Lexicon Pharmaceuticals Q3 2026 Earnings Call Transcript
Lexicon Pharmaceuticals (NASDAQ:LXRX) reported third-quarter financial results on Thursday. The transcript from the company’s third-quarter earnings call has been provided below.
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Summary
Lexicon Pharmaceuticals reported total revenues of $11.3 million for Q3 2026, a decrease from $14.2 million in Q3 2025, with milestone revenue from Novo Nordisk and net sales of INPEFA contributing to the results.
The company completed patient enrollment for the phase 3 SONATA-HCM study on sotagliflozin, with top-line results expected in Q1 2027, and is preparing for the resubmission of the Zynquista NDA in type 1 diabetes, also expected in Q1 2027.
Lexicon continues to expand its global regulatory footprint for sotagliflozin with its licensee Beatrice, securing approvals in the UAE and Bahrain, and submitting applications in additional countries.
The LX9851 obesity treatment program, led by Novo Nordisk, is advancing with milestone payments received, and Lexicon is exploring pilavapetin for obesity, showing promising preclinical results.
Lexicon has strengthened its leadership team by appointing a new Chief Commercial Officer and adding expertise in marketing and market access to support pre-commercial planning.
The company maintains operating expense guidance for 2026 between $100 and $110 million, with a strong cash position of $183.2 million as of September 30, 2026.
Management expressed optimism about the potential of their cardiometabolic portfolio, particularly sotagliflozin, and its ability to address unmet needs in HCM and type 1 diabetes.
Full Transcript
OPERATOR
At this time, all participants are in 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, November 5, 2026. I will now turn the call over to Lisa DeFrancesco, Vice President, Investor Relations and Corporate Communications for Lexicon Pharmaceuticals. Please go ahead, Lisa.
Lisa DeFrancesco (Vice President, Investor Relations and Corporate Communications)
Thank you, operator. Good morning and welcome to our third quarter 2026 earnings call. Joining me today are Dr. Michael Exton, Lexicon’s Chief Executive Officer and Director; Dr. Craig Granowitz, Senior Vice President and Chief Medical Officer; and Scott M. Coiante, Senior Vice President and Chief Financial Officer. This morning, Lexicon issued a press release announcing our financial results for the third quarter of 2026, which is available on our website at www.lexpharma.com and through our SEC filings. A webcast of this call along with 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 use the remainder of the time to answer your questions.
Before we begin, let me remind you that we will be making forward-looking statements, including statements relating to the safety, efficacy, clinical development, regulatory status, and therapeutic and commercial potential of sotagliflozin, pilavapetin, LX9851, and our other drug programs, as well as our business generally. This call may contain forward-looking statements relating to our growth and future operating results, discovery and development of our drug candidates, strategic alliances, and intellectual property, as well as other matters that are not historical facts or information.
Various risks may cause our actual results to differ materially from those expressed or implied in such forward-looking statements and we refer you to our most recent annual report on Form 10-K and other SEC filings for detailed information describing such risks. I would now like to turn the call over to Mike Exton. Mike.
Michael Exton (Chief Executive Officer)
Thank you, Lisa. Good day, everyone, and thanks for joining us. As we approach the end of 2026, a year of tremendous focus and strategic evolution for Lexicon, I want to highlight the significant progress we’ve made across the business. First and foremost, in HCM, we completed patient enrollment in our phase 3 SONATA-HCM study. The baseline characteristics reflect the broad spectrum of patients being treated for HCM today, which we believe positions the study to evaluate sotagliflozin across both non-obstructive HCM, where significant unmet need remains, and obstructive HCM, where many patients continue to experience symptoms despite available treatment options. Importantly, the baseline KCCQ score of 59 reflects a highly symptomatic patient population with substantial room for symptomatic improvement.
We’re very pleased with the overall enrollment profile of SONATA-HCM and look forward to reporting top-line results in the first quarter of 2027. Now moving to Zynquista, we continue to make strong progress towards the resubmission of our NDA in type 1 diabetes supported by new prospective safety data from the investigator-initiated Steno 1 study. We are extremely pleased with the Steno 1 safety data, with rates of DKA that were low and comparable to standard of care as well as the background rate among T1D patients in Denmark. It’s worth remembering why this matters. Insulin remains the only glucose-lowering therapy for people with type 1 diabetes, and even with today’s pumps and sensors only about 1 in 5 adults reaches the A1C goal of 7%.
And while much of our recent focus has understandably been on providing the additional safety data requested by the FDA, we don’t want to lose sight of the strong efficacy results demonstrated in our phase 3 inTandem program. Those results are equally important to evaluating the overall profile of Zynquista, and, taken together, we believe the inTandem efficacy results and the new Steno 1 safety data provide a compelling benefit-risk profile for Zynquista and a strong foundation for our NDA resubmission.
