Sign in

You're signed outSign in or to get full access.

Lexicon Pharmaceuticals - Earnings Call - Q2 2025

August 6, 2025

Executive Summary

  • Revenue and EPS materially beat Wall Street: Q2 revenue $28.87M vs $4.87M consensus and diluted EPS $0.01 vs $(0.08) consensus, driven by $27.54M of LX9851 licensing revenue recognition; net product (INPEFA) revenue was $1.32M. S&P Global consensus used for comparisons.*
  • Management cut 2025 total OpEx guidance to $105–$115M (from $135–$145M), with R&D cut to $70–$75M (from $100–$105M) and SG&A maintained at $35–$40M, reflecting an R&D-focused repositioning and cost transfers to Novo under the LX9851 license.
  • Pipeline execution advanced: pilavapadin Phase 2b analyses support 10 mg dose for Phase 3 with partnership discussions underway; SONATA-HCM Phase 3 passed 100 sites across 20 countries; LX9851 IND-enabling on track for 2025 completion with Novo to file the IND; Viatris initiated ex-U.S. filings and reported first approval in UAE for sotagliflozin.
  • Near-term stock catalysts: full pilavapadin Phase 2 data presentation (Sept), additional SONATA site ramp to 130 by Q3-end 2025, incremental ex-U.S. sotagliflozin filings/approvals driving potential 2026 royalty streams; consensus revisions likely to reflect one-time LX9851 license recognition and lower OpEx run-rate.

What Went Well and What Went Wrong

  • What Went Well

    • Licensing-driven P&L inflection: Q2 revenue jumped to $28.87M (from $1.65M YoY) with $27.54M recognized from the Novo LX9851 agreement; net turned positive ($3.25M) vs $(53.43)M YoY.
    • Cost discipline: SG&A fell to $9.35M vs $39.19M YoY on strategic repositioning; OpEx cut and FY25 OpEx guidance lowered materially.
    • Pipeline momentum and partner leverage: “Partnership discussions for pilavapadin are underway…,” SONATA-HCM site initiations >100 across 20 countries; Novo collaboration progressing with IND enabling on track; Viatris progressing global filings/first UAE approval for sotagliflozin.

  • What Went Wrong

    • Commercial softness: INPEFA net product revenue of $1.32M declined vs $1.62M YoY amid significantly reduced U.S. marketing; U.S. sales remain modest.
    • Non-recurring revenue mix: Q2 topline and profitability depended on LX9851 license recognition ($27.54M), a one-time driver; $17.5M remains to be recognized in H2 as obligations are completed.
    • Continued cash drawdown: Cash/investments fell to $139.0M (plus $29.0M restricted) from $194.8M at 3/31/25 and $238.0M at 12/31/24, reflecting severance and operations despite debt reduction steps.
View the full earnings report

Transcript

Speaker 2

Welcome to the Lexicon Pharmaceuticals second quarter 2025 financial results conference call. At this time, all participants are in a listen-only mode. Following management's prepared remarks, we will hold a brief question-and-answer session. As a reminder, this call is being recorded today, August 6, 2025. I will now turn the call over to Lisa DeFrancesco, Senior Vice President, Investor Relations and Corporate Communications for Lexicon Pharmaceuticals. Please go ahead, Lisa.

Thank you, Josh. Good morning and welcome to our second quarter 2025 conference call. Joining me today are Dr. Mike Exton, Lexicon Pharmaceuticals' Chief Executive Officer and Director, Dr. Craig Granowitz, Senior Vice President and Chief Medical Officer, and Scott Coiante, Senior Vice President and Chief Financial Officer. This morning, Lexicon Pharmaceuticals issued a press release announcing our financial results for the second quarter of 2025, which is available on our website at www.lexpharma.com and through our SEC filing. 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 press release, provide a corporate update, and then use the remainder of our time to answer your questions.

Before we begin, let me remind you that we will be making forward-looking statements, including statements related to the safety, efficacy, clinical development, regulatory status, and therapeutic and commercial potential of Pilocarpine, LX-9851, Sotalflozin, and our other drug programs, as well as our business generally. These statements may also include characterizations and projections relating to the clinical development, regulatory status, and market opportunity for our drug programs, and the commercial performance of M-PEPA for heart failure. This call may also contain forward-looking statements relating to our growth and future operating results, discovery and development of our drug candidates, strategic alliances, and intellectual property, as well as other matters that are not historical facts or information.

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?

