About Vertex Pharmaceuticals Inc

Vertex Pharmaceuticals Incorporated operates as a global biotechnology company that invests in scientific innovation to create transformative medicines for people with serious diseases, with a focus on specialty markets. The company has four approved medicines that treat the underlying cause of cystic fibrosis (CF), a life-threatening genetic disease, and one approved therapy that treats severe sickle cell disease (SCD) and transfusion dependent beta thalassemia (TDT), life shortening inherited blood disorders. The company’s pipeline includes clinical-stage programs in CF, sickle cell disease, beta thalassemia, acute and neuropathic pain, APOL1-mediated kidney disease, type 1 diabetes, myotonic dystrophy type 1 and alpha-1 antitrypsin deficiency. The company’s marketed medicines that treat people with CF are TRIKAFTA/KAFTRIO (elexacaftor/tezacaftor/ivacaftor and ivacaftor), SYMDEKO/SYMKEVI (tezacaftor/ivacaftor and ivacaftor), ORKAMBI (lumacaftor/ivacaftor) and KALYDECO (ivacaftor). Collectively, the company’s four marketed CF medicines are being used to treat nearly three quarters of the approximately 92,000 people with CF in North America, Europe and Australia. Through label expansions, approval of new medicines, and expanded reimbursement, the company focuses on increasing the number of people with CF who are eligible and able to receive its medicines. The company is evaluating its medicines in additional patient populations, including younger children, with the goal of having small molecule treatments for all people who have at least one mutation in their cystic fibrosis transmembrane conductance regulator (CFTR) gene that is responsive to its CFTR modulators. The company has completed Phase 3 development of a triple combination of vanzacaftor/tezacaftor/deutivacaftor, which has demonstrated the potential to provide additional clinical benefits, as well as once-daily dosing, to people with CF who have at least one mutation in their CFTR gene that is responsive to CFTR modulators. The company plans to submit global regulatory filings for this new triple combination regimen by mid-2024. In addition, the company has initiated the multiple ascending dose portion of the Phase 1/2 clinical trial of VX-522, an investigational messenger ribonucleic acid (mRNA) therapeutic it is developing in collaboration with Moderna, Inc. (Moderna). The company is continuing its research and development of CFTR modulators, with the aim of developing best-in-class medicines that can help more patients achieve carrier levels of CFTR function, and it is investigating additional potential treatments for people with CF who do not make full-length CFTR protein and cannot benefit from CFTR modulators. The company’s marketed therapy is CASGEVY (exagamglogene autotemcel, or exa-cel), an ex-vivo, non-viral CRISPR/Cas9 gene-edited cell therapy, which has been approved in the United States (U.S.), the European Union (E.U.), the United Kingdom (U.K.), the Kingdom of Saudi Arabia (Saudi Arabia), and the Kingdom of Bahrain (Bahrain) for the treatment of SCD and TDT. In January 2024, the company announced positive results from its Phase 3 clinical trials evaluating VX-548, a non-opioid investigational NaV 1.8 inhibitor, for the treatment of moderate-to-severe acute pain. The company plans to submit for regulatory approval of VX-548 in moderate-to-severe acute pain in the U.S. by mid-2024. In addition, in December 2023, the company announced positive results from the Phase 2 clinical trial evaluating VX-548 for the treatment of diabetic peripheral neuropathy (DPN), a type of peripheral neuropathic pain. The company expects to advance VX-548 into pivotal development in DPN in 2024. Beyond CF, SCD, TDT and pain, the company is advancing programs across multiple disease areas and modalities, including: APOL1-Mediated Kidney Disease: The company is evaluating inaxaplin, its investigational small molecule for the treatment of APOL1-mediated kidney disease (AMKD) in a Phase 2/3 clinical trial. The company expects to select a dose and move to the Phase 3 portion of the clinical trial in the first quarter of 2024. Type 1 Diabetes: The company is evaluating VX-880, an investigational allogeneic stem-cell derived, fully differentiated islet cell therapy, for the treatment of type 1 diabetes (T1D) in a Phase 1/2 clinical trial in which patients also receive immunosuppressive therapy to protect the islet cells from immune rejection. The company has completed enrollment in Part C of this clinical trial. VX-880 is on a protocol-specified pause, pending review of the totality of the data by the independent data monitoring committee and global regulators. The company’s second clinical program in T1D, VX-264, in which the implanted islet cells are encapsulated in an immunoprotective device, is ongoing. The company has completed Part A of this Phase 1/2 clinical trial and it has initiated Part B in multiple centers and countries. Myotonic Dystrophy Type 1: The company is exploring multiple approaches to address the underlying causal biology for myotonic dystrophy type 1 (DM1), including small molecules. The company initiated a Phase 1/2 clinical trial evaluating VX-670, an oligonucleotide-based approach that it has in-licensed