Drug Development and Clinical Trials - The company is commercializing INPEFA (sotagliflozin) to reduce the risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure visits in adults with heart failure or type 2 diabetes, chronic kidney disease (CKD), and other cardiovascular risk factors[31]. - The FDA issued a complete response letter in December 2024 regarding the company's NDA for ZYNQUISTA (sotagliflozin) as an adjunct to insulin therapy for glycemic control in adults with type 1 diabetes and CKD, with ongoing proceedings for a public Notice of Opportunity for Hearing[35]. - The company is conducting a Phase 3 clinical trial, SONATA HCM, to evaluate the efficacy and safety of sotagliflozin in approximately 500 patients with hypertrophic cardiomyopathy (HCM) over a 26-week treatment period[33]. - Pilavapadin (LX9211) has received Fast Track designation from the FDA for the treatment of diabetic peripheral neuropathic pain (DPNP), with three completed Phase 2 clinical trials demonstrating evidence of effect[18][21]. - In the PROGRESS Phase 2b clinical trial, the 10 mg dose of pilavapadin achieved a reduction in average daily pain score (ADPS) of 1.74 compared to 1.31 in the placebo arm, although the study did not reach statistical significance on the primary endpoint[23]. - The RELIEF-DPN-1 Phase 2 clinical trial showed a statistically significant reduction in ADPS of 1.39 points in the low dose arm compared to 0.72 in the placebo arm (p=0.007), meeting the study's primary endpoint[24]. - The company is developing LX9851 for obesity and associated cardiometabolic disorders, with IND-enabling studies currently underway[28]. - The company is developing pilavapadin for neuropathic pain, LX9851 for obesity and cardiometabolic disorders, and sotagliflozin for HCM, with ongoing research and development efforts[118]. - Clinical trials are inherently risky and may not demonstrate safety and efficacy, potentially delaying regulatory approval[119]. Financial Performance and Capital Requirements - The company has a history of net losses and expects to continue incurring net losses, which may affect profitability[116]. - The company incurred an aggregate net loss of approximately $479.5 million for the three-year period ended December 31, 2024, with an accumulated deficit of approximately $2.0 billion[173]. - The company has approximately $100.3 million of indebtedness as of December 31, 2024, which may limit cash flow available for business investments[179]. - Future capital requirements are expected to be substantial, and the company may need to raise additional funds to continue planned operations[167]. - The company expects to continue incurring significant expenses for the research and development of pilavapadin, LX9851, and sotagliflozin[175]. - The company's operating results have fluctuated in the past and are likely to continue to do so, making period-to-period comparisons unreliable[176]. - The company may not have sufficient capital to support Phase 3 development of pilavapadin in neuropathic pain, which could require additional financing[171]. Collaborations and Licensing Agreements - The company entered into an exclusive license agreement with Viatris Inc. for the development and commercialization of sotagliflozin, receiving a $25 million upfront payment and potential milestone payments totaling up to $197 million[38]. - Viatris is responsible for all regulatory and commercialization activities for sotagliflozin in the licensed territory, including conducting additional clinical trials[39]. - The company established a drug discovery alliance with Bristol-Myers Squibb, receiving $86 million in upfront payments and research funding, with potential milestone payments of up to $76 million for each drug developed[40][41]. - The company has agreed to pay Bristol-Myers Squibb up to $34.5 million in clinical and regulatory milestones for the first indication of pilavapadin and up to $40 million in commercial milestones[42]. - The company collaborates with various pharmaceutical and biotechnology companies, receiving fees for generating knockout mice and providing phenotypic data, with potential milestone or royalty payments[43]. Regulatory Environment and Compliance - The FDA requires a substantial user fee for the submission of a New Drug Application (NDA), which must include comprehensive data on chemistry, manufacturing, and clinical efficacy[61]. - FDA approval processes can take many years, with significant variability based on the drug's complexity and the disease it targets, potentially delaying market entry[63]. - The FDA may grant conditional marketing authorizations for products with incomplete clinical datasets if the risk-benefit balance is