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©2026 Vertex Pharmaceuticals Incorporated ©2026 Vertex Pharmaceuticals Incorporated FIRST QUARTER 2025 FINANCIAL RESULTS ©2025 Vertex Pharmaceuticals Incorporated Third Quarter 2026 Financial Results November 2, 2026 Presentation intended for the investment community
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©2026 Vertex Pharmaceuticals Incorporated 2 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 Wagner, Executive Vice President and Chief Operating & Financial Officer
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©2026 Vertex Pharmaceuticals Incorporated 3 Safe harbor statement & non-GAAP financial measures This presentation contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, including, without limitation, the information provided regarding future financial and operating performance, including the statements under “Raising full year 2026 revenue guidance,” “Crinetics Pharmaceuticals acquisition impact,” and statements regarding (i) expectations, goals, development and commercialization plans and timelines for the company’s products, product candidates and pipeline programs, (ii) beliefs with respect to the treatable patient population for CF and the benefits of treatment early in life, expectations to continue to extend market leadership and sustain growth with respect to the company’s CF medicines, including from label expansions and treatment of younger patients, our our expectations regarding ALYFTREK, including with respect to clinical benefits, that the majority of patients will switch to ALYFTREK from TRIKAFTA over time, advancing global regulatory submissions for ALYFTREK in patients 2 to 5 years of age, the progress of the ongoing commercial launch of ALYFTREK, continued uptake in younger patients and expansion in to additional geographies, our expectations with respect to the clinical benefits of other next generation CF compounds, potential advancement of next-generation 3.0 CF regimen once all data are available, for continued progress in next-generation 4.0 programs, and the clinical benefits of VX-828, (iii) beliefs regarding the potential benefits of atumelnant for the treatment of CAH and ACTH-dependent Cushing’s Syndrome, including with respect to treatable patient population, significant unmet need, and potential clinical benefits, expectations for the Phase 3 study of atumelnant in adults with CAH, including to complete enrollment in the first quarter of 2027, share data at a medical conference in 2027, and for the Phase 2/3 pediatric study, including to engage with regulators and progress rapidly to Phase 3, and plans with respect to the Phase 2/3 study of atumelnant in ACTH-dependent Cushing’s Syndrome, (iv) expectations for the company’s T1D program, including with respect to study advancement for VX-017 as the lead islet therapy for T1D and thereby doubling the market opportunity as compared to zimislecel, and plans for enrolling and dosing patients in the Phase 1/2 study and targeting initiation of pivotal development in 2027, (v) expectations regarding progress across the company’s kidney portfolio, including with respect to estimated patient populations, the company’s beliefs regarding data from Phase 3 study of povetacicept in IgAN and that povetacicept is a potential best-in-class treatment for IgAN, our beliefs regarding launch readiness for povetacicept in IgAN, including with respect to the field team, commercial coverage and patient onboarding capabilities, our expectations to drive Phase 3 enrollment and continue dosing in the Phase 3 study of povetacicept in pMN, and to share data from the Phase 2 study of povetacicept in gMG in H1 2027, (vi) expectations for inaxaplin as a treatment for AMKD, including our beliefs around AMPLIFIED study data and plans to perform interim analysis and to share data in early 2027 from the AMPLITUDE pivotal trial, and our expectation that positive study data from the AMPLITUDE study will support accelerated approval in the U.S., (vii) expectations for CASGEVY, including with respect to reaching more eligible patients and securing additional pediatric approvals, acceleration of patient infusions, CASGEVY’s commercial potential, including potential as a multi-billion dollar franchise, progress toward contributing meaningfully to the $500 million revenue goal for non-CF products in 2026, and line of sight into 2026 and 2027 revenue, (viii) expectations for JOURNAVX, including with respect to launch momentum in the U.S. and continuing to drive prescriptions and revenue growth, our beliefs regarding strong clinical reception, physician enthusiasm, and a growing body of real world evidence, our expectations regarding the progress towards more than 3x prescription growth and more than 3x revenue growth in 2026 versus 2025, beliefs regarding the patient support program in 2026 and gross-to-net revenue in 2027, plans to secure regulatory approval in Canada, plans to complete enrollment in both ongoing studies evaluating suzetrigine in DPN by the end of 2026 and share data in 2027, and plans to complete enrollment in the Phase 2 study of VX-993 in DPN by the end