Lexicon Pharmaceuticals, Inc.

Welcome to the Lexicon Pharmaceuticals fourth quarter and full year 2025 financial results conference call. At this time, all participants are in a listen-only mode. Following management's prepared remarks, we will hold a brief question and answer session. As a reminder, this call is being recorded today, March 5th, 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 Chianti, 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 Sotocliflozin, Pilavapidin, 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, market opportunity for our drug programs, commercial performance of IMPEFA 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?

Yeah, thanks, Lisa. Good day, everyone. Thanks for joining us today. So 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 three very strong, novel, late-stage programs in the therapeutic areas of cardiometabolic disease and chronic pain. In cardiometabolic, we have Sotocliflozin, which is currently in late-stage development in hypertrophic cardiomyopathy. Also planning an NDA submission for Sotocliflozin in type 1 diabetes and collaborating with our licensee, Beatrice, on making Sotocliflozin available in patients outside the US 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 pilavapidin, a phase three 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 three trial of SOTA for obstructive and non-obstructive 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 Stena 1 study can support an NDA resubmission for Zinclista 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, Navinordisk and Beatrice, while also exploring new partnerships where appropriate to augment our capabilities, including seeking a partner for Phase 3 development of Pillar Bafferton. 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 two meeting with Kilobapidin in DPNP with no objections raised by the FDA to advancement into phase three 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 three study of Sotoclosen for HCM, surpassing 50% enrollment completion earlier this quarter and progressed our work towards a potential resubmission of our NDA for Zynclista in type 1 diabetes later this year, if the Steno 1 patient exposure and safety data requirements identified by the FDA are achieved. So as you can see, we're very much off 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 two primary therapy areas, first being cardiometabolic disease and the second being chronic pain. I'll start with our cardiometabolic platform and Sotaglifosin. As we approach important upcoming milestones for Sotaglifosin in both HCM and T1D, it is an opportune time to review Sotaglifosin'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 pseudoglyphosin, 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 non-obstructive 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 may support a resubmission of our NDA for Zynqvistin 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 the 50% enrollment target earlier this quarter and on track to complete enrollment by mid-year. As I mentioned earlier, as a dual inhibitor of SGLT1 and SGLT2, we believe that sodaglifosin 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 non-obstructive HCM. Additionally, sotagliflozin is already approved for heart failure with 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 two investigator-initiated trials, the Sotopicardia and the Sotacross studies. Sotopicardia, data from which was presented at the American Heart Association meeting last November, evaluated the effects of sotaglifosin 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 non-obstructive HCN. Data from Sotacardia showed improvements in patient symptoms, such as KCCQ score and six-minute walk test, as well as cardiac functions, such as left ventricular mass, and left atrial filling pressure, findings which support the rationale for Sotaglifosin's use in nonobstructive HCM. Sotacross is a crossover study evaluating Sotaglifosin 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 sodaglifosin's unique potential for reducing cardiovascular events. This slide highlights recent data presented at the AHA Scientific Sessions and the HCM Society in an upcoming presentation at the American College of Cardiology's 75th Annual Scientific Sessions that highlight sodaglifosin's impact on cardiac remodeling in HCM, the benefits of sodaglifosin 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 HCC and several HCM-related medical meetings in the second half of this year. Now, turning to Zynqvista, 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 steno-1, a third-party-funded, investigator-initiated study of sodaglifosin being conducted by the Steno Diabetes Center in Denmark, appears to be sufficient to support a review of a resubmission of our NDA for Zynqvista in T1D. Based on current steno-1 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 three ready non-opioid asset for neuropathic pain, pilavapidin. Pilavapidin is a novel investigative agent targeting AAK1. And like sotaglifosin, pilavapidin has a broad pipeline in a pill potential. Our lead indication for pilavapidin is DPMP, supported by two phase two studies that provide evidence of consistent and clinically meaningful pain reduction. We have accumulated data from more than 600 patients treated with pilavapidin and have demonstrated a well-understood and acceptable safety and tolerability profile. Beyond DPMP, we believe there are other potential applications for pilavapidin, The AK1 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 2 meeting with the FDA for pilobapidin and DPNP. During that meeting, FDA raised no objections to the advancement of pilobapidin into phase three development in that indication. The phase three program would include two placebo-controlled, 12-week, two-arm registrational studies comparing the 10 daily dose of placebo. The primary endpoint of the phase three studies would be the placebo-controlled change in average daily pain support from baseline to week 12.

The FDA also confirmed that it will not require any additional pre-clinical or pre-clinical studies that would be expected to complicate or delay the advancement of this program into phase three development in the potential regulatory submission. With this regulatory alignment in hand, we are continuing our ongoing discussions with potential partners for Philadelphia. 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 MPEFA 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 MPEFA. 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 MPEFA 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 2 clinical trial, partially offset by increased investment in our Sonata Phase 3 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 MPEFA 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 14 cents per share, compared to a net loss of 200.4 million, or 63 cents per share, in the same period in 2024. For the fourth quarters of 2025 and 2024, net loss included non-cash 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 non-cash stock-based compensation expense of $12.5 million and $13.5 million, respectively. As of December 31st, 2025, Lexicon had $125.2 million in cash investments and restricted cash, as compared to $238 million in cash and investments as of December 31st, 2024. Subsequent to year end, Lexicon straightened 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 MPEFA 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 and 110 million. R&D expenses are expected to be between 63 and 68 million, and do not include costs associated with phase three pivotal studies of filibapidin, 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 and 42 million. I will now turn it back to Mike for closing remarks.

Yeah, 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 three core programs, we have multiple upcoming catalysts that we believe can drive substantial value creation. From Pilavapidin's partnership opportunities and 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 were 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.