positive[74]. - Orphan drug designation in the U.S. provides tax credits of up to 25% for qualified clinical trial expenses and can offer seven years of market exclusivity for rare diseases affecting fewer than 200,000 people[68]. - The FDA's Fast Track and priority review programs aim to expedite the approval process for drugs addressing serious conditions, with priority review reducing the initial review time to six months[69]. - The 21st Century Cures Act enhances FDA processes for drug approval, including the use of real-world evidence and complex adaptive trial designs[70][76]. - Compliance with FDA regulations is mandatory for drug manufacturers, including adherence to current Good Manufacturing Practices (cGMP) and regular inspections[62][65]. - The FDA restricts marketing and promotion of drugs to approved uses only, with potential penalties for non-compliance[66][67]. - Federal and state healthcare laws impose strict compliance requirements on the company, with significant penalties for violations[79]. - The company is subject to various federal and state laws regarding the collection and use of personal information, which may increase operational costs and create liability risks[80]. - The Physician Payments Sunshine Act requires manufacturers to report certain payments to physicians, potentially impacting sales and marketing activities due to compliance burdens[81]. - For products covered by Medicaid, the company must offer substantial rebates and discounts, which complicates pricing strategies and compliance efforts[82]. - The Affordable Care Act (ACA) has significantly impacted the healthcare industry, including increased Medicaid rebates and new pricing methodologies for biopharmaceutical products[85]. - The Inflation Reduction Act of 2022 introduces penalties for drug price increases above inflation rates and government price-setting for certain Medicare drugs starting in 2026[87]. - The company’s compliance with environmental and worker safety regulations may require significant capital expenditures in the future[93]. Competition and Market Dynamics - The company faces significant competition in the biotechnology and pharmaceutical industries, with competitors having greater resources and capabilities[47]. - The principal competition for pilavapadin includes duloxetine and pregabalin, while LX9851 competes with approved weight loss drugs[50][51]. - The company expects competition for sotagliflozin in treating hypertrophic cardiomyopathy from generic beta blockers and cardiac myosin inhibitors[53]. - Third-party payers are increasingly limiting coverage and reimbursement for new drugs, creating uncertainty in pricing and demand[154]. - The COVID-19 pandemic has disrupted business operations and clinical trials, potentially impacting future commercialization efforts[158]. - The emergence of new COVID-19 variants could further disrupt recruitment for clinical trials and overall business operations[159]. - The company faces intense competition from other pharmaceutical and biotechnology firms, which may hinder the commercialization of its drug candidates[156]. Intellectual Property and Trade Secrets - The company faces challenges in protecting its intellectual property, which could adversely affect its competitive position in the market[192]. - The patent positions of biotechnology and pharmaceutical companies, including the company, are generally uncertain and may not provide sufficient protection against competitors[193]. - The company may incur substantial costs in defending its patents and intellectual property rights, with uncertain outcomes that could negatively impact its business[194]. - The company is at risk of being blocked from using its drug candidates if third-party patents are issued, which could limit its ability to commercialize products[195]. - The company relies on trade secret protection for proprietary information, but measures taken may not provide adequate protection against competitors[198]. Workforce and Management - As of February 28, 2025, the company employed 103 persons, with 19 holding M.D. or Ph.D. degrees and 33 holding other advanced degrees[108]. - The company has experienced substantial growth in employee numbers, which may place significant demands on its management and operational resources[210]. - The loss of key personnel could impair the company's ability to operate and expand its operations effectively[212]. - The company may face challenges in recruiting and retaining qualified personnel, which is critical for advancing its research and development efforts[213]. - The company’s executive team includes experienced leaders from major pharmaceutical firms, enhancing its strategic capabilities[97][98][99].