of 2026 and share data mid-2027, (ix) beliefs regarding the expected clinical benefits, significant unmet need, and eligible patient population for PALSONIFY as a treatment for acromegaly, expectations regarding the integration of Crinetics’ business and launch progress for PALSONIFY in the U.S., including plans to grow the patient and prescriber bases and begin the European launch in H2 2027, (x) expectations to share data in 2027 from the AGLOW study of VX-407 in ADPKD, and (xi) expectations to share interim results in H2 2026 from the Phase 1/2 study of VX-670 in DM1. While Vertex believes the forward-looking statements contained in this presentation are accurate, these forward-looking statements represent the company's beliefs as of the date of this presentation and there are risks and uncertainties that could cause actual events or results to differ materially from those expressed or implied by such forward-looking statements. Those risks and uncertainties include, among other things, that the company's expectations regarding future revenues or expenses may be incorrect, that the company may be unable to continue increasing revenues from its commercialized medicines, that that regulatory submissions or approvals may not occur on the anticipated timeline, or at all, that data from clinical trials may not to be indicative of final results, that anticipated commercial launches may be delayed, if they occur at all, the company may not realize the anticipated benefits from acquisitions or collaborations with third parties, that actual patient populations eligible for the company’s products may be smaller than anticipated, that data from the company's development programs may not be available on expected timelines, or at all, that data may not support registration or further development of its potential medicines due to safety, efficacy or other reasons, that external factors may have different or more significant impacts on the company's business or operations than the company currently expects, and other risks listed under the heading “Risk Factors” in Vertex's annual report and subsequent quarterly reports filed with the Securities and Exchange Commission at www.sec.gov and available through the company's website at www.vrtx.com. You should not place any undue reliance on these statements, or the data presented. Vertex disclaims any obligation to update the information contained in this presentation as new information becomes available. In this presentation, Vertex's financial results and financial guidance are provided in accordance with accounting principles generally accepted in the United States (GAAP) and using certain non-GAAP financial measures. In particular, non-GAAP financial results and guidance exclude from Vertex's pre-tax income (i) stock-based compensation expense, (ii) intangible asset amortization expense, (iii) gains or losses related to the fair value of the company's strategic investments, (iv) increases or decreases in the fair value of contingent consideration, (v) acquisition-related costs, (vi) acquired inventory fair value step-up expense, (vii) an intangible asset impairment charge, and (viii) other adjustments. The company's non-GAAP financial results also exclude from its provision for income taxes the estimated tax impact related to its non-GAAP adjustments to pre-tax income described above and certain discrete items. These results should not be viewed as a substitute for the company’s GAAP results and are provided as a complement to results provided in accordance with GAAP. Management believes these non-GAAP financial measures help indicate underlying trends in the company's business, are important in comparing current results with prior period results and provide additional information regarding the company's financial position that the company believes is helpful to an understanding of its ongoing business. Management also uses these non- GAAP financial measures to establish budgets and operational goals that are communicated internally and externally, to manage the company's business and to evaluate its performance. The company’s calculation of non-GAAP financial measures likely differs from the calculations used by other companies. The company provides guidance regarding combined R&D, AIPR&D and SG&A expenses and effective tax rate on a non-GAAP basis. Unless otherwise noted, the guidance regarding combined R&D, AIPR&D and SG&A expenses does not include estimates associated with any potential future business development transactions, including collaborations, asset acquisitions and/or licensing of third-party intellectual property rights. The company does not provide guidance regarding its GAAP effective tax rate because it is unable to forecast with reasonable certainty the impact of excess tax benefits related to stock-based compensation and the possibility of certain discrete items, which could be material. Non-GAAP financial measures are presented compared to corresponding GAAP measures in the appendix hereto. A reconciliation of the GAAP financial results to non-GAAP financial results is included in the company’s Q3 2026 press release dated November 2, 2026.
