VERTEX PHARMACEUTICALS INC / MA (VRTX) Business

ITEM 1.BUSINESS

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.

The following chart sets forth our approved products, clinical-stage programs, and select pre-clinical programs:

We are advancing five pivotal programs across multiple disease areas:

•IgA Nephropathy. We are developing povetacicept, a dual inhibitor of the B cell activating factor (“BAFF”) and a

proliferation-inducing ligand (“APRIL”) pathways, as a potentially best-in-class approach to treat IgA nephropathy

(“IgAN”), a serious, progressive, life-threatening kidney disease that often progresses to end-stage renal disease. We

completed enrollment in the IgAN Phase 3 clinical trial and submitted the first module of the rolling Biologics

Licensing Application (“BLA”) for povetacicept in IgAN in the fourth quarter of 2025. We expect to complete the

submission for potential accelerated approval in the U.S. in the first half of 2026.

•APOL1-Mediated Kidney Disease. We are developing inaxaplin, a small molecule inhibitor of APOL1 as a potential

first-in-class treatment for APOL1-mediated kidney disease (“AMKD”). We have completed the enrollment of the

interim analysis cohort of the Phase 2/3 clinical trial and will conduct the pre-planned interim analysis once this

cohort reaches 48 weeks of treatment. We expect to share data from the interim analysis in late 2026 or early 2027.

•Peripheral Neuropathic Pain. We are developing suzetrigine, a selective non-opioid NaV1.8 pain signal inhibitor,

for diabetic peripheral neuropathy (“DPN”), a common form of peripheral neuropathic pain. We are evaluating

suzetrigine for the treatment of DPN in two Phase 3 clinical trials. We expect to complete enrollment in both Phase

3 clinical trials by the end of 2026.

2

•Type 1 Diabetes. Zimislecel is an allogeneic stem-cell derived, fully differentiated islet cell therapy in pivotal

development for the treatment of type 1 diabetes (“T1D”). We have completed enrollment in the Phase 1/2/3 clinical

trial of zimislecel in people with T1D. We have temporarily postponed completion of the dosing in this clinical trial,

pending an ongoing internal manufacturing analysis.

•Primary Membranous Nephropathy. We are also developing povetacicept to treat primary membranous nephropathy

(“pMN”), a rare and serious autoimmune glomerular disease that can lead to kidney damage and renal failure, and

which has no treatments specifically approved for this condition. We continue to enroll and dose patients in the

adaptive Phase 2/3 pivotal trial in 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.

Our core strategy is to discover, develop, and commercialize innovative medicines by combining transformative

advances in the understanding of human disease and the science of therapeutics, to dramatically advance human health. We

focus on validated targets that address causal human biology, predictive lab assays and clinical biomarkers, rapid paths to

registration and approval, and product candidates that hold the potential for transformative patient benefit. Our approach

includes advancing multiple compounds or therapies from each program into early clinical trials to obtain patient data that

can inform selection of the most promising therapies for later stage development as well as inform our ongoing 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. We plan to continue investing to advance our strategy, fostering scientific innovation by

identifying additional product candidates through internal research efforts, and investing in business development

transactions to access emerging technologies, products and product candidates.

Our serial innovation approach is intended to increase the likelihood of successfully bringing transformative medicines to

patients and to provide durable clinical and commercial success. We are working to ensure broad access for eligible patients

with these conditions in all countries with regulatory approval. Within our clinical pipeline, we are rapidly progressing

multiple programs into pivotal development. We maintain a strong financial profile as we continue to invest in our serial

innovation strategy, launch new products, advance our diverse pipeline, and expand geographically.

3

MARKETED PRODUCTS

Information regarding our marketed products, including information regarding the disease area, initial approval and age

group for which the therapy is approved, are set forth in the table below.

(1) Specifies the youngest eligible age group in any major market.

CF

CF is a life-shortening genetic disease caused by a defective or missing cystic fibrosis transmembrane conductance

receptor (“CFTR”) protein resulting from mutations in the CFTR gene. The absence of working CFTR protein results in poor

flow of salt and water into and out of cells in a number of organs, including the lungs, where mucus builds up, causing

chronic lung infections and progressive lung damage. Our CFTR modulators, including ivacaftor, deutivacaftor, lumacaftor,

tezacaftor, elexacaftor, and vanzacaftor, target the underlying cause of disease by improving CFTR protein function, and as

such have been shown to provide transformative benefit for people living with CF.

Our marketed CF medicines, ALYFTREK (vanzacaftor/tezacaftor/deutivacaftor), TRIKAFTA/KAFTRIO (elexacaftor/

tezacaftor/ivacaftor and ivacaftor), SYMDEKO/SYMKEVI (tezacaftor/ivacaftor and ivacaftor), ORKAMBI (lumacaftor/

ivacaftor) and KALYDECO (ivacaftor), are being used by nearly three quarters of the approximately 97,000 people with CF

in the U.S., Europe, Australia, and Canada. We estimate that there are approximately 112,000 people with CF in all target

markets.

4

Our CF medicines are reimbursed or accessible in more than 60 countries across six continents. ALYFTREK, our most-

recently approved triple combination CF medicine, has the benefit of a once-daily dosing regimen and demonstrated non-

inferiority to TRIKAFTA in ppFEV1, a measure of lung function, and an improvement in sweat chloride levels as compared

to TRIKAFTA. We expect that the majority of people with CF will transition to ALYFTREK over time.

Sickle Cell Disease and Transfusion-Dependent Beta Thalassemia

SCD and TDT are hemoglobinopathies, a group of inherited blood disorders that result from gene mutations that alter

hemoglobin, a protein in red blood cells that delivers oxygen throughout the body.

SCD is caused by the change of a single amino acid in the β-hemoglobin gene that causes red cells to change shape in

settings of low oxygen. These sickled cells block blood flow and can lead to severe pain (known as vaso-occlusive crises),

organ damage, and shortened life span. Treatment is typically focused on relieving pain and minimizing organ damage,

requiring medication and, for some patients, monthly blood transfusions and frequent hospital visits.

Beta thalassemia is caused by loss-of-function mutations in the same β-hemoglobin gene that lead to severe anemia in

patients, which causes fatigue and shortness of breath. In infants, beta thalassemia causes failure to thrive, jaundice, and

feeding problems. Complications of beta thalassemia can lead to an enlarged spleen, liver and/or heart, misshapen bones and

delayed puberty. Treatment for beta thalassemia varies depending on the disease severity for each patient. People with TDT,

the most severe form of the disease, require regular blood transfusions, as frequently as every two to four weeks. Repeated

blood transfusions eventually cause an unhealthy buildup of iron in the patient, leading to organ damage.

CASGEVY (exagamglogene autotemcel), our ex-vivo, non-viral CRISPR/Cas9-based gene-editing therapy for severe

SCD and TDT, is approved in the U.S. and across multiple geographies including Europe, Canada, and the Middle East. We

estimate approximately 60,000 people with severe SCD or TDT are or could become eligible for CASGEVY in these

geographies. To receive CASGEVY, patients first undergo a treatment at an authorized treatment center (“ATC”) that

mobilizes a population of hematopoietic stem and progenitor cells (“HSPC”) from the bone marrow into the bloodstream.

These cells are collected from the patient’s bloodstream and transferred to a manufacturing facility where the HSPCs are

isolated and CRISPR/Cas9 gene-editing is performed on the cells. The gene-editing procedure results in a precise and specific

gene-edit in a non-coding intron of the BCL11A gene. Following manufacturing, the edited cells, now called CASGEVY, are

transferred back to the ATC. Patients are preconditioned with a myeloablative conditioning treatment that ablates their bone

marrow to create space for the edited cells. After CASGEVY is infused into the patient and the edited cells engraft, the levels

of fetal hemoglobin erythrocytes increase, thereby reducing or eliminating symptoms associated with disease. Efficacy data

support the profile of CASGEVY as a potential one-time functional cure for people with severe SCD and TDT.

CASGEVY is broadly reimbursed by third-party payors in the U.S., including the federal government and commercial

payors. In addition, we have agreements with national and regional payors covering more than 275 million lives, to provide

access to CASGEVY. Outside of the U.S., patients have access to CASGEVY in Austria, Denmark, the U.K., Italy,

Luxembourg, Bahrain, Saudi Arabia, the UAE, and Kuwait. We continue to expand access and pursue additional long-term

reimbursement arrangements and to engage with payors in the E.U. and the Middle East.

Globally in 2025, approximately 300 people with SCD or TDT initiated treatment with CASGEVY, 147 people had their

first cell collection for CASGEVY, and 64 people received infusions of CASGEVY. In 2026, we expect to reach more

eligible patients and drive patient infusions through our global ATC network.

Acute Pain

Acute pain is a disabling condition that may occur suddenly but typically lasts less than 90 days and resolves in days or

weeks (for example, following surgery or an injury). It is estimated that over 80 million people are prescribed a medicine for

acute pain every year in the U.S. Currently available treatments have limitations around efficacy or side effects, including a

risk of addiction with opioids. Because of these challenges, over- and under-utilization, as well as misutilization, of current

pain medicines may occur.

JOURNAVX (suzetrigine) is a first-in-class, oral pain signal inhibitor that is highly selective for voltage-gated sodium

channel NaV1.8. Through this mechanism, JOURNAVX provides effective relief of pain without evidence of the several

limitations of other currently available therapies, including the addictive potential of opioids. JOURNAVX was approved by

the U.S. Food and Drug Administration (“FDA”) in January 2025 for the treatment of moderate-to-severe acute pain in

adults.

5

Since JOURNAVX became available at U.S. pharmacies in March 2025 and through the end of 2025, more than 550,000

prescriptions were written and filled across the hospital and retail settings in different acute pain conditions, consistent with

the product’s broad label. We have secured access for JOURNAVX with all three national pharmacy benefit managers, and

as of January 2026, more than 200 million individuals across commercial and government payors have coverage to

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

COMMERCIALIZATION OF OUR MEDICINES

We sell our medicines primarily to a limited number of specialty pharmacy and specialty distributors globally, as well as

to certain major wholesalers in the U.S. Our customers in the U.S. subsequently resell our medicines to patients, health care

providers, retail pharmacies, hospitals, or ATCs. Outside of the U.S., we generate sales primarily through distributor

arrangements and to retail pharmacies, as well as to hospitals and clinics, many of which are government-owned or supported

customers. In certain markets, we may not utilize a specialty distributor or specialty pharmacy to distribute CASGEVY and

instead may sell CASGEVY directly to ATCs. We contract with government agencies so that our medicines will be eligible

for purchase by, or partial or full reimbursement from, such third-party payors.

We promote the use of our medicines directly to healthcare professionals and organizations such as doctors, nurse

practitioners, physician assistants, pharmacists, hospitals, and pharmacy benefit managers. Through our field sales and

medical organizations, we explain the risks and benefits of our medicines to these healthcare professionals and organizations.

