Lexicon Pharmaceuticals Inc (LXRX) 2024 Q4 法說會逐字稿

Welcome to the Lexicon Pharmaceuticals fourth quarter 2024 financial results conference call. (Operator Instructions) As a reminder, this call is being recorded today, March 6, 2025.

I will now turn the call over to Lisa DeFrancesco, SVP, Investor Relations and Corporate Communications for Lexicon. Please go ahead, Lisa.

Thank you, Gigi. Good afternoon, and welcome to the Lexicon Pharmaceuticals fourth quarter and full year 2024 financial results conference call. Joining me today for prepared remarks are Dr. Mike Exton, Lexicon's Chief Executive Officer and Director; and Scott Coiante, Senior Vice President and Chief Financial Officer. Dr. Craig Granowitz, Senior Vice President and Chief Medical Officer, will also join us for Q&A.

Earlier this afternoon, Lexicon issued a press release announcing our financial results for the fourth quarter of 2024, which are available on our website at www.lexpharma.com and through our SEC filings. A webcast of this call, along with the slide presentation is also available on our website.

During this call, we will review the information provided in the release, provide a corporate update and 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 safety, efficacy, clinical development, regulatory status and therapeutic and commercial potential of pilavapadin, LX9851, sotagliflozin 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 INPEFA for heart failure. This call may also contain forward-looking statements related 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?

Great. Thanks, Lisa, and good afternoon, everyone. Thanks for joining the call. Look, we've had a busy start to 2025 already, including our announcement on Monday of top line results from our PROGRESS Phase IIb study of pilavapadin in diabetic peripheral neuropathic pain, or DPNP. But as we take a moment to look back and reflect on 2024, I'm immensely proud of the resilience and adaptability of the team in keeping our pipeline of novel medicines moving forward and advancing our lead to succeed strategy.

Last year, we strategically repositioned Lexicon to focus the company and its resources on our clinical development programs and some key highlights from these programs included the early completion of enrollment for our PROGRESS study, great progress in our pivotal Phase III SONATA-HCM study of sotagliflozin in hypertrophic cardiomyopathy, or HCM, where we continue to enroll patients as planned, advancing IND-enabling studies of LX9851 in obesity and related cardiovascular disorders.

And lastly, we reinvigorated our business development efforts, including a significant licensing agreement with Viatris for sotagliflozin outside of the US and Europe. Now I want to begin today's overview with our most recent significant development. On Monday, we issued a press release and held a conference call to discuss the top line results for PROGRESS, the Phase IIb dose-finding study of pilavapadin, our oral non-opioid drug candidate for DPNP.

Now the two most important takeaways from our top line announcement this week are: first, in all doses in the PROGRESS study, including placebo, we observed a clear separation in ADPS from baseline with the 10-milligram dose also showing meaningful improvement compared to placebo; secondly, all pilavapadin treated arm showed improved tolerability when compared with our previous RELIEF-DPN study. Indeed, the 10-milligram dose of pilavapadin showed particularly better tolerability as compared to RELIEF.

And for these reasons, we successfully achieved our corporate objectives for progress with the 10-milligram dose. And so, these data in combination with the data from the RELIEF study give us greater confidence in the potential of pilavapadin to be the first novel oral non-opioid DPNP medication in more than two decades, and we're moving forward with a 10-milligram dose. As you can see in this slide, pilavapadin 10 milligrams performed strongly, improving ADPS at week 8, reducing it by 1.74 points from baseline.

Now as we continue to analyze the data, there are already signals that give us even greater confidence to advance the 10-milligram dose into pivotal trials. Pooling the two arms that utilize 10 milligrams, the 10-milligram dose plus the 10 plus the 20 plus 10 arm, this post-hoc analysis shows an approximately 0.6 ADPS reduction versus placebo as early as week 2, which is maintained throughout the treatment period. Interestingly, while the pain reduction curve of the placebo arm appears to flatten out in the last 4 weeks of the trial, the 10-milligram dose continues to consistently reduce ADPS scores, suggesting that in pivotal trials of 12 weeks duration, further separation may be achievable.

