[Overview and Business Update](index=1&type=section&id=Overview%20and%20Business%20Update) The company repositioned to prioritize its R&D pipeline, highlighting progress in key programs and positive clinical data [Strategic Repositioning and CEO Remarks](index=1&type=section&id=Strategic%20Repositioning%20and%20CEO%20Remarks) Lexicon Pharmaceuticals prioritized its R&D pipeline in 2024, highlighting progress in its key clinical programs - The company has completed a repositioning to focus on advancing its **R&D pipeline** as its core priority[3](index=3&type=chunk) - The CEO highlighted three key pipeline opportunities: **pilavapadin for DPNP, LX9851 for obesity, and sotagliflozin for HCM**[3](index=3&type=chunk) [Pipeline Highlights](index=1&type=section&id=Pipeline%20Highlights) The company provided updates on key clinical programs including pilavapadin, LX9851, and sotagliflozin [Pilavapadin (LX9211) for DPNP](index=1&type=section&id=Pilavapadin%20(LX9211)%20for%20DPNP) The Phase 2b study identified a 10 mg dose for Phase 3 trials despite not meeting the primary endpoint - The **10 mg dose** of pilavapadin achieved meaningful pain reduction versus placebo and was well-tolerated, supporting its advancement into a Phase 3 program in 2025[3](index=3&type=chunk)[4](index=4&type=chunk) - The overall study **did not meet its primary endpoint** for statistical significance because the 20 mg dose arm did not show separation from placebo[4](index=4&type=chunk) [LX9851 for Obesity](index=2&type=section&id=LX9851%20for%20Obesity) The novel, non-incretin oral candidate LX9851 is on track for a 2025 IND submission for obesity - LX9851 is a **novel, non-incretin oral development candidate** for obesity and weight management[5](index=5&type=chunk) - The company is on track to submit an **IND application for LX9851 in 2025**[5](index=5&type=chunk) [Sotagliflozin (INPEFA and Zynquista)](index=2&type=section&id=Sotagliflozin%20(INPEFA%20and%20Zynquista)) Enrollment is underway for the Phase 3 HCM study while promotion of INPEFA has ceased - Enrollment is underway in the **SONATA HCM Phase 3 study**, with global site initiation expected to be complete by Q3[12](index=12&type=chunk) - The company has reprioritized SG&A investment by **ceasing active promotion of INPEFA**[6](index=6&type=chunk) - Preparations for a potential Zynquista launch in type 1 diabetes were **discontinued** after receiving a complete response letter from the FDA[7](index=7&type=chunk) [Data and Publications](index=2&type=section&id=Data%20and%20Publications) A recent publication highlighted sotagliflozin's unique ischemic benefits in reducing major adverse cardiovascular events - A prespecified analysis of the SCORED trial, published in The Lancet, concluded that sotagliflozin **reduced major adverse cardiovascular events**, including heart attack (MI) and stroke[13](index=13&type=chunk) - This ischemic benefit on both MI and stroke reduction **has not been observed with other SGLT inhibitors**, providing a key point of differentiation for sotagliflozin[13](index=13&type=chunk) [Financial Performance](index=2&type=section&id=Financial%20Performance) The company reported a significant revenue increase driven by a licensing agreement, alongside a wider net loss due to higher R&D expenses [Q4 and Full Year 2024 Financial Results](index=2&type=section&id=Q4%20and%20Full%20Year%202024%20Financial%20Results) Revenues surged in Q4 and FY2024 due to a licensing payment, while the net loss widened on increased R&D spending Financial Results Summary | Metric | Q4 2024 | Q4 2023 | Full Year 2024 | Full Year 2023 | | :--- | :--- | :--- | :--- | :--- | | **Total Revenues** | $26.6M | $0.7M | $31.1M | $1.2M | | **R&D Expenses** | $26.7M | $14.8M | $84.5M | $58.9M | | **SG&A Expenses** | $32.3M | $32.6M | $143.1M | $114.0M | | **Net Loss** | $(33.8)M | $(49.8)M | $(200.4)M | $(177.1)M | | **Net Loss Per Share** | $(0.09) | $(0.20) | $(0.63) | $(0.80) | - The significant increase in 2024 revenues was driven by increased sales of INPEFA and a **$25.0 million upfront payment** from the Viatris INPEFA licensing agreement in October 2024[9](index=9&type=chunk) - The rise in full-year R&D expenses was primarily due to investments in the **SONATA Phase 3 study** (sotagliflozin) and the **PROGRESS Phase 2b study** (pilavapadin)[10](index=10&type=chunk) [Financial Position](index=3&type=section&id=Financial%20Position) The company ended 2024 with a significantly strengthened cash position and increased stockholders' equity Balance Sheet Highlights | Balance Sheet Item (in thousands) | Dec 31, 2024 | Dec 31, 2023 | | :--- | :--- | :--- | | **Cash and investments** | $237,957 | $170,026 | | **Total assets** | $298,420 | $229,429 | | **Long-term debt, net** | $100,298 | $99,508 | | **Total stockholders' equity** | $145,950 | $93,110 | [Corporate Information](index=3&type=section&id=Corporate%20Information) Covers investor communications, corporate background, and forward-looking statement disclosures [Conference Call and Webcast](index=3&type=section&id=Conference%20Call%20and%20Webcast) Management held a conference call and webcast to review financial results and provide a business update - A conference call and webcast was held at 5:00 pm ET to discuss financial results and provide a business update[16](index=16&type=chunk) [About Lexicon Pharmaceuticals](index=3&type=section&id=About%20Lexicon%20Pharmaceuticals) Lexicon is a biopharmaceutical company using its proprietary genomics platform to discover and develop new medicines - Lexicon uses its proprietary **Genome5000™ genomics platform** to identify novel protein targets for drug discovery and development[17](index=17&type=chunk) [Safe Harbor Statement](index=3&type=section&id=Safe%20Harbor%20Statement) The press release includes forward-looking statements subject to significant risks and uncertainties - The press release contains **forward-looking statements** based on management's current assumptions, which involve risks and uncertainties[18](index=18&type=chunk) - Key risks include the ability to meet capital requirements, successfully commercialize products, conduct clinical development, and obtain regulatory approvals[18](index=18&type=chunk) [Product Information: INPEFA (sotagliflozin)](index=6&type=section&id=Product%20Information%3A%20INPEFA%20(sotagliflozin)) Details the indication, dosing, and important safety information for the company's product INPEFA [Indication and Dosing](index=6&type=section&id=Indication%20and%20Dosing) INPEFA is an oral SGLT1/SGLT2 inhibitor indicated to reduce cardiovascular risks in adults with heart failure - INPEFA is an oral inhibitor of both **SGLT2 (kidney) and SGLT1 (gastrointestinal tract)**[22](index=22&type=chunk) - The drug is indicated to **reduce the risk of cardiovascular death and heart failure events** in adults with heart failure or with T2DM, CKD, and other CV risk factors[23](index=23&type=chunk)[30](index=30&type=chunk) [Important Safety Information](index=6&type=section&id=Important%20Safety%20Information) Key safety warnings for INPEFA include risks of ketoacidosis, volume depletion, and serious urinary tract infections - INPEFA **increases the risk of ketoacidosis**, and is not indicated for glycemic control[25](index=25&type=chunk) - The drug can cause **intravascular volume depletion**, with increased risk for elderly patients, those with impaired renal function, or patients on loop diuretics[27](index=27&type=chunk) - **Serious urinary tract infections**, including urosepsis and pyelonephritis, have been reported with SGLT2 inhibitors[28](index=28&type=chunk) - The most commonly reported adverse reactions (≥ 5% incidence) were **urinary tract infection, volume depletion, diarrhea, and hypoglycemia**[32](index=32&type=chunk)

