UPDATE Q3 Earnings November 6, 2025 Forward-Looking Statements 2 • This presentation, including any oral presentation accompanying it, contains "forward-looking statements," including statements about Lexicon's strategy and operating performance and events or developments that we expect or anticipate will occur in the future, such as projections of our future results of operations or of our financial condition, the potential therapeutic and commercial potential of pilavapadin (LX9211), LX9851, sotagliflozin ...

Core Insights - Lexicon Pharmaceuticals has made significant progress in its R&D initiatives and operational strategies, positioning itself for a pivotal year in 2026 [3][4]. R&D and Pipeline Highlights - Pilavapadin (LX9211) is being developed for Diabetic Peripheral Neuropathic Pain (DPNP) and has shown a two-point reduction in average daily pain scores in a Phase 2b study [7]. - All IND-enabling studies for LX9851, a drug for obesity, have been completed and submitted to Novo Nordisk, with potential milestone payments of up to $1 billion [5][7]. - The SONATA-HCM Phase 3 study of sotagliflozin is on track for enrollment completion by 2026, with 130 sites initiated across 20 countries [14]. Financial Performance - Total revenues for Q3 2025 increased to $14.2 million from $1.8 million in Q3 2024, primarily driven by licensing revenue from Novo Nordisk [9]. - R&D expenses decreased to $18.8 million in Q3 2025 from $25.8 million in Q3 2024, reflecting lower external research costs [10]. - SG&A expenses significantly decreased to $7.6 million in Q3 2025 from $39.6 million in Q3 2024 due to strategic repositioning [11]. Net Loss and Cash Position - The net loss for Q3 2025 was $12.8 million, or $0.04 per share, a reduction from a net loss of $64.8 million, or $0.18 per share, in Q3 2024 [12]. - As of September 30, 2025, Lexicon had $145.0 million in cash and investments, down from $238.0 million at the end of 2024 [13].

Pipeline Progress - Pilavapadin 10 mg consistently delivered clinically meaningful pain reduction in Phase 2 trials[8] - Lexicon plans to present full Phase 2 results for Pilavapadin in September 2025 and partnership discussions are ongoing[5] - IND-enabling studies of LX9851 are on track to be completed in 2025[5] - Accelerated site initiations are underway for the Phase 3 SONATA-HCM study of sotagliflozin in HCM[5] Sotagliflozin in HCM - Approximately 1.1 million people in the U S have either obstructive or non-obstructive HCM[15] - 30% of HCM patients are diagnosed with oHCM and 70% are diagnosed with nHCM[16] - The SONATA-HCM Phase 3 study is evaluating sotagliflozin 400 mg versus placebo in 500 patients with oHCM and nHCM[22] - Enrollment in the SONATA-HCM Phase 3 study is accelerating, with all sites expected to be active by the end of Q3 2025[23] Financial Performance - Lexicon reported $28.9 million in total revenues for Q2 2025, including $1.3 million in net product revenues and $27.5 million in licensing revenue[30] - The $27.5 million in licensing revenue includes an upfront payment for the exclusive licensing agreement of LX9851 with Novo Nordisk[31] - Total operating expenses for 2025 are now expected to be between $105 million and $115 million[33]

Core Insights - Lexicon Pharmaceuticals is making significant progress in its R&D strategy, with ongoing partnership discussions for pilavapadin and IND-enabling studies for LX9851 on track for completion in 2025 [3][4][8] - The company reported a substantial increase in total revenues for Q2 2025, reaching $28.9 million, compared to $1.6 million in Q2 2024, primarily driven by licensing revenue from Novo Nordisk [11][21] - Lexicon's net income for Q2 2025 was $3.3 million, a notable improvement from a net loss of $53.4 million in the same period last year [14][21] Partnership and Product Development - Partnership discussions for pilavapadin are ongoing, with full Phase 2 data expected to be presented at an upcoming medical meeting [3][8] - LX9851, a novel oral candidate for obesity, is in preclinical development, with an exclusive licensing agreement with Novo Nordisk that includes an upfront payment of $45 million and potential milestone payments up to $1 billion [8][11] - The SONATA Phase 3 study for sotagliflozin in hypertrophic cardiomyopathy (HCM) is progressing well, with over 100 sites initiated across 20 countries [3][16] Financial Performance - Total revenues for Q2 2025 were $28.9 million, consisting of $27.5 million in licensing revenue and $1.3 million from INPEFA® sales [11][21] - Research and development expenses decreased to $15.7 million in Q2 2025 from $17.6 million in Q2 2024, reflecting optimized resource allocation [12][21] - Selling, general, and administrative expenses significantly decreased to $9.4 million in Q2 2025 from $39.2 million in Q2 2024 due to strategic repositioning [13][21] Cash Position and Investments - As of June 30, 2025, Lexicon had $139 million in cash and investments, down from $238 million at the end of 2024, primarily due to severance payments related to strategic changes [15][21] - The company also reported $29 million in restricted cash as of the same date [15][21] Pipeline and Future Outlook - Lexicon is focused on advancing its pipeline, with sotagliflozin being commercially available in the U.S. for heart failure as INPEFA® [7][19] - The company is also preparing for regulatory filings for sotagliflozin in various international markets, with submissions already made in the UAE and Saudi Arabia [16][19]

Business Highlights - Lexicon entered an exclusive worldwide licensing agreement with Novo Nordisk for LX9851[5, 21] - Pilavapadin (LX9211) PROGRESS readout identified a de-risked dose of 10mg to move into Phase 3 trials[5] - The company reduced debt and strengthened its financial position[5] - Pilavapadin 10 mg has consistently delivered clinically meaningful pain reduction[7] Market Opportunity - Approximately 9 million people in the U S living with diabetes suffer from DPNP[10] - It is projected that there will be 13 million DPNP patients in the U S by 2035[10] - Approximately 70% of patients with neuropathic pain do not achieve partial pain management[10] - Approximately 11 million people in the U S have either obstructive or non-obstructive HCM[14] Financial Overview - As of March 31, 2025, Lexicon had $1948 million in cash, cash equivalents, and short-term investments[26] - Total debt was $586 million as of March 31, 2025[26] - Total revenues for Q1 2025 were $13 million compared to $11 million in Q1 2024[26] - The company expects total 2025 operating expenses to be between $135 million and $145 million[29]

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]