Okay, we're going to get started. I'm Andrew Tsai, senior biotech analyst at Jefferies. Thanks for joining me today, and it's my pleasure to have the Lexicon team with me. To my direct left is Craig Granowitz, CMO, and to his left, Mike Exton, CEO. Welcome, both of you. Thanks, Andrew. Help us level set what Lexicon is working on, what you're trying to achieve, and the milestones over the next 6-8 months could be helpful. Great. Thanks, Andrew, and thanks, Jefferies, for the invite. Look, we've come here really at a very important time for Lexicon's history. Over the last couple of years, we've really taken a determined effort to become a focused cardiometabolic company, and really put heavy attention into our pipeline, and we're here on the precipice today of a number of very significant developments for us. I'd like to take you through those, and we can deep dive into those a little bit more. First and foremost, hypertrophic cardiomyopathy is a topic that has really become a focus of investor and physician attention over the last couple of years, and has increased investment and data comes with HCM. We've talked about our SONATA Phase III trial that's ongoing, and we've always guided everyone that we would be completely enrolled by mid-year. In fact, we informed study sites that on the 19th of June, so in a couple of weeks, screening will stop. Really, we are right on track to complete the enrollment by mid-year, which is a very important time for us as we have this 500-patient phase III trial in both obstructive, non-obstructive HCM. That puts us squarely in our commitment to have data in Q1 of next year. Really exciting time for us on that one, Andrew. With that, we also have guided that sotagliflozin under the brand name Zynquista we will resubmit to the FDA for glycemic control in type 1 diabetes by mid-year, and we're getting well prepared to make that resubmission in our collaboration with the Steno group out of Denmark, where that new prospective data is coming from, which the FDA, over the last couple of years through our conversations with them, has always requested. We've been able to really collaborate with the DDLO division of the FDA to determine that data in both the exposure and rates of DKA that we would get from that study would be acceptable to the FDA as part of that submission. Indeed, the good news with that is because it's an open label study, we get the data in real time, both in exposure and DKA rates. We've guided publicly that in both of those cases, they're well in line with what our expectation is for a successful resubmission. As I mentioned, we'll resubmit that soon and we'll likely disclose some more color on that data that we're seeing and give the street and everyone a bit more visibility into what we're seeing from that particular data set. That's really exciting for us as well. Thirdly, for pilavapadin in diabetic peripheral neuropathic pain, as we've spoken about before, we had a successful end of phase II meeting and received the minutes earlier this year that have guided us towards being able to commit to the phase III program with no addiction potential, which has been recognized by the FDA. It's very important in neuropathic pain, where oral opioids still take up about 20% of the treatment regime that bringing new non-opioid oral medicines to the market is an important aspect for the FDA, and they've recognized here that pilavapadin has no addiction potential, so it's non-opioid, obviously. We are currently working with potential partners on a model that will ensure that that additional investment that doesn't come from our balance sheet right now, we're not using money on our balance sheet for that particular set of studies, will allow us to not only continue the phase III program under a potentially separate vehicle, but in addition really have a significant stake in the outcomes post phase III, which is really valued significantly by strategics as we receive feedback along the way. Finally, really an exciting time for LX9851, for which we sold the license to Novo Nordisk last March. This is a novel target in obesity, the only drug of its kind that is really being developed at a very fast pace by Novo Nordisk. It went into clinical trials earlier this year. We received two $10 million milestone payments from the IND and the fifth patient in the SAD study, and expect a further $10 million milestone payment later this year as it goes into the multiple ascending dose. In fact, just give a plug, it actually featured on the page four of their Q1 earnings report earlier this year, which just really shows how enthused Novo Nordisk is by this particular drug and the mechanism. If you fast-forward into Q1 of next year, you can paint the picture of Lexicon being a completely transformed company with a readout in HCM, with a launch in type 1 diabetes, moving into phase III for diabetic neuropathy, and LX9851 in the hands of Novo Nordisk moving into phase II. Really exciting time for the company, Andrew. Great. Thank you very much and very helpful. Maybe starting with HCM, congratulations on completing enrollment very soon. Big picture, how would you position sotagliflozin here relative to CMI in both obstructive and non-obstructive? I appreciate non-obstructive, maybe there's only one CMI potentially in the market soon. Yeah The positioning. Well, look, we've talked about, in our company, we have what we've coined a lead to succeed strategy, and that is that we want to bring our medicines as either first-in-class or only-in-class to particular indications. As we mentioned, HCM has really evolved pretty rapidly because there's been attention from a number of companies, both approved agents in obstructive disease, and agents that are being investigated. All of these products really target the sarcomere. CMI and others that are being developed really focus on that interplay between actin and myosin. The difference with SOTA obviously being a dual SGLT1 and SGLT2 