Vertex Pharmaceuticals

“The data from our product development activities may not support advancement or regulatory approval of our product candidates, or label expansions for our marketed products, or provide sufficient data to support the successful commercialization of our approved products. Extensive testing is required for our product candidates and for new indications of our marketed products. The outcomes of such clinical and non-clinical testing are highly uncertain, may not generate sufficient safety, efficacy, or other data, and may not support regulatory approval of our product candidates.”

Annual report 2025A · The company itself

“We invest in research and development to discover and develop transformative medicines for people with serious diseases, with a focus on specialty markets.”

Annual report 2025A · The company itself

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

Annual report 2025A · The company itself

“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.”

Annual report 2025A · The company itself

“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.”

Annual report 2025A · The company itself

“Our success depends, in significant part, on our ability to obtain, maintain, and enforce patents and intellectual property rights such as trademarks and copyrights that protect our products, product candidates, and technologies.”

Annual report 2025A · The company itself

“(in millions, except percentages) $827.9 3% $804.5 14% $705.6 3,081.6 9% 2,825.8 15% 2,457.3 Total research and development expenses $3,909.5 8% $3,630.3 15% $3,162.9 Over the past three years, we have incurred approximately $10.7 billion in research and development expenses associated with product discovery and development.”

Annual report 2025A · The company itself

“Alpine Immune Sciences, Inc. - povetacicept On May 20, 2024, we acquired all of the issued and outstanding shares of common stock of Alpine, a publicly traded biotechnology company focused on discovering and developing innovative, protein-based immunotherapies for approximately $5.0 billion.”

Annual report 2025A · The company itself

“As a result, $4.4 billion of fair value attributed to povetacicept was expensed to AIPR&D in 2024.”

Annual report 2025A · The company itself

“CRISPR-Cas9 Gene-editing Therapies Agreements In 2015, we entered into a strategic collaboration, option and license agreement (the “CRISPR Agreement”) with CRISPR and its affiliates to collaborate on the discovery and development of potential new treatments aimed at the underlying genetic causes of human diseases using CRISPR-Cas9 gene-editing technology.”

Annual report 2025A · The company itself

“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.”

Annual report 2025A · The company itself

“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.”

Annual report 2025A · The company itself

“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.”

Annual report 2025A · The company itself

“Financial Information and Significant Customers We operate in one segment, pharmaceuticals.”

Annual report 2025A · The company itself

“If we are unable to successfully develop and commercialize medicines for acute and neuropathic pain, our business could be materially harmed. A portion of the value attributed to our company by investors is based on the expected commercial success of JOURNAVX for acute pain and on our development programs for both acute and peripheral neuropathic pain.”

Annual report 2025A · The company itself

“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.”

Annual report 2025A · The company itself

“•We are developing povetacicept, a dual inhibitor of B cell activating factor (“BAFF”) and a proliferation-inducing ligand (“APRIL”) cytokines, for multiple diseases. Povetacicept represents a potentially best-in-class approach to control B cell activity in immunoglobulin A nephropathy (“IgAN”). •We completed enrollment in the Phase 3 clinical trial evaluating povetacicept for IgAN and, in the fourth quarter of 2025, we initiated the rolling Biologics Licensing Application (“BLA”) filing for U.S. accelerated approval with submission of the first module.”

Annual report 2025A · The company itself

“•Inaxaplin is our small molecule for the treatment of APOL1-mediated kidney disease (“AMKD”). We completed enrollment in the interim analysis cohort of the global Phase 2/3 pivotal clinical trial evaluating inaxaplin in people with primary AMKD (“AMPLITUDE”).”

Annual report 2025A · The company itself

“Recent investments in external innovation include: •An exclusive global license agreement with WuXi Biologics to develop and commercialize a trispecific T cell engager for B cell-mediated autoimmune diseases, which is currently in preclinical development.”

Annual report 2025A · The company itself

“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.”

Annual report 2025A · The company itself

“In most markets outside of the U.S., the pricing and reimbursement medicines is subject to governmental control and governments are making greater efforts to reduce drug prices and limit drug spending. The reimbursement process in ex-U.S. markets vary widely and can take a significant time to complete, and reimbursement decisions are made on a country-bycountry and region-by-region basis.”