We are now preparing that resubmission, and because Steno 1 is an investigator-initiated study and was not designed for regulatory purposes, significant work has been required to analyze, format, and prepare the data for submission and review. What remains is bringing this academic data set up to agreed-upon regulatory submission standards. We are completing that work in parallel with ongoing discussions with FDA with the goal of submitting the highest-quality package possible and maximizing the probability of a successful review.
While this process is taking longer than we originally anticipated, we expect to complete the resubmission in the first quarter of 2027. We’ve been unwavering in our commitment to people living with type 1 diabetes and to making sotagliflozin available as a new treatment option. I’m incredibly proud of the work our team has done to get us to this point and grateful to the Steno 1 investigators for their collaboration in helping us pursue an innovative regulatory path forward.
Now, in heart failure, our licensee Beatrice continues to expand the global regulatory footprint for sotagliflozin, with regulatory submissions across a growing number of markets outside the U.S. and Europe. To date, Beatrice has obtained regulatory approvals in the United Arab Emirates and Bahrain and submitted applications in more than a dozen additional countries, including Saudi Arabia, Canada, and Australia. Turning to LX9851, our first-in-class ACSL5 inhibitor for obesity, the phase 1 study being conducted by our licensee Novo Nordisk is progressing nicely. During the third quarter, we received our third $10 million milestone payment of the year from Novo, with the potential to receive additional milestone payments as the program advances. We’re very pleased with the progress of this promising compound and excited to see Novo continue to move the program forward.
And finally, turning to pilavapetin, our conviction in the potential of this agent and its novel AAK1 inhibition mechanism continues to grow. Last quarter I mentioned that we had exciting work underway exploring its potential in additional high-value indications, and today I’m pleased to share some of that work, particularly in obesity and weight management. In preclinical studies, pilavapetin has produced significant reductions in body weight both as a monotherapy and in combination with semaglutide.
While this work remains early, we are encouraged by what we’ve seen and believe it points to an intriguing new opportunity for this program. We look forward to sharing more on this and additional preclinical programs with pilavapetin. Lastly, and importantly, we’ve remained steadfast in our commitment to operational excellence and disciplined investment as we advance our programs and prepare for the opportunities ahead. To that end, we recently appointed Rachel Martins as Chief Commercial Officer and added new leaders in marketing and market access to advance our pre-commercial planning in HCM and T1D. I’m extremely pleased with the caliber of talent that we have and continue to attract at Lexicon Pharmaceuticals, which I believe speaks to the strength of our programs and the opportunities ahead of us.
Now, before I turn the call over to Craig, I’d like to return to HCM and spend a few minutes on why we believe this represents such a compelling opportunity for Lexicon and why sotagliflozin may be uniquely positioned to address the significant unmet need across the disease. HCM is a genetic disease characterized by adverse cardiac remodeling, including myocardial hypertrophy, diastolic dysfunction, and fibrosis. Importantly, this underlying biology is the fundamental pathology across both non-obstructive and obstructive HCM, and while today much of the innovation in HCM is centered on cardiac myosin inhibitors, which target the contraction mechanism of the heart, sotagliflozin takes a fundamentally different approach through its dual SGLT1 and SGLT2 inhibition. We believe sotagliflozin may influence the metabolic and other biological processes that contribute to diastolic dysfunction in HCM.
That distinction is important because the underlying abnormalities in cardiac structure, function, and metabolism extend across both forms of HCM, and we believe this gives sotagliflozin the potential to deliver meaningful benefits in both obstructive and non-obstructive disease, something SONATA-HCM is specifically designed to evaluate. Now, the HCM market is a large and rapidly growing opportunity for a novel agent like sotagliflozin. Awareness and treatment of HCM is accelerating in the U.S. and around the world, but patients continue to experience significant symptom burden that impacts their life. Today in the U.S., more than 800,000 patients have been diagnosed with either obstructive or non-obstructive disease, but there are many more remaining undiagnosed. Currently in nHCM in particular, a treatment gap remains, with no disease-specific therapies currently approved.
Despite a patient population growing quickly with rising levels of obesity and diabetes, there’s strong support for an option that is simple, safe, and easy to use. For the busy and growing cardiology practices, we believe sotagliflozin’s once-daily oral profile, together with its differentiated mechanism and potential applicability across both obstructive and non-obstructive HCM, could provide an attractive option for physicians and patients. With that, Craig Granowitz, our Chief Medical Officer, will provide additional color on our pipeline.
Craig Granowitz (Senior Vice President and Chief Medical Officer)
Thank you, Mike, and good morning, everyone. As Mike mentioned, SONATA-HCM is the ongoing phase 3 study for patients with symptomatic HCM, the top-line results of which are expected in the first quarter of next year. SONATA-HCM was designed to evaluate sotagliflozin in a broad HCM population reflective of real-world clinical practice. With the baseline characteristics of the study now available, we are very pleased. that the final study population met that objective. Importantly, the demographic and clinical characteristics of both the non-obstructive and obstructive HCM cohorts are generally consistent with those reported in previous clinical studies of other agents in those respective patient populations. The overall study population had a mean baseline KCCQ score of 59. The primary efficacy endpoint of the pivotal study is improvement in symptoms compared to placebo as measured by the change from baseline in KCCQ at week 26.