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©2026 Vertex Pharmaceuticals Incorporated 4 Excellent Q3:26 performance across the board Commercial • Total revenue +12% Y/Y • Strong growth across all products & regions • $10M contribution from Crinetics acquisition for month of September (closed 9/1) • Meaningful progress gaining reimbursed access across CF, SCD/TDT, acute pain, acromegaly • Launch-ready in renal, with pove IgAN PDUFA Nov 30, 2026 Clinical • Recently announced: • Positive Inaxaplin AMPLIFIED Ph2 • Positive VX-828 patient data in CF • ASN presentation & NEJM publication of pove IgAN Ph3 RAINIER IA • Completed enrollment: • Inaxaplin AMPLITUDE Ph3 in AMKD • Povetacicept ETNA Ph2 in gMG • VX-407 AGLOW Ph2 in ADPKD • On track to complete enrollment by YE: • 2 suzetrigine Ph3s in DPN • VX-993 Ph2 in DPN • Expect interim results by YE: • VX-670 Ph2 PoC in DM1 • Expect results early 2027: • AMPLITUDE Ph2/3 IA in AMKD Regulatory • Pove: BLA for IgAN under priority review for accelerated approval in U.S. and KSA • CASGEVY: Expanded labeling in SCD/TDT: 2 to <12 years in U.S., Bahrain, UAE; 5 to <12 years in the U.K. • VX-017 Ph1/2 study underway in T1D • Compatible with all blood types, doubling target patient population to ~120K from ~60K • Enrollment and dosing underway SCD: sickle cell disease; TDT: transfusion dependent beta thalassemia; IgAN: immunoglobulin-A nephropathy; ADPKD: autosomal dominant polycystic kidney disease; AMKD: APOL1 mediated kidney disease; DPN: painful diabetic peripheral neuropathy; DM1: myotonic dystrophy type 1; T1D: type 1 diabetes.
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©2026 Vertex Pharmaceuticals Incorporated 5 CF: Extending leadership and driving sustained growth ALYFTREK Younger patients & rare mutations • Treating early in life may prevent organ damage & holds promise to extend life expectancy • Global regulatory submissions in progress for ALYFTREK in patients ages 2-5 years • Recent label expansions increase eligible population: ~95% of people with CF now eligible for treatment with VRTX CFTR modulators • Best CFTR protein function, as measured by sweat chloride, plus once-daily dosing • Expect majority of patients to switch to ALYFTREK from TRIKAFTA over time • New data at NACFC demonstrated that early intervention with ALYFTREK can help achieve independence from pancreatic enzyme replacement therapy (PERT) Serial innovation • Next gen 3.0 family of compounds: • VX-828 triple combo: Phase 1 data in F/MF patients showed 6.6 & 9.4 mmol reductions in sweat chloride at & through Day 28, respectively, vs. TRIKAFTA baseline; safe & well tolerated, once daily dosing with favorable drug-drug interaction profile • VX-581 and VX-272: both in Phase 1 healthy volunteer studies • Given high bar set by ALYFTREK, wait for all next gen data to select regimen for advancement • Next-generation 4.0 programs continue to make progress in pre-clinical development CFTR: cystic fibrosis transmembrane conductance regulator; SwCl: sweat chloride; NACFC: North American Cystic Fibrosis Conference.
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©2026 Vertex Pharmaceuticals Incorporated 6 Emerging VX-828 data in CF cohort resulted in improvement in sweat chloride versus a baseline on TRIKAFTA Visit Cohort E1 N=8 Baseline SwCl (Day 0) Mean (SD) 61.9 (8.7) Absolute change at Day 28 Mean (95% CI) -6.6 (-14.1, 1.0) Absolute change through Day 28 Mean (95% CI) -9.4 (-19.3, 0.5) Sweat chloride (SwCl) change from TRIKAFTA baseline by visit Study assessed patients with F/MF genotype from TRIKAFTA baseline The VX-828 regimen is oral, once-daily Good safety and tolerability profile †At Day 28 is the measurement taken on Day 28. Through Day 28 is the mean of the measurements on Days 15, 22, and 28.
