Slides
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1 Second Quarter 2025 Earnings Presentation August 6, 2025
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2 Forward-Looking Statements • 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 and our other drug programs, the success of our commercialization efforts with respect to INPEFA® (sotagliflozin) and any other approved products, the results of and expected timing of the completion of ongoing and future clinical trials, the expected timing and outcome of discussions with regulatory authorities regarding such trials and any applications for approval based on such trials, our other research and development efforts, and the anticipated trends in our business. • These forward-looking statements are based on management’s current assumptions and expectations and involve risks, uncertainties and other important factors that may cause our actual results to be materially different from any future results expressed or implied by such forward-looking statements. • Information identifying such important factors is contained in our most recent annual report on Form 10-K and quarterly reports on Form 10-Q, including the sections entitled “Risk Factors,” as well as our current reports on Form 8-K, in each case filed with the Securities and Exchange Commission. • Lexicon undertakes no obligation to update or revise any such forward-looking statements, whether as a result of new information, future events or otherwise.
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3 Mike Exton, Ph.D. Director and Chief Executive Officer Business Overview
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4 Strong execution against strategic pivot to R&D focused company Pilavapadin full Phase 2 results to be presented September 2025; partnership discussions ongoing Excellent progress with Viatris to make sotagliflozin available outside the U.S. and EU On track to complete IND- enabling studies of LX9851 in 2025 Well positioned to continue advancing and investing in innovative R&D pipeline Accelerated site initiations in Phase 3 SONATA- HCM study of sotagliflozin in HCM Company Overview
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5 Craig Granowitz, M.D., Ph.D. Senior Vice President and Chief Medical Officer Pipeline Overview
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6 Pilavapadin 10 mg has consistently delivered clinically meaningful pain reduction ADPS: a vera ge daily pain score *Pilavapadin (LX9211) 100/10 mg: included 100 mg as day 1 loading dose **Pilavapadin (LX9211) 20 mg for 7 days and then 10 mg thereafter PROGRESS Phase 2b ADPS Reduction -1.74 -1.70 -1.31 -2.0 -1.5 -1.0 -0.5 0.0 LS Mean Change from Baseline at week 8 PLACEBO RELIEF Phase 2a ADPS Reduction -1.39 -0.72 -2.0 -1.5 -1.0 -0.5 0.0 LS Mean Change from Baseline at week 6 PLACEBO Pilavapadin 100/10 mg* Pilavapadin 10 mg Pilavapadin 20/10 mg** Pilavapadin
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7 Pilavapadin Pilavapadin demonstrated clinically meaningful efficacy Pilavapadin demonstrated acceptable safety and tolerability profile 10 mg identified as the appropriate dose for registrational studies Provided considerations forcontinued improvement of study design to lower placebo response and improve adherence Advisory board supported key findings in PROGRESS topline data Secondary data analysis of comprehensive Phase 2 program ongoing
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8 Pilavapadin: Validated MOA, compelling profile, and broad applicability Clinically meaningful pain reduction demonstrated across three Phase 2 trials* A full portfolio with a Phase 3- ready lead indication in DPNP and additional indications ready for Phase 2 IND-enabling work complete in multiple neuroscience indications Extensive safety and tolerability experience with >600 pilavapadin- treated patients Long patent life through 2040 when including anticipated five- year patent term extension Pilavapadin A portfolio in a pill with multiple near-term catalysts *2 Phase 2 studies in DPNP, 1 Phase 2 study in PHN
