Q4 2025 Lexicon Pharmaceuticals Inc Earnings Call

March 5, 2026

Operator: Welcome to the Lexicon Pharmaceuticals Q4 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, 5 March 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.

Speaker #2: 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 .

Speaker #2: 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 .

Lisa DeFrancesco: Thank you, Michelle. Good morning. 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 Q4 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, then use the remainder of our time to answer your questions.

Speaker #2: Please go ahead . Lisa

Speaker #3: Thank you Michel . Good morning and welcome to our Q4 and full year 2025 earnings conference call . Joining me today are doctor Mike Exton , Lexicon's Chief Executive Officer and Director , Doctor Craig Granowitz Senior Vice President and chief medical officer .

Speaker #3: 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 and through our SEC filings.

Speaker #3: 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 this 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 pill , WL 95 one and our other drug programs , as well as our business generally .

Lisa DeFrancesco: 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, 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.

Speaker #3: 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 Mpupha for heart failure .

Speaker #3: 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 materially from those expressed or in such forward looking statements , and we refer most recent annual report on Form 10-K and other SEC filings for detailed information describing such risks .

Lisa DeFrancesco: Various risks may cause our actual results to differ materially from those expressed or implied in such forward-looking statements. 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.

Speaker #3: I would now like to turn the call over to Mike . Mike .

Mike Exton: Thanks, Lisa. Good day, everyone. Thanks for joining us today. 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. 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 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 US and Europe.

Speaker #4: Yeah , thanks , Lisa . Good day everyone . Thanks for joining us So I reflect back on this year , my first full year as CEO at lexicon .

Speaker #4: 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 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 .

Speaker #4: 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 Sotagliflozin , which is currently in late stage development in hypertrophic cardiomyopathy .

Speaker #4: Also, planning an NDA submission for sotagliflozin in type 1 diabetes, and collaborating with our licensee Viatris on making sotagliflozin available to patients outside the US and Europe.

Mike Exton: 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 3-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. 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. Looking ahead, we've set clear goals for what we need to achieve in 2026.

Speaker #4: We also have our novel oral early stage program in obesity 9851 , which is being advanced by Novo Nordisk within chronic pain , we have a phase three ready drug candidate for diabetic peripheral neuropathic pain Each of these programs have key potential catalysts .

Speaker #4: Upcoming, which we will cover shortly. Any one of these programs alone would represent a significant opportunity in scientific achievement—to be excited about.

Speaker #4: 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 .

Speaker #4: So looking ahead , we've set clear goals for what we need to achieve in 2026 . The Sonata HCM phase three trial of soda for obstructive and Nonobstructive HCM is enrolling well , and we expect to complete enrollment in the middle of this year .

Mike Exton: The SONATA-HCM phase 3 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 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 3 development of pilavapadin. Last but not least, we're financially well-positioned following our recent capital raise.

Speaker #4: We received feedback from the FDA that data from the third party, Stenner. One study can support an NDA resubmission for zinc Vista for glycemic control in type 1 diabetes.

Speaker #4: 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 existing licensees Novo Nordisk and Viatris .

Speaker #4: While also exploring new partnerships where to augment our capabilities , including seeking a partner for phase three development of Pitavastatin And last but not least , we're financially well positioned following our recent capital raise .

Mike Exton: 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, that has really continued in the first few months of the year. In January and February alone, we announced a successful end of phase 2 meeting with pilavapadin in DPNP, with no objections raised by the FDA to advancement into phase 3 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.

Speaker #4: 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 .

Speaker #4: Strategy and action . Now we entered 2026 with significant momentum and that is 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 Pitavastatin in Dpnp with no objections raised by the FDA to advancement into phase three development .

Speaker #4: 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 .

Mike Exton: We continued enrollment in the ongoing SONATA-HCM phase 3 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 re-requirements identified by the FDA are achieved. 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?

Speaker #4: We continued enrollment in the ongoing Sonata HCM phase three study of Sotagliflozin for HCM , surpassing 50% enrollment completion earlier this quarter , and progressed our work towards a potential resubmission of our NDA for zinc in type one diabetes later this year .

Speaker #4: If the steno one patient exposure and safety data requirements identified by the FDA are achieved So , as you can see , we're very much off and running .

Speaker #4: And so much more to come. With that, I'll ask Craig to provide a deeper dive into our lead programs. Craig.