Group 1 - Lexicon Pharmaceuticals will participate in a fireside chat at the Leerink Partners Global Healthcare Conference 2025 on March 12 at 10:00 a.m. ET [1] - The event will be accessible live and as a replay on the company's website [1] Group 2 - Lexicon Pharmaceuticals is a biopharmaceutical company focused on pioneering medicines that transform patients' lives [2] - The company utilizes the Genome5000™ program to study nearly 5,000 genes, identifying over 100 protein targets with significant therapeutic potential [2] - Lexicon has advanced multiple medicines to market and has a pipeline of drug candidates in various stages of development for conditions such as heart failure, neuropathic pain, obesity, cardiology, and diabetes [2]

Financial Data and Key Metrics Changes - Lexicon Pharmaceuticals ended 2024 with $238 million in cash, cash equivalents, and short-term investments, compared to $170 million as of December 31, 2023 [28] - The company reported $26.6 million in revenue for Q4 2024 and $31.1 million for the full year 2024, including a $25 million upfront payment from the Beatrice licensing agreement [28] - Research and development expenses for Q4 2024 increased to $26.7 million from $14.8 million in Q4 2023, while full-year R&D expenses decreased to $84.5 million from $106 million in 2023 [29] - Net loss for Q4 2024 was $33.8 million, or $0.09 per share, compared to a net loss of $49.8 million, or $0.20 per share, in Q4 2023 [31] Business Line Data and Key Metrics Changes - The PROGRESS Phase 2b study of pilabapatin showed a clear separation in Average Daily Pain Score (ADPS) from baseline, with the 10-milligram dose demonstrating meaningful improvement compared to placebo [11][14] - The Sonata Phase 3 study of sotagliflozin in hypertrophic cardiomyopathy (HCM) is ongoing, with patient enrollment proceeding as planned [10] Market Data and Key Metrics Changes - Diabetic peripheral neuropathic pain (DPNP) affects approximately nine million people in the US, indicating a significant market opportunity for new treatment options [17] - Current treatments for DPNP are inadequate, with about 60% of patients having tried multiple therapies and only a third being somewhat satisfied with their treatment [19] Company Strategy and Development Direction - Lexicon Pharmaceuticals has strategically repositioned to focus on clinical development programs, including advancing IND enabling studies for LX9851, an oral ACSL5 inhibitor for obesity [10][21] - The company aims to enhance its clinical and commercial capabilities through partnership discussions, particularly for its novel therapies [36] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the potential of pilabapatin to be the first novel oral, non-opioid DPN medication in over two decades, with plans to advance the 10-milligram dose into pivotal trials [14][16] - The company anticipates total operating expenses for 2025 to be in the range of $135 million to $145 million, with R&D expenses projected between $100 million to $105 million [33] Other Important Information - Lexicon Pharmaceuticals has ceased all promotion of Impepper in the U.S. heart failure market due to a challenging market access environment [24] - The company is actively working with Beatrice on registration and regional development efforts for sotagliflozin outside the U.S. and Europe [25] Q&A Session Summary Question: What is the clinical development plan for LX9851? - Management sees LX9851 being developed as both monotherapy and combination therapy, with a standard Phase 1 program focusing on weight loss, tolerability, and mechanistic differentiation from GLP-1 [42][44][48] Question: How is enrollment progressing in the HCM study? - Enrollment is on track with approximately 500 patients targeted, and final study results are expected towards the end of 2026, with an FDA filing anticipated in Q1 2027 [54][56] Question: Will the Phase 2b data support pivotal trial status? - The current assumption is that the Phase 2b trial will not be considered pivotal, with plans for two pivotal trials in the Phase 3 program [76] Question: What are the commercialization plans for sotagliflozin? - The company plans to commercialize sotagliflozin in the U.S. while seeking a partner for Europe, focusing on centers of excellence for HCM patients [84][86]

Core Insights - Lexicon Pharmaceuticals reported a quarterly loss of $0.09 per share, better than the Zacks Consensus Estimate of a loss of $0.11, and improved from a loss of $0.20 per share a year ago, indicating an earnings surprise of 18.18% [1] - The company achieved revenues of $26.55 million for the quarter ended December 2024, surpassing the Zacks Consensus Estimate by 215.37%, compared to revenues of $0.7 million in the same quarter last year [2] - Lexicon shares have declined approximately 54.5% year-to-date, contrasting with the S&P 500's decline of -0.7% [3] Earnings Outlook - The future performance of Lexicon's stock will largely depend on management's commentary during the earnings call and the company's earnings outlook [4] - Current consensus EPS estimate for the upcoming quarter is -$0.12 on revenues of $3.05 million, and for the current fiscal year, it is -$0.45 on revenues of $17.35 million [7] Industry Context - The Medical - Biomedical and Genetics industry, to which Lexicon belongs, is currently ranked in the top 27% of over 250 Zacks industries, suggesting a favorable outlook compared to lower-ranked industries [8] - Empirical research indicates a strong correlation between near-term stock movements and trends in earnings estimate revisions, which can be tracked using tools like the Zacks Rank [5][6]

[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]