VERTEX PHARMACEUTICALS INC / MA (VRTX)

Item 2. Management’s Discussion and Analysis of Financial Condition and Results of Operations

OVERVIEW

We are a global biotechnology company that invests in scientific innovation to create transformative medicines for

people with serious diseases, with a focus on specialty markets. We have seven approved medicines: five that treat the

underlying cause of cystic fibrosis (“CF”), a life-threatening genetic disease, one that treats severe sickle cell disease

(“SCD”) and transfusion dependent beta thalassemia (“TDT”), life shortening inherited blood disorders, and one that treats

moderate-to-severe acute pain. We are also preparing for the anticipated launch of povetacicept, a potential treatment for IgA

nephropathy (“IgAN”). Our clinical-stage pipeline spans a range of programs targeting CF, SCD, beta thalassemia,

neuropathic pain, type 1 diabetes, IgA nephropathy, primary membranous nephropathy and other autoimmune diseases and

cytopenias, APOL1-mediated kidney disease, autosomal dominant polycystic kidney disease and myotonic dystrophy type 1,

reflecting our commitment to addressing significant unmet medical needs globally.

Financial Highlights

Q2 2025

Q2 2026

December 31, 2025

June 30, 2026

Note: Charts above may not add due to rounding.

Business Updates

Marketed Products

Cystic Fibrosis

We expect that the number of people with CF taking our medicines will continue to grow through new approvals and

reimbursement agreements, treatment of younger patients, increased survival and expansion into additional geographies.

Recent progress in activities expanding our CF business is included below:

•In the second quarter of 2026, we secured reimbursement for ALYFTREK in four additional countries, including

Spain, bringing the total number of countries where ALYFTREK is reimbursed to 25. We also signed a letter of

intent with the Pan-Canadian Pharmaceutical Alliance for reimbursement of ALYFTREK for eligible patients six

years of age and older in Canada.

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Sickle Cell Disease and Beta Thalassemia

•In the second quarter of 2026, we recorded $76.4 million of CASGEVY product revenues, representing a 78%

increase compared to the first quarter of 2026 and a 151% increase compared to the second quarter of 2025.

•The U.S. Food and Drug Administration (the “FDA”) approved CASGEVY in children two years of age and older

with SCD or TDT, making it the first genetic therapy indicated for children as young as two years of age for both

SCD and TDT. Approximately 5,500 patients with SCD or TDT may be eligible for treatment with CASGEVY for

the first time with this approval. We also completed regulatory submissions in the Kingdom of Saudi Arabia (“Saudi

Arabia”) and the United Kingdom for the treatment of children five to eleven years of age.

•In May, we secured reimbursement for CASGEVY for eligible patients 12 years and older with SCD or TDT in

Germany. We are committed to working with government and reimbursement authorities globally to ensure

sustainable access for eligible patients.

Acute Pain

•In the second quarter of 2026, we recorded $49.6 million of JOURNAVX product revenues, representing a 71%

increase compared to the first quarter of 2026 and a more than 300% increase compared to the second quarter of

2025.

•In the second quarter and first six months of 2026, approximately 535,000 and 900,000 prescriptions, respectively,

have been filled for JOURNAVX across the hospital and retail settings.

•We have reached agreements with two additional major pharmacy benefit managers for Medicare Part D coverage of

JOURNAVX. As a result, seniors covered by three of the four major Medicare Part D pharmacy benefit managers

have reimbursed access. Twenty-three states provide coverage for JOURNAVX via Medicaid. In total,

approximately 260 million individuals have reimbursed access to JOURNAVX across a wide range of commercial

and government payers.

Pipeline

We continue to advance a diversified pipeline of potentially transformative medicines for serious diseases utilizing a

range of modalities. Recent and anticipated progress in activities supporting these efforts is included below:

Cystic Fibrosis

•Following positive results from the Phase 3 clinical trial evaluating ALYFTREK in children with CF two to five

years of age, we initiated global regulatory submissions for this age group.

Acute and Peripheral Neuropathic Pain

•During the second quarter of 2026, Health Canada accepted our new drug submission for suzetrigine for the

treatment of moderate-to-severe acute pain, and review is underway.

•We expect to complete enrollment in both Phase 3 clinical trials evaluating suzetrigine in diabetic peripheral

neuropathy, a form of peripheral neuropathic pain, by the end of 2026.

IgA Nephropathy and Other B Cell-Mediated Diseases

•We are developing povetacicept, a dual inhibitor of B cell activating factor (“BAFF”) and a proliferation-inducing

ligand (“APRIL”) cytokines, for multiple diseases. Povetacicept represents a potentially best-in-class approach to

control B cell activity in IgAN.

