third-party investigator data, the STENO1 data. And that data and that process continues.

For pilavapadin, we concluded the PROGRESS trial, the Phase IIb trial and completed analyses across the Phase II program such that we recently held the end of Phase II meeting and are continuing to engage potential partners to progress that into Phase III. And finally, for LX9851, we secured a worldwide exclusive license with Novo Nordisk. We're incredibly pleased with that arrangement, and we completed all the IND-enabling work towards the end of last year.

All of this is built on operational excellence, where we've really taken very tight control of our spend. We have an INPEFA virtual sales force to be able to make INPEFA continually available to patients with heart failure. We've had the first ex-U.S. approval of INPEFA via our relationship with Viatris and submissions are ongoing outside of the U.S. and outside of Europe.

So in 2026, we've set up with a very clear goal of what we need to achieve. We need to partner pilavapadin and progress that into Phase III trials. We need to complete the enrollment of the SONATA Phase III trial for HCM. We're evaluating the regulatory pathway for Zynquista with a potential resubmission and approval in 2026. We're supporting the international expansion of sota by Viatris and really maintaining our discipline to support long-term growth.

Let me take a deep dive into our cardiometabolic platform. Really, HCM has become a topic of huge investor and clinical interest as more agents come online, the 2 approved agents, CMIs for obstructive HCM. We have a plan and have an ongoing trial -- Phase III trial in HCM called the SONATA trial, where we're looking at both obstructive and non-obstructive HCM in the 1 trial. That's accelerating nicely. The enrollment is going very well, such that we will conclude the enrollment in the first half of this year with potential top line data in the first quarter of next year.

In type 1 diabetes, we're on track for a resubmission to the FDA for the treatment of glycemic control in type 1 diabetes as an adjunct to insulin. It's hard to believe that since the invention of insulin, there's been no adjunct to control blood glucose in type 1 diabetes. This could potentially be the first adjunct in that over a century of history.

Like I mentioned, hypertrophic cardiomyopathy has been an area of intense interest recently. There's about 1 million people living with HCM. And it's really a very debilitating disease. People have shortness of breath, fatigue, activities of daily living are highly impacted. And it has significant downstream consequences can lead to heart failure and stroke.

And of that 1 million people, about 50% have an outflow tract obstruction or obstructive HCM and about half have non-obstructive HCM with underlying disease pathogenesis of altered metabolism, cardiac energetics across both of those. And that's what sotagliflozin targets.

So sotagliflozin, because of SGLT1 and SGLT2 dual inhibition is the only drug that works inside and outside the heart in HCM. The SGLT1 is expressed on the myocardium and it's by the expression of SGLT1, which has been up until now pretty underappreciated that sotagliflozin has its impact on altering cardiac energetics in the heart. And thereby allows it to potentially be a first-line agent with no grams in obstructive and non-obstructive HCM.

As I mentioned, we continue our Phase III SONATA trial, but that is really complemented by 2 other investigator-initiated trials that give us significant read-through into the Phase III outcome. SOTA-P-CARDIA was presented at the American Heart Association meeting last November. And it looked at the mechanistic benefits of sotagliflozin in patients with true HFpEF with an ejection fraction above 50.

Importantly, SGLT2 inhibitors, which have been around for a while, have both shown no efficacy in this type of population. Clinically, these patients really present very similar to non-obstructive HCM. The data showed that both from a symptomology perspective as well as from a functional perspective, sotagliflozin significantly improved disease dynamics in this group of patients, which really gives us confidence that this has the potential to impact non-obstructive HCM.

SOTA-CROSS is a crossover study looking at sotagliflozin in non-obstructive HCM. It's a 12-week crossover study, and that is ongoing. Now finally, in addition to both heart failure and HCM, sotagliflozin is on the precipice of being potentially resubmitted and potential approval to the FDA in 2026.

When we issued the CRL in 2025 at the end of 2025, the FDA was very explicit that they were needing more prospective data to demonstrate that the risk of diabetic ketoacidosis with sotagliflozin was acceptable. They had already accepted that the efficacy of Zynquista supports an approval, and they needed new prospective data.

And it just so happened that an investigator study called STENO, probably the largest study in type 1 diabetes ever, 2,000 patients looking at cardiac outcomes over 5 years was acceptable to look within that enrollment of patients to look at the exposure to sotagliflozin and what the rate of DKA could potentially be.

That open-label ongoing study in our estimation would allow us to both file and potentially have an approval in type 1 diabetes this year. We've been really impressed with the ongoing support of the type 1 diabetes patient population who continue to support and advocate for the approval of this medicine.

So let me switch now to pain. It's been an area that is really starting to get significant attention across the scientific community. And we are focused very much on neuropathic pain, the form of chronic pain. And pilavapadin is being investigated for diabetic peripheral neuropathic pain, or DPNP, which is a huge unmet need.

Neuropathic pain is chronic pain that comes about from damage to the nerve. And the biggest cause of that is diabetes. There are about 9 million patients in the U.S. living with DPNP. And the treatment paradigm for this typically involves gabapentinoids. So pregabalin, Lyrica, which was brought to the market over 2 decades ago.

Patients are really dissatisfied with these treatment options. They're not well tolerated. They're not very effective. And so typically, patients cycle in and out of treatments over time and eventually drop out of treatment altogether. So it's a really high unmet need, but it's -- and there's been little innovation in this area in a long time.

Nevertheless, there's a huge desire politically to have new non-opioid medicines. The alternatives to PAIN Act and the recent submission of the Relief of Chronic Pain Act show that the government has -- or there's bipartisan support to ensure that there is access to new non-opioid medicines going forward.

Pilavapadin is an inhibitor of AAK1, which is involved in the mediation of endocytosis, essentially involved in modulating the receptor vesicle recycling, which modulates the neurotransmitter exposure in the synaptic cleft, thereby leading to downstream abrogation of pain signals in the dorsal horn of the spinal cord. And we've been the first company to really show very significantly placebo-adjusted improvements in pain score in DPNP across a number of studies in our Phase II program.

We've shown biological activity. We've demonstrated that the 10-milligram dose of pilavapadin reduces ADPS, the average daily pain score by 2 points, and it has an acceptable tolerability profile. So this really now supports advancement into Phase III trials, and it would potentially be the first non-opioid treatment for DPNP in 2 decades.

As I mentioned, there's significant political and advocacy interest in developing new medicines. The FDA has recently provided draft guidelines on how to develop new medicines for DPNP and other forms of neuropathic pain. And we continue to advocate for new medicines in this space.

So what's next? We've completed the end of Phase II meeting. We continue to refine our Phase III protocol to ensure that we manage variability in particular, placebo responses moving forward. And we're reengaging with partners as soon as we receive the minutes from that meeting in the very near future.

So finally, let me just wrap up with where the company is right now. We very pleased that we've been able to do 2 very significant deals in the recent past. Firstly, we've expanded the geographic reach of sotagliflozin by a deal with Viatris to promote sotagliflozin across indications outside of the U.S. and outside of Europe. They've submitted in Saudi, Canada, Australia, New Zealand, Mexico and Malaysia. And in fact, had their first launch in the UAE on Monday.

And secondarily, we licensed LX9851, a novel non-incretin oral medicine to Novo Nordisk. And we recently triggered a $10 million milestone payment, are on track to receive another $20 million payment this year as we move -- as they move that into the clinic. That's incredibly exciting option as we now have oral semaglutide, and they are really focusing on how do they bring other non -- other oral medicines either a stand-alone or combination.

At the end of last year, we ended with about $125 million in cash and cash equivalents, which supports our operations into 2027. And as I mentioned, the milestones from Novo are excluded in that forecast.

So what does 2026 bring for us? Well, we're going to advance our late-stage pipeline in SONATA-HCM and for Zynquista in type 1 diabetes. We'll continue to support our partnerships with Novo and with Viatris, and continue our discipline in managing cash so that we really allocate capital in a way that benefits the long-term value of the company.

So with that, I thank you very much for your attention and look forward to questions.

Thanks, Mike. Maybe starting with the cardiometabolic side. What gives you confidence in the potential utility in HCM and where everything would fit in the current treatment paradigm?

