Slides
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Second Quarter 2026 Earnings August 6 , 2026 Lexicon pharmaceuticals
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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 sotagliflozin, pilavapadin, LX9851 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 Q2 2026 Highlights Mike Exton Ph.D. Director and Chief Executive Officer
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4 Highlights SONATA-HCM Enrollment Complete Pivotal study of sotagliflozin fully randomized; topline data anticipated Q1 2027 >500 Patients randomized, substantially exceeding enrollment target 130+ Clinical sites across 20 countries Q1 2027 Topline results anticipated nHCM + oHCM Only ongoing Phase 3 study in both HCM subtypes Study highlights • Largest Phase 3 study to date including both non-obstructive (nHCM) and obstructive (oHCM) hypertrophic cardiomyopathy • Substantial majority of patients have nHCM, a group with limited effective treatment options • Randomized, double-blind, placebo-controlled trial; primary endpoint is change from baseline to week 26 in KCCQ Clinical Summary Score • Sotagliflozin is a dual SGLT1 + SGLT2 inhibitor with a differentiated mechanism vs available HCM treatments "Having a well-tolerated medication with a distinct mechanism of action that can complement other therapies would be an important advance for physicians and patients" Sharlene M. Day, M.D., co-principal investigator for SONATA-HCM, Presidential Professor, Director of Translational Research of the Penn Cardiovascular Institute, University of Pennsylvania
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5 Highlights Second Quarter 2026 R&D Highlights Advancing our pipeline of novel targeted therapies Neuropathic Pain DPNP regulatory path to Phase 3 pivotal studies clear Other Indications IND-enabling work ongoing across multiple indications P I L A V A P A D I N A A K 1 T1D Patient exposure identified by FDA as adequate to be achieved end of August Data reflects DKA rates similar to standard of care in STENO1 HCM Phase 3 SONATA-HCM enrollment now complete Topline data expected Q1 2027 S O T A G L I F L O Z I N Obesity Phase 1 study underway by Novo Nordisk; second of three potential $10M milestone payments received L X 9 8 5 1 Heart Failure — Global Expansion Viatris launch underway in UAE; regulatory submissions expanding across ex-US and ex-Europe markets HCM: hypertrophic cardiomyopathy; DPNP: diabetic peripheral neuropathic pain; T1D: type 1 diabetes; STENO1: Multifactorial Intervention to Reduce Cardiovascular Disease in Type 1 Diabetes, Steno Diabetes Center Copenhagen (https://clinicaltrials.gov/study/NCT06082063) C a r d i o m e t a b o l i c
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6 Pipeline Updates Craig Granowitz, M.D. Ph.D. Senior Vice President and Chief Medical Officer
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7 Cardiometabolic S OTAG L I F LO Z I N Late-stage development programs in HCM and type 1 diabetes
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8 Hypertrophic cardiomyopathy (HCM) is characterized by adverse cardiac remodeling associated with myocardial hypertrophy, diastolic dysfunction, and fibrosis Qin, Fuzhong & Pimentel, David & Baka, Tomas & Zhang, Aifeng & Croteau, Dominique & Luptak, Ivan & Colucci, Wilson. (2025). Abstract 4343284: Dual SGLT1 and 2 Inhibition with Sotagliflozin Ameliorates Adverse Cardiac Remodeling and Diastolic Dysfunction in Mice with HCM Due to Tropomyosin E180G Mutation. Circulation. 152. 10.1161/circ.152.suppl_3.4343284.
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9 DIASTOLIC DYSFUNCTION The heart is too stiff to fill properly during relaxation Sotagliflozin in HCM Many presentations… one disease Without Obstruction HYPERTROPHIC CARDIOMYOPATHY oHCM The hallmark of obstructive disease is a physical blockage in the Left Ventricular Outflow Tract (LVOT). LVOT Gradient ≥ 30 mmHg nHCM Characterized by global or localized thickening without a significant outflow tract pressure gradient. LVOT Gradient < 30 mmHg With Obstruction Diastolic Dysfunction is the Underlying Fundamental Issue of Both oHCM and nHCM Source: HCMAi, Hypertrophic Cardiomyopathy Association
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10 Sotagliflozin in HCM Mechanistic Benefits of SGLT1 in HCM Enhanced calcium handling for myocardial relaxation Improved energy utilization of ketones versus glucose Reduced inflammation and fibrosis Reduced epicardial fat Sotagliflozin Predominantly Improves Diastolic Dysfunction By Improving Cardiac Metabolism SGLT1i expressed predominantly in the myocardium1 and increased in ventricular hypertrophy Works directly on the heart, improving cardiac metabolism in HCM 1. Li Y, Xu G. Sodium glucose cotransporter 1 (SGLT1) inhibitors in cardiovascular protection: Mechanism progresses and challenges. Pharmacological Research 176 (2022). doi.org/10.1016/j.phrs.2021.106049 2. Fonseca-Correa JI, Correa-Rotter R.Sodium-Glucose Cotransporter-2 Inhibitors Mechanisms of Action: A Review. Frontiers in Medicine. 2021;8:777861.