•The FDA accepted our biologics license application for accelerated approval of povetacicept for adults with IgAN

and assigned a PDUFA target action date of November 30, 2026. If approved, povetacicept will become the first

commercialized therapy in our emerging nephrology franchise.

•We have completed our regulatory submission for accelerated approval of povetacicept in adults with IgAN in Saudi

Arabia, and the Saudi Food and Drug Authority has granted Breakthrough Designation to povetacicept.

•Povetacicept represents a potentially best-in-class approach to control B cell activity in primary membranous

nephropathy (“pMN”), another B cell-mediated disease. We completed the Phase 2B portion of the Phase 2/3

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OLYMPUS pivotal trial evaluating povetacicept in people with pMN, and we confirmed the dose selection for the

Phase 3 portion, which is underway.

APOL1-Mediated Kidney Disease

•Inaxaplin is our small molecule for the treatment of APOL1-mediated kidney disease (“AMKD”). We expect to

complete full enrollment in the AMPLITUDE Phase 2/3 pivotal clinical trial evaluating inaxaplin in the second half

of 2026.

•We expect to share data from the interim analysis of the AMPLITUDE clinical trial in early 2027. We expect to

conduct the pre-planned interim analysis for potential U.S. accelerated approval once the interim analysis cohort has

been treated for 48 weeks.

Type 1 Diabetes

•Zimislecel is an allogeneic, stem cell-derived, fully differentiated, insulin-producing islet cell replacement therapy,

using standard immunosuppression to protect the implanted cells. We are enrolling and dosing patients in the Phase

1/2/3 clinical trial of zimislecel in people with type 1 diabetes (“T1D”).

•The FDA cleared the Investigational New Drug Application for VX-017, our stem cell-derived, fully differentiated

islet cell therapy designed to treat all eligible patients with T1D, regardless of blood type. We plan to initiate a Phase

1/2 clinical trial to evaluate the safety and efficacy of VX-017 in people with T1D in the near term.

•We expect to provide updated timelines for the zimislecel and VX-017 programs in 2026.

Investment in External Innovation

•In July, we entered into an agreement and plan of merger (the “Crinetics Merger Agreement”) to acquire all of the

issued and outstanding shares of common stock of Crinetics Pharmaceuticals, Inc. (“Crinetics”) for $85.00 per share

in cash, for a total equity value of approximately $10.0 billion (the “Crinetics Acquisition”). We expect the

transaction to close in the third quarter of 2026, subject to certain customary conditions. Crinetics’ PALSONIFY®

(paltusotine) is a once-daily oral therapy for adults with acromegaly, a rare and debilitating condition caused by a

pituitary tumor that secretes excess growth hormone, who had an inadequate response to surgery and/or for whom

surgery is not an option. PALSONIFY is approved by the FDA and the European Medicines Agency, and is under

review by other global regulatory bodies. Crinetics’ most advanced pipeline candidate, atumelnant, is a once-daily

oral adrenocorticotropic hormone receptor antagonist in Phase 3 development for congenital adrenal hyperplasia.

Our Business Environment

In the first half of 2026, our total product revenues came primarily from the sale of our medicines for the treatment of

CF. Our CF strategy involves continuing to develop and obtain approval and reimbursement for treatment regimens that will

provide benefits to all people with CF and increasing the number of people with CF eligible and able to receive our

medicines. Outside of CF, we continue to advance the commercialization of CASGEVY for the treatment of SCD and TDT,

and JOURNAVX for the treatment of acute pain, and we are preparing for a potential launch of povetacicept for the treatment

of IgAN. In addition, we are advancing our pipeline of product candidates for the treatment of serious diseases outside of CF,

SCD, TDT and acute pain.

Our strategy is to combine transformative advances in the understanding of causal human biology and the science of

therapeutics to discover and develop innovative medicines. This approach includes advancing multiple compounds or

therapies from each program, spanning multiple modalities, into early clinical trials to obtain patient data that can inform

selection of the most promising therapies for later-stage development, as well as to inform discovery and development

efforts. We aim to serially innovate in our disease areas of interest and follow our first-in-class therapies with potential best-

in-class candidates to provide durable clinical and commercial success.

In pursuit of new product candidates and therapies in specialty markets, we invest in research and development. We

believe that pursuing research in diverse areas allows us to balance the risks inherent in product development and may

provide product candidates that will form our pipeline in future years. To supplement our internal research programs, we

acquire technologies and programs and collaborate with biopharmaceutical and technology companies, leading academic

research institutions, government laboratories, foundations and other organizations, as needed, to advance research in our

areas of therapeutic interest and to access technologies needed to execute on our strategy.

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Discovery and development of a new pharmaceutical or biological product is a difficult and lengthy process that requires

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[Excerpt truncated for page length; source filing is linked above.]