Yes. Thanks, Alex. So we have a number of pieces of evidence that both in our own clinical trials and in investigator-initiated trials that have read-through into the ability of sota to be a significant factor in helping non-obstructive HCM in particular. So we're confident that, that gives us good grounds to believe that SONATA will be positive.

Further to that, we're very pleased to ensure and look that we will have a place in the treatment paradigm that is likely earlier on in the management of HCM than what you're seeing with those medicines that have a complex REMS or complex logistics in getting them initiated.

So that gives us a feeling that if SONATA is positive, we have the potential to have a broad patient population that could be applicable for sotagliflozin and not just be restricted to certain high throughput centers.

Yes, I'll add a little bit more context. Thanks, Mike. It's Craig Granowitz, I'm the Chief Medical Officer at Lexicon. The important thing to think about with sotagliflozin, as Mike mentioned during his prepared remarks, it's the only agent that acts both on the heart directly and indirectly. So you're getting all of the SGLT2 effects on the renal and the SGLT1 effects on renal function, reducing preload and afterload and overall heart failure benefits, symptomatic relief reduction, particularly improvement in KCCQ score and 6-minute walk.

The unique attributes of sotagliflozin is the only dual inhibitor of SGLT1 and 2 is that you're getting direct effects on the myocardium. As Mike mentioned in his prepared remarks, the issue with HCM is you have both a hyperdynamic contractility, which is where the CMIs are acting, but you also have a metabolic disorder in the myocardium that's probably both mitochondrial-driven and ex mitochondrial driven.

And as Mike mentioned, we've demonstrated with significant both clinical tissue explants and animal model data that sota is acting to improve the energetics and much more efficient use of ATP and energy in the cells. And it's that long-term diastolic dysfunction that leads to cardiac fibrosis and ultimate heart failure with a stiff large left ventricle.

Great. Maybe as we're thinking about the market sizing between obstructive versus non-obstructive, where do you see that going and fitting in and especially with the recent regulatory time lines for OHCM?

Yes. So our best knowledge is currently, it's about a 50-50 split between obstructive and non-obstructive. Most of the obstructive patients have been diagnosed because it's very easy to see it on an echo. And what we're finding now is, in fact, the non-obstructive population is growing significantly faster, not because all of a sudden, there are more non-obstructive HCM patients, but in fact, it's the awareness is being raised by new medications and people are thereby discerning non-obstructive HCM patients from what may have previously just been diagnosed as a HFpEF patient.

So we think with SONATA, because we're having a single study across both obstructive and non-obstructive, there's an opportunity for us to be broadly applicable across the 2 categories of disease. They may be applied a little bit differently. The CMIs are clearly having an indication currently for obstructive HCM. They're quite effective at reducing that outflow tract obstruction. And so sota could be potentially used on top of the CMI for obstructive. For non-obstructive, we think that there really is the potential for broad use in that population because, as Craig mentioned, sota is really getting to the underlying pathology of the disease, the cardiac energetics.

On Zynquista, so needed advance for type 1, right, aiming to submit an NDA. What's been your recent dialogue with the FDA, kind of your time line of resubmission? And just what gives you confidence this time?

FDA only had a single question in the CRL is, can you bring to us prospective data that would give us confidence that in another data set, the rate of diabetic ketoacidosis would be acceptable. And so we need to define with FDA a few things. What was acceptable in their mind, and I think they've clarified that. They've also clarified how much exposure do you need? Because DKA, fortunately, is a pretty rare event so that you need a significant amount of patient exposure and experience in order to accumulate enough patient years of exposure to have a rate of diabetic ketoacidosis that you can have confidence in.

So the more data you have, the more confidence you have in that point estimate of the rate of DKA and that the confidence interval starts to shrink. So primarily, the discussion with the FDA around the STENO trial has been, first of all, that FDA has agreed that this trial is suitable to address their question. That was a critical milestone. The second is that we've agreed with FDA of what an acceptable rate of diabetic ketoacidosis would be. And the third is we've also gained alignment with FDA of roughly how much total patient exposure do we need in order to achieve that.

And those are really the parameters that we're working against as we accumulate that data to reach those thresholds that FDA and we have agreed, working very closely with this third-party group in Denmark called STENO, which has a 40-year history of running really world-class type 1 diabetes studies and includes nearly every type 1 center in the entire country of Denmark. And as Mike mentioned, STENO1 is probably the largest type 1 -- largest and longest type 1 study that's ever been conducted with 2,000 patients as a target enrollment.

Got you. Thanks. Maybe shifting to pain on DPNP, Phase II data from the potential. How would you describe the overall opportunity? And what are you hoping for ultimately in a partner?

The opportunity is massive for a couple of reasons. The size of the patient population is very large, as I mentioned, just in the U.S. alone, 9 million diagnosed patients, 9 million patients who have received some sort of treatment recently. But perhaps more importantly, the fact that there are just no good options. And as we mentioned, that patients cycle through the available options, which are the gabapentinoids, the dual reuptake inhibitors, mostly duloxetine as well as then the potential to move to opioids. And opioids clearly have significant efficacy in this space but come both with side effect and social issues that may not make them optimal.

So for that reason, having pilavapadin potentially be the first and only approved agent, I think there will be significant demand both from patients and physicians for that medicine as well as the tailwinds of legislative support, if you like, for ensuring that passes through payers and access in a smooth way.

Got it. And then on obesity, obviously exploding, everything is going on there. Partner program with Novo 9851, what's differentiating about that? And what do you think the bar will be ultimately for these next-gen therapies coming to market?

Yes. I think the question is going to be any drug that's acting on absorption is going to be GI tolerability and GI tolerability, both independently and on top of GLP-1 in the case of Novo with semaglutide. The benefits of this agent is currently a large majority of patients don't stay on these drugs for very long. And in fact, you see even in the media today, various media stars coming out and saying, I can't stay on my GLP-1. And when I go off my GLP-1, I regain 20 or 30 pounds.

So I think the long-term future of this category, if you listen to those at Lilly, Novo and other leading companies, is to switch to from an injectable market to an oral market and a market that you can either cycle therapies that you have nonoverlapping toxicities or that you have something that is better tolerated over the long run.

And last one for me, I would love to open it up to everyone else. But what are you most excited for in 2026 with Lexicon?

Just continuing to advance our pipeline, both with HCM, but perhaps most importantly, getting Zynquista over the line. And the demand there and the need from patients is extreme for a new option to help them manage their blood glucose. And so we're really excited for that. And of course, finally, then partnering pilavapadin and having that move into late-stage development to make it available for a patient group that really has a huge need.

Great. Thank you. Awesome. Well, thank you very much. Thanks, everyone, for coming.

Thanks so much.

Thank you.

Thank you, everyone, for tuning in. I'm Andrew Tsai, Senior biotech analyst at Jefferies, and it's my pleasure to have the Lexicon team with me today. Sitting to the direct right of me is Craig Granowitz, CMO; and to his right is Mike Exton, CEO. Welcome, both of you.

So maybe to start, give us a brief overview of Lexicon, what you're trying to achieve, what you're working on, catalyst flow over the next 6 to 12 months could be helpful.

Yes. No, fantastic. So delighted to be here. It's been a wonderful meeting so far. And in fact, an incredible 2025 really for Lexicon up until this point. So we've had a number of very significant advances of the pipeline over the last 11 months. And let me just outline briefly where we're at across those developments.

So first of all, for pilavapadin, our novel AAK1 inhibitor for neuropathic pain, we read out our Phase IIb trial, the PROGRESS trial this year. And over the last 6 months, we've analyzed the totality of evidence from that Phase II program and have submitted an end of Phase II meeting request to the FDA and submitted our briefing book.

That meeting will take place this year. And so we're looking forward to engaging with them to understand their expectations around the Phase III program and so being in a position to advance that into pivotal trials next year. At the same time, we're engaging with potential partners on looking how we partner that asset and move that not only into pivotal trials, but forward into commercial products. that's gone incredibly well.