Our marketing is limited to the approved uses of the particular medicine. We also continue to develop scientific data and

other information about potential additional uses of our medicines and provide such information through clinical or medical

affairs teams as scientific exchange at scientific congresses or in other ways, including the development of publications, or in

response to unsolicited inquiries from healthcare professionals and organizations. In the U.S., we also market directly to

consumers by communicating the approved uses, benefits and risks.

We are dedicated to helping patients obtain access to our therapies. We work to gain access for our medicines on

formularies and reimbursement plans (lists of formulary-recommended or approved medicines and other products) by

providing information about the clinical profiles of our medicines. Our patient support representatives help patients

understand their insurance coverage and, in the U.S., we have established programs that provide co-pay assistance or free

medicine for qualified uninsured or underinsured patients, based on specific eligibility criteria.

RESEARCH AND DEVELOPMENT PROGRAMS

We invest in research and development to discover and develop transformative medicines for people with serious

diseases, with a focus on specialty markets. Our research strategy is to combine transformative advances in the understanding

of human disease and in the science of therapeutics to dramatically advance human health. We focus on:

•disease areas with known causal human biology;

•targets validated by causal human biology;

•predictive lab assays and clinical biomarkers;

•potential for transformative benefit regardless of modality; and

•efficient path to registration and approval.

Our development-stage product candidates are focused on the treatment of serious diseases. In pursuit of serial

innovation, our research and development approach includes advancing multiple candidates into clinical trials and pursuing

multiple modalities with the goal of bringing first-in-class and/or best-in-class therapies to patients.

Our research and development strategy has been validated through our success in moving novel product candidates into

clinical trials and obtaining marketing approvals for our five CF medicines, CASGEVY, and JOURNAVX. Our approach to

drug discovery has been further validated by ongoing pivotal development in five additional disease areas: in IgAN and pMN

with povetacicept, in AMKD with inaxaplin, in T1D with zimislecel, and in diabetic peripheral neuropathy with suzetrigine.

To augment our internal programs, we acquire businesses and technologies and collaborate with biopharmaceutical and

technology companies, leading academic research institutions, government laboratories, foundations and other organizations

to advance research in our disease areas of interest, as well as to access technologies needed to execute on our strategy. Our

6

internal and external innovation approaches are based on the same strategy, which enables us to effectively integrate and

execute on new internal capabilities as we invest in external innovation. Our investments in external innovation include our

collaboration with CRISPR, which resulted in the successful development and approval of CASGEVY; our acquisition of

Semma Therapeutics, Inc. (“Semma”), which established and advanced our T1D program; our expansion of our renal

programs through our acquisition of Alpine Immune Sciences, Inc. (“Alpine”); our mRNA therapeutic, VX-522, for

treatment of CF through our collaboration with Moderna; and our intracellular therapeutic for myotonic dystrophy type 1

(“DM1”), VX-670, through our collaboration with Entrada.

CF

Our goal in CF is to continue to extend our leadership by developing treatment regimens that will provide benefits to all

people with CF. We have completed the Phase 3 clinical trial evaluating TRIKAFTA/KAFTRIO in children one year to less

than two years of age. The data showed that TRIKAFTA was generally safe and well-tolerated, consistent with the

established safety profile. Treatment with TRIKAFTA in this age group resulted in rapid, robust, and clinically meaningful

improvement in the secondary endpoint of sweat chloride reduction. We expect to begin submissions for global regulatory

approvals in this age group in the first half of 2026. We completed the global trial evaluating ALYFTREK in children 2 to 5

years of age. The data showed that ALYFTREK was generally safe and well-tolerated, consistent with the established safety

profile. Treatment with ALYFTREK in this age group resulted in a clinically meaningful improvement in the CFTR function

as measured by sweat chloride. We expect to submit for approval with global regulators in this age group in the first half of

2026. In addition, we initiated a pivotal trial evaluating ALYFTREK in children one to less than two years of age.

We estimate that nearly 95% of people with CF could benefit from our five approved medicines, and, in connection with

our serial innovation approach, we continue to identify and develop additional CFTR modulators with the goal of developing

best-in-class medicines that can treat more people with CF. We have advanced several next-generation, 3.0 CFTR modulators

into the clinic. VX-828 is the first of these and is being evaluated in a proof-of-concept clinical trial of people with CF. We

expect to complete enrollment and dosing in the first half of 2026. We are also enrolling and dosing in a Phase 1 clinical trial

of VX-581, another corrector in the next-generation 3.0 class, in healthy volunteers.

To treat people with CF who do not make full-length CFTR protein, and as a result, cannot benefit from our CFTR

modulators, we are researching and developing genetic therapies, such as mRNA, and gene-editing approaches to CF. In

collaboration with Moderna, we are developing VX-522, a nebulized CF mRNA therapeutic designed to treat the underlying

cause of CF lung disease for these people by enabling cells in the lungs to produce functional CFTR protein. We are targeting

completion of dosing in the multiple ascending dose portion of the Phase 1/2 clinical trial evaluating VX-522 and disclosure

of the data in the second half of 2026.

Sickle Cell Disease and Transfusion-Dependent Beta Thalassemia

In December 2025, we presented positive data from the pivotal trials evaluating CASGEVY in children 5 to 11 years of

age with severe SCD (the CLIMB SCD-151 clinical trial) and TDT (the CLIMB THAL-141 clinical trial). We expect to

initiate global regulatory submissions for this age group, including in the U.S., in the first half of 2026. In the U.S.,

CASGEVY has received a Commissioner’s National Priority Voucher for use in this age group, which is meant to accelerate

the FDA’s review of the application once submitted.

In connection with our serial innovation approach, we are advancing preclinical assets for myeloablative conditioning

agents with improved tolerability profiles, which we refer to as “improved conditioning agents,” which could be used in

connection with treatment with CASGEVY, significantly broadening the eligible SCD and TDT patient population. We are

also investigating in vivo gene-editing approaches and small molecules for the potential treatment of SCD and TDT.

Pain

Pain can be debilitating and develop from a variety of conditions. Most commonly, people with pain can be categorized

as suffering from one of three types of pain: acute pain, chronic neuropathic pain (caused primarily by damage or dysfunction

of peripheral nerves), or chronic musculoskeletal pain (caused primarily by damage to muscle, joints or bone). Acute pain

usually resolves in days or weeks (for example, following surgery or an injury), while chronic pain generally lasts greater

than three months due to unresolved or ongoing damage to tissues or nerves. Currently available treatments have limitations

7

around efficacy or side effects, including a risk of addiction. Because of these challenges, over, under, and mis-utilization of

current pain medicines may occur.

The sodium channels NaV1.8 and NaV1.7 play important roles in the physiology of pain. We have discovered multiple

selective small molecule inhibitors of NaV1.8 as potential treatments for pain. We obtained pharmacological validation of

NaV1.8 inhibition with a first generation NaV1.8 inhibitor in acute pain, chronic neuropathic pain, and chronic

musculoskeletal pain.

Acute Pain

In August 2025, we announced results from the Phase 2 placebo-controlled dose-ranging clinical trial evaluating the

safety and efficacy of VX-993, an investigational selective NaV1.8 pain signal inhibitor, for the treatment of acute pain

following bunionectomy surgery. The clinical trial was powered to determine whether VX-993 would result in higher clinical

efficacy than previously demonstrated with the NaV1.8 pathway. Based on the efficacy results of the clinical trial, we did not

expect VX-993 to be superior to suzetrigine and therefore chose not to further advance VX-993 as monotherapy in acute pain.

VX-993 was generally safe and well-tolerated.

Peripheral Neuropathic Pain

There are no approved medicines in the U.S. that are labeled for the treatment of peripheral neuropathic pain. We are

evaluating suzetrigine, our selective non-opioid NaV1.8 pain signal inhibitor, for the treatment of DPN, a type of peripheral

neuropathic pain, in two Phase 3 clinical trials. We expect to complete enrollment in both Phase 3 clinical trials by the end of

2026. The FDA granted Breakthrough Therapy Designation to suzetrigine in DPN. We are also enrolling and dosing people

with DPN in a Phase 2 clinical trial evaluating VX-993.

In connection with our serial innovation approach, we are advancing multiple NaV1.8 inhibitors and NaV1.7 inhibitors,

which could be used alone or in combination, for the treatment of acute pain and peripheral neuropathic pain.

IgA Nephropathy

IgAN is a serious, progressive, life-threatening chronic kidney disease driven by uncontrolled autoreactive B cell activity

that causes inflammation and damage to the kidneys. It is the most common cause of primary glomerulonephritis worldwide.

We estimate that IgAN affects approximately 330,000 people in the U.S. and Europe, and, globally, more than 1.5 million

people are diagnosed with IgAN. A high percentage of people with IgAN progress to end-stage kidney disease.

IgAN is thought to occur when the body produces an abnormal form of IgA, a type of antibody that normally helps the

body fight infections. The body generates an abnormal immune response, including antibodies (autoantibodies), against this

abnormal IgA, and these antibodies can combine to create larger molecules called immune complexes. These immune

complexes can deposit in the kidneys, triggering damage and inflammation, especially within the glomeruli, impairing the

kidneys’ ability to properly filter waste and fluid.

We are developing povetacicept for multiple diseases and believe that it has pipeline-in-a-product potential. Povetacicept

is a potent dual inhibitor of the BAFF and APRIL cytokines, which promote B cell proliferation, differentiation and survival,

and provides B cell control by inhibiting the ability of BAFF and APRIL to drive the pathogenesis of multiple autoimmune

diseases, such as IgAN, pMN and generalized myasthenia gravis (“gMG”) (as described below). Povetacicept was

specifically engineered to achieve improvements in binding affinity, potency, pharmacokinetics, and tissue distribution.

Povetacicept has demonstrated potential best-in-class efficacy in a global Phase 1/2 clinical trial in people with IgAN. A

small volume dose of povetacicept is expected to be self-administered at home once every four weeks via a subcutaneous

auto-injector.

We completed enrollment in RAINIER, the global Phase 3 pivotal trial of povetacicept versus placebo in people with

IgAN. The clinical trial design contemplates a pre-planned interim analysis evaluating the change from baseline in urine

protein-to-creatine ratio (“UPCR”) after a certain number of patients reach 36 weeks of treatment. We expect to share data

from the interim analysis in the first half of 2026. If positive, the interim analysis may serve as the basis to seek accelerated

approval in the U.S. The final analysis will occur when patients reach two years of treatment and will evaluate total eGFR

(estimated glomerular filtration rate) slope. The FDA has granted Breakthrough Therapy Designation for povetacicept in

IgAN. We submitted the first module of the IgAN BLA to the FDA at the end of 2025 under the rolling submission pathway,

8

and we expect to complete the submission in the first half of 2026, pending positive results from the interim analysis. We are

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

Our serial innovation approach continues with respect to IgAN and other B cell-mediated diseases.