Annual report 2025A · The company itself

“In the U.S. and Europe, we estimate that there are approximately four million people diagnosed with T1D.”

Annual report 2025A · The company itself

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

Annual report 2025A · The company itself

“We estimate that there are approximately 300,000 people diagnosed with ADPKD in the U.S. and Europe.”

Annual report 2025A · The company itself

“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.”

Annual report 2025A · The company itself

“Our CF medicines are reimbursed or accessible in more than 60 countries across six continents.”

Annual report 2025A · The company itself

“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.”

Annual report 2025A · The company itself

“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.”

Annual report 2025A · The company itself

“Our ex-U.S. total revenues increased 3% in 2025, as compared to 2024, primarily due to solid CF performance across multiple geographies and increased CASGEVY product revenues, partially offset by a decline in product revenues in Russia, where we are continuing to experience a violation of our intellectual property rights.”

Annual report 2025A · The company itself

“We make international 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.”

Annual report 2025A · The company itself

“Any such disruption with respect to our commercial products could result in a failure to meet market demand, could negatively affect our patients, could reduce our net product revenues and/or increase our costs.”

Annual report 2025A · The company itself

“Sales of our products depend, to a large degree, on the extent to which our products are reimbursed by third-party payors, such as government health programs, commercial insurance and managed health care organizations. Reimbursement for our products, including our potential pipeline therapies, cannot be assured and may take significant periods of time to obtain.”

Annual report 2025A · The company itself

“We are required to make estimates for our product revenues related to government, commercial, and private payor rebates, chargebacks, discounts and fees, collectively rebates. The values of the rebates provided to third-party payors per course of treatment vary significantly and are based on government-mandated discounts and our arrangements with other third-party payors. Our most significant estimate relates to determining amounts due pursuant to the Medicaid Drug Rebate Program, including estimating the level of expected utilization of the rebates based on the amount of product sold to eligible patients.”

Annual report 2025A · The company itself

“We may not be able to increase or maintain CASGEVY product revenues. The future commercial success of CASGEVY depends on physicians, patients, or payors accepting it as medically useful, cost-effective, ethical, safe, and preferred with respect to current and potential future competitive therapies, and on payors providing adequate reimbursement.”

Annual report 2025A · The company itself

“Our customers in the U.S. subsequently resell our medicines to patients, health care providers, retail pharmacies, hospitals, or ATCs.”

Annual report 2025A · The company itself

“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.”

Annual report 2025A · The company itself

“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.”

Annual report 2025A · The company itself

“Revenues from our products depend, to a large degree, on the extent to which the products are purchased by customers, such as wholesalers, pharmacies, and hospitals, and reimbursed by third-party payors, such as government health programs, commercial insurers, and managed health care organizations. Increasingly, these third-party payors are becoming more critical in evaluating and reimbursing medicines.”

Annual report 2025A · The company itself

“We expect that the number of people with CF taking our medicines will continue to grow through new approvals and reimbursement agreements, treatment of younger patients, increased survival and expansion into additional geographies. •ALYFTREK is reimbursed for eligible people with CF in the U.S., England, Ireland, Germany, Denmark, Northern Ireland, Norway, Wales, Italy, Australia, New Zealand and Luxembourg. We are working to secure access for eligible patients in additional countries.”

Annual report 2025A · The company itself

“•Since pharmacy availability in March 2025 through year-end 2025, more than 550,000 prescriptions for JOURNAVX were written and filled across the hospital and retail settings in different acute pain conditions, consistent with JOURNAVX’s broad label. •We have secured access for JOURNAVX with all three national pharmacy benefit managers, and, as of January 2026, over 200 million individuals across commercial and government payers have coverage, representing twothirds of U.S. covered lives.”

Annual report 2025A · The company itself

“Our customers in the U.S. subsequently resell our products to patients, health care providers, retail pharmacies, hospitals, or authorized treatment centers (“ATCs”) for CASGEVY.”

Annual report 2025A · The company itself

“In addition to risks generally associated with the commercialization of medicines, the cell collection processes, manufacturing and other procedures required to manufacture and administer CASGEVY are more complex, resource-intensive, and operationally demanding than for small molecules. For example, the cost of manufacturing CASGEVY as a percentage of revenue is significantly higher than for our CF medicines.”