from Entrada Therapeutics, Inc. (Entrada). The clinical trial is active and enrolling in Canada and will initiate in the U.K. in the near term. Alpha-1 Antitrypsin Deficiency: The company continues to enroll and dose healthy volunteers in Phase 1 clinical trials for VX-634 and VX-668, its next-wave investigational molecules with significantly improved potency and drug-like properties as compared to its previous alpha-1 antitrypsin (AAT) correctors. In addition to the programs, the company has additional research programs aimed at diseases that fit its research and development strategy and follow-on programs in its existing disease areas in accord with its serial innovation approach. The company’s core strategy is to discover and develop innovative medicines by combining transformative advances in the understanding of human disease and the science of therapeutics to dramatically advance human health. That strategy focuses 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. The company’s 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 its ongoing discovery and development efforts. The company’s serial innovation approach is intended to increase the likelihood of successfully bringing transformative medicines to patients and to provide durable clinical and commercial success. The company’s CF medicines are the exemplar of this strategy, as it continues to reach more people with CF than ever before through label expansions, approvals of new medicines and expanded reimbursement. In addition, the company has obtained historic approvals for CASGEVY for the treatment of SCD and TDT and is working towards broad access for eligible patients to this potentially curative treatment option. The company continues to advance its broad and diverse pipeline and prepare for potential near-term global commercial launches in new disease areas. Marketed Products CF The company’s CF medicines are collectively being used by nearly three quarters of the approximately 92,000 people with CF in North America, Europe, and Australia. CF is a life-shortening genetic disease caused by a defective or missing CFTR protein resulting from mutations in the CFTR gene. To develop CF, children must inherit two defective CFTR genes, which are referred to as alleles; one allele is inherited from each parent. The vast majority of patients with CF carry at least one F508del mutation. The F508del mutation results in a defect in the CFTR protein in which the CFTR protein does not reach the surface of the cells in sufficient quantities and does not adequately transport chloride ions. The company’s CFTR regimens target the underlying cause of disease and have been shown to improve CFTR protein function in people with CF, and as such have been shown to provide transformative benefit for people living with CF. The company’s CF medicines are used by patients in over 60 countries, and TRIKAFTA/KAFTRIO is now approved and reimbursed or accessible in more than 40 of these countries. In addition to the E.U. and the U.S., the company markets its products in additional countries, including the U.K., Australia, Canada, Brazil and Switzerland. The company continues to increase the number of patients eligible and able to receive its current medicines through label expansions and expanded reimbursement. Sickle Cell Disease and Transfusion-Dependent Beta Thalassemia CASGEVY, the company’s therapy for SCD and TDT, was recently approved in the U.S., the E.U., the U.K. Saudi Arabia, and Bahrain. 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. CASGEVY, the company’s ex-vivo, non-viral CRISPR/Cas9-based gene-editing therapy, was developed for the treatment of severe SCD and TDT, with its collaborator, CRISPR Therapeutics AG (CRISPR). The company’s global launch strategy for CASGEVY focuses on disease education and awareness for patients, caregivers, health care professionals, payors, and policymakers, as well as engagement with the scientific and medical community regarding CASGEVY clinical data. The company’s strategy is also focused on activation of ATCs to ensure their readiness to treat patients and establishing a globally-enabled manufacturing and supply chain to meet patient demand. In addition, its approach concentrates on achieving access for patients through reimbursement agreements with governments and commercial payors, as well as through early access programs where applicable. Research and Development Programs The company invests in research and development to discover and develop transformative medicines for people with serious diseases, with a focus on specialty markets. The company’s research strategy is to combine transformative advances in the understanding of human disease and in the science of therapeutics to dramatically advance human health. The company focuses 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. The company’s development-stage product candidates for the treatment of the serious diseases on which it focuses include CF, SCD, TDT, acute and neuropathic pain, AMKD, T1D, DM1, and AAT deficiency (AATD). In pursuit of serial innovation, the company’s 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. The company’s research and development strategy has been validated through its success in moving novel product candidates