Furthermore, as we outlined on Monday, the 10-milligram dose was well tolerated. In progress, as many patients with 10-milligram pilavapadin as with placebo completed the trial, conclusively ascribing the tolerability performance in the previous RELIEF study to the day one tenfold loading dose.

This gives us confidence in the tolerability of 10 milligrams of pilavapadin in Phase III trials. We continue to analyze further data and look forward to presenting the full findings from the PROGRESS study at a future medical meeting. So now I want to talk about what pilavapadin can potentially mean for patients. DPNP is a large and growing condition that impacts approximately 9 million people in the US It's a chronic and progressive pain disorder that severely impairs people's quality of life with the majority of patients experiencing moderate to severe pain.

When we speak with patients and physicians, it's truly devastating to hear how it impacts their everyday life, their ability to sleep at night, their mental health and their relationships. DPNP can also lead to loss of sensation, loss of balance, falls and fractures and a wealth of other complications. But importantly, currently available treatments simply don't provide adequate relief. It's estimated about 60% of patients have tried multiple therapies and only 1/3 are somewhat satisfied with their treatment. In our market research, we heard numerous HCPs and patients report an immense need for new treatment options and in particular, a simple, easy-to-use non-opioid treatment options for DPNP.

And finally, with about 1/3 of DPNP patients still resorting to short-term opioid use for pain relief, even today, when we know the potentially devastating effects of these treatments, this space is primed for reform. HCPs, legislators and policymakers via initiatives such as the Alternative to Pain Act (sic) Alternatives to PAIN Act provide tailwinds to support movement towards new non-opioid options. Next, I'd like to discuss LX9851, where we are continuing to advance IND-enabling studies. LX9851 is our first-in-class oral ACSL5 inhibitor for the treatment of obesity and related cardiometabolic disorders. In November, we presented clinical in vivo efficacy data from two studies related to LX9851 at ObesityWeek.

The first study showed the treatment with LX9851 resulted in significant reductions in weight, food intake and fat mass in diet-induced obese mice and that LX9851 mitigated weight regain following discontinuation of the GLP-1 analog semaglutide. The second study characterized the novel mechanism of action of LX9851 and how it activates the ileal brake to induce satiety and lower desire for additional food consumption.

We remain on track for an IND submission for LX9851 in 2025 as we evaluate potential partnership opportunities for this innovative mechanism. So now I want to briefly touch on the current status of sotagliflozin. We have a significant potential opportunity to expand our label in hypertrophic cardiomyopathy, a disease state with high unmet need that impacts about 1 million patients in the US

We're currently enrolling SONATA-HCM, a global pivotal Phase III study, including patients with both obstructive and nonobstructive HCM. Upon completion of the HCM study with additional evidence and data in hand, we will revisit the totality of the sotagliflozin asset potential in the US In terms of what we're doing today, though, as we bridge to this future opportunity, as you can recall, we made the necessary decision to cease all promotion of INPEFA in the US for heart failure due to the difficult market access environment dominated by two major SGLT2 inhibitors.

Currently, sotagliflozin is available on the US market with our continued commitment to maintain awareness and provide tools to support patients in an extremely cost-effective approach. Outside of the US and Europe, we're actively working with our exclusive licensee, Viatris, on supporting their efforts towards registration and regional development. Our medical affairs, data generation and publication activities remain ongoing, and we continue to engage with the scientific community through numerous investigator-initiated third-party funded studies to build upon our compelling body of medical evidence in CV conditions and outcomes and support sotagliflozin as a differentiated inhibitor of both SGLT1 and 2.

Now to that end, I wanted to briefly acknowledge a notable recent publication in The Lancet Diabetes & Endocrinology, which highlighted the effects of sotagliflozin to reduce major adverse cardiovascular events or MACE, myocardial infarction and stroke among patients with Type 2 diabetes, chronic kidney disease and high cardiovascular risk.

The findings show that sotagliflozin significantly and meaningfully reduces MACE versus placebo, demonstrating early and broad cardiovascular protection in this population. This research also highlighted that sotagliflozin is the only SGLT inhibitor to show significant reductions in both MI and stroke, indicating the potential role of SGLT1 inhibition in reducing ischemic events, an important distinction from selective SGLT2 inhibitors.