In total, Sonata HCM enrolled 542 patients, with 440 classified as non-obstructive at baseline and 102 as obstructive. The trial also includes patients on stable background therapies, including cardiac myosin inhibitors. The scientific evidence for sotagliflozin continues to accumulate, strengthening the rationale for its effectiveness and mechanisms in HCM and providing important insights into the potential differentiation of dual SGLT1 and SGLT2 inhibition. In a preclinical murine model of HCM, sota improved baseline measures of cardiac structure and function, including diastolic function, hypertrophy, and fibrosis.
Separate research has also demonstrated sota’s inhibition of platelet activation and thrombus formation, which were greater than those observed with the SGLT2 inhibitor empagliflozin, highlighting the importance of the SGLT1 effects in impacting thrombotic events. New investigator-led research being presented at the upcoming AHA meeting this weekend includes work in living human HCM heart tissue where SGLT1 inhibition directly reduced myocardial work, with sota showing greater potency at higher afterloads compared to empagliflozin.
A separate study in healthy adults treated with EMPA or sota found a significant reduction in thrombus formation from baseline with sota, while the reduction with EMPA did not reach significance. We believe that body of evidence will continue to grow. The investigator-initiated SotaCross study being conducted at the University of Pennsylvania is evaluating sota in patients with non-obstructive HCM, including its effects on cardiac function, exercise performance, and quality of life, with completion now expected in 2027. We believe these findings provide increased scientific and clinical support for the differences between the dual SGLT1/2 inhibitor sota and SGLT2 inhibitors.
Additionally, the HCM-specific data reinforce our excitement as we approach the expected Sonata HCM top-line readout in the first quarter of 2027. Moving to Zynquista, to expand upon what Mike highlighted earlier, the inTandem program demonstrated important benefits for people with type 1 diabetes, including a reduction in HbA1c of about 0.4 percentage points, roughly three hours per day of time in range, fewer hypoglycemic events, reduced body weight, and lowered blood pressure. The FDA requested additional prospective data characterizing the risk of DKA as a precondition for resubmission of the NDA.
We have subsequently worked with the agency on a path forward using data from the Steno1 trial. The FDA agreed that Steno1 could provide the prospective data needed to assess DKA rates in a large sotagliflozin-treated population, provided the study achieved sufficient patient exposure comparable to the approximate 200 patient-years of sota treatment in the inTandem clinical program. Indeed, we have now met the criteria outlined by the FDA, including the required level of patient exposure, and have received the data from Steno needed to support our resubmission.
The inTandem efficacy results together with the new Steno safety data give us increased confidence in the overall profile of Zynquista as we prepare to resubmit our NDA. Looking at the Steno data in more detail, we are encouraged by the safety results observed in the trial. As shown on this slide, the rate of DKA amongst patients receiving sotagliflozin was approximately one DKA event per 100 patient-years of sota exposure. This was comparable both to the standard-of-care group in the Steno1 trial and the historic rates in Denmark in people with type 1 diabetes. The rate of DKA is well below that of the rates observed in the sota arms of the inTandem studies.
Importantly, as of the end of August 2026, which we are using as the cutoff date to support the FDA resubmission, the study included 496 patients randomized to sota and 708 patients receiving standard of care, which provides the level of patient exposure agreed with the FDA. As Mike mentioned, significant work is ongoing with Steno, in conjunction with alignment from the FDA on analysis parameters, to properly prepare the data for FDA submission and review.
While the administrative process is taking longer than initially projected, we remain confident in the robustness of the data set and we are encouraged by our progress towards resubmission, which we now expect will occur in the first quarter of 2027. Turning now to pilavapitin, the selective AAK1 inhibitor, we continue to explore the program’s potential beyond its established development path in neuropathic pain. We have been investigating the potential application of pilavapitin in additional indications based on its ability to affect biological pathways involved in several processes, including nerve transmission involved in gastrointestinal motility. The results shown here provide encouraging early evidence of that potential in obesity and weight management.
In this preclinical study, 10 milligrams per kilogram of pilavapitin reduced body weight by 14% after 28 days of treatment. When pilavapitin was combined with semaglutide, the mice experienced a reduction of 31% of body weight, greater than the 25% body weight reduction observed for semaglutide alone. Although these are early findings, these results suggest that pilavapitin may have activity as a standalone agent and may also provide incremental benefit when combined with a GLP-1 therapy.
We believe that this potential is particularly interesting as the obesity treatment landscape continues to evolve and the need remains for differentiated mechanisms and combination approaches. We are continuing to evaluate these findings and advance additional work needed to better define the opportunity, and we look forward to providing further updates as this program progresses. I’ll now turn it over to Scott to discuss our financial results.