into clinical trials and obtaining marketing approvals for TRIKAFTA/KAFTRIO, KALYDECO, ORKAMBI, and SYMDEKO/SYMKEVI for the treatment of CF, and CASGEVY for the treatment of SCD and TDT. The company’s approach to drug discovery has been further validated by its successful demonstration of clinical proof-of-concept in four additional disease areas: in acute and neuropathic pain with its NaV1.8 inhibitors, in AMKD with inaxaplin, and in T1D with a stem cell-derived islet cell therapy. The company continues to make significant internal investments in cell and genetic therapies. These investments include the development of a Boston-based campus for research and current Good Manufacturing Practices (cGMP) clinical manufacturing capabilities dedicated to its portfolio of cell and genetic therapy technologies and teams. To augment its internal programs, the company acquires businesses and technologies and collaborate with biopharmaceutical and technology companies, leading academic research institutions, government laboratories, foundations and other organizations to advance research in its disease areas of interest, as well as to access technologies needed to execute on its strategy. The company’s internal and external innovation approaches are based on the same strategy, which enables it to effectively integrate and execute on new internal capabilities as it invests in external innovation. The company’s investments in external innovation include its collaboration with CRISPR, which resulted in the successful development and approval of CASGEVY and the establishment and advancement of other pipeline programs, including its T1D program through its acquisition of Semma Therapeutics, Inc. (Semma), its mRNA therapeutic, VX-522, for the treatment of CF through its collaboration with Moderna, and its intracellular therapeutics for DM1, including VX-670, through its collaboration with Entrada. CF The company has completed the Phase 3 global program evaluating a once-daily investigational triple combination of vanzacaftor/tezacaftor/deutivacaftor. The company’s Phase 3 program consisted of two 52-week randomized, controlled clinical trials, SKYLINE 102 and SKYLINE 103, which evaluated the safety and efficacy of the new combination relative to TRIKAFTA in approximately 950 people with CF 12 years of age and older, and the single arm RIDGELINE trial, evaluating vanzacaftor/tezacaftor/deutivacaftor in children with CF 6 to 11 years of age. In February 2024, the company announced positive data from this Phase 3 program. The data from these trials demonstrate that this triple combination provides additional benefit beyond TRIKAFTA for people with CF who have the F508del mutation on at least one allele that is CFTR modulator responsive. This new triple combination regimen was safe and well-tolerated in all three clinical trials. The company expects to submit global regulatory filings for this triple combination by mid-2024, including a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA), using a priority review voucher, and Marketing Authorization Applications to the EMA and Health Canada, for people with CF 6 years of age and older. As of December 31, 2023, the company completed dosing in the single ascending dose part of the Phase 1/2 clinical trial for VX-522 in people with CF, and it initiated the multiple ascending dose part of the clinical trial. The company expects to share data from this clinical trial in late 2024 or early 2025. Sickle Cell Disease and Transfusion-Dependent Beta Thalassemia Two global Phase 3 clinical trials evaluating CASGEVY in people 5 to 11 years of age with severe SCD (the CLIMB SCD-151 clinical trial) and TDT (the CLIMB THAL-141 clinical trial) are ongoing. The company has completed enrollment in these two clinical trials. In connection with its serial innovation approach, the company is working on preclinical assets for myeloablative conditioning agents with improved tolerability profiles which could be used in connection with treatment with CASGEVY, significantly broadening the eligible SCD and TDT patient population. In addition, the company is investigating small molecules for the potential treatment of SCD and TDT. Pain The company has discovered multiple selective small molecule inhibitors of NaV1.8 as potential treatments for pain. The company obtained pharmacological validation of NaV1.8 inhibition with a first generation NaV1.8 inhibitor in all three clinical pain types: acute pain, chronic neuropathic pain, and chronic musculoskeletal pain. In acute pain, the company completed two randomized, placebo-controlled Phase 3 clinical trials for its lead compound, VX-548, evaluating patients with moderate-to-severe acute pain following abdominoplasty or bunionectomy surgery. The company also completed a single-arm clinical trial evaluating the safety and effectiveness of VX-548 in multiple other types of moderate-to-severe acute pain. In January 2024, the company announced positive results from these clinical trials. The clinical trials demonstrated that treatment with VX-548 led to statistically significant improvement on the primary endpoint of the time-weighted sum of the pain intensity difference compared to placebo, as well as clinically meaningful reduction in pain from baseline on the