Slides
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Presentation Corporate November 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 2025 on track to fully deliver on our ambition Reduce operational expenses INPEFA virtual sales First ex-US INPEFA approval INPEFA submissions ex-US, ex-Europe T1D STENO-1 data submitted to FDA Type D process underway PROGRESS + Phase 2 analyses EOP2 Meeting scheduled Engaging potential partners HCM All sites initiated Accelerating enrollment SOTA-CROSS Operational Excellence & Partnerships Pilavapadin Sotagliflozin LX9851 WW license with Novo Nordisk IND-studies completed
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4 Company Overview 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
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5 Partnering Partnership strategy poised for continued value creation Innovative and flexible strategy in action to unlock long-term value • IND-enabling studies fully completed and delivered to Novo Nordisk • Potential to achieve remaining near -term development milestones of $30 million Global development of LX9851 on track • Sotagliflozin recently approved in UAE for recent and worsening heart failure • Recent submissions in Saudi Arabia, Canada, Australia and New Zealand • Filings in Mexico and Malaysia expected by year-end Geographic expansion through Viatris’ global capabilities
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6 Pilavapadin Pilavapadin: Validated MOA, compelling profile, broad potential A portfolio in a pill with multiple near-term catalysts *2 Phase 2 studies in DPNP, 1 Phase 2 study in PHN 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, leveraging novel AAK1 pathway Extensive safety and tolerability experience with >600 pilavapadin- treated patients Long patent life through 2040 when including anticipated five- year patent term extension
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7 Pilavapadin Conclusions from pooled analyses of Phase 2 studies in DPNP Analyses support advancement of 10 mg into Phase 3 development based on: 1 Validated biological activity , as evidenced by a linear relationship between increased plasma levels of pilavapadin and pain reduction. 2 Clinically meaningful efficacy of the 10mg dose, with a 2 -point average daily pain score (ADPS) reduction from baseline at 12 weeks. 3 Acceptable tolerability profile of the 10mg dose, with placebo -like treatment completion rates. 4 Acceptable safety profile in line with standard of care, further bolstered by additional studies.
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8 Pilavapadin What’s next for pilavapadin? meeting scheduled in 2025 with written feedback anticipated early 2026 to reduce variability, including placebo effect; validated by scientific advisory board flexible approach for potentially broad partnership Request for end of Phase 2 meeting accepted by FDA Optimized Phase 3 protocol Partnership discussions progressing
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9 Sotagliflozin Sotagliflozin, the emergence of a new class of SGLT Studies underway continuing to generate evidence to complement positive outcome studies in HCM, HF and MACE SONATA-HCM Phase 3 trial enrolling globally in both obstructive and non- obstructive HCM New data submitted to FDA to support potential resubmission of NDA for Zynquista in type 1 diabetes MACE: major adverse cardiac events Validated mechanism of action, strong clinical evidence,regulatory progression underway
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10 Sotagliflozin in HCM HCM: A significant and underpenetrated market with high disease burden 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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11 Also acts directly on the myocardium Once-daily oral dosing enables broad potential adoption, potentially as a first-line agent with no REMS Approved for heart failure with no observed increased risk of Afib to date Sotagliflozin in HCM Results from recent studies indicate potential shift in first-line treatment approach Proposed indication for both nHCM and oHCM with potential for use alone or in combination 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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12 Sotagliflozin in HCM Enrollment accelerating in SONATA-HCM Phase 3 study for oHCM and nHCM Target achieved all 130+ sites initiated with enrollment accelerating Global footprint Sites active in U.S., EU, Israel, and LATAM Broad potential Only ongoing trial in both obstructive and non- obstructive HCM SONATA-HCM Study Schema Patient Population • Adults with HCM • 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 Scalescore Double-Blind Treatment 26 weeks Sotagliflozin 400 mg (n = 250) Placebo (n = 250) 4-week follow up randomize
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13 SOTA-CROSSSOTA-P-CARDIA Sotagliflozin in HCM 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 • 88 patients • Readout mid-to-late 2026 • Evaluate sotagliflozin in symptomatic nHCM • 12-week crossover study • 26 patients SONATA-HCM • Evaluate sotagliflozin in patients with both subtypes of symptomatic HCM • 26-week study • 500 patients • Key endpoints include change in KCCQ and NYHA class improvementEndpoints 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 Sotagliflozin in T1D Evaluating potential resubmission for Zynquista Lexicon has submitted new data and is committed to working with the FDA on a potential resubmission Overwhelming support for approval from the T1D community High unmet need remains for adjunctive glycemic control in 1M adults with T1D, with no currently approved oral therapies
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15 LX9851 IND-enabling studies under strategic license with Novo Nordisk for LX9851 fully completed 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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16 Conclusions Strong execution results in significant catalysts into 2026 Pilavapadin EOP2 meeting by end of 2025 Ongoing partnership discussions IND-enabling work for additional indications DPNP LX9851 Obesity IND-enabling studies completed Potential for $30 million near-term milestones Sotagliflozin IIS data beginning late 2025 SONATA enrollment completed; on target for 2026 HCM Regulatory submissions and approvals by Viatris ex-U.S. / ex-Europe ongoing Heart Failure FDA feedback on potential resubmission Q4 2025 Patients strongly advocate for approval Type 1 Diabetes
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