Craig Granowitz: Thank you, Mike. Good morning, everyone. As most of you know, our pipeline is focused in two primary therapy areas. The first being cardiometabolic disease. The second being chronic pain. I'll start with our cardiometabolic platform. 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.

Speaker #5: Thank you , Mike , and good morning , everyone . As most of you know , our pipeline is focused in two primary therapy areas .

Speaker #5: 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 T1 It is an opportune time to review Sotagliflozin unique mechanism of action .

Speaker #5: As the only dual inhibitor of both Sglt1 and Sglt2 . We want 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 .

Speaker #5: We believe that inhibition of SGLT1 in the GI tract is important in postprandial glycemic control in patients with T1. Similarly, we believe that inhibition of SGLT1 in the heart has important effects on myocardial health, particularly in disease states like HCM.

Craig Granowitz: 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 in endothelium may be an important in reduction of ischemic events like stroke NMI. 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.

Speaker #5: It is also thought that inhibition of SGLT1 in endothelium may be important in reducing ischemic events like stroke and MI. The graphic on the next slide demonstrates the distribution of SGLT1 and SGLT2 protein expression in human tissues.

Speaker #5: 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 .

Speaker #5: 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.

Speaker #5: 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.

Craig Granowitz: 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 non-obstructive HCM. Our SONATA-HCM Phase 3 study includes patients from both populations, and top-line results are expected in Q1 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.

Speaker #5: Regarding HCM, interest and awareness of the disease have 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.

Speaker #5: Our Sonata HCM phase three study includes patients from both populations and top line results are expected in the first quarter of 2027 . In type one diabetes , lexicon has been committed to the development of a novel treatment for glycemic control in patients for t 1d for many years .

Speaker #5: The FDA has provided feedback that clinical trial data from Steno one , a third party funded investigator , initiated study of Sotagliflozin , may support a resubmission of our NDA for T1 .

Craig Granowitz: 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 3 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 non-obstructive HCM. The study is pragmatic in design, allowing for patients currently being treated on a CMI.

Speaker #5: Based on the study data , we've seen to date . We're preparing to resubmit the NDA and potentially receive regulatory approval in 2026 .

Speaker #5: Elaborating further on the opportunity for HCM , our phase three 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 .

Speaker #5: 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 non-obstructive HCM.

Speaker #5: 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 are on track to complete enrollment by mid-year .

Craig Granowitz: 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 sotagliflozin could offer distinct advantages for the treatment of obstructive and non-obstructive 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.

Speaker #5: 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.

Speaker #5: It acts directly on the myocardium to modify cellular energetic 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 .

Craig Granowitz: 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 non-obstructive HCM. Data from SOTA-P-CARDIA showed improvements in patient symptoms such as KCCQ score, and six-minute walk test, as well as cardiac function, such as left ventricular mass, and left atrial filling pressure, findings which support the rationale for sotagliflozin's use in non-obstructive HCM.

Speaker #5: 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 Sota Picardia and the Sota Cross studies Sota Picardia .

Speaker #5: Data from which was presented at the American Heart Association meeting last November evaluated the effects of sotagliflozin in patients with HF-PEF without diabetes, with a baseline ejection fraction greater than 50%.

Speaker #5: Clinically , these patients have a number of symptomatic and anatomical characteristics similar to those with non-obstructive HCM Data from Sota Cardia showed improvements in patient symptoms such as .

Speaker #5: Kccq scores and six minute walk test , as well as cardiac function such as left ventricular mass and left atrial filling pressure . Findings , which support the rationale for sotagliflozin use in non obstructive HCM .

Craig Granowitz: SOTA-CROSS is a crossover study evaluating sotagliflozin in symptomatic non-obstructive 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 and the HCM Society in an upcoming presentation at the American College of Cardiology 75th Annual Scientific Sessions that highlight 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 two 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.

Speaker #5: Soda 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 as unique potential for reducing cardiovascular events This slide highlights recent data presented at the Scientific Sessions and HCM society , and an upcoming presentation at the American College of Cardiology 75th Annual Scientific Sessions that highlight Sotagliflozin impact on cardiac remodeling in HCM .

