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©2026 Vertex Pharmaceuticals Incorporated ©2026 Vertex Pharmaceuticals Incorporated FIRST QUARTER 2025 FINANCIAL RESULTS ©2025 Vertex Pharmaceuticals Incorporated Fourth Quarter and Full Year 2025 Financial Results February 12, 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 and statements regarding (i) expectations, goals, development and commercialization plans and timelines for the company’s products, product candidates and pipeline programs, including beliefs regarding the emerging renal business, multiple launch opportunities, treatable patient populations, and additional opportunities in mid-and-late stage programs, including more than 10 disease areas with multi-billion dollar market potential, (ii) expectations for sustained growth with respect to the company’s CF medicines, including with respect to the ongoing commercial launch of ALYFTREK, that the majority of eligible CF patients will switch from TRIKAFTA to ALYFTREK over time, treating younger patients, filing for approval for TRIKAFTA in patients 1 to 2 years of age in H1 2026, initiating global regulatory submissions in H1 2026, CF population growth and patients living longer, reaching additional geographies, the goal to advance additional small molecules to be able to bring all eligible patients to carrier levels of CFTR function, and extending the CF portfolio’s market leadership with IP through 2040, (iii) plans to complete dosing in the MAD portion of the Phase 1/2 study of VX-522 to reach the ~5,000 CF patients who cannot benefit from a CFTRm and data in H2 2026, expectations to complete enrollment and dosing in the CF patient cohort for VX-828 in H1 2026, and plans to advance other next-generation CF compounds, (iv) expectations for CASGEVY, including with respect to the acceleration of patient infusions, CASGEVY’s commercial potential, including as a potential multi-billion dollar franchise, reaching more eligible patients and treating younger patients, expanding patient access to CASGEVY in new countries, initiating submissions for regulatory approval for 5 to 11 year olds in H1 2026, beliefs regarding transformative patient outcomes and survival rates, and the potential to improve conditioning associated with CASGEVY, (v) expectations for JOURNAVX in 2026, including with respect to prescription and revenue growth in the U.S., the expansion of the number of covered lives and scaling the number of hospitals with pathways to JOURNAVX, converting prescriptions to revenue, doubling the commercial field team, targeting more than 3x prescription growth, and plans to file for regulatory approval in Canada H1 2026, (vi) expectations for the pain program, including plans to complete enrollment in both ongoing studies evaluating suzetrigine in DPN by the end of 2026 and to continue to progress the Phase 2 study of VX-993 in DPN, (vii) expectations regarding povetacicept in IgAN, including expectations to complete the BLA submission in H1 2026, if results are supportive, and secure accelerated approval in the U.S., and the company’s beliefs regarding the clinical benefits of povetacicept in IgAN, including as a potential best-in-class asset, and for the potential launch of povetacicept in IgAN, (viii) expectations regarding the company's capabilities and potential leadership in renal medicine, including with respect to development and commercialization, and beliefs with respect to povetacicept as a potential a pipeline-in-a- product, povetacicept's clinical benefits and potential to treat additional B cell driven renal and other non-kidney diseases, and with respect to expectations to complete the Phase 2 portion of study in pMN and initiate Phase 3 in mid-2026, and to initiate a Phase 2 study in gMG in H1 2026, (ix) expectations for the T1D program, including with respect to zimislecel as a potentially curative treatment, and expectations to resume dosing in the Phase 1/2/3 study once internal manufacturing review is complete, (x) expectations for inaxaplin, including with respect to data from the Phase 3 interim analysis of AMPLITUDE at year end 2026 or in early 2027, filing for U.S. accelerated approval if results are supportive, and complete full enrollment in AMPLITUDE in H2 2026, and expectations to share data from AMPLIFIED by mid-2026, (xi) expectations for the clinical development of VX-407 in ADPKD, including to complete enrollment in the AGLOW study by the end of 2026, and plans for serial innovation to reach all ADPKD patients, and (xii) expectations for VX-670 in DM1 patients, including with respect to completing enrollment and dosing in the Phase 1/2 clinical trial of VX-670 in DM1 by mid-2026. 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 further successfully commercialize its marketed products, that regulatory submissions or approvals may not occur on the anticipated timeline, or at all, that data from clinical trials, especially if based on a limited number of patients, may not to be indicative of final results, that anticipated commercial launches may be delayed, if they occur at all, 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 (loss) (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) an intangible asset impairment charge, and (vii) 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 (loss) described above and certain discrete items. For full-year 2024, the company’s non-GAAP weighted-average common shares outstanding included the estimated effect of potentially dilutive securities that was not used in the calculation of GAAP diluted weighted-average common shares outstanding because the company incurred a GAAP net loss for the period. 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 Q4 2025 press release dated February 12, 2026.