numeric pain rating scale after abdominoplasty surgery or bunionectomy surgery. VX-548 was safe and well tolerated in all three Phase 3 studies. The company also announced its plans to submit an NDA to the FDA by mid-2024, with the goal of securing a broad label for the treatment of moderate-to-severe acute pain. In neuropathic pain, in December 2023, the company announced results from a Phase 2 clinical trial evaluating VX-548 in people with DPN, a common form of peripheral neuropathic pain. The clinical trial demonstrated that treatment with VX-548 led to a statistically significant and clinically meaningful reduction in the primary endpoint of change from baseline in the weekly average of daily pain intensity on a numeric pain rating scale at week 12. VX-548 was generally well-tolerated at all doses tested in the clinical trial. The company also announced its plans to advance VX-548 for the treatment of DPN into pivotal development, with the ultimate goal of securing a broad label for the treatment of peripheral neuropathic pain. In support of this broad peripheral neuropathic pain indication it seeks, in December 2023, the company initiated a second Phase 2 clinical trial in lumbosacral radiculopathy, which is pain caused by impairment or injury to nerve roots in the area of the lumbar spine, another type of peripheral neuropathic pain. There are no approved medicines in the U.S. that are labeled for the treatment of peripheral neuropathic pain. In keeping with its serial innovation approach, the company has also completed a Phase 1 clinical trial evaluating an oral formulation of VX-993, a next generation NaV1.8 inhibitor, and it anticipates initiating Phase 2 clinical trials evaluating VX-993 for the treatment of moderate-to-severe acute pain and for the treatment of peripheral neuropathic pain in 2024. The company also anticipates initiating a Phase 1 clinical trial evaluating an intravenous formulation of VX-993 in 2024. Additionally, the company is advancing multiple NaV1.8 inhibitors and NaV1.7 inhibitors through research and earlier stages of development for pain. APOL1-Mediated Kidney Disease The company is evaluating multiple novel small molecules that inhibit the function of the mutant APOL1 protein with the potential to treat APOL1-mediated kidney disease. In a Phase 2 proof-of-concept clinical trial, patients with APOL1-mediated FSGS treated with inaxaplin on top of standard of care achieved a statistically significant, substantial, and clinically meaningful reduction of proteinuria. In this clinical trial, inaxaplin was well tolerated by patients. Based on this positive Phase 2 data, the company initiated pivotal development of inaxaplin in a single Phase 2/3 adaptive clinical trial in patients with AMKD in 2022. Enrollment in the Phase 2B portion of the Phase 2/3 clinical trial has completed. The company expects to select a dose and begin the Phase 3 portion of the clinical trial in the first quarter of 2024. Type 1 Diabetes The company is 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. The company is pursuing three programs for the transplant of functional islets into patients: transplantation of islet cells alone following immunosuppression to protect the implanted cells, implantation of the islet cells inside a novel immunoprotective device, and development of hypoimmune islet cells to optimize protection of the implanted islet cells from the immune system. VX-880, the company’s first program, is a stem cell-derived, allogeneic, fully differentiated, insulin-producing islet cell replacement therapy, using standard immunosuppression to protect the implanted cells. The Phase 1/2 study is designed as a sequential, multi-part clinical trial to evaluate the safety and efficacy of VX-880. In Part A, the first two patients received half the target dose of VX-880 cells and the results demonstrated proof-of-concept that VX-880 can restore glucose-regulated insulin production and improve glycemic control. In Part B, patients received the full target dose. The company has completed enrollment in Part C of the clinical trial, with concurrent dosing at the full target dose, with trial sites in the U.S., Canada, Norway, the U.K., Italy, Germany, Switzerland, the Netherlands and France. Data presented to date from the VX-880 clinical trial continue to demonstrate unprecedented efficacy and curative potential. Safety data is consistent with the immunosuppressives, the perioperative period, and past medical history. The company has placed the clinical trial on a protocol-specified pause, pending review of the totality of the data by an independent data monitoring committee and global regulators, following two patient deaths both of which were determined by the trial investigators to be unrelated to VX-880. In its second program, the company is evaluating VX-264, in which the allogeneic stem cell-derived, fully differentiated, insulin-producing islet cells are encapsulated in an immunoprotective device that is implanted in patients. The company is enrolling and dosing patients with VX-264 in a Phase 1/2 clinical trial that is a sequential, multi-part study to evaluate the safety, tolerability and efficacy of VX-264. Part A of the study dosed patients with a partial dose of cells/devices and a stagger