Good day and welcome to the Lexicon Pharmaceuticals' Third Quarter 2023 Financial Results Conference Call. Today all participants will be in a listen-only mode. After today's presentation, there will be an opportunity to ask questions. Please note that today's event is being recorded. I would now like to turn the conference over to Carrie Siragusa. Please go ahead.

Thank you, Chris. Good morning and welcome to the Lexicon Pharmaceuticals' third quarter 2023 financial results conference call. Joining me today are Lonnel Coats, Lexicon's Chief Executive Officer; Jeff Wade, Lexicon's President and Chief Financial Officer; Dr. Craig Granowitz, Lexicon's Senior Vice President and Chief Medical Officer; and Tom Garner, Lexicon's Senior Vice President and Chief Commercial Officer. Earlier this morning, Lexicon issued a press release announcing our financial results for the third quarter of 2023, which is available on our website at www.lexpharma.com and through our SEC filings. A webcast of this call along with a slide presentation is 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 relating to the safety, efficacy, clinical development, regulatory status, and therapeutic and commercial potential of INPEFA, LX9211, and our other drug programs. These statements may also 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. These risks include uncertainties related to our commercial launch of INPEFA, our discussions with the FDA and other regulatory authorities regarding our drug programs, the timing and results of clinical trials and preclinical studies of our drug candidates, our dependence upon strategic alliances and other third-party relationships, our ability to obtain patent protection for our discoveries, limitations imposed by patents owned or controlled by third parties, and the requirements of substantial funding to conduct our planned research, development, and commercialization activities. I would now like to turn the call over to Lonnel Coats.

Thank you, Carrie. Good morning, everyone. And thank you for joining us on the call. The third quarter represents the first full quarter of the INPEFA launch. While it is still early, the market is what we expected, both with near-term challenges and substantial near- and long-term opportunities. As expected, market access has proven to be a near-term restraint on early launch growth. We have dedicated enormous effort to break through and secure broad formulary access. Encouragingly, we have been seeing increasing prescription demand and clinical utilization for INPEFA, and notwithstanding limited access, are now starting to see major formulary wins, with some of the more notable becoming effective on November 1. With INPEFA's significant clinical share of voice and publications at medical meetings coupled with additional expected formulary wins and increasing uptake from a broadening base of priority physicians, we are confident that the momentum behind INPEFA will continue to accelerate as we enter 2024. Our new Chief Commercial Officer, Tom Garner, will walk you through the early launch dynamics and more details shortly. Turning to LX9211, we have commenced late-stage development in diabetic peripheral neuropathic pain with patient enrollment expected to begin this quarter and a Phase 2b dose optimization clinical trial. LX9211, not two on one, could become the first new non-opioid drug for neuropathic pain in over two decades. Neuropathic pain represents a significant market opportunity. We have aligned our development plan with recently received FDA feedback to move forward with a strategy that is designed to optimize development time and efficiency while also maximizing the likelihood of a successful path to regulatory approval. I will now turn the call over to Tom Garner, who recently joined Lexicon as Chief Commercial Officer, to provide his perspective on the commercial launch of INPEFA.