Secondarily, for sotagliflozin, we are now accelerating the enrollment in the SONATA trial. This is a trial for non-obstructive and obstructive HCM, hypertrophic cardiomyopathy. It's enrolling incredibly well. We've now got all sites worldwide open. And so with that, the patient recruitment is really steadily increasing. And we expect to close the enrollment of that certainly in H1 of 2026, if not by Q1, if we continue to really perform very well there.

This is an incredible area where if we have data at the end of 2026, we could potentially be the first medicine that has positive data in nonobstructive HCM. As you know, there's current medicines that have had positive data in obstructive HCM, which is an important component, but a huge unmet need in nonobstructive HCM. So that's a great opportunity for us.

And we have recently, with sotagliflozin, the same asset; reengaged with the FDA around type 1 diabetes, as you're well aware, Andrew. And we've had incredibly constructive engagement with the FDA ever since our end of review meeting in May of this year.

And we now have submitted to them a third-party investigator-initiated study, the protocol, the design and in fact, some data from this open-label study that will support a potential resubmission for Zynquista. It's really what the FDA has requested from us now for the last couple of years.

As new prospective data in somewhat unique position, the FDA has accepted this data or accepted this trial, which is an IIS from Denmark as potentially being supportive of a resubmission. So that's fantastic for folks with type 1 diabetes who've really been an incredible advocate for having this medicine approved.

And then finally, we, earlier this year, had a worldwide license, exclusive license with Novo Nordisk for our novel obesity agent, LX9851, that targets another novel target discovered by the Genome5000 platform.

It was on us to complete the IND studies, IND-enabling studies for that asset. They're all now done. And so we've handed over the full data package to Novo Nordisk, who really have demonstrated their enthusiasm and desire to push this program forward at pace.

And so we're now waiting on them to submit the -- prepare and submit the IND, and that will enable some early milestone payments of up to $30 million, and we look seeing how that asset progresses in the clinic.

So really a heap going on for us, a number of catalysts across the cardiometabolic space, the neuropathic pain space and obviously, with obesity as well.

Great. So 3 late-stage programs plus a very differentiated obesity program on top of that. Okay. So maybe we can talk about type 1 diabetes. You alluded to how the FDA seems to be collaborative. But can you give us a brief history of what's happened since the initial CRL that you received? What exactly was the FDA bothered by? And how have you addressed it in a sense you alluded to earlier?

Yes. Thank you, Andrew. And the FDA letter has now been made public by the FDA of our CRL. And I think we've shared publicly what the three key elements were.

The first is that FDA recognizes the unmet need and the patient request and demand for a non-insulin-based therapy to improve glycemic control in type 1 diabetes because only 20% of patients get to goal.

The second is that they realize that they need to be more collaborative with us and expressed a real willingness. And honestly, those words have been matched by their deeds to be very open and quite constructive in their dialogue with us.

And the third is their openness of using nontraditional company-sponsored sort of Phase III-type trial, which was really the significant issue we've had with the FDA throughout is how do you document it with prospective data, the rate of diabetic ketoacidosis, which by its very definition is a rare event. So how in a group of patients, which is relatively rare with type 1 diabetes, do you run a study in a reasonable period of time with a reasonable cost with a clear outcome to meet the FDA's request?

So I think by FDA's willingness to accept, and as Mike mentioned, and I think we publicly stated this is the STENO trial, which again is publicly listed on clinical trials; it's a 2,000-patient trial being run by the STENO group and funded through the Novo Foundation, who is their funding source. So Lexicon is not paying for this trial.

The trial was already running, so that saved a significant amount of time. So we've reduced our cost to essentially just free drug. The timeline significantly [ reduced ] because the trial was already running. And then to really discuss with FDA, the trial design, the way that they are collecting data, the way that they're collecting DKA events; those seem to be acceptable to the agency.

So right now, we're really working through the agency of exactly what criteria they want to see in order to satisfy their concern about benefit risk on DKA rates and then the amount of data and exposure data that will be required to meet their test and then will the data actually support the contention that the rates of diabetic ketoacidosis are at or below those that were seen in the [ tandem ] program.

I see. And can you give us a framework of how big of a market opportunity this is peak sales-wise, if you were to get this approved?

Yes. So this is a pretty sizable market opportunity. There's 1.7 million type 1 diabetics in the U.S. As Craig said, only 20% of them get to goal. So really, there's a huge need for further glycemic control, which they haven't had for over a century. It's hard to believe actually that that's the case.

And the important piece for us is that type 1 diabetes offers a different commercial opportunity to what we saw with INPEFA and heart failure. And the reason for that is this will be the first and only in its class approved for this particular indication. That affords you a completely different access situation, it affords you the potential to price it very differently to what saw with INPEFA.

And clearly, we are very connected with the patient community, with the physician community through our work with type 1 diabetes, through our work with [ phlobaphene ] in diabetic neuropathy. And so we believe that this is a very significant commercial opportunity for Lexicon.

I think, Andrew, the other part, again, we, in a sense, already have a prepaid life cycle management program as well. And I think that's important to remember because in many cases, it's a significant additional expense on the P&L to run a significant LCM.

But you have the STENO trial running, which is looking at reducing rates of MACE in an enhanced treatment regimen that includes sotagliflozin and/or semaglutide and/or Finerenone. I think that will be very helpful.

There's a trial that's running a double-blind placebo-controlled study in with type 1 diabetes and symptomatic heart failure. So that trial is also running in accruing patients and again, is being paid for by third parties.

And then there's another trial that's running as well type 1 patients with chronic kidney disease and looking at modification of disease progression in that group. So all of that is already ongoing and prepaid.

And then there's also another whole set of studies that are being supported by the NIH that are all using sotagliflozin to look at the mechanism of diabetic ketoacidosis and acidosis in general. So all of that work is already paid for and going.

I see. And specifically, the STENO, because it's open label, you're able to provide the data, DKA rates, whatever the FDA needs in real-time?

That's right. Andrew, that's a really critical sort of in-the-weeds point. But the fact that it is an open-label trial, we [ can't ] provide with collaboration with STENO because it's their trial of that data to the agency.

Understood. So meeting with the FDA in Q4, fair to assume we hear back the Street in early 2026, maybe you wait for the meeting minutes. Is that fair? Or could we expect an update actually in Q4?

Look, I think it will be around about that time. We expect to have clarity around the end of this year. And so we'll be either engaging with the Street end of this year or in '26. And importantly, that would give us the possibility, we believe, to have a potential resubmission early in 2026 as well. So yes, that's a very near-term opportunity for us.

And if the FDA says "No, not at this time, we're not yet convinced," do you just stay on the sidelines, wait for these other trials to accumulate more data then go back to the FDA? Or would you consider running a separate trial, for instance?

I think here with the FDA, we are both very aligned on this time around working together in a way where we believe this is an approvable drug. And so I'm not really anticipating. Of course, we don't know how the data will show out. We know what the data is looking like right now. Of course, we will see as time progresses.

But I think both the FDA and for Lexicon, we're fully aligned that this is an opportunity that we need to provide folks with type 1 diabetes.

Yes. The two major technical variables are the enrollment in the trial and exposure and then the rates of DKA that are actually demonstrated in the trial. So I think those are really the two main variables.

Right, right. So if this is approved, you mentioned that you could price this differently to INPEFA, which is underlying the same drug. Any kind of color on the pricing differential...

It's probably a little premature, Andrew. It's a nice question, but probably a little bit early to comment on that. We've actually conducted some research at the end of last year when we were looking to potentially have an approval. We will sort of double-click on that and confirm our assumptions, and we'll probably be able to comment further early next year.

Sure. And then maybe last question because sotagliflozin has been in the clinic for quite some time. Remind us the patent [ estate ] of Zynquista?

Yes. So we have until 2033.

Okay. Very good. And so moving on to HCM. It sounds like data could be second half 2026. Is that the case? Phase III data?

Again, trial will be enrolled in the first half, then you got to treat the patients for 6 months and roll the data up. So I think the number that we're currently publicly communicated is first -- data, first quarter '27.

Okay. We're pushing hard to enroll as quickly as possible. So yes, look, this is an area of high unmet need for the patient and obviously, great opportunity. So we expect data certainly by Q1 of 2027 and pushing hard to accelerate as much as we can.