Annual report 2025A · The company itself

“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.”

Annual report 2025A · The company itself

“In the U.S. and Europe, we estimate that there are approximately four million people diagnosed with T1D.”

Annual report 2025A · The company itself

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

Annual report 2025A · The company itself

“We estimate that there are approximately 300,000 people diagnosed with ADPKD in the U.S. and Europe.”

Annual report 2025A · The company itself

“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.”

Annual report 2025A · The company itself

“Our CF medicines are reimbursed or accessible in more than 60 countries across six continents.”

Annual report 2025A · The company itself

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

Annual report 2025A · The company itself

“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.”

Annual report 2025A · The company itself

“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.”

Annual report 2025A · The company itself

“Globally, in 2025, 147 people with SCD or TDT had their first cell collection for CASGEVY. •As of the end of 2025, approximately 90 percent of people with SCD or TDT in the U.S. have reimbursed access to CASGEVY, which is also reimbursed in the U.K., Italy, Austria, Denmark, Luxembourg, Saudi Arabia, the UAE, Bahrain, and Kuwait.”

Annual report 2025A · The company itself

“In addition, 21 states provide coverage via Medicaid. •More than 100 of the targeted 150 healthcare systems and more than 950 individual hospitals of the 2,000 targeted institutions have added JOURNAVX to formularies, protocols or order sets.”

Annual report 2025A · The company itself

“Our U.S. total revenues increased 13% in 2025, as compared to 2024, due to continued strong patient demand, new patient initiations and higher realized net prices.”

Annual report 2025A · The company itself

“In addition to the items described above, we have a strategic agreement with Lonza to support the manufacture of T1D cell therapy product candidates, pursuant to which we have partnered with Lonza to build a 130,000 square foot dedicated new facility operated by Lonza in New Hampshire. Lease payments will begin in the first quarter of 2026 and continue through the tenth anniversary of the facility’s regulatory approval for commercial production.”

Annual report 2025A · The company itself

“We generate product revenues from sales in the U.S. and in international markets. We sell our products principally to a limited number of specialty pharmacy and specialty distributors as well as certain major wholesalers in the U.S., which account for the largest portion of our total revenues.”

Annual report 2025A · The company itself

“Further, we may face additional challenges identifying and enrolling sufficient patients for clinical trials for rare diseases and cell and gene therapies due to small patient populations.”

Annual report 2025A · The company itself

“Compliance with the regulatory requirements for biologics and cell and gene therapies can be more burdensome, expensive and time-consuming than for other, better known or more extensively studied types of medicines, such as small molecules.”

Annual report 2025A · The company itself

“The commercialization of cell and genetic therapies involves processing more personal data than traditional therapies, increasing our risk exposure.”

Annual report 2025A · The company itself

“The processes for biological and cell and genetic therapies can be more complex than those required for small molecule drugs and require additional investments in different systems, equipment, facilities and expertise.”

Annual report 2025A · The company itself

“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.”

Annual report 2025A · The company itself

“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.”

Annual report 2025A · The company itself

“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.”

Annual report 2025A · The company itself

“(in millions, except percentages) Research Expenses: Salary and benefits $203.9 (3)% $210.7 14% $184.1 94.8 (15)% 112.1 21% 92.4 Outsourced services and other direct expenses 286.2 5% 271.4 15% 237.0 Infrastructure costs 243.0 16% 210.3 9% 192.1 Total research expenses $827.9 3% $804.5 14% $705.6 Our research expenses reflect investment in our pipeline and expansion of our cell and genetic therapy capabilities, which has increased our outsourced services and other direct expenses and infrastructure costs in 2025 as compared to 2024.”

Annual report 2025A · The company itself

“CRISPR-Cas9 Gene-editing Therapies Agreements In 2015, we entered into a strategic collaboration, option and license agreement (the “CRISPR Agreement”) with CRISPR and its affiliates to collaborate on the discovery and development of potential new treatments aimed at the underlying genetic causes of human diseases using CRISPR-Cas9 gene-editing technology.”

Annual report 2025A · The company itself

“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.”