Scott M. Coiante (Chief Financial Officer)
Thank you, Craig, and good morning. I’ll begin with a review of our financial results for the quarter. Total revenues were $11.3 million for the quarter ended September 30, 2026, compared to $14.2 million for the corresponding period in 2025. Revenues for the third quarter of 2026 included $10 million in milestone revenue recognized from the Novo Nordisk licensing agreement and net sales of INPEFA of $1.2 million. Revenues for the third quarter of 2025 included $13.2 million of licensing revenue from the Novo agreement and net sales of INPEFA of $1.0 million.
Research and development expenses for the third quarter of 2026 were $16.2 million compared to $18.8 million in the corresponding period of 2025, reflecting lower external clinical trial expenses as a result of the completion of our PROGRESS Phase 2b clinical trial in 2025, partially offset by higher Sonata HCM Phase 3 clinical trial expense in 2026. Selling, general and administrative expenses for the third quarter of 2026 were $9.5 million compared to $7.6 million in the corresponding period of 2025, reflecting increased employee benefit costs and increased pre-commercialization expenses.
Net loss for the third quarter of 2026 was $14.0 million, or $0.03 per share, compared to a net loss of $12.8 million, or $0.04 per share, in the corresponding period in 2025. Net loss for the third quarters of 2026 and 2025 includes non-cash stock-based compensation expense of $3.4 million for each of these periods. As of September 30, 2026, Lexicon Pharmaceuticals had $183.2 million in cash, cash equivalents, and short-term investments, as compared to $125.2 million of cash, cash equivalents, short-term investments, and restricted cash as of December 31, 2025. As previously noted, third quarter revenue included the third $10 million milestone payment received this year from Novo Nordisk following the achievement of a Phase 1 development milestone for LX9851.
We continue to maintain our operating expense guidance for 2026 of between $100 and $110 million, with R&D expected to be between $63 and $68 million, and SG&A expected to be between $37 and $42 million, which includes targeted investments in pre-commercial activity. We remain incredibly pleased with our financial accomplishments thus far in 2026. As we prepare for several important milestones across our portfolio, we remain focused on maintaining the financial flexibility needed to support execution and advance our key strategic priorities, while continuing to evaluate opportunities to unlock additional value across the portfolio.
I will now turn it back to Mike for closing remarks.
Michael Exton (Chief Executive Officer)
Thanks, Scott. Now stepping back, we believe Lexicon is entering a potentially transformational 12-month period supported by multiple opportunities across our cardiometabolic portfolio, sotagliflozin in HCM. We are approaching the pivotal Phase 3 Sonata HCM top-line data readout expected in the first quarter of 2027. While continuing our pre-commercial planning and readiness activities in type 1 diabetes, we’re working towards the resubmission of the Zynquista NDA supported by additional safety data from Steno1, with resubmission expected in the first quarter of 2027.
Beyond these near-term priorities, the Phase 1 program for LX9851 continues to advance with the potential to create additional development milestone opportunities. With pilavapitin, we have a Phase 3–ready pain program as well as an emerging opportunity in obesity that we are actively investigating. Taken together, these programs provide multiple potential paths of value creation. We believe our progress reflects the strength of our science, the breadth of our portfolio, and most importantly, the commitment to creating new opportunities for people living with serious cardiometabolic diseases to live longer, healthier lives. Thank you again for joining today. We now look forward to taking your questions.
OPERATOR
Hello, I do show our next question in the queue comes from the line of Steve Seedhouse from Cantor. Please go ahead.
Steve Seedhouse (Analyst)
Oh, good morning. Can everyone hear me?
OPERATOR
Yeah, sorry about that interruption, Steve. Not sure what happened, but please go ahead and ask your question.
Steve Seedhouse (Analyst)
Terrific. Thanks so much. Wanted to ask a couple on the Sonata baseline demographics. First, just on the, I think it could be accurately characterized as a bit of an overrepresentation of non-obstructive HCM in Sonata. Certainly there’s more patients, but maybe even more than sort of like the prevalence or overall demographic of the disease would suggest. So what do you think is maybe driving that, just in terms of patient motivation or physician motivation to enroll non-obstructive?
And then I wanted to also clarify the percent on background CMI, which you indicated is 9%. Is that among the obstructive patients, or is that overall — so essentially roughly half of the obstructive patients?
Michael Exton (Chief Executive Officer)
Yeah, thanks, Steve, appreciate the question. So let me take the first one and Craig perhaps can take the second one.
Craig Granowitz (Senior Vice President and Chief Medical Officer)
I think there was a strong representation of non-obstructive which, as you know, represents what is happening in clinical practice, perhaps a little stronger than what might be within the clinic. But we have to remind ourselves that these clinical trials are being conducted often by these large academic centers, and these academic centers are where there are available treatments for obstructive HCM. And so I think the need in non-obstructive, together with availability of an approved treatment in obstructive disease, means that likely that was a contributor to the preponderance of non-obstructive patients in the trial.