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©2026 Vertex Pharmaceuticals Incorporated 7 Rare endocrine: Atumelnant, an oral, selective ACTH antagonist for Congenital Adrenal Hyperplasia and ACTH-dependent Cushing’s Syndrome X Congenital Adrenal Hyperplasia (CAH) • Significant unmet need • First therapy with the potential to reduce BOTH excess adrenal androgens AND exogenous glucocorticoids • Orphan Drug Designation U.S., EU, Japan • Adult: Phase 3 pivotal study underway • Goal to complete enrollment Q1:27 • Pediatric: Phase 2 study underway • Goal to progress rapidly to Phase 3, following regulatory interactions • Significant unmet need • OUS: Phase 2/3 study initiated • U.S.: Engaging with FDA on trial initiation • Granted Orphan Drug Designation ACTH-dependent Cushing’s Syndrome (ADCS)
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©2026 Vertex Pharmaceuticals Incorporated 8 T1D: Accelerating VX-017 as lead islet cell therapy for Type 1 diabetes •Doubles initial market opportunity for islet cell therapy to ~120K patients from ~60K •Similar target product profile to zimislecel •Enrolling and dosing patients in a Phase 1/2 study for patients of all blood types •Targeting initiation of pivotal development in 2027 VX - 017 is an allogenic, off - the - shelf, glucose - responsive, insulin - producing, fully differentiated islet cell therapy
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©2026 Vertex Pharmaceuticals Incorporated 9 B cell driven renal diseases Povetacicept – IgAN2 ~330K (1.5M globally) Povetacicept – pMN ~150K (>600K globally) Other B cell driven diseases Povetacicept – gMG ~175K (>300K globally) APOL1- mediated kidney disease (AMKD) Inaxaplin – AMKD ~150K Inaxaplin – AMKD with modest proteinuria or diabetes ~100K (with comorbidities) Autosomal dominant polycystic kidney disease VX-4073 Up to ~30K Serial innovation to reach all ADPKD patients ~300K (incl. 30K) Nephrology: Rapid progress across the kidney portfolio 1. Estimated patient population in the U.S. and Europe, unless otherwise noted. 2. IgAN patients continue to be studied in RUBY-3. 3. Targets a patient population with a subset of variants in the PKD1 gene. IgAN: IgA nephropathy; pMN: primary membranous nephropathy; gMG: generalized myasthenia gravis; AMKD: APOL1-mediated kidney disease. PATIENTS1 RESEARCH PHASE 1 PHASE 2 PHASE 3 APPROVED IA data in early 2027 PDUFA: Nov 30 Proof-of-concept study fully enrolled, dosing continues Proof-of-concept study fully enrolled, dosing continues Enrollment and dosing well underway Completed Pre-clinical progress continues
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©2026 Vertex Pharmaceuticals Incorporated 10 Povetacicept: Statistically significant and clinically meaningful reduction in proteinuria Substantial reductions in 24-hour UPCR with povetacicept • 52.0% decrease from baseline with povetacicept at Week 36 • Povetacicept treatment effect at Week 36: 49.8% (95% CI: 39.2%, 58.6%); P <0.0001 PRIMARY ENDPOINT: Percent Change from Baseline in 24-hour UPCR at Week 36 52.0% 4.3% Proportion of Participants with 24-hour UPCR <0.5 g/g at Week 36 Pove was generally safe and well tolerated in the study; most AEs were mild-to-moderate, SAEs of infection were balanced at 0.5% in the both the pove and placebo groups; no opportunistic infections, and no discontinuations due to infections 42.2% Achieved KDIGO-aligned goal of UPCR <0.5 g/g • Proportion of patients who achieved 24-hour UPCR <0.3 g/g 18.0% with povetacicept and 1.5% with placebo at Week 36
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©2026 Vertex Pharmaceuticals Incorporated 11 AMPLIFIED data add to evidence base for inaxaplin as potential first- and best-in-class treatment targeting the underlying cause of AMKD AMKD: APOL1-mediated kidney disease; CI: Confidence interval; SD: Standard deviation; UACR: Urine albumin to creatinine ratio; UPCR: Urine protein to creatinine ratio; FSGS: focal segmental glomerulosclerosis PARAMETER Cohort 1: Patients with AMKD with modest proteinuria N=22a Cohort 2: Patients with AMKD and Type 2 diabetes N=17a Primary Endpoint (UACR) Mean baseline UACR g/g (SD) 0.28 (0.09) 0.67 (0.87) Geometric mean % change of UACR at Week 13 compared to baseline (95% CI)b -42.7% (-58.3%, -21.1%)c -17.3% (-36.3%, 7.2%)c Other Endpoint (UPCR) Mean baseline UPCR g/g (SD) 0.46 (0.20) 1.12 (1.51) Geometric mean % change of UPCR at Week 13 compared to baseline (95% CI)b -44.7% (-60.9%, -21.9%)c -25.4% (-45.1%, 1.4%)c aAccording to the pre-specified statistical analysis plan, two people, one in each cohort, who were noncompliant with treatment were not included in the efficacy analyses; bAnalyses include those on treatment who had an assessment at Week 13: 18 and 14 people in cohort 1 and 2, respectively; c95% CI were generated post-hoc. dNo serious adverse events (SAEs) related to inaxaplin. All adverse events (AEs) were mild or moderate in severity. Most common AE (occurring in >5% of subjects) was headache (7.3%). Five patients had isolated, asymptomatic transaminase elevations, which resolved. • Cohort 1 efficacy mirrors that of inaxaplin proof-of- concept Phase 2 study in AMKD patients with FSGS • Majority of patients in both cohorts did not have FSGS • Generally safe and well tolerated d
