Vertex Pharmaceuticals Investor Presentation — October 2022

Document content

©2022 Vertex Pharmaceuticals Incorporated 12AGENDA

Susie Lisa, CFA, Senior Vice President, Investor Relations

CEO Perspective and Pipeline Update

Reshma Kewalramani, M.D., Chief Executive Officer and President

Stuart Arbuckle, Executive Vice President and Chief Operating Officer

Charlie Wagner, Executive Vice President and Chief Financial Officer

©2022 Vertex Pharmaceuticals Incorporated3SAFE HARBOR STATEMENT & NON-GAAP FINANCIAL MEASURES

This presentation contains forward -looking statements as defined in the Private Securities Litigation Reform Act of 1995, as ame nded, including, without limitation, the information provided regarding future

financial performance and operations, fiscal year 2022 financial guidance, and statements regarding our ( i) expectations, development plans, anticipated timelines for and potential benefits of the company’s

products and product candidates, including study designs, clinical site initiations, patient enrollment, data availability, a nticipated regulatory filings, approvals, and timing thereof, (ii) outlook for sustained growth in

the number of CF patients treated with our products, including reaching more CF patients who can benefit from our marketed pr oducts, (iii) plans to treat additional CF patients with mRNA and views on treatable

patient population, expectations for a CFTR mRNA IND filing before the end of 2022 with clinical trials thereafter, (iv) expe ctations for our next -in-class, once -daily, oral triple regimen for CF patients, including

beliefs on enhanced patient benefit and development of Phase 3 trials and program expectations, (v) expectations for our exa -celprogram, including the continued potential for exa -celto be a curative approach for

patients with TDT and SCD and our views on treatable patient population, plans to initiate regulatory filings in the U.S. in November with completion expected in Q1 2023, and submit regulatory filings in Europe and

the U.K. before the end of 2022, as well as potential commercial opportunities and preparations, (vi) expectations regarding the potential benefits of our pain program, including the belief that VX -548 could reduce

in prevalence of opioids in the treatment of pain, the continued advancement of VX -548 into its Phase 3 trial in acute pain, com mercial opportunities, preparations, and market analysis for VX -548, and plans to

study VX -548 in a Phase 2 dose -ranging proof -of-concept study for neuropathic pain towards year -end 2022, as well as enrollment expectations in both studies, (vi) our plans regarding our pivotal program

underway for inaxaplin in AMKD, including enrollment expectations, and our beliefs regarding anticipated results of the study and the possibility fo r accelerated approval in the U.S., (vii) expectations for the