between patients, and Part B will dose patients with a full target dose and a stagger between patients before moving to concurrent, full dosing in Part C. The clinical trial is enrolling patients in the U.S., Canada, the U.K., Switzerland, Italy, Germany, and the Netherlands, with additional global sites to be activated in the coming months. The company has completed Part A of the clinical trial and Part B has been initiated in multiple centers and countries. In its third program, research is directed toward developing hypoimmune cells by gene-editing the same stem cells used in the VX-880 and VX-264 programs prior to differentiation into fully differentiated islets in order to cloak them from the immune system. This program continues to advance in pre-clinical development. Myotonic Dystrophy Type 1 DM1 is an inherited disease that results in the weakening and destruction of skeletal muscles over time. The company has an internal small molecule program for DM1 and, in 2022, it established a collaboration with Entrada focused on enabling efficient intracellular delivery of an oligonucleotide. The company’s Phase 1/2 clinical trial evaluating the first candidate, VX-670, in patients with DM1 has been initiated in Canada and will initiate in the U.K. in the near term. Alpha-1 Antitrypsin Deficiency AATD is a severe disease of the liver and lung, caused by inherited mutations in the SERPINA1 gene that encodes the AAT protein. The company has discovered multiple small molecule correctors that restore folding of the mutant Z-AAT protein (the most common mutant form of SERPINA1 in AATD patients), leading to increased production of functional AAT protein. The company continues to enroll and dose subjects in Phase 1 clinical trials evaluating VX-634 and VX-668, the next-wave of investigational small molecule AAT correctors with significantly improved potency and drug-like properties compared with its previous AATD correctors. Commercialization of Medicines Commercial Organization The company’s commercial organization focuses on supporting the appropriate use of TRIKAFTA/KAFTRIO, SYMDEKO/SYMKEVI, ORKAMBI, KALYDECO and CASGEVY in the markets where these products have been approved. The company’s sales and marketing organizations are responsible for promoting products to health care providers, ensuring its products are distributed effectively, ensuring the safe use of its products, and obtaining reimbursement for its products from third-party payors, including governmental organizations in the U.S. and ex-U.S. markets. The company markets its products through personal interactions with physicians and allied health care professionals. In parallel, the company’s government affairs and public policy group advocates for policies that promote life sciences innovation and increase awareness of the diseases on which it focuses with state and federal legislatures, government agencies, public health officials and other policymakers. Commercialization of CF Medicines In the U.S., the company primarily sells its CF products to a limited number of specialty pharmacy and specialty distributors. In international markets, it sells its CF products primarily through distributor arrangements and to retail pharmacies, as well as to hospitals and clinics, many of which are government-owned or supported. The company’s U.S. field-based CF commercial team consists of a small number of individuals to support commercialization of its medicines for CF. The company focuses its CF marketing efforts in the U.S. on a relatively small number of physicians and health care professionals who write most of the prescriptions for CF medicines. Many of these physicians and health care professionals are located at a limited number of accredited centers in the U.S. focused on the treatment of CF. In international markets, the company or its distributors have small sales forces that support TRIKAFTA/KAFTRIO, SYMDEKO/SYMKEVI, ORKAMBI and KALYDECO in jurisdictions where these products are approved. The company also has established programs in the U.S. that provide its CF products to qualified uninsured or underinsured patients at no charge or at a reduced charge, based on specific eligibility criteria. Commercialization of CASGEVY The company has begun the commercial launch of CASGEVY, following approvals in the U.S., the E.U., the U.K., Saudi Arabia, and Bahrain. As CASGEVY is the first CRISPR-based therapy to be approved, the company’s global launch strategy focuses on educating physicians, patients and caregivers, payors, and policymakers about the significant disease burden of SCD and TDT and the availability of CASGEVY as a treatment option. In addition, the company is concentrating on communications with the scientific and medical community regarding the clinical profile of CASGEVY and data demonstrating its safety and efficacy. The company has also established a global manufacturing network to ensure adequate production and supply of CASGEVY at a commercial scale. The company has activated 12 ATCs in the U.S., three ATCs in Europe, and one ATC in Saudi Arabia, and it is working to activate additional centers. In the U.S., the company is working to develop medical policies and identify reimbursement pathways for people with SCD or TDT through both government