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©2026 Vertex Pharmaceuticals Incorporated 12 AMPLITUDE pivotal trial of inaxaplin in patients with AMKD with severe proteinuria fully enrolled; interim analysis on track for early 2027 Note: At the end of treatment, patients have an option to enroll in a long-term open label extension study. A Key inclusion criteria: • Aged 10 to 65 years • APOL1 genotype of G1/G1, G2/G2, G1/G2 • Proteinuric kidney disease Key exclusion criteria: • History of diabetes mellitus • Uncontrolled hypertension • Solid organ or bone marrow transplant Key Eligibility Criteria Primary endpoints • Interim analysis (IA) • Percent change in UPCR from baseline at Week 48 • eGFR slope (with ≥48 weeks of eGFR data) • Final analysis • eGFR slope (with ≥2 years of eGFR data) Assessments
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©2026 Vertex Pharmaceuticals Incorporated 13 Approved R&D portfolio is broad, deep, and rapidly advancing Follow-on molecules for multiple programs VX-407 ADPKD Inaxaplin AMKD Suzetrigine DPN Zimislecel Type 1 diabetes Povetacicept IgA nephropathy Small molecule Huntington’s disease Islet cells + targeted immunosuppression + hypoimmune islet cells Type 1 diabetes Improved conditioning CASGEVY – SCD & TDT Na V1.7 inhibitor Pain VX-670 DM1 VX-993 DPN *In addition, the following Phase 1/2 trials have completed: Inaxaplin (AMPLIFIED: AMKD), VX-828 (CF), and pove (RUBY-4: immune thrombocytopenia, warm autoimmune hemolytic anemia, cold agglutin disease). SCD: sickle cell disease; TDT: transfusion-dependent beta thalassemia; CF: cystic fibrosis; AMKD: APOL1-mediated kidney disease; ADPKD: autosomal dominant polycystic kidney disease; DPN: diabetic peripheral neuropathy; DM1: myotonic dystrophy type 1; pMN: primary membranous nephropathy; gMG: generalized myasthenia gravis. Povetacicept IgA nephropathy Submitted for Accelerated Approval Pivotal development Phase (1)/2* (in patients, ongoing) Phase 1 in healthy volunteers Select next wave programs Research stage VX-017 Type 1 diabetes Atumelnant CAH Atumelnant ACTH-dependent Cushing’s Syndrome Povetacicept gMG Povetacicept pMN
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©2026 Vertex Pharmaceuticals Incorporated 14 Strong commercial performance and outlook across all disease areas Key performance indicators and growth drivers >18K ~200 >1.6M >40% Growth from increased penetration and label expansion into younger patients Growth from increasing depth of use and continued positive real-world experience Growth from new and repeat prescribers in patients initiating & switching therapies patients now benefiting from ALYFTREK worldwide Growth from label expansions into rare mutations and younger patients, plus additional geographies infusions completed since launch patients treated since launch brand share among patients starting or switching therapy
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©2026 Vertex Pharmaceuticals Incorporated 15 ALYFTREK: A highly efficacious, once-daily CFTR modulator delivering equivalent improvement in lung function1 and greater CFTR function2 vs. TRIKAFTA CF: Continued global revenue growth 1. Lung function as measured by improvements in ppFEV 1 vs. TRIKAFTA. 2. CFTR function as measured by improvements in sweat chloride vs. TRIKAFTA. • ALYFTREK sales Q1-Q3 surpassed $1B • Switching & new rare mutation patients OUS highlights U.S. highlights • Strong ALY European launches • 31 countries now with ALY reimbursement $3.3B Q3 global CF revenue 18,000 patients worldwide now on ALYFTREK
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©2026 Vertex Pharmaceuticals Incorporated 16 CASGEVY: Acceleration continues towards multi-$B potential • Expanded pediatric labeling: ages 2 to <12 U.S., Bahrain, and UAE; ages 5 to <12 in the U.K. • Four consecutive quarters of >100 initiations • Double number of infusions first 9 months 2026 vs. all 2025 • Contributing meaningfully to $500M+ revenue goal • Excellent line of sight into FY2026 and 2027 revenue UAE: United Arab Emirates.