Speaker #5: The benefits of sotagliflozin in HFpEF and sotagliflozin effects on MACE events in patients with type 2 diabetes. In summary, we are excited to complete enrollment in HCM and look forward to upcoming data presentations at HC, at ACC, and several HCM-related medical meetings in the second half of this year. Now, turning to our sotagliflozin program in type 1 diabetes.

Craig Granowitz: Turning to Zynquista, our sotagliflozin program in Type 1 Diabetes. 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 US, 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.

Speaker #5: As we previously announced , we had a we had productive meetings with the FDA in late 2025 , during which they confirmed that Steno one , 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 zinc in 20 , based on current Steno one enrollment estimates and safety data , we've received to date , we're planning for an NDA resubmission and potential regulatory approval in 2026 .

Speaker #5: There are approximately 1 million patients with type one 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 .

Speaker #5: Alongside insulin . That is an unacceptable status quo . The outpouring of support for zinc from the diabetes community has been remarkable , and reinforces what we've always known .

Craig Granowitz: 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.

Speaker #5: These patients desperately need new treatment options . If approved , would be the first and only oral therapy in its class for type one diabetes .

Speaker #5: 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.

Speaker #5: Global development of WL 951 and 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 the with potential for another $20 million in additional milestones in 2026 .

Speaker #5: 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 .

Craig Granowitz: Just this week, the Journal of the 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 3-ready non-opioid asset for neuropathic pain, pilavapadin. pilavapadin is a novel investigative agent targeting AAK1, and like sotagliflozin, pilavapadin has a broad pipeline in a pill potential. Our lead indication for pilavapadin is DPNP, supported by two Phase 2 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.

Speaker #5: These preclinical data provide some insights as to the potential of Acsl5 as a target and LL-951 as a drug candidate for obesity and chronic weight management.

Speaker #5: In addition to our cardiometabolic programs , lexicon also has a phase three ready non-opioid asset for neuropathic pain . Palovarotene . Pitavastatin is a novel investigative agent targeting aak1 and like Sotagliflozin , has a broad pipeline and a pill potential Our lead indication for Pitavastatin is Dpnp supported by two phase two studies that provide evidence of consistent and clinically meaningful pain reduction .

Speaker #5: have accumulated data from more than 600 patients treated with pill , and have demonstrated a well understood and acceptable safety and tolerability profile beyond Dpnp .

Craig Granowitz: 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 two meeting with the FDA for pilavapadin in DPNP. During that meeting, FDA raised no objections to the advancement of pilavapadin 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 score from baseline to week 12.

Speaker #5: We believe there are other potential applications for pill of in 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 .

Speaker #5: As Mike mentioned, we had a successful end-of-Phase Two meeting with the FDA for pill in Dpnp. During that meeting, the FDA raised no objections to the advancement of pill into Phase Three in that indication.

Speaker #5: The phase three program would include two placebo controlled 12 week , two arm registrational studies comparing the ten milligrams daily dose to placebo .

Speaker #5: The primary endpoint of the phase three studies would be the placebo controlled change in average daily pain score from baseline to week 12 .

Craig Granowitz: The FDA also confirmed that it will not require any additional preclinical or pre-clinical studies that would be expected to complicate or delay the advancement of this program into phase 3 development and the 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.

Speaker #5: 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 into phase development and potential regulatory submission With this regulatory alignment in hand , we are continuing our ongoing discussions with potential partners for pill of evidence I will now turn it over to Scott to provide an update on the company's financials .

Scott Coiante: Thank you, Craig. We begin this morning with our results for both the Q4 and full year of 2025. Total revenues were $5.5 million and $49.8 million for the quarter and year ended 31 December 2025, respectively. Revenues for the Q4 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 31 December 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 Q4 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.

Speaker #5: Thank you . Craig We begin this morning with our results for both fourth quarter and full year 2025 . Total revenues were 5.5 million and 49.8 million .

Speaker #6: For the quarter and year ended December 31st , 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 MPA of 1.1 million .

Speaker #6: 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 MPA.

Speaker #6: Total revenues for the fourth quarter and full year 2024 include the upfront payment of $25 million received upon entering into the license agreement, and net sales of MPA 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.

Scott Coiante: Research and development expenses for Q4 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 Q4 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.

Speaker #6: 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.

Speaker #6: Phase two clinical trial , partially offset by increased investment in our phase three clinical trial . Selling , general and administrative expenses for the fourth quarter of 2025 decreased to 8.8 million from 32.3 million in 2024 .

