Lexicon Pharmaceuticals at H.C. Wainwright: Strategic Program Updates

On Monday, 08 September 2025, Lexicon Pharmaceuticals (NASDAQ:LXRX) presented at the H.C. Wainwright 27th Annual Global Investment Conference, providing a strategic overview of its key programs. The company’s leadership highlighted significant progress in drug development, while also addressing challenges and future plans. The focus was on pilibapadin, sotagliflozin, and LX9851, with efforts to seek partnerships and regulatory approvals.

Key Takeaways

• Lexicon completed Phase 2 trials for pilibapadin and is preparing for an FDA meeting.
• Sotagliflozin development in hypertrophic cardiomyopathy (HCM) is advancing with the SONATA trial.
• LX9851 studies are set to be handed over to Novo Nordisk by year-end.
• Lexicon is not investing further in Zynquista for type 1 diabetes but continues to evaluate its potential.
• The company is actively seeking partnerships, particularly for pilibapadin.

Operational Updates

Pilibapadin:

• Phase 2 trials for diabetic peripheral neuropathic pain (DPNP) are complete.
• An end-of-Phase-2 meeting with the FDA is planned.
• Positive results were also seen in post-herpetic neuralgia (PHN) studies.
• Preclinical data shows potential for chemotherapy-induced neuropathy and multiple sclerosis pain.
• Phase 3 trials will use a 10 mg dose, with discussions for partnerships ongoing.

Sotagliflozin:

• Development in HCM is ongoing with the SONATA trial, expected to conclude in 2026.
• The SOTA-PCARDIA study focuses on cardiorenal benefits in HFpEF, with data expected by year-end.
• Regulatory submissions are progressing outside the U.S. and Europe.
• Recent data challenges the efficacy of beta blockers, positioning sotagliflozin as a potential first-line treatment.

LX9851:

• R&D enabling studies are on track to be completed and transferred to Novo Nordisk.
• Lexicon has a licensing agreement with Novo Nordisk, including milestone and royalty payments.

Zynquista:

• Despite not actively investing, Lexicon submitted additional data to the FDA.
• The FDA has encouraged leveraging investigator-sponsored studies for further evaluation.
• Zynquista shows efficacy in glycemic control and reducing hyperglycemia events.

Future Outlook

• Lexicon is focused on cardiometabolic medicine and leveraging its U.S. presence.
• The company aims to establish sotagliflozin as a first-line agent for HCM.
• Positive preclinical data may expand pilibapadin’s indications.

Q&A Highlights

• Two Phase 3 trials for pilibapadin in DPNP are expected, each with two arms.
• The SOTA-CROSS study complements SONATA by focusing on morphological changes.
• Enrollment in the SONATA HCM trial may be impacted by other ongoing studies.

In conclusion, Lexicon Pharmaceuticals is strategically advancing its programs and seeking partnerships to enhance its cardiometabolic focus. For more detailed insights, refer to the full transcript below.

Full transcript - H.C. Wainwright 27th Annual Global Investment Conference:

Lander, Senior Research Associate, H.C. Wainwright: Everyone, my name is Lander. I’m a Senior Research Associate at H.C. Wainwright. We’re pleased to have you with us today, and it is now my pleasure to introduce our next presenter. Please join me in welcoming Mike Exton, CEO of Lexicon Pharmaceuticals, a biopharmaceutical company focused on cardiovascular medicine and its associated disorders. Mike, over to you.

Mike Exton, CEO, Lexicon Pharmaceuticals: Thanks so much, Lander. Pleasure to be here and wonderful to tell you the Lexicon story and all of the great activity that we’ve been up to this year. Of course, I’ll make some forward-looking statements within the course of the presentation. As you all know, at the start of this year, we pivoted our efforts to focus on our portfolio, on our R&D pipeline, and really we’ve made excellent progress in the first two-thirds of the year. Still a ton of activity yet to go. That has resulted in us, firstly, now having pilibapadin phase 2 data across the entire phase 2 platform. The discussions are ongoing ahead of an end-of-phase-2 meeting, which will happen later on this year.

We’re on track to complete all of our R&D enabling studies, in fact, quite soon for LX9851, the drug that we have partnered out to Novo Nordisk for a worldwide license in obesity and related conditions. That will take place towards the end of this year. Importantly, we’ve accelerated the recruitment in the phase 3 SONATA trial for hypertrophic cardiomyopathy with sotagliflozin. Finally, we’re making great progress in getting submissions and approvals, actually, for sotagliflozin in heart failure outside of the U.S. and outside of Europe with our partner, Vieitrace. I’ll talk about all of these in the coming slides, but we’re really in a great position to capitalize on what is a great and expansive portfolio. Really focused across these three areas, firstly with pilibapadin, which all of our medicines are once-a-day oral medicines and really offer a portfolio and a pill type of opportunity.

With pilibapadin, our lead indication in diabetic peripheral neuropathic pain, as we mentioned, we’ve closed out the entire phase 2 program and are preparing to have our end-of-phase-2 meeting with the FDA. We’ve also done a phase 2 study in post-herpetic neuralgia, which was positive as well, and we are planning a potential phase 2 study in spasticity. In sotagliflozin, as you know, we have an indication in the U.S. for heart failure and are expanding that outside of the U.S. and Europe with our partner, Vieitrace. We continue to really generate a lot of differentiating data, both in heart failure and in hypertrophic cardiomyopathy, that I think will really demonstrate that SOTA, because of its SGLT1 mechanism, is the SGLT inhibitor of choice, particularly in HFpEF and hypertrophic cardiomyopathy. As we mentioned, the SONATA trial is ongoing with data to be fully enrolled in 2026.

Finally, with LX9851, as we mentioned, we’re making great progress to hand over the full data package for the R&D to be submitted by our partner, Novo Nordisk. Speaking of Novo Nordisk, what we decided to do at the start of this year was make sure that we focused on our core expertise of cardiometabolic medicine and in the U.S. where we have our presence. By doing that, we’ve licensed ex-U.S. and ex-EU to Vieitrace for all indications. We have done a worldwide licensing agreement with Novo Nordisk for LX9851, which had a significant upfront and, of course, significant milestones and royalty payments that’ll be associated with it. We’re continuing our discussions for pilibapadin partnering for DPNP and other indications for this particular mechanism.

We’ve taken a very flexible approach to doing those types of deals and ones that not only provide us the best financial perspective, but importantly, really take advantage of the breadth of these portfolios in a pill medication. Looking forward to continuing to engage those discussions for pilibapadin, which really, over the last couple of months, as we’ve finalized all of the phase 2 data from progress and looked across our platform, have been validated by what I would say is perhaps one of the strongest scientific advisory boards that I’ve seen in my few decades of working in the industry, that really gave us great confidence that moving into our end-of-phase-2 meeting, we’ve got a drug that, first of all, shows really great biological activity.

This is important in neuropathic pain where you get significant placebo responses and making sure that you can tease out what the drug is actually doing. This advisory board confirmed that pilibapadin has great biological activity and that it’s clinically meaningful. These are folks across regulatory, clinical, and trialists that really reinforce that what we’re seeing is a clinically meaningful benefit to the patient. As we mentioned, that 10 mg is unequivocally the dose that we will take into phase 3 and that the tolerability and safety profile is acceptable and in line with other agents that are used in diabetic peripheral neuropathic pain.

Finally, really gave us some good ideas around how we can continue to ensure that there isn’t great variability within the placebo response and manage the placebo response from a clinical trial design perspective and improve adherence within the trial itself to optimize that phase 3 program. To sum, we really have great data across the portfolio for pilibapadin. We’ve now run three positive phase 2 trials in PHN and DPNP. It’s really the leading medicine that’s shown separation from placebo in neuropathic pain. We’ve got a full portfolio with the phase 3 ready lead indication, DPNP, and other indications potentially ready for phase 2. We’ve got a lot of data that we’ve shared with some of our partnering discussions that go well beyond neuropathic pain and even beyond neuroscience indications, to be honest.

I think what we’re seeing is that AAK1 is becoming a really relevant biological mechanism across neuroscience and other biological activity. Importantly, we’ve got a ton of safety and tolerability information for pilibapadin and a great IP situation. This is a really significant proposition for potential partnering. We’re just getting a glimpse of the data. September’s going to be incredibly busy. September, October, as we release a number of pieces of data at various conferences. Just recently at NUPCIG in Berlin, for example, we revealed for the first time preclinical data in chemotherapy-induced neuropathy and multiple sclerosis pain that showed significant biological activity preclinically, just demonstrating that there is potential expansion of the indication within neuropathic pain and a potential broad indication for pilibapadin in neuropathic pain. Perhaps, excitingly, over the next month, we’re presenting a ton of data.

We have recently participated in Pain Week in Las Vegas, where we really understood the patient perspective and how important it is for a new medicine, a new non-opioid oral medicine, which they’re really keen to have in their hands because there’s so little innovation, the data in NUPCIG that we’ve just discussed. Importantly, the final important data from progress will be presented at both Neurodiab and AASD in September next week, where we’ll present the important selected data from progress. Finally, at the Pain Therapeutic Summit, I’d like to call everyone’s attention to that one in particular, which will occur in mid-October. This is a longer presentation where we will present comprehensive data from the full phase 2 platform.

I think that will really demonstrate to everyone why we have such confidence taking pilibapadin into phase 3 and hopefully to eventual approval and the first approval in diabetic peripheral neuropathic pain for about 20 years of a non-opioid oral candidate. Great stuff is happening with neuropathic pain, but perhaps most sort of contemporary relevance right now coming off the back of ESC is in HCM. We are developing sotagliflozin in hypertrophic cardiomyopathy. It’s a huge unmet need for about a million patients in the U.S. that have a number of issues with cardiac energetics and diastolic dysfunction, which is a really key sign of HCM. They experience symptoms that are similar to what you get in heart failure. They have shortness of breath, fatigue, dizziness, and they really have a pretty miserable day-to-day existence because of these symptoms restricting the types of things that they can do.

More importantly, HCM usually has a pretty nasty sequelae leading to heart failure, AFib, and stroke. Despite that, there’s really very little innovation that has happened in the field over the last 10 to 20 years. The cardiomyosin inhibitors are now being studied with one of them available. Despite that, the market penetration has been very low, so about 1% of the total addressable market being understood at the moment. ESC showed us a couple of important read-throughs that the first-line treatment for HCM is not really going to do the job. For sotagliflozin, it’s the only medicine that works inside and outside the heart for HCM and directly works to reduce heart failure and MACE and stroke. It acts directly on the myocardium, and it has the potential to be a broad first-line agent.

The reason for saying that is that at ESC, we were surprised to see that the current first-line option for HCM, a beta blocker, not only had no effect, but in fact, tended to show harm. This is causing a complete rethink of the field in HCM, and clearly sotagliflozin being a highly efficacious, safe, and potentially broad utilization has the potential to operate in that first-line space. An indication for both obstructive and non-obstructive, as you’ll see with the SONATA trial where we’re investigating HCM in both obstructive and non-obstructive HCM, is possible for sotagliflozin. I think it’s important to call out that of all the entry criteria in SONATA, we have an ejection fraction as low as 50%.

The reason for that is we prevent the exacerbation of heart failure, whereas a number of other agents will typically have ejection fraction starting entry criteria much higher because they reduce ejection fraction, causing reduced ejection fraction heart failure. What we end up with is a situation where both in HCM and HFpEF, we have the potential to really be an effective agent. We now have two pretty important clinical studies that complement SONATA HCM. The first, SOTA-PCARDIA, is looking at the cardiorenal benefits in HFpEF, and we should have data by the end of the year. The second one, SOTA-CROSS, is looking at sotagliflozin in symptomatic non-obstructive HCM. What’s important here between HFpEF and HCM, non-obstructive HCM, is that in community cardiology, where the vast majority of patients with HCM are treated, HFpEF and non-obstructive HCM present the same way. They present with diastolic dysfunction.

They present with those symptomology that I talked to you about. They have a normal ejection fraction. They have shortness of breath. They feel dizzy. It’s difficult to tell them apart. It’s easy to identify obstructive HCM, but for the community cardiologists, it’s quite difficult. We already have a label for HFpEF and potentially in non-obstructive HCM. That, combined with the fact that beta blockers are being called into question as the first-line agent, we believe there’s a great opportunity here for sotagliflozin to be a one-stop shop as a first-line agent due to the safety, tolerability, ease of use, and effectiveness. We’re really looking forward to these data reading out. I won’t touch on this. It’s very clear what we’re doing. Give enough time for questions here, Lander. The rest of this year, we’ve got a lot going on in DPNP.

We’ll work towards the end-of-phase-2 meeting with the FDA, and those partnering discussions are really becoming pretty constructive as we head towards that particular time point. In HCM, we’re accelerating the enrollment, and we’ve got all study sites up and running by the end of Q3. In fact, pretty soon. The regulatory submissions are really going very well with Vieitrace for HFpEF. You may have seen, actually, that just today we mentioned that we submitted some more data to the FDA for Zynquista in type 1 diabetes, something we haven’t talked about much. The FDA released or made public our CRL together with a number of other CRLs from December 2024. Clearly, this is an area where we still believe that Zynquista is a very important addition to insulin in type 1 diabetes. The patients advocate very strongly for that.

In LX9851, we will conclude all of our R&D enabling studies. Let me just say one thing about Zynquista because, as I said, Lander, we haven’t spoken about that much. If you read the CRL that, as I mentioned, is public now, the FDA really encouraged us with three things. The first is they said they will accept data from prospective non-Lexicon initiated studies, so investigator-sponsored studies, in a very pragmatic way. It’s quite an unusual step for this division and the FDA. The second is they wanted us to leverage that data in a new submission. Secondarily, they believe that this is a huge unmet need for patients, that they recognize that Zynquista has shown great signs of efficacy, and that is unquestionable. Patients need a medicine, and they thirdly want to work very collaboratively with us to continue to evaluate the potential of Zynquista in type 1 diabetes.

We are going to continue that path. We’re not investing any further in Zynquista, but these investigator-sponsored studies allow us to continue the path on behalf of folks with type 1 diabetes. I’ve tried to rush through that as quick as we can so we can get to a few questions, Lander. Thank you very much.

Unidentified speaker: Thanks for the nice overview, Mike. We have time for some questions. Anyone in the audience? OK, so maybe Mike, regarding the reactivation of Zynquista for type 1D, would the target population still be type 1D plus CKD or type 1D overall?

Mike Exton, CEO, Lexicon Pharmaceuticals: Type 1 diabetes overall.

Unidentified speaker: Overall.

Mike Exton, CEO, Lexicon Pharmaceuticals: Overall, yes. In the CRL, they really encourage us to, as I said, the efficacy of Zynquista, sotagliflozin, in T1D has been clearly established, both from a glycemic control and a reduction in events of hyperglycemia. They just want to see evidence of the DKA rates that are in line with what we believe is a beneficial risk-benefit profile. That’s for the whole population.

Unidentified speaker: OK, OK. Yeah.

Unidentified speaker: With regard to the neuropathic pain, you’re entering phase 3. Can you tell us a little bit about what the FDA said in terms of what kind of responses they want to see and what magnitude?

Mike Exton, CEO, Lexicon Pharmaceuticals: Yeah, so we’ve previously met with the FDA. We’re going to meet with them at the end-of-phase-2 meeting later this year. Our understanding in the previous discussions, and in fact, has been reinforced by what they’ve informed other companies, is that you need two phase 3 trials in DPNP. We believe that the design is actually very similar to how we’ve designed it in PROGRESS, with the caveat that we’ll just have two arms in each trial, one for placebo, one for active, for pilibapadin. It’s very important. We actually were very purposeful to have a dose finding study as our PROGRESS study at phase 2 because we know that the more arms you have in a trial, the greater the variability and the higher the placebo response.

By now being able to just have two arms in that phase 3 trial, we believe that has a great likelihood of success. Simple. Keep it simple, stupid.

Unidentified speaker: All right. Mike, can you elaborate a little bit more on how the investigator-initiated SONATA-CROSS can complement SONATA?

Not SOTA-CROSS can complement SONATA HCM because are the primary endpoints the same from both trials?

Mike Exton, CEO, Lexicon Pharmaceuticals: They’re not the same. In the SONATA trial, it’s KCQ, whereas in SOTA-CROSS, it’s primarily exercise capacity. Peak oxygen consumption is the primary focus, with other secondary endpoints, both morphology and exercise capability and KCQ, et cetera. Where it will complement is it will also show these morphological changes, which will be very important for showing that sotagliflozin targets the direct underlying nature of the disease. It’s not just looking at outflow obstruction, as we see in obstructive HCM, but really what’s common in non-obstructive and obstructive disease is the energetics. We believe SOTA directly targets the energetics of the cardiomyocyte.

Unidentified speaker: Perfect. Just to wrap it up, do you think that enrollment in SONATA HCM can be affected by other CMI studies ongoing?

Mike Exton, CEO, Lexicon Pharmaceuticals: The other point at ESC was Odyssey was closed out and Maple, the two big trials that were running concurrently with SONATA. Both of those are now concluded. We’re seeing that in the enrollment right now, particularly with the Europeans coming back from their summer vacation. We’re seeing strong enrollment come from Europe now that we’ve got all sites open and rolling. We think that will help certainly beneficially drive enrollment towards the conclusion of SONATA.

Unidentified speaker: Perfect. Feel free to reach out to management during the conference if you have additional questions. Thanks again to Lexicon Pharmaceuticals from H.C. Wainwright.

Mike Exton, CEO, Lexicon Pharmaceuticals: Wow, thanks so much.

Unidentified speaker: Thank you, Lander.

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