APOL1-Mediated Kidney Disease

AMKD is a rapidly progressive, proteinuric kidney disease caused by variants in the APOL1 gene. In AMKD, the

kidney’s filtering units, known as the glomeruli, and within them the cells known as podocytes, are damaged, leading to

leakage of protein into the urine, deterioration in kidney function, scarring, and, ultimately, end stage renal disease. People

with AMKD progress to end stage kidney disease at a faster rate than those with other forms of chronic kidney disease and

reach kidney failure at a median age of 45 years old. AMKD occurs in people with African ancestry, with an estimated

patient population of approximately 150,000 people in the U.S. and Europe. In addition, we estimate that there are

approximately 100,000 people with AMKD with comorbidities, such as type 2 diabetes, in the U.S. and Europe.

In a Phase 2 proof-of-concept clinical trial, people with APOL1-mediated focal segmental glomerulosclerosis (“FSGS”)

treated with inaxaplin on top of standard of care achieved a statistically significant, substantial, and clinically meaningful

reduction of proteinuria. Inaxaplin was generally safe and well tolerated by patients. Based on the positive Phase 2 data, the

FDA granted Breakthrough Therapy Designation to inaxaplin for FSGS and the European Medicines Agency (“EMA”)

granted Priority Medicines (“PRIME”) designation to inaxaplin for AMKD. We initiated pivotal development of inaxaplin in

a single Phase 2/3 adaptive clinical trial (“AMPLITUDE”) in people with AMKD in 2022. We completed enrollment of the

interim analysis cohort of AMPLITUDE in 2025 and we expect to conduct the pre-planned interim analysis once this cohort

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

complete full enrollment in the AMPLITUDE clinical trial in the second half of 2026.

Our serial innovation strategy in AMKD focuses on indication expansion: evaluating inaxaplin in new populations of

people with AMKD not included in the AMPLITUDE clinical trial. The Phase 2 clinical trial (“AMPLIFIED”) evaluates

inaxaplin as a treatment for people with AMKD with moderate proteinuria, or with AMKD and type 2 diabetes, two

populations that are not being studied in the AMPLITUDE trial. We expect to complete the AMPLIFIED clinical trial and

share results in mid-2026.

Type 1 Diabetes

T1D is a chronic metabolic disorder caused by insufficient insulin secretion by the beta cells in the pancreas. In people

with T1D, the insulin-producing islet cells of the pancreas are destroyed by the person’s own immune system, resulting in a

lack of insulin and impairment of blood glucose control. While insulin therapy allows patients to live for decades with the

disease, challenges of insulin therapy include inadequate control of blood sugar (both hyper- and hypo-glycemia), a

substantial burden of care on patients and families, and long-term vascular complications. Current standards of care do not

address the underlying causes of the disease, and there are limited treatment options beyond insulin for the management of

T1D.

We are developing non-autologous (allogeneic) fully differentiated, stem-cell derived islet cell therapies designed to

replace insulin-producing islet cells that are destroyed in people with T1D, with the goal of delivering a functional cure.

Zimislecel, our first program, is a stem cell-derived, allogeneic, fully differentiated, insulin-producing islet cell replacement

therapy, using standard immunosuppression to protect the implanted cells. We believe that zimislecel has the potential to

transform the lives of eligible people with T1D. In the U.S. and Europe, we estimate that there are approximately four million

people diagnosed with T1D. At initial launch, we expect there will be approximately 65,000 people with high unmet need

who experience severe hypoglycemic events who will be eligible for zimislecel.

We have completed enrollment in the Phase 1/2/3 clinical trial evaluating the safety and efficacy of zimislecel. We have

temporarily postponed completion of the dosing pending an ongoing internal manufacturing analysis. The most recent data

from this trial, published online in the New England Journal of Medicine in June 2025, continue to demonstrate the

transformative potential of zimislecel with consistent and durable patient benefit. The safety profile is generally consistent

with the immunosuppressive regimen used in the trial, the infusion procedure, and complications from long-standing

diabetes. Zimislecel has been granted Regenerative Medicine Advanced Therapy and Fast Track designations from the FDA,

PRIME designation from the EMA, Breakthrough Medicine designation from the Kingdom of Saudi Arabia (“Saudi

9

Arabia”), and has secured an Innovation Passport under the Innovative Licensing and Access Pathway from the U.K.

Medicines and Healthcare products Regulatory Agency (the “MHRA”).

In March 2025, we announced results from the Phase 1/2 clinical trial evaluating VX-264, which encapsulated zimislecel

in an immunoprotective device. VX-264 was generally safe and well-tolerated but did not meet its efficacy endpoint, and we

have discontinued development of this program.

In connection with our serial innovation approach, we are pursuing research-stage programs to evaluate additional

approaches that could provide transformative benefits to people with T1D and reduce or eliminate the need for standard

immunosuppressive regimens, including targeting improved immunosuppression for zimislecel.

Primary Membranous Nephropathy

pMN is a serious, progressive, life-threatening chronic kidney disease driven by uncontrolled autoreactive B cell activity

that causes inflammation and damage to the kidneys. It is a rare autoimmune glomerular disease that occurs when the body

generates an abnormal immune response, including antibodies (autoantibodies), against proteins that are part of the kidney.

We estimate that pMN affects approximately 150,000 people in the U.S. and Europe, and more than 600,000 people globally.

Autoantibodies trigger damage and inflammation, especially within the glomeruli, impairing the kidneys’ ability to properly

filter waste and fluid.

People with pMN can experience a variety of serious complications, including blood clots, infection, and heart disease.

At time of diagnosis, most people with pMN are at risk of progression to end-stage renal disease. There are no therapies

specifically approved for the treatment of pMN.

We believe povetacicept represents a potentially best-in-class approach to control B cell activity in people with pMN.

We have received Fast Track Designation from the FDA and PRIME designation from the EMA for povetacicept in pMN.

Based on the strength of the Phase 2 results in the RUBY-3 clinical trial, we completed the End of Phase 2 meeting with the

FDA and reached agreement on an adaptive Phase 2/3 pivotal development program for pMN; we are enrolling and dosing

people with pMN in that clinical trial. We expect to complete the Phase 2 portion of the clinical trial and to initiate the Phase

3 portion of the trial in mid-2026.

Autosomal Dominant Polycystic Kidney Disease

ADPKD is a life-shortening genetic kidney disease characterized by the growth of numerous kidney-enlarging cysts that

impair kidney function and can ultimately lead to end stage renal disease. In most cases, ADPKD is caused by variants in the

PKD1 and PKD2 genes; the majority of ADPKD patients have a variant in the PKD1 gene. Around half of people with

ADPKD experience kidney failure by the age of 60. We estimate that there are approximately 300,000 people diagnosed with

ADPKD in the U.S. and Europe.

VX-407 is a first-in-class small molecule corrector that is designed to target the underlying cause of ADPKD in people

with a subset of PKD1 variants, which represents up to approximately 10% of the overall patient population living with

ADPKD. We are enrolling and dosing patients in a Phase 2 proof-of-concept clinical trial evaluating VX-407 (“AGLOW”)

for the treatment of ADPKD. We expect to complete enrollment in the AGLOW clinical trial by the end of 2026.

In connection with our serial innovation approach, we are progressing multiple research-stage assets in ADPKD.

Myotonic Dystrophy Type 1

DM1 is an inherited disease that results in the weakening and destruction of skeletal muscles over time. Muscle

weakness, muscle wasting and myotonia (sustained muscle contraction and difficulty relaxing muscles) are the hallmark

features of DM1. It is a serious life-shortening disease with no approved treatments, and we estimate that it affects

approximately 110,000 people in the U.S. and Europe.

VX-670, our lead approach for DM1, holds the potential to address the underlying cause of DM1. VX-670 is an

oligonucleotide connected to a cyclic peptide to promote effective delivery into cells. We continue to enroll and dose in the

multiple ascending dose portion of the global Phase 1/2 clinical trial of VX-670 in people with DM1 (“GALILEO”), which

evaluates both safety and efficacy of VX-670. We expect to complete enrollment and dosing in this trial in mid-2026.

Our serial innovation approach in DM1 includes a small molecule program in preclinical development.

10

Generalized Myasthenia Gravis

gMG is a serious, chronic, and debilitating B cell-mediated immune disorder. This rare condition is caused by the

formation of pathogenic autoantibodies to key proteins that function in neuromuscular transmission. These pathogenic

antibodies block, alter, or damage the neuromuscular junction, which is the connection point between nerve cells and the

muscles they control. As a result, people with gMG experience muscle weakness and fatigue, which can lead to inability to

perform the activities of daily living and, in severe cases, compromise of respiratory muscles that can lead to life-threatening

respiratory failure. Current therapies address only subsets of the gMG population, and many advanced treatments require

cyclic treatment and drug holidays due to safety challenges and immunosuppression. As a consequence, there is significant

unmet medical need for improved therapies. We estimate that gMG affects approximately 175,000 people in the U.S. and

Europe and more than 300,000 people globally.

Povetacicept is a potent dual inhibitor of BAFF and APRIL, two cytokines that are elevated in gMG, where they play

distinct roles in the proliferation, differentiation, and survival of B cells. In gMG, elevated expression of both BAFF and

APRIL drives uncontrolled B cell growth and activation, triggering overproduction of the pathogenic autoantibodies driving

disease activity. By inhibiting both BAFF and APRIL, we believe povetacicept represents a potential best-in-class approach

to reducing production of these pathogenic autoantibodies in gMG.

We expect to initiate a placebo-controlled, Phase 2 dose-ranging proof-of-concept clinical trial evaluating povetacicept

for the treatment of people with gMG in the first half of 2026.

STRATEGIC TRANSACTIONS

As part of our business strategy, we seek to license or acquire technologies, products, product candidates, and businesses

that are aligned with our corporate and research and development strategies and that complement and advance our ongoing

research and development efforts. In addition, we establish business relationships with collaborators to support our research

activities and to lead or support development and/or commercialization of certain product candidates. We expect to continue

to identify and evaluate potential acquisitions, licenses and collaborations that may be similar to or different from the

transactions that we have engaged in previously.

Acquisitions

In 2024, we acquired Alpine for approximately $5.0 billion. Alpine’s lead molecule, povetacicept, is a highly potent and

effective dual inhibitor of BAFF and APRIL. We are currently evaluating povetacicept in a pivotal trial as a potentially best-

in-class approach to treat IgAN. We also believe povetacicept holds pipeline-in-a-product potential for other indications, such

as pMN and gMG.

We previously made other acquisitions which have expanded and advanced our pipeline, including:

•In 2019, we established our T1D program through our acquisition of Semma, a privately held company focused on

the use of stem cell-derived human islets as a potentially curative treatment for T1D. We are evaluating zimislecel

for the potential treatment of T1D in a Phase 1/2/3 clinical trial.

•In 2017, we enhanced our CF portfolio through our acquisition of certain CF assets, including deutivacaftor, from

Concert Pharmaceuticals Inc. In 2024, the FDA approved ALYFTREK for people with CF 6 years of age and older.

We expect to continue to identify and make acquisitions to expand and advance our pipeline and business.

