Safe Harbor Statement & Non-GAAP Financial Measures ©2026 Vertex Pharmaceuticals Incorporated ©2026 Vertex Pharmaceuticals Incorporated J.P. Morgan Healthcare Conference Reshma Kewalramani, M.D. CEO and President January 2026 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, devel ...

Core Insights - Vertex Pharmaceuticals experienced steady double-digit revenue growth in Q3, driven by the expansion of its cystic fibrosis franchise and new product launches in acute pain and genetic therapies [1] - Despite revenue growth, the market reacted negatively due to margin compression and operational investments impacting overall sentiment [1] Financial Performance - Revenue reached $3.08 billion, exceeding analyst estimates of $3.06 billion, reflecting an 11% year-on-year growth [6] - Adjusted EPS was reported at $4.80, beating analyst expectations of $4.58 by 4.9% [6] - Adjusted EBITDA stood at $1.44 billion, surpassing estimates of $1.37 billion, with a margin of 46.8% [6] - The company slightly raised its full-year revenue guidance to $11.95 billion from $11.93 billion [6] - Operating margin decreased to 38.6% from 40.3% in the same quarter last year [6] - Market capitalization is currently at $103.9 billion [6] Analyst Insights - Analysts raised questions regarding the adoption of ALYFTREK, with management indicating that most newly eligible U.S. patients have begun using the therapy [6] - Inquiry into the long-term effects of proteinuria reductions with povetacicept was addressed, with expectations of correlation to stabilized eGFR [6] - Capital allocation priorities were discussed, with a focus on reinvestment in R&D and commercialization [6] - The importance of monthly auto-injector dosing for povetacicept was highlighted as a differentiator in the renal market [6] - The rationale behind the FDA's breakthrough therapy designation for povetacicept was explained, citing unmet needs and strong data [6]

Financial Performance - Q3 2025 total revenues reached $3.08 billion, representing an 11% year-over-year growth[5,45] - TRIKAFTA/KAFTRIO contributed $2.65 billion in Q3 2025[45] - ALYFTREK generated $247 million in revenue during Q3 2025[45] - CASGEVY revenues were $17 million in Q3 2025 and are expected to exceed $100 million for the full year 2025[45,32] - JOURNAVX revenues were $20 million in Q3 2025[45] - Non-GAAP operating income was $1.38 billion with a 45% margin in Q3 2025[45] - Non-GAAP net income was $1.24 billion, or $4.80 per diluted share in Q3 2025[45] - The company refined its 2025 revenue guidance to $11.9-12.0 billion and non-GAAP OpEx to $5.0-5.1 billion, while lowering the tax rate guidance to 17%-18%[8] Pipeline and Approvals - ALYFTREK is now approved in the U S, U K, European Union, Canada, New Zealand, and Switzerland for patients aged 6 and older[9,26] - TRIKAFTA pivotal study in 12 to <24-month-old children completed, showing a mean sweat chloride reduction of more than 70 mmol/L from baseline through week 24[8]

Group 1 - Vertex is entering a new phase of revenue and commercialization diversification with three ongoing commercial launches: ALYFTREK for cystic fibrosis, CASGEVY for sickle cell disease and beta-thalassemia, and JOURNAVX for acute pain [3] - The company has four ongoing Phase III programs and plans to start a fifth soon, focusing on diabetic peripheral neuropathy in the pain franchise and three in the kidney space [4]

Core Viewpoint - Vertex Pharmaceuticals Inc reported better-than-expected earnings for the second quarter, with revenue of $2.97 billion exceeding estimates of $2.90 billion and adjusted EPS of $4.52 surpassing estimates of $4.29 [1][2] Financial Performance - The company's revenue for the second quarter was $2.97 billion, compared to estimates of $2.90 billion [1] - Adjusted EPS was reported at $4.52, exceeding the expected $4.29 [1] Product Performance - Vertex's three product launches—ALYFTREK, JOURNAVX, and CASGEVY—contributed to strong revenue growth [2] - The company is advancing its clinical programs alongside product launches [2] Clinical Study Results - Vertex announced topline results from a Phase 2 study of VX-993 for treating acute pain after bunionectomy surgery, which did not show statistically significant improvement on the primary endpoint [3] - The lack of significant results from the clinical study appears to have pressured the company's shares [3] Stock Performance and Analyst Ratings - Following the earnings announcement, Vertex Pharmaceuticals shares fell 18.8% to $383.40 [3] - Analysts adjusted their price targets for Vertex Pharmaceuticals, with several maintaining their ratings but lowering targets significantly [4][9] - Price target adjustments include: - HC Wainwright & Co. from $550 to $478 [9] - Morgan Stanley from $460 to $439 [9] - Stifel from $494 to $455 [9] - Cantor Fitzgerald from $535 to $485 [9] - BMO Capital from $557 to $530 [9] - UBS from $582 to $553 [9] - RBC Capital from $430 to $405 [9] - Scotiabank from $442 to $438 [9] - Truist Securities from $520 to $490 [9]