And my understanding is the primary endpoint is based on the KCCQ symptom score. And so what kind of data would you -- efficacy would you want to see across both obstructive and nonobstructive? What do you deem as successful?

Well, from a regulatory standpoint, I think it's the same thing that is seen as clinically meaningful is anything greater than a placebo-adjusted improvement of 4 to 5 points is seen as sort of a benchmark. And I think that's what others in this space have really looked for.

I would say that if you look at the recent data that was presented on HFpEF in a placebo-controlled trial in a study called [ SOTA CARDIA ] at AHA, there was a double-digit difference in KCCQ. And I think there are many that look at HFpEF as a read-through at least for nonobstructive HCM.

So those are the numbers that unlike any of the other drugs that are being looked at in HCM, we have a long track record with, again, over 12,000 patients in heart failure. So I think we've got a good understanding of the symptomatic relief. And HCM is just really a subset of HFpEF.

Understood. And would you expect efficacy to look different between nonobstructive and obstructive?

Well, I think if you talk to a lot of the KOLs, and again, all this is speculation; it's unlikely that SOTA is going to have a dramatic effect on reducing a significant outflow of tract obstruction. So I think that there are some that say, "Gee, maybe you'll get a larger reduction." If you have a very large outflow tract obstruction and a large gradient, that nonobstructive could give you a greater improvement than not.

But remember, we are allowing patients to be on a CMI as well. As long as the patients have a KCCQ score of below 80, that's the inclusion criteria. So I think this is going to be really the first data set that's going to have patients on CMIs.

And also the interesting group of patients who did have an obstruction or on a CMI and are now nonobstructive, but are still symptomatic, so I think that's going to be a really interesting group. We don't know how many people that will be.

But I think you're going to have every flavor of patient type. And I think that's going to be very important data for providers because this will be the first data set that's been done in a high-quality placebo-controlled trial on top of CMI.

I see. And let's just say this was approved, would this drug be positioned to be used ahead of [ CMIs ] or afterwards in your view?

Yes. Look, I think there's a couple of factors that really suggest this could be used first line. The first is that this is a very simple medicine to take. It's a once-a-day oral medicine that has a very well-known safety profile.

And if the efficacy certainly in nonobstructive turns out anything like we've seen in HFpEF, it will be a very, very compelling proposition to use first line, especially because the MAPLE data was read out by Cytokinetics showed that beta blockers at best do nothing and likely are not very helpful in obstructive HCM. So it's really causing physicians to rethink the treatment paradigm. And SOTA has a great potential to be used as a first-line agent because of that.

But that notwithstanding, of course, one of the issues that CMIs will always have, independent of whether it's [ maAR or AfI ], is the logistics and the burden that's put in place to initiate and maintain a patient on a CMI. And so that automatically gravitates towards a later treatment course if a patient is initiated on something and is still symptomatic.

So we think there's a great opportunity for SOTA to take a first-line in both obstructive and nonobstructive HCM.

And in the meantime, there is this third-party ISC SOTA-CROSS that has data in mid-2026 in nonobstructive HCM. Can you remind us the trial design, how long it is? How many patients? How much read-through could there be from that study to your own study?

Yes. So again, this is an NIH-sponsored trial being run at the University of Pennsylvania by the same investigator happens to be one of our co-PIs, Dr. Sharlene Day. It's -- in terms of patient numbers, it is relatively small. But the power of the trial is extremely high because it is a crossover design, hence the name SOTA-CROSS. And we really are looking at this as the totality of the data. So I think SOTA-CROSS is going to provide many of those other metrics that will complement what we're doing in SONATA.

So what we tried to do in SONATA is to have the most streamlined, most efficient, easiest-to-enroll trial for a registrational study and then to complement not only with the SOTA-CROSS data, but the SOTA-P-CARDIA data, again, also provides complementary data.

So when you look at that, you're going to have genomics, you're going to have proteomics, you're going to have a lot of MRI-based metrics. You're going to have additional physiologic metrics out of SOTA-CROSS and SOTA-P-CARDIA that will then complement the primary endpoint of the KCCQ in, again, high-quality studies that are run across the board.

In the very unusual circumstance where SOTA-CROSS shows a mixed signal, is there any way for you to make adjustments to your own SONATA trial?

My guess is by then to what Mike was saying before, the trial be fully enrolled. Again, there's always an opportunity before you close the database that you can change your SAP, but we haven't really thought through that.

Understood. And FDA, however, has given you the [ GreenLIGHT-1 ] study as enough for FDA approval?

Just like all the other companies. And I think you even saw that with the later studies that are done with the CMIs in the nonobstructive that FDA was satisfied with a single trial with the KCCQ primary endpoint.

Okay. So INPEFA, Zynquista and now this HCM, all rooted on sotagliflozin, are you filing sNDAs for type 1 diabetes in theory and HCM? Or are there unique NDAs to -- maybe that helps with pricing differential?

Zynquista is an NDA that was started before we even did the heart failure program. It goes back a long, long way. I think really the opportunity set with INPEFA for HCM, it would probably be an sNDA.

Okay. And do you have the intention, let's just say, everything worked out, to market this yourselves in the U.S.?

Yes, two different opportunities. I think for Zynquista, we're going to explore everything for the commercialization of Zynquista. We're certainly prepared to take an access first type of commercialization approach. And that then really lends itself to a somewhat sort of flexible model, somewhat virtual or certainly hybrid model and which we're now getting great experience with our INPEFA sales actually, which is promoted fully virtually.

And then in addition to that, there's the potential opportunity for co-promotes with companies who are deep in the diabetes and specifically type 1 diabetes space. So we're going to explore all of those.

For HCM, certainly in the U.S., I see that very much as a Lexicon opportunity that we would commercialize ourselves. We understand the space very well, and we would gear up to drive the commercialization of that ourselves.

Speaking of commercialization, Mike, maybe I'll just spend a moment since Viatris was on the agenda today here at your meeting. And I think it was notable that, that was mentioned repeatedly during their presentation. I think they've been very satisfied. I know we've been very satisfied with them as a partner.

They've already filed and gained approval and reimbursement approval in the United Arab Emirates and have filed and/or will be filing in 6 additional countries this year. And that's within 1 year of signing the deal with them. And they've additionally filed in Canada, Australia and New Zealand, in addition to the UAE, Saudi. And they have plans to file before the end of the year in a couple of other markets as well.

Understood. And then last couple of minutes, shifting to pilavapadin, a novel AAK1 inhibitor. You mentioned you'll start Phase III studies hopefully in 2026. Maybe talk about the big picture macro landscape around chronic pain, how that's changed? What's the FDA's view on that compared to before? Is it looks seeming more favorable basically?

I think, Andrew, the market has really developed in a very favorable way, even from a policy standpoint. So I think there have been two important things outside of Lexicon that have taken place. The first is FDA actually issued a few months ago a draft guidance for running studies in chronic neuropathic pain, which was very much in alignment with our expectations and our dialogue with them. So I think FDA recognizes the fact that they put all the effort of putting a draft guidance out and are currently seeking external feedback on that.

The other is that there's just legislation that would cover Medicare coverage of chronic pain that's been submitted in the Senate. And we believe that there also is a strong push to submit that into the House to have two separate bills, and that would dramatically expand the mandatory coverage similar to what was done with the NOPAIN Act in terms of acute pain.

So in addition to all the work that we're doing, I think there are significant policy support for this, both from the FDA and from the U.S. House and Senate in terms of the need for non-opioids options.

I see. So the macro is definitely on your side right now. And so you're talking to the FDA about the Phase III in Q4? And when should we hear about an outcome?

I think that would be early in 2026. So -- once we have the meeting and 30 days later, we should have the minutes and then we can describe what we've heard.

And then maybe last question. Should you start Phase III studies in 2026, when could we expect data you think?

I think we haven't talked about that specifically, but for progress, the IIb study was a year's time to get that fully completed.

