Earnings Call Transcript - LXRX Q2 2024

Operator, Operator

Good day and welcome to Lexicon Pharmaceuticals Second Quarter 2024 Financial Results Conference Call. All participants will be in a listen-only mode. After today's presentation, there will be an opportunity to ask questions. Please note this event is being recorded. I would now like to turn the conference over to Lisa DeFrancesco, Head-Investor Relations and Corporate Strategy. Please go ahead.

Lisa DeFrancesco, Head of Investor Relations and Corporate Strategy

Thank you, Betsy. Good afternoon, and welcome to the Lexicon Pharmaceuticals second quarter 2024 financial results conference call. Joining me today are Dr. Mike Exton, Lexicon's new Chief Executive Officer and Director; Jeff Wade, President and Chief Financial Officer; Tom Garner, Senior Vice President and Chief Commercial Officer; Dr. Craig Granowitz, Senior Vice President and Chief Medical Officer; and Dr. Alan Main, Executive Vice President, Innovation and Chemical Sciences. Earlier this afternoon, Lexicon issued a press release announcing financial results for the second quarter of 2024, which is available on our website and through our SEC filings. 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 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, relating to the safety, efficacy, clinical development, regulatory status and therapeutic and commercial potential of INPEFA, Zynquista, LX9211, LX9851 and our other drug programs as well as our business generally. These statements may include characterizations and projections relating to our commercial launch of INPEFA in heart failure, as well as the clinical development, regulatory status and market opportunity for all of our drug programs. 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 that 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 Exton, CEO

Thanks, Lisa, and good day everyone. Thanks for joining us on the call. Before we begin our discussion on Lexicon's results for the second quarter of 2024, let me start by saying that even in my first few weeks here as CEO, I can already see what a tremendous opportunity we have to bring innovative new therapies to patients, transform the treatment landscape of multiple therapeutic areas, and indeed transform Lexicon as a company. Now moving on to our accomplishments for the year, which are indeed incredibly significant. First of all, our INPEFA business continued to grow modestly. We saw progress across all areas of focus in this highly competitive market. Importantly, we also resubmitted our NDA for Zynquista and have received a PDUFA goal date of December 20, 2024, setting us up for a potential commercial launch in this untapped market in early 2025. Furthermore, our Phase 3 study for Sotagliflozin in hypertrophic cardiomyopathy is underway, with sites already open and beginning to enroll patients. In addition, our Phase 2b study for LX9211 in diabetic peripheral neuropathic pain is on track to meet its timelines and objectives with top-line data anticipated in the second quarter of 2025. Finally, our exciting novel drug candidate LX9851, an oral therapy for obesity and weight management, which we believe has the potential to become an innovative next-generation treatment in this large market, is progressing into preclinical development. These are all really solid opportunities for Lexicon, not only for next-generation projects, but well beyond. So let's take a look at Sotagliflozin in particular. We see a significant opportunity for value and growth with this compound across additional indications where Sotagliflozin's unique mechanism of action has potential for beneficial effect. Lexicon has taken a purposeful approach in each area that we're exploring, and as a result, we're now preparing for the next near-term opportunity to commercially launch Zynquista for glycemic control in adults with type 1 diabetes and chronic kidney disease while working towards a longer-term goal of expanding Sotagliflozin into HCM. In both of these areas, there are no SGLT therapies indicated and we believe that the dual inhibition of SGLT1 and SGLT2 offers unique advantages. These areas of unmet need are also highly concentrated in terms of treatment landscape, and they're very different from the competitive environment we're experiencing in heart failure, which currently is dominated by two larger players within a complex treatment and reimbursement environment. These are really very exciting near- and long-term opportunities for Lexicon, and as we advance this pipeline of current and potential indications for Sotagliflozin, we'll continue to weigh and consider where this unique innovation can have the most impact for patients. So with that overview, I'd like to now turn it over to Jeff Wade, President and COO, to discuss in detail the business and financial results. Over to you, Jeff.