Annual report 2025A · The company itself

“We may not be able to increase or maintain CASGEVY product revenues. The future commercial success of CASGEVY depends on physicians, patients, or payors accepting it as medically useful, cost-effective, ethical, safe, and preferred with respect to current and potential future competitive therapies, and on payors providing adequate reimbursement.”

Annual report 2025A · The company itself

“In 2019, we elected to exclusively license three targets, including CF, pursuant to the CRISPR Agreement.”

Annual report 2025A · The company itself

“Further, we may face additional challenges identifying and enrolling sufficient patients for clinical trials for rare diseases and cell and gene therapies due to small patient populations.”

Annual report 2025A · The company itself

“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.”

Annual report 2025A · The company itself

“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.”

Annual report 2025A · The company itself

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

Annual report 2025A · The company itself

“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.”

Annual report 2025A · The company itself

“We estimate that there are approximately 300,000 people diagnosed with ADPKD in the U.S. and Europe.”

Annual report 2025A · The company itself

“We estimate that there are approximately 112,000 people with CF in all target markets.”

Annual report 2025A · The company itself

“Our business is substantially dependent on the success of our CF medicines. Substantially all our net product revenues have been derived from the sale of our CF medicines.”

Annual report 2025A · The company itself

“Alpine’s lead molecule, povetacicept, is a dual inhibitor of B cell activating factor (“BAFF”) and a proliferation-inducing ligand (“APRIL”) pathways. As of the acquisition date, povetacicept was in Phase 2 development and had shown potential best-in-class efficacy in IgAN, a serious progressive, life-threatening kidney disease that often progresses to end-stage-renal disease.”

Annual report 2025A · The company itself

“Due to its mechanism of action as a dual BAFF/APRIL inhibitor, povetacicept also holds the potential to benefit patients with multiple diseases, such as pMN and generalized myasthenia gravis.”

Annual report 2025A · The company itself

“In 2024, we acquired Alpine for approximately $5.0 billion.”

Annual report 2025A · The company itself

“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.”

Annual report 2025A · The company itself

“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.”

Annual report 2025A · The company itself

“As part of our business strategy, we seek to enter into strategic transactions to acquire, license, or collaborate with other entities, in each case that have potential to complement and advance our ongoing research, development, manufacturing, and commercialization efforts. Over the last several years we have engaged in a number of strategic transactions and collaborations, including our acquisition of Alpine and its lead asset, povetacicept, as well as several smaller transactions and collaboration arrangements.”

Annual report 2025A · The company itself

“In 2024, we acquired Alpine and its lead molecule, povetacicept, for approximately $5.0 billion. Povetacicept has shown potential to treat multiple diseases or conditions and become a pipeline-in-a-product.”

Annual report 2025A · The company itself

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

Annual report 2025A · The company itself

“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.”

Annual report 2025A · The company itself

“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.”

Annual report 2025A · The company itself

“Revenues from our products depend, to a large degree, on the extent to which the products are purchased by customers, such as wholesalers, pharmacies, and hospitals, and reimbursed by third-party payors, such as government health programs, commercial insurers, and managed health care organizations. Increasingly, these third-party payors are becoming more critical in evaluating and reimbursing medicines.”

Annual report 2025A · The company itself

“For example, despite considerable non-clinical testing, the clinical study of VX-264 in T1D did not meet its efficacy endpoint.”

Annual report 2025A · The company itself

“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.”

Annual report 2025A · The company itself

“We believe that zimislecel has the potential to transform the lives of eligible people with T1D.”

Annual report 2025A · The company itself

“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.”

Annual report 2025A · The company itself

“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.”

Annual report 2025A · The company itself

“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.”

Annual report 2025A · The company itself

“We are generally required to make an upfront payment upon execution of our license agreements; development, regulatory and commercialization milestones payments upon the achievement of certain F-19 product research, development and commercialization objectives; and royalty payments on future sales, if any, of commercial products resulting from our collaborations.”