Thank you, Lonnel, and good morning, everyone. It's a pleasure to speak with you all today. Starting with heart failure market dynamics, the updated treatment guidelines and growing clinical evidence continue to help fuel the growth of heart failure indicated SGLT inhibitors for that indication. SGLT inhibitor use in heart failure has grown by 73% year-over-year through August of 2023, with the entire heart failure branded market growing by almost 40% from 2021 to 2022, representing a rapidly growing opportunity of at least $3 billion. Even with this significant momentum, the utilization of SGLT inhibitors for the treatment of heart failure was only around 10% last year, providing tremendous opportunity for a new treatment like INPEFA, which has compelling and differentiated data in this specific patient population. On the next slide, you will see two critical focus areas for the INPEFA launch, namely demand generation and formulary access. We are encouraged by the momentum that we are building on both of these fronts. As we look at demand generation, our teams have been focused on driving awareness and trials of INPEFA with high-volume writers who treat the majority of heart failure patients in the United States. As a result of these efforts, the number of unique prescribers for INPEFA has grown throughout Q3 and will remain a key strategic focus for our cross-functional teams moving forward. Importantly, we are seeing meaningful increases in INPEFA demand, as evidenced by submitting claims data that has outpaced filled prescriptions, which is expected as formulary access continues to build. It's worth noting that as we close out the first full quarter of our commercial launch, we have seen an acceleration in our prescription data reflecting improving access conditions for INPEFA. In terms of formulary access, the team has been focused on discussions with both national and regional payer plans and have successfully engaged with all targeted plans with multiple layers of engagements throughout Q3. As we announced in our press release this morning, key formulary access contracts were executed in Q3 in both Medicare and commercial channels, and we expect access to continue throughout Q4. We will also share more information today about integrated delivery networks, or IDNs, which also remain a strategic focus given the uniqueness of the SOLOIST patient population and valuable rehospitalization data for INPEFA. Turning to additional quarterly launch metrics, you will see here a view of ex-factory shipments to wholesalers, data on prescriptions and unique prescribers, and a summary of demand data. Ex-factory shipments continued through the third quarter as wholesalers used the initial orders received in June, a trend that we have continued to see accelerate throughout the quarter. As mentioned previously, we are hyper-focused on growing the unique prescriber base for INPEFA, which has expanded to nearly 500 healthcare professionals throughout the quarter, the majority of whom are from key high-priority high prescriber targets. We have been encouraged to see the growing clinical demand data outpacing our full prescription data by a ratio of nearly five to one. With contracted access continuing to build with large national payers, we believe that this growing clinical demand will lead to additional filled prescriptions as INPEFA achieves greater formulary coverage. As you will see on the next slide, filled prescriptions continue to grow week-over-week throughout Q3 2023, with an acceleration in the last few weeks of the quarter. It's also worth noting that this number reflects prescriptions being reported directly through IQVIA and SYMPHONY, alongside those that are going through our specialty pharmacy, which are not visible to third-party agencies. As mentioned on the prior slide, top-line demand has outpaced the number of prescriptions filled with nearly 5,000 submitted claims through Q3, clearly demonstrating the impact of our field teams and customer belief in the clinical value offered by INPEFA. Turning to our progress on payer coverage, we have been pleased to see coverage for INPEFA grow throughout Q3 across both commercial and Medicare formularies. The additions to Medicare plans are particularly significant given that these are early additions outside of the normal contracting process with major national payers. We do expect additional planned coverage to be added through Q4 and into next year. Turning to IDNs, integrated delivery networks remain a key component of our launch strategy. Given the typical new-to-market block for IDN formulary additions, our primary focus in Q3 has been on building the foundations for coverage. The team has initiated contract negotiations with all four major group purchasing organizations, two of which have already been fully executed. The executed contracts represent around 60% of heart failure lives in our targeted institutions. Once GPO contracting is completed, IDN systems will be able to evaluate INPEFA both clinically and financially during their formulary product reviews, which we expect to begin later this year and into 2024. In summary, Q3 was an important quarter for the launch of INPEFA, with meaningful progress made on the execution of the launch strategy across the entire commercial organization. We're pleased by the positive reception given by the clinical community to INPEFA as the only SGLT-1/2 inhibitor indicated for the treatment of heart failure. The team remains laser-focused on further accelerating the positive momentum we have begun to build since launch and helping even more patients with worsening heart failure wherever they may be cared for. I will now turn the call over to Craig to give an overview of the most recent scientific and medical data releases for INPEFA.