Financial Performance & Guidance - Q2 2025 total revenues reached $2.96 billion, compared to $2.65 billion in Q2 2024[48] - The company reiterated its 2025 total revenue guidance of $11.85-$12.0 billion[7] - Non-GAAP operating income for Q2 2025 was $1.33 billion, with a 45% operating margin[48] - Non-GAAP net income for Q2 2025 was $1.17 billion, or $4.52 per share diluted[48] - The company expects combined non-GAAP R&D, AIPR&D, and SG&A expenses to be $4.9-$5.0 billion for 2025[49] Key Product Updates - ALYFTREK generated $157 million in revenue in Q2 2025 and is approved for ages 6+ in the U S, U K, EU & Canada[33,48] - CASGEVY generated $30 million in revenue in Q2 2025, with 29 total patients infused since launch[40,48] - JOURNAVX generated $12 million in revenue in Q2 2025, with >110,000 prescriptions successfully filled as of mid-July[47,48] Pipeline Development - The company plans global regulatory submissions for Zimislecel (T1D) in 2026, targeting an initial launch to ~60,000 severe T1D patients[7,12] - Povetacicept (IgAN) Phase 3 interim analysis cohort is fully enrolled, with potential U S filing for accelerated approval in H1 2026[7,19] - VX-407 (ADPKD) Phase 2 proof-of-concept study is set to begin in Q3 2025, targeting up to ~30,000 patients with a subset of variants in the PKD1 gene[7,30]

Group 1 - Vertex Pharmaceuticals has successfully launched its fifth CFTR modulator, ALYFTREK, in the U.S. [3] - The company is building momentum for the CASGEVY launch, which is considered a foundational year after 2024 [3] - Vertex has also recently launched JOURNAVX for acute pain management, marking its entry into a new therapeutic area [2][3] Group 2 - The company is focused on executing its launches and expanding its pipeline over the next 12 to 18 months [2] - Vertex is strategically positioned with multiple product launches, enhancing its market presence in both cystic fibrosis and pain management [2][3]

Financial Performance & Guidance - Vertex reported Q1 2025 total revenue of $2.77 billion, compared to $2.69 billion in Q1 2024[56] - The company raised the low end of its 2025 total revenue guidance to $11.85-$12.0 billion[11] - Q1 2025 non-GAAP operating income was $1.18 billion, with a non-GAAP operating margin of 43%[56] - Q1 2025 non-GAAP net income was $1.05 billion, or $4.06 per share diluted[56] Key Product Updates & Pipeline Progress - ALYFTREK was approved in the U S and U K for CF patients ages 6+, with a strong U S launch and $54 million in revenue in Q1 2025[11, 56] - JOURNAVX, approved in the U S for acute pain, saw strong early uptake with over 20,000 prescriptions filled through April 18th[11, 55] - CASGEVY launch is gathering momentum across all regions, with $14 million in revenue in Q1 2025[11, 56] - The pivotal trial for Zimislecel in T1D is expected to complete enrollment and dosing in Q2 2025, with potential global regulatory submissions in 2026 targeting ~60,000 severe T1D patients in the U S and Europe[11, 17] - Enrollment is complete in the interim analysis cohort for Povetacicept in IgAN, with potential for U S accelerated approval in H1 2026[11, 32] - VX-407 for ADPKD is advancing to Phase 2 in H2 2025, targeting up to ~30,000 patients with a subset of variants in the PKD1 gene[11, 39]