ITEM 7.MANAGEMENT’S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF

OPERATIONS

Our discussion and analysis of our financial condition and results of operations for 2025 as compared to 2024 are

discussed below. For a discussion of our financial condition and results of operations for 2024 as compared to 2023, please

refer to Item 7, “Management’s Discussion and Analysis of Financial Condition and Results of Operations” in our 2024

Annual Report on Form 10-K, except as set forth below.

OVERVIEW

We are a global biotechnology company that invests in scientific innovation to create transformative medicines for

people with serious diseases, with a focus on specialty markets. We have approved medicines for cystic fibrosis (“CF”),

sickle cell disease (“SCD”), transfusion dependent beta thalassemia (“TDT”), and acute pain, and we continue to serially

innovate and advance next-generation clinical and research programs in these areas. Our mid- and late-stage clinical pipeline

includes programs across a range of modalities in additional serious diseases, including IgA nephropathy, APOL1-mediated

kidney disease, neuropathic pain, type 1 diabetes, primary membranous nephropathy, autosomal dominant polycystic kidney

disease, and myotonic dystrophy type 1.

Collectively, our five CF medicines, led by TRIKAFTA/KAFTRIO, are being used to treat nearly three quarters of the

people with CF in the U.S., Europe, Australia, and Canada. ALYFTREK, our newest CF medicine, is approved in the United

States (the “U.S.”), the United Kingdom (the “U.K.”), the European Union (the “E.U.”), Canada, New Zealand, Switzerland,

Australia and Israel.

CASGEVY, our ex-vivo, non-viral CRISPR/Cas9 gene-edited cell therapy, is approved in the U.S., the E.U., the U.K.,

the Kingdom of Saudi Arabia (“Saudi Arabia”), the Kingdom of Bahrain (“Bahrain”), Qatar, the United Arab Emirates (the

“UAE”), Kuwait, Switzerland and Canada for the treatment of people 12 years of age and older with SCD or TDT.

JOURNAVX, our selective non-opioid NaV1.8 pain signal inhibitor, is approved in the U.S. for the treatment of people

with moderate-to-severe acute pain. We are continuing our commercial launch of JOURNAVX for eligible adults.

Financial Highlights

$0.1

45

$0.1

2024

2025

December 31, 2025

December 31, 2024

Note: Charts above may not add due to rounding.

Business Updates

Marketed Products

Cystic Fibrosis

We expect that the number of people with CF taking our medicines will continue to grow through new approvals and

reimbursement agreements, treatment of younger patients, increased survival and expansion into additional geographies.

•ALYFTREK is reimbursed for eligible people with CF in the U.S., England, Ireland, Germany, Denmark, Northern

Ireland, Norway, Wales, Italy, Australia, New Zealand and Luxembourg. We are working to secure access for

eligible patients in additional countries.

Sickle Cell Disease and Beta Thalassemia

•In 2025, we recorded $115.8 million of CASGEVY product revenues. This reflects 64 patients receiving infusions

of CASGEVY in 2025, including 30 people infused in the fourth quarter. Globally, in 2025, 147 people with SCD or

TDT had their first cell collection for CASGEVY.

•As of the end of 2025, approximately 90 percent of people with SCD or TDT in the U.S. have reimbursed access to

CASGEVY, which is also reimbursed in the U.K., Italy, Austria, Denmark, Luxembourg, Saudi Arabia, the UAE,

Bahrain, and Kuwait. In January 2026, we secured reimbursed access to CASGEVY for eligible people with SCD in

Scotland, consistent with the reimbursement agreement reached in 2025 for people with TDT.

•We expect to begin global regulatory submissions for approvals for CASGEVY in children 5 to 11 years of age, in

the first half of 2026. The FDA awarded Vertex with a Commissioner’s National Priority Voucher for this pediatric

submission, indicating an accelerated timeline for review once the submission is complete.

Acute Pain

•Since pharmacy availability in March 2025 through year-end 2025, more than 550,000 prescriptions for

JOURNAVX were written and filled across the hospital and retail settings in different acute pain conditions,

consistent with JOURNAVX’s broad label.

•We have secured access for JOURNAVX with all three national pharmacy benefit managers, and, as of January

2026, over 200 million individuals across commercial and government payers have coverage, representing two-

thirds of U.S. covered lives. In addition, 21 states provide coverage via Medicaid.

•More than 100 of the targeted 150 healthcare systems and more than 950 individual hospitals of the 2,000 targeted

institutions have added JOURNAVX to formularies, protocols or order sets.