Jeff Wade, President and CFO

Thank you, Mike. I'd like to begin with our INPEFA results. Net sales for the second quarter of 2024 were $1.6 million, and $2.7 million for the first half of 2024. We saw improvements in filled TRx and number of new prescribers, a modest expansion in access and greater pull-through. This progress is due to the strong efforts of the team assembled by and aligned under Tom Garner since he had joined the company last year. Achieving better market access remains the key to more significant growth for INPEFA in heart failure. Our goal has been and remains to achieve formulary access that is favorable for patients and equitable in light of INPEFA’s value, and we are continuing to have discussions with payers driven by INPEFA’s value and differentiating data. Payer coverage improved slightly in the second quarter to 48%. Although most of this coverage still requires step through of competing therapies, an obstacle that we're focused on eliminating. Some payers have been taking longer to make coverage decisions due to uncertainties associated with the IRA, particularly around the prices to be announced by CMS on September 1 for the first group of products selected for negotiation, a group that includes three major heart failure medications. We expect improvements in coverage as these uncertainties are resolved and as we continue to demonstrate the value of INPEFA for patients, providers, and payers. It's important to note that SGLT use remains highly underpenetrated in heart failure, with significant room for growth. Despite strong recommendations within the ACC treatment guidelines and consensus statements for both HFrEF and HFpEF, based on substantial INPEFA data, especially related to initiation of therapy after hospitalization. I'd now like to move to Zynquista, which has the opportunity to be the first-ever oral adjunct to insulin therapy indicated to improve glycemic control in adults with Type 1 diabetes. Our approach with Zynquista is part of our overall strategy to expand the use of Sotagliflozin beyond the competitive heart failure market into high-value opportunities where other SGLT inhibitors are not indicated and in which we believe Sotagliflozin’s unique SGLT1 mechanism offers advantages. We've made a lot of progress this past quarter and in the time since. We resubmitted our NDA for Zynquista in June as an adjunct to insulin in adults with Type 1 diabetes and CKD. The FDA notified us in July that they considered our resubmission to be a complete response to their 2019 action letter, and they gave us a PDUFA goal date of December 20, 2024. Based on our recent communications with FDA, it is likely we will have the opportunity for an advisory committee meeting. We look forward to the chance to present and discuss with the committee and key stakeholders, including, importantly, the patient community, the opportunity for Zynquista to address the significant unmet need for adjunctive glycemic control in this population. From our preliminary market research, we expect more than 400,000 adults in the U.S. with Type 1 diabetes and chronic kidney disease could be eligible for treatment. We've seen strong enthusiasm for an improved adjunct to insulin among the concentrated group of endocrinologists who manage treatment decisions in Type 1 diabetes. From our payer research, we expect the market access environment to be considerably more favorable in Type 1 diabetes than in heart failure. Our opportunity to be the first adjunct to insulin therapy in a market where patients are highly engaged and an indication that is not subject to extensive management are all important factors for achieving favorable and timely market access. We believe that Sotagliflozin’s unique dual SGLT1 and SGLT2 mechanism offers advantages in addressing the challenges in people who have Type 1 diabetes and chronic kidney disease. Both are relevant to Type 1 diabetes, but the inhibition of SGLT1, the primary transporter for glucose uptake from the GI tract, offers particular benefits. SGLT1 inhibition slows the uptake of glucose from meals, blunting post-prandial glucose peaks and reducing glycemic variability. And unlike SGLT2 inhibition, the effects of SGLT1 inhibition do not decline with reduced renal function that characterizes chronic kidney disease. The focus of our NDA resubmission on people with Type 1 diabetes and chronic kidney disease aligns both with a population where better glycemic control is more important and also with Sotagliflozin’s unique mechanism of action. We believe that the greater benefit in this population weighs favorably against the increased risk of diabetic ketoacidosis, or DKA, that has been observed in clinical studies of all SGLT inhibitors, including Sotagliflozin in Type 1 diabetes. We are pleased to say that we have initiated our pivotal Phase 3 SONATA trial for HCM with the opportunity to transform the standard of care in this area of high unmet need. We are leveraging outcomes data from our SCORED Trial in heart failure, KCCQ data from SOLOIST, and other evidence, providing a strong scientific rationale for the potential of Sotagliflozin in this indication. This slide shows the design of SONATA HCM, a pivotal, Phase 3, placebo-controlled study with a targeted enrollment of 500 