Slides
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UPDATE Q3 Earnings November 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 Business Highlights Mike Exton Ph.D. Director and Chief Executive Officer
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4 Progress pilavapadin to be ready for Phase 3 registrational trials Fully evaluate potential path forward for Zynquista Submit an IND for LX9851 in obesity Accelerate enrollment in SONATA Phase 3 study for HCM Partner appropriate assets Company Overview By the end of 2025 we aimed to:
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5 Reduce operational expenses INPEFA virtual sales First ex-US INPEFA approval INPEFA submissions ex-US, ex-Europe Company Overview 2025 on track to fully deliver on our ambition 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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6 Partnering Partnership strategy poised for continued value creation for Lexicon 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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7 Zynquista 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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8 • Representatives across clinical, patient advocacy, and other experts actively advocating for recognition of chronic pain • Focused on including people suffering from chronic pain in important pieces of legislation Pilavapadin Environment supportive of non-opioid innovation in chronic pain FDA Draft Guidance contemplates indication strategies and clinical trial design Legislation introduced to expand access to non-opioid treatments for Medicare Part D patients Chronic Pain Roundtable | Oct 7, 2025 Catalysts in chronic pain management
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9 Pipeline Updates Craig Granowitz, M.D. Ph.D. Senior Vice President and Chief Medical Officer
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10 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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11 Analyses support advancement of 10 mg into Phase 3 development based on: Pilavapadin Conclusions from pooled analyses of Phase 2 studies in DPNP 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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12 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 Pilavapadin What’s next for pilavapadin?
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13 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 Mechanism of action, clinical, regulatory MACE: major adverse cardiac events
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14 Sotagliflozin in HCM Upcoming presentations at AHA 2025 support sotagliflozin potential in diverse patient population, including patients with HCM Oral presentation Dual SGLT1 and 2 Inhibition with Sotagliflozin Ameliorates Adverse Cardiac Remodeling and Diastolic Dysfunction in Mice with HCM Due to Tropomyosin E180G Mutation Dr. Fuzhong Qin, BU Medical Center, Boston, MA Late-breaker oral presentation SOTA-P-CARDIA Trial: a Randomized Trial of Sotagliflozin in HFpEF patients without diabetes Dr. Juan Badimon, Mount Sinai School of Medicine, NY Saturday, November 8, 20252:20 PM CTFriday, November 7, 2025 3:00 PM CT Poster presentation Effects on major adverse cardiovascular events in persons treated with sotagliflozin: Prespecified pooled analyses of the Phase 3 type 2 diabetes program Dr. Darren McGuire, UT Southwestern, Dallas, TX Saturday, November 8, 20253:10 PM CT Presentations
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15 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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16 Financial Overview Scott Coiante Chief Financial Officer
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17 Financials Q3 2025 Financial Summary Q3 2025 Q3 2024 Revenue: Net product revenues $1.0 $1.7 Licensing revenue $13.2 --- Total revenues $14.2 $1.8 Operating expenses: R&D $18.8 $25.8 SG&A $7.6 $39.6 Total operating expenses $26.4 $65.4 Net loss ($12.8) ($64.8) Net loss per common share ($0.04) ($0.18) As of September 30, 2025 As of December 31, 2024 Cash, cash equivalents, short- term investments and restricted cash $145.0 $238.0 Total assets $205.9 $298.4 Total debt $56.5 $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
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18 Financials Q3 and Full Year 2025 Financial Highlights Q3 2025 Key Financial Highlights Full Year 2025 Operating Expenses* • Recognized $13.2 million of licensing revenue in Q3 under our agreement with Novo Nordisk • YTD through Q3: $40.7 million • Q4 expected: remaining $4.3 million • Quarter over quarter operating expenses decreased by $39.1 million • Total 2025 operating expenses expected to be between $105 - $115 million • R&D expected between $70 - $75 million • Excludes expenses related to Phase 3 pilavapadin trials • SG&A expected between $35 - $40 million *As of November 6, 2025
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19 Summary Mike Exton Ph.D. Director and Chief Executive Officer
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20 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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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