Collaboration and Licensing Arrangements

Joint Development and Commercialization Agreement with CRISPR

In 2017, we entered into a joint development and commercialization agreement (“Original JDCA”) with CRISPR

Therapeutics AG (“CRISPR”), pursuant to which we are co-developing and co-commercializing CASGEVY for SCD and

TDT. In 2021, we and CRISPR amended and restated the Original JDCA (the “A&R JDCA”).

Pursuant to the A&R JDCA, we lead global development, manufacturing and commercialization of CASGEVY, with

support from CRISPR. Subject to the terms and conditions of the A&R JDCA, we have the right to conduct all research,

11

development, manufacturing, and commercialization activities relating to the product candidates and products under the A&R

JDCA (including CASGEVY) throughout the world, subject to CRISPR’s reserved right to conduct certain activities.

The net profits and net losses incurred pursuant to the A&R JDCA with respect to CASGEVY are allocated 60% to us

and 40% to CRISPR, subject to certain adjustments, while all other product candidates and products under the A&R JDCA

have net profits and net losses shared equally between the parties.

Either party may terminate the A&R JDCA upon the other party’s material breach, subject to specified notice and cure

provisions, or, in our case, in the event that CRISPR becomes subject to specified bankruptcy, winding up, or similar

circumstances. Either party may terminate the A&R JDCA in the event the other party commences or participates in any

action or proceeding challenging the validity or enforceability of any patent that is licensed to such challenging party

pursuant to the A&R JDCA. We also have the right to terminate the A&R JDCA for convenience at any time after giving

prior written notice. If circumstances arise pursuant to which a party would have the right to terminate the A&R JDCA on

account of an uncured material breach, such party may elect to keep the A&R JDCA in effect and cause such breaching party

to be treated as if it had exercised its opt-out rights with respect to the products associated with such uncured material breach

and the royalties payable to the breaching party would be reduced by a specified percentage.

Either party may opt out of the development of a product candidate under the A&R JDCA after predetermined points in

the development of the product candidate, on a candidate-by-candidate basis. In the event of such opt-out, the party opting-

out will no longer share in the net profits and net losses associated with such product candidate and, instead, the opting out

party will be entitled to high single to mid-teen percentage royalties on the net sales of such product, if commercialized.

In-License Agreements

We have entered into various agreements pursuant to which we have obtained access to technologies from third parties

and are conducting research and development activities with collaborators. Pursuant to these arrangements, we have obtained

development and commercialization rights to resulting product candidates. Depending on the terms of the arrangements, we

may be responsible for the costs of research activities, required to make upfront payments and/or milestone payments upon

the achievement of certain research, development, and commercial objectives, and/or pay royalties on future sales, if any, of

commercial products resulting from the collaboration. Our current in-license agreements include:

•CRISPR Therapeutics AG. In addition to our arrangement with CRISPR described above, we have exercised options

to exclusively license treatments for specific targets, including CF, that were subject to the research program under

the collaboration agreement we entered into with CRISPR in 2015. In 2019, we obtained exclusive worldwide rights

to CRISPR’s intellectual property for Duchenne muscular dystrophy (“DMD”) and DM1 gene-editing products

through a new agreement with CRISPR. In 2023, we obtained non-exclusive rights to CRISPR’s intellectual

property for the development of hypoimmune gene-edited cell therapies for T1D through a new agreement with

CRISPR.

•Moderna, Inc. In 2016, we entered into a collaboration with Moderna for the identification and development of

mRNA therapeutics encoding CFTR for the treatment of CF. We are evaluating VX-522, an mRNA therapeutic,

pursuant to this collaboration.

•Entrada Therapeutics, Inc. In 2022, we established a collaboration with Entrada focused on enabling efficient

intracellular delivery of an oligonucleotide for DM1. This collaboration includes VX-670, an investigational

candidate for the treatment of DM1 that is in clinical development. We are evaluating VX-670 in people with DM1

pursuant to this collaboration.

Out-license Agreements

We have entered into various agreements pursuant to which we have out-licensed rights to certain product candidates to

third-party collaborators. Pursuant to these out-license arrangements, our collaborators are responsible for certain costs

related to the continued development of such product candidates and obtain development and commercialization rights to

these product candidates. Depending on the terms of the arrangements, our collaborators may be required to make upfront

payments, milestone payments upon the achievement of certain research and development objectives and/or pay royalties on

future sales, if any, of commercial products licensed under the agreement.

12

In 2025, we entered into agreements with Zai Lab Limited (“Zai”) and Ono Pharmaceuticals Co., Ltd (“Ono”) related to

the development and commercialization of povetacicept in certain Asian markets. Zai licensed povetacicept for mainland

China, Hong Kong SAR, Macau SAR, Taiwan region, and Singapore, while Ono licensed povetacicept for Japan and South

Korea. Zai and Ono will help advance povetacicept clinical trials and will be responsible for obtaining marketing

authorizations and commercialization activities in the licensed territories, if povetacicept becomes an approved product.

Cystic Fibrosis Foundation

In 2004, we entered into an agreement (the “CFF Agreement”) with the Cystic Fibrosis Foundation (the “CFF”), as

successor in interest to the Cystic Fibrosis Foundation Therapeutics, Inc., to support research and development activities.

Pursuant to the CFF Agreement, as amended, we have agreed to pay tiered royalties ranging from single digits to sub-teens

on covered compounds first synthesized and/or tested during a research term on or before February 28, 2014, including

ivacaftor, lumacaftor and tezacaftor, and royalties ranging from low-single digits to mid-single digits on net sales of certain

compounds first synthesized and/or tested between March 1, 2014 and August 31, 2016, including elexacaftor. We do not

have any royalty obligations on compounds first synthesized and tested on or after September 1, 2016. For combination

products, such as ORKAMBI, SYMDEKO/SYMKEVI, TRIKAFTA/KAFTRIO, and ALYFTREK, sales are allocated

equally to each of the active pharmaceutical ingredients in the combination product, and royalties are then paid for any

royalty-bearing components included in the combination. For TRIKAFTA/KAFTRIO, the CFF Agreement does not identify

a specific date on which royalty obligations terminate. To qualify as a royalty bearing “Drug Product” as defined under the

CFF Agreement, a compound must be covered by intellectual property protection (including patents) that Vertex has the legal

right to license to another party.

INTELLECTUAL PROPERTY

Patents and other intellectual property rights such as trademarks, trade secrets, and copyrights are critical to our business.

We actively seek protection for our products and proprietary information by means of U.S. and foreign patents, trademarks,

and copyrights, as appropriate. In addition, we rely upon trade secret protection and contractual arrangements to protect

certain of our proprietary information.

Patents provide a period of exclusivity that can make it more difficult for competitors to market and use our technology.

We own and control patents and pending patent applications that relate to compounds, formulations, synthetic routes,

intermediates, devices, treatment of diseases, and other inventions.

To protect our intellectual property, we typically apply for patents several years before a product receives marketing

approval. Under current law, a patent expires 20 years from its first effective filing date. Since the drug development process

may last for many years, there may be a period of time in which we have an issued patent but not marketing approval to sell

the drug. To compensate for patent term lost while a product is in clinical trials and undergoing review for marketing

approval, we may be able to apply for patent term extensions or supplementary protection certificates (“SPCs”) in some

countries. In addition to patent protection, we receive regulatory exclusivity from U.S. and European regulatory agencies for

the active pharmaceutical and biological agents and, where applicable, their approved orphan indications for a certain time

period. Regulatory exclusivity runs concurrently with patent exclusivity and provides complementary protection for our

products.

For our approved commercial products, and those in development, we own or hold exclusive and non-exclusive licenses

to several hundred patents around the world. In the U.S., once a New Drug Application (“NDA”), or a supplement thereto, is

approved we are required to list with the FDA each U.S. patent with claims that cover our product or a method of using the

product. The FDA publishes the patents we list in a book referred to as the Orange Book. We have fourteen issued U.S.

patents listed in the Orange Book that cover the active pharmaceutical ingredients in KALYDECO, its marketed

formulations, and/or its approved indication. We have 22 issued U.S. patents listed in the Orange Book that cover the active

pharmaceutical ingredients in ORKAMBI, its marketed formulations, and/or its approved indication. We have 25 issued U.S.

patents listed in the Orange Book that cover the active pharmaceutical ingredients in SYMDEKO, its marketed formulations,

and/or its approved indication. We have 34 issued U.S. patents listed in the Orange Book that cover the active pharmaceutical

ingredients in TRIKAFTA, its marketed formulations, and/or its approved indication. We have 35 issued U.S. patents listed

in the Orange Book that cover the active pharmaceutical ingredients in ALYFTREK, its marketed formulations, and/or its

approved indication. We have an issued patent listed in the Orange Book that covers the active pharmaceutical ingredient in

JOURNAVX, its marketed formulation, and/or its approved indication.

13

Products approved by the FDA under a BLA, including CASGEVY, receive 12 years of regulatory exclusivity in the

U.S. from a product’s approval date. Additionally, we have licenses to dozens of issued U.S. patents that cover CASGEVY,

its approved indication, and/or its manufacture. Products approved by the FDA under a BLA are not subject to the Orange

Book patent listing requirement.

The table below sets forth the year of projected expiration for the basic product patent covering each of our approved

products. For products that are combinations of two or more active ingredients, the table lists the projected expiration of the

latest expiring patent covering any of the active pharmaceutical ingredients (lumacaftor for ORKAMBI, tezacaftor for

SYMDEKO/SYMKEVI, elexacaftor for TRIKAFTA/KAFTRIO and vanzacaftor for ALYFTREK). Unless otherwise noted,

patent term extensions, and pediatric exclusivity periods are not reflected in the expiration dates listed in the table below and

may extend protection. In some instances, we also own later-expiring patents and applications relating to solid forms,

formulations, methods of manufacture, or the use of these drugs in the treatment of particular diseases or conditions. In some

cases, however, such patents may not protect our drug from generic competition after the expiration of the basic patent.

1 Includes pediatric exclusivity.

2 Expiration date reflects SPCs granted in the five major European markets (France, Germany, Italy, Spain and the U.K.).

3 SPC expires in 2028 in Germany; application for pediatric extension pending in France, Italy, Spain, and the U.K.

4 Expiration year reflects the expiration of regulatory exclusivity, which expires later than the basic product patent for this product in this market.

5 Expiration year reflects the expiration of regulatory exclusivity in the E.U., which expires later than the basic product patent for this product in

this market.

6 Product is approved in Great Britain with regulatory exclusivity until November 2033, which is later than the expiration of the basic product

patent.

In addition to protecting our marketed products, we actively file patent applications in the U.S. and in foreign countries

on inventions relating to our pipeline. For example, we also own and/or control U.S. and foreign patents and/or patent

applications relating to the following:

•Other CF potentiators and correctors and many other related compounds, and the use of those compounds for the

treatment of CF.

•VX-522 and other mRNA-based approaches for treating CF.