Core Insights - Lexicon Pharmaceuticals reported positive topline results from the Phase 2b PROGRESS study of pilavapadin, a novel non-opioid therapy for diabetic peripheral neuropathic pain (DPNP), indicating a meaningful pain reduction at the 10 mg dose, which is set to advance into Phase 3 development in 2025 [3][7] - The company is focusing on its R&D pipeline, with significant progress on three key programs: pilavapadin for DPNP, LX9851 for obesity, and sotagliflozin for hypertrophic cardiomyopathy (HCM) [3][4] - Financial results for Q4 2024 showed a substantial increase in revenues, driven by sales of INPEFA and a $25 million upfront payment from a licensing agreement [11][12] Group 1: Clinical Development - Pilavapadin (LX9211) demonstrated meaningful pain reduction and was well-tolerated in the PROGRESS Phase 2b study, supporting its advancement to Phase 3 trials [3][7] - LX9851 is progressing towards an IND filing in 2025, targeting obesity and related metabolic disorders [5] - Enrollment is ongoing for the SONATA Phase 3 study of sotagliflozin in HCM, with a target of 500 patients [8] Group 2: Financial Performance - Q4 2024 revenues increased to $26.6 million from $0.7 million in Q4 2023, and full-year revenues rose to $31.1 million from $1.2 million in 2023, reflecting increased sales of INPEFA and the licensing agreement [11] - R&D expenses for Q4 2024 rose to $26.7 million from $14.8 million in Q4 2023, primarily due to investments in clinical trials [12] - The net loss for Q4 2024 was $33.8 million, an improvement from a net loss of $49.8 million in Q4 2023 [14] Group 3: Strategic Focus - The company is strategically repositioning to prioritize R&D efforts, aiming to address significant unmet medical needs in its pipeline [3][4] - Lexicon's focus on generating clinical data for sotagliflozin aims to differentiate it in the market, particularly in reducing cardiovascular risks [18] - The company has a strong cash position of $238 million as of December 31, 2024, up from $170 million a year earlier, providing a solid foundation for ongoing development [15]