inhibitor is that it's focusing directly on cardiac energetics, on the myocardium. We're going to be playing alone in that space, which is important not only from a commercial perspective, but also from an ability to be used in combination with other therapies as well. From where we see SOTA potentially being used in obstructive and non-obstructive disease, I think, the benefit that SOTA obviously has is it's an oral once-a-day medicine with a known safety profile. So long as the KCCQ benefit is robust, that it makes a natural first-line agent, certainly in non-obstructive disease, where currently there are either no approved treatments, and we've obviously seen the outcome of ACADIA. In addition, also in obstructive disease to be used in combination or alone with CMI. Great. Just to add a couple points on that is that we believe that sotagliflozin, only sotagliflozin as a dual inhibitor of SGLT1 and SGLT2, are acting really in three subtype independent ways. The first is we're acting as a cardiorenal agent like an SGLT2 inhibitor, which reduces all of the preload issues and the fluid overload that occurs with all patients with heart failure regardless of the genesis of that heart failure. The second, and unique to SOTA, is it's acting primarily on cardiac energetics, unlike the CMI and the SGLT2s are not acting on the myocardium the same way because there are no SGLT2 receptors on the myocardium. The third, which again is unique really to SOTA and SOTA only, is there is a lot of data supporting the thromboembolic benefits of sotagliflozin and only sotagliflozin because patients that have HCM have very high rates, potentially, of thromboembolic events between both high rates of AFib and a very large left atria. We believe that the risk profile of this agent, we're acting across three very different areas, and in areas that are separate and distinct from the SGLT2 only inhibitors and from the myosin inhibitors. I see. Cardiorenal, myocardium MACE benefits, enabled by the SGLT1/2 mechanism, whereas other SGLTs only hit two. SGLT2. Correct. That explains it and your confidence. The question is what have you shown in other studies, indications, for instance, to prove this? Again, we have claims, and an indicated use for sotagliflozin under the brand name INPEFA for heart failure. Those studies also include reductions in stroke and MI. We show a 30% reduction in stroke and MI. The SGLT2 inhibitors do not show that benefit in their heart failure trials. There's a significant amount of both secondary analyses of our heart failure program in patients that have left ventricular hypertrophy without hypertension, showing a 50% reduction in heart failure events and a 50% reduction in MACE events, as well as a lot of mechanistic data now, both animal, in vitro, and human explant data across all of these range of benefits, including the cardiac energetic effects. Okay. That's why other SGLTs have not pursued HCM, whereas you can, basically. Well, I'm not going to say what other companies have chosen to do or not do. I can only focus. Yes What we're doing and why we're confident in our dual mechanism on the benefits. Great. In this phase III trial that reads out in Q1 of 2027, I think it's a 26-week study, over 500 patients. How did you power the study? What is statistically significant? You want to take that, Craig? Sure. Yeah. We powered that based on the feedback we had from cardiologists and experts in HCM. That's going to be similar to what the CMI have powered their trials at around a five-point difference in KCCQ score. The variance that we're assuming in that is similar to what the CMI have either powered for or have achieved in their clinical trials. I see. Success is driven by the overall population of both obstructive and non-obstructive? That's correct. Okay. Would you expect any kind of efficacy differential between the two subgroups? Again, based on our mechanism of action, we think it's going to be relatively independent of whether they have obstructive or non-obstructive disease because obstructive and non-obstructive disease have the same basic underlying physiologic problem. The obstructive group just has an additional anatomical issue of blood outflow. Again, even within the HCM group, there's a continuum of outflow tract obstructions, and there's not a great correlation of symptomatology necessarily in magnitude of the outflow tract obstruction based on gradient. The mix of patients, obstructive versus non-obstructive, is it 50/50? Is that how you've tried to stratify? What is the mix going to be? Yeah, it's not capped. Patients get enrolled as they get enrolled. I think we can expect that there'll be more non-obstructive, simply because there is an approved agent at the time of the trial in obstructive disease. Obviously at that time that we conducted enrollment for the majority of it, there's a much larger need in non-obstructive disease. We are yet to see what the exact balance is going to be like. We'll see that at the end of enrollment. We will present these baseline demographics as we come to a medical meeting so that people can get an understanding of what that balance looks like. Good. In terms of the regulatory pathway, you have confirmation from the FDA that one phase III is sufficient for both subpopulations or just a label for HCM broadly, and that KCCQ, your primary endpoint, is sufficient to support an approval. You don't need any co-primary endpoints to be clear? That's correct. Okay. Very good. Should this be approved, how do we think about price exactly? Yeah When we're talking sotagliflozin, INPEFA is technically approved here. Correct As the brand. How do you? No, it's a good question. Obviously we continue to do that work. You have a situation where mavacamten and aficamten are priced at a higher specialty tier level, INPEFA at a retail therapy level. We'll continue to do that work with HCM, and there are a number of ways that we will work to differentially price in hypertrophic