•VX-993, VX-973, and other compounds being studied for the potential treatment of pain.

•Povetacicept for the treatment of IgAN, pMN and gMG.

•Inaxaplin for the potential treatment of AMKD.

•Zimislecel and other cell-based approaches for treating T1D.

•VX-407 and other compounds being studied for the potential treatment of ADPKD.

•VX-670 for the treatment of DM1.

•Other pre-clinical and clinical candidates and the use of such candidates to treat specified diseases.

14

•The manufacture, pharmaceutical compositions, related solid forms, formulations, dosing regimens, and methods of

use of many of the above compounds.

We and CRISPR intend to rely upon a combination of rights, including patent rights, trade secret protection, and

regulatory exclusivities to protect CASGEVY. CRISPR has licensed certain rights to a worldwide patent portfolio that covers

various aspects of the CRISPR/Cas9 editing platform technology including, for example, compositions of matter and methods

of use, including their use in targeting or cutting DNA, from Dr. Emmanuelle Charpentier. In addition to Dr. Charpentier, this

patent portfolio has named inventors who assigned their rights to the Regents of the University of California or the University

of Vienna, to whom we refer, together with Dr. Charpentier, as the CVC Group. CRISPR has non-exclusive or co-exclusive

rights to the patent rights that protect the core CRISPR/Cas9 gene-editing technology. For example, certain third parties,

including competitors, have reported obtaining a license to rights in this patent portfolio in certain fields. In addition, patents

and patent applications in this patent portfolio are the subject of adversarial proceedings in the U.S., Europe, and other

jurisdictions, including proceedings in the U.S. Patent and Trademark Office (the “USPTO”), between the CVC Group and,

separately, Sigma-Aldrich, Co. LLC (“Sigma-Aldrich”), ToolGen, Inc. (“ToolGen”), and the Broad Institute, Harvard

University, and Massachusetts Institute of Technology (collectively, “Broad”). To date, both the CVC Group and Broad have

obtained granted patents that purport to cover aspects of CRISPR/Cas9 editing platform technology. The patents and patent

applications within the patent portfolios of the CVC Group, Broad, Sigma-Aldrich and/or ToolGen are, or may in the future

be, involved in proceedings similar to interferences or priority disputes in Europe or other foreign jurisdictions. In December

2023, we entered into an agreement with Editas Medicine, Inc. (“Editas”), providing us a non-exclusive sublicense to certain

patents relating to CRISPR/Cas9 technology, owned by Broad and Harvard, which are licensed to Editas. In addition to the

patent portfolios licensed from Dr. Charpentier, Broad, and Harvard, we own patents and/or patent applications relating to the

composition, manufacture, and use of CASGEVY.

We and our CASGEVY manufacturing partners are engaged in patent litigation against ToolGen in the U.S., the U.K.,

and the Netherlands. In these cases, ToolGen alleges that the CASGEVY manufacturing process infringes its patents relating

to CRISPR/Cas9. We have argued in the U.K. and the Netherlands that ToolGen’s patents are invalid, and we filed

oppositions at the European Patent Office seeking the revocation of the patents asserted in the U.K. and the Netherlands

cases. We intend to respond to the U.S. case in the first half of 2026.

From time to time, we enter into exclusive and non-exclusive license agreements for proprietary third-party technology

used in connection with our research activities. These license agreements typically provide for the payment by us of a license

fee but may also include terms providing for milestone payments or royalties for the development and/or commercialization

of our drug products arising from the related research.

We cannot be certain that issued patents we own or license will be enforceable or provide adequate protection or that

pending patent applications will result in issued patents. The existence of patents does not guarantee our right to practice the

patented technology or commercialize the patented product. Litigation, interferences, oppositions, inter partes reviews,

administrative challenges or other similar types of proceedings may be necessary in some instances to determine the validity

and scope of certain patents, regulatory exclusivities or other proprietary rights, and in other instances to determine the

validity, scope or non-infringement of intellectual property rights that may be claimed by third parties to be pertinent to the

manufacture, use or sale of our products.

MANUFACTURING

As we market and sell our approved products and advance our product candidates through clinical development toward

commercialization, we continue to build and maintain our supply chain and quality assurance resources. We rely on internal

capabilities and a global network of third parties to manufacture and distribute our product candidates for clinical trials, as

well as our products for commercial sale and post-approval clinical trials. In addition to establishing supply chains for newly

approved products, we must adapt our supply chains for existing products to increase scale of production or to include

additional formulations. We are focused on ensuring the stability of the supply chains for our current products, including our

CF medicines, CASGEVY, and JOURNAVX, and for our pipeline programs. We are also focused on identifying and

ensuring efficient manufacturing and delivery processes for the biologics and cell and genetic therapies we are developing,

including our stem cell therapy program for T1D, and biologics manufacturing for povetacicept.

We have established our own small molecule manufacturing capabilities in Boston, which we use for clinical trial and

commercial supplies, including certain manufacturing steps related to our commercial supply of TRIKAFTA/KAFTRIO. We

15

expect to continue to rely on third parties to meet our commercial supply needs and a significant portion of our clinical

supply needs for the foreseeable future.

Our supply chain for sourcing raw materials and manufacturing our products and product candidates, including obtaining

all necessary supplies, is a multi-step, global endeavor. In general, these raw materials and other necessary supplies are

available from multiple sources. Third-party contract manufacturers, including some based in China, perform different parts

of our manufacturing process. Contract manufacturers supply us with raw materials, convert these raw materials into drug

substance and/or convert the drug substance or product into final dosage form. In addition, third parties assist us with

packaging, warehousing, and global distribution of our products. Establishing and managing this global supply chain for each

of our products and product candidates requires a significant financial commitment and the creation and maintenance of

numerous third-party contractual relationships. We have established and we maintain second sources for the vast majority of

our commercial products, including active ingredients, drug product, and finished dosage form packaging. Similarly,

commercial manufacturing for the vast majority of our small molecule drug products is in the U.S.

The manufacturing processes for biologics and cell and genetic therapies are more complex than those required for small

molecule drugs and require different systems, equipment, facilities, and expertise. Additionally, we are unable to utilize a

single process for all of our biologics and cell and genetic therapies; they must be customized for each program and therapy.

We are investing and plan to continue to invest significant resources in expanding and strengthening our manufacturing

infrastructure and capabilities, such as current Good Manufacturing Practices (“cGMP”) clinical manufacturing, both

independently and through third-party networks, in an effort to develop and commercialize our biologics and cell and genetic

therapies. We have secured agreements to meet our current demands for these products and product candidates. We continue

to evaluate additional suppliers for all of our late-stage clinical programs for additional capacity and redundancy to support

commercial supply.

We rely on third-party manufacturers to produce or process cell culture reagents and gene-editing components, such as

Cas9 protein and guide RNA molecules, for clinical trials and commercial supply of CASGEVY, and to generate gene-edited

cells to supply CASGEVY. The manufacturing process for CASGEVY involves a number of steps prior to the final infusion

of drug product into patients. Following mobilization and collection of blood cells from the patient, cells are transferred to a

manufacturing site where HSPCs are purified and CRISPR/Cas9 gene-editing is performed. The edited cellular product,

called CASGEVY, is frozen and transported back to the authorized treatment center where it is stored prior to infusion into

the patient. Each step must be completed successfully, and in a timely manner, requiring coordination between us, authorized

treatment centers, third-party manufacturers and shipping vendors. We are making investments to enhance the CASGEVY

manufacturing process, to secure additional capacity, and to coordinate manufacturing, testing, and logistics activities at a

larger scale across multiple facilities to serve the geographies in which we are treating and expect to treat additional people

with CASGEVY.

In addition, we have established cell therapy manufacturing capabilities at our facilities in the Boston area to supply

clinical and potentially commercial quantities of our cell therapies as our needs evolve, including our plans to utilize our own

manufacturing capabilities in Boston for additional commercial supply of CASGEVY. To further expand our ability to supply

clinical and potentially commercial quantities of our cell therapies, we have a strategic agreement with Lonza to support the

manufacture of T1D cell therapy product candidates. We also rely on third-party manufacturers to produce drug substance

and finished drug product for clinical trials for povetacicept. In addition, we have obligations to supply product to global third

parties that support the development and commercialization of povetacicept.

We have developed systems and processes to track, monitor, and oversee our and our third-party manufacturers’

activities, including a quality assurance program intended to ensure that our third-party manufacturers comply with cGMP

and the foreign jurisdictional equivalents when applicable. We devote substantial time, resources, and effort in the areas of

production, quality control, and quality assurance to maintain cGMP compliance. We regularly evaluate the performance of

our third-party manufacturers with the objective of confirming their continuing capabilities to meet our needs compliantly,

efficiently, and economically. Manufacturing facilities, both foreign and domestic, are subject to inspections by or under the

authority of the FDA and other U.S. and foreign government authorities. Although we actively engage with regulatory

authorities, the timing of inspections and regulatory approvals for each of these facilities is the remit of the third-party

manufacturer and not within our control and may be delayed for a number of reasons.

16

COMPETITION

The pharmaceutical industry is characterized by extensive research efforts, rapid technological progress, and intense

competition. There are many public and private companies, including pharmaceutical companies and biotechnology

companies, engaged in developing products for the indications our medicines are approved to treat and the therapeutic areas

we are targeting with our research and development activities. Potential competitors also include academic institutions,

government agencies, other public and private research organizations and charitable venture philanthropy organizations that

conduct research, seek patent protection and/or establish collaborative arrangements for research, development,

manufacturing and commercialization. Mergers and acquisitions in the pharmaceutical, biotechnology and gene therapy

industries may result in a larger concentration of resources among a smaller number of our competitors. Some of our

competitors may have substantially greater financial, technical, sales and marketing, and human resources than we do.

Competition may be based, among other things, on efficacy, safety, availability, patient convenience, frequency of

dosing, ease of use, delivery devices and overall patient experience; formulary placement, price, payer coverage and

reimbursement rates; regulatory approvals and exclusivity; patent and other intellectual property positions; marketing

effectiveness; and research and development of new products, processes, modalities, indications, and uses. Early market entry

and rapid patient access can also be important to achieve product acceptance and success. Accordingly, the relative speed

with which we can develop therapies, complete the testing and approval process, and supply commercial quantities of such

therapies will have a significant impact on our competitive position.

Our therapies must compete with other branded or generic products already on the market or those that are developed in

the future. The introduction of new products or technologies, including the development of new processes or technologies by

competitors or new information about existing products or technologies, results in increased competition for our marketed

products and pricing pressure on our marketed products. For example, the number of compounds available to treat a

particular disease typically increases over time and can result in slowed sales growth or reduced sales of our products in that

therapeutic area. The development of new or improved treatment options could eliminate the use of our medicines or may

limit the utility and application of ongoing clinical trials for our product candidates. Similarly, developments of new

standards of care practices, treatment options or cures for the diseases our medicines treat could have similar impacts.