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©2026 Vertex Pharmaceuticals Incorporated 17 ~80,000 physicians prescribing JOURNAVX Up from ~70,000 previously >750,000 prescriptions in Q3 Multiple studies show lower opioid utilization JOURNAVX: Strong Rx growth and gaining traction across customer base Growing body of JOURNAVX real world evidenceStrong clinical reception Physician enthusiasm On track to deliver >3x Rx growth and >3x revenue growth 2026 vs 2025 PSP to remain “on” through 2026, with GTN normalizing mid-2027 Over 1.6M patients treated #1 Oral Branded Analgesic Total Knee Arthroplasty, acute dental pain, etc. PSP: Patient Support Program.
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©2026 Vertex Pharmaceuticals Incorporated 18 Acromegaly is a rare, serious chronic disease with significant unmet need ◎ ✓ In the U.S., patients are treated by approximately 3,000 endocrinologists. Persistent disease causes most patients to require lifelong therapy Oral therapy providing rapid and sustained biochemical + symptom control PALSONIFY: convenient once-daily oral option for patients who had an inadequate response to surgery or for whom surgery is not an option First and only SST2-selective agonist designed for sustained control without injection-site burden Known causal biology Meaningful opportunity Ongoing disease burden Unmet need SST2-selective agonist: somatostatin receptor type 2. Benign pituitary tumor A benign pituitary tumor produces excess growth hormone, driving acromegaly ~40K patients across the U.S. and key OUS markets ~50% patients require lifelong treatment
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© Vertex Pharmaceuticals Incorporated2026 PALSONIFY launch is off to a strong start 19 1. Build a broad base of repeat HCP writers for PALSONIFY 2. Drive growth in both the new and switch settings 3. Serve more patients around the globe ~80% Broad payer access of U.S. lives covered ~500 Repeat HCP prescribers 40%+ Leading brand share among patients seeing their HCP ~$60M Revenue through 9/30/26 Areas of focus
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©2026 Vertex Pharmaceuticals Incorporated 20 Renal: Building our fifth pillar, starting with povetacicept in IgAN ExperienceReadyTrifecta • Field team fully staffed and trained, largest in IgAN, >90% nephrology experience • Engaged targeted HCPs in IgAN disease educational activities since early this year • Personalized & seamless patient onboarding, leveraging Vertex’s CF experience and capabilities • Patient population is >70% commercial; VRTX has been engaging payers for >1 year • 89% of surveyed nephrologists anticipate prescribing pove 1, with proteinuria efficacy as leading motivator 2 • 96% of surveyed patients prefer autoinjector * and 80% prefer Q4W dosing for greater convenience 3 Differentiated profile Ready to activate Patient-first infrastructure Ready to serve Scaled field engine Ready to engage 1Spherix Data, Q3 2026; 2Povetacicept HCP ATU Pulse, Aug – Sep 2026 measuring intent among pipeline assets; 3Health Economics and Outcomes Research (HEOR) ASN 2026 Patient Preference Poster by Joel Iff, et al. *Due to needle concealment and easier administration SeamlessLaunchPovetacicept
