Slide 1: Third Quarter 2025 Financial Results
FIRST QUARTER 2025 FINANCIAL Third Quarter 2025 RESULTS Financial Results November 3, 2025 Presentation intended for the investment community ©2025 Vertex Pharmaceuticals Incorporated ©2025 Vertex Pharmaceuticals Incorporated ©2025 Vertex Pharmaceuticals Incorporated
Slide 2: Agenda
Agenda Introduction Susie Lisa, CFA, Senior Vice President, Investor Relations CEO Perspective and Pipeline Update Reshma Kewalramani, M.D., Chief Executive Officer and President Commercial Update Duncan McKechnie, Executive Vice President and Chief Commercial Officer Financial Results Charlie Wagne
Slide 3: Safe harbor statement & non-GAAP financial measures
Safe harbor statement & non-GAAP financial measures This presentation contains forward-looking statements that are subject to risks, uncertainties and other factors. All statements other than statements of historical fact are statements that could be deemed forward-looking statements, including all
Slide 4: Vertex delivered strong Q3:25 results with 11% growth Y/Y and continued pipeline progress
Expand CF leadership • Complete studies in lower age groups with approved CFTR medicines • TRIKAFTA 1–2-year-old study completed; mean sweat chloride reduction of more than 70 mmol/L from Vertex delivered baseline through week 24, largest reduction with any CFTR modulator in any population to date •
Slide 5: Expanding CF leadership: ALYFTREK now approved in multiple regions
Expanding CF leadership: ALYFTREK now approved in U.S., U.K., European Union, Canada, New Zealand and Switzerland Vertex CFTR modulators have the potential to transform the lives of ~95% of patients with CF in our core markets Patients 1 month and older Patients 1 year and older Patients 6 years and
Slide 6: TRIKAFTA for 12 to <24 months of age pivotal study now complete
TRIKAFTA for 12 to <24 months of age pivotal • TRIKAFTA was generally safe and well-tolerated study now complete; largest sweat chloride in children with CF 12 to <24 months of age reduction seen in any population to date • Treatment with TRIKAFTA resulted in rapid, Absolute Change in SwCl (mmol/L)
Slide 7: Pain program R&D highlights
Pain program R&D highlights Topline results show safety and effectiveness consistent with the pivotal Acute pain: program, with substantial reductions in opioid use Completed enrollment in two Phase 4 trials evaluating suzetrigine, initiated pre-operatively and as part of multi- modal approaches to
Slide 8: Rapid progress across the kidney portfolio
Rapid progress across the kidney portfolio with multiple programs now in mid- and late- stage clinical development PATIENTS1 RESEARCH PHASE 1 PHASE 2 PHASE 3 APPROVED Rolling BLA submission Povetacicept – IgAN2 ~300K for AA to begin YE 2025 (>750K China) Full trial enrolled B cell driven ~150K Phase
Slide 9: Povetacicept: Rapid clinical progress and regulatory success across multiple indications
Povetacicept: Rapid clinical progress and regulatory success across multiple indications • Certain autoimmune diseases are driven by uncontrolled B cells Potential transformative • Pove specifically engineered for better tissue distribution and to deliver optimized, targeted dual benefit inhibition
Slide 10: Clinical portfolio is broad, diverse, and rapidly advancing
Clinical portfolio is broad, diverse, and rapidly advancing On track to meet goal of 5 launches over 5 years (by 2028) Select, Next Wave Phase 1 Phase (1)/2 Pivotal Development Approved Research-stage Programs in Healthy Volunteers in Patients Ongoing & planned Follow-on Improved conditioning VX-993
Slide 11: ALYFTREK: Approved for ages 6+ in multiple regions
ALYFTREK: Approved for ages 6+ in U.S., U.K., EU, Canada, New Zealand and Switzerland U.S. launch progressing well across all patient groups; OUS early launch off to a strong start in multiple markets INITIATE TRANSITION • Current TRIKAFTA/KAFTRIO • Newly eligible patients patients • Discontinued pa
Slide 12: CASGEVY momentum continues to build
Infusions occurring in all regions for both sickle cell CASGEVY momentum continues to build disease and transfusion dependent beta Expect $100M+ in CASGEVY revenue for FY 2025 thalassemia; at least one ATC in each region has initiated 20 or more patients Patients Initiated 1st Cell Collections Unite
Slide 13: JOURNAVX: Ongoing launch delivering strong reception across the board
JOURNAVX: Ongoing Rapid progress with payers* launch delivering strong • ~170 million covered lives with reimbursed access to JOURNAVX reception across the • Formal coverage gained with 2 out of 3 large national pharmacy benefit board managers (PBMs) • 19 state Medicaid plans passed legislation to s
Slide 14: Povetacicept is a dual BAFF + APRIL inhibitor with best-in-class potential
Povetacicept is a dual BAFF + APRIL inhibitor with best-in-class potential Engineered for high tissue distribution, target affinity and potency In clinical data to date, pove has an excellent benefit:risk profile with substantial reductions in Gd-IgA1, hematuria and proteinuria Differentiated dosing
Slide 15: Q3 2025 financial highlights
Q3 2025 financial highlights ($ in millions except where noted or per share data and percentages) Q3:24 FY:24 Q3:25 TRIKAFTA/KAFTRIO 2.59B 10.24B 2.65B ALYFTREK – – 247 Other product revenues* 187 782 176 Total revenues $2.77B $11.02B $3.08B Combined non-GAAP, Acquired IPR&D and SG&A expenses 1.08B
Slide 16: Updated full year 2025 financial guidance
Updated full year 2025 financial guidance Current Previous Commentary FY 2025 Guidance FY 2025 Guidance Full year revenue guidance assumes continued growth in CF, including the global launch of Total Revenue $11.9 - 12.0B $11.85 - $12.0B ALYFTREK; continued uptake of CASGEVY; and early contributions
Slide 17: Anticipated Key Milestones
Anticipated Key Milestones TRIKAFTA (CF) Completed pivotal study for 12 to <24 months of age; file for approval with global regulators in H1:2026 Continue to drive launch in U.S. and initiate OUS launch in 6+ yo ALYFTREK (CF) Complete Phase 3 study in children ages 2-5 years VX-522 (CF) Continue to
Slide 18: Third Quarter 2025 Financial Results
FIRST QUARTER 2025 FINANCIAL Third Quarter 2025 RESULTS Financial Results November 3, 2025 Presentation intended for the investment community ©2025 Vertex Pharmaceuticals Incorporated ©2025 Vertex Pharmaceuticals Incorporated ©2025 Vertex Pharmaceuticals Incorporated
Slide 19: Appendix A: GAAP to non-GAAP Financial Information
Appendix A GAAP to non-GAAP Financial Information ($ in millions except as noted, per share data and percentages) Q3:24 FY:24 Q3:25 Combined R&D, Acquired IPR&D and SG&A GAAP 1.26B 9.72B 1.48B Non-GAAP 1.08B 8.82B 1.28B Operating income (loss) GAAP 1.12B (233) 1.19B Non-GAAP 1.31B 696 1.38B Operatin
Slide 20: Appendix B: Vertex targeted disease area epidemiology estimates
Appendix B Vertex targeted disease area epidemiology estimates DISEASE STATE ASSET APPROACH/MODALITY PATIENT OPPORTUNITY Cystic fibrosis 5 approved, incl. ALYFTREK Small molecules ~109,000 COMMERCIALIZED Sickle cell disease + TDT CASGEVY Cell and gene therapy ~60,000 severe Acute Pain JOURNAVX Small