Speaker 0

Yes, thank you, Lisa, and good day, everyone. Thanks for joining. We're really excited to give you updates on the quarter and all of the great work going on at Lexicon Pharmaceuticals. When we entered 2025, if you recall, we're still in the early days of our strategic pivot to being an R&D-focused company. Now, in the second half of the year, I can say that this transformation has truly taken shape. We've made great strides against our objectives for the year across the board. We're now in a very strong position to advance our innovative portfolio of potential medicines. I'm pleased to report that all of our lead R&D programs continue to be on track. We've made important progress against each of them in the second quarter, which I'd like to highlight briefly.

For Pilocarpine, we've completed the secondary analysis of our phase IIb progress results following the announcement of top-lining data in the first quarter. We're now in the process of analyzing the totality of phase II data, which supports the broad potential for this novel mechanism, while re-engaging in discussions with potential partners with this additional data in hand. Secondly, LX-9851, our first-in-class candidate for the treatment of obesity, is on track to complete IND-enabling studies in 2025. We look forward to continued collaboration with our licensee, Novo Nordisk. For Sotalflozin, we've really hit the accelerator on our phase III Sonata HCM trial in hypertrophic cardiomyopathy, or HCM, which is the only phase III HCM program enrolling currently, evaluating Sotalflozin in both obstructive and non-obstructive subtypes of HCM. We've made excellent progress on site initiations globally, and Craig will elaborate on this shortly.

Lastly, but importantly, we're also working closely with our licensee, Beatrice, on expanding the reach of Sotalflozin in territories outside of the U.S. and EU, and we're making great progress on that front as well. In summary, the team's hard at work, and it was an incredibly productive quarter for us that I'm very proud of. Now, before I turn the call over to Craig to talk in detail about the great progress in the pipeline, I want to take a moment to acknowledge a milestone. July marked one year since I joined as CEO of Lexicon Pharmaceuticals, and as I reflect on all the changes that we've seen in that 12 months, I'm truly proud of the dedication and adaptability of this team. We've successfully advanced multiple programs to late-stage development and beyond, and we look forward to reporting even more progress to come.

On that note, I'd like Craig to give a more detailed update on our pipeline program. Over to you, Craig.

Speaker 2

Thanks, Mike. I'll start by discussing Pilocarpine. First quarter, we announced top-line results of our phase IIb PROGRESS study of Pilocarpine in DPMP. DPMP is a chronic and progressive pain disorder that impacts approximately 30% of people with type 1 diabetes and up to 50% of those with type 2 diabetes. These patients experience burning pain, loss of sensation, and other side effects that can severely impact their quality of life. Importantly, in both our phase IIb PROGRESS study and our phase IIa RELIEF study, Pilocarpine 10 mg delivered consistent, clinically meaningful reductions in these painful symptoms. Based on these data, we have concluded the 10 mg dosage strength warrants further evaluation and is the appropriate dose to take forward into late-stage development. We recently convened a scientific advisory board with expertise across clinical development, regulatory, and neuropathic pain to review the full body of evidence for Pilocarpine in DPMP.

This esteemed group provided encouraging feedback and validated our key findings from the top-line data readouts, including the following: First, the advisory board confirmed that Pilocarpine demonstrates clinically meaningful efficacy. Second, they confirmed the 10 mg dose is the appropriate dose for future registrational studies. This gives us clarity on our path forward and validates the dose-finding work we've done to date. Third, the board reaffirmed the safety and tolerability profile of the 10 mg supports advancement into late-stage development. Finally, they provided validation and valuable input into phase III study design, including suggestions to potentially lower the placebo response rate, which we believe could reduce potential study variability. The panel support gives us tremendous confidence as we prepare for our next steps and engage with potential partners for Pilocarpine.

It reinforces our belief that we have a potentially transformative therapy for the millions of patients living with this debilitating condition. I also wanted to acknowledge that our analysis of the Pilocarpine development program supports its compelling value proposition with a validated mechanism of action of AAK1, compelling clinical profile, and broad potential applicability across multiple indications, and demonstrates why we believe Pilocarpine represents a true portfolio and a pill opportunity. Overall, beginning with efficacy, Pilocarpine has demonstrated consistent and clinically meaningful pain reduction across three separate phase II trials in neuropathic pain. While our lead indication in DPMP represents a mature clinical development program that is ready for phase III advancement, several secondary indications, such as spasticity, are also phase II ready, providing significant pipeline expansion opportunities. In addition, our preclinical work has been extensive.