and commercial payors. In the U.K., the company also has begun engagement with the National Institute for Health and Care Excellence (NICE), which is the start of the process for seeking government reimbursement of CASGEVY. In the E.U., the company is working with national health authorities to achieve access and reimbursement. In France, the National Authority for Health (HAS) approved its request for the implementation of an early access program (EAP) for the use of CASGEVY to treat eligible people with TDT, and the company is pursuing a similar program for SCD. In the Middle East, the company has established a local presence in the region and are working with local healthcare authorities in Saudi Arabia and Bahrain to achieve access and reimbursement. Near-Term Launch Opportunities The company is also preparing for near-term potential launches for two product candidates: one for its triple combination of vanzacaftor/tezacaftor/deutivacaftor for the treatment of CF and one for VX-548 for the treatment of acute pain. CF The company expects to support the launch of the vanzacaftor/tezacaftor/deutivacaftor triple combination with its existing commercial infrastructure. Acute Pain For its near-term opportunity in acute pain, the company focuses on the estimated 80 million patients in the U.S. who are prescribed a medicine for their moderate-to-severe acute pain each year. The company has made significant progress in building its organization to support the launch of VX-548 and is hiring additional key teams that will support the use of VX-548 at hospitals and other settings in the U.S. The company is working with policymakers and institutions that establish practice guidelines to support the appropriate use of non-opioid pain medications, including avoiding meaningful financial barriers to patients accessing such medicines relative to generic opioids. Strategic Transactions and Collaborations Strategic Transactions In 2017, the company enhanced its CF portfolio through its acquisition of certain CF assets, including deutivacaftor, from Concert Pharmaceuticals Inc. The company announced positive results from its Phase 3 clinical trials evaluating its new, once-daily investigational triple combination therapy, vanzacaftor/tezacaftor/deutivacaftor, for people with CF 6 years of age and older. In 2019, the company established its T1D program through its acquisition of Semma, a privately held company focused on the use of stem cell-derived human islets as a potentially curative treatment for T1D. The company is evaluating VX-880 for the potential treatment of T1D in a clinical trial and have completed enrollment in Part C of that trial. In addition, the company’s second clinical program in T1D, VX-264, in which the implanted islet cells are encapsulated in an immunoprotective device, is ongoing. The company has completed dosing in Part A of that trial and Part B is underway. Collaboration and Licensing Arrangements Joint Development and Commercialization Agreement with CRISPR In December 2017, the company entered into a joint development and commercialization agreement (Original JDCA) with CRISPR, pursuant to which it is co-developing and co-commercializing CASGEVY for SCD and TDT. The company entered into the Original JDCA following its exercise of an option to co-develop and co-commercialize the hemoglobinopathies program that was contained in the collaboration agreement that it entered into with CRISPR in 2015. Pursuant to the A&R JDCA, the company leads global development, manufacturing and commercialization of CASGEVY, with support from CRISPR. Subject to the terms and conditions of the A&R JDCA, the company has the right to conduct all research, 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. In-License Agreements The company’s in-license agreements include: CRISPR Therapeutics AG: In addition to its arrangement with CRISPR, the company has exercised options to exclusively license treatments for specific targets, including CF, that were subject to the research program under the collaboration agreement it entered into with CRISPR in 2015. In 2019, the company 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, the company 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.: n 2016, the company entered into a collaboration with Moderna for the identification and development of mRNA therapeutics encoding CFTR for the treatment of CF. In December 2022, the FDA cleared its Investigational New Drug Application (IND) for VX-522, an mRNA therapeutic it is developing with Moderna pursuant to this collaboration. At the end of 2023, the company completed dosing in the single ascending dose part of the Phase 1/2 clinical trial for VX-522 in people with CF, and it initiated the multiple ascending dose part of the clinical trial. Entrada Therapeutics, Inc. In 2022, the company established a collaboration with Entrada focused on enabling efficient intracellular delivery of an oligonucleotide. This collaboration includes ENTR-701, known as VX-670, an investigational candidate for the treatment of DM1 that is in clinical development. The clinical trial evaluating VX-670 is active and enrolling in Canada and will initiate in the U.K. in the near term. Out-license Agreements The company has entered into various