As I shared just a moment ago, this supports our goal of demonstrating differentiation of sotagliflozin and presents compelling additional support as Viatris on regulatory submissions in key ex US and ex European markets throughout 2025.

I'll now turn it over to Scott to walk you through our financial results for the quarter and the year ended December 31, 2024.

Thanks, Mike. Lexicon ended 2024 with $238 million in cash, cash equivalents and short-term investments as compared to $170 million as of December 31, 2023. As noted in this afternoon's press release, we reported $26.6 million in revenue in the fourth quarter and $31.1 million in revenue for the full year 2024. Revenues for INPEFA were $1.7 million in the fourth quarter of 2024 and $6 million for the full year 2024. Total revenues for both the fourth quarter and full year include an upfront payment of $25 million received in connection with the Viatris licensing agreement.

Research and development expenses for the fourth quarter increased to $26.7 million from $14.8 million in the fourth quarter of 2023. Full year 2024 research and development expenses increased to $84.5 million in 2023, primarily due to our investments in Phase II and Phase III clinical trials, including the SONATA Phase III study of sotagliflozin in HCM and the PROGRESS Phase IIb study of pilavapadin in DPNP.

Selling, general and administrative expenses for the fourth quarter of 2024 were of $32.3 million were comparable to the $32.6 million of SG&A expenses in the fourth quarter of 2023. Full year 2024 SG&A expenses increased to $143.1 million from $114 million in 2023. This increase in 2024 reflects higher marketing costs related to the commercialization of INPEFA and increased employee salaries and benefit costs prior to the reduction in our field sales force in late 2024, as well as severance costs associated with our strategic repositioning.

Net loss for the fourth quarter of 2024 was $33.8 million or $0.09 per share as compared to a net loss of $49.8 million or $0.20 per share in the corresponding period in 2023. And net loss for the full year 2024 was $200.4 million or $0.32 per share in 2024 as compared to a net loss of $177.1 million or $0.80 per share for the same period in 2023.

During 2024, Lexicon took steps to first reduce and then to eliminate all promotional efforts for INPEFA. These included a significant reduction of employees and elimination of all promotional efforts for INPEFA in heart failure in the US We believe these steps will reduce operating expenses moving forward.

For 2025, we expect total operating expenses to be in the range of $135 million to $145 million. We expect research and development expenses to be in the range of $100 million to $105 million and G&A expenses to be in the range of $35 million to $40 million. Research and development expenses include costs associated with the ongoing development of sotagliflozin for HCM, preparations for the Phase III development of pilavapadin and preclinical costs associated with preparations for the IND filing of LX9851.

Research and development expenses for 2025 do not include the costs of pivotal Phase III trials for pilavapadin as the size and scope of these trials will be determined as part of our end of Phase II review discussions with the FDA.

I'll now turn it back to Mike for closing remarks.

Yeah. Thanks, Scott. And look, in summary, we've got a full and exciting year ahead. The work we did in 2024 really set the foundation, and we look forward to updating you all as the year progresses. For pilavapadin, we've got a number of important upcoming catalysts, including disclosure of the full progress data set, the end of Phase II meeting with the FDA and data presentations at upcoming endocrinology and pain-focused medical meetings.

In addition to the important upcoming milestones we discussed today, we're also very actively engaged in partnership discussions that will enhance our clinical and commercial capabilities and help us maximize the potential of all of our novel therapies. This will be a critical focus for the company in the coming months.

And so, with that, Scott, Craig and I have time to take all of your questions. So I'll turn it back to you, operator.

(Operator Instructions)

Joseph Stringer, Needham & Co.

Hi, thanks for taking our questions. From us, want to ask on the 9851 oral obesity asset and kind of the clinical development plan there. A couple of questions on that. Is that only being considered as a combo therapy with, say, a GLP drug? Or is there an option for monotherapy? And then what are the potential indications and/or trial designs that you're thinking of for an initial Phase I?

And then lastly, if a decision is made to ultimately partner that program, how much clinical data do you think you need to generate before it would make sense to engage or turn it over to a potential partner?