Thank you, Tom, and great to have you on the team. We're continuing to communicate meaningful and differentiated scientific and medical data on INPEFA to the broad scientific community. As you can see on this slide, our data presentations over the last several months have focused on four key differentiating areas for INPEFA: clinical analysis, real-world evidence, pharmacoeconomic data, including both cost-effectiveness and budget impact, and mechanism of action. Quite recently, we supported a post-hoc analysis of our Phase 3 SCORED study at the Heart Failure Society of America Annual Scientific Meeting that looked at the reduction in the risk of cardiovascular events in patients with less ventricular hypertrophy without hypertension. This data is of particular interest to heart failure specialists and to Lexicon as we evaluate future opportunities for broadening the use of INPEFA. At the American Managed Care Pharmacy Nexus 2023 meeting, we presented cost-effectiveness data and budget impact modeling data for INPEFA, which were also published in the Journal of Managed Care and Specialty Pharmacy. These studies serve as evidence that INPEFA is an affordable treatment that offers important clinical value for heart failure patients and significant value for payers. Last weekend, the American Society of Nephrology held its Annual Kidney Week meeting where Lexicon supported several presentations addressing the challenges and complications of diabetes and chronic kidney disease. Of note, ASN itself selected one of the presentations for a featured independent press release, highlighting the analysis of sotagliflozin and kidney and cardiorenal outcomes from the SCORED trial. We are proud of this independent recognition from ASN as we continue to study the clinical benefits of sotagliflozin, and we at Lexicon are committed to working diligently to broadly inform the scientific evidence demonstrated. Now, turning to the future, we are also looking forward to the American Heart Association scientific sessions that are starting in just a few days. We will be supporting data presentations across all domains we have identified as differentiating: clinical, real-world evidence, pharmacoeconomic data, and the INPEFA mechanism of action. We expect that the oral presentation of data assessing sotagliflozin's effect on early clinical benefit for heart failure in atherosclerotic events will be of particular interest to the scientific and medical communities. Well, I have just shared with you data that Lexicon and our academic collaborators have been publishing on INPEFA. I'd now like to share with you data that the academic community itself has published independently of Lexicon regarding the opportunity that exists in addressing the needs of patients with heart failure. A recent publication in the Journal of the American Heart Association entitled 'Acute heart failure is a malignant process, but we can induce remission' noted that acute heart failure, due to both increasing prevalence and early readmission and death rates of greater than 30% annually, make heart failure a malignant condition. Beyond the poor medical outcomes of heart failure patients, the publication also noted that acute heart failure represents one of the largest drivers of healthcare costs globally. The publication also examined several studies recently published in the peer-reviewed literature which have demonstrated that remission in this malignant process can be induced if therapy is instituted rapidly. It is important to note that two studies from the SGLT class were included in this analysis, including the SOLOIST-WHF study of INPEFA that is seen in panel A of the figure. Data from the SOLOIST-WHF study, which included stabilized patients hospitalized for heart failure, were included in this composite figure and show the evidence of sotagliflozin's early benefit in this at-risk population. This represents a key differentiating aspect in our promotional strategy. The publication concludes that there is an urgent call for all stakeholders to come together to address the gaps in implementation and enable healthcare providers to induce durable remissions in patients with acute heart failure. We strongly support this messaging and will continue to support the community by providing continuing medical education about the importance of the early initiation of SGLT inhibitors like INPEFA at discharge or promptly following an acute heart failure event. Now, we will turn briefly to an update on LX9211. We believe LX9211 has a promising profile based on two completed proof-of-concept studies and a substantial market opportunity. LX9211 has the potential to overcome many of the shortcomings of current therapies and could become a welcomed new innovation for those suffering from diabetic peripheral neuropathic pain or DPNP on a daily basis. This large and growing market has high unmet medical need, with more than 20 million Americans experiencing neuropathic pain and approximately 5 million with DPNP in the U.S. in 2022 alone. As a reminder, Lexicon has been granted Fast Track designation by the FDA for the development of LX9211 in DPNP. As we have shared in previous updates, we are advancing LX9211 into late-stage clinical development with a program directed toward DPNP regulatory approval. Our plan is reflective of the feedback we recently received from the FDA, including ADPS remaining the primary endpoint of future studies and targeting a DPNP population similar to that enrolled in our Phase 2 proof-of-concept study. The FDA also agreed with the potential for inclusion of the phrase 'early onset pain relief with persistent effect' in the label, if supported by clinical evidence in our approach for dose selection of the Phase 3 studies. The first late-stage trial named PROGRESS will be a dose optimization study with an extension designed to satisfy ICH guidelines for long-term exposure requirements that will run in parallel with the planned NxStage Phase 3 trials. As a reminder, the PROGRESS study was specifically designed to enable a more efficient Phase 3 study execution as well as to derisk investment while maintaining overall program timelines and costs. Finally, turning to the PROGRESS study design, it will have an eight-week treatment duration and will enroll adult patients with either Type 1 diabetes or Type 2 diabetes who have moderate to severe diabetic peripheral neuropathic pain. Our teams have been hard at work completing the startup of the study throughout Q3, and we expect initiation of dosing in early December '23, with early data readout expected in Q2 2025. I'd now like to turn the call over to Jeff to take us through the financial results for the third quarter of 2023.