Yes. Maybe I'll just give a time frame of the size of the study. We're really looking at probably 2 parallel trials. And there are 2 arms, so just 2-arm trials and roughly 350 patients per arm. So you're looking at studies that are not particularly large. And to Mike's point, we believe could be enrolled in about a year, you're looking at a 12 weeks treatment follow-up. So within a couple of years, you could have data.

Great. I think that's all the time we have, but thank you so much.

Thanks so much.

Thank you, Andrew.

Welcome to the Lexicon Pharmaceuticals Third Quarter 2025 Financial Results Conference Call. [Operator Instructions] As a reminder, this call is being recorded today, November 6, 2025.

I will now turn the call over to Lisa DeFrancesco, Senior Vice President for Investor Relations and Corporate Communications for Lexicon. Please go ahead, Lisa.

Thank you, Mila. Good morning, and welcome to our third quarter 2025 conference call. Joining me today are Dr. Mike Exton, Lexicon's Chief Executive Officer and Director; Dr. Craig Granowitz, Senior Vice President and Chief Medical Officer; and Scott Coiante, Senior Vice President and Chief Financial Officer.

This morning, Lexicon issued a press release announcing our financial results for the third quarter of 2025, which is available on our website at www.lexpharma.com and through our SEC filings. A webcast of this call, along with the slide presentation is also available on our website. During the call, we will also review the information provided in the press release, provide a corporate update and then use the remainder of our time to answer your questions.

Before we begin, let me remind you that we will be making forward-looking statements, including statements related to the safety, efficacy, clinical development, regulatory status and therapeutic and commercial potential of pilavapadin, LX9851, sotagliflozin and our other drug programs as well as our business generally. These statements may include characterizations and projections relating to the clinical development, regulatory status and market opportunity for our drug programs and the commercial performance of INPEFA for heart failure.

This call may also contain forward-looking statements relating to our growth and future operating results, discovery and development of our drug candidates, strategic alliances and intellectual property as well as other matters that are not historical facts or information. Various risks may cause our actual results to differ materially from those expressed or implied in such forward-looking statements, and we refer you to our most recent annual report on Form 10-K and our other SEC filings for detailed information describing such risks.

I would now like to turn the call over to Mike Exton. Mike?

Okay. Great. Thank you, Lisa, and good day, everyone. Great to have you all with us this morning. We're really excited to give you updates on this quarter and all the great work that's going on here at Lexicon.

Now as we approach the final weeks of the year, I wanted to really begin by regrounding you on the ambitious set of strategic imperatives that we set out at the start of this year, which were designed to drive long-term value for the company. Now these goals were, firstly, to progress pilavapadin to be ready for Phase III registrational trials. Secondly, submit an IND for LX9851, our novel non-incretin candidate in obesity. Thirdly, to recruit patients and accelerate recruitment into our ongoing Phase III clinical trial in hypertrophic cardiomyopathy, or HCM, named SONATA; continue the ongoing discussions with FDA on Zynquista and establish a path forward in type 1 diabetes. And finally, to add targeted partnerships to maximize the value of our R&D programs.

Now throughout the past 3 quarters, we've made really excellent progress, not only against these goals, but within our pipeline and across our organization. In addition, we've continued to make strategic decisions to further advance our position across cardiometabolic disease with high unmet need. In so doing, we've successfully repositioned the company to really focus on R&D. We've achieved this focus by developing our innovative pipeline, maximizing operational efficiency and elevating the focus on targeted partnering.

So allow me to outline the substantial progress in R&D. For pilavapadin, we recently presented a post-hoc analysis of the aggregated results of our Phase II program in diabetic peripheral neuropathic pain or DPNP. All of our findings to date reinforce the broad clinical potential for this novel molecule as well as its Phase III readiness, and we're working with the FDA on next steps as well as engaging with potential partners.

For LX9851, I'm really pleased to say that we've completed our IND-enabling studies. And as you know, earlier this year, we entered into an exclusive agreement with a strong partner who have the capabilities to develop this asset as quickly and as broadly as possible.

And finally, for sotagliflozin, all 130-plus sites are now active in our Phase III SONATA study in HCM, which is the only Phase III HCM program enrolling both obstructive and non-obstructive subtypes.

Now operationally, we are very mindful of resource utilization here at Lexicon across all parts of the business. This has enabled us to significantly reduce our operating expenses while preserving investment in areas where we believe we have the highest probability of value creation.

Embedding an efficiency mindset has also resulted in us implementing innovative ways to drive our business forward. For example, as many of you are aware, a substantial proportion of the current evidence generation for SOTA is conducted and funded by third parties.

On the commercial side of our business, we've recently introduced an innovative virtual sales support system for INPEFA here in the U.S. as we look to move INPEFA from a stable breakeven business to a growing profitable revenue stream for Lexicon in 2026 and beyond.

Now before Craig takes us through specific updates on the pipeline, I'd like to take a few moments to talk about some other internal and external pillars that we believe will continue to positively shape our business moving forward.

First of all, as we continue to advance the science and explore the clinical potential of our assets, strategic and thoughtful partnering is vital to increasing the likelihood of our potential products reaching patients. Now we've demonstrated our ability to partner with strong organizations, and I'm really impressed not only by the capability and drive our partners are demonstrating, but how seamlessly and effectively our teams are really working together, and we can already see our strategy in action.

Firstly, we're working closely with Viatris on expanding the reach of SOTA for heart failure in major markets and territories outside of the U.S. and Europe, and they're making really excellent progress. Really, really happy with that partnership with Viatris.

Secondly, we aim to maximize the potential of LX9851 with our licensee Novo Nordisk, who, as you know, are a global expert in obesity and related conditions. And our recent completion of IND-enabling studies of LX9851 in obesity means that we may earn up to $30 million in near-term milestone payments as LX9851 enters future phases of development.

Lastly, partnership discussions are ongoing with pilavapadin, where we aim to collaborate with a high-quality partner to unlock the pipeline and appeal potential of this asset globally and across multiple indications. So our approach to partnership remains flexible as we aim to stay focused internally on our core cardiometabolic expertise.

Second, I'd like to turn your attention to Zynquista as our engagement with the FDA has progressed significantly. In September, we shared that we've submitted additional data to the FDA supporting the benefit risk profile of Zynquista as an adjunct to insulin for glycemic control in adults with type 1 diabetes. These data were from an ongoing third-party funded investigator-sponsored trials of Zynquista and were submitted as part of a Type D process to address the concerns the FDA had raised in its December 2024 complete response letter. Now we feel that these data support a positive benefit risk of Zynquista and address the concerns raised. And we're committed to working with the FDA on a path forward. In fact, the agency confirmed that they expect to provide written feedback by the end of this year. And following alignment with the FDA, Lexicon would target a resubmission as early as possible in 2026.

And finally, with health care on the political agenda in D.C. and beyond, we see positive shifts and opportunities in this environment for our portfolio. Now one area where this is particularly apparent is neuropathic pain management. Neuropathic pain is a type of chronic pain in which there's been little advancement in treatments for over 2 decades despite its significant impact on patients' quality of life. For those with chronic pain, many have prescribed oral opioids despite the known serious risks of misuse. Better, safer options are not only needed, but in fact, being demanded.

And there have been 3 major developments this quarter that I want to update you on. Firstly, as a part of our advocacy efforts this year, Lexicon convened the first ever chronic pain roundtable in D.C. with representatives across clinical, patient and payer communities. We're really inspired by this discussion with all of these experts, all of whom are actively advocating for recognition of chronic pain in legislation and the need for new innovation and access to non-opioid treatment options.

Second and most recently, just a few days ago, a new bill, the Relief of Chronic Pain Act was introduced into the U.S. Senate to increase access to non-opioid therapies for Medicare patients with chronic pain. And finally, the FDA recently issued new draft guidance to expand non-opioid options for chronic pain management. So these 3 factors, together with additional legislative efforts that are currently making their way through Congress really underscore the critical bipartisan demand for opioid alternatives in pain management.

So overall, we're encouraged to see that not only these signals from the broader legislative environment, but also other important catalysts for change. From regulatory openness, evolving access dynamics, AI exploration and overall changes in clinical care, all of these changes are huge opportunities for our company.