cardiomyopathy. The proof point really is as we move forward with our Zynquista submission, because that's obviously further progressed, where we have a completely novel NDA, NDC, and a brand name and packaging, et cetera, under the brand name Zynquista. Our engagement with payers have been for a long time that we can price this at a premium to where we're at with INPEFA, completely separate populations, separate need, and that will be the proof point that we will rinse and repeat with HCM. Albeit, Zynquista will remain likely still at a sort of a retail-based price, because of the prevalence of the population. In HCM, it's a different story. That will be different, but the principles remain the same. Got it. Yeah. Yes. Do you intend to commercialize HCM yourselves? The same question applies to type 1 diabetes as well. Yeah, great question. We have prioritized our efforts squarely on HCM. I think as a company, we see that really as the top of our pyramid, the pointy end, so to speak, of this cardiometabolic strategy for the company. Clearly, a huge unmet need, but also the possibility of commercializing ourselves, in fact. We haven't made a determination, and we won't make a determination of that yet. We need to really look at the data once we have it. We are starting to prepare, in fact, for that possibility. We recently hired a number of MSLs who will start to educate physicians around the benefit of this dual SGLT1 and SGLT2 inhibition, which is really the leading edge of it. We are bringing a couple of commercial people on from an access and marketing perspective. We're doing the pre-launch preparation so that we can make that determination. Type 1 diabetes is a different situation, and we are engaged in thinking about partnerships here. I think that there's a number of companies that are pretty deep into type 1 diabetes, unlike in HCM where there's really a couple of companies. In type 1 diabetes, there's device and therapeutics companies that have a lot of expertise. That may allow us to really focus all of our resources into a potential HCM launch post Q1 2027. More to come on that, and yeah, we'll keep you posted in the not-too-distant future. Great. Yeah. Great. Shifting to type 1 diabetes Zynquista. Long story short, it's encouraging to hear you with the access to the open label data in real time around DKA safety rates. It sounds like it's within the bounds. What is actually the threshold of an acceptable DKA threshold or exposure, to be clear? Yeah. The end of review letter that came out from the FDA, which was made public as part of that divulgence of CRL documents, I think laid it out pretty clearly in the dialogue we've had with FDA has been consistent with that, is that they wanted to see a rate of diabetic ketoacidosis in a prospective set of patients that was at or below that which was seen in the inTandem program, which was around three and a half cases of diabetic ketoacidosis per 100 patient years. I think you can see based on that relatively low rate. That's why we needed a large sample set and a relatively long period of time to get that cumulative exposure to establish a point estimate and confidence interval around what is a reasonably confident rate of DKA in a prospective data set. I see. Just to give us a sense, Steno, is it 2,000 patients, but maybe a proportion of that are sotagliflozin patients, so how many patients? That's right, Andrew. The trial is a treatment algorithm study, so it compares an enhanced treatment algorithm in a group of patients that, depending upon their baseline characteristics, are going to be allocated after optimization of their A1c and their lipids to either sotagliflozin, semaglutide, or finerenone based on baseline characteristics. We believe that there'll be at least a third of those patients or more that will be on sotagliflozin, so that's 1,000 of the patients. The other 1,000 of the patients is standard of care with optimization of lipids and A1c, it's a five-year trial looking at rates of MACE. We actually have two trials that we're supporting looking at MACE outcomes, one in type 1 diabetes that we're using for STENO and another with a company called Cleerly. It's an imaging company also looking at plaque progression and stroke, which again goes back to the unique attributes of sotagliflozin acting on plaque and stroke and MI. Overall, there'll probably be around 300-400 patients on SOTA in the STENO trial, and they will be treated ultimately out to as long as five years. I see. Great. Sounds like you're on track to submit almost any day now if you're saying mid-2026. It's a six-month potential review is your expectation? That's correct, because it's a resubmission of new clinical data after a CRL. Okay. Then help us frame actually the market opportunity here. How many patients per year? Yeah, that'd be helpful. There's 1 million patients with type 1 diabetes in the U.S. We're focusing very much our efforts on the U.S. Outside the U.S., we've licensed sotagliflozin to Viatris outside of the U.S. and Europe. They are focused at the moment on heart failure but have the optionality to also launch it in type 1 diabetes. I think the market opportunity is large, both from a patient number, but again, you have to remember in type 1 diabetes as opposed to type 2 diabetes, they only have one thing to treat their hyperglycemia, and that's insulin. In type 2, of course, there are many different compounds, this will be the only product that is being promoted for the control of hyperglycemia in type 1 diabetes. We're doing that forecasting work at the moment, but it's a significant opportunity. Yeah, I'll just frame it just from a medical standpoint. Only about 20% of patients are at their A1C goal in type 1 diabetes. Despite pumps, despite all of the technology, about 20% of patients are at their A1C goal. More importantly to patient wellbeing and long-term benefit, though, is probably a concept called time in range, where they're within a