patients with obstructive or non-obstructive HCM. We have sites up and running and have commenced patient recruitment in the study. The primary endpoint of the study is change from baseline in KCCQ score, an endpoint that has been accepted by the FDA as the primary endpoint in this and other label enabling HCM trials and with which we have previously achieved success in our SOLOIST heart failure trial. Importantly, SONATA HCM is studying a broader patient population than that studied in other ongoing trials in HCM, as we are allowing patients to be on cardiac myosin inhibitors as well as allowing the use of beta blockers and calcium channel blockers. We are also enrolling patients with an ejection fraction down to 50%, which is lower than the studies of cardiac myosin inhibitors for which heart failure is a risk. Of course, Sotagliflozin is already indicated, as INPEFA to reduce heart failure, which is the major risk for these patients. We have obtained feedback from FDA that success in this single study could support a broad label for Sotagliflozin in HCM, once again an indication in an important area of unmet need that would be unique to Sotagliflozin among SGLT inhibitors. Current estimates suggest that around 1 million patients in the United States today have HCM. Many are not diagnosed, in part because of the non-specific nature of HCM symptoms, but diagnostic rates have been rising rapidly, a trend which is expected to continue over the next decade with increased focus on the disease. Looking further into our pipeline, we have LX9211, another opportunity to redefine the standard of care in an important area of need, in this case in neuropathic pain. LX9211 has the potential to be the first new non-opioid treatment for neuropathic pain in over two decades. Our PROGRESS Phase 2b dose optimization study began enrolling towards the end of 2023 and is well on track for top-line data in the first half of 2025. It is important to note that this study, like our proof of concept studies is placebo-controlled and allows patients to remain on stable dose standard of care therapy, rather than removing all pain medications, consistent with how DPNP drugs are likely to be used in real world practice. We learned a great deal in our Phase 2 RELIEF DPN study, which we are applying to this Phase 2b PROGRESS study with a key hypothesis being that we can improve tolerability by eliminating the 10x first-day loading dose in the prior study. At this point, we feel confident about where we are in this study and are very much looking forward to the results next year. Approximately 20 million patients in the United States are suffering with some type of neuropathic pain, of which about 5 million have DPNP, with significant growth predicted in the future. We believe LX9211 could offer a real benefit to patients and to the clinical community who are looking for better options to improve outcomes for patients with DPNP. Our newest drug candidate to emerge from our Genome5000 platform is LX9851 in the exciting area of obesity and weight management. We believe that LX9851 has the potential, like our other assets, to be developed in additional indications and to be used as a combination therapy as well. LX9851 is a small molecule inhibitor of the target acyl-CoA synthetase-5 that we believe could be given orally for chronic weight management with a target product profile that reduces body fat, spares lean body mass, and favorably affects overall metabolic profile. In preclinical studies, it has reduced cholesterol and triglycerides, improved insulin sensitivity, and demonstrated potential in additional related indications such as metabolic syndrome. The obesity and weight management space is an area of tremendous interest and we're very excited about the potential for an oral once-daily therapy with these mechanisms that complement and enhance current therapies. We've moved into IND-enabling studies and we are very focused on submitting data to upcoming medical meetings. Now we will review some of the key elements of our second quarter 2024 financial results. You can find more financial details in the press release that we issued earlier today and in our 10-Q that will be filed shortly with the SEC. We ended the quarter with $310 million in cash and investments. As indicated in our press release this afternoon, we had $1.6 million in revenues in the second quarter of 2024, almost all from net sales of INPEFA, and had minimal revenues for the same period in 2023. R&D expenses for the second quarter of 2024 increased to $17.6 million from $14.5 million for the corresponding period in 2023, primarily due to higher external R&D expenses as our development programs progress. SG&A expenses for the second quarter of 2024 increased to $39.2 million from $30 million for the corresponding period in 2023, reflecting the investment in the commercial launch of INPEFA. In total, net loss for the second quarter of 2024 was $53.4 million, or $0.17 per share, compared to a net loss of $44.9 million, or $0.22 per share, in the corresponding period in 2023. For the second quarters of 2024 and 2023, net loss included noncash stock-based compensation expense of $4.9 million and $3.8 million, respectively. Now I'll turn it back over to Mike for some closing remarks.