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9 HCM: A significant and underpenetrated market with high disease burden Sotagliflozin HCM 30% 70% ~1% ~1.1 million people in the U.S. have either obstructive or non-obstructive HCM* 43% Diagnosed with oHCM Diagnosed with nHCM CMI total market penetration Progress to heart failure Common symptoms shortness of breath, fatigue, dizziness** HCM can lead to heart failure, atrial fibrillation, and stroke *CVrg Market Strategies. Cardiovascular Resource Group, Oct. 2023. ** Zaiser, Erica, et al. “Patient Experiences with Hypertrophic Cardiomyopathy: A Conceptual Model of Symptoms and Impacts on Quality of Life.” Journal of Patient-Reported Outcomes, vol. 4, no. 1, Dec. 2020 Common signs include altered cardiac energetics, fibrosis, and diastolic dysfunction
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10 Also acts directly on the myocardium Once-daily oral dosing enables broad potential adoption with no REMS Approved for heart failure with no observed increased risk of Afib to date Broad potential for sotagliflozin within HCM treatment landscape Broad proposed indication for both nHCM and oHCM with potential for use alone or in combination Sotagliflozin HCM Only HCM agent that works inside and outside the heart to reduce symptoms of HCM as well as to reduce HF and MACE events
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11 Significant data support sotagliflozin as only SGL T inhibitor to work inside and outside the heart for HCM Sotagliflozin HCM Data generated validate use of dual SGLT1 and SGLT2 inhibition with sotagliflozin in HCM Animal models in HCM* and HFpEF* • Improved diastolic function • Reduced • Wall thickness • Fibrosis • Cardiac inflammation Ex vivo in HCM myocardial slices* • Reduced stroke work • Increase metabolites associated with improved cardiac energetics Lexicon and IIS clinical studies • SONATA-HCM • SOTA-CROSS (nHCM)* • SOTA-P-CARDIA (HFpEF)* *IIS: Investigator-initiated studies
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12 SONA T A-HCMPhase 3 study for oHCM and nHCM Sotagliflozin 400 mg (N = 250) Placebo (N = 250) R 1:1 Up to 21 days screening 4-week Follow-up26-week double-blind treatment period Global Phase 3 SONATA-HCM Trial Inclusion Criteria • Adults with HCM (obstructive/non-obstructive) • LVEF ≥50% or ≥55% for those on cardiac myosin inhibitor • KCCQ23 CSS <85 • NYHA Class II or III Primary Endpoint • Change from baseline in KCCQ Clinical Summary Scale (CSS) score Enrollment accelerating – on track for all sites active by end of Q3 2025 Sites opened in U.S., EU, Israel, and LATAM Only ongoing trial to evaluate both obstructive and non-obstructive HCM Potential for supplemental new drug application (sNDA) with broad label Sotagliflozin HCM
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13 SOTA-CROSSSOTA-P-CARDIA Investigator-initiated studies complement registrational study and may support sotagliflozin use in HCM • Readout late 2025/early 2026 • Investigate cardiorenal mechanistic benefits of sotagliflozin in HFpEF • 6-month, placebo- controlled study • 88 patients • Readout mid-to-late 2026 • Evaluate sotagliflozin in symptomatic nHCM • 12-week, placebo- controlled, crossover study • 26 patients Sotagliflozin HCM SONATA-HCM • Evaluate sotagliflozin in patients with symptomatic HCM • 26-week, placebo- controlled study • 500 patients • Key endpoints include change in KCCQ and NYHA class improvement Endpoints include measures related to cardiac function, exercise performance, and quality of life (KCCQ) HFpEF: heart failure with preserved ejection fraction; nHCM: non-obstructive hypertrophic cardiomyopathy; *KCCQ: Kansas City Cardiomyopathy questionnaire
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14 IND-enabling studies under strategic licensewith Novo Nordisk for LX9851 remain on track LX9851 First-in-class, potent, selective, orally bioavailable, investigational small molecule ACSL5 inhibitorLX9851 Exclusive, worldwide license to develop, manufacture, and commercialize LX9851 in all indications Positioned to benefit from Novo Nordisk size, scale and capabilities – IND-enabling studies on track to complete by end of 2025 $75 million in upfront and potential near-term milestone payments ($45 million upfront payment received in April); up to $1 billion in total upfront and potential milestones; tiered royalties Potential differentiation in the obesity market with shift in focus to orals, combinations, and improved weight-loss maintenance ACSL5: Acyl-CoA synthetase 5
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15 Scott Coiante Chief Financial Officer Financial Overview