So with that, I'll turn it over to Craig to further update you on our assets under development. Over to you, Craig.

Thank you, Mike. As Mike mentioned, we have made significant progress across our pipeline this year. It has been a busy and productive 3 quarters. I'd like to begin with pilavapadin, our novel non-opioid AAK1 inhibitor. Data and analyses from 3 separate Phase II trials in neuropathic pain provide evidence of consistent and clinically meaningful pain reduction and validate the response and tolerability profiles of pilavapadin. While our lead indication in DPNP represents a mature clinical program, several secondary indications are also Phase II-ready, providing significant expansion opportunities.

In addition, the AAK pathway is central to a number of cellular processes such as synaptic signaling between neurons. With this in mind, we've also conducted IND-enabling work in multiple neuroscience indications, underscoring pilavapadin as a potential pipeline in a pill. We've accumulated data from more than 600 patients treated with pilavapadin and have demonstrated a well-understood and acceptable safety and tolerability profile.

Finally, patent protection on the pilavapadin molecule extends through 2040 when including an anticipated 5-year extension. This provides a long period of exclusivity to maximize the value of any investment related to this asset. For the past several weeks, we have presented data on pilavapadin in DPNP at a number of important medical meetings.

For context, earlier this year, we shared top line data from PROGRESS, our Phase IIb study of pilavapadin in patients with DPNP. The study met its objective of identifying 10 milligrams as the appropriate dose to advance into Phase III development. Since that time, we have completed additional post-hoc analyses and an additional renal impairment study to further clarify the product profile.

We set out to achieve a few objectives with these analyses. One, to investigate an exposure response relationship; second, to evaluate adherence across treatment arms; third, to validate the robustness of the 10-milligram dose; and finally, to confirm the safety and tolerability profile by evaluating pilavapadin’s pharmacokinetic profile in a broader patient population.

The post-hoc PROGRESS and RELIEF analysis that we presented in September and October successfully addressed these key objectives, leading us to a few important conclusions. There is a linear relationship between increased plasma levels of pilavapadin and reduction in pain score. The post-hoc analysis confirmed the biological activity of this drug.

Second, pilavapadin’s effects on pain is clinically meaningful. Notably, the 10-milligram dose achieved a 2-point drop in ADPS from baseline by week 12. Third, the 10-milligram dose demonstrates an acceptable tolerability profile with nearly the same percentage of patients completing the study on treatment arm as the placebo arm.

And lastly, we conducted additional human studies that have concluded there are no cardiac signals such as QTc prolongation. And in patients with mild to moderate renal impairment, no pilavapadin dose adjustments will be required. These are important findings that support a broader potential patient population to be included in the Phase III studies.

So what's next for pilavapadin? With the results from our Phase II program, our request for an end of Phase II meeting with the FDA has been granted. We are scheduled to meet with the agency by the end of this year and receive written feedback from the agency by early next year. In parallel, we are progressing our planning for a Phase III program in DPNP. We have incorporated the input from our Scientific Advisory Board who were supportive of our Phase III development approach as well as elements from the recent guidance from the FDA on non-opioid clinical development. In conjunction with this activity, we continue to have ongoing engagement with potential partners.

Now, to shift our attention to sotagliflozin, where we believe our opportunity continues to strengthen with time. INPEFA has remained on the market in the U.S., and we see steady sales from our base of loyal prescribers. We also continue to build distinguishing evidence from investigator-initiated studies supporting sotagliflozin's mechanism in hypertrophic cardiomyopathy, heart failure and in major adverse cardiac events, or MACE.

Beyond heart failure, where sotagliflozin has been approved in the U.S. based on clinical data from 2 large outcome studies, enrollment in our Phase III program of sotagliflozin in HCM continues to accelerate. And lastly, as Mike outlined earlier, we are maintaining close communication with the FDA about the potential resubmission of Zynquista in type 1 diabetes. We strongly believe these 3 factors are integral in establishing sotagliflozin's potential as a new class of therapy.

We have 3 upcoming data presentations this week at the AHA Scientific Sessions and the HCM Society meetings, which will highlight sotagliflozin's unique potential across diverse patient populations. As you may know, cardiac care is complex, involving multimodal treatment in an effort to improve overall patient outcomes. Of particular importance for us, many patients who have hypertrophic cardiomyopathy go on to experience major adverse cardiac events such as myocardial infarction, stroke or heart failure. At this weekend's meetings, Dr. Qin from Boston University Medical Center; Dr. Badimon from Mount Sinai in New York City; and Dr. McGuire from the University of Texas will highlight, respectively, sotagliflozin's impact on cardiac remodeling in HCM, an AHA late breaker on the benefits of sotagliflozin in HFpEF and a presentation on the effects of MACE events in patients with type 2 diabetes.

SONATA-HCM is a large global registration trial with a KCCQ endpoint designed to support a regulatory filing and broad label in HCM. SONATA-HCM is the only ongoing registrational trial currently evaluating a treatment in both obstructive and non-obstructive HCM. We recently completed the target 130-plus site initiations in 20 countries across the United States, Europe, Israel and Latin America. This is an important milestone for the program, and I couldn't be more proud of the team's significant efforts in achieving this goal. With these site initiations complete, there has been a significant acceleration in study enrollment.

I'll now turn over to Scott to provide an update on the company's financials.

Thank you, Craig, and good morning, everyone. For the third quarter of 2025, we reported total revenue of $14.2 million compared to total revenue of $1.8 million for the third quarter of 2024. Q3 2025 revenue consisted primarily of $13.2 million of licensing revenue recognized from our agreement with Novo Nordisk. Licensing revenue under this agreement is being recognized as the IND-enabling work is completed. Through September 30, 2025, a total of $40.7 million has been recognized as licensing revenue from this agreement with the remaining $4.3 million expected to be recognized in Q4. Total revenue for the quarter also included net product revenue of $1 million from sales of INPEFA.

Research and development expenses for the third quarter of 2025 decreased to $18.8 million from $25.8 million in Q3 2024, primarily reflecting lower external research expenses associated with the completion of our PROGRESS clinical trial, partially offset by increased investment in our SONATA Phase III clinical trial in HCM.

Selling, general and administrative expenses for the third quarter of 2025 decreased to $7.6 million compared to $39.6 million in 2024. The continued decrease reflects lower costs as a result of our strategic repositioning in late 2024 and significantly reduced marketing efforts in 2025 for INPEFA as well as general diligence and focus on operating our business efficiently.

Net loss for the third quarter of 2025 was $12.8 million or $0.04 per share as compared to a net loss of $64.8 million or $0.18 per share in the corresponding period in 2024. We ended the third quarter with $145 million in cash, short-term investments and restricted cash as compared to $238 million as of December 31, 2024.

I would also like to note a few other items from the quarter. On the expense side, we continue to reduce costs and streamline our operations. Quarter-over-quarter operating expenses decreased by $39.1 million, primarily due to the strategic repositioning as an R&D-focused company.

We are maintaining our full year 2025 guidance for operating expenses. Total operating expenses are expected to remain between $105 million and $115 million, with R&D expenses projected to be between $70 million and $75 million. SG&A expenses are expected to range between $35 million and $40 million. Our R&D expense assumptions do not include costs associated with Phase III pivotal studies of pilavapadin as our goal would be to take this asset forward with a development partner.

Overall, we are in a strong position with the resources needed to advance our ongoing clinical programs while maintaining a disciplined approach to capital allocation and a focus on creating value for our shareholders.

I will now turn it back to Mike for his closing remarks.

Yes. Thanks, Scott. Look, you can see that we have achieved quite a lot already in 2025, and I'm excited about where we continue our strong execution to wrap up this year.

As I shared earlier regarding pilavapadin, we're planning for an end of Phase II meeting by year's end. Our preclinical work continues as we explore the broad potential value of this asset and evaluate expansion into additional indications. Additionally, a partnership for pilavapadin will allow us to become therapeutically focused on our core cardiometabolic programs and expertise.