Mike Exton, CEO

Yes, thanks, Jeff. Look, in summary, the next 18 months for Lexicon includes several important planned catalysts. First of all, we've got the potential to launch Zynquista in the early part of next year, which for us is an exclusive opportunity and importantly, a much-needed additional treatment option for the Type 1 diabetes community. Secondly, we've initiated our SONATA Phase 3 study of Sotagliflozin in HCM, and that presents a new and promising area of focus. Thirdly, our PROGRESS Phase 2b study of LX9211 in DPNP is on track with top-line data in Q2 of next year. Finally, we've commenced IND-enabling studies of LX9851 in the rapidly evolving area of obesity and weight management, where current treatments are primed for next-generation and combination therapies. Each of these opportunities shares a common trait—they're all in large markets with significant areas of unmet need. Within each of these areas, we have the potential to be the first or only truly exclusive in our approach, unlike what we're experiencing in heart failure currently. Each of these opportunities is supported by thoughtful clinical development that is informed by discussions with the FDA and designed to incorporate real-world elements of how the drug would actually be used in the market. As we enter the back half of the year, we’re evaluating our strategy and resource allocation to ensure that we are optimized for success across these programs. We believe that over the next 18 months, we’ll have the opportunity to significantly improve treatment paradigms, transform Lexicon as a company, and create significant value for all of our stakeholders, most importantly including the patients that we serve. With that, I'd like to turn it back to the operator to open up the Q&A.

Operator, Operator

We will now begin the question-and-answer session. The first question today comes from Yasmeen Rahimi with Piper Sandler. Please go ahead.

Yasmeen Rahimi, Analyst

Great. Thank you so much, team, for all the updates. A few questions on Zynquista. Did you mention, I think it sounded like in the prepared remarks that you guys were preparing for an outcome? I guess, you could maybe talk about whether an outcome is expected, when it could occur, what could be possible topics? That’s sort of like big bucket one. And then bucket two is, if you could talk about commercially how you’re thinking about sort of, do you need to add more salespeople? Is there any – as you will be focused on patients that are under the care of endocrinologists, what would the launch trajectory look like in a more endocrinology-focused setting versus a cardiovascular focus? Would appreciate any color around that as well, and I’ll jump back into the queue for any other questions.

Mike Exton, CEO

Thanks a lot, Yasmeen. I heard two big buckets; not sure if you had a third, but let me pass the first one to Craig for the AdCom and what we’re thinking of timing and expectations, etc.

Craig Granowitz, Chief Medical Officer

Yes. Thank you for the question, Yas. At this point, we expect that we will get an AdCom from the FDA, and it really would focus on the risk-benefit of treatment. As I think we’ve shared at prior calls and at other meetings and communications that we’ve worked hard to find a population where the risk-benefit is more favorable. We currently are committed, and the FDA has been committed to our target action date of December 20 of this year. I think I’ll just take a moment on the risk-benefit— we believe that this group of patients with chronic kidney disease are at a much higher rate of disease progression to end-stage disease across a range of underlying diseases, such as end-stage kidney disease, heart failure, stroke, myocardial infarction, severe retinopathy, and other diseases. So glycemia is actually a marker for that. The indication we’re seeking, as a reminder, is a glycemic control indication with that group of patients with underlying chronic kidney disease. We’re not seeking an indication for preventing necessarily progression of chronic kidney disease, but that is a marker of patients that are going to have more rapidly progressive disease across a range of complications of type 1 diabetes. In that regard, we’ve gotten great feedback from the patient and physician community, and in prior communications from FDA, some of which were public, they acknowledged that insulin alone is not enough in type 1 diabetes patients. They’ve acknowledged that those who don’t have tight glycemic control are at risk of more rapid progression of disease. So we look forward to the opportunity, if there is an AdCom, to share all of this with both the FDA and the medical community.