Speaker #6: Full year 2025 G&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 are significantly reduced marketing and promotional efforts for MPA in 2025 .

Scott Coiante: 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 Q4 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 Q4s of 2025 and 2024, net loss included non-cash stock-based compensation expense of $2.8 million and $1.5 million, respectively.

Speaker #6: 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 .

Speaker #6: 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 .

Speaker #6: For the fourth quarter 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 .

Scott Coiante: 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 31 December 2025, Lexicon had $125.2 million in cash investments and restricted cash as compared to $238 million in cash and investments as of 31 December 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 Q4 and full year of 2025.

Speaker #6: 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 .

Speaker #6: 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.

Speaker #6: 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 fourth quarter of 2025 as compared to the fourth quarter of 2020 .

Scott Coiante: In addition to the revenue highlights, which I mentioned previously, operating expenses were reduced by $39 million for Q4 2025 as compared to Q4 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 a hundred and twenty-nine and a half million for 2025 as compared to 2024, 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.

Speaker #6: For 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 M-Pesa in 2025 .

Speaker #6: 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 .

Scott Coiante: R&D expenses are expected to be between $63 and $68 million and do not include costs associated with phase 3 pivotal studies of pilavapadin as our goal would be to move this asset forward with a development partner.

Speaker #6: R&D expenses are expected to be between 63 and 68 million , and do not include costs associated with phase three . Pivotal studies of .

Speaker #6: As our goal would be to move this asset forward with a development partner , G&A expenses , which include sales and marketing expenses , are expected to range between 37 and 42 million .

Craig Granowitz: 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.

Mike Exton: 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've 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.

Speaker #6: I will now turn it back to Mike for closing remarks

Speaker #4: Yeah . Thanks , Scott . Now , before we turn to Q&A , I just say again how excited we are about the year ahead in 2026 .

Speaker #4: 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.

Speaker #4: With multiple upcoming catalysts that we believe can drive substantial value creation from partnership opportunities and neuropathic pain to sotagliflozin multiple shots on goal across HCM , heart failure and type one diabetes to 951 near-term milestone potential in obesity .

Speaker #4: 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 .

Mike Exton: We have the pipeline, we have the team, and we have the momentum, and I'm incredibly excited about what lies ahead. Thanks, I'll hand it over to the operator, Craig, Scott, and I will take your questions.

Speaker #4: We have the pipeline . We have the team , and we have the momentum . And I'm incredibly excited about what lies ahead So thanks .

Speaker #4: And I'll hand it over to the operator. Craig Scott and I will take your questions.

Operator: Thank you. To ask a question at this time, please press star one one on your telephone and wait for your name to be announced. To withdraw your question, please press star one one again. We ask that you please limit yourselves to one question and 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.

Speaker #2: Thank you To ask a question at this time , please press star one one on your telephone and wait for your name to be announced .

Speaker #2: To withdraw your question , please press star one one again . We ask that you please limit yourself to one question and one follow up before re-entering the queue .

Speaker #2: One moment for our first question Our first question will come from the line Andrew Tye with Jefferies . Your line is open . Please go ahead

[Analyst] (Jefferies): Hey, good morning. This is Matt dialing in for Andrew Tai. Congrats on the progress this quarter. Just a couple of questions from 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? What are the exact timelines from submission to approval that you're expecting? Is this gonna be a Class 1 or Class 2 resubmission here?

Speaker #7: Hey . Good morning . This is Matt Dowling in for Andrew Tsai Congrats on the progress this quarter . Just a couple of questions for me .

Speaker #7: How much patient worth of data does open label extension one study have on DKA safety right now for you to be able to guide to a potential approval in 2026 ?

Speaker #7: And then what are the exact timelines from submission to approval that you're expecting ? Is this going to be a class one or class two resubmission here ?

Mike Exton: Yeah. Thanks, Matt. I'll let Craig talk about the data. We're expecting a six-month review here. Re-emphasizing 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 wanna talk about the data that we're seeing?

Speaker #4: Yeah . Thanks , Matt . I'll let Craig talk about the data . So we're expecting a six month review here . So Re-emphasizing that the data that we're seeing , we expect a submission this year .