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Select R&D Pipeline Programs

We continue to advance a diversified pipeline of potentially transformative medicines for serious diseases utilizing a

range of modalities. Recent and anticipated progress in activities supporting these efforts is included below:

Cystic Fibrosis

•We completed the global trial evaluating ALYFTREK in children 2 to 5 years of age. Following positive results

from this clinical trial, we expect to submit for approval with global regulators in this age group in the first half of

2026. We also initiated a pivotal trial of ALYFTREK in children 1 year to less than 2 years of age.

•Following positive results from the clinical trial evaluating TRIKAFTA in children 1 year to less than 2 years of age,

we expect to begin submissions for global regulatory approvals in this age group in the first half of 2026.

IgA Nephropathy

•We are developing povetacicept, a dual inhibitor of B cell activating factor (“BAFF”) and a proliferation-inducing

ligand (“APRIL”) cytokines, for multiple diseases. Povetacicept represents a potentially best-in-class approach to

control B cell activity in immunoglobulin A nephropathy (“IgAN”).

•We completed enrollment in the Phase 3 clinical trial evaluating povetacicept for IgAN and, in the fourth quarter of

2025, we initiated the rolling Biologics Licensing Application (“BLA”) filing for U.S. accelerated approval with

submission of the first module. We expect to release interim analysis data in the first half of 2026 and we expect to

complete the submission in the first half of 2026, if data from the interim analysis are supportive. We are using a

priority review voucher to expedite the review of the povetacicept BLA from ten months to six months.

APOL1-Mediated Kidney Disease

•Inaxaplin is our small molecule for the treatment of APOL1-mediated kidney disease (“AMKD”). We completed

enrollment in the interim analysis cohort of the global Phase 2/3 pivotal clinical trial evaluating inaxaplin in people

with primary AMKD (“AMPLITUDE”). We expect to conduct the pre-planned interim analysis once this cohort has

been treated for 48 weeks and we expect to share data from the interim analysis in late 2026 or early 2027. We

expect to complete full enrollment in AMPLITUDE in the second half of 2026.

Peripheral Neuropathic Pain

•We previously initiated the first Phase 3 clinical trial evaluating suzetrigine for the treatment of people with diabetic

peripheral neuropathy (“DPN”), a common form of peripheral neuropathic pain, and have initiated a second Phase 3

clinical trial evaluating suzetrigine in DPN in the fourth quarter of 2025. We expect to complete enrollment in both

Phase 3 clinical trials by the end of 2026.

Type 1 Diabetes

•Zimislecel is an allogeneic, stem cell-derived, fully differentiated, insulin-producing islet cell replacement therapy,

using standard immunosuppression to protect the implanted cells. We have completed enrollment in the Phase 1/2/3

clinical trial of zimislecel in people with type 1 diabetes (“T1D”). We have temporarily postponed completion of

dosing in this clinical trial, pending an internal manufacturing analysis.

Primary Membranous Nephropathy

•Povetacicept represents a potentially best-in-class approach to control B cell activity in primary membranous

nephropathy (“pMN”), another B cell-mediated disease. We are enrolling and dosing patients in the adaptive Phase

2/3 pivotal clinical trial of povetacicept for the treatment of people with pMN. We expect to complete the Phase 2

portion of the clinical trial and to initiate the Phase 3 portion in mid-2026.

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External Innovation

Recent investments in external innovation include:

•An exclusive global license agreement with WuXi Biologics to develop and commercialize a trispecific T cell

engager for B cell-mediated autoimmune diseases, which is currently in preclinical development.

Our Business Environment

In 2025, our net product revenues were primarily from the sale of our medicines for the treatment of CF. Our CF strategy

involves continuing to develop and obtain approval and reimbursement for treatment regimens that will provide benefits to all

people with CF and increasing the number of people with CF eligible and able to receive our medicines. Outside of CF, we

continue to advance the commercialization of CASGEVY for the treatment of SCD and TDT, and JOURNAVX for the

treatment of acute pain. In addition, we are advancing our pipeline of product candidates for the treatment of serious diseases

outside of CF, SCD, TDT and acute pain.

Our strategy is to combine transformative advances in the understanding of causal human biology and the science of

therapeutics to discover and develop innovative medicines. This approach includes advancing multiple compounds or

therapies from each program, spanning multiple modalities, into early clinical trials to obtain patient data that can inform

selection of the most promising therapies for later-stage development, as well as to inform discovery and development

efforts. We aim to serially innovate in our disease areas of interest and follow our first-in-class therapies with potential best-

in-class candidates to provide durable clinical and commercial success.

In pursuit of new product candidates and therapies in specialty markets, we invest in research and development. We

believe that pursuing research in diverse areas allows us to balance the risks inherent in product development and may

provide product candidates that will form our pipeline in future years. To supplement our internal

[Excerpt truncated for page length; the complete text is on the linked full-MD&A page.]