We've completed IND-enabling studies across multiple neuroscience indications, both central and peripheral, establishing a broad foundation for further clinical development beyond our current focus areas. We've accumulated data from more than 600 patients treated with Pilocarpine to date, demonstrating a suitable safety and tolerability profile. This extensive safety database will be valuable as the program moves into late-stage development and regulatory discussions. Finally, Pilocarpine benefits from patent protection extending through 2040 when including an anticipated five-year patent term extension. This provides substantial commercial exclusivity to maximize the value of our investment in this area. Moving on to Sotalflozin in HCM, there are more than a million people with HCM in the U.S. Of those, our previous research suggests approximately one-third have non-obstructive HCM and two-thirds have obstructive HCM, in which the thickening of the heart muscle wall blocks or reduces the blood flow to the heart.

However, more recent technology, including a more sensitive diagnostic and AI-assisted tools, suggests that the incidence of non-obstructive HCM could be much higher, potentially 50% or greater. This chronic progressive disease can lead to more serious complications. 43% of patients with HCM have progressive heart failure, and HCM can also lead to atrial fibrillation and stroke. The medical community's understanding of how to diagnose and treat HCM has grown significantly in recent years, as there are a number of innovations in development for HCM, including the approval of cardiac myosin inhibitors for obstructive HCM. However, despite substantial commercial investment and increased awareness of HCM, CMIs have only penetrated approximately 1% of the total HCM market. With this treatment landscape in mind, we believe Sotalflozin offers several unique advantages as a potential therapeutic option for HCM.

First, it has a novel MOA as a dual mechanism SGLT1/SGLT2 inhibitor and is the only HCM agent under investigation that works both inside and outside the heart. This enables treated patients to potentially achieve symptom reduction while simultaneously targeting other outcomes such as heart failure and major adverse cardiovascular events, where Sotalflozin has demonstrated benefits. Second, as more data is generated, it is becoming increasingly clear that Sotalflozin is uniquely myocardial targeted. From a practical standpoint, the once-daily oral dosing profile facilitates broad clinical adoption, convenience, and compliance. Importantly, this comes without the burden of a risk evaluation and mitigation strategies or REMS requirements that can complicate treatment. It is worth noting that Sotalflozin is already approved for heart failure. To date, we've observed no increased risk of atrial fibrillation, which is a critical consideration in this patient population.

Looking forward, we're pursuing a broad proposed indication that encompasses both non-obstructive and obstructive HCM phenotypes. This positions Sotalflozin for potentially either use as monotherapy or in combination with other agents, providing clinicians with valuable flexibility in treatment planning. We have amassed a wealth of data from studies confirming Sotalflozin's mechanism of action in HCM and related conditions summarized here. Specifically, the animal models studied demonstrate Sotalflozin improves cardiac function and reduces wall thickness, left ventricular mass and fibrosis, and cardiac inflammation, while the ex vivo models demonstrated the direct effects of Sotalflozin on the myocardium by reducing both stroke work and increasing metabolites associated with improved cardiac energetics. Collectively, these studies provide evidence that Sotalflozin has a unique ability to work across multiple markers of the disease.

Now, I want to spend some time talking through the current ongoing clinical program, beginning with our own phase III Sonata HCM study of Sotalflozin in HCM. Sonata HCM is a large global registration trial with a KCCQ primary endpoint designed to support a regulatory filing and broad label in HCM. Sonata HCM is the only ongoing registrational trial currently evaluating a treatment in both obstructive and non-obstructive HCM. We have recently surpassed 100 sites initiated in 20 countries, including the U.S., Europe, Israel, and Latin America, and we're well positioned to meet our goal of 130 sites actively enrolling patients by the end of the third quarter of 2025. There are two important investigator-initiated studies underway that are designed to evaluate cardiac function of Sotalflozin in HCM. The first is SOTA-PCARDIA being conducted by Dr.

Juan Bottoman and colleagues at the Mount Sinai School of Medicine in New York City. This study is designed to investigate the cardiorenal mechanistic benefits of Sotalflozin in 88 non-diabetic patients with HFpEF, which, as you recall, is a subset of HCM. It is a six-month study comparing Sotalflozin 400 mg and placebo on the following endpoints: change in left ventricular mass, functional performance, and quality of life measurements. This study was completed in July 2025, and the investigators are currently evaluating the data. The second study I wanted to highlight is SOTA-CROSS, a 12-week crossover study funded by the NIH and being conducted by Dr. Charlene Day at the Penn School of Medicine, comparing Sotalflozin and placebo on exercise capacity, physical activity, symptoms, and diastolic function in patients with symptomatic non-obstructive HCM. We already have shown that Sotalflozin strongly improves diastole in HFpEF.