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11 Key Eligibility Criteria • Adults with HCM (oHCM or nHCM) • KCCQ23 CSS <85 Primary endpoint: Change from baseline in KCCQ CSS Sotagliflozin 400 mg* Placebo *For patients not tolerating treatment, sotagliflozin (and matching placebo) down-titrated to 200 mg starting at Week 4. 4-week Follow-up 26-week double-blind treatment periodUp to 14 days Screening R 1:1 Sotagliflozin in HCM SONATA-HCM Phase 3 Study for oHCM and nHCM Enrollment complete; 26-week study with topline data anticipated Q1 2027 SONATA-HCM Enrollment Complete >500 patients randomized, including both nHCM and oHCM Topline results anticipated Q1 2027 Largest Phase 3 study to date of both nHCM and oHCM LVOT = left ventricular outflow tract; NYHA = New York Heart Association; KCCQ = Kansas City Cardiomyopathy Questionnaire; R = randomization.
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12 Data Received to Date from STENO1 Supports ZYNQUISTA NDA Resubmission Sotagliflozin in T1D Adequate enrollment achieved to provide patient exposure levels discussed with FDA STENO1 providing patient-level data; NDA resubmission anticipated in Q4 2026 Diabetic ketoacidosis (DKA) rates in the exposed population similar to standard of care and well below InTandem studies
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13 Partnering Phase 1 Trial of LX9851 Ongoing by Novo Nordisk • First-in-class, non-incretin, oral, small molecule inhibitor of ACSL5 in development for obesity and associated metabolic disorders • Phase 1 study of LX9851 initiated in March • $20 million in development milestones achieved year-to-date ACSL5: Acyl-CoA Synthetase 5 Potential to achieve a third $10 million milestone in 2026
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14 Financial Overview Scott Coiante Chief Financial Officer
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15 Financials As of June 30, 2026 As of December 31, 2025 Cash, cash equivalents, short- term investments and restricted cash $190.6 $125.2 Total assets $250.1 $185.0 Total debt $51.4 $54.0 Q2 2026 Q2 2025 Total revenues $0.7 $28.9 R&D ($17.4) ($15.7) SG&A ($9.8) ($9.4) Total operating expenses ($27.2) ($25.1) Net income (loss) ($31.8) $3.3 Net income (loss) per common share ($0.07) $0.01 $ (in millions except per share amounts) Q2 2026 Financial Summary
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16 Financials Q2 2026 Financial Highlights and FY 2026 Guidance Q2 2026 Key Financial Highlights • Entered into $100 million loan facility with Hercules Capital • Strengthened balance sheet and expanded access to non-dilutive capital • $55 million funded at close to repay existing loan facility with Oxford Finance • Two additional tranches totaling $45 million available under certain conditions • Total 2026 operating expenses expected to be between $100 - $110 million • R&D expected between $63 - $68 million • Excludes expenses related to Phase 3 pilavapadin trials • SG&A expected between $37 - $42 million • Includes targeted investment in pre- commercialization activities Full Year 2026 Guidance Operating Expenses* *As of August 6, 2026
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17 Summary Mike Exton Ph.D. Director and Chief Executive Officer
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18 Conclusion Lexicon’s Lead to Succeed strategy in action Driving value and growth with opportunities for the greatest patient impact Large markets with significant need First or only in therapy or class Leading clinical and medical expertise
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19 Sotagliflozin in HCM Potential to be a first-line therapy in symptomatic HCM The only HCM agent that works inside and outside the heart to reduce symptoms of HCM, as well as reduce HF and MACE events Sotagliflozin is both a Hemodynamic and Metabolic Agent in HCM Anticipated ease of adoption for patients and prescribers would enable broad uptake, as a potential first-line agent with no REMS Novel MOA, with SGLT1 inhibition acting directly on the myocardium to modify cellular energetics Designed to treat both types of HCM by addressingcellular stiffness (diastolic dysfunction) and energy starvation, which happen in all HCM hearts
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20 Reshaping Lexicon Over the Next 12 Months T1D Data provided to FDA supports potential approval Additional patient-level data in process from STENO1 for anticipated NDA resubmission Q4 HCM SONATA on target for topline data Q1 2027 S O TA G L I F L O Z I N Neuropathic Pain and other high-value indications Ongoing evaluation of strategic options IND-enabling work for additional indications continues P I L A V A P A D I N Obesity Phase 1 study ongoing $20 million in milestones received; potential for additional $10 million near-term milestone L X 9 8 5 1 C a r d i o m e t a b o l i c Conclusion Heart Failure Viatris ex-U.S. / ex- Europe efforts ongoing with launch in UAE and several approvals anticipated, including Canada and Australia A A K 1 Financial Discipline Continued focus on maintaining a strong balance sheet and prudent financial spending M A I N TA I N I N G O P E R AT I O N A L E X C E L L E N C E Commercial Pre-Launch Readiness Measured investments in medical education, marketing preparation and market access in process
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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 Q&A
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THANK YOU