Slides
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N o v e m b e r 5, 2026 Third Quarter 2026 Earnings
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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. 2
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Q3 2026 Highlights Mike Exton Ph.D. Director and Chief Executive Officer 3
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Overview Year-to-Date 2026 Highlights Advancing our pipeline of novel therapies for serious cardiometabolic diseases SOTAGLIFLOZIN HCM - Phase 3 SONATA- HCM enrollment complete; supports potential broad label - Topline data expected Q1 2027 T1D - STENO1 (third - party IIS) data package received & supports NDA resubmission - DKA rates are low and comparable to standard of care in STENO1 Heart Failure — Global Expansion - Viatris launch underway; approved in UAE and Bahrain - Additional regulatory submissions in ex - US and ex-Europe markets LX9851 Obesity - Phase 1 study ongoing by Novo Nordisk - Three $10M milestone payments received in 2026 PILAVAPADIN Diabetic Peripheral Neuropathic Pain Clear regulatory path to Phase 3 pivotal studies Obesity & Additional Indications Preclinical studies across multiple non-pain indications including recent data in obesity CONTINUED COMMITMENT TO OPERATIONAL EXCELLENCE STRATEGIC HIRING TO SUPPORT PRE-COMMERCIAL AND CLINICAL PLANNING 4
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Mechanistic Benefits of SGLT1 in HCM Works directly on the heart, improving diastolic dysfunction and cardiac metabolism in HCM Sotagliflozin in HCM 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 Many presentations… one disease Without Obstruction HYPERTROPHIC CARDIOMYOPATHY With Obstruction Improving cardiac metabolism in HCM by working directly on the heart Enabled by unique SGLT1 mechanistic benefits Source: HCMAi, Hypertrophic Cardiomyopathy Association 5
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Sotagliflozin in HCM Significant Need Remains for Patients with HCM >800K diagnosed HCM patients in the U.S.1 POPULATION MOMENTUM nHCM population is growing strongly with rising levels of obesity and diabetes ~2/3 of symptomatic patients are nHCM – many more remain undiagnosed2 TREATMENT GAP Currently no FDA -approved therapies for nHCM patients SAFE + SIMPLE Strong need for an option that is safe with simple dosing ACCESS BARRIERS REMS complexity and cost - associated restrictions limit penetration of new medicines 61: JACC, https://www.jacc.org/doi/10.1016/j.jacadv.2025.102552. 2: JACC, https:// www.jacc.org/doi/10.1016/j.jacadv.2025.102552.
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Pipeline Updates Craig Granowitz, M.D. Ph.D. Senior Vice President and Chief Medical Officer 7
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Primary endpoint: Change from baseline in KCCQ CSS Sotagliflozin 400 mg Placebo 4-week Follow-up 26-week double-blind treatment periodUp to 5 weeks Screening R 1:1 Sotagliflozin in HCM SONATA-HCM Phase 3 Study for Symptomatic HCM Baseline characteristics reflect broad and clinically relevant HCM population Enrollment Complete; Topline Results Q1 2027 • Patient demographics consistent with prior studies of other agents in HCM and reflect real-world clinical practice • Average KCCQ score of 59, signaling meaningful room to demonstrate a clinically relevant treatment benefit • Evaluation in broad HCM population, emphasizing nHCM, where currently no FDA-approved treatment option exists • 542 patients randomized; substantial over-enrollment strengthens statistical power • Inclusion of background CMI therapy (~9%) supports potential complementary positioning KCCQ CSS = Kansas City Cardiomyopathy Questionnaire Clinical Summary Score; R = randomization. 8
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Sotagliflozin in HCM Growing Body of Recent Evidence Supports Sotagliflozin in HCM Highlights differentiation of dual inhibition compared to SGLT2 alone PRECLINICAL BIOLOGY CLINICAL READTHROUGH HCM CLINICAL PROGRAM J Mol Cell Cardiol Plus 2026 | HCM Society 2025 HCM mouse model Improved cardiac structure and function: normalized diastolic function, reversed hypertrophy progression and reduced fibrosis, with lower oxidative stress. J Clin Invest 2026 Platelets and thrombosis Sotagliflozin, but not SGLT2-selective empagliflozin, reduced platelet activation and thrombus formation without adversely affecting hemostasis. HCM: hypertrophic cardiomyopathy; oHCM/nHCM: obstructive/nonobstructive HCM; KCCQ: Kansas City Cardiomyopathy Questionnaire; NYHA: New York Heart Association; SGLT: sodium glucose co -transporter . Qin F, et al. J Mol Cell Cardiol Plus. 2026;100873. Stanger L, et al. J Clin Invest. 2026 . Taichman R B, et al. AHA Scientific Sessions 2026. Zafar MU, et al. AHA Scientific Sessions 2026; SOTA-CROSS: University of Pennsylvania (NCT06433050). AHA 2026 – To Be Presented | University of Pennsylvania Human myocardial slices In living HCM heart tissue, SGLT inhibitors directly reduced myocardial work, with sotagliflozin showing greater potency at high afterload. AHA 2026 – To Be Presented | Ichan School of Medicine Thrombus formation In healthy adults, sotagliflozin significantly reduced thrombus formation vs. baseline; empagliflozin did not reach significance. Investigator-initiated | University of Pennsylvania SOTA-CROSS: nHCM 26 patients, 12-week crossover study; evaluating cardiac function, exercise performance and KCCQ. Completion expected 1H2027. Phase 3 registrational SONATA-HCM: oHCM and nHCM >500 patients with both subtypes of HCM , 26 weeks: key endpoints include change in KCCQ and NYHA class. Topline data expected Q1 2027 9