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©2026 Vertex Pharmaceuticals Incorporated 4 FY 2025 total revenue +9% Y/Y and creates strong base for 2026 commercial priorities Cystic fibrosis portfolio CASGEVY PovetaciceptJOURNAVX Continue to expand market leadership Leverage established global ATC network to drive patient infusions Build on momentum of first year launch to grow Rx’s and revenue Submit for U.S. Accelerated Approval; prepare to win with potential best-in-class asset ATC: Authorized treatment center
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©2026 Vertex Pharmaceuticals Incorporated 5 CF: Multiple factors extend leadership and drive sustained growth ALYFTREK launch CF population growth Additional geographies Younger patients •Increases eligible population •TRIKAFTA: Target global regulatory submissions in patients ages 1-2 years, starting H1:26 •ALYFTREK: for patients ages 2-5 years, Phase 3 data demonstrated safety & efficacy, a 9.6 mmol/L reduction in sweat chloride from a TRIKAFTA baseline, and 65% of patients below carrier levels of sweat chloride; on track to initiate global regulatory submissions H1:26 •ALYFTREK: initiated study in patients ages 1 to <2 years •Best CFTR protein function, as measured by sweat chloride, plus once-daily dosing •Approved for additional response mutations •Expect majority of patients to switch to ALYFTREK from TRIKAFTA over time •CF patients are living longer •~3% CF population average annual growth rate 2020-20251 •Expanding beyond traditional core markets to new geographies •Brazil and Turkey Additional therapies •Serial innovation: NG 3.0 compounds, including VX-828 and VX-581 •VX-522 mRNA for last ~5,000 patients who do not make any CFTR protein; on track for data read-out in H2:26 1. Vertex internal research NG = next generation Key CF Growth Factors
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©2026 Vertex Pharmaceuticals Incorporated 6 Povetacicept: Potential best-in-class asset in IgAN Binding affinity for BAFF + APRIL Potency Pharmacokinetics Tissue distribution, including the kidney At-home administration Subcutaneous autoinjector Monthly dosing Small volume (0.46mL) 27 gauge needle <1.5 second injection time RUBY-3 Phase 2 data demonstrated potential best-in-class profile Specifically engineered to achieve improved… Differentiated monthly dosing and patient-centric features Reductions in Proteinuria Hematuria Gd-IgA1 stable renal function (eGFR) BLA submission for U.S. Accelerated Approval initiated Q4:25, on track to complete H1:26 *Gd-IgA1: galactose deficient immunoglobulin-A1; eGFR: estimated glomerular filtration rate
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©2026 Vertex Pharmaceuticals Incorporated 7 PATIENTS1 CURRENT PHASE 2026 MILESTONES B cell driven renal diseases Povetacicept – IgAN ~330K (>1.5M globally) Phase 3 trial enrollment complete • On track to complete submission H1:26 for U.S. AA, if results are supportive • Prepare for U.S. launch Povetacicept – pMN ~150K (>600K globally) Phase 2/3 pivotal trial ongoing • Complete Phase 2 portion and initiate Phase 3 mid-2026 Recently granted Orphan Drug status Other non-kidney Povetacicept – gMG ~175K (~300K globally) Phase 2 trial initiating H1:26 • Initiate Phase 2 and drive enrollment APOL1- mediated kidney disease (AMKD) Inaxaplin – Primary AMKD ~150K Phase 3 trial IA cohort enrollment complete • Phase 3 IA results YE:26 or early 2027; file for U.S. AA thereafter, if results are supportive • Complete full trial enrollment H2:26 Inaxaplin – AMKD with moderate proteinuria or diabetes ~100K Phase 2 trial ongoing • Share data mid-2026 Autosomal dominant polycystic kidney disease (ADPKD) VX-407 Up to ~30K Phase 2 trial • Continue to enroll & dose patients Serial innovation to reach all ADPKD patients ~300K (incl. ~30K) Research stage • Progress research-stage assets Rapid progress across renal portfolio, with multiple near-term catalysts 1. Estimated patient population in the U.S. and Europe, unless otherwise noted. IgAN: IgA nephropathy; pMN: primary membranous nephropathy; gMG: generalized myasthenia gravis; IA: interim analysis; AA: accelerated approval