Annual report 2025A · The company itself

“The total cash paid to acquire Alpine, allocation of consideration to the assets acquired and liabilities assumed and AIPR&D was as follows: (in millions) Cash consideration to acquire Alpine’s outstanding common stock $4,536.9 Cash consideration for Alpine’s vested and unvested equity awards 420.6 Total cash consideration paid to Alpine 4,957.5 Less: Expense related to unvested equity awards (197.6) Transaction costs 40.7 Total consideration allocated $4,800.6 $31.9 Current marketable securities 209.5 48.5 Deferred tax asset 105.5 Total other assets 19.5 (37.5) Total identifiable assets acquired, net 377.4 Acquired in-process research and development expense 4,423.2 Total consideration allocated $4,800.6 In-license Agreements We have entered into several in-license agreements to advance and obtain access to technologies and services related to our research and early-development activities.”

Annual report 2025A · The company itself

“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.”

Annual report 2025A · The company itself

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

Annual report 2025A · The company itself

“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.””

Annual report 2025A · The company itself

“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.”

Annual report 2025A · The company itself

“In 2025, other revenues were $30.7 million, which included $20.6 million and $10.0 million related to upfront payments received from our agreements with Ono and Zai, respectively.”

Annual report 2025A · The company itself

“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.”

Annual report 2025A · The company itself

“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.”

Annual report 2025A · The company itself

“•In 2025, we recorded $115.8 million of CASGEVY product revenues. This reflects 64 patients receiving infusions of CASGEVY in 2025, including 30 people infused in the fourth quarter.”

Annual report 2025A · The company itself

“Outside of CF, we continue to advance the commercialization of CASGEVY for the treatment of SCD and TDT, and JOURNAVX for the treatment of acute pain.”

Annual report 2025A · The company itself

“In 2025, “Other product revenues” included $115.8 million from CASGEVY and $59.6 million from JOURNAVX.”

Annual report 2025A · The company itself

“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.”

Annual report 2025A · The company itself

“Collectively, our five CF medicines, led by TRIKAFTA/KAFTRIO, are being used to treat nearly three quarters of the people with CF in the U.S., Europe, Australia, and Canada.”

Annual report 2025A · The company itself

“Flaws, biases, or malfunctions in these systems could lead to operational disruptions, data loss, or erroneous decision-making, impacting our operations, financial condition, and reputation. Ethical and legal challenges may arise, including biases or discrimination in generated outcomes, non-compliance with data protection regulations and laws specifically governing the use of artificial intelligence systems and tools, and lack of transparency.”

Annual report 2025A · The company itself

“Our strategy is to combine transformative advances in the understanding of causal human biology and the science of therapeutics to discover and develop innovative medicines.”

Annual report 2025A · The company itself

“To supplement our internal research programs, we acquire technologies and programs and collaborate with biopharmaceutical and technology companies, leading academic research institutions, government laboratories, foundations and other organizations, as needed, to advance research in our areas of therapeutic interest and to access technologies needed to execute on our strategy.”

Annual report 2025A · The company itself

“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.”

Annual report 2025A · The company itself

“Our customers in the U.S. subsequently resell our medicines to patients, health care providers, retail pharmacies, hospitals, or ATCs.”

Annual report 2025A · The company itself

“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.”

Annual report 2025A · The company itself

“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.”

Annual report 2025A · The company itself

“If any of our third parties violate, or are alleged to have violated, any laws or regulations, including anti-corruption or anti-bribery regulations, the GDPR, or other laws and regulations, during the performance of their obligations to us, we could suffer financial and reputational harm or other negative outcomes, including possible legal consequences.”

Annual report 2025A · The company itself

“Cybersecurity incidents can cause the loss of critical or sensitive information, including personal information, and could give rise to legal liability and regulatory action under data protection and privacy laws.”

Annual report 2025A · The company itself

“For example, actions taken with respect to tax-related matters by associations such as the Organisation for Economic Co-operation and Development and the European Commission could influence tax laws in jurisdictions in which we operate, such as the enactments by both E.U. and non-E.U. member countries of a global minimum tax.”

Annual report 2025A · The company itself

“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.”

Annual report 2025A · The company itself

“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 more restrictive policies in jurisdictions with existing controls and measures, could limit our revenues.”

Annual report 2025A · The company itself

“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.”