Mike Exton, CEO

Great. Thanks, Craig. We feel very confident going into that AdCom and look forward to presenting all of our and independent data at that time. So I’ll throw the second question, the second big bucket to Tom, the Chief Commercial Officer, which really focuses on the commercial footprint for Zynquista and particularly around field force. Tom, if you could take that question.

Tom Garner, Chief Commercial Officer

Absolutely, yes. Thanks, Mike, and thanks for the question, Yas. As you’re well aware, we’ve spent significant amounts of time and effort really building a highly capable commercial infrastructure, and that crosses field sales, access, and going deep into patient support programs as well. Since I joined the company, I’ve taken time to ensure that we’re focusing all of our efforts in the right place on INPEFA but with the knowledge that Zynquista is probably going to be coming down the track at some point in the future as well. I think as you’re aware, this is going to be a somewhat more concentrated marketplace than what we see for heart failure. We estimate that there will be between 3,000 to 4,000 endocrinologists who treat the lion’s share of these patients. Given that existing infrastructure that we have, we currently have around 150 representatives for INPEFA, our plan is to leverage that team as far as possible to deliver on the value that we know we can unlock with Zynquista very quickly, while also ensuring that we continue to support INPEFA as needed.

Yasmeen Rahimi, Analyst

Thank you so much.

Mike Exton, CEO

Thanks.

Operator, Operator

The next question comes from Andrew Tsai with Jefferies. Please go ahead.

Andrew Tsai, Analyst

Hey, thanks. I appreciate you taking my questions. Maybe just on the AdCom, going back to the AdCom. Would it be safe to presume that you’re preparing for hypothetical voting decisions or questions around the risk-benefit and as well as a risk mitigation strategy of Zynquista, or is there anything else you’re specifically preparing for? And then secondly, do you think based on the comments so far today that Zynquista’s launch could be stronger than what you’re seeing with INPEFA right now? Thanks.

Mike Exton, CEO

Great. Same order; I’ll throw to you first with Craig, then Tom.

Craig Granowitz, Chief Medical Officer

Thank you, Andrew. Again, we really feel strongly that based on all of the discussions we have had with the FDA over these past months, they are really going to focus on the risk-benefit. What we've talked about is that in this subgroup, which has a much higher risk of complications, that tight glycemic control is even more important. The data shows both in the entire inTandem program, nearly 3,000 patients, and also in that renal subgroup, that we have similar and significantly controlled glycemia, whether on baseline insulin or optimized insulin therapy, and that tight glycemic control is associated with less progressive disease. Also, we have shown that the risk of diabetic ketoacidosis seems to be similar in that subgroup with chronic kidney disease than in the overall population. We feel strongly that FDA will ask about overall risk-benefit.

Mike Exton, CEO

Great. Thanks, Craig. Tom, to you.

Tom Garner, Chief Commercial Officer

Absolutely, thanks for the question, Andrew. As we think about Zynquista for Type 1 diabetes versus INPEFA for heart failure, this is going to be a very different space compared to what we encountered with heart failure. As Mike mentioned during his remarks, this is going to be a space that's basically untapped. We know there is some small amount of off-label usage of SGLTs at the moment, but largely speaking, this is not a market that has really been brought to the fore. We believe that given the unmet need, given the fact that we know we have a group of endocrinologists who have been wanting to use these products for quite some time, there’s clearly untapped potential here that we think we're going to be able to capture very quickly. The other thing that I would point out is the competitive dynamics. The challenge we faced with INPEFA is that heart failure is tightly managed with competitors offering significant rebate dollars. We’re continuing to push very hard, but the feedback we’ve received from payers regarding Zynquista is that the profile and potential utilization management will look and feel very different compared to what we face with heart failure right now. So, yes, we do see that this will potentially be a space where we can make a very meaningful impact quickly, given the concentrated market we are entering.