Speaker #4: And as well . An approval before the end of 2026 . Craig , do you want to talk about the data

Craig Granowitz: Yeah. Again, Matt, I need to be a bit careful 'cause this isn't our trial. It's investigator-initiated study. As a reminder, this is a large trial that's 2,000 patients total. 1,000 patients were drawn or 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 Corindia, depending upon baseline patient demographics. The study has enrolled the majority of the patients, and again, I don't wanna overstep Dr. Rossing and the Steno group, but enrollment has proceeded briskly. I think you can see some of their updates on ClinicalTrials.gov and the enrollment as we laid out with FDA is proceeding to plan.

Speaker #5: Yeah . So again Matt , I need to be a bit careful because this is an R trial . It's a investigator initiated study .

Speaker #5: But as a reminder , this is a large trial . It's 2000 patients total 1000 patients with Tirana the standard of care . And then another 1000 , 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 baseline patient demographics .

Speaker #5: The study has enrolled the majority of the patients , and again , I don't want to overstep Doctor Rossing and the steno group , but enrollment has proceeded briskly .

Speaker #5: I think you can see some of their updates on ClinicalTrials.gov and the enrollment. As we laid out with FDA, it is proceeding to plan.

Craig Granowitz: 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 mg 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 and a half cases per 100 patient years.

Speaker #5: We pre-agreed with the FDA on two important criteria for resubmission. The first would be the total exposure required. The second would be a rate of DKA.

Speaker #5: That 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 .

Craig Granowitz: 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.

Speaker #5: I'm sorry , three and a half cases per 100 patient years . I can tell you that currently we are tracking in a 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

Operator: Thank you. One moment for our next question. Our next question comes from the line of Ygal Nochomovitz with Citigroup. Your line is open. Please go ahead.

Speaker #2: Thank you. And one moment for our next question. Our next question comes from the line of Yigael Chamovitz with Citigroup. Your line is open.

Ygal Nochomovitz: Okay. Thank you. I've got a question on the partnerships for the pain program. You had the end of Phase 2 meeting. Could you just talk about how much that the results from that meeting have accelerated the partnering discussions since then? Is there a clearer line of sight to transacting something this year? Thank you.

Speaker #2: Please go ahead

Speaker #8: Okay . Thank you . I've got a question on on the the partnerships for the pain program . So you had the end of phase two meeting .

Speaker #8: 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 a to transacting something this year ?

Mike Exton: Yeah. Thanks, Ygal. I wouldn't say that they accelerated because we're in constant dialogue with a number of partners that we have been communicating with. It allowed the conversations to be a little more specific and obviously provide some confidence around the program being able to move into phase 3 and take away that sort of regulatory risk, if you like, which has been incredibly well received by partners. We continue to sort of talk details with them and look forward to providing some more updates in the very near future.

Speaker #8: Thank you

Speaker #4: Yeah . Thanks guys . 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 .

Speaker #4: But it 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 , take away that sort of regulatory risk .

Speaker #4: If you like , which has been incredibly well received by by partners . So we we continue to sort of talk details with them and look forward to providing some some more updates in the very near future

Ygal Nochomovitz: Okay. Also, how much more can you say about what Novo plans to do with LX9851, you know, in terms of how it's gonna 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?

Speaker #8: Okay . And also how much more can you say about what what Novo plans to do with 9851 ? You know , in terms of how it's going to be inserted into the into the development program , meaning in combo with the GLP one or for those perhaps not responding well enough or perhaps even as a , as a maintenance therapy , you know , following a course of GLP one therapy .

Mike Exton: 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. Certainly with some of the background for their enthusiasm. Before I do that, Igor, let me just reinforce how impressed we've been with the Novo team. I think, you know, 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.

Speaker #8: What can you say there ? Or is that really , you know , Novo's call now

Speaker #4: Yeah . I don't necessarily want to speak on Novo , but I think I've sort of hypothesized where I think that 9851 would fit into the treatment paradigm and , and certainly with some of the background for their enthusiasm .

Speaker #4: But before I do that , let me just reinforce how impressed we've been with the Novo team . And I think , you know , 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 .

Mike Exton: 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.

Speaker #4: And really , we've had that hypothesis all along that the future of 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 , etc.

Speaker #4: , because it allows you to get synergies by combining different Moas and orals . Obviously facilitate that ability to to . Drive combinations .

Speaker #4: 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, or whether it becomes a maintenance therapy.

Mike Exton: 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 I development. 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?

