Small Molecules, Gene Editing, Cell Therapy

Vertex Pharmaceuticals Incorporated is dedicated to the discovery, development, and production of innovative medicines aimed at treating serious diseases. The company employs a unique approach to drug discovery, focusing on understanding the underlying causes of diseases to create therapies that can significantly improve patients' lives. Their research and development pipeline includes a variety of programs targeting conditions such as cystic fibrosis, pain management, sickle cell disease, and Duchenne muscular dystrophy, among others. Vertex emphasizes the importance of scientific innovation and collaboration, utilizing advanced technologies like CRISPR/Cas9 gene-editing and mRNA therapeutics to develop potential treatments.

In addition to their scientific endeavors, Vertex fosters a culture of innovation through various programs designed to inspire and empower their employees. Initiatives such as the Vertex Fellows and Physician Investigator programs provide opportunities for early-career scientists and physicians to engage directly with drug development processes. The company also hosts innovation tournaments and seminars featuring industry leaders to encourage creative problem-solving and continuous learning among its workforce. This commitment to innovation not only enhances their research capabilities but also aligns with their mission to transform the lives of patients with serious diseases.

United States

Vertex is a global biotechnology company that invests in scientific innovation to create transformative medicines for people with serious and life-threatening diseases.

We discovered and developed the first medicines to treat the underlying cause of cystic fibrosis (CF), a rare, life-threatening genetic disease. In addition to clinical development programs in CF, Vertex has more than a dozen ongoing research programs focused on the underlying mechanisms of other serious diseases.

Founded in 1989 in Cambridge, Massachusetts, our corporate headquarters is now located in Boston’s Innovation District, and our international headquarters is in London, United Kingdom. We currently employ approximately 3,500 people in the United States, Europe, Canada, Australia and Latin America with nearly two-thirds of our staff dedicated to research and development.

Vertex is consistently recognized as one of the industry’s top places to work by Science Magazine, The Boston Globe, Boston Business Journal and the San Diego Business Journal. Our research and medicines have also received esteemed recognitions, including the Robert J. Beall Therapeutics Development Award, the French Prix Galien and the British Pharmacological Society awards.

Endocrine System Diseases

Genetic Diseases

Hematologic Diseases

Kidney Diseases

Lung Diseases

Metabolic Diseases

Musculoskeletal Diseases

Pathological Conditions

Vertex Pharmaceuticals Incorporated

Cystic fibrosis

The CFTR protein is a chloride channel present at the surface of epithelial cells in multiple organs. The F508del mutation results in protein misfolding, causing a defect in cellular processing and trafficking that targets the protein for degradation and therefore reduces the quantity of CFTR at the cell surface. The small amount of F508del-CFTR that reaches the cell surface is less stable and has low channel-open probability (defective gating activity) compared to wild-type CFTR protein. Lumacaftor improves the conformational stability of F508del-CFTR, resulting in increased processing and trafficking of mature protein to the cell surface. Ivacaftor is a CFTR potentiator that facilitates increased chloride transport by potentiating the channel-open probability (or gating) of the CFTR protein at the cell surface. In vitro studies have demonstrated that both lumacaftor and ivacaftor act directly on the CFTR protein in primary human bronchial epithelial cultures and other cell lines harboring the F508del-CFTR mutation to increase the quantity, stability, and function of F508del-CFTR at the cell surface, resulting in increased chloride ion transport. In vitro responses do not necessarily correspond to in vivo pharmacodynamic response or clinical benefit.

ORKAMBI® (lumacaftor/ivacaftor)

Elexacaftor and tezacaftor bind to different sites on the CFTR protein and have an additive effect in facilitating the cellular processing and trafficking of F508del-CFTR to increase the amount of CFTR protein delivered to the cell surface compared to either molecule alone. Ivacaftor potentiates the channel open probability (or gating) of the CFTR protein at the cell surface. The combined effect of elexacaftor, tezacaftor and ivacaftor is increased quantity and function of F508del-CFTR at the cell surface, resulting in increased CFTR activity as measured by CFTR mediated chloride transport.

TRIKAFTA® (elexacaftor/tezacaftor/ivacaftor and ivacaftor)

In people with certain types of mutations in the CFTR gene, the CFTR protein is not processed and cannot move through the cell normally. This results in little to no protein at the cell surface. VX-121 and tezacaftor are designed to increase the amount of mature protein at the cell surface by targeting the processing and trafficking defect of the CFTR protein. VX-561 (deutivacaftor) is an investigational potentiator designed to keep CFTR proteins at the cell surface open longer to improve the flow of salt and water across the cell membrane, which helps hydrate and clear mucus from the airways. The VX-121/tezacaftor/VