Lexicon Pharmaceuticals, Inc. Citigroup’s Biopharma Back to School Summit 2026

Yeah, no, great. Thanks, Yigal. Perhaps before diving into SOTA, I can give you a little bit of where we're at as a company. Over the last couple of years, really, we focused on driving our R&D programs on establishing financial flexibility and completing a number of partnerships that have gotten us to, I think, a really good state, particularly with SOTA, but across the board. Now we're on the precipice of a very important data readout in HCM, hypertrophic cardiomyopathy, with SOTA. We expect data in Q1 of next year. Really that is the North Star for the company. As we sort of execute that, all of the data into the trial, in parallel to that, we start to think around what the commercial opportunity is for us in this pretty important space.

We recently just promoted Rachel Martens in our company to Chief Commercial Officer. Rachel's been leading our BD&L and partnership strategy, and was the driver behind our partnership with Novo Nordisk. Really pleased to have her in that position. She ran the insulin businesses for Sanofi and has worked in biotech. We're going to form a very small but very mighty commercial team. We now have a head of marketing and on the precipice of bringing in a market access person, who are really going to do all the pre-launch preparation in HCM because that is our number one commercial opportunity. Beyond that, of course, we're very soon to resubmit sotagliflozin for T1D. In addition to that, we have pilavapadin, which is a phase III-ready program in DPNP. Of course, our program with Novo Nordisk, which is in phase I, LX9851 for obesity.

A lot of things over the next six months where, if you think at the end of Q1 of next year, we could be in a situation where we have data from SONATA-HCM, a potential launch in T1D, have started a phase III program in DPNP, and Novo starting the phase II program in weight management for LX9851. Really important time for the company. Lots of things happening, but with a clear focus for us in HCM.

Yeah. Thank you, Yigal. Important questions you are asking. The primary endpoint that has been identified by health authorities is improvement in feeling and function. Since we have a long history with the molecule sotagliflozin in heart failure, and not only have improvement in symptoms in heart failure, but also improvement in cardiac mortality and reduction in heart failure events. Outside the U.S., our partner has gotten approval also for use to reduce stroke and MI with the agent. FDA and we agreed and have, before we started the study, that the primary endpoint would be in this KCCQ score, and the secondary endpoint would be in the New York Heart Association score. Change in those scores, placebo controlled and adjusted. That is consistent with HCM. The regulatory hurdle is to improve patient functionality and feeling. There are no long-term outcome studies.

The CMIs that have been approved do not have long-term outcomes associated with that agent. In part, they needed a dual endpoint because these are unproven agents that have never been on the market. I think there was a concern that KCCQ score alone would not be enough, and that is why they have a co-primary endpoint, particularly outside the U.S., for a physical function benefit of peak VO2. In our trial design, and I hope as we go to market, we have really tried to take a very broad and pragmatic approach and really think about being first and only in mechanism, and complementary in use no matter what the agent. The trial design really takes those criteria into account. We have the broadest range of ejection fraction included. We have the broadest range of baseline medications, including CMIs in the trial.

Not requiring all of the physical testing like peak VO2 or exercise testing, it also allowed more centers to enroll more patients more rapidly. That was the philosophy behind the trial. I think the result of that is we enrolled the trial quickly at relatively modest cost compared to some of these other trials. As you have already pointed out, we actually over-enrolled the study.

Maybe if I just add on to that, Yigal, because you mentioned a 4 or 5-point delta versus placebo. The study was certainly powered for that, and having an over-enrollment improves that powering, obviously. What our expectation for success is has really been set by the marketplace. A delta placebo adjusted at 3 points that is statistically significant, we think given the benefit risk profile of SOTA would be a home run for us commercially, and anything above and beyond that is obviously upside for us. We think we have a great chance of this being a very important part of the armamentarium in HCM.

Yigal, you are doing such a good job answering the question, I just wanted you to continue. But the trial is designed for the combined group together to be analyzed as one. So all of the 500 plus patients as one primary group. As we have mentioned, the trial is stratified based on baseline obstructive or non-obstructive, but as you have already pointed out so elegantly, the mechanism really is going to be independent of the underlying mechanism. I think there is an expectation in the field, which may or may not be borne out, that the obstructive group is less heterogeneous than the non-obstructive group. The non-obstructive group seems to probably be an amalgamation of different diseases. Certainly, the sarcomeric mutations is going to be a more severe and a relatively more pure form of the disease.