Andrew Tsai, Analyst

Makes sense. Thank you.

Mike Exton, CEO

Just, if you allow me, Andrew, to just add to that, that's how we see the rest of the pipeline. As we go through the strategic review, we see that each of our assets offers this opportunity for a pipeline in a pill, which is multiple indications, in spaces where, like for Zynquista, will be the first and only player either as an adjunct or standalone therapy. That provides significantly different payer dynamics and provider interaction. Thus, we feel very confident that Zynquista has the opportunity to be a very significant medicine for Lexicon. Thank you.

Joe Pantginis, Analyst

Good afternoon, thanks for taking the question. First, I wanted to focus on the HCM program. It's good that the program's up and running. I wanted to talk about your views about the evolution of the space. So when you recently had your R&D Day, you positioned Sotagliflozin in connection to other treatments like beta blockers on the front end and CMIs on the back end. How do you envision Sotagliflozin fitting in as of this point, since you can also include the CMI population?

Mike Exton, CEO

Yes, great question. Over to you again, Craig.

Craig Granowitz, Chief Medical Officer

Yes. I believe they have different mechanisms of action that are complementary. We are enrolling patients that are symptomatic, regardless of their underlying therapy. The inclusion criteria include those with a KCCQ score of less than 80, allowing the maximum flexibility to providers to manage symptomatic relief in these patients. Other agents that are in development are also using KCCQ as the primary endpoint, similar to the endpoint of the SONATA HCM trial. This inclusion criterion really stacks up favorably.

Joe Pantginis, Analyst

That's very helpful. Thank you. I'm curious about potential timelines. I don't know if you're ready to discuss that now, since it's just started. On the second question, Mike, you mentioned in the prepared comments about strategy and resources and strategic review. What potential outcomes or goals are you looking for?

Mike Exton, CEO

Yes. Fantastic, Craig. Firstly, for the timeline of HCM.

Craig Granowitz, Chief Medical Officer

Yes, we’ve shared general timelines previously. As a reminder, we got this study up and running extraordinarily quickly, and we're looking at having final data towards the end of 2026, early 2027. This is because we have a treatment duration that's shorter than in other studies, with the drug being already proven in other heart failure related indications. We're looking at a 26-week treatment duration, not a 52-week treatment duration, which accelerates timelines quite a bit.

Mike Exton, CEO

And maybe Joe, if you would allow me to elaborate, we foresee Sotagliflozin potentially being an adjunct to all indicated therapies for HCM. There's a considerable timeline gap in initiating basal therapies and CMIs, due to the complexity of logistics faced by treatment centers. Where we have a demonstrated safety profile, an easy oral therapy, we see it can fit uniquely into the treatment paradigm for HCM. As for the strategic review, we’ve started that with my team immediately. What are we looking to achieve is a simple equation: we have many opportunities but need to be thoughtful about how we deploy our resources across them to maximize outcomes. That’s where we are.

Joe Pantginis, Analyst

Absolutely. Thank you very much for all the details.

Mike Exton, CEO

I appreciate it. Thanks.

Operator, Operator

The next question comes from Roanna Ruiz with Leerink Partners. Please go ahead.

Roanna Ruiz, Analyst

Great afternoon, everyone. Continuing with questions about the Phase 3 SONATA trial in HCM, what has the feedback been from trial sites and investigators so far? And could you remind us about what standards you plan to use to ensure tight execution of that trial?

Mike Exton, CEO

Right. Another one for you, Craig.