Annual report 2025A · The company itself

“The containment of health care costs continues to be a priority for many governments, and drug pricing has been a focus in this effort. The U.S. federal government and state legislatures and foreign governments have shown significant and evolving interest in implementing cost-containment programs, including price controls, restrictions on reimbursement, value-based and reference pricing, compulsory licensing, including the pursuit of socalled “march in” rights, and mandatory substitution with generic products, all of which could limit the prices of, or access to, our products.”

Annual report 2025A · The company itself

“In the U.S., pricing and access is primarily governed by practices of private managed care providers and institutional and governmental purchasers, federal laws and regulations related to Medicare and Medicaid, including the ACA and the IRA, and state activities, including the establishment of PDABs and price transparency rules.”

Annual report 2025A · The company itself

“Any such disruption with respect to our commercial products could result in a failure to meet market demand, could negatively affect our patients, could reduce our net product revenues and/or increase our costs.”

Annual report 2025A · The company itself

“In 2025, our total revenues increased to $12.0 billion as compared to $11.0 billion in 2024, primarily due to continued strong demand for TRIKAFTA/KAFTRIO as well as contributions from our launches of ALYFTREK, JOURNAVX and CASGEVY.”

Annual report 2025A · The company itself

“(in millions, except percentages) TRIKAFTA/KAFTRIO $10,312.7 1% $10,238.6 14% $8,944.7 ALYFTREK 837.8 ** — ** — Other product revenues 820.1 5% 781.5 (15)% 924.5 11,970.6 9% 11,020.1 12% 9,869.2 30.7 ** — ** — $12,001.3 9% $11,020.1 12% $9,869.2 ** Not meaningful In 2025, our net product revenues increased $950.5 million, or 9%, as compared to 2024, primarily due to continued strong demand for TRIKAFTA/KAFTRIO as well as contributions from our launches of ALYFTREK, JOURNAVX and CASGEVY.”

Annual report 2025A · The company itself

“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.”

Annual report 2025A · The company itself

“We could be subject to significant supply interruptions for our commercial products or product candidates as a result of disruptions to our internal manufacturing capabilities or those of our suppliers or partners. Supply disruptions may result from a variety of factors, including shortages in product raw materials or labor, technical difficulties, regulatory inspections or restrictions, delays in construction, regulatory approval, and inspection of new facilities or the expansion of existing facilities, shipping or customs delays, inability to maintain compliance with quality or other regulations, including cGMP requirements, general global supply chain disruptions, and performance failures by us or any third-party manufacturer on which we rely.”

Annual report 2025A · The company itself

“We must attract and retain highly qualified and trained scientists, as well as employees with experience in the development, manufacture, and commercialization of medicines, including biologic and cell and genetic therapies. We face intense competition for such talent from our competitors, other companies, academic institutions, and other organizations throughout our industry, especially with respect to employees with expertise in cell or genetic therapies.”

Annual report 2025A · The company itself

“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.”

Annual report 2025A · The company itself

“We also rely on third-party manufacturers to produce drug substance and finished drug product for clinical trials for povetacicept.”

Annual report 2025A · The company itself

“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.”

Annual report 2025A · The company itself

“If we discover safety or efficacy issues with any of our products, commercialization efforts for the product could be negatively affected, the approved product could lose its approval, and our business could be materially harmed. After regulatory approval and launch, our products are used over longer periods of time and by larger populations of patients than during pre-approval clinical trials.”

Annual report 2025A · The company itself

“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.”

Annual report 2025A · The company itself

“(“Semma”), which established and advanced our T1D program; our expansion of our renal programs through our acquisition of Alpine Immune Sciences, Inc.”

Annual report 2025A · The company itself

“(“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.”

Annual report 2025A · The company itself

“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.”

Annual report 2025A · The company itself

“If we or our third-party clinical trial providers, including contract research organizations (“CROs”), do not successfully conduct and manage our clinical activities or adequately comply with regulatory requirements, our clinical trials may experience delays or increased costs, and the potential regulatory approval of a product candidate or expansion of a label for a marketed product may be delayed or denied.”

Annual report 2025A · The company itself

“Establishing, managing and expanding our global manufacturing capabilities and supply chain, particularly as we enter new therapeutic modalities, requires significant financial commitment.”