We believe our long-term competitive success depends on discovering and developing or acquiring transformative

medicines for people with serious diseases and continuously improving the productivity of our operations in a highly

competitive environment. There can be no assurance that our efforts will result in commercially successful medicines, and it

is possible that our medicines will be, or will become, uncompetitive from time to time. See also Item 1A., Risk Factors –

“Competing products and technological advances from our competitors may negatively affect our business and market

position.” of this Annual Report on Form 10-K.

GOVERNMENT REGULATION

Our operations and activities are subject to extensive regulation by numerous government authorities in the U.S., Europe

and other countries, including with respect to the testing, manufacture, labeling, storage, record keeping, approval, pricing

and price reporting, and advertising and promotion of our products.

Regulations Concerning Product Development and Approval

United States. The process for obtaining regulatory approvals to market a new pharmaceutical product, or an additional

indication of an existing product, requires substantial effort and financial resources and takes several years to complete. The

applicant must complete preclinical tests and submit protocols to the FDA before commencing clinical trials. Clinical trials

are intended to establish the safety and efficacy of the pharmaceutical product and typically are conducted in sequential

phases, although the phases may overlap or be combined. If the required clinical testing is successful, the results are

submitted to the FDA in the form of an NDA or BLA requesting approval to market the product for one or more indications.

The FDA reviews an NDA or BLA to determine whether a product is safe and effective for its intended use and whether its

manufacturing is compliant with cGMP.

The FDA can employ several tools to facilitate the development of certain drugs or expedite certain applications,

including fast track designation, Breakthrough Therapy designation, regenerative medicine advanced therapy designation,

priority review, accelerated approval, incentives for orphan drugs developed for rare diseases and others.

17

Compliance with regulatory requirements is assured through periodic, announced or unannounced inspections by the

FDA and other regulatory authorities, and these inspections associated with clinical development may include the sponsor,

investigator sites, laboratories, hospitals and manufacturing facilities of our subcontractors or other third-party manufacturers.

Failure to comply with applicable regulatory requirements can result in enforcement action by the FDA, including rejection

of an NDA or BLA.

Even if an NDA or a BLA receives approval, the applicant must comply with post-approval requirements. For example,

holders of an approval must report adverse reactions, provide updated safety and efficacy information and comply with

requirements concerning advertising and promotional materials and activities. Also, quality control and manufacturing

procedures must continue to conform to cGMP after approval, and certain changes to the manufacturing procedures and

finished product must be submitted and approved by the FDA prior to implementation. The FDA periodically inspects

manufacturing facilities to assess compliance with cGMP, which imposes extensive procedural and record keeping

requirements. In addition, as a condition of approval, the FDA may require post-marketing testing and surveillance to further

assess and monitor the product's safety or efficacy after commercialization, which may require additional clinical trials,

patient registries, observational data or additional work on chemistry, manufacturing and controls. Any post-approval

regulatory obligations, and the cost of complying with such obligations, could expand in the future. Further, the FDA

continues to regulate product labeling and prohibits the promotion of products for unapproved or “off-label” uses along with

other labeling restrictions.

Outside the United States. We are subject to similar regulatory requirements outside the United States for approval and

marketing of pharmaceutical products. We must obtain approval of a clinical trial application or product from applicable

supervising regulatory authorities before it can commence clinical trials or marketing of the product in target markets. The

approval requirements and process for each country can vary, and the time required to obtain approval may be longer or

shorter than that required for FDA approval in the United States. For example, we may submit marketing authorizations in

the E.U. under either a centralized or decentralized procedure. The centralized procedure is mandatory for the approval of

biotechnology products and many pharmaceutical products and provides for a single marketing authorization that is valid for

all E.U. member states. Under the centralized procedure, a single marketing authorization application is submitted to the

European Medicines Agency. After the agency evaluates the application, it makes a recommendation to the European

Commission, which then makes the final determination on whether to approve the application. The decentralized procedure

provides for mutual recognition of individual national approval decisions and is available for products that are not subject to

the centralized procedure.

In April 2023, the European Commission adopted a proposal to revise the E.U. pharmaceutical legislation. In April 2024,

the European Parliament introduced amendments to the European Commission’s proposal. The legislative process remains

ongoing, with several stages still required before the reform can receive final approval. Once completed, the reform is likely

to be the most comprehensive overhaul of E.U.’s medicines regulation in over 20 years, with a wide range of impacts

including on approval procedures, regulatory data protection, and environmental protection measures. Once approved, certain

provisions of the reform could potentially have an adverse impact on our business.

The requirements governing the conduct of clinical trials and product licensing also vary. In addition, post-approval

regulatory obligations such as adverse event reporting and cGMP compliance generally apply and may vary by country. For

example, after a marketing authorization has been granted in the E.U., periodic safety reports must be submitted and other

pharmacovigilance measures may be required.

Regulations Concerning Pricing and Reimbursement

Sales of our products depend, to a large degree, on the extent to which our products will be reimbursed by third-party

payors, such as government health programs, commercial insurance companies, and managed health care organizations.

Increasingly, these third-party payors are becoming stricter in the ways they evaluate and reimburse medical products and

services. Additionally, the containment of health care costs has become a priority of many governments, and the prices of

drugs have been a focus in this effort. The U.S. government, state legislatures and foreign governments have shown

significant interest in implementing cost-containment programs, including price controls, restrictions on reimbursement and

requirements for substitution of generic products. Adoption of price controls and cost-containment measures, and adoption of

18

more restrictive policies in jurisdictions with existing controls and measures, could limit our revenues. Decisions by third-

party payors to not cover a product could reduce physician usage of the product.

United States. In the U.S., we participate in the Medicaid Drug Rebate Program, Medicare, and other governmental

pricing programs. Medicaid is a joint federal and state program that is administered by the states for low-income and disabled

beneficiaries. Under the Medicaid Drug Rebate program, we are required to pay a rebate to each state Medicaid program for

our covered outpatient drugs, which includes select inpatient drugs for which there is “direct reimbursement.” Medicaid

rebates are based on pricing data reported by us on a monthly and quarterly basis to CMS, the federal agency that administers

the Medicaid and Medicare programs.

Any company that participates in the Medicaid Drug Rebate Program also must participate in the 340B drug pricing

program (the “340B program”), and the Federal Supply Schedule (“FSS”) pricing program. The 340B program, which is

administered by the Health Resources and Services Administration, requires participating companies to agree to charge

statutorily defined “covered entities” no more than the 340B “ceiling price” for covered outpatient drugs. The 340B ceiling

price is calculated using a statutory formula, which is based on pricing data calculated under the Medicaid Drug Rebate

Program. The FSS pricing program, which is administered by the Department of Veterans Affairs (“VA”), also requires

participating companies to extend discounted prices to the VA, Department of Defense, Coast Guard, and Public Health

Service. Similar to the 340B program, FSS prices are calculated utilizing pricing data reported by us to the VA on a quarterly

and annual basis.

Medicare is a federal program that is administered by the federal government. The program covers individuals age 65

and over as well as those with certain disabilities. Medicare Part A generally covers certain inpatient hospital services for

eligible beneficiaries. Prescription drugs that are used as part of an inpatient hospital stay will be covered by Medicare Part A,

and these products typically are paid as part of a bundled or composite rate (e.g., diagnosis related group).

Medicare Part D provides coverage to enrolled Medicare patients for self-administered drugs (i.e., drugs that are not

administered by a physician). Medicare Part D is administered by private prescription drug plans approved by the U.S.

government. Subject to certain statutory parameters, each drug plan establishes its own Medicare Part D formulary for

prescription drug coverage and pricing, which the drug plan may modify from time-to-time. The prescription drug plans

negotiate pricing with manufacturers and pharmacies, and may condition formulary placement on the availability of

manufacturer discounts.

The U.S. government has shown significant interest in implementing cost-containment programs for medicines and has

enacted reforms at the federal level designed to, among other things, modify prescription drug reimbursement amounts and

methodologies, and otherwise control health care costs. For example, the Patient Protection and Affordable Care Act

(“ACA”) was enacted in March 2010 and was designed to expand coverage for the uninsured while at the same time

containing overall health care costs. With regard to pharmaceutical products, among other things, the ACA was designed to

expand and increase manufacturer rebates for drugs covered under Medicaid programs, impose an annual fee on branded

pharmaceutical manufacturers, subject biological products to potential competition by lower-cost biosimilars, and make

changes to the coverage requirements under the Medicare Part D program. Additionally, in August 2022, the Inflation

Reduction Act (“IRA”) was enacted, establishing a Medicare Drug Price Negotiation Program, a Medicare inflationary

rebate, and a redesign of the Part D benefit structure. Certain drugs, including our CF medicines and CASGEVY, currently

are excluded from the IRA negotiation program. Nevertheless, other elements of the IRA may have a material impact on our

business, including the redesign of the Part D benefit and the Manufacturer Discount Program, which requires manufacturers

to take on more of the beneficiary cost previously subsidized by the federal government through the application of increased

drug discounts.

We anticipate that the U.S. government will continue to engage in activities seeking to address drug pricing and

reimbursement. Furthermore, certain states have enacted laws establishing Prescription Drug Affordability Boards

(“PDABs”). Some state PDABs, including those in Colorado, Maryland, Washington, and Minnesota, either have the

authority or have defined a pathway pursuant to which they may be granted the authority to establish upper payment limits

for prescription drugs. In certain states, there is pending litigation that would establish a PDAB or expand the authority of an

existing PDAB. Additionally, the U.S. government continues to focus on obtaining most-favored-nation pricing on U.S.

prescription drug prices in government programs. For example, CMS recently issued a proposed rule called the Guarding

U.S. Medicare Against Rising Drug Costs Model (“GUARD”). GUARD is a proposed mandatory model that would assess

rebates for certain drugs payable under Medicare Part D if the prices exceed those paid in economically comparable

19

countries. While there is significant uncertainty around the potential implementation of GUARD and related executive orders

and rulemaking, implementation of mandatory initiatives could result in reduced pricing and reimbursement for our products.

Outside the United States. In Europe and other foreign jurisdictions, the success of our products depends largely on

obtaining and maintaining government reimbursement, because patients are generally unable to access prescription

pharmaceutical products that are not reimbursed by their governments. In some countries, such as Germany, commercial

sales of a new product may begin while pricing and reimbursement terms are under discussion. In other countries, a company

must complete reimbursement negotiations prior to the commencement of commercial supply of the pharmaceutical product.

The requirements governing drug pricing vary widely country-by-country and region-by-region. For example, the

member states of the E.U. can restrict the range of drugs for which their national health insurance systems provide

reimbursement and can control the prices of prescription drugs. Many countries in the E.U. also attempt to contain drug costs

by engaging in some form of reference pricing in which authorities examine pre-determined internal or external markets for

published prices of a product or national class of drugs. In addition, many ex-U.S. government payors require companies to

provide health economic assessments of products, which are evaluated by government agencies set up for this purpose. A

member state may approve a specific price for the drug, or it may instead adopt a system of direct or indirect controls on the

total amount of money that a company may receive for supply of a drug. Countries also may consider increasing mandatory

discounts over time in an attempt to manage increased demands on healthcare budgets. Reimbursement discussions in foreign

countries often result in a reimbursement price that is lower than the net price that companies can obtain for the product in the

U.S.