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16 Q2 2025 Financial Summary Q2 2025 Q2 2024 Revenue: Net product revenues $1.3 $1.6 Licensing revenue $27.5 --- T otal revenues $28.9 $1.6 Operating expenses: R&D $15.7 $17.6 SG&A $9.4 $39.2 T otal operating expenses $25.1 $57.0 Net income / (loss) $3.3 ($53.4) Net income / (loss) per common share $0.01 ($0.17) As of June 30, 2025* As of December 31, 2024 Cash, cash equivalents, short-term investments and restricted cash $168.0 $238.0 T otal assets $225.6 $298.4 T otal debt $56.1 $100.3 $ (in millions except per share amounts) Revenue includes $27.5 million of revenue upfront payment for exclusive licensing agreement of LX9851 with Novo Nordisk Financials
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17 Q2 2025 Financial Highlights Q2 2025 Key Financial Highlights Full Year 2025 Operating Expenses* • The $45 million upfront payment (received in April) under licensing agreement with Novo Nordisk was used to improve balance sheet by reducing long- term debt. • Quarter over quarter operating expenses were down $31.9 million primarily due to the strategic repositioning as R&D focused company in late 2024. • Total 2025 operating expenses now expected to be between $105 - $115 million (previously $135 - $145 million) • R&D is now expected between $70 - $75 million (previously $100 - $105 million) • Excludes clinical trial costs related to Phase 3 pivotal studies of pilavapadin • SG&A remains expected between $35 - $40 million *As of June 30, 2025 Financials
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18 Summary Mike Exton, PhD Director and Chief Executive Officer
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19 Partnership strategy intended to enable focus on core cardiometabolic expertise Geographic expansion through Viatris’ global capabilities Maximizing asset value with Novo’s leadership position in obesity Unlock value globally and across multiple indications Approved Pre-Clinical Phase 3 Exclusive licensing agreement for sotagliflozin in all indications All markets outside of the U.S. and Europe $25M upfront; eligible for up to almost $200M in milestone payments Exclusive licensing agreement for LX9851 in all indications Global markets $75M in upfront and potential near-term milestones; eligible for up to $1B in total upfront and milestone payments Partnering to fully realize the “pipeline in a pill” potential of this novel mechanism and accelerate speed to market for DPNP Pilavapadin Partnering Innovative and flexible strategy in action to unlock long-term value
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20 Well-positioned with a portfolio of potential “pipelines in a pill” Exploring opportunities across multiple therapeutic areas Sotagliflozin Heart Failure expansion ex-US Hypertrophic Cardiomyopathy (HCM) Pilavapadin* Diabetic Peripheral Neuropathic Pain (DPNP) LX9851 Obesity/Weight Management Postherpetic Neuralgia (PHN) Additional differentiation data Spasticity 2025 2026 2027 2028 2029 Regulatory Approval Ph3 Planning / Execution Ph2 Planning / Execution ex-US, ex-EU Launches IND-Enabling Studies Regulatory Approval Regulatory Approval Regulatory Approval Ph3 Planning / Execution Timelines are illustrative and represent potential scenarios aligned to Lexicon’s overall strategy *Execution of trials and subsequent regulatory support would require partnership or additional funding ** IIS: Investigator-initiated studies IIS** Studies Underway Ph3 Ongoing Exclusive license for all indications Conclusion
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21 Pilavapadin • Full PROGRESS data anticipated in Q3 • End of Phase 2 meeting before year-end • Ongoing partnership discussions • Diabetic Peripheral Neuropathic Pain (DPNP) LX9851 • Obesity and Weight Management • Ongoing collaboration withNovo Nordisk; IND- enabling studieson track for completion by end 2025 Well positioned for continued progress across all programs throughout 2025 Sotagliflozin • US, EU, Israel and LATAM sites enrolling • All Phase 3 study sites running by Q3 • Data from IIS beginning late 2025 readout • Hypertrophic Cardiomyopathy INPEFA® (sotagliflozin) • Regulatory submissions and approvals by Viatris ex- U.S. and EU – ongoing • Heart Failure ZYNQUISTA® (sotagliflozin) • End of review evaluation process ongoing • Patients continue to strongly advocate for approval • Type 1 Diabetes Conclusion
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22 Q&A Mike Exton, Ph.D. Director and Chief Executive Officer Craig Granowitz, M.D., Ph.D. Senior Vice President and Chief Medical Officer Scott Coiante Senior Vice President and Chief Financial Officer
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23 Thank You