Speaker #4: I think all of those options are on the table for them . And and they're really driving very , very hard Which gives us confidence .

Speaker #4: 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.

Speaker #4: 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 Granowitz: 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 the 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 ileal brake, 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.

Speaker #4: Craig , do you have any additional thoughts or .

Speaker #5: I'll just add from the scientific standpoint , the mechanism is complementary to semaglutide . You know , as we've communicated , I think as nicely summarized in the Journal of Endocrine Society paper , that just came out this week .

Speaker #5: As we mentioned during the prepared remarks , this mechanism is thought to be the really the only agent that is in development acting on what's called the ileal brake , which is a very different neuro endocrine signal of satiety that we've seen .

Speaker #5: 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 .

Craig Granowitz: 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. Again, we don't wanna speak for Novo, our partner.

Speaker #5: 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 a in an additional combination with both Amylin analog and Semaglutide analog .

Ygal Nochomovitz: Okay, thank you.

Speaker #5: But again, we don't want to speak for Novo. Our partner—

Operator: Thank you. One moment for our next question. Our next question is going to come from the line of Joe Pantginis with H.C. Wainwright. Your line is open. Please go ahead.

Speaker #8: Okay . Thank you .

Speaker #2: Thank you . And one moment for our next question Our next question is going to come from the line of Joe Pangonis with H.C.

Joseph Pantginis: Hey, guys. Good morning. Thanks for taking the question. Mike, I know the intent for pilavapadin is, you know, moving forward with an expected partner, but I wanna ask the question this way. Based on your, you know, 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 this study on your own prior to getting a partner?

Speaker #2: Wainwright . Your line is open . Please go ahead

Speaker #9: Hey , guys . Good morning . Thanks for taking the question . So , Mike , I know the intent for Pill of Apatin is , you know , moving forward with an expected partner .

Speaker #9: But I want to ask the question this way . So based on your , you know , 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 ?

Mike Exton: 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. You know, we're really very much focused on our near-term cardiometabolic opportunities. I think what we see in the opportunity with T1D for sotagliflozin as well as HCM are both incredibly large commercial opportunities for us. We're very much focused on driving that forward. We have been continuing to do some work in preparation of what the phase 3 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 timeframe of what would be expected moving forward. Even that is changing as we speak.

Speaker #4: Yeah , it's a it's a great question , Joe . And it's a it's a it's a great position to be in when you've got a number of opportunities ahead of you .

Speaker #4: And you know , where really very much focused on our near-term cardiometabolic opportunities . I think what we see in the opportunity with T1 for soda , as well as HCM , are both incredibly large commercial opportunities for us .

Speaker #4: And so we're very much focused on driving that forward, have been continuing to do some work in preparation of what the phase three program would look like for Pill of Aberdeen 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.

Mike Exton: As you know, the recent announcement by Dr. Makary for one trial possibility is something that is coming into our thought process as well. We need to consider that as a possibility for pilavapadin as we will be for all programs. We are doing work in parallel, but we're not going to invest the financial commitment to commencing a phase three 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?

Speaker #4: And even that is changing as we speak . As you know , the the recent announcement by doctor McCree , for one trial possibility is something that is coming into our thought process as well .

Speaker #4: And we need to consider that as a possibility for pill gabapentin 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 of the phase three trial for pill of an , because we really want to invest that cash for both T1 and HCM at the moment .

Craig Granowitz: 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. 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 DPNP, are at much higher risk of actually developing opiate addiction. 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.

Speaker #4: Do you have anything else?

Speaker #5: Yeah I think Mike you summarized the strategic part really well . I just wanted to reinforce the importance of the patient groups and the legislative dimension as well .

Speaker #5: 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 as , you know , Joe , a lot has been done in the acute pain setting , particularly in light of the opiate situation .

Speaker #5: Patients who are on chronic pain treatment , like Dpnp , 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 .

Craig Granowitz: We're really trying to approach this from multiple different ways, a regulatory, legislative, patient access standpoint, as well as Mike said, we've really now finalized what the development program would be under standard conditions based on the end of phase 2 meeting. We continue to really look at all of these areas, as the discussions continue because we don't wanna just have the asset sitting there.

Speaker #5: 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 .

Speaker #5: 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 .

Mike Exton: Yeah. No, exactly. 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. 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.