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10 Sotagliflozin in T1D Clinical Data Support ZYNQUISTA’s Resubmission Patient-years of exposure achieved; DKA rates support positive benefit:risk profile DKA: diabetic ketoacidosis; NDA: new drug application; T1D: type 1 diabetes. STENO1: Multifactorial Intervention to Reduce Cardiovascular Disease in Type 1 Diabetes, Steno Diabetes Center Copenhagen (NCT06082063), a third-party funded investigator-initiated study. InTandem: Lexicon’s Phase 3 clinical program of sotagliflozinin T1D. Evidence from inTandem + STENO1 FDA-RECOGNIZED OUTCOMES IN T1D 1 HbA1c reduction 2 Increased time in range 3 Lower blood pressure 4 Reduced hypoglycemic events 5 Reduced body weight ~1M U.S. adults with T1D, with no approved treatment options beyond insulin If approved, the first and only oral adjunct to insulin for glycemic control in T1D FDA RESUBMISSION CRITERIA ACHIEVED 1 Prospective study FDA confirmed STENO1 is adequate to support resubmission 2 Patient exposure Achieved the years of exposure discussed with FDA 3 DKA rates Similar to standard of care in STENO1 and below rates in the inTandem studies inTandem clinical program STENO1 investigator-initiated study
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Sotagliflozin in T1D STENO1 DKA Rates are Low and Comparableto Standard of Care ENROLLMENT SNAPSHOT Group Randomized patients, n DKA rate per 100 patient years Historic Rate in Denmark T1D Patients1 n/a ~1.0 Sotagliflozin 496 ~1.0 Standard of Care 708 ~1.0 Enrollment Summary as of August 30, 2026 NDA resubmission anticipated in Q1 2027 111Stougaard EB, et al. Diabetes Care. 2023;46:1897–1902. doi:10.2337/dc23-0475.
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Pilavapadin Significant Reduction in Body Weight from Baseline, Alone and in Combination With Semaglutide -25.51% -13.93% -31.14% -40 -30 -20 -10 0 10 0 4 7 11 14 18 21 25 28 % Body weight Study Day % Body Weight Change vs Vehicle Semaglutide (0.04 mg/kg) Pilavapadin (10 mg/kg) Pilavapadin (10 mg/kg) + Semaglutide (0.04 mg/kg) Pilavapadin drove a 13.9% reduction alone Combined with semaglutide, body-weight reduction reached 31.1% by Day 28 12
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Financial Overview Scott Coiante Chief Financial Officer 13
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Financials As of September 30, 2026 As of December 31, 2025 Cash, cash equivalents, short- term investments and restricted cash $183.2 $125.2 Total assets $242.0 $185.0 Total debt $51.9 $54.0 Q3 2026 Q3 2025 Total revenues $11.3 $14.2 R&D ($16.2) ($18.8) SG&A ($9.5) ($7.6) Total operating expenses ($25.7) ($26.4) Net loss ($14.0) ($12.8) Net loss per common share ($0.03) ($0.04) $ (in millions except per share amounts) Q3 2026 Financial Summary 14
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Financials Q3 2026 Financial Highlights and FY 2026 Guidance Q3 2026 Key Financial Highlights • Recognized $11.3 million in total revenue • Includes third $10 million payment from Novo Nordisk license agreement • Total of $30 million of milestone payments received from Novo Nordisk in 2026 • $1.2 million in net sales of INPEFA • 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 November5, 2026 15
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Summary Mike Exton Ph.D. Director and Chief Executive Officer 16
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Conclusion Lexicon is Well Positioned for a Transformational Next 12 Months OUR VISION A future where people living with serious cardiometabolic diseases have more opportunities to live longer, healthier lives 01 SOTAGLIFLOZIN HCM HEART FAILURE • Pivotal Phase 3 readout Q1 2027 • Potential broad HCM label path • Pre-commercial planning and readiness ongoing • Ex-U.S. HF launch progressing 02 ZYNQUISTA TYPE 1 DIABETES • NDA resubmission anticipated Q1 2027 • Pending approval, poised to be first and only adjunct to insulin for glycemic control in decades 03 LX9851 OBESITY • Phase 1 program advancing • Potential path into later-stage development • Additional milestones possible 04 PILAVAPADIN PAIN OBESITY AAK1 • Phase 3 ready pain program • Obesity investigation advancing • Broader AAK1 opportunities under evaluation Multiple potential value-creation paths across a broad cardiometabolic portfolio 17
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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