Yeah, Steve, it’s a great question. I think it leads into your second question: if you look at the percentage of patients that are on a myosin inhibitor, it’s actually the same percentage of patients on a CCB. And again, I think that would be quite different than if you looked in the overall population of the number of patients being treated in the United States on a calcium channel blocker versus those on a CMI. The percent on a CCB would be much higher than that, again, in the general population.
So I think in discussions we had with the PIs in our steering committee, they thought that the numbers and the distribution of obstructive versus non-obstructive was not surprising to them. We had shared with the steering committee while the trial was running the numbers as they were evolving, and they strongly urged us not to cap enrollment of one subgroup or another. When you look at the number of patients that are on a myosin inhibitor, the total number is 49 out of the 542. And just to put that in perspective, there are 50 patients on a calcium channel blocker, which, again, is not that different. The CCB usage, if you look across Sonata to the trials that were done with both AFI and MAVA, if you look at the distribution, it’s about 12% of the patients.
And again, let me define, because it’s an important point, the use of CMIs: every single person that was on a CMI had obstructive disease before they were on the CMI, because, remember, the inclusion criteria of the study is that they’re on a stable dose of any underlying therapy for, I believe, a period of six months prior to enrollment in the trial. So all of those patients had a gradient presumably greater than 50 when they were put on the CMI.
To me, the interesting thing is that you have the selection of patients that both at the entry to Sonata have an outflow tract obstruction or not an outflow tract obstruction, but all of them remain highly symptomatic. So I’m sorry, that was a really long answer. Please pull it apart if there are other concerns. Yeah, go ahead, Mike.
Steve Seedhouse (Analyst)
I was gonna say that was great. If you had anything to add, please feel free. I have a follow-up question though. Unrelated.
Michael Exton (Chief Executive Officer)
No, go ahead.
Steve Seedhouse (Analyst)
Okay. Wanted to also ask on the— I mean, there’s some interesting data on the pilavapadin and weight loss first. What’s the mechanism behind that, do you think? And then given both pilavafidin itself and the mechanism broadly has been studied in humans before, was there any weight loss from any of the clinical studies? I recall there were some tolerability issues, I think, at the highest dose in the pain Phase 2 program. So do you think there’s an adequate therapeutic index here in humans for obesity or weight loss indications?
Craig Granowitz (Senior Vice President and Chief Medical Officer)
Yeah, great question, Steve. And again, I think this goes back to the perspective that Mike raised during the prepared comments that we’ve continued to explore what we think is a really interesting mechanism of action of AAK1. There are really sort of two domains of activity of AAK1 that I think can largely be looked at. The first is around cell surface receptor recycling, which we believe is the mechanism both in neuropathic pain and probably in obesity.
And I’ll come back to that in a second. The other issue is that there is an issue related to the NUMB/Notch pathway and triggering cell replication. And there are some other indications that we’ll probably be reporting on next year related to that pathway and shifting the balance of Notch and NUMB around cellular replication versus differentiation. But getting back to your question, specifically on the weight loss data, we did see weight loss in the knockout mice originally back to the original phenotype. We believe that the mechanism is probably the same mechanism that we’ve also talked about, that there was a slight increase in both blood pressure and heart rate in the neuropathic pain program that we’ve disclosed. And that’s probably related to the balance of sympathetic versus parasympathetic tone both in the cardiovascular system related to blood pressure and heart rate.
And in the counterpoint in obesity, you’re actually increasing the vagal tone, which actually slows down gastric emptying. So we believe that the mechanism, the weight loss that we see in the animal models, is probably related to that increase in ratio of vagal versus sympathetic tone in the GI tract. Now, in the human clinical program, we did go back and look at our PROGRESS study results and we did see a reduction in body weight in both the 10 milligram and 20 milligram arm. It was greater in the 20 than the 10. Again, to your point, we had a concern that that could be both a bit of nausea and vomiting as well as actual weight loss. But in the 10 milligram dose arm, as you recall, the percentage of patients that finished the treatment period was the same as placebo.
So we are seeing a couple kilogram weight loss. And again, you’re only talking about eight weeks of treatment, only six weeks at dose. So we do think, even though the trial was not designed that way—this was not an obesity-enriched population, nor were there any parameters to control weight loss or other parameters that you would put in a formal obesity trial—we did see a reduction in weight loss in the PROGRESS study.
Michael Exton (Chief Executive Officer)
No, I just wanted to add on to Craig’s point here to just remind folks that the important thing with the data we’re presenting on pilavapadin is while they are preclinical data, potentially this allows us to move pretty rapidly into a proof-of-concept Phase 2 study in obesity and some of these other indications. And it’s been our intent as we await some of the critical readouts that we have coming up over the coming months that we build a package of data across a number of indications with AAK1 that really demonstrate the overall value of the mechanism, and we can think then strategically how we take that forward as we evaluate some of the other important catalysts that we’ve got going on.
Steve Seedhouse (Analyst)
Thank you all very much.
Michael Exton (Chief Executive Officer)
Thanks, Steve.
OPERATOR
Thank you. One moment for the next question please. Our next question will be coming from the line of Joe Pantginis of H.C. Wainwright. Please go ahead.
Joe Pantginis (Analyst)
Hey guys, good morning. Thanks for all the details today. I’m sorry if any of this was covered in the beginning; I didn’t hear something for quite some time on the call. First, Craig, I was hoping a little bit of profiling for SOTA and HCM because the field is really expanding quite quickly with the CMIs. Aficamten has the potential to be approved in both non-obstructive and obstructive as well as the upcoming PDUFA for exercise capacity. It’s really where do you think SOTA fits?
Also, additionally, Edgewise confirmed today with regard to their FDA discussions that they’re looking for less or no echoes at all as part of their platform or pivotal pathway. Curious about your quick comments or what have you for the profiling of SOTA about where it may fit, number one. Number two, obviously you know you are deep in the filing preparation for T1D, so just curious what you feel is outstanding to get to the completion of the NDA.
Thanks a lot.
Michael Exton (Chief Executive Officer)
Yeah, thanks, Joe. Maybe I’ll take the first point again and Craig can take the second one. So look, I think in HCM this is a large market and there’s going to be plenty of room for multiple pathways, multiple mechanisms to treat the disease. Clearly it’s not going to be a one-shot-fits-all relating to the treatment of HCM. Now, where SOTA potentially fits within that paradigm will be somewhat dependent on how the data reads out, obviously. But what we can say is that SOTA has not only potentially the efficacy advantages—data pending, of course—but having a once-daily oral medicine that, with a known safety record, immediately avails itself to broad potential, both from a patient base but perhaps more importantly from a prescriber base where a large number of prescribers can potentially use this medicine.
So whether that comes as the first choice after beta blockers or it’s used in combination with a sarcomeric agent will be dependent on data and we’ll see as the space evolves. But I think having a one and only medicine where we can play our own game, if you like, and let the sarcomeric agents battle against themselves for various risks and benefits is going to be the way that we’ll play the game. Craig?
Craig Granowitz (Senior Vice President and Chief Medical Officer)
Yeah, Joe, I’m happy to come back if there’s any further clarifications on the question on the positioning of SOTA versus the CMIs or potentially other sarcomeric agents. I’ll answer the questions on T1D. You know, as I think I mentioned in the prepared remarks, we only crossed the threshold with Steno at the end of August. That’s why we had in the slide that cut date. Obviously, the studies continue to both enroll patients, at least in the standard-of-care arm.
The MFI arm is fully enrolled, but the exposure continues to accumulate on SOTA during that study, and we expect—and FDA in fact has already told us—that over the course of the review they’d like updates on the data, and we wanted to make sure that the DKA rate on the SOTA arm was also stable before we submitted the package. I guess I’ve been trying to come up with analogs of how to sort of frame this compared to a company-sponsored trial because, remember, this was an investigator-initiated trial that was set up in a manner that was never designed to do the level of oversight and intensive monitoring that you would see, like we see in Sonata or any of the other regulatory labeling studies. So we’ve really been spending a lot of time; in fact, we’ve provided significant additional resource to Steno to help them clean the database.
And it really is a matter of trying to get all of the values and assure ourselves that there is accuracy in all of the data reporting—not to the standard of an academic publication, but to the standard of a potential FDA review, which, as you know, are two very different standards. So we feel quite confident in the rates of DKA that we’re reporting. The issue is that FDA is going to also potentially want to look at other parameters to assure themselves of the quality control and oversight and a lot of the other administrative aspects that would be required for FDA filing. Things like financial disclosures, just a whole host of issues related to database quality. You have issues with GDPR in terms of getting data from a European study to a U.S. study that was never designed that way.
We had to go back, for example, and get changes to the informed consent so that the data could be sent out. I mean, this has been a whole host of issues that we’ve been working through with Steno. Now we do feel that these are in hand, but, you know, it’s just taken time. It’s a very large data set, it’s close to 2,000 patients, and we just want to make sure that we’re going to put in the highest quality submission.
Joe Pantginis (Analyst)
Very, very helpful. Thanks for all the color.
OPERATOR
Deb. Thank you. One moment for the next question. Our next question will be coming from the line of Yasmin Rahimi of Piper Sandler. Please go ahead.
Yasmin Rahimi (Analyst)
Good morning, team. Thank you so much for all the great updates and really exciting new data from Televaptin showing weight loss. Would love to understand. You know you have a great partner with Novo that’s working on LX9851. Have you had the opportunity to share some of these Pelovastin data with them? Would love to hear your thoughts around that. And then also a second question is in regards to HCM. With such a large distribution of patients with non-obstructive, is there a statistical hierarchy that allows you to statistical separation in KCCQ in non-obstructive as a sole subgroup? That would be super helpful and appreciate your color. And then one last follow-up as well.