Speaker #4: Yeah . No , exactly . So I think Craig summarized that well , there's there's a bunch of activity that we're doing to continue the preparation for the program , in part in parallel with the discussions .

Speaker #4: But our investment of capital is squarely focused at this time on zinc and HCM , because we see those opportunities coming at us very , very fast .

Joseph Pantginis: That's very helpful. Thank you. Maybe 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?

Speaker #9: That's very helpful . Thank you . And maybe 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 .

Speaker #9: Could potentially impact future sodas and or the marketing potential . As you look at the broadening profile for soda and HCM .

Craig Granowitz: 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. 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. 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.

Speaker #5: 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.

Speaker #5: 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 .

Speaker #5: But not add dramatically to the cost or slow enrollment . And in that regard , we're really looking at soda , cross soda , Cardia and a number of other trials that we've been discussing .

Speaker #5: 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 .

Craig Granowitz: 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 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.

Speaker #5: But also to differentiate the dual mechanism of soda in the sglt1 effects from the Sglt2 inhibitors , which are not being studied and have no data in HCM .

Mike Exton: Yeah, no. 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. As we noted, we did raise, you know, close to $100 million earlier this year. We're spending a small portion of that this year at the moment, as Scott gave in his guidance for the year.

Speaker #4: Yeah . No . And just allow me to throw a little more color onto that Joe . Because it's a it's a very important element of our portfolio .

Speaker #4: And we think it's a great opportunity not only for soda and patients with HCM , but for lexicon . So as we noted , we did raise you know , close to $100 million .

Speaker #4: Earlier this year and we're spending a small portion of that this year at the moment as as sorry Scott gave in guidance for the year .

Mike Exton: 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, you know, 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 SOTA-CROSS and SOTA-P-CARDIA, which are very important elements, but a lot of the mechanistic evidence, one of which we presented today.

Speaker #4: 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 what is a ton of evidence .

Speaker #4: Now showing the reason to believe of Sglt1 as being a new class of medicine and being and having , you know , a lot of evidence that indicates it will be a very significant medicine for both obstructive and non-obstructive HCM .

Speaker #4: 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 soda cross and soda picardia , which are very important elements , but a lot of the mechanistic evidence , one of which we presented today .

Mike Exton: I think as we sort of educate the physician community beyond top KOLs, they'll really see why Sota has significant potential in HCM. It's really an important focus for the company over the next 12 months.

Speaker #4: And I think as we sort of educate the physician community beyond top , they will really see why soda has significant potential in HCM .

Speaker #4: So it's it's really an important focus for the company over the next 12 months .

Joseph Pantginis: Thank you, guys.

Operator: Thank you. 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.

Speaker #9: Thank you guys .

Speaker #2: 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 .

Operator: Hi, this is Shannon on for Yas Rahimi. 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? Also, is the cadence of that enrollment, is that the same in both cohorts for NHCM and OHCM?

[Analyst] (Piper Sandler): Hi, this is Shannon on for Yas Rahimi. 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? Also, is the cadence of that enrollment, is that the same in both cohorts for NHCM and OHCM?

Speaker #2: Please go ahead .

Speaker #10: Hi . This is Shannon on for Yazami . Congrats on the progress and thanks for taking my 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 the cadence of that enrollment ?

Speaker #10: Is that the same in both cohorts for HCM and OCM

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

Craig Granowitz: Yeah, 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+ countries, and we're at that, what I would call, steep part of the S-shaped 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. Enrollment has really ticked up consistent or ahead of our projections at this point. 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 US, Europe, and Latin America are all contributing.

Speaker #4: Yeah , great . Great question . So I'll let Craig have first go with that one .

Speaker #5: Yeah, Shannon, it's a great question. We have a really nice window right now of enrollment, and there are not a lot of competing global trials right now.

Speaker #5: 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-shaped enrollment curve .

Speaker #5: 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 .

Speaker #5: 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 .

Craig Granowitz: 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. We're seeing even more patient inflow for the non-obstructive cohort than the obstructive cohort. We believe that we have enough patients in both cohorts to achieve what we set out in the trial. As we mentioned, the trial is stratified but not capped. 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.

Speaker #5: The US , 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 .

Speaker #5: 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 .

Speaker #5: So we're seeing even more patient inflow 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 .

Speaker #5: 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 .