certain glucose boundary. The ideal is around 70%-80% time in range of a day, and the average patient today is no more than about 50%-60%. In this regard, Zynquista would be the first and only agent ever indicated beyond insulin for glycemic management in type 1. We think that is going to be seen very favorably. We know that already from the patient community and the physician community about the desire and want for this drug. Yeah, if you don't mind me piling onto that as well there, Andrew. If you remember at the AdCom that we had towards the end of 2024, there was an open public forum, as there is in all AdComs, and there were over 140 submissions from the community, and they were unanimously supportive of sotagliflozin's Zynquista being approved in type 1 diabetes. I've been in this game a long time. I haven't seen, and I've had many AdComs, as many submissions or the uniformity of response. Really, that's been the case from the community, which is unsurprising, again, given the sort of relatively poor options that folks with T1D have for glycemic control. Really with that in mind, we are very much focused on bringing this to market, and one of the benefits that Zynquista has upon launch is, in fact, the unaided branded awareness. If you're a commercial person, you always want, what's the unaided branded awareness when I launch? It's very high. Why is that? Because we've been talking about it now for a while, and so we would expect that once we do get the approval, in fact, the launch uptake is very promising. Okay. Yeah. In terms of the IP, because this applies to both HCM, I think, and type 1 diabetes. Yeah What's the current IP? Should you be approved, is there a way actually to extend the IP on an approval? Yeah. The composition of matter is 2033 for the molecule. There's a number of different options specific to HCM. The first being, there's of course, if we explore this, there's the opportunity for orphan designation, which brings some regulatory coverage. Importantly, we have built and continue to build a suite of IP, particularly around left ventricular hypertrophy and HCM as more and more data and the richness of this differentiation of SGLT1 comes to bear. We will continue to support that with further IP that has the potential to extend beyond 2040. Two, actually three late-stage programs. There's pain too. Correct. Non-dilutive capital. In the meantime, you're getting some from the Novo partnership for your obesity asset. Any color how much in milestones, actually, you could be receiving in the next 2026, 2027 timeframe? Yeah. No. As you know, and we mentioned upfront, we've had two tranches of $10 million from Novo, because of the submission of the IND and the commencement of the single-ascending dose. We expect another $10 million from the commencement of the multiple-ascending dose later this year. Novo has indicated that they will move directly into phase II, when satisfaction from both of those studies, and that would mean another $60 million in the first part of 2027. We need to keep in mind additionally that Viatris is selling sotagliflozin in the UAE and expects a number of further approvals this year. While not necessarily of the magnitude of $60 million from Novo, that will also contribute to revenue over the course of 2026 and increasingly so in 2027 and beyond. Non-dilutive capital continues to flow into the company. Right. Lastly, on the pain program. Your phase III-ready sounds like you're exploring or entertaining some ways to fund this program. Yeah. Any further color on that? I think what we have learned over the time and what we've been able to do has helped us form our perspective on how to take this forward. I think the first thing, we were very much focused on partnering this with a strategic early on, because at that stage, we were thinking we would use that non-dilutive capital, the upfront payment from a partnership, to fund HCM and well beyond the data from HCM. That was very much our focus. Now, we had the opportunity and were somewhat opportunistic like that to raise close to $100 million earlier this year. That was fantastic, obviously, for the balance sheet, but also allowed us to reformulate our debt provisions and, in fact, switch lenders, which afforded us a lot more flexibility. It afforded us the potential for additional debt if we so desire. In addition to that, delayed our principal payment by a good 12 months out until November of 2027, and potentially even beyond that. That gives us a lot more flexibility from a cash runway. That negated the, if you like, somewhat urgency to partner it. At the same time, we learned that strategics in the pain space are willing to pay a significant increase, if you like, a significant premium on a phase III data set, at least to have phase III data. I think it's an area where not many strategics have a lot of clinical expertise, and so they're willing to really up the ante in what that deal could look like. That means that we would be doing both Lexicon and our shareholders a disservice in, if you like, going for second best. We have the opportunity, we think, via maybe a special-purpose vehicle or other types of programs to get capital that's not on our balance sheet right now. I want to make sure everyone's clear on that. We're not using any of our current capital to fund this program, but to do the phase III program, which is about $200 million, a little over. If we deliver significant phase III data, you can imagine on a drug that has a minimum of $4 or $5 billion peak sales potential, that the return on invested capital here is very significant. I think from those perspectives, it really behooves us to be very thoughtful and take that forward in a way that best creates value for the company. Makes a lot of sense. Well, I think that's all the time we have. I appreciate you sharing all the updates, best of luck on your milestones coming up. Thanks so much, Andrew. Thank you, Andrew. Take care, everyone. Bye-bye.