Vertex Pharmaceuticals Incorporated : Q2 2023 Presentation

SECOND QUARTER 2023 FINANCIAL RESULTS

AUGUST 1, 2023

©2023 Vertex Pharmaceuticals Incorporated

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

Stuart Arbuckle, Executive Vice President and Chief Operating Officer

Financial Results

Charlie Wagner, Executive Vice President and Chief Financial Officer

©2023 Vertex Pharmaceuticals Incorporated

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SAFE HARBOR STATEMENT & NON-GAAP FINANCIAL MEASURES

This presentation contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, the information provided regarding expectations for future financial and operating performance, full-year 2023 financial guidance, and statements regarding our (i) expectations, development plans, and timelines for the company's products, product candidates, and pipeline programs, including expectations for five potential launches in five years, multiple clinical-stage programs with launch potential by 2030, anticipated benefits of new products, patient populations, study designs, study enrollment, data availability, anticipated regulatory filings, regulatory approvals, and timing thereof, (ii) expectations for continued growth in the number of CF patients treated with our existing therapies, including expected KAFTRIO/TRIKAFTA approval in patients aged 2 to 5 years in the EU by the end of 2023 and new reimbursement agreements, (iii) expectations to reach all CF patients eligible for CFTRm and the last ~5,000 CF patients (ineligible for a CFTRm) with VX-522, our plans to complete a single ascending dose study and initiate multiple ascending dose study for VX-522 in 2023, (iv) expectations for the benefits of vanzacaftor triple combination therapy, plans to complete Phase 3 studies in 2023, expectations for data in early 2024, and expectations for near-term launch, commercial potential and lower royalty burden, (v) expectations for the exa-cel program, including the potential of exa-cel to be a one-time, functional cure for patients with SCD and TDT and potential of exa-cel regulatory approval(s), and expectations for near-term launch and commercial potential, including potential participation in early access programs, expected patient population and expectations regarding providers and payers, (vi) expectations for our pain program, including its potential to treat acute pain without the limitations of opioids, the anticipated timeline to complete Phase 3 pivotal program for VX-548 in acute pain and complete Phase 2 studies of VX-548 in neuropathic pain, expectations for timelines of pain data, and plans for near-term commercial launch in moderate-to-severe acute pain, (vii) our expectations and beliefs regarding our pivotal program for inaxaplin, including its potential to treat the underlying cause of AMKD, plans to complete Phase 2B portion of studies in 2023, and our beliefs regarding anticipated results of the study, (viii) expectations for the development of our T1D programs, including the patient population, potential curative benefits and safety of VX-880, plans to present updated clinical data in October 2023, plans to begin Part C with concurrent dosing with VX-880 at full target dose, expectations for enrollment and dosing in VX-264 study, and expected use of CRISPR/Cas9 gene editing in our hypoimmune program, (ix) plans for continued advancement of VX-634 and VX- 864, (x) plans for our DMD and DM1 programs, including expectations to file INDs, and (xi) expectations regarding the company's tax rates, revenue growth, and the impact of foreign exchange rates on revenue growth. While Vertex believes the forward-looking statements contained in this presentation are accurate, these forward-looking statements represent the company's beliefs only as of the date of this presentation and there are a number of 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 financial and operating performance may be incorrect (including because one or more of the company's assumptions underlying its expectations may not be realized), that our regulatory submissions could be delayed and our products may not receive regulatory approval on expected timelines, or at all, that external factors may impact the company's business or operations differently than the company currently expects, that data from preclinical testing or clinical trials, especially if based on a limited number of patients, may not be indicative of final results, that patient enrollment in our trials may be delayed, that actual patient populations able to participate in our trials or eligible for our products may be smaller than anticipated, that reimbursement for our therapies may be more difficult to obtain or maintain than expected, that data from the company's development programs may not be available on expected timelines, or at all, and may not support registration or further development of its potential medicines due to safety, efficacy or other reasons, and other risks listed under "Risk Factors" in Vertex's annual report filed with the Securities and Exchange Commission (SEC) and available through the company's website at www.vrtx.com and on the SEC's website at www.sec.gov. You should not place undue reliance on these statements, or the scientific 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) gains or losses related to the fair value of the company's strategic investments, (iii) increases or decreases in the fair value of contingent consideration, (iv) acquisition-related costs, (v) an intangible asset impairment charge, and (vi) 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, Acquired IPR&D and SG&A expenses and effective tax rate on a non-GAAP basis. Unless otherwise noted, the guidance regarding combined GAAP and non-GAAP R&D, Acquired IPR&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 Q2 2023 press release dated August 1, 2023.

©2023 Vertex Pharmaceuticals Incorporated

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CONTINUED STRONG MOMENTUM IN THE SECOND QUARTER

Continue the journey in cystic fibrosis (CF)

• Serially innovate to bring highly efficacious CFTRm to all eligible patients
• Reach the last ~5,000 patients (ineligible for a CFTRm) with mRNA therapy
• Continue to build unparalleled portfolio of real-world and long-term data

Prepare for potential near-term commercial launches

• Exa-celin SCD and TDT: FDA granted Priority Review for SCD (PDUFA: December 8,
  2023); TDT (PDUFA: March 30, 2024); reviews in the EU and U.K. are well underway
• VX-548in moderate to severe acute pain: all Phase 3 studies expected to complete by end of 2023
• Vanzacaftor triple in CF: Phase 3 studies expected to complete by end of 2023

Accelerate diversified R&D pipeline

• Five potential launches in the next five years

Deliver financial performance

• Strong results; raising 2023 revenue guidance $100-150M on continued revenue growth from treating more patients with CF; raising 2023 non-GAAP OpEx guidance $200M on higher YTD acquired IPR&D expenses from new business development
• Specialty model sustains strong operating margins while allowing for significant investments in the pipeline and commercial capabilities

©2023 Vertex Pharmaceuticals Incorporated

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EXECUTING ON VERTEX BUSINESS MODEL AND R&D STRATEGY WITH RAPID PROGRESS ON A ROBUST PIPELINE

FIVE POTENTIAL LAUNCHES IN THE NEXT FIVE YEARS

Revenue growth: high operating margins and significant cash flow

Investment of majority

of OpEx in R&D and

BD/external innovation

Creation of

DIFFERENTIATED high-value transformative

BUSINESS medicines for

MODELspecialty markets

Limited SG&A expenses and infrastructure

We focus on

• Validated targets that address causal human biology
• Predictive lab assays and clinical biomarkers
• Rapid path to registration and approval

In order to deliver a portfolio with

• transformative benefit, regardless of modality
• greater likelihood of clinical success

4 Approved medicines in cystic fibrosis

8	Programs
in mid- or
late-stage
development

Near-termcommercial opportunities Exa-cel(SCD)

Exa-cel (TDT)

Vanzacaftor triple (CF)

VX-548 (acute pain)

Mid/late-stageclinical pipelineInaxaplin (AMKD) - Post PoC VX-880(T1D) - Post PoC

VX-548 (neuropathic pain) - Phase 2 VX-864 (AATD) - Phase 2

PoC: proof of concept; SCD: sickle cell disease; TDT: transfusion-dependent beta thalassemia; AMKD: APOL1-mediated kidney disease; T1D: type 1 diabetes; AATD: Alpha-1 Antitrypsin Deficiency

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©2023 Vertex Pharmaceuticals Incorporated