So, Joey, it's Craig. I'll answer the first two questions and probably turn it back over to Mike for the third. We really see this molecule as being developed both as monotherapy and combination therapy, monotherapy alone or monotherapy after discontinuation of an injectable or other GLP-1 agonist knowing with the data that's come in with the injectables at least that a vast majority of patients don't remain on therapy for more than a year. In fact, the median duration is somewhere between 6 and 12 months. So what we've demonstrated in the animal models is, the activity of the drug is independent and additive on top of semaglutide, even maximum dose semaglutide.

And if you withdraw the semaglutide and then add the 9851 that you largely maintain the weight loss, whereas if you don't add the 9851, weight returns very quickly to baseline, which is also situation in patients. So we see that there's an opportunity in both mono and combination therapy. The second question on the clinical program. I think the Phase I program is going to be pretty standard. What we've communicated before is, we have a few critical goals that would be a part of the Phase I clinical program.

First and most importantly is, do patients actually lose weight similar to what we see in the animal models. The second is, the tolerability of the therapy because, again, you always have to wonder in these treatments. The question is, will it be well tolerated, especially with the novel mechanism of action like ileal brake. We haven't seen anything in the animal models to suggest that would be an issue with tolerability, but that would be an important component. And the third is to demonstrate that there is a clear mechanistic differentiation from the GLP-1 mechanism.

So I think those would really be the three critical goals that we've certainly thought about in running the Phase I program. And I'll turn it back over to Mike for the last part of your question.

Yeah, no. Thanks for the question. And as you could imagine, with a completely novel and orthogonal mechanism to the GLP-1 and incretin-based mechanisms, there's a number of companies that have not only been interested in this particular asset, but have engaged in the data over the last months. We've been talking to a number of players. And what it would take to move into a partnership from a data perspective is really quite varied.

And we're prepared if we do have the right partner with the right conditions at any particular time to move into partnership because ultimately, we believe that this program is best served with a partner to really capitalize on the breadth of indications, again, with the potential for indications beyond obesity, as well as the commercialization of this particular mechanism ultimately. So that's where we're at with 9851 and potential partnering opportunities.

Great thank you so much for taking our questions.

Yasmeen Rahimi, Piper Sandler.

Hi, this is Tina on for Yas. My first question is, could you kindly provide some color on how enrollment is progressing into your SONATA study and when you expect enrollment completion? And with that, how soon could you engage with the FDA for the end of Phase II meeting for pilavapadin and start planning for Phase III? And finally, what are some of the rate-limiting steps to complete for the IND filing for 9851, which was previously discussed?

Great. Three great questions on 3 different programs. I'll let Craig have a stab at those.

Yeah. Thanks, Tina. I'll answer them in order. On the HCM program, we've been really pleased by the feedback we've gotten. We've had a number of investigator meetings, both in the US and outside the US We focus first and initially on opening sites in the US.

We've communicated that we're targeting about 30 sites in the United States, 120 sites overall with a target enrollment of about 500 patients, 250 each stratified for obstructive and non-obstructive. I can say that we've made outstanding progress in getting all the government approvals necessary to have those conversations in countries outside the US, and we have sites open in non-US countries right now.

Again, we have not been forthcoming with exactly what those are, but we can say that we are opening sites on plan. We have patients that are actively in screening and actively in treatment today, similar to the time lines we've set. The time lines I think we've talked about is that, we're looking to have final study results towards the end of '26, which means that we would be filing with the FDA probably sometime in the first quarter of '27. Those are our current time lines. Obviously, it's early days in the trial, but those are the time lines that we've put forward, and there's nothing at this point that we think is going to be significantly changing those time lines at the moment.

So if that, Tina, answers your questions on HCM, I'll move forward to pilavapadin. For pilavapadin, we've communicated -- I'm sorry, I didn't mean to cut you off. For pilavapadin, we're really, as Mike mentioned, and I think we mentioned in the call on Monday, we're really looking to get down to the FDA and have the end of Phase II meeting sometime in the second half of this year with the possibility of starting Phase III -- the Phase III program before the end of 2025.

Obviously, that will be dependent on a number of other factors, but those are the time lines that we feel comfortable at. And just to reiterate what Mike said is that, we are more confident than ever in that 10-milligram dose as being the right dose and that the PROGRESS study really clarified the open issues that we had going into the study about what is the best dose to go into Phase III, balancing both safety and efficacy and do you need the loading dose or not.