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©2026 Vertex Pharmaceuticals Incorporated 8 R&D portfolio is broad, deep, and rapidly advancing Follow-on molecules: • CF • Pain • AMKD VX-407 ADPKD Approved Pivotal Development Phase (1)/2 in Patients Phase 1 in Healthy Volunteers Select, Next Wave Research-stage Programs Inaxaplin AMKD Suzetrigine DPN (2 studies) Zimislecel Type 1 diabetes Povetacicept IgA nephropathy Povetacicept pMN** Small molecule Huntington’s disease Islet cells + alternative immunosuppression Hypoimmune islet cells Type 1 diabetes Improved conditioning CASGEVY – SCD & TDT Na V1.7 inhibitor Pain VX-522 CFTR mRNA VX-670 DM1 VX-993 DPN *Phase 2 trial to initiate in H1:26. **In Phase 2 portion of Phase 2/3 trial. SCD: sickle cell disease; TDT: transfusion-dependent beta thalassemia; alt. IS: alternative immunosuppression; CF: cystic fibrosis; AMKD: APOL1-mediated kidney disease; ADPKD: autosomal dominant polycystic kidney disease; DPN: diabetic peripheral neuropathy; CFTR mRNA: cystic fibrosis transmembrane conductance regulator messenger RNA; DM1: myotonic dystrophy type 1; pMN: primary membranous nephropathy; gMG: generalized myasthenia gravis; wAIHA: warm autoimmune hemolytic anemia. VX-828 Cystic fibrosis Povetacicept wAIHA Povetacicept gMG*
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©2026 Vertex Pharmaceuticals Incorporated 9 ALYFTREK: A highly efficacious, once-daily CFTR modulator delivering equivalent improvement in lung function* and greater CFTR function** vs. TRIKAFTA CF: Q4 growth driven by multiple factors, including ALYFTREK launch and uptake in younger patients OUS: Outside U.S. *Lung function as measured by improvements in ppFEV1 vs. TRIKAFTA. **CFTR function as measured by improvements in sweat chloride vs. TRIKAFTA. • ALYFTREK rollout continues to progress well • Uptake in younger patients • Higher net realized prices OUS highlights U.S. highlights • ALYFTREK launches off to a strong start in EU • Secured reimbursement access H2:25: • England, Wales, Northern Ireland, Ireland, Germany, Denmark, Norway • Recently gained reimbursement in Australia, New Zealand and Italy • ~1,500 CF patients in Italy now able to access a CFTR modulator for the first time
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©2026 Vertex Pharmaceuticals Incorporated 10 109 301 2024 2025 2026+ 54 147 2024 2025 2026+ CASGEVY: Acceleration continues into 2026+ towards multi-$B potential Delivered $116M CASGEVY revenue in FY 2025 Accelerate patient infusions through existing global ATC network Expand to younger patients Broad coverage U.S.: ~90% Medicaid & commercial OUS: Access in 12 countries with more to come 2024 2025 2026+ Patients initiated 1st Cell collections Cell infusions Provide transformative patient outcomes* +31 yrs survival SCD +18 yrs survival TDT >90% projected reduction in lifetime VOCs & RBCTs *VRTX data projections over a lifetime horizon from TDT and SCD models that apply CASGEVY clinical efficacy data from the U.S. prescribing information to a cohort of patients with TDT and SCD that are approximately 20 years old, based on mean age at baseline in CASGEVY pivotal trials. ATCs: Authorized Treatment Centers; VoCs: vaso-occlusive crises; RBCTs: red blood cell transfusions. 64 5 111 in Q4:25 37 in Q4:25 30 in Q4:25