Annual report 2025A · The company itself

“For example, we rely on third parties such as CROs for the day-to-day management and oversight of our clinical trials, on CMOs for active ingredient manufacturing and finishing operations, and on logistics providers for the distribution of our products.”

Annual report 2025A · The company itself

“Our ex-U.S. total revenues increased 3% in 2025, as compared to 2024, primarily due to solid CF performance across multiple geographies and increased CASGEVY product revenues, partially offset by a decline in product revenues in Russia, where we are continuing to experience a violation of our intellectual property rights.”

Annual report 2025A · The company itself

“Third-party contract manufacturers, including some based in China, perform different parts of our manufacturing process.”

Annual report 2025A · The company itself

“We rely on a global network of third parties, including some in China, and our internal capabilities to manufacture and distribute our products for commercial sale and post-approval clinical trials and to manufacture and distribute our product candidates for clinical trials. In addition to establishing supply chains for each newly approved product, we adapt our supply chain for existing products to include additional formulations or to increase scale of production for existing products as needed.”

Annual report 2025A · The company itself

“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.”

Annual report 2025A · The company itself

“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.”

Annual report 2025A · The company itself

“For example, as part of FDA approval for CASGEVY, we are required to conduct post-marketing safety studies to assess certain long-term risks associated with the treatment.”

Annual report 2025A · The company itself

“In January 2026, we secured reimbursed access to CASGEVY for eligible people with SCD in Scotland, consistent with the reimbursement agreement reached in 2025 for people with TDT. •We expect to begin global regulatory submissions for approvals for CASGEVY in children 5 to 11 years of age, in the first half of 2026. The FDA awarded Vertex with a Commissioner’s National Priority Voucher for this pediatric submission, indicating an accelerated timeline for review once the submission is complete.”

Annual report 2025A · The company itself

“We expect to release interim analysis data in the first half of 2026 and we expect to complete the submission in the first half of 2026, if data from the interim analysis are supportive.”

Annual report 2025A · The company itself

“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.”

Annual report 2025A · The company itself

“For example, we depend on China-based suppliers for portions of our supply chain. Finding alternative suppliers due to geopolitical developments or otherwise may not be feasible or could take a significant amount of time and involve significant expense due to the nature of our products and the need to obtain regulatory approvals.”

Annual report 2025A · The company itself

“Our global operations subject us to risks that could adversely affect our business and revenue. In addition to the ex-U.S. risks we face with respect to compliance with local laws and regulatory requirements, pricing and reimbursement, intellectual property, manufacturing capabilities and supply chain, foreign exchange risks, and reliance on third parties, risks associated with operating a global biotechnology company include the potential for: •economic weakness, including recession and inflation, or political instability globally or with respect to particular foreign economies and markets; •business interruptions resulting from geo-political actions, including war and terrorism; •import and export licensing requirements, tariffs, trade barriers, and other trade and travel restrictions, the risks of which appear to have increased in the current political environment; •credit risks related to our customers, which may be higher in less developed markets; and •global or regional public health emergencies.”

Annual report 2025A · The company itself

“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.”

Annual report 2025A · The company itself

“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.”

Annual report 2025A · The company itself

“For example, we depend on China-based suppliers for portions of our supply chain. Finding alternative suppliers due to geopolitical developments or otherwise may not be feasible or could take a significant amount of time and involve significant expense due to the nature of our products and the need to obtain regulatory approvals.”

Annual report 2025A · The company itself

“For example, U.S. legislation has been introduced to limit certain U.S. biotechnology companies from using equipment or services from select Chinese biotechnology companies, and others in Congress have advocated for limitations on those Chinese service providers’ ability to engage in business in the U.S. We cannot predict what actions may ultimately be taken with respect to trade relations between the United States and China or other countries, what products and services may be subject to such actions, the effective date or duration of such actions, or what actions may be taken by the other countries in response to actions by the United States.”

Annual report 2025A · The company itself

“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.”

Annual report 2025A · The company itself

“Third-party manufacturers may be able to sell generic versions of our products in countries that do not provide effective mechanisms for enforcement of our patents or other intellectual property rights. For example, we have experienced a violation of our intellectual property rights in Russia, where a copy product that infringes our patents has been made available.”

