Vertex Pharmaceuticals Incorporated : 2024 VRTX William Blair Growth Stock Conference Presentation vFinal

WILLIAM BLAIR 44TH ANNUAL GROWTH STOCK CONFERENCE

RESHMA KEWALRAMANI, M.D.

CEO AND PRESIDENT

JUNE 4, 2024

©2024 Vertex Pharmaceuticals Incorporated

SAFE HARBOR

STATEMENT & NON-

GAAP FINANCIAL

MEASURES

©2024 Vertex Pharmaceuticals Incorporated

This presentation contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, including, without limitation, the information provided regarding and expectations for future financial and operating performance and statements regarding (i) expectations, development plans and timelines for the company's medicines and pipeline programs, including expectations for five potential launches over five years, anticipated near-term commercial opportunities for the vanzacaftor triple in CF and suzetrigine in acute pain, anticipated benefits of potential new products and relevant patient populations, and plans to broaden and deepen R&D pipeline across modalities, (ii) plans to launch CF medicines in younger age groups globally and to bring additional molecules to market to get CF patients to carrier levels CFTR function, (iii) expectations for the vanzacaftor triple, including expectations for a substantially lower royalty burden, (iv) plans to advance VX-522 mRNA to reach the >5,000 CF patients who cannot benefit from CFTR modulators, (v) expectations for CASGEVY, including the potential benefits for patients with SCD or TDT, and plans to obtain approvals in additional geographies,

1. expectations for our pain program, including plans for near-term launch and commercial potential in acute pain, expectation for treatment of acute pain without non-opioid medicine, expectations related to acute pain regulatory filings and potential for a broad label in acute pain, and our plans and expectations for our VX-993 studies, (vii) expectations for our T1D program, including expectations to complete dosing in the 17-patient trial for VX-880, expectations for the VX-264 studies and plans to share updated data at a conference in June 2024, and (viii) expectations for povetacicept, including expectations for the Phase 3 trial to begin in the second half of 2024, and expectations that povetacicept offers "pipeline-in-a-product" opportunities, and plans to accelerate povetacicept development. 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 data from clinical trials, especially if based on a limited number of patients, may not to be indicative of final results, regulatory submissions may not be completed on the anticipated timeline, or at all, expected benefits of the Alpine acquisition may not be achieved, the company may not be able to scale up manufacturing of our product candidates, actual patient populations eligible for our products may be smaller than anticipated, data from the company's development programs may not be available on expected timelines, or at all, support registration or further development of its potential medicines due to safety, efficacy or other reasons, 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.govand 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 references financial guidance and results that have been provided in accordance with US GAAP and certain non-GAAP financial measures. 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. A reconciliation of the GAAP financial results to non-GAAP financial

results is included in the appendix hereto.	2

DIFFERENTIATED VERTEX BUSINESS MODEL AND R&D STRATEGY

Revenue growth: high operating margins and significant cash flow

Investment of majority

of OpEx in R&D and

BD/external innovation

DIFFERENTIATED

BUSINESS MODEL

Limited SG&A expenses and infrastructure

Creation of high-value transformative medicines for specialty markets

WE FOCUS ON

• Diseases where causal human biology is known
• Validated targets
• Biomarkers that translate from bench to bedside
• Best modality (i.e., modality agnostic)
• Efficient development & regulatory pathways

IN ORDER TO DELIVER

• Transformative medicines for patients
• Greater likelihood of clinical success
• Sustained innovation
• Shareholder value

©2024 Vertex Pharmaceuticals Incorporated

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EXPANDING LEADERSHIP IN CF AND ENTERING A NEW ERA OF DIVERSIFICATION IN MULTIPLE SERIOUS DISEASES

Approved medicines

across CF, sickle cell disease

and beta thalassemia

Additional near-term

commercial opportunities*

• Vanzacaftor triple (CF)
• Suzetrigine (acute pain)

Broad, diversified pipeline in patients in mid- and late- stage clinical development

• Inaxaplin (AMKD)
• Suzetrigine (DPN)
• Povetacicept (IgAN)
• Suzetrigine (LSR)
• VX-880(T1D)
• VX-264(T1D)
• VX-522(CF - mRNA)
• VX-670(DM1)
• Povetacicept (additional indications)

AMKD: APOL1-mediated kidney disease; T1D: type 1 diabetes; DPN: diabetic peripheral neuropathy; IgAN: IgA nephropathy; LSR: lumbosacral radiculopathy; DM1: myotonic-dystrophy type 1
*Subject to regulatory approval	4
©2024 Vertex Pharmaceuticals Incorporated

WE HAVE A BROAD PORTFOLIO OF DISEASE AREAS UNDER EVALUATION IN THE CLINIC

STRONG PROGRESS TOWARDS OUR GOAL OF FIVE LAUNCHES OVER FIVE YEARS (2028)	Type 1	Acute Pain
							Neuropathic Pain
						IgA Nephropathy & Diabetes
					Autosomal Other B-Cell Mediated
			Myotonic	Dominant	Diseases
			Polycystic
			Dystrophy	Kidney Disease
			Alpha-1 Antitrypsin	Type 1
		APOL1-Mediated	Deficiency
	Cystic Fibrosis	Kidney Disease
Sickle Cell Disease										90M
Beta Thalassemia
									(U.S.)
						250,000	>400,000	3.8M
	92,000	100,000	100,000	110,000
		(U.S.)
35,000	+ additional countries
							~125,000
severe
+ KSA & Bahrain	>5,000*				~25,000#		severe
Images not to scale; Illustrative purposes. Patient populations include U.S., Europe, and select geographies.
*Over 5,000 people with CF cannot benefit from CFTR modulators and thus may potentially benefit from VX-522, our mRNA program.
#Select PKD1 mutations.									global.vrtx.com	5
©2024 Vertex Pharmaceuticals Incorporated