Core Insights - Lexicon Pharmaceuticals will release its fourth quarter and full year 2024 financial results on March 6, 2025, after market close [1] - A conference call and live webcast will be held at 5:00 p.m. ET on the same day to discuss the financial results and provide a business update [1][2] Company Overview - Lexicon Pharmaceuticals is a biopharmaceutical company focused on pioneering medicines that transform patients' lives [3] - The company utilizes the Genome5000™ program, a unique genomics target discovery platform, to study nearly 5,000 genes and identify over 100 protein targets with significant therapeutic potential [3] - Lexicon has advanced multiple medicines to market and has a pipeline of promising drug candidates in various therapeutic areas, including heart failure, neuropathic pain, obesity, cardiology, and diabetes [3]

Core Insights - Lexicon Pharmaceuticals announced positive topline results from the PROGRESS Phase 2b study of pilavapadin, an investigational AAK1 inhibitor for diabetic peripheral neuropathic pain (DPNP), achieving meaningful pain reduction compared to placebo and demonstrating good tolerability at the 10 mg dose [1][5][6] Study Results - The PROGRESS study met its objectives, identifying the 10 mg dose as effective for pain reduction and tolerability, advancing it into Phase 3 development [2][5] - In the PROGRESS study, the 10 mg, 20 mg/10 mg, and 20 mg dose arms achieved reductions in average daily pain scores of 1.74, 1.70, and 1.38, respectively, compared to a reduction of 1.31 in the placebo arm [3] - The 10 mg dose arm showed significant separation from placebo in pain reduction, while the 20 mg dose did not reach statistical significance [3] Adverse Events - Adverse events were more frequent in pilavapadin treatment arms but were milder compared to the RELIEF-DPN-1 study, with dizziness and nausea being the most common [4][6] - The 10 mg dose was generally well-tolerated, while the 20 mg dose had a higher incidence of adverse events leading to patient discontinuations [4] Market Potential - The neuropathic pain market represents a multibillion-dollar opportunity, and pilavapadin could become the first oral non-opioid treatment approved for neuropathic pain in 20 years [6][12] - The results from the PROGRESS study have generated significant interest from potential partners, and the company plans to accelerate discussions while preparing for Phase 3 development [6] Study Background - The PROGRESS study enrolled 496 adult patients with moderate to severe DPNP and was designed to evaluate the efficacy of pilavapadin against placebo [9] - The study's primary endpoint was the change in average daily pain score from baseline to Week 8 [9] Future Plans - A full analysis of the PROGRESS study results will be presented at a medical conference and submitted for publication in a peer-reviewed journal [7]