Michael Exton (Chief Executive Officer)
Yeah, great. Yes. Let me take again the first and Craig, the second. Look, we’re actually in touch with Novo pretty regularly, as you can imagine. Not only on LX9851, but there’s a lot of things that are common across our portfolios, and we have had the chance to discuss this with a couple of people within Novo, not the broader team. There’s certainly interest there, as you can imagine, and we’ll continue to engage with them and other people as we build on this and other data.
As you can imagine, the chart that we presented to you here is just one piece of data from that series of studies. There’s a lot of other interesting data in behind that that is quite robust, and it really, I think, shows the value of the mechanism of AAK1 and, as Craig mentioned, we’ll continue to build on that. In fact, we’ve got other data we’ll continue to share, you know, when the time is right, to show you that this is a really interesting and important mechanism.
Craig Granowitz (Senior Vice President and Chief Medical Officer)
Yeah, it’s a great question on the distribution of patients, and in fact we spent a lot of time internally with our steering committee, with some very well-regarded external academic statistical input—many of the names I think you would know for sure—and then also regulatory input on the population. And the strong consensus across everyone is to maintain the primary endpoint as is with the overall study population. We’ve looked at a number of different scenarios related to trying to pull out separately the non-obstructive group from the obstructive group. I think at the long and the short of it we’ve decided, with a lot of input, to keep the primary endpoint as is. I think in the SAP there are still some issues around the hierarchy in which your secondary endpoints that we’re looking at as we continue to do some modeling on the data. And again, we want to finalize the SAP soon, but like many other companies, they don’t finalize their SAPs till right before the database closes.
So we certainly have some time. But we feel quite confident that the primary endpoint of this trial is robust. I think the fact that we have significantly over-enrolled the trial, as well as the fact that the therapy has been well tolerated during treatment, gives us a high degree of confidence in the power to detect the endpoint in the study with about a 5 to 5.5 point difference in KCCQ score. So we feel really good about that. We feel really also about the way the treatment is running and the completion rates of patients, and again the trial is still ongoing so I don’t want to say too much, but we feel quite good about the statistics of the trial so far.
Michael Exton (Chief Executive Officer)
Yeah, and Yaz, that really represents our belief in sotagliflozin in HCM and the unmet need that exists across both obstructive and non-obstructive disease, and having the overall KCCQ delta as the primary endpoint in both obstructive and non-obstructive is important because, as we see here, there are still folks on existing treatments that are highly symptomatic. The need in obstructive is significant, as it is in non-obstructive disease. So it’s important, based on the underlying biology and the market need, that we really can address both obstructive and non-obstructive disease.
Yasmin Rahimi (Analyst)
Great. Thank you so much.
OPERATOR
Thank you. One moment for the next question. Our next question will be coming from the line of Nigel of Citigroup. Please go ahead.
Nigel (Analyst)
Hi. Thank you. So I just had a few more sort of nitty-gritty questions on Sonata. I think, Craig, you just mentioned that you have some flexibility on the secondary endpoint in terms of the hierarchy there. So what sort of factors govern the decision on shifting around secondaries in terms of maximizing the evidence set? And then also regarding background diuretic therapy. So that’s an interesting one in terms of how that could impact the outcome. You can imagine, obviously, on the sota arm you might see less need for that, whereas you may see more of that on the control arm, but that could also impact outcomes. So how do you reconcile that in terms of normalizing for that possible difference in the background diuretic therapy to make sure you get a clean readout?
Craig Granowitz (Senior Vice President and Chief Medical Officer)
Yeah, I’ll answer the first question again on the secondary endpoints. And again, the primary endpoint of KCCQ in the overall population is going to stay the primary. The key secondary of New York Heart in the overall population is going to stay there. Right now we are going to continue the hierarchy as planned down the overall study population versus sort of looking at the non-obstructive versus the obstructive in that hierarchy. As you go down the overall parameters—and there’s a number of echo parameters and enzyme parameters as secondary or exploratory endpoints—you know, I think those are really far more of interest to the academic publication than from the regulatory file, and certainly the PIs of the study. And we have an eye towards getting the highest possible tier publication. So those are the kinds of things that we’re talking about in the hierarchy. But from a regulatory standpoint and from a claim standpoint, I don’t think those are really going to change appreciably.
Moving on to the diuretic issue, there are very few patients in the study that are on diuretics. In fact, it doesn’t even really come up, as you can see, in the baseline characteristics that we’ve shared and that Dr. Day shared at the Boston HCM meeting about a week or two ago. The largest group of patients on underlying therapy is beta blockers. There are about 80% of patients on a beta blocker. And as was previously mentioned—I’m sorry for being repetitive—the next commonly most used agents that are acting on the cardiovascular system are calcium channel blockers and CMIs that are similar, both at about 10% of the patients.