Thank you, Craig. I will review some key aspects of our third quarter 2023 financial results. More financial details can be found 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 $218.4 million in cash and investments. We believe that our existing capital resources provide us with the appropriate level of funding to support the commercial launch of INPEFA and to make our planned investments in research and clinical development. Our loan facility with Oxford Finance, which offers up to $50 million in additional borrowing capacity, provides financial flexibility as we continue the launch of INPEFA. We anticipate that our existing cash and investments, together with capacity under the loan facility will provide us sufficient resources to manage our operations well into 2025. As indicated in our press release this morning, we had $160,000 in revenues in the second quarter of 2023 compared to minimal revenues in 2022. INPEFA net revenues from launch in late June through September 30 totaled approximately $400,000. Research and Development expenses for the third quarter of 2023 increased to $17.6 million from $10.6 million for the corresponding period in 2022, primarily due to higher manufacturing costs and higher external R&D expenses related to the LX9211 program, partially offset by lower professional and consulting fees. Selling, general, and administrative expenses for the third quarter of 2023 increased to $32.2 million from $12.6 million for the corresponding period in 2022, primarily due to increases in personnel, professional, consulting, and marketing costs relating to the commercial launch of INPEFA. In total, the net loss for the third quarter of 2023 was $50.5 million or $0.21 per share, as compared to a net loss of $23.4 million or $0.13 per share in the corresponding period in 2022. For the third quarters of 2023 and 2022, net loss included non-cash stock-based compensation expense of $3.9 million and $2.6 million, respectively. As with the prior quarter, we are also including a view of our 2023 full year expense guidance. This includes expected R&D expenses of between $60 million and $70 million, SG&A expenses of between $110 million and $120 million, and total operating expenses of between $170 million and $190 million, a $10 million reduction from our prior guidance. This includes non-cash expenses of $17 million to $18 million for stock-based compensation, depreciation, and amortization. I would now like to open up the call to take your questions.

We will now begin the question-and-answer session. Today's first question comes from Yigal Nochomovitz with Citi.

Thank you. And this is Karl Li on for Yigal. We just wanted to drill down a bit on the market access side. You mentioned about 25% of lives covered, I think, at the end of the quarter, and that's expected to increase further in the fourth quarter. Just curious when you would expect to really have the vast majority of lives covered and we could potentially really see an inflection point in the launch? Thank you.

Carly, that's an insightful question. As we mentioned in the last conference call, we believe it's important to focus on the first quarter of next year. Given our current trajectory, we anticipate that most of the opportunities for us to secure coverage will arise in the first half of next year. This is when we expect to see a significant change for the brand. Building on Tom's comments, we're optimistic about the existing demand. We recognize that access needs to align with this demand. When that alignment occurs, we anticipate a substantial improvement. Therefore, I project that we will have covered the majority of what is necessary by the second quarter of next year.

Okay. Got it. That's helpful. And then just as a follow-up, curious if there's any insight that you have into the profile of the initial patients that are being prescribed in INPEFA, if there's any subgroup or consistency in terms of patient characteristics where you feel like the demand is particularly strong? Thank you.

I'll turn it over to Tom.

Yeah. Good morning. Thanks for the question. I think, I mean, the initial profile seems to be, as you would expect, kind of the heart failure patient who is either recently out of hospital or could be being discharged from hospital. I mean that's where obviously the SOLOIST data, I think, speaks most loudly. But if you look at kind of strategically where we've been focused, I mean it's been both inpatient and outpatient as we consider kind of where those patients sit today and how they move through the system. So nothing specific at this point in time that's kind of calling out an INPEFA patient versus a different patient, but I think we will learn considerably more over the coming period.

Okay. Great. That's helpful. Thank you for taking the question.

The next question comes from Andrew Tsai with Jefferies. Please proceed.

Hey, good morning. Thanks for taking our questions. So maybe two questions. The first one is more about the Q3 sales breakdown, how much inventory build or drawdown was there in the quarter? And then secondly, what were the gross to nets like? Were they below 50%? And then secondly, interestingly, in one of your slides, it looks like there are 5,000 claims as of Q3, whereas 1,000 have been filled. So the question is what percentage of those 5,000 would or could get converted? And how quickly could they get converted? Thanks.

Great question. Jeff, let me have you take the first part of that.

The gross to net remains consistent with last quarter, staying in the low 40% range. Regarding inventory, we've significantly reduced it. Initially, we had an inventory build with the B HAP drug in the channel. As we've processed through that inventory, we're now approaching a more stable situation. Much of what was filled in the third quarter was aimed at reducing this inventory build, and we are replacing it regularly now. At this point, after that initial fill of the channel, we're closer to a steady state.