So we feel quite strongly positive now to move to the end of Phase II, publish the data this year and then move into Phase III. On 9851, we've mentioned, and I think Mike talked about that our plan is to have all of the IND-enabling studies done this year to get down to the FDA and have that meeting and be ready to start the first-in-human studies before the end of the year. That's the time lines that we continue to track to. We're doing all of the IND-enabling studies right now. We had to do the dose finding from the animal studies to do the final toxicology studies that are required as part of the standard IND package, and we're working actively against those targets.

Thank you so much.

Joe Pantginis, HC Wainwright.

Hey everybody, good afternoon. Thanks for taking the questions. Two questions, if you don't mind. So for pilavapadin data that you just put out, sort of a looking forward question. Craig on the call earlier said some broad strokes as to what the Phase III program might look at look like. Can you discuss anything right now with regard to what you feel might be the key open questions and/or wish list that you might have going into the FDA meeting? And, of course, they could absolutely change tomorrow.

Yeah. Joe, great question. I think we mentioned perhaps at least in passing on Monday, some of the critical things that we're going to look at as we get the final data set in. A couple of them we've really talked about some of the key secondary endpoints that we think are most meaningful to patients, as Mike talked about, is particularly sleep interruption and burning pain. So those are going to be important endpoints that we want to take a look at as we get the full data set in.

Another one that we believe is pretty important to look at is the use of the acetaminophen rescue protocol. As you remember from RELIEF, that correlated really nicely with response that there was much greater and earlier use of the acetaminophen rescue in the placebo arm than in the active arm. And we feel comfortable that those three particularly are going to be important elements that will be consistent or hopefully consistent with the primary endpoint data that we shared and we're certainly consistent in the RELIEF study.

I think the other area that we have an interest, and I know a number of people that have asked have interest is, what was the response regardless of the underlying single DPNP medication use. And as a reminder, in RELIEF, we demonstrated activity independent from the underlying DPNP medication and on top of the DPNP medication.

So I think that is going to be another important question because I think going into Phase III, if we could demonstrate we have activity both with or without underlying DPNP medication use, I think that will be very important for patients, health care providers and payers to know. We'll also continue to look at some of the additional safety parameters in reference to DPNP use, looking at that in some of the demographic factors.

As I think we mentioned, there were some notable differences in the demographics, particularly the representation of Black Americans in the trial was nearly doubled. So we will continue to look at some of those factors as well. I hope that wasn't too long a list, Joe.

No, no, that's fantastic. I appreciate that color. And then just quickly, I guess, a financial logistical question, if you will. Just wanted to make sure, have the INPEFA onetime charges worked through the system already? Or should we expect any for the first quarter?

Joe, it's Scott. No, I would say that it's a safe assumption that all the costs were accrued certainly accrued as of the end of the year.

Perfect, thanks for all the color guys.

Andrew Tsai, Jefferies.

Hey, thanks. Good afternoon. Appreciate all the updates. Maybe two questions on pain on my side. For the upcoming FDA and a Phase II meeting, could it make sense to ask them if this Phase IIb counts as a supporting pivotal? And by extension, do you have a base case or upside case internally? And then secondly, at this juncture, do you think you would be powering the Phase IIIs to what you saw in the Phase IIa or the Phase IIb for the 10 mg dose?

Yeah, Andrew, thanks for the question. Certainly, that would be an upside in our current scenario planning of having this trial be counted as a pivotal. We would see it counting strongly as a supportive trial, but our base assumption would not be that this was a pivotal trial. And I think as we've previously shared, our current thinking, which obviously will be impacted by FDA is that, we'd be looking at two pivotal trials going into the Phase III program, each one of which would have roughly 300 to 400 patients in size. And to your question, we would probably power it similar that we powered both of these current trials for the statistics of a 0.6 drop on a placebo-adjusted basis.

And I wanted to reaffirm one of the points that Mike made in passing is that, we demonstrated in the PROGRESS study that at the 10-milligram dose, the pain scores continue to decline at a linear rate that was really consistent from week 3 on. So you saw a sharp drop in the first couple of weeks. And then the slope of the curve changed but remained pretty consistent from week 3 or so to week 8. We don't see any reason why that would particularly mitigate between week 8 and week 12. And if you sort of straight line that out, we think that, that pain score is going to continue to significantly drop.