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©2026 Vertex Pharmaceuticals Incorporated 11 Pain: Transforming the standard of care for the treatment of acute pain 2025 execution positions JOURNAVX for significant growth in 2026 and beyond >200M covered lives >550K prescriptions >35K prescribers PAYERS PATIENTSPRESCRIBERS *Third national PBM contract effective 1/1/26. Hospital and ambulatory surgery center access pathways include formularies, order sets, and/or discharge protocols. 2025 2026 • Expand # of covered lives • Scale # hospitals with pathways • Convert Rx’s to revenue Targeting >3x prescriptions vs. 2025 Double field team to drive HCP adoption and depth All 3 national PBMs* contracted and >950 hospitals with access pathways Excellent breadth of prescribers and adoption across multiple specialties Strong early success and positive reception from patients with surgical and non- surgical pain
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©2026 Vertex Pharmaceuticals Incorporated 12 Establishing nephrology leadership with pove pipeline-in-a-product potential, including pMN, and additional programs in AMKD and ADPKD Comprehensive, dedicated patient support capabilities, informed by CF expertise • Proven capabilities in securing rapid & broad patient access • Completed engagement with 60+ payers representing ~190M covered lives in 2025 Expertise in high-science sales informed by transformative therapies in CF, Heme, and moderate-to-severe Acute Pain; field force hiring well underway and first-contingent in the field Renal: We plan to win in renal medicine, starting with pove in IgAN Vertex capabilities in developing and commercializing transformative medicines are now being applied to a broad and rapidly advancing kidney portfolio BIC: best-in-class; pMN: primary membranous nephropathy; AMKD: APOL1-mediated kidney disease; ADPKD: autosomal dominant kidney disease
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©2026 Vertex Pharmaceuticals Incorporated 13 Q4 and full year 2025 financial highlights 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 May 5, 2025, August 4, 2025, November 11, 2025, and February 12, 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. *Includes CASGEVY revenues of $8M Q4:24, $10M FY:24, $14M Q1:25, $30M Q2:25, $17M Q3:25, $54M Q4:25, $116M FY:25; JOURNAVX revenues of $1M Q1:25, $12M Q2:25, $20M Q3:25, $27M Q4:25, $60M FY:25. ($ in millions except where noted or per share data and percentages) Q4:24 FY24 Q1:25 Q2:25 Q3:25 Q4:25 FY25 TRIKAFTA/KAFTRIO 2.72B 10.24B 2.54B 2.55B 2.65B 2.57B 10.31B ALYFTREK - - 54 157 247 380 838 Other product revenues* 191 782 171 236 176 237 820 Product revenues, net 2.91B 11.02B 2.76B 2.94B 3.08B 3.19B 11.97B Other revenues - - 10 21 - - 31 Total revenues 2.91B 11.02B 2.77B 2.96B 3.08B 3.19B 12.00B Combined non-GAAP R&D, Acquired IPR&D and SG&A expenses 1.30B 8.82B 1.23B 1.24B 1.28B 1.36B 5.12B Non-GAAP operating income 1.20B 696 1.18B 1.33B 1.38B 1.37B 5.26B Non-GAAP operating margin % 41% 6% 43% 45% 45% 43% 44% Non-GAAP net income 1.04B 111 1.05B 1.17B 1.24B 1.29B 4.75B Non-GAAP net income per share – diluted $3.98 $0.42 $4.06 $4.52 $4.80 $5.03 $18.40 Cash, cash equivalents & total marketable securities (period-end) 11.2B 11.2B 11.4B 12.0B 12.0B 12.3B 12.3B
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©2026 Vertex Pharmaceuticals Incorporated 14 2026 financial guidance FY 2025 Actuals FY 2026 Guidance Commentary Total Revenue $12.00B $12.95 - $13.1B Full year revenue guidance includes expectations for continued growth in CF, as well as $500 million or more in revenue from non-CF products. Combined GAAP R&D, Acquired IPR&D and SG&A Expenses* $5.80B $6.3 - $6.45B Includes expectations for continued investment in multiple mid- and late-stage clinical development programs and commercial and manufacturing capabilities, as well as ~$100M of currently anticipated AIPR&D expenses. Combined Non-GAAP R&D, Acquired IPR&D and SG&A Expenses* $5.12B $5.65 - $5.75B Non-GAAP Effective Tax Rate 17.3% 19.5% - 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.