Core Insights - Lexicon Pharmaceuticals announced a conference call and webcast to share topline results from the Phase 2b PROGRESS study evaluating pilavapadin (LX9211) for diabetic peripheral neuropathic pain (DPNP) [1][2] Group 1: PROGRESS Study Details - The PROGRESS study began in December 2023, enrolling 496 adult patients with diabetes and moderate to severe DPNP [3] - The study was placebo-controlled, with the primary endpoint being the change from baseline to Week 8 in the Average Daily Pain Score (ADPS) compared to placebo [3] - Three treatment groups received once-daily doses of pilavapadin: 10 mg, 20 mg, or 20 mg for seven days followed by 10 mg thereafter [3] - Secondary endpoints included changes in burning pain and pain interference on sleep from baseline to Week 8 [3] - Patients were allowed to remain on stable-dose DPNP therapies, aligning with practical usage of new DPNP drugs [3] Group 2: Diabetic Peripheral Neuropathic Pain (DPNP) - DPNP is a chronic complication of diabetes characterized by burning pain, numbness, and other symptoms in extremities [4] - Approximately 9 million patients in the U.S. suffer from DPNP [4] Group 3: Pilavapadin Overview - Pilavapadin (LX9211) is an investigational AAK1 inhibitor, designed to be a potent, once-daily, orally delivered small molecule [5] - It targets neuropathic pain by inhibiting neurotransmitter reuptake and recycling without affecting opiate pathways [5] - Preclinical studies indicated that pilavapadin penetrates the central nervous system and reduces pain behavior in neuropathic pain models [5] Group 4: Company Background - Lexicon Pharmaceuticals is focused on pioneering medicines that transform patients' lives through its Genome5000™ program [6] - The company has identified over 100 protein targets with therapeutic potential across various diseases [6] - Lexicon has advanced multiple medicines to market and has a pipeline of drug candidates in various stages of development, including heart failure, neuropathic pain, obesity, and diabetes [6]

Core Insights - The article highlights the unique clinical advantages of sotagliflozin, a dual SGLT1 and SGLT2 inhibitor, in reducing life-threatening cardiovascular outcomes compared to empagliflozin [2][3] - A published study in The Lancet Diabetes & Endocrinology confirms the ischemic benefits of sotagliflozin, showing significant reductions in major adverse cardiovascular events (MACE), myocardial infarction (MI), and stroke among patients with type 2 diabetes (T2D), chronic kidney disease (CKD), and high cardiovascular risk [3][5] Study Findings - The study titled "Reduction in Major Adverse Cardiovascular Events with Sotagliflozin" is a secondary analysis of the SCORED trial, which was a double-blind, placebo-controlled, randomized clinical trial [4] - Sotagliflozin demonstrated a lower rate of MACE outcomes at 4.8 events per 100 person-years compared to 6.3 events per 100 person-years in the placebo group, with a hazard ratio of 0.77 [5] - The reduction in MI was significant, with 1.8 events per 100 person-years in the sotagliflozin group versus 2.7 events per 100 person-years in the placebo group, yielding a hazard ratio of 0.68 [5] - Stroke rates were also lower in the sotagliflozin group at 1.2 events per 100 person-years compared to 1.8 events per 100 person-years in the placebo group, with a hazard ratio of 0.66 [5] Expert Commentary - Dr. Deepak L. Bhatt emphasized that sotagliflozin is the only SGLT inhibitor to show significant reductions in both heart attack and stroke [6] - Craig Granowitz, M.D., noted that the comprehensive findings illustrate how sotagliflozin stands apart from other SGLT inhibitors [7] Company Overview - Lexicon Pharmaceuticals is focused on pioneering medicines that transform patients' lives, utilizing its Genome5000™ program to discover therapeutic targets [9] - The company has a pipeline of drug candidates in various stages of development, addressing conditions such as neuropathic pain, hypertrophic cardiomyopathy, and obesity [9]

Core Insights - The study published in The Lancet Diabetes & Endocrinology highlights the clinical advantages of sotagliflozin, a dual SGLT1 and SGLT2 inhibitor, in reducing life-threatening cardiovascular outcomes compared to empagliflozin [2][3] - Sotagliflozin demonstrated a significant reduction in major adverse cardiovascular events (MACE), myocardial infarction (MI), and stroke among patients with type 2 diabetes (T2D), chronic kidney disease (CKD), and high cardiovascular risk [3][5] Study Findings - The secondary analysis of the SCORED trial revealed that patients receiving sotagliflozin had a lower rate of MACE outcomes at 4.8 events per 100 person-years compared to 6.3 events per 100 person-years in the placebo group, with a hazard ratio of 0.77 [4][5] - The study also found that sotagliflozin reduced the rate of MI to 1.8 events per 100 person-years versus 2.7 events per 100 person-years in the placebo group, with a hazard ratio of 0.68 [5] - Additionally, the rate of stroke was reduced to 1.2 events per 100 person-years in the sotagliflozin group compared to 1.8 events per 100 person-years in the placebo group, with a hazard ratio of 0.66 [5] Company Overview - Lexicon Pharmaceuticals is focused on pioneering medicines that transform patients' lives, utilizing its Genome5000™ program to discover therapeutic targets [9] - The company has a pipeline of drug candidates in various stages of development, addressing conditions such as neuropathic pain, hypertrophic cardiomyopathy, and obesity [9]