Annual report 2025A · The company itself

“For example, new proposals or requirements regarding local manufacturing of pharmaceutical products, enhanced data security and privacy measures, sustainability, importation restrictions, embargoes, or trade sanctions may negatively impact our business.”

Annual report 2025A · The company itself

“Our global operations subject us to risks that could adversely affect our business and revenue. In addition to the ex-U.S. risks we face with respect to compliance with local laws and regulatory requirements, pricing and reimbursement, intellectual property, manufacturing capabilities and supply chain, foreign exchange risks, and reliance on third parties, risks associated with operating a global biotechnology company include the potential for: •economic weakness, including recession and inflation, or political instability globally or with respect to particular foreign economies and markets; •business interruptions resulting from geo-political actions, including war and terrorism; •import and export licensing requirements, tariffs, trade barriers, and other trade and travel restrictions, the risks of which appear to have increased in the current political environment; •credit risks related to our customers, which may be higher in less developed markets; and •global or regional public health emergencies.”

Annual report 2025A · The company itself

“Fluctuations in currency exchange rates and interest rates, changes in the value of our investment portfolio, and inflation have affected and will continue to affect our cash flows, results of operations, and financial condition. The exchange rates among our reporting currency, the U.S. dollar, and the currencies in which we do business are volatile and our efforts to mitigate against these risks may not be successful.”

Annual report 2025A · The company itself

“We use cloud technologies and any failure by cloud or other technology service providers to adequately safeguard their systems and prevent cyber-attacks or data privacy incidents could disrupt our operations and result in misappropriation, corruption, or loss of confidential or proprietary information. The third parties upon which we rely face similar risks and when they experience a security breach of their systems, our security can be adversely affected.”

Annual report 2025A · The company itself

“Our stock price is subject to significant fluctuations. From January 1, 2025 to December 31, 2025, our common stock traded between $362.50 and $519.68 per share.”

Annual report 2025A · The company itself

“Fluctuations in currency exchange rates and interest rates, changes in the value of our investment portfolio, and inflation have affected and will continue to affect our cash flows, results of operations, and financial condition. The exchange rates among our reporting currency, the U.S. dollar, and the currencies in which we do business are volatile and our efforts to mitigate against these risks may not be successful.”

Annual report 2025A · The company itself

“We intend to rely on our existing cash, cash equivalents and current marketable securities together with our operating profitability as our primary source of liquidity. We expect that cash flows from our product sales together with our cash, cash equivalents and current marketable securities will be sufficient to fund our operations for at least the next twelve months.”

Annual report 2025A · The company itself

“We could be subject to significant supply interruptions for our commercial products or product candidates as a result of disruptions to our internal manufacturing capabilities or those of our suppliers or partners. Supply disruptions may result from a variety of factors, including shortages in product raw materials or labor, technical difficulties, regulatory inspections or restrictions, delays in construction, regulatory approval, and inspection of new facilities or the expansion of existing facilities, shipping or customs delays, inability to maintain compliance with quality or other regulations, including cGMP requirements, general global supply chain disruptions, and performance failures by us or any third-party manufacturer on which we rely.”

Annual report 2025A · The company itself

“These include our povetacicept programs acquired from Alpine, pain and T1D programs, which together have increased our outsourced services and other direct expenses.”

Annual report 2025A · The company itself

“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.”

Annual report 2025A · The company itself

“These include leases for our corporate headquarters at Fan Pier in Boston, Massachusetts, which continues through June 2044, and office and laboratory space at the Jeffrey Leiden Center for Biologics, Cell and Genetic Therapies Campus (the “Leiden Campus”) near our corporate headquarters.”

Annual report 2025A · The company itself

“We have significant future capital requirements, including: •Expected operating expenses to conduct research and development activities, manufacture and commercialize our existing and future products, and to operate our organization. •Cash that we pay for income taxes. •Royalties we pay related to sales of our CF products. •Facility, operating and finance lease obligations as described below. •Firm purchase obligations related to our supply and manufacturing processes.”

Annual report 2025A · The company itself

“For example, new proposals or requirements regarding local manufacturing of pharmaceutical products, enhanced data security and privacy measures, sustainability, importation restrictions, embargoes, or trade sanctions may negatively impact our business.”

Annual report 2025A · The company itself