For SOTA in HCM, we're really excited to share results from complementary studies of SOTA starting this upcoming weekend with AHA, which could provide valuable additional insights on this therapeutic candidate. In parallel, our SONATA study sites in the U.S., EU, Israel and LatAm are enrolling according to plan with all Phase III sites up and running.

For INPEFA, our partner, Viatris, continues to make progress against plans for regulatory approval. Sotagliflozin was recently approved in UAE and now has been submitted for approval in Saudi Arabia, Canada, Australia and New Zealand, where there are a significant number of potential patients in need. In addition, Viatris has announced plans to submit for approval in additional markets, including Mexico and Malaysia by the end of this year. That's a total of 6 important markets to be filed by the end of the year, and we're thrilled with the momentum that we're building together with Viatris.

For Zynquista, we're working closely with the FDA on a potential path forward for T1D. The agency confirmed that they expect to provide written feedback by year's end. And following alignment with the FDA, we'd work to submit our NDA as early as possible in 2026.

And finally, LX9851, our IND-enabling studies for obesity have been completed, and we anticipate that Novo will expediently prepare and file the IND and advance into clinical development.

So looking ahead to 2026, we plan to maintain focus on what we believe makes Lexicon well positioned for success. We got a strong pipeline of differentiated assets, not only first-in-class, but first-to-market potential in therapeutic areas of high unmet need. We're excited to embrace these opportunities and showcase what we achieved going into next year in our future updates.

So we've got time now for some Q&A. So I'll turn it back over to the operator to manage the questions.

[Operator Instructions] Our first question comes from the line of Andrew Tsai from Jefferies.

Congrats on the progress. This is [ John ] on for Andrew. So for Zynquista in type 1 diabetes, you're seeking regulatory feedback in Q4. Are you looking for like a simple yes or no? Or just looking for like whether a resubmission would make sense? Or is there like perhaps more color that you're seeking? And then if you're able to resubmit in 2026, would it be a Class I or Class II resubmission?

Yes. Thank you for the question, John. It's Craig Granowitz. As Mike has mentioned and we've discussed previously, we're really leveraging ongoing trials, particularly the STENO trial in Denmark to use the exposure data in a very large number of patients to address the single concern that FDA raised at their end of review meeting, which is a prospective study to document rates of diabetic ketoacidosis. And as you might recall and as the CRL letter that was made public by the FDA a few months ago mentioned, "FDA accepts that there is efficacy with this drug, has meaningful reductions in A1c, meaningful reductions in severe hypo effects and obviously, the proven outcome that we've already seen in the labeling we have in patients with type 1 diabetes and heart failure.” So we are using the STENO trial with adequate levels of exposure, which is what we're really discussing with the FDA to prepare a submission really focused on that one single issue.

To answer your second question, while we don't have final written confirmation of this with the FDA, our expectation is that this would be as a resubmission, a 6-month review clock.

I think, John, just to provide a little more color from my side, I think what's really pleasing here is that the FDA has endorsed and accepted that the STENO protocol and patients that they're capturing are acceptable and the way they're capturing DKA is acceptable. So as we move forward, it really is around appropriate exposure levels to be able to give them confidence that the positive data that we are seeing gives them confidence for resubmission.

Great. And then maybe one more, if I can. For those third-party IST studies for SOTA in HCM and HFpEF, how do you expect the non-HCM data to perhaps give you greater conviction in the Phase III SONATA study success?

Yes, it's a great question. Clearly, there's an overlap between HFpEF and HCM. From a clinical standpoint, they are, in essence, indistinguishable. You see a very similar profile. You have normal ejection fraction, but you have patients that have symptomatic dysfunction, particularly diastolic dysfunction. And I think as you've seen with the CMIs, they're actually trying to go from HCM into HFpEF. I think they're having some challenges with that because a lot of patients are then developing ejection fractions that are dropping below 50%. We believe that by demonstrating data, and you'll see some of that as early as this weekend in the [ SOTA-P-CARDIA ], which is an oral late breaker at AHA as well as our continued mechanistic data that will be presented on tomorrow, actually Friday at the HCM Society meeting, we are distinguishing the effects of sotagliflozin in both the preclinical models, the animal models on energetics and cardiac remodeling that will fit very nicely with some of the clinical results that you might be seeing in HFpEF patients that will be presented at the SOTA-P-CARDIA data on Saturday at HCM.

So it continues to build a wall of evidence that is similar between HFpEF and HCM regarding cardiac energetics, cardiac remodeling, cardiac fibrosis and ultimately improved functionality and symptomatology in patients either with HFpEF or with HCM.

And John, again, allow me to sort of pile on there, I guess, more from a sort of commercial bent of how we see this. We have this program in HCM for both obstructive and non-obstructive thinking that a medicine that is oral once daily, easy to use and a well-known and understandable side effect profile, particularly given the data coming out of MAPLE really gives us a great opportunity potentially to work alongside CMIs, but in a first-line position in HCM.

And that first-line position, particularly as you're sort of expanding outside of the HCM centers into retail cardiologists and large-scale cardiology practices allows HFpEF and HCM, the patients present very similarly in those offices. And so having SOTA as an option for both HFpEF and a differentiated option for HFpEF and HCM gives the cardiologists peace of mind that they can use this medicine very successfully in either condition and particularly in non-obstructive where diagnosing the difference between the 2 is a little more challenging.

So both from a utilization as well as scientifically, we continue to generate additional data that will help support the use of this in a broad range of cardiology patients in across the cardiology community in the U.S.

Our next question comes from the line of Yigal Nochomovitz from Citigroup.

Congrats on the progress. This is [ Joohwan Kim ] on for Yigal. Maybe just 2 quick ones from us. Regarding the partnership opportunity in DPNP, can you orient us on how far along you are in identifying a partner and remind us whether or not you are awaiting to complete the discussions for the end of Phase II meeting with FDA before completing any partnership agreements?

Yes, that's a great question. So over the last, I'd say, 4 to 6 weeks, we've reengaged with a range of partners who we had originally discussed the top line data with. Obviously, the data that we presented over the last month, including the totality of the Phase II program, we've had the opportunity to talk with all of these partners. The end of Phase II meeting is a very important milestone in those discussions. I think it's fair to say in a space where there's been nothing developed for 2 decades in a space where new draft guidance has come out, it's important to have that confirmation as a part of those overall discussions.

So we're really looking forward now that, that end of Phase II meeting is scheduled for this year to continue to progress around that. We feel very confident actually with the dossier that we've submitted and are really looking forward to having the FDA's endorsement on what we think is a robust Phase III program that reflects their draft guidance, and that will certainly be a part of the partnering discussions that we're having.

Got it. And just one more, if I may. Understanding that you're seeking a broad HCM label. But in your discussions with the FDA, have they suggested the possibility that you would also be able to get approval for specifically non-obstructive or obstructive HCM as data from SONAT is stronger in one particular subgroup?

Yes. Very good question. We're approaching it similar to how we approached heart failure, and we had a broad label for heart failure regardless of whether it was HFrEF or HFpEF. And we're really taking that same approach with the FDA and the commitment we have on them when we met with them to discuss the protocol before initiating the trial was that this -- if the study is positive as conducted, would give us a label that would include both obstructive and non-obstructive patients. So we are seeking that. We are looking to have 2 groups of 250 patients each within the study. There is a stratification by obstructive versus non-obstructive, but the overall endpoint is anchored to the overall population.

Our next question comes from the line of Joseph Pantginis from H.C. Wainwright.

So a few as well, if you don't mind. So first, I think it would be helpful if you remind us when SONATA moves forward and if it were to be positive. Can you discuss the positioning, especially with the continued growing excitement in the HCM space and the role of CMIs and the hopefully upcoming approval of aficamten. So where would SOTA be positioned with regard to these other assets?

Yes. It's a great question, Joe. So I think it's firstly important to note that patients on a CMI are actually eligible to enroll in SONATA. And we've purposefully taken the approach again of using a very pragmatic trial that SOTA can be used in conjunction with underlying meds that are used in hypertrophic cardiomyopathy. Now, where I would see the positioning is typical across a lot of chronic medications in as much as those medicines that are somewhat more laborious, somewhat more costly often depending on sort of where it ranges and often positioned as sort of later lines in therapy.