So the diuretic use really isn’t a significant issue. I mean, there you’re talking about patients with severe heart failure, and then you’re sort of looking at the overall pillars for patients with either HFrEF or HFpEF, but there really is not much use of diuretics in this population. All right, thank you.
OPERATOR
Thank you. One moment for the next question, please. The next question is coming from the line of Andrew Tay of Jefferies. Please go ahead.
Andrew Tay (Analyst)
Hi there. Good morning. Thanks for taking my question. Thanks for the updates. At the IHCM conference, when you guys shared the Phase 3 baseline patient population for Sonata in HCM, we noticed that the obstructive subgroup had a lower baseline KCCQ score compared to the two other CMI trials, suggesting a more severe symptom burden at baseline. And I think for non-obstructive baseline, the KCCQ is maybe in line, if not lower. So the net of this is, the question: Is this a favorable or unfavorable dynamic for sotagliflozin to show a positive benefit in Phase 3 on KCCQ?
Craig Granowitz (Senior Vice President and Chief Medical Officer)
Yeah, great question, Andrew. Again, the other trials that have been published out there—some have baseline KCCQs, some don’t. But certainly, as you point out, the baseline KCCQ for Sonata is 55 in the obstructive group versus what was reported for SEQUOIA at about 75. You can also see that the EF of the patients in Sonata at 67 or 68 is significantly lower than that in SEQUOIA and EXPLORER because they set, as you recall, a threshold for enrollment that’s much higher for left ventricular function.
And that group of patients is really a more hyperdynamic group of patients just based on the entry criteria of the selection. It is interesting in that group though that the BNPs are about the same, and the outflow tract obstruction is actually somewhat larger, as you would expect, in SEQUOIA and EXPLORER because the threshold is set at 50 as opposed to 30 in Sonata. So, you know, based on the feedback we had from our steering committee, they were really pleased with the number of women that actually were enrolled in the trial, which is important and meaningful. The fact that you do have patients on a CMI still that are symptomatic with obstructive disease, that they really feel that this group of patients is important. And I would argue that the lower baseline KCCQ is really helpful for trying to show a larger delta in KCCQ, because we know the lower the baseline KCCQ generally, the greater the change in KCCQ with treatment.
Andrew Tay (Analyst)
Agreed. Yes. Thank you. And then secondly, for the top-line release in Q1, how much data can we expect you to share? Can you give us a teaser on what kind of efficacy, safety data? And then what would you be saving otherwise for a medical conference? Thank you.
Craig Granowitz (Senior Vice President and Chief Medical Officer)
I think what we would certainly plan to release is the top line of the primary and secondary endpoints. I mean, those are going to be the key. I think a lot of these analyses by these subgroups we’re probably not going to be releasing because a lot of that will require full analysis—particularly when you look at the impact of those that have sarcomeric mutations versus not, the effects on outcome by underlying medication use—that will probably not be released.
And we’ll release something probably on the top line of safety-related effects in the trial—you know, the major, major safety effects. So I think those are really going to be the critical issues that are going to be released at top line trial.
Andrew Tay (Analyst)
Makes sense. Thank you.
Craig Granowitz (Senior Vice President and Chief Medical Officer)
Thanks, Andrew.
OPERATOR
Thank you. One moment for the next question. And our next question will be coming from the line of Aronna Rovitz of Lyric Partners. Please go ahead.
Frank (Analyst)
Hey, guys. Good morning. This is Frank on for Aronna. My question relates to the Sonata HCM trial with 440 non-obstructive patients and 102 obstructive patients. Kind of curious: What level of consistency across the two groups would you need to support a broad HCM label? If the overall result is positive, but the obstructive group, for example, is inconclusive, would that kind of limit the indication? Thanks.
Craig Granowitz (Senior Vice President and Chief Medical Officer)
Yeah, it’s a great question. And you know, normally what is done—and we have experience on this with what we did with heart failure when we had both HFrEF and HFpEF in a single population—and what we discussed and agreed with the FDA is to really look at an interaction p-value in that. I think, like all of these things, that will become a review issue as part of the overall package that we submit to the FDA. I think as long as they are directionally the same, that’s been our experience with the agency that they would probably grant the broad label.
That’s certainly the spirit in which we went down to the FDA when we initially submitted this trial for review and comment.
Frank (Analyst)
Super helpful. Thanks, guys.
OPERATOR
Thank you. That concludes the Q and A session. I would now like to turn the call over to Michael Exton, CEO, for closing remarks. Please go ahead.
Michael Exton (Chief Executive Officer)
Thanks, everyone, and apologies for the technical glitches here on the presentation. But nevertheless, hopefully you’ve seen this great progress that the company has made, Q3 to date. And we’ve got a lot more coming up over the next six to 12 months that we believe are quite transformational for the company across a number of late-stage and earlier catalysts. So really look forward to sharing more with you in the coming weeks and months. Thanks very much and have a great day.
OPERATOR
Thank you for joining today’s programming. You may now disconnect.
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