Craig Granowitz, Chief Medical Officer

Yes, Roanna, it's a great question. The feedback has been positive. We've identified all the sites needed for the trial in multiple countries. The trial began at the end of June, and the largest contributors of sites will be in the United States. It’s a therapy that requires little friction, can be used alone or on top of existing therapies. It's oral once-daily, allowing an ejection fraction down to 50%. Important, we do not require all the echoes and have a pragmatic endpoint in KCCQ. Feedback on execution has been favorable; investigators believe this drug is likely to be effective. We included both obstructive and non-obstructive HCM because their pathophysiology is more similar than dissimilar.

Mike Exton, CEO

Roanna, regarding controls or mechanisms for appropriate execution, Craig and his team have shown execution excellence in prior clinical trials, and we are currently running on a tight schedule with recruitment and look forward to updates soon.

Roanna Ruiz, Analyst

Got it. A quick follow-up on the obesity program. Can you elaborate more on LX9851 and how this product profile could layer into the treatment paradigm, especially if more products are approved and we have combo regimens?

Mike Exton, CEO

Yes, absolutely. Alan, would you like to take this?

Alan Main, Executive Vice President

Yes, absolutely. The weight management field is incredibly exciting. Treatment is evolving. Despite the success of GLP‐1 agonists, we believe there are questions around cost, ease of use, reduction of lean body mass, and tolerability. With LX9851, we think we're addressing these issues. It’s an oral product that could be easy to manufacture. In preclinical studies, we’ve seen a nice reduction in fat only, with no change in lean body mass and tolerability. We haven’t seen evidence of diarrhea in our studies, including our knockout models, indicating good tolerability over a long duration. The mechanisms complement and enhance current therapies.

Mike Exton, CEO

Alan, it's clear we’re excited about this asset. We predict that the obesity weight management space will evolve greatly in the coming years, likely towards combination therapies. New mechanisms of action are always welcome as combo therapies, especially in diabetes. We look forward to learning more through clinical development in the years to come.

Unidentified Analyst, Analyst

Hi, this is Hosni Mubarak on for Yigal. Thanks for taking my questions. A follow up on the obesity program. I think you believe LX9851 might be differentiated on diarrhea, but what about the nausea profile? How has the duration of therapy been explored in preclinical models?

Mike Exton, CEO

Great. Yes, thanks very much. Alan, over to you for the question on nausea and duration of therapy.

Alan Main, Executive Vice President

Sure. Nausea is difficult to assess in preclinical studies, but it's important to note that inhibiting this enzyme doesn't completely reduce free fatty acid absorption. It delays absorption, triggering the Ileal Brake Mechanism. We’ve only done studies lasting about one month and will conduct long-duration preclinical tests for three and six months.

Mike Exton, CEO

If I may elaborate, there’s evidence suggesting that nausea might not be an issue. Craig, can you discuss that?

Craig Granowitz, Chief Medical Officer

Certainly. Our knockout mouse models indicate tolerability over their life span. There's also limited human genetics data indicating that knockdown variants of ACSL5 have no long-term issues. They lead normal lives after adapting diet for the first few weeks. We’re confident this can be safely dosed for long periods.

Unidentified Analyst, Analyst

That's super helpful. If I could ask one more on this topic. I’m considering potential applicability outside of diabetes, especially regarding mechanisms. Could there be relevance in heart failure as large players are exploring? Thanks.

Mike Exton, CEO

Yes, the answer is yes. Alan has data indicating LX9851's potential in metabolic conditions. We plan to present this data at upcoming medical conferences.

Unidentified Analyst, Analyst

Thanks very much.

Operator, Operator

This concludes our question-and-answer session. I would like to turn the conference back over to management for any closing remarks.

Mike Exton, CEO

I'd just like to thank you all for attending today's Q2 earnings call. We're incredibly pleased with the progress made today. We've got a busy back half of the year and into 2025, but that provides us many opportunities that we're really looking forward to. I look forward to continued dialogue, and we’ll speak to you all soon.

Operator, Operator

The conference has now concluded. Thank you for attending today's presentation. You may now disconnect.