In addition, reimbursement discussions may take a significant period of time resulting in commercialization delays. In

some countries where reimbursement has not yet been obtained, or where there are a limited number of eligible people and

our medicines or therapies are unregistered, the governments of such countries may agree to purchase our medicines and

therapies on an unlicensed and/or named patient basis. Reimbursement for our products cannot be assured because a country

or region may only provide for reimbursement on terms that we do not deem adequate.

Further, many governments outside of the U.S. have introduced or are in the process of introducing legislation focusing

on cost containment measures in the pharmaceutical industry. The impact of these laws where finalized, the final form of

laws under consideration, and their relevant practical application, are unknown at this time, but may lead to lower prices,

paybacks, or other forms of discounts or special taxes. Reforms in our product markets, including those that may stem from

periods of uneven economic growth or downturns or uncertainty, or as a result of high inflation, emergence, or escalation of,

and responses to, international tension and conflicts, or government budgeting priorities, may continue to result in added

pressure on pricing, access, and reimbursement for our products.

Other Regulations

The manufacturing process for pharmaceutical products is highly regulated and regulators may shut down manufacturing

facilities that they observe are not complying with regulations. We, our commercial manufacturing organizations (“CMOs”)

and our corporate partners are subject to cGMP, which are extensive regulations governing manufacturing processes, stability

testing, record keeping and quality standards as defined by FDA and EMA. Similar regulations are in effect in other

jurisdictions. Suppliers of key components and materials must be named in the NDA or marketing authorization application

filed with the regulatory authority for any product candidate for which we are seeking marketing approval, and significant

delays can occur if the qualification of a new supplier is required. Even after our facilities or a third-party supplier is qualified

by the regulatory authority, investment and effort must continue to be expended in the areas of production and quality control

to maintain full compliance with applicable regulatory requirements, including cGMP. Our manufacturing operations and

third-party suppliers are subject to regular periodic inspections by regulatory authorities following initial approval.

Pharmaceutical companies must also monitor information on side effects and adverse events reported during clinical

studies and after marketing approval and report such information and events to regulatory agencies. Non-compliance with the

applicable safety reporting requirements may result in civil or criminal penalties. Side effects or adverse events that are

reported during clinical trials can delay, impede or prevent marketing approval. Based on new safety information that

emerges after approval, the FDA can mandate product labeling changes, impose risk evaluation and mitigation strategies,

require new post-marketing studies (including additional clinical trials) or suspend or withdraw approval of the product.

These requirements may affect our ability to maintain marketing approval of our products or require us to make significant

expenditures to obtain or maintain such approvals.

20

Pharmaceutical companies are also subject to various laws pertaining to healthcare “fraud and abuse,” including the

federal Anti-Kickback Statute (“AKS”), the False Claims Act (“FCA”), and other state and federal laws and regulations in

and outside of the U.S. In the U.S., the Anti-Kickback Statute generally makes it illegal to knowingly and willfully solicit,

offer, receive or pay any remuneration in return for or to induce the referral of business, including the purchase or

prescription of a particular drug that is reimbursed by a state or federal health care program. The FCA prohibits knowingly

and willingly presenting or causing to be presented for payment to third-party payors (including Medicare and Medicaid), any

claims for reimbursed drugs or services that are false or fraudulent, claims for items or services not provided as claimed or

claims for medically unnecessary items or services. Violations of fraud and abuse laws may be punishable by criminal and/or

civil sanctions, including fines and civil monetary penalties, as well as by the possibility of exclusion from federal healthcare

programs (including Medicare and Medicaid). Liability under the FCA may also arise when a violation of certain laws or

regulations related to the underlying products (e.g., violations regarding improper promotional activity, manufacturing

regulations, or unlawful payments) contributes to the submission of a false claim. If we were subject to allegations

concerning, or convicted of violating, these laws, our business could be harmed.

Laws and regulations also have been enacted by the federal government and various states to regulate the sales and

marketing practices of pharmaceutical manufacturers. The laws and regulations generally limit financial interactions between

manufacturers and health care providers, require manufacturers to adopt certain compliance standards or require disclosure to

the government and public of such interactions. The laws include U.S. federal and state “sunshine” provisions. The federal

sunshine provisions apply to pharmaceutical manufacturers with products reimbursed under certain government programs

and require those manufacturers to disclose annually to the federal government (for re-disclosure to the public) certain

payments and other transfers of value made to physicians, physicians assistants, advanced practice registered nurses, and

teaching hospitals. State laws may also require disclosure of pharmaceutical pricing information and marketing expenditures.

Many of these laws and regulations contain requirements that are subject to interpretation. Outside the U.S., other countries

have implemented laws and regulations limiting financial interactions between manufacturers and health care providers and

providing requirements for disclosure of financial interactions with healthcare providers and additional countries may

consider or implement such laws.

We are subject to various federal and foreign laws that govern our international business practices with respect to

payments to government officials. Those laws include the U.S. Foreign Corrupt Practices Act (“FCPA”), which prohibits

U.S. companies and their representatives from paying, offering to pay, promising, or authorizing the payment of anything of

value to any foreign government official, government staff member, political party, or political candidate for the purpose of

obtaining or retaining business or to otherwise obtain favorable treatment or influence a person working in an official

capacity. In many countries, the health care professionals we regularly interact with may meet the FCPA’s definition of a

foreign government official. We are also subject to U.K. Bribery Act 2010 (“the Bribery Act”), which proscribes giving and

receiving bribes in the public and private sectors, bribing a foreign public official, and failing to have adequate procedures to

prevent employees and other agents from giving bribes. U.S. companies that conduct business in the U.K. generally will be

subject to the Bribery Act.

We are subject to extensive privacy and data protection laws and regulations concerning the collection, use and sharing

of personal data. We routinely collect and use sensitive personal information relating to health. The legislative, regulatory and

litigation landscape for privacy and data protection requirements is rapidly evolving and changing, and may limit our ability

to use data globally or across borders. For example, the E.U. General Data Protection Regulation (“GDPR”) imposes

obligations on us with respect to our processing of personal data and the cross-border transfer of such data, including higher

standards of obtaining consent, more robust transparency requirements, data breach notification requirements, requirements

for contractual language with our data processors, and stronger individual data rights. In addition, several U.S. jurisdictions

have similar data privacy laws, such as the California Consumer Privacy Act and California Privacy Rights Act. Data

protection requirements are not universal and can conflict between jurisdictions. There has also been an increase in

enforcement actions from the Federal Trade Commission, with a specific focus on companies operating health-related

websites. Compliance with these laws and regulations is made more complex by the lack of consistent standards, common

definitions, or clear regulatory expectations. At the same time, enforcement of these laws and regulations is increasing and

litigation, fines, and penalties are also becoming more common.

In addition, as we expand our pipeline and contemplate different approaches that may incorporate the use of medical

devices, such approaches may necessitate compliance with regulatory laws applicable to medical devices, including those

governing the testing, manufacture, approval, distribution, and marketing of medical devices. Furthermore, the extent of

government regulation, which might result from future legislation or administrative action, cannot accurately be predicted.

21

EMPLOYEES AND HUMAN CAPITAL MANAGEMENT

As of December 31, 2025, we had approximately 6,400 employees. Of these employees, approximately 5,200 were based

in the U.S. and approximately 1,200 were based outside the U.S. None of our U.S. employees are covered by a collective

bargaining agreement. A small number of employees outside the U.S. are covered by such agreements due to local law or

industry requirements. We consider our relations with our employees to be good.

We rely on skilled, experienced, and innovative employees to conduct the operations of our company. The biotechnology

industry is very competitive, and recruiting and retaining such employees is important to the continued success of our

business. We are committed to building an outstanding, committed, and passionate team, and we focus on a culture that

values all employees. We focus on recruiting, retaining, and developing qualified and talented employees from a range of

backgrounds to conduct our research, development, commercial, and other business activities because we believe that each

employee brings unique perspectives and strengths, and by embracing these strengths, we can do our best work for patients.

We support our employees through a variety of initiatives including learning resources and forums that promote

belonging in our workplaces; five global employee resource networks open to all employees that promote connectivity and

collaboration across levels and functions; and investments that advance access to opportunity in our surrounding

communities.

To promote our employees’ continued well-being, we offer comprehensive benefits and resources, including those

focused on health and income protection, such as life insurance and retirement savings programs. We continue to promote

and enhance wellness tools supporting our employees’ mental, social, physical and financial health. We continually review

and augment our programs to include benefits that support the evolving needs of our workforce.

In addition, we provide our employees with career development and advancement opportunities, including job rotations,

mentoring, and training. We are committed to identifying and developing our next generation of leaders, which is reflected in

our manager excellence and talent readiness programs designed for critical roles in our organization.

OTHER MATTERS

Financial Information and Significant Customers

We operate in one segment, pharmaceuticals. Financial information about our revenue by product and significant

customers is set forth in Note Q, “Segment Information,” to our consolidated financial statements included in this Annual

Report on Form 10-K.

Information Available on the Internet

Our internet address is www.vrtx.com. Our annual reports on Form 10-K, quarterly reports on Form 10-Q and current

reports on Form 8-K, and all amendments to those reports, are available to you free of charge through the “Investors/

Financial Information/SEC Filings” section of our website as soon as reasonably practicable after those materials have been

electronically filed with, or furnished to, the Securities and Exchange Commission.

Corporate Information

Vertex was incorporated in Massachusetts in 1989, and our principal executive offices are located at 50 Northern Avenue

Boston, Massachusetts 02210.

22

INFORMATION ABOUT OUR EXECUTIVE OFFICERS

The names, ages and positions held by our executive officers are as follows:

Dr. Kewalramani has been our Chief Executive Officer (CEO”) and President since April 2020 and a member of our

Board of Directors since February 2020. Dr. Kewalramani was our Executive Vice President and Chief Medical Officer from

April 2018 through April 2020. She was our Senior Vice President, Late Development from February 2017 until April 2018.

Dr. Kewalramani also served on the board of Ginkgo Bioworks from September 2021 to June 2024. From August 2004 to

January 2017, she served in roles of increasing responsibility at Amgen Inc., most recently as Vice President and Head of

U.S. Medical Organization. From 2014 through 2019, Dr. Kewalramani was the industry representative to the FDA’s

Endocrine and Metabolic Drug Advisory Committee. She completed her internship and residency in Internal Medicine at the

Massachusetts General Hospital and her fellowship in Nephrology at the Massachusetts General Hospital and Brigham and

Women’s Hospital combined program. Dr. Kewalramani holds a B.A. from Boston University and an M.D. from Boston

University School of Medicine. She is an alumna of the Harvard Business School, having completed the General

Management Program.