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©2026 Vertex Pharmaceuticals Incorporated 21 Q3 2026 financial highlights ($ in millions except where noted or per share data and percentages) Q3:25 FY:25 Q3:26 TRIKAFTA/KAFTRIO 2.65B 10.31B 2.44B ALYFTREK 247 838 706 Other CF product revenues 139 645 131 Total CF product revenues 3.04B 11.80B 3.27B CASGEVY 17 116 99 JOURNAVX 20 60 58 PALSONIFY — — 10 Total product revenues 3.08B 11.97B 3.44B Other revenues — 31 — Total revenues 3.08B 12.00B 3.44B Combined non-GAAP R&D, Acquired IPR&D and SG&A expenses 1.28B 5.12B 1.53B Non-GAAP operating income 1.38B 5.26B 1.41B Non-GAAP operating margin % 45% 44% 41% Non-GAAP net income 1.24B 4.75B 1.21B Non-GAAP net income per share-diluted $4.80 $18.40 $4.76 Cash, cash equivalents & marketable securities (period-end) 12.0B 12.3B 9.8B Notes: An explanation of non-GAAP financial measures and reconciliation of combined non-GAAP R&D, Acquired IPR&D and SG&A expenses, non-GAAP operating income, non-GAAP net income and non- GAAP net income per share – diluted to corresponding GAAP measures are included in the company’s press releases dated February12, 2026 and November 2, 2026. Non-GAAP financial measures are presented compared to corresponding GAAP measures in the appendix of this presentation. Totals above may not add due to rounding.
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©2026 Vertex Pharmaceuticals Incorporated 22 Raising full year 2026 revenue guidance Current FY 2026 Previous FY 2026 Commentary Total revenue $13.15B to $13.25B $13.1B to $13.2B Full year revenue guidance includes expectations for continued growth in CF, $500 million or more in revenue from CASGEVY & JOURNAVX, and contribution from PALSONIFY Legacy non-CF product revenue (CASGEVY , JOURNAVX) Unchanged $0.5B or greater PALSONIFY revenue (Sept-Dec) $40 to $50M Combined GAAP R&D, AIPR&D, and SG&A expenses * $7.15 to $7.2B $6.3 to $6.45B Includes expectations for continued investment in multiple mid- and late-stage clinical development programs and commercialization capabilities, as well as ~$250M of Crinetics operating expenses and ~$100M of currently anticipated AIPR&D expenses. Combined non-GAAP R&D, AIPR&D, and SG&A expenses* ~$6.0B $5.65 to $5.75B Non-GAAP effective tax rate Unchanged 19.5% to 20.5% *The difference between the combined GAAP R&D, AIPR&D and SG&A expenses and the combined non-GAAP R&D, AIPR&D and SG&A expenses guidance relates primarily to $650 million to $700 million of stock -based compensation expense, and approximately $500 million of compensation and transaction costs related to the Crinetics Pharmaceuticals acquisition.
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© 2026 Vertex Pharmaceuticals Incorporated 23 Crinetics Pharmaceuticals acquisition impact Q3:26 results and revised FY26 guidance Crinetics impact (Sep.) Total company (Vertex + Crinetics) Prior guidance (Aug. 3) Projected Crinetics impact (Sep–Dec) Current total company guidance Revenue $10M $3,441M $13.1–$13.2B ~$40-50M $13.15–$13.25B Non-GAAP OpEx* ~$60M OpEx & integration costs $1,533M $5.65–$5.75B Expect to be at high end of range ~$250M OpEx & integration costs ~$6.0B Non-operating items Interest expense & non-GAAP other expense, net (~$50M) ($50M) (~$105M) N/A Interest income ($15M) forgone interest $118M ($60M) forgone interest N/A Q3:26 Results FY 2026 Guidance *Combined non-GAAP R&D, Acquired IPR&D and SG&A expenses; Crinetics Pharmaceuticals acquisition impact reflects the Sept. 1 - Dec. 31 post-close period. An explanation and reconciliation of combined GAAP R&D, Acquired IPR&D and SG&A expenses to non-GAAP R&D, Acquired IPR&D and SG&A expenses for Q3:26 is included in the company’s press release dated November2, 2026. Q3:26 interest expense and non-GAAP other expense, net in the table above includes ~$36M of GAAP interest expense and ~$14M of non-GAAP other expense. A reconciliation of GAAP other income (expense), net to non-GAAP other expense, net is included in the company’s press release dated November 2, 2026.