And we would see sotagliflozin as we discussed a little bit earlier, as being a broad potential not only being used in the somewhat restrictive academic centers that have HCM study sites and clinical sites, but really across the broad scope of cardiology because it's a known mechanism. It's easy to use. And if we get positive results out of SONATA in both obstructive and non-obstructive, it allows this broad utilization and particularly given the results of the MAPLE trial, which showed that, in fact, beta blockers don't necessarily add any value, and there's a question as to whether, in fact, they may be causing some harm in HCM. I think that offers for us a really good opportunity to become a first-line agent in HCM, both obstructive and non-obstructive.

Mike, if you don't mind, I just want to add one other point. I think it's becoming more clear, Joe, and I think you've seen and heard some of these presentations even very, very recently that all of the CMIs that are currently under regulatory review will have REMS of some sort. And that certainly does put significant paperwork and process in place for patients being initiated. I think that inherently is going to limit the sites that are willing to do that because you need to have a critical mass in order to create the paper workflow. And there'll be many places that will have HCM patients in relatively low numbers that will not be willing to take on that burden.

So I do think the fact that the CMIs will have REMS and there might be differentiated REMS between them, but they will be what I would call significant limitations that are always a part of a REMS, and we don't have any inclination that, that would be the case with SOTA, which is a well-known agent that has already an indication for heart failure.

That's really helpful. And then I'll just ask my last 2 questions together. So first, with regard to the upcoming end of Phase II study, you've already provided some nice details around that. I just want to make sure I understood, you already have a lot of great feedback. Is there anything you would describe as questions that are left to address or finalize, number one?

And then if Zynquista were to move forward on the regulatory front in a positive fashion, what kind of commercial plan would you potentially be looking at, bringing it forward on yourself, a potential partner or what have you?

Great. I might throw the first one to Craig, and I'll take the second one.

Yes. Joe, great question on the end of Phase II. I think when it comes to the endpoint, the duration of the study, the patient population, I think we feel very comfortable with that, and I think that's been validated as well for other companies that are in Phase III in neuropathic pain and diabetic neuropathic pain that it will be 2 trials of roughly 300 to 350 patients each with a 12-week visual analog pain score with an average daily pain score outcome.

I think with any centrally acting agent, some of the areas of discussion are going to be regarding potential for central effects such as drowsiness. I think there's always going to be a question with any agent in this regard, even though there is no reason to believe and we don't believe that there is any issue of human addiction potential type activities. But we don't believe that there are any meaningful or significant next-day drowsiness or other central effects of this agent. And there is no indication in that large Phase II program that we've run, including a blinded withdrawal that there is any issue around addiction potential, but those certainly are areas that could be points of discussion with the FDA.

Right. And I very much appreciate, Joe, the question on the commercialization of Zynquista and to a degree, also thinking forward for HCM. And just allow me a couple of moments here to talk a little bit more generally and philosophically about how we're commercializing sotagliflozin. As you know, one of the first things that we did when I came into Lexicon was unfortunately having to relook at how we commercialize INPEFA. I want to state categorically that both Zynquista and for HCM are not going to be INPEFA situations for a couple of reasons.

As you know, INPEFA was third to market, actually fourth really in a space where there were 3, particularly 2 major incumbents and that made market access incredibly difficult. What we're seeing actually is that when physicians use this medicine and patients use them, it's incredibly sticky, but access was a very difficult situation. That is not the case for Zynquista and HCM. Why is that? Because it will be the first and only SGLT inhibitor potentially indicated in each of these indications. That does a couple of things. First, it allows us to completely rethink our pricing in both of these indications, and that has certain implications, particularly in HCM, where the CMIs are priced at a significant multiple to what other medicines are being used. But secondly, and perhaps more importantly, there's not an ability at the payer level to substitute, to step through.

And so the access conditions for Zynquista and HCM are very, very different. Now that does not mean that we intend to go with a full-blown commercial model -- traditional commercial model. And in fact, that's part of our installing the INPEFA virtual sales support system that we've got, which is all encompassing, and we'll have an opportunity perhaps to talk you through that, which is a good way for us to learn over the coming months of how we do this in a nontraditional way, whether that be completely virtual field presence, whether that be looking at a hybrid, whether it be even partnering on co-promotion, which could be an option. We're exploring all of these details in parallel.

And of course, the other thing that makes us really excited is we have partnered with patient groups over years now, well before I joined the company, and there's interesting commercial models that we can use and utilize some of this patient-driven advocacy like, for example, in my experience, we've seen with migraine and other conditions where patients just have this built-up pent-up demand, and we can do it in a very unique way. So more to come on that, but we're certainly exploring how we intend to potentially promote Zynquista should it come on the market.

And especially on the last commentary, it sounds like you have the ability to leverage a lot of optionality.

Our next question comes from the line of Yasmeen Rahimi from Piper Sandler.

This is [ Dominic ] on for Yasmeen Rahimi. Congrats on a great quarter. So we were looking at HCM. We know it's going to be an exciting year this year and especially considering that there's going to be a few presentations on the SGLT1 and 2 inhibitor class in HCM in the preclinical models. Could you help us understand how much proof-of-concept data we could gain from these presentations in HCM?

Yes. Thank you, Dominic. We look at any one of these presentations and particularly a preclinical model as part of a broader tableau around the mechanism of action and particularly the functionality of both the SGLT1 and the SGLT2 effects of SOTA, whether we're looking at the effects on stroke and MI, whether we're looking at the effects in HFpEF over looking at the effects in HCM. And as you know, we've generated data on all of those over the past year and have published on that extensively.

The data from the Boston group that will be presented tomorrow at the HCM meeting, I think, continues that narrative. And in a particular murine model, this group has a lot of experience and a long track record. And the effects that they've seen with SOTA in that model, and I don't want to presage their presentation, but I think are quite dramatic. And I'll just sort of provide the overview is that it's affecting the energetics and there are some mechanistic data around the energetics effects of SOTA in that model. And by affecting and improving cardiac energetics, you're improving fibrosis and other cardiac remodeling, but most importantly, ultimately, diastolic function.

And as you know, the major physiologic issue in HCM is diastolic stiffness. So there's really 2 main issues physiologically in human hypertrophic cardiomyopathy. In obstructive, there is a physical barrier to outflow tract obstruction, and that really is what distinguishes between obstructive and non-obstructive HCM. But fundamentally, the issue that is common, whether it's obstructive or non-obstructive is cardiac hyperdynamic function that the actin and myosin are overly active, and there's also an issue around altered energetics.

And we believe that sotagliflozin is acting on both of those fundamental physiologic characteristics. And that's why we believe and we had strong support from the medical community and the FDA that we could study both obstructive and non-obstructive in the same trial because the underlying pathophysiology is the same regardless of whether they are obstructive or non-obstructive, which is really defined anatomically as opposed to physiologically.

Great. That was definitely helpful. And then we just had one more. Once pilavapadin's end of Phase II meeting is complete, and I know you touched on this a little bit earlier, but how soon do you envision a partnership materializing? And then what are your thoughts on the type of deal that you could explore you would be interested in?

Yes. I think we will continue those engagements after the end of Phase II meeting and certainly into the start of 2026. I think the type of partnership that we're -- and the type of partners that we're engaging with are really pretty diverse. And I think that gives us optionality as to how we take our involvement with pilavapadin forward. And so we'll continue to engage with them. We'll wait for the minutes, obviously, to have that formalized, which will be in early 2026, and then we'll take it from there.

I am showing no more further questions. We will now turn it over to Mike Exton, Chief Executive Officer of Lexicon for closing remarks.

Well, thanks very much, everyone. Thanks for the great questions. I really enjoyed those and look forward to discussing in more detail with you soon. I think -- and I hope that what you've seen is that this year, Lexicon has really put our nose to the grindstone and focused on reshaping the company and advancing our pipeline forward. We have a number of great things happening in the next couple of months really as we close out the end of the year and into 2026. So look forward to sharing more information on all of those at future updates. So thanks very much, and have a great day.

Thank you for your participation in today's conference. This does conclude the program. You may now disconnect.