Speaker #5: But we have not set a formal cap of a specific number of each group . And that we did discuss in line with FDA before we started the trial .

Mike Exton: Yeah. Shannon, it's a great point is, as all those people know who run clinical trials, enrollment is never linear in any clinical trial. 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 then a data readout in Q1 of 2027.

Speaker #4: And . Then it's a it's a great point , is , is all all those people know who've run clinical trials , enrollment is never linear in any clinical trial .

Speaker #4: And , you know , we have our target curve and our enrollment curve is 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 then a data readout in Q1 of 27 .

[Analyst] (Leerink Partners): Great. Thank you so much.

[Analyst] (Piper Sandler): Great. Thank you so much.

Operator: Thank you, one moment for our next question. Our next question comes from the line of Roanna Ruiz with Leerink Partners. Your line is open. Go ahead.

Speaker #10: Great. Thank you so much.

Speaker #2: Thank you. And one moment for our next question. Our next question comes from the line of Rhona Ruiz with Leerink Partners. Your line is open.

[Analyst] (Leerink Partners): Hi, this is Michael on for Roanna Ruiz at Leerink Partners. Thank you for taking our question. I have a question about phase 3 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 3? Like for instance, will you require like minimum pain score threshold, things like that? Thank you.

Speaker #2: Go ahead .

Speaker #7: Hi .

Speaker #11: This is Michael on for Warner Ruiz at Leerink Partners . Thank you for taking our question . I have a question about phase three design of program .

Speaker #11: 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 ?

Speaker #11: But for instance , will you require like minimum pain score threshold , things like that ? Thank you .

Craig Granowitz: Yeah. Great question, Michael. Thank you for that question. I think the changes that we're gonna have, as we've mentioned, probably the single largest change we're gonna have is actually to expand enrollment. 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. 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.

Speaker #5: Yeah , great . 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 .

Speaker #5: And we believe that having a renal impairment study completed with no impact on clearance , with GFR 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 .

Speaker #5: 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 .

Craig Granowitz: 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. 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 approximately one year.

Speaker #5: I think the only change that we looked at, when 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.

Speaker #5: And again , this was all retrospective . Looking back at the completed data , was the duration of their neuropathy prior to enrollment .

Speaker #5: 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 , with 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 .

Craig Granowitz: 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. We now have a large number of study sites that have significant experience with us running these trials 'cause we've now run 2 large trials, 2 large phase 2 trials. 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.

Speaker #5: But with the sites and the patients is another element that we think that we can do to have more consistency across patient enrollment .

Speaker #5: 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 2 trials.

Speaker #5: 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

[Analyst] (Leerink Partners): Great. Thank you so much.

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

Speaker #11: Great . Thank you so much .

Mike Exton: 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 2 data for pilavapadin. We needed to find a path forward for ZYNQUISTA. We needed to accelerate the enrollment of SOTA in HCM. Fast-forward to, you know, nearly at the end of Q1 2026, we now have clarity on pilavapadin and partnership discussions are ongoing. We're on the precipice of a resubmission for ZYNQUISTA, we're nearly closing the enrollment of HCM study SONATA with a readout in 2027.

Speaker #2: Thank you . And I'm showing no further questions at this time . And I would like to hand the conference back over to Michael Exton for closing remarks .

Speaker #4: 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 .

Speaker #4: In my opinion . If you think about where we were last year , we needed to really summarize all of the phase two data for all of Aberdeen .

Speaker #4: We needed to find a path forward for zinc . We needed to accelerate the enrollment of soda in HCM and fast forward to , you know , nearly at the first quarter of 2026 .

Speaker #4: And we now have clarity on pill of Aberdeen, and partnership discussions are ongoing. We're on the precipice of a resubmission for zinc.

Mike Exton: 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. We feel very good. We're pushing very hard and look forward to giving you some more updates as the year progresses. Thanks very much everyone.

Speaker #4: And we're nearly closing the enrollment of the HCM study Sonata, with a readout in '27. So we've got an amazing set of opportunities ahead of us.

Speaker #4: 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 .

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

Speaker #4: We're pushing very hard and look forward to giving you some more updates as the year progresses . So thanks very much everyone .

Q4 2025 Lexicon Pharmaceuticals Inc Earnings Call

Request a DemoDemo

LXRX

Lexicon Pharmaceuticals

Earnings