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©2026 Vertex Pharmaceuticals Incorporated 24 Ma Anticipated key milestones Marketed CFTR modulators • Expand number of people treated: ultra-rare mutations, younger patients, additional geographies ALYFTREK (CF) • Expand CF leadership and reach more patients around the globe by driving U.S. adoption and ongoing OUS launches in 6+ year olds • Completed pivotal study for 2 to 5 years; began global regulatory submissions Next-generation 3.0 (CF) • VX-828: Study completed, delivered positive results; continue to advance VX-581 and VX-272 in FIH studies; determine next steps based on all data CASGEVY (SCD/TDT) • Reach more eligible patients ages 2+ year-olds through global ATC network, where approved • Secure additional pediatric approvals around the globe JOURNAVX (pain) • Acute: Continue to drive JOURNAVX Rx & revenue growth; plan forward to sunset PSP to normalize gross-to-net • Secure approval in Canada • DPN: Complete enrollment of both Phase 3 studies by YE 2026; share data mid-2027 VX-993 (pain) • DPN: Complete enrollment of Phase 2 study by YE 2026; share data mid-2027 PALSONIFY (acromegaly) • Drive U.S. launch to grow patients and prescriber base • Plan forward for EU launch in H2 2027 VX-017 and Zimislecel (T1D) • Enroll and dose Phase 1/2 evaluating VX-017 (Type O, “universal donor”) in people with T1D; zimislecel trial continues Inaxaplin (AMKD) • AMPLITUDE Phase 3 study (“primary” AMKD population) completed full enrollment; perform interim analysis and share data in early 2027 • If positive, AMPLITUDE will support potential accelerated approval in the U.S.; discuss AMPLIFIED Ph 2b results with FDA in the context of AMPLITUDE Povetacicept (IgAN, pMN, gMG) • IgAN: PDUFA target action date of November 30 in U.S.; launch ready • pMN: Drive Phase 3 enrollment and dosing well underway • gMG: Completed enrollment in Phase 2 study; share data in H1 2027 VX-407 (ADPKD) • Completed enrollment in the AGLOW Phase 2 proof-of-concept study; share data in 2027 VX-670 (DM1) • Completed enrollment and dosing in Phase 1/2 study; share interim results in H2 2026 Atumelnant (CAH and Cushing’s Syndrome) • CAH (adult): Complete enrollment in Q1 2027 • CAH (pediatric): Continue to enroll and dose Phase 2 study; engage with regulators to advance to pivotal trial • ACTH-dependent Cushing’s Syndrome: Enroll and dose Phase 2/3 trial OUS and engage with regulators to initiate pivotal study in U.S.
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©2026 Vertex Pharmaceuticals Incorporated ©2025 Vertex Pharmaceuticals Incorporated FIRST QUARTER 2025 FINANCIAL RESULTS ©2025 Vertex Pharmaceuticals Incorporated Third Quarter 2026 Financial Results November 2, 2026 Presentation intended for the investment community
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©2026 Vertex Pharmaceuticals Incorporated 26 Appendix GAAP to non-GAAP financial information ($ in millions except where noted or per share amounts and percentages) Q3:25 FY:25 Q3:26 Combined R&D, AIPR&D and SG&A GAAP 1.48B 5.80B 2.21B Non-GAAP 1.28B 5.12B 1.53B Operating income GAAP 1.19B 4.17B 0.71B Non-GAAP 1.38B 5.26B 1.41B Operating Margin % GAAP 39% 35% 21% Non-GAAP 45% 44% 41% Net income GAAP 1.08B 3.95B 0.65B Non-GAAP 1.24B 4.75B 1.21B Net income per share-diluted GAAP $4.20 $15.32 $2.56 Non-GAAP $4.80 $18.40 $4.76 Shares used in per share calculations GAAP 257.6 258.0 255.2 Non-GAAP 257.6 258.0 255.2 Notes: An explanation of non-GAAP financial measures and reconciliation of combined non-GAAP R&D, Acquired IPR&D and SG&A expenses, non-GAAP operating income, non-GAAP net income and non-GAAP net income per share – diluted to corresponding GAAP measures are included in the company’s press releases dated February 12, 2026 and November 2, 2026.