Lexicon Pharmaceuticals FY Conference Summary Company Overview - **Company**: Lexicon Pharmaceuticals (NasdaqGS:LXRX) - **Conference Date**: December 04, 2025 - **Key Speakers**: Scott Coiante (SVP and CFO), Craig Granowitz (SVP and Chief Medical Officer) Key Areas of Focus 1. **Zynquista for Type 1 Diabetes** - Received feedback from the FDA indicating a path for resubmission with new safety data from ongoing trials [2][5] - Acknowledged the urgency for additional glycemic control options beyond insulin, as only 20% of patients achieve their time-in-range goals [5][17] - FDA accepted the drug's efficacy in lowering A1C and reducing severe hypo events but requested fresh data on diabetic ketoacidosis (DKA) rates [6][12] 2. **Sonata Trial for Hypertrophic Cardiomyopathy (HCM)** - The Sonata trial is progressing well with projected enrollment completion in the first half of next year [2] - The primary endpoint is the Kansas City Cardiomyopathy Questionnaire (KCCQ), aiming for a clinically meaningful effect size of 4-5 points on a placebo-adjusted basis [13][16] 3. **Licensing and Partnerships** - Licensed LX9851 (obesity asset) to Novo Nordisk for over $1 billion, with ongoing IND submission preparations [3] - Partnered Impefa (heart failure drug) with Viatris, which has received approval in the UAE and filed in five additional jurisdictions [3] 4. **Pilavapadin for Diabetic Peripheral Neuropathic Pain (DPNP)** - The largest phase 2 program for DPNP with nearly 700 patients treated, showing significant efficacy [25] - Plans to anchor the phase 3 program with FDA on the selected 10 mg dose and conduct two positive parallel trials for approval [28][30] Regulatory and Market Insights - **Zynquista**: The FDA is open to non-traditional data routes to address DKA concerns, leveraging data from a large Danish trial [6][12] - **HCM**: Combination therapy is emphasized as essential for effective treatment, with sotagliflozin positioned uniquely to address both cardiac work and myocardial energetics [14][23] - **Pilavapadin**: The development model aims for a large partner to assist in market development during phase 3, given the global market opportunity [25] Additional Considerations - **Sotagliflozin's Role**: Seen as a potential first agent approved for type 1 diabetes alongside insulin, addressing a significant unmet need in the market [17][19] - **Placebo Mitigation Strategies**: Emphasis on minimizing placebo effects in trials by limiting the number of arms and reinforcing patient education [31][32] - **Novo Nordisk's Interest**: Novo is enthusiastic about LX9851 due to its oral administration and unique mechanism targeting satiety rather than appetite [34] Conclusion Lexicon Pharmaceuticals is actively advancing multiple programs with significant potential in diabetes and cardiovascular diseases, focusing on regulatory engagement and strategic partnerships to enhance their market position and address critical patient needs.

Disease Overview - Rheumatic heart disease is an old disease affecting young people, striking children and teenagers [4][5] - It starts with common infections like infected skin sores or strep throat, leading to an abnormal immune response [11][12] - The abnormal immune response damages heart valves, causing blood to flow backward, potentially leading to heart failure and death [13][17] Prevalence and Disparities - In developed countries like the US and Denmark, rates of rheumatic fever and rheumatic heart disease plummeted in the 20th century due to improved living conditions and antibiotics [19] - However, in the Northern Territory, remote communities, and other regions, rates are as high as those seen 100 years ago in developed countries [20][21] - In some communities, over 5% (one in 20) of school-aged children have been diagnosed with rheumatic heart disease [21] - Screening reveals that over 50% of cases in Australia and over 90% in Teimolestee are new, previously undiagnosed cases [23] Community-Based Solutions - Communities want to find undiagnosed children and get them on treatment to prevent heart failure, surgery, and death [29] - Communities prefer local Aboriginal health workers, practitioners, doctors, and nurses to be trained to diagnose and treat the disease [31][32] - Training local healthcare providers is not only possible but also better, enabling them to use technology to diagnose and treat rheumatic heart disease [33][34] Call to Action - The industry should listen to communities, understand their priorities, and work together to address challenges like rheumatic heart disease [25][27] - The industry should support policy changes to address poverty and the effects of colonization [28] - The industry should walk alongside communities, learn from their perspective, and empower them to lead the solutions [26][35]

Health Status - The subject experienced mild swelling in the lower legs, prompting a thorough evaluation [1] - Vascular studies revealed chronic venous insufficiency, a common condition in individuals over 70 [2] - No evidence of deep vein thrombosis or arterial disease was found [2] - Laboratory testing results, including complete blood count, comprehensive metabolic panel, coagulation profile, D-dimer, BT type, natriotic peptide, and cardiac biomarkers, were all within normal limits [2][3] - An echocardiogram confirmed normal cardiac structure and function, with no signs of heart failure, renal impairment, or systemic illness [3] - Minor bruising on the back of the hand is consistent with soft tissue irritation from frequent handshaking and aspirin use [4] Medication & Prevention - Aspirin is taken as part of a standard cardiovascular prevention regimen [4] - Bruising is a well-known and benign side effect of aspirin therapy [4]