If you look at the placebo and what has traditionally been seen in pain studies with placebo is that, that tends to plateau at somewhere between 4 and 8 weeks. And you can already see hints of that in this trial and in the RELIEF trial that the plateau, that the placebo is beginning to plateau. So we feel quite confident or comfortable that, that wedge, that growing wedge of difference from the placebo in pain score to the drug will continue to grow between week 8 and week 12 and that, that 0.6 drop is something that we think is we can comfortably achieve.

Thanks appreciate it.

Thanks, Andrew.

Roanna Ruiz, Leerink Partners.

Hi, this is, Mazion from Roanna. I just, we just had two commercialization questions kind of around sotagliflozin and HCM. So for one, what are your thoughts around partnership and commercialization for that asset? And it's kind of a 2-parter. And the second part being, how does that differ across different regions where CMI use may be impacted in countries in Africa and Asia, I think that we are seeing that use is a lot less. And so, I just kind of wanted your insights around that, please.

No. Great question. So firstly, for HCM ex US and ex Europe, that is entirely licensed to Viatris, our sotagliflozin partner. So if you like, rest of world, Viatris and we're closely connected with them to help them in the registration process, et cetera, for HCM, as well as the other indications.

For the US and -- well, for Europe, I think we've mentioned before, we don't have any intention in expanding our presence and certainly not our commercial presence outside of the US So we would be seeking a partner for Europe where there is a pretty substantial CMI use, as you know. And then it comes to the US And really, we feel we've got the expertise and capabilities to commercialize HCM, sotagliflozin for HCM.

And as we've mentioned before, it's going to be a very different payer situation for HCM as the first and only SGLT inhibitor approved for HCM to what we see for INPEFA in heart failure. And so, that will provide us with a much different potential commercialization trajectory. Now, one interesting and final aspect to that commercialization approach is, unlike the CMIs, and I think this will continue, both with currently approved and future approved CMIs, that will be used in a pretty focused way in centers of excellence that treat HCM patients. General cardiology see HCM patients and are able to diagnose. And the SGLT as a class is very well-known by general cardiologists.

And so, really, there is an opportunity although we certainly see ourselves playing a significant role commercially in the US, there may be other partnering opportunities as we move forward. But we will hold a very significant, if not, sole approach to commercializing that in the US

Oh great. Okay. Actually, to follow up on that then, as we think about the baseline characteristics for SONATA, are there any targets for the amount of patients that could be on background beta blocker CMI therapy?

Great question, Mazi. We have not put limitations on any baseline or background therapy. We took a very similar approach to what we did with the SCORED and SOLOIST trials, where we included all patients with heart failure in those trials regardless of whether they are HFrEF or HFpEF. In this trial, we're taking all patients that remain symptomatic as defined by a baseline KCCQ score. So they can be on any underlying medication, including a CMI in that regard.

And what we really care most about is that, they have an adequately low KCCQ score at baseline. That's really the major criteria. As a reminder, also, the ejection fraction that we allow is an EF down to 50%. So I think the opportunity to include both obstructive, non-obstructive background therapies that exist, including CMIs and an EF down to 50%, as well as having the primary endpoint as KCCQ, the secondary endpoint is New York Heart and no requirement for all of the echoes that the CMIs require that has all of the other physiologic testing, the peak VO2 and others that really make it very difficult to enroll those trials and limit the number of centers in those trials, we believe that our trial offers a number of different upsides in that regard.

Very helpful. Thank you all for the added color.

Yeah, thanks man.

Thank you.

At this time I would not like to turn the conference back over to Mike Exton for closing remarks.

Well, thanks everyone for joining us this afternoon. It was, great to have you all here and, give you a complete update across, the three pretty significant programs that we have, for solos and for Philliapin and LH9851. We've got a busy quarter ahead of us, and, really look forward to updating you as we progress throughout the quarter and indeed throughout the year. So, thank you very much, operator, and, see everyone later.

This concludes today's conference call. Thank you for participating. You may now disconnect.