Core Insights - Lexicon Pharmaceuticals is hosting a virtual webcast titled "LX9211 - Changing the Paradigm for Treatment of Neuropathic Pain" on January 28, 2025, from 9:00 a.m. to 11:00 a.m. ET [1] - The event will provide an in-depth overview of LX9211, a novel non-opioid treatment for diabetic peripheral neuropathic pain (DPNP), ahead of the anticipated topline data from the Phase 2b PROGRESS trial [2] - The webcast will feature presentations from Lexicon leadership and an expert panel, along with a Q&A session focused on DPNP [2] Company Overview - Lexicon Pharmaceuticals is a biopharmaceutical company dedicated to pioneering medicines that transform patients' lives, utilizing its Genome5000™ program to study nearly 5,000 genes and identify over 100 protein targets with therapeutic potential [3] - The company has a pipeline of promising drug candidates in various stages of discovery and development, targeting indications such as cardiology, neuropathic pain, and metabolism [3]

Core Insights - Lexicon Pharmaceuticals received a complete response letter (CRL) from the FDA regarding the New Drug Application (NDA) for Zynquista™ (sotagliflozin) as an adjunct to insulin therapy for glycemic control in adults with type 1 diabetes and chronic kidney disease (CKD) [4] - The company has decided to discontinue launch preparations for Zynquista and will focus on its clinical development pipeline [2] - Lexicon is committed to advancing its clinical pipeline, particularly LX9211 for diabetic neuropathic pain (DPNP), with top line data from the PROGRESS Phase 2b study expected in Q1 2025 [6] Company Overview - Lexicon Pharmaceuticals is a biopharmaceutical company focused on pioneering medicines that transform patients' lives, utilizing its Genome5000™ program to study nearly 5,000 genes and identify over 100 protein targets with therapeutic potential [5] - The company has a pipeline of promising drug candidates in various stages of development, targeting conditions such as neuropathic pain, hypertrophic cardiomyopathy (HCM), obesity, and metabolism [5]

Core Insights - Lexicon Pharmaceuticals has successfully completed patient enrollment in the PROGRESS study, exceeding the target by 20% with a total of 494 patients enrolled, and finishing eight weeks ahead of schedule [2][3][4] - Top-line data from the PROGRESS study is expected to be announced in Q1 2025, which will provide critical insights for the Phase 3 design of LX9211 [3][4] Study Details - The PROGRESS study is a Phase 2b trial evaluating LX9211 for diabetic peripheral neuropathic pain (DPNP), a condition with significant unmet treatment needs [2][5] - The primary endpoint of the study is the reduction of Average Daily Pain Score (ADPS) at 8 weeks, with secondary endpoints including changes in burning pain and pain interference with sleep [5] - The study design allows patients to maintain one stable-dose DPNP therapy, aligning with real-world treatment practices [5] Background on DPNP - Diabetic peripheral neuropathic pain (DPNP) affects approximately 5 million patients in the U.S., resulting from nerve damage due to chronically high blood sugar levels [6] - DPNP can lead to debilitating symptoms such as pain and numbness in extremities, highlighting the urgent need for new non-opioid treatment options [6][4] About LX9211 - LX9211 is a novel, orally delivered, selective small molecule inhibitor of adaptor-associated kinase 1 (AAK1), identified through Lexicon's gene science approach [7] - Preclinical studies have shown that LX9211 can penetrate the central nervous system and reduce pain behavior without affecting opiate pathways [7] - The drug has received Fast Track designation from the U.S. FDA for development in DPNP [7] Company Overview - Lexicon Pharmaceuticals is focused on pioneering medicines that transform patients' lives, utilizing its Genome5000™ program to identify therapeutic targets [8] - The company has a pipeline of drug candidates in various stages of development for conditions including neuropathic pain, hypertrophic cardiomyopathy, and obesity [8]