Thank you. To ask a question at this time, please press star 11 on your telephone and wait for your name to be announced. To withdraw your question, please press star 11 again. We ask that you please limit yourselves to one question or one follow-up before reentering the queue. One moment for our first question. Our first question will come from the line of Andrew Tai with Jefferies. Your line is open. Please go ahead.

Hey, good morning. This is Matt dialing in for Andrew Tai. Congrats on the progress this quarter. Just a couple of questions for me. How much patient worth of data does Open Label IST Stenum 1 study have on TKA safety right now for you to be able to guide to a potential approval in 2026? And then what are the exact timelines from submission to approval that you're expecting. Is this going to be a Class 1 or Class 2 resubmission here?

Yeah, thanks, Matt. I'll let Craig talk about the data. So we're expecting a six-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?

Yeah, so again, Matt, I need to be a bit careful because this is an R 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 what is considered the standard of care, and then another 1,000 which are randomized based on baseline characteristics to enhanced care, which would include and a significant percentage of patients, but also the possibility of being on semaglutide and or corandia, 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 FDA is proceeding to plan. We pre-agreed with FDA on two 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 in tandem program, which in the FDA's parlance was a number needed to harm of about 26, which corresponds to a rate of about one case, I'm sorry, three and a half 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 timelines that both Mike and I highlighted during the call.

Thank you, and one moment for our next question. Our next question comes from the line of Yigal Notramovitz with Citigroup. Your line is open. Please go ahead.

Okay, thank you. I've got a question on the partnerships for the pain program. So you had the end of phase two meeting. Could you just talk about how much 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? Thank you.

Yeah, thanks, Igar. I wouldn't say that they accelerated because we're in constant dialogue with a number of partners that we've 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 three 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 NOVA plans to do with 9851, you know, 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, you know, following the course of GLP-1 therapy? What can you say there? Or is that really, you know, Novo's call now?

Yeah. 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 with some of the background for their enthusiasm. But before I do that, Igar, 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 standalone 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 two further milestones this year, which would really be an accelerated phase one development. And we're excited about the possibility of clearing that hurdle and then really getting into phase two and beyond, which would be very material for the company. Craig, do you have any additional thoughts?

I'll just add from the scientific standpoint, the mechanism is complementary to semaglutide. You know, 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 illegal 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 a semaglutide analog. But again, we don't want to speak for Novo, our partner. Okay, thank you.

Thank you, and one moment for our next question. Our next question is going to come from the line of Joe Pant-Guinness with H.C. Wingwright. Your line is open. Please go ahead.

Hey, guys. Good morning. Thanks for taking the question. So Mike, I know the intent for Pilavapidin is moving forward with an expected partner, but I want to ask the question this way. So based on 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?

Yeah. 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 soda, 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 three program would look like for pill of apidin 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. Macari 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 pilavapidin 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 three trial for pilavapidin because we really want to invest that cash for both T1D and HCM at the moment. Ray, have you got anything else?

Yeah, 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 opiate situation. Patients who are on chronic pain treatment like DPMP are at much higher risk of actually developing opiate addiction. So there's been a really strong interest across the board in the pain community, both on the opiate 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 two meeting. So we continue to really look at all of these these areas as the discussions continue because we don't want to just have the assets sitting there.

Yeah, 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 Zinclister and HCM because we see those opportunities coming at us very, very fast.

That's very helpful. Thank you. And maybe a question for Craig here. When you look at the soda 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 soda and HCM.

Yeah, thanks for the question, Joe. You know, 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 Sotacross, Sotacardia, 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 could 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.

Yeah, no. And just allow me to throw a little more color onto that, Joe, because it's a very important element of our portfolio, and we think it's a great opportunity, not only for SOTA and patients with HCM, but for Lexicon. So, as we noted, we did raise, you know, close to $100 million earlier this year, and we're spending a small portion of that this year at the moment, as 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 having a lot of evidence that indicates it will be a very significant medicine for both obstructive and non-obstructive HCM. 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 SodaCross and SodaP Cardio, 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'll really see why soda has significant potential in HCM. So it's really an important focus for the company over the next 12 months.

Thank you, guys.

Thank you. And one moment for our next question. Our next question comes from the line of Yasmeen Rahimi with Piper Sandler. Your line is open. Please go ahead.

Hi, this is Shannon on . Congrats on the progress and thanks for taking our question. 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 a cadence of that enrollment? Is that the same in both cohorts for NHCM and OHCM?

Yeah, great, great question. So, I'll let Craig have first go at that one.

Yeah, Shannon, it's a great question. We have 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 prepare 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. 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 non-obstructive 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 non-obstructive 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 non-obstructive, 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.

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, you know, 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 mid-year target. which will have been a data readout in Q1 of 27.

Great. Thank you so much. Thank you. And one moment for our next question. Our next question comes from the line of Rowana Ruiz with Learing Partners. Your line is open. Go ahead.

Hi. This is Michael. I'm for Rowana Ruiz at Learing Partners. Thank you for taking our question. I have a question about phase three design of a pilavapidin 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 three? Like for instance, will you require like minimum pain score threshold, things like that? Thank you.

Yeah, 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 two study was six months but to extend that to to approximately one year the other major elements that in talking to our advisors 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 two large trials, two large phase two 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 DPMP studies.

Great. Thank you so much.

Thank you, 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.

Yeah, 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 pilavapidin. We needed to find a path forward for Zinquista. We needed to accelerate the enrollment of soda in HCM. And fast forward to, you know, nearly at the end of the first quarter of 2026, and we now have clarity on Filavapidin and partnership. Discussions are ongoing. We're on the precipice of a resubmission for Zinquista. and we're nearly closing the enrolment 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.