EXPANDING LEADERSHIP IN CF AND RAISING THE BAR WITH SERIAL INNOVATION

~92,000

patients with CF*

~20,000

eligible patients not

on CFTR

modulators

GROWTH DRIVERS

• Treating younger patients
• Patients living longer
• Serial CFTRm innovation
• mRNA for last >5,000 patients

Best-in-class	Goal: carrier levels
medicines
of CFTR function

VX-522

mRNA • For the last >5,000 patients who cannot benefit from CFTR modulators

Cystic Fibrosis

Approvals

Vanzacaftor	•	Completed regulatory submissions for ages 6+ in the U.S. and the EU
triple	•	Non-inferior on lung function, superior on sweat chloride vs. TRI in 12+
	•	Convenient, once-daily dosing
	•	Substantially lower royalty burden

*Patient populations include North America, Europe, and Australia.

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©2024 Vertex Pharmaceuticals Incorporated

CASGEVY: BEGINNING OF NEW ERA OF DIVERSIFICATION

Rapid pace of global approvals:

• Approved for eligible patients ages 12+ with sickle cell disease or transfusion-dependent beta thalassemia by
• • U.S.
  • Great Britain
  • European Union
  • Kingdom of Saudi Arabia
  • Kingdom of Bahrain
• Completed regulatory submissions for CASGEVY in

Switzerland and Canada

CRISPR/Cas9 precisely targets the erythroid-specific enhancer region of the BC11A gene.

The first precise, durable, CRISPR/Cas9 gene-edited therapy, delivering a potential one-time functional cure for patients with SCD and TDT

©2024 Vertex Pharmaceuticals Incorporated

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WE AIM TO TRANSFORM TREATMENT OF ACUTE PAIN WITH SUZETRIGINE,

• NON-OPIOIDPOTENTIAL MEDICINE AND FIRST NEW CLASS OF PAIN MEDICINES IN >2 DECADES

Origin of pain

Selectively inhibits	TODAY
NaV1.8 channel in
peripheral nerves

Inhibition of NaV1.8 reduces	FUTURE
action potential signaling,
preventing pain transmission

• NaV1.8 and 1.7 are validated targets for pain

• Compelling combination of strong efficacy and safety in Phase 3 results
• Rolling NDA submission progressing as planned; suzetrigine has Fast Track and Breakthrough Therapy designations
• Seeking a broad label in moderate to severe acute pain

©2024 Vertex Pharmaceuticals Incorporated

Anti-Inflammatory/	Opioids
Analgesics

Pain signal inhibitors, starting with VX-548

• Acute pain is a multi-billion-dollar market today: 80M patients annually and over 1B calendar days of treatment in the U.S.
• Significant unmet need: Existing treatment options have limitations around efficacy, side effects and addiction potential
• High concentration of prescribing, will target with specialty infrastructure and commercial team build-outwell underway

global.vrtx.com

TYPE 1 DIABETES: ADVANCING POTENTIALLY CURATIVE TREATMENTS FOR ~3.8M PATIENTS IN NORTH AMERICA & EUROPE

EDITED, FULLY DIFFERENTIATED,

HYPOIMMUNE ISLET CELLS

VX-264: FULLY DIFFERENTIATED

CELLS + DEVICE

VX-880: FULLY DIFFERENTIATED CELLS	•
WITH STANDARD IMMUNOSUPPRESSION	•

• • Same cells as VX-880, edited to eliminate need for immunosuppressants
  • Research program continues to progress
• Same cells as VX-880, encapsulated in a device designed to eliminate the need for immunosuppressants
• Phase 1/2 multi-part study ongoing:
• • Part A completed
  • Part B ongoing in multiple countries

Phase 1/2 trial: 17-patient trial fully enrolled and expect to complete dosing soon

Plan to share updated data at American Diabetes Association 84th Scientific Sessions Conference in June 2024

©2024 Vertex Pharmaceuticals Incorporated

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ACQUISITON OF

ALPINE IMMUNE SCIENCES:

~$5B CASH

BAFF: B-cell activating factor; APRIL: a proliferation-inducing ligand; IgAN: immunoglobulin A

nephropathy; pMN: primary membranous nephropathy; LN: lupus nephritis Transaction closed on May 20, 2024.

• Compelling fit with the Vertex strategy of investing in serial innovation to create transformative medicines that target serious diseases with high unmet need in specialty markets
• Alpine's lead asset, povetacicept ("pove"), is a Phase 3- ready, innovative, and potentially transformative approach to IgAN, a serious, progressive, autoimmune kidney disease
• • Best-in-classpotential; Phase 3 trial to begin H2:24
• Povetacicept, given dual BAFF/APRIL inhibition, also offers promise of "pipeline-in-a-product" in multiple other serious autoimmune renal diseases and cytopenias
• Vertex capabilities will accelerate povetacicept development in IgAN and other indications, while Alpine adds protein engineering and immunotherapy expertise to Vertex

global.vrtx.com 10

©2024 Vertex Pharmaceuticals Incorporated