Dr. Leiden is our Executive Chairman, a position he has held since in April 2020. He was our Chief Executive Officer

and President from 2012 through March 2020. He has been a member of our Board of Directors since July 2009, the

Chairman of our Board of Directors since May 2012, and served as our lead independent director from October 2010 through

December 2011. Dr. Leiden was a Managing Director at Clarus Ventures, a life sciences venture capital firm, from 2006

through January 2012. Dr. Leiden was President and Chief Operating Officer of Abbott Laboratories, Pharmaceuticals

Products Group, and a member of the Board of Directors of Abbott Laboratories from 2001 to 2006. From 1987 to 2000, Dr.

Leiden held several academic appointments, including the Rawson Professor of Medicine and Pathology and Chief of

Cardiology and Director of the Cardiovascular Research Institute at the University of Chicago, the Elkan R. Blout Professor

of Biological Sciences at the Harvard School of Public Health, and Professor of Medicine at Harvard Medical School. He is

an elected member of both the American Academy of Arts and Sciences and the Institute of Medicine of the National

Academy of Sciences. Dr. Leiden was a director and the non-executive Vice Chairman of the board of Shire plc, from 2006

to January 2012, a director of Quest Diagnostics, from December 2014 to May 2019, and the Chairman of Revolution

Healthcare Acquisition Corp., from April 2021 to December 2022. Dr. Leiden received his M.D., Ph.D. and B.A. degrees

from the University of Chicago.

Dr. Atkinson has been our Executive Vice President, Chief Technical Operations Officer, Head of Biopharmaceutical

Sciences and Manufacturing Operations since August 2023. He previously served as our Senior Vice President, Head of

Commercial Manufacturing and Supply Chain since July 2020. Prior to joining us, Dr. Atkinson served in various roles at

Bristol-Myers Squibb Co., including as Senior Vice President, Global Manufacturing Operations from September 2019 to

June 2020; Vice President and Integration Leader, Corporate Cell Therapy and Global Development and Manufacturing from

January 2019 to September 2019; Vice President, Internal Manufacturing, Biologics from June 2017 to January 2019; and

Vice President, Biologics Development and Clinical Manufacturing from 2012 to June 2017. Before Bristol-Myers Squibb,

he held various roles at Cook Pharmica, LLC (now owned by Novo Holdings) and Eli Lilly. Dr. Atkinson served as a

23

member of the Board of Directors of 89bio, Inc. from February 2022 until October 2025, when it was acquired by Roche. Dr.

Atkinson holds a B.S. in Biology from Indiana University and a Ph.D. in Biological Sciences from Stanford University.

Mr. Biller has been our Executive Vice President, Chief Legal Officer since September 2022. From November 2019 until

he joined us, Mr. Biller served in several executive roles at Agios Pharmaceuticals, Inc., including Chief Legal Officer and,

most recently, Chief Financial Officer and Head of Corporate Affairs. Prior to Agios, he served as Executive Vice President,

General Counsel at Celgene from July 2018 to November 2019, where he was responsible for their global legal function, and

served as Senior Vice President, Tax and Treasury from 2011 to June 2018. Prior to Celgene, Mr. Biller was General

Counsel, Chief Tax Officer and Secretary at Bunge Limited, a global publicly traded agriculture and food company. Earlier in

his career he held various leadership roles at Alcon, Inc. and was a partner at Hopkins & Sutter and Foley & Lardner. Mr.

Biller holds a B.A. from Brown University and a J.D. from Yale Law School.

Dr. Bozic is our Executive Vice President, Global Medicines Development and Medical Affairs, a position she has held

since October 2019, and she has been our Chief Medical Officer since April 2020. She was our Senior Vice President and

Head of Global Clinical Development from May 2019 to October 2019. Prior to joining us, Dr. Bozic spent more than 20

years at Biogen Inc., a biotechnology company focused on neurological diseases, most recently as Senior Vice President of

Global Development and Portfolio Transformation from 2015 to May 2019 and as Senior Vice President of Clinical and

Safety Sciences from 2013 to 2015. Dr. Bozic has served as the industry representative to the FDA’s Risk Communication

Advisory Committee, and was a member of PhRMA’s Clinical and Preclinical Development Committee and the Board of

Managers at BioMotiv. She received her M.D., C.M., completed her residency, and was Chief Resident in Internal Medicine

at McGill University. She completed her fellowship in Pulmonary and Critical Care Medicine at Brigham and Women’s

Hospital and was an Associate Physician at Beth Israel Deaconess Medical Center and Harvard Medical School before

joining the biopharmaceutical industry.

Dr. Bunnage is our Executive Vice President and Chief Scientific Officer, a position he has held since February 2026. He

was our Senior Vice President & Head of Global Research from March 2024 through January 2026, our Senior Vice

President & Head of Research from July 2021 to March 2024, and our Senior Vice President & Site Head, Boston Research,

from August 2016 to July 2021. Prior to joining Vertex, Dr. Bunnage had a 20-year career at Pfizer Inc. where he held

positions of increasing responsibility, including Vice President, Worldwide Medicinal Chemistry and Head of Medicinal

Chemistry, Sandwich Laboratories. Dr. Bunnage is a Fellow of the Royal Society of Chemistry and a Fellow of the Royal

Society of Biology. He also serves as a visiting professor in chemistry at the University of Oxford, United Kingdom, and is a

member of the Strategic Advisory Board for the Department of Chemistry at the University of Durham, United Kingdom. Dr.

Bunnage received his B.Sc in Chemistry from the University of Durham and his D.Phil in Chemistry from the University of

Oxford. He completed his postdoctoral research as a NATO Fellow at The Scripps Research Institute in La Jolla, California.

Mr. McKechnie is our Executive Vice President, Chief Commercial Officer, a position he has held since July 1, 2025.

Mr. McKechnie previously served as our Senior Vice President, Head of North America Commercial from October 2018 to

July 2025, and as our Vice President of Global Marketing from June 2013 to September 2018. Prior to joining Vertex, Mr.

McKechnie held positions of increasing responsibility at Novartis AG, including Vice President, Respiratory Franchise from

January 2013 to June 2013; Vice President and Head Brand Maximization and Established Medicines from April 2012 to

April 2013; and Vice President, Cardiovascular Marketing from November 2008 to March 2012. Before Novartis, Mr.

McKechnie held various roles at GlaxoSmithKline plc. Mr. McKechnie holds a Business & Marketing degree from the

University of Plymouth in England.

Mr. Sachdev is our Executive Vice President, Chief Patient and External Affairs Officer, a role he has held since July

2023. From October 2019 to July 2023, he was our Executive Vice President, Chief Patient Officer. In addition, Mr. Sachdev

served in the role of Chief of Staff to the CEO from April 2020 to March 2023. He served as our Executive Vice President

and Chief Regulatory Officer from January 2017 until September 2019, and as our Executive Vice President, Policy, Access

and Value from October 2014 through December 2016. In 2010, he established our first international commercial operations

in Canada. In 2007, he joined us as a Senior Vice President, to establish our government affairs and public policy activities,

as well as our patient advocacy programs. Prior to joining us, Mr. Sachdev served as Executive Vice President, Health, of the

Biotechnology Industry Organization (BIO) and was the Deputy Commissioner for Policy at the FDA, where he also served

in several other senior positions. Prior to the FDA, Mr. Sachdev served as Majority Counsel to the Committee on Energy and

Commerce in the U.S. House of Representatives and practiced law at the American Chemistry Council, and subsequently at

the law firm of Ropes & Gray LLP. He served as a member of the Board of Directors of Eiger BioPharmaceuticals from

24

April 2019 to September 2024. Mr. Sachdev holds a B.S from Carnegie Mellon University and a J.D. from Emory University

School of Law.

Dr. Tatsis is our Executive Vice President, Chief Regulatory and Quality Officer, a position she has held since August

2020. Previously, she was our Senior Vice President and Chief Regulatory Officer from October 2019 to August 2020, and

our Senior Vice President, Global Regulatory Affairs from September 2017 to October 2019. Prior to joining us, Dr. Tatsis

held positions of increasing responsibility at several pharmaceutical companies, including Sanofi, Stemnion, Pfizer, and

Wyeth. Most recently, from 2014 to 2017, she was Vice President, Head of Global Regulatory Affairs, at the Sanofi

Genzyme Business Unit focused on Inflammation/Immunology, Rare Disease, Multiple Sclerosis, Ophthalmology,

Neurology, and Oncology/Immuno-Oncology. Dr. Tatsis also worked as an associate staff scientist and research fellow in

Immunology and Vaccine Development at the Wistar Institute and completed a post-doctoral research fellowship in

Immunology at Thomas Jefferson University. Dr. Tatsis has served as a member of the board of directors at Odyssey

Therapeutics since October 2025, and previously served on the board of directors of Verve Therapeutics from June 2024 until

July 2025, when it was acquired by Eli Lilly. She received her Ph.D. in Cell and Molecular Biology from the University of

Vermont and holds a B.S. in Biology from Temple University.

Mr. Wagner is our Executive Vice President, Chief Operating & Financial Officer, a position he has held since July

2025. Mr. Wagner was our Executive Vice President, Chief Financial Officer from April 2019 through June 2025. Prior to his

role at Vertex, Mr. Wagner was Chief Financial Officer and Executive Vice President, Finance, of Ortho Clinical

Diagnostics, a Carlyle Group portfolio company, from June 2015 to March 2019. In that role, he led the finance, accounting,

tax, treasury, global financial systems, lender relations, and acquisitions and divestiture groups. From July 2012 to June 2015,

Mr. Wagner served as Executive Vice President, Chief Financial Officer of Bruker Corporation, a scientific instruments

manufacturer. Prior to that, Mr. Wagner served as Chief Financial Officer for Progress Software Corporation, a provider of

enterprise software, and Millipore Corporation, a global provider of products and services in the life science tools market. Mr.

Wagner served as a director of Good Start Genetics, Inc., from April 2014 to August 2017 and served as a director and

member of the Audit Committee of Bruker Corporation from August 2010 to June 2012. He has served as a member of the

Board of Directors of The TJX Companies, Inc., since September 2023. Mr. Wagner holds a B.S. in Accounting from Boston

College and a M.B.A from Harvard Business School.

Ms. Ambrose is our Senior Vice President, Chief Accounting Officer, a position she has held since May 2021. Ms.

Ambrose previously served as our Senior Vice President, Accounting, Tax, Treasury, Strategic Sourcing and Corporate

Services since March 2021. From February 2003 until she joined us, Ms. Ambrose held roles of increasing responsibility at

Boston Scientific Corporation, a medical device company, most recently as Vice President of Finance and Controller of the

Global Endoscopy Division from July 2019 to March 2021 and as Vice President of Global Internal Audit from February

2017 to June 2019. Prior to Boston Scientific Corporation, Ms. Ambrose served as an accountant at Ernst & Young LLP. She

received her B.S. in Commerce from the University of Virginia and is a Certified Public Accountant.