Maybe I'll take the second question. So in relation to the 5,000 claims. So as we mentioned, we're encouraged by the fact that doctors are putting pen to paper; they clearly see the value for INPEFA, and they want to try for heart failure. So that's very encouraging. As we stated, as we exited Q3, our coverage was about 25% within the quarter as we exited, and that didn't obviously reflect some of the bigger wins that we've announced over the last few weeks. So that number is going to improve pretty dramatically. We do anticipate through this quarter and then beyond. So rather than being a 20% conversion rate, that will continue to tick upwards into the 30s and the 40s and even higher as we gain further wins. So we do anticipate that this will continue to grow quickly, especially with ESI going live last week, which is a pretty major win, and we have others on the way as well. So that's kind of how we see this developing over time.

Great. Thank you very much.

Thank you, Andrew.

The next question is from Joseph Stringer with Needham & Company. Please proceed.

Hi, thanks for taking questions. Just a follow-up on the gross-to-net commentary. You mentioned that it's in the low 40% range for the third quarter. Is this the expectation for what you would expect it to look like at steady state? Maybe some additional color there? And then just quickly on the Phase 2b pain trial. Can you remind us how similar the patients are going into the Phase 2b relative to the Phase 2a trial in terms of inclusion, exclusion criteria and guidance for top-line results from the Phase 2b? Thanks.

I'll take that first part. I'd just say it's too early to give you steady state on gross to net. We're negotiating agreements every day. And so I think as we get another quarter or two under our belt, then we'll be able to give you some clear guidance. But at this moment, lots of negotiations are ongoing with the intent of broadening access. So stay tuned on that one. The second part, I'll turn it over to Craig.

Yeah. Thank you, Joey. Great question. And this is one that we spent a lot of time thinking about with our study sites or the high-performing sites from our two DPNP programs that enrolled the majority of the patients, and we're including all of our best-performing sites that we're all excited to participate in the program again, as well as feedback from our regulatory consultants as well as the FDA itself. We really want to focus on those patients similar to the 2a with long-standing DPNP, stable in their diabetes care, whether it's Type 1 or Type 2 diabetes, but with significant pain. We're also allowing, like the Phase 2a study, those to be on an underlying DPNP medication, and we learned a lot in terms of some of the PROs and other metrics that we're putting into the study. So we're really going with a population that has significant unmet medical need which includes a very large number of patients. There is a large number of these patients with significant need that is not being met by current care, and we feel confident based on all of the work that we've done that we can enroll the study in the time frame that we've set out. The second part of your question related to the timing is that we're really looking at first patient enrolled as I've already mentioned in early December. All the site validation work and site initiation work has been completed. IRBs are approving the protocol, and we expect to have data from that eight-week treatment period in the second quarter of '25. As I mentioned, all the patients will have the opportunity to roll over into a long-term follow-up study on drugs, which allows us both to have additional data but also is a good inducement to get patients to participate in a blinded study with placebo. So we've really tried to optimize based on what we've learned from our study sites, the patients, and the FDA.

We are now operating in a non-COVID environment, and we have gained valuable insights from our previous experiences. In the past, our progress was hindered by the pandemic during trials. Having a proven concept from our initial study makes it easier to gain Institutional Review Board support and encourages sites to participate, allowing us to move forward more quickly than we did earlier.

Great. Thank you for taking my questions.

You bet.

At this time, we are showing no further questioners in the queue, and this does conclude our question-and-answer session. I would now like to turn the conference back over to Mr. Lonnel Coats for any closing remarks.

Well, let me say thank you to everyone for joining us on the call today and your continued support of Lexicon. Let me close out by summarizing our upcoming key milestones and events. First, we are on target with the late-stage development plans we shared for LX9211 and diabetic peripheral pain. This is another large and growing market, still in need of innovative treatments, and we expect the PROGRESS study to begin enrollment in December of this year. Second, we are highly focused on delivering a successful launch of INPEFA. We have a focused commercial strategy that leverages our unique clinical data, and we're entering a market that is just beginning to reflect the growth driven by the new treatment guidelines, which include SGLTs as a pillar of heart failure treatment. We are pursuing market access for INPEFA across all channels, and have been able to see early access additions throughout this quarter and expect to be able to share incremental news as we move into 2024. I remain remarkably encouraged, and I'm very pleased that Tom Garner has chosen to join us as we make efforts to accelerate this launch in 2024. Finally, importantly, Lexicon is in a strong cash position with the ability to fund operations well into 2025. Thank you very much.

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