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©2026 Vertex Pharmaceuticals Incorporated 15 Anticipated Key Milestones TRIKAFTA (CF) Completed pivotal study for 12 to <24 months of age; begin global regulatory submissions in H1 2026 ALYFTREK (CF) Continue to drive adoption in U.S. and execute ongoing OUS launches in 6+ year olds Following positive data from Phase 3 study in children ages 2-5 years, initiate global regulatory submissions in H1 2026 Advance Phase 3 study in patients ages 1-2 years VX-522 (CF) Complete dosing in the MAD portion of the Phase 1/2 study; share data in H2 2026 Next-generation 3.0 (CF) VX-828: Complete enrollment and dosing in H1 2026; advance VX-581 and other next-generation 3.0 candidates CASGEVY (SCD/TDT) • Reach more eligible patients ages 12+ year-old and accelerate infusions through global ATC network • Initiate global regulatory submissions in patients ages 5-11 H1 2026; received FDA Commissioner’s National Priority Voucher Suzetrigine (pain) • Acute: Leverage first year JOURNAVX success to drive Rx & revenue growth in U.S. launch; file in Canada in H1 2026 • DPN: Complete enrollment of both Phase 3 studies by YE 2026 VX-993 (pain) • DPN: Continue to progress Phase 2 study Zimislecel/VX-880 (T1D) • Resume dosing post completion of internal manufacturing review Inaxaplin (AMKD) • AMPLITUDE: share data from Phase 3 interim analysis in late 2026 or early 2027; complete full enrollment in H2 2026 • AMPLIFIED (AMKD patients with moderate proteinuria or diabetes): share data mid-2026 in this expanded population Povetacicept (IgAN, pMN) • IgAN: First module of BLA submitted; complete submission of BLA in H1 2026 for potential U.S. accelerated approval; prepare for launch • pMN: Continue to enroll and dose Phase 2/3 pivotal trial; complete Phase 2 portion of study and initiate Phase 3 in mid-2026 • gMG: Initiate gMG Phase 2 study H1 2026 VX-407 (ADPKD) Complete enrollment in the AGLOW Phase 2 proof-of-concept study by the end of 2026 VX-670 (DM1) Complete enrollment and dosing of DM1 patients in the Phase 1/2 study mid-2026
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©2026 Vertex Pharmaceuticals Incorporated ©2026 Vertex Pharmaceuticals Incorporated FIRST QUARTER 2025 FINANCIAL RESULTS ©2025 Vertex Pharmaceuticals Incorporated Fourth Quarter and Full Year 2025 Financial Results February 12, 2026 Presentation intended for the investment community
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©2026 Vertex Pharmaceuticals Incorporated 17 Appendix GAAP to non-GAAP Financial Information 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 May 5, 2025, August 4, 2025, November 11, 2025, and February 12, 2026. (in millions except per share amounts and percentages) Q4:24 FY24 Q1:25 Q2:25 Q3:25 Q4:25 FY25 Combined R&D, Acquired IPR&D and SG&A GAAP 1.46B 9.72B 1.40B 1.41B 1.48B 1.52B 5.80B Non-GAAP 1.30B 8.82B 1.23B 1.24B 1.28B 1.36B 5.12B Operating income (loss) GAAP 1.03B (233) 630 1.15B 1.19B 1.21B 4.17B Non-GAAP 1.20B 696 1.18B 1.33B 1.38B 1.37B 5.26B Operating Margin %: GAAP 35% (2)% 23% 39% 39% 38% 35% Non-GAAP 41% 6% 43% 45% 45% 43% 44% Net income (loss) GAAP 913 (536) 646 1.03B 1.08B 1.19B 3.95B Non-GAAP 1.04B 111 1.05B 1.17B 1.24B 1.29B 4.75B Net income (loss) per share – diluted GAAP $3.50 $(2.08) $2.49 $3.99 $4.20 $4.65 $15.32 Non-GAAP $3.98 $0.42 $4.06 $4.52 $4.80 $5.03 $18.40 Shares used in diluted per share calculations GAAP 260.5 257.9 259.5 258.9 257.6 256.1 258.0 Non-GAAP 260.5 260.9 259.5 258.9 257.6 256.1 258.0