SOTA-CROSS will aim to specifically ascribe such functional benefits in non-obstructive HCM as well. Together with the Sonata HCM trial, this study could potentially be a major therapeutic advance for a large subset of patients who have limited treatment options. Last but not least, we remain on track to complete the IND-enabling studies this year for LX-9851, our first-in-class ACSL5 inhibitor for the treatment of obesity and related metabolic disorders. LX-9851's oral administration, preclinical findings to date, and possibility for both monotherapy and combination applications provide a compelling profile and the potential to occupy a unique space in the treatment landscape. We look forward to working with our partner, Novo Nordisk, to maximize the potential of this innovative investigational medicine. With that, Scott Coiante, our CFO, will now provide a report of our financial results for the second quarter.

Speaker 4

Thank you, Craig, and good morning, everyone. For the second quarter of 2025, we reported $28.9 million in revenue, compared to $1.6 million for the second quarter of 2024. Q2 2025 revenue consisted primarily of $27.5 million of licensing revenue recognized from the Novo Nordisk agreement. As a reminder, we received the upfront payment of $45 million from Novo Nordisk in April, which was initially recorded as deferred revenue and is being recognized as revenue throughout the remainder of 2025 as the IND-enabling work is completed. Total revenues for the quarter also include net product revenue of $1.3 million from sales of INPEFA. Research and development expenses for the second quarter of 2025 decreased to $15.7 million from $17.6 million in Q2 2024, primarily reflecting lower external research expense on our PROGRESS clinical trial study, partially offset by increased investment in our Sonata HCM phase III clinical study.

Selling, general, and administrative expenses for the second quarter of 2025 decreased to $9.4 million, compared to $39.2 million in 2024. The decrease reflects lower costs as a result of our strategic repositioning announced in late 2024 and the significantly reduced marketing efforts in 2025 for INPEFA. Net income for the second quarter of 2025 was $3.3 million or $0.01 per share, as compared to a net loss of $53.4 million or $0.17 per share in the corresponding period in 2024. The net income for the quarter was primarily a result of the revenue recognized from the Novo Nordisk licensing agreement in Q2. We expect to recognize the remaining $17.5 million of licensing revenue from the Novo Nordisk agreement in the second half of this year as the IND-enabling work is completed.

We ended the second quarter with $168 million in cash, short-term investments, and restricted cash, as compared to $238 million as of December 31, 2024. In summarizing our financials, I would like to note a few highlights from the quarter. We've used the $45 million upfront payment received from the Novo Nordisk licensing agreement to strengthen our balance sheet by reducing a portion of our long-term debt. On the expense side, we've made significant progress reducing our costs and streamlining our operations. Quarter-over-quarter operating expenses decreased by $31.9 million, primarily due to the strategic repositioning as an R&D-focused company announced late in 2024. Reviewing our full-year 2025 guidance, we're lowering our operating expense projections for the year. Total operating expenses are now expected to be in the range of $105 million to $115 million, from $135 million to $145 million previously announced.

R&D expenses are now projected to be in the range of $70 million to $75 million, down from a range of $100 million to $105 million, primarily as a result of the transfer of costs to Novo Nordisk under our licensing agreement with them. SG&A expenses remain between $35 million and $40 million. Our R&D expense assumptions do not include costs associated with phase III pivotal studies of Pilocarpine, as our goal will be to take this asset forward with a development partner. Overall, we are in a strong position with the resources we need to advance our ongoing clinical programs while maintaining a disciplined approach to capital allocation and a focus on creating value for our shareholders. Now, I'll turn the call back to Mike for closing remarks.

Speaker 0

Yeah, thanks, Scott and Dr. Craig Granowitz. Now, as you.

Speaker 2

Please stand by. Your conference will resume momentarily. Please stand by. Your conference will resume momentarily. Please stand by. Your conference will resume momentarily. Please stand by.

Speaker 0

Apologies for that brief interruption when I'm getting to the punchline here. Let me go back and say that we've got lots of exciting updates in the second half of 2025. Clearly, as we've outlined, partnering is an essential part of how we plan to advance all of our assets. On this slide, it really highlights the partnership strategy and action. Firstly, Beatrice is making great progress and has recently received its first approval of Sotalflozin in the United Arab Emirates, which was a really short turnaround time, and has also filed for regulatory approval in Saudi Arabia and is expecting to file for regulatory approval in Canada, Australia, New Zealand, Mexico, and a number of Southeast Asian countries before the end of this year.