agreements pursuant to which it has out-licensed rights to certain product candidates to third-party collaborators. Pursuant to these out-license arrangements, its collaborators are responsible for all costs related to the continued development of such product candidates and obtain development and commercialization rights to these product candidates. Cystic Fibrosis Foundation In 2004, the company entered into a collaboration agreement with the Cystic Fibrosis Foundation, as successor in interest to the Cystic Fibrosis Foundation Therapeutics, Inc., to support research and development activities. Pursuant to the collaboration agreement, as amended, the company has 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 potential net sales of certain compounds first synthesized and/or tested between March 1, 2014 and August 31, 2016, including elexacaftor. For combination products, such as ORKAMBI, SYMDEKO/SYMKEVI and TRIKAFTA/KAFTRIO, sales are allocated equally to each of the active pharmaceutical ingredients in the combination product. Intellectual Property The company has thirteen 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. The company has 20 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. The company has 24 issued U.S. patents listed in the Orange Book that cover the active pharmaceutical ingredients in SYMDEKO, its marketed formulation, and/or its approved indication. The company has 28 issued U.S. patents listed in the Orange Book that cover the active pharmaceutical ingredients in TRIKAFTA, its marketed formulation, and/or its approved indication. Products approved by the FDA under a Biologics Licensing Application (BLA), including CASGEVY, receive 12 years of regulatory exclusivity in the U.S. from a product’s approval date. Additionally, the company has licenses to dozens of issued U.S. patents that cover CASGEVY, its approved indication, and/or its manufacture. In addition to protecting its marketed products, the company actively files patent applications in the U.S. and in foreign countries on inventions relating to its pipeline. For example, the company also owns and/or controls the U.S. and foreign patents and/or patent applications relating to the following: Vanzacaftor, deutivacaftor, and other CF potentiators and correctors and many other related compounds, and the use of those compounds for the treatment CF. VX-522 and other mRNA-based approaches for treating CF. VX-548 and other compounds being studied for the potential treatment of pain. Inaxaplin and other compounds being studied for the potential treatment of AMKD. VX-880, VX-264, and other cell-based approaches for treating T1D. VX-634, VX-668, and other compounds being studied for the potential treatment of AATD. VX-670 for the treatment of DM1. Other pre-clinical and clinical candidates and the use of such candidates to treat specified diseases. The manufacture, pharmaceutical compositions, related solid forms, formulations, dosing regimens, and methods of use of many of the above compounds. The company 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 the company refers, 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). As of December 31, 2023, 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, the company entered into an agreement with Editas Medicine, Inc. (Editas), providing it 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, the company owns patents and/or patent applications relating to the composition, manufacture, and use of CASGEVY. From time to time, the company enters into exclusive and non-exclusive license agreements for proprietary third-party technology used in connection with its research activities. Trademarks VERTEX, KALYDECO, ORKAMBI, SYMDEKO, SYMKEVI, TRIKAFTA, KAFTRIO, and CASGEVY are registered trademarks of the company. Government Regulation Products the company manufactures or distributes pursuant to FDA approvals are subject to continuing regulation by the FDA, including among other things: record-keeping requirements; reporting of adverse experiences with the product; providing the FDA with updated safety and efficacy information; drug sampling and distribution requirements; notifying the FDA and gaining its approval of specified manufacturing or labeling changes; complying with certain electronic records and signature requirements; and complying with FDA promotion and advertising requirements. The company is subject to various federal and foreign laws that govern the company’s international business practices with respect to payments to government officials. Those laws include the U.S. Foreign Corrupt Practices Act (‘FCPA’), which prohibits the 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. The company is 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. The company is subject to federal laws, including the Medicaid Drug Rebate Program, the 340 program, and the FSS pricing program, that require pharmaceutical manufacturers to report certain calculated product prices to the government or provide certain discounts or rebates to government authorities or private entities, often as a condition of reimbursement under government healthcare programs. History Vertex Pharmaceuticals Incorporated was founded in 1989. The company was incorporated in Massachusetts in 1989.