We aim to maximize the potential of LX-9851 with our licensee, Novo Nordisk, a global expert in obesity and related conditions, and partnership discussions are ongoing for Pilocarpine, where we hope to collaborate with a high-quality partner to unlock the pipeline and the pill potential of this asset globally and across multiple indications. This flexible partnership strategy is intended to allow us to follow the science broadly, but really remain focused internally on our core cardio-metabolic expertise. As you can see on this slide, we're exceptionally well positioned with a number of pipeline opportunities, from our late-stage assets to our newest opportunities, and whether organically or with a partner, we expect these programs to continue to add value and bring new innovation to patients over the longer term. As we look further into 2025, we're excited about where Lexicon stands at this moment.

Starting with Pilocarpine, we're expecting full progress data to be presented in Q3. We're also planning our end of phase II meeting with timing to be dependent on our partnership discussions. Our preclinical work to broaden the value of this asset into additional indications continues, and additionally, a broad partnership for Pilocarpine will allow us to become therapeutically focused on our core cardio-metabolic programs and expertise. For Sotalflozin in HCM, our Sonata HCM trial is making excellent progress. Sites in the U.S., EU, Israel, and LATAM are currently enrolling, and we expect all phase III sites to be running by Q3. We also expect results from certain investigator-initiated studies of Sotalflozin as early as Q4 of this year, which could provide valuable additional insights to the body of data on this therapeutic candidate. For M-PEPA, Beatrice is continuing to handle regulatory submissions and approvals outside the U.S. and EU.

They've been really a fantastic partner, fully engaged and motivated, and we expect that these approvals will build significantly on the stabilized sales of M-PEPA in the U.S., where my team has achieved by a strong mix of focused execution and innovation. For Zynquista, the end-of-review evaluation process is underway. As you've no doubt seen, there's been an outpouring of patient support advocating for the approval of Zynquista in type 1 diabetes, and we're committed to pursuing all potential avenues for this program. Last but not least, LX-9851, our IND-enabling studies for obesity are progressing really, really well, with a target completion by the end of the year. If you look across this pipeline, any of these programs have the potential to transform patient lives and create significant value for Lexicon Pharmaceuticals.

We believe that the simultaneous advancement of all five programs makes our position very compelling as we move through 2025, where we have a significant amount of opportunities for success. With that, we conclude our introductory remarks and turn it to you, operator, for some Q&A.

Speaker 2

Thank you. As a reminder, to ask a question, please press star one-one on your telephone and wait for your name to be announced. To withdraw your question, please press star one-one again. One moment for questions. Our first question comes from Yasmeen Rahimi with Piper Sandler. You may proceed.

Hi, this is Liam Ahn for Yasmeen Rahimi. Great presentation this morning. We just were really impressed by the SOTA-CROSS trial that's upcoming with potential data mid to late 2026. We were just wondering maybe if you can kind of walk us through, given the small sample size of the study, what are the doses being assessed and how much the inclusion/exclusion criteria resembles Sonata, and in that vein, whether you expect to see a static separation on the efficacy endpoint and also why non-obstructive HCM was selected rather than an obstructive HCM patient population.

Speaker 0

Yeah, thank you, Liam, for the question. We're really excited about working with Dr. Day on this NIH-supported mechanistic trial. I think the idea behind the NIH's interest in this was to continue to look at therapeutic options outside the CMIs that would be much more widely applicable and more readily implementable across the U.S. for this large unmet medical need. Non-obstructive HCM, I think, was also the target for the NIH grant because there are options available for obstructive. There are surgical options and now medical options, but there are no treatment options that have been approved for non-obstructive. The relative small size of the study belies its significant power to accomplish its goals. By having a crossover design, you use the patient as their own control in the study, and the study has a number of important diagnostics, both imaging and physiologic outcomes.

The inclusion criteria is very similar to that in the Sonata HCM trial, which is a very broad cross-section of patients without diabetes who have a non-obstructive HCM. The only difference is that in SOTA-CROSS, there's not an allowance for patients on a CMI, but in Sonata HCM, there actually is. Sonata HCM is even more broadly applicable. We believe that if you look at all of the data together in its totality, and what we try to do really as we think about lifecycle management strategically is to look at the totality of the benefit of Sotalflozin both mechanistically, imaging, and clinically across a range of heart failure, MACE, and HCM, using different trials to look at different aspects.

One of the reasons we presented all three of Sonata HCM, SOTA-CROSS, and the SOTA-PCARDIA study is that they are looking at different aspects of the physiology and clinical findings of patients with HFpEF and HCM.

Thanks so much.

Speaker 2

Thank you. Our next question comes from Andrew Tsai with Jefferies. You may proceed.

Hi, good morning. Thanks for the updates and thank you for taking my questions. A couple of questions on pain. Recently, RFK Jr. mentioned how he wanted to promote the development of non-opioid pain drugs like Vertex, Zanaflex. Is there something you guys can do to take advantage of this new development? Could it, for instance, make sense to apply to the Commissioner's National Priority Voucher program? Thanks.

Speaker 0

Yeah, thanks, Andrew. In fact, my team has been very actively engaged from a legislative perspective, particularly with the Alternatives to Pain Act, which is the act that's supporting the use of non-opioid medications in chronic pain. We've been really supporting the utility and the passing of that particular act. We're seeing bipartisan support for this very important facet of the management of pain. In addition to that, like we have done with type 1 diabetes, it's also patient advocacy groups that are very compelled to get new treatments. All of those things are just a factor for, I think, what is really a zeitgeist in the realization that, particularly for chronic pain, actually, even though there are new alternatives for acute pain, the real issue for non-opioid alternatives lies within the realm of chronic use over many years, where the addictive potential is clearly much more significant.

We're very encouraged by the bipartisan enthusiasm in this area. We think that as we progress Pilocarpine into phase III and then beyond, this not only gives great support for continuing to develop Pilocarpine, but importantly, once it achieves commercial reality, clearly it provides a pathway for great access and ease of patients getting onto this non-opioid medication.

Thank you. It sounds like you will have the FDA meeting by year-end now. In theory, in that meeting, to you guys, what would be the realistic, quote-unquote, "worst-case scenario" that can arise from that meeting?

Yeah, thank you, Andrew. It's Craig. I can answer your question. I mean, it actually is validating hearing other companies talk about what their pain program phase III approach is in DPMP. As you recall, we have already met with the FDA on this program. I think their feedback is going to be very similar to what we've already heard from them. I think what other companies have also acknowledged is that you're going to need two parallel studies in the lead indication for neuropathic pain. It is highly unlikely that with a single indication or a single study in two indications that you could get a broad neuropathic pain indication. That was always our expectation. That was affirmed by the FDA. That was affirmed in our ad board. I think it's been affirmed by other companies that are out there.

When you think about the timing of our program and the magnitude of our program, I think it remains pretty much unchanged to what it was. It would be two parallel trials in DPMP, potentially with different geographies or slightly different designs, but primarily the same primary endpoint of a pain score at week 12. I think based on all the data we've seen across the totality of our program, we think that the size of those studies to appropriately power them is very similar to what we've already been communicating to you of two arm studies of roughly 600 patients each with a single active arm and a placebo-controlled arm.

Thank you.

Speaker 2

Thank you. Our next question comes from Caroline DePaul with Jefferies. You may proceed.

Hi, this is Caroline on for Yogal and Dr. Novitz. We'd like to know, what is Novo's plan for the phase I in obesity? Are there plans to combine with GLP-1?

Speaker 0

I think, in our discussions with Novo Nordisk, I really wanted to thank our entire team for really having a great collaboration with Novo Nordisk. I think as you've heard in the marketplace and I think you've seen from both Lilly and Novo Nordisk and other companies that the market is going to be moving towards oral options and combination options. I think the data that we've already demonstrated and that presented on the use of LX-9851 as an oral once-daily agent or the expectation of that, both with semaglutide and other agents that are being studied in development for weight loss and the potential for triple combinations. I think you've seen other companies talking about moving both to oral and triple combinations. I think LX-9851 is really rightly positioned to be a part of that set of development programs.

If I could just provide one comment over the top of that. We've been really blessed with both of our partners, with our licensees, with Beatrice and Novo Nordisk. The enthusiasm and capabilities that they bring to bear for both of these assets are really stellar. Although obviously Novo Nordisk is undergoing some changes at the moment, our engagement and interaction and their enthusiasm and drive for this asset is unbridled, so to speak. It's really incredible to see the team in action. We expect that Novo Nordisk will attack the phase I program with vigor shortly after the IND.

Speaker 2

Thank you. Our next question comes from Joe Pantginis with H.C. Wainwright. Right, you may proceed.

Hey, everybody. Good morning. Thanks for taking the questions. A couple, if you don't mind. First, it's a housekeeping question. With regard to the operating expense guidance, does this include or not include stock-based compensation?

Speaker 0

It does include stock-based compensation.

Great, thank you. A couple of comments here have been coming up about the end of phase II meeting for Pilocarpine. Just curious how you feel, you know, that that's still on track, but more specifically, do you feel this is the ultimate rate-limiting step for your partnering plans?

I don't think it's a rate-limiting step, Joe. I think what has been our approach here is to have the initial round of discussions with partners with the top line, helping them understand. Now, two important things have happened. We have, A, completed the secondary analyses from PROGRESS, or three important things, I would say. Completed the secondary analysis where bringing the totality of the phase II program data to bear so that we understand the totality of evidence. Most importantly, or perhaps most importantly, we've convened the scientific advisory board. You know, we won't sort of go into who the people were, the members of that advisory board, but I can assure you these are the top, top people that have been involved in this space from a regulatory development and mechanistic perspective for some time.

Having their endorsement of, as we theorized all along, straight from the top line of 10 milligrams being the appropriate dose to move forward into phase III really gives us confidence not only internally, but to re-engage in those discussions and start to progress the discussions to a more concrete basis over the coming months. I think how we approach the end of phase II meeting will be sort of dependent on now the engagement from partners around whether they want to be a part of that, whether they want to sort of see the outcome and move forward. We're progressing that at speed.

Totally fair. Thanks. Just quickly on HCM, I don't know if Dr. Craig Granowitz would want to give any color on this. I think it's been a pretty impressive ramp on the number of sites that you have. Just curious, as you're looking to really ramp up enrollment as well, are there any comments from the field with regard to, you know, views towards CMI or CMI competition for patients or what have you? Even though, you know, you have a different profile of where Sotalflozin might fit.

Yeah, great question, Joe. I'll answer that sort of in two very different ways. The first is that we have this open window of enrollment. There are no active ongoing registrational trials now in HCM. The fact that Odyssey ended, in a sense, without a long-term extension, there's a fair runoff period in that trial from what we understand. Those patients are also available with no treatment options. We really have a nice golden opportunity here from an enrollment standpoint as you have a lot of sites with available patients that are symptomatic, both obstructive and non-obstructive, whether they're on a CMI or not, that can be included in the trial. In that regard, I think that's been a real upside.

The interesting aspect, actually, when you think about enrollment, and I think this is what you're seeing already with some of the companies that are marketing products in obstructive HCM, is there seems to be a speed limit in the capacity of the field to start new patients on CMIs because of the echoes. While we do not require multiple echoes during treatment, unlike the CMI studies or CMIs themselves, we do require a baseline echo. Scheduling echoes is an issue for enrollment, at least in the U.S. It is interesting to see that flow through from the commercial market. In the U.S., I would say the very early enrollment, and again, we're just looking at blinded data, but we know that whether patients are obstructive or non-obstructive, there are more non-obstructive patients being enrolled currently in the U.S.

than obstructive, which is to be expected because one of the CMIs is already approved and on the market in the U.S. There are no options available at all for the non-obstructive. In the U.S., we're seeing more non-obstructive than obstructives, but we think that's going to rapidly shift ex-U.S. because the CMIs are largely not available outside the U.S. Joe, what I hear over the last sort of three to six months speaking with KOLs is a couple of things. One, they're becoming more and more aware of Sotalflozin and HCM. I think that's twofold. One, we're progressing Sonata, and that enrollment is going nicely. Two, there's obviously been noise in the marketplace, particularly around non-obstructive and conjecture around, you know, will Applicantum be successful? They see, because of some of the other evidence that we have with Sonata, that this could be a real option for non-obstructive.

They’re enthused about the possibility of that. More broadly, sort of having worked in this space with Entresto and understanding that general cardiology practices across the country have HCM patients, have HFpEF patients, and the potential to have one medicine that can potentially treat both very significantly without sort of fear or favor, is really compelling beyond the academic sites into the general cardiology practices where, as you know, actually the vast majority of HCM patients are being treated.

Appreciate it. Thanks a lot.

Speaker 2

Thank you. As a reminder, to ask a question, please press star one-one on your telephone. One moment for questions. Our next question comes from Ali Mohammed with Leerink Partners. You may proceed.

Yep. Hi, everyone. This is Maisie on for Rowana. Just two from us, but I guess the first one is, given Vertex's recent announcement about their VX-993 and its inability to meet its primary endpoint in the phase II, how does that, I guess, impact your confidence in the overall pain market and the ability to conduct a careful phase III trial? I guess the second one, just to follow up to what you just said. I noticed that you mentioned that there's going to be an echo for every patient when they start the trial. Is that something that you would expect if approved as well into the market? Would it be something that you would expect commercially that they would have an echo before being started on the drug?

Speaker 0

Yeah, great couple of questions. Please pass on our best regards to Rowana. I hope it's all going well with the bub. Let me take a first go with the pain question and Vertex. Obviously, we followed their earnings yesterday. I think, in fact, that gives us even greater confidence in our own program. Why is that? We've now shown three times across phase II programs in neuropathic pain that we can separate from placebo with a 10 mg dose. We, I think, have always been a little bit skeptical of NAV1.8, particularly in neuropathic pain. I think the evidence in acute pain, despite 993's results yesterday in post-bunionectomy, are not reading out positively.

It allows us confidence in our program and having a novel mechanism of action compared to the number of companies that are now pursuing NAVs, which, you know, really the evidence is mixed, one would have to say, apart from acute. Certainly in neuropathic pain, the evidence is mixed at best. Actually, it's probably pretty much not great, so to speak. It's one of those instances where being on a novel MOA with proven efficacy really, we think, is something that we appreciate and gives us confidence moving forward. Importantly, partners will appreciate as we sort of go back and have this next round of discussions. Craig, any other thoughts on that?

Speaker 2

Yeah, Mike, I think that was well said. I think just scientifically, there are a couple of important points. I don't want to draw undue attention to another company's communications, but they did demonstrate or they communicated that with 993, they did get more exposure with more dose, and they had no additional efficacy. I think that the question is, there is certainly a ceiling on the effect of NAV 1.7 to mitigate pain. I think that's also reflective of the fact that they're looking at developing combinations of NAV 1.7 and 1.8, which presupposes that they're looking for more efficacy. I think that's an important point. As Mike said, in neuropathic pain, the NAVs have not demonstrated separation from placebo. They've demonstrated similar drops in pain score compared to pregabalin. As we know, pregabalin doesn't always separate from placebo in the pregabalin registration trials.

That's the whole issue around placebo effect. I think those are just a couple of additional comments. I think it also reaffirms from a regulatory standpoint that you're going to need to do two separate trials in a pain indication to seek approval. I think those were some important findings that we had from what we heard the other day. Switching gears on the echo, I don't think that's going to be a major impediment. All these patients are going to be getting an echo regardless. I think a lot of the issues in HCM, frankly, are related to the echoes because of the fact that CMIs reduce ejection fraction. I think we don't have that issue, right? We're a drug that treats heart failure, whether you have low ejection fraction heart failure or normal ejection fraction heart failure.

I think part of what's going on in the HCM field has been modified by the level of the agents and the fact that the current agents that have either been approved or under study actually have a negative inotropic effect on the heart by their very design. Because of that, getting an echo and following ejection fraction closely is a very important safety signal, which is the basis of the REMS that exist. I think FDA will probably label our drug the way that we studied it, that there'll be an echo. I think that the requirement or the necessity of the echo from a patient suitability standpoint might be less with Sotalflozin, even though following the echo and following ejection fraction in patients with symptomatic heart failure is sort of standard of care today anyways, at least in the U.S.

Great. Thank you, guys.

Thank you. I would now like to turn the call back over to Dr. Mike Exton for any closing remarks.

Speaker 0

Thank you very much for joining, everyone. Thank you for the questions, folks. I really appreciate those. I've done a number of these quarterly earnings calls since I've been here. In the last couple, we've had some major announcements with data readouts, with a refocus on strategy. All of those have been very important announcements. I think so far in my short tenure here, this is probably the quarter that I'm most proud of, mostly because of two things. One, the team has really driven all programs in parallel to the point of their next stage of catalyst, to their next sort of inflection point, to their next natural development. Importantly, we've done so in a way where we've really focused our resources and are allocating capital in a way that's really focused on adding value for us and all stakeholders.

Both of those things have resulted in a quarter where the pipeline has advanced dramatically. We've done so revising the outlook for expenses for the year, mostly because of LX-9851, but some of it due just to looking at all of our expenses and making sure we're spending wisely. I couldn't be prouder of the team. Looking forward to Q3 as we go through a number of important developments over the next three months and updating you all then. Thank you very much.

Speaker 2

Thank you. This concludes the conference. Thank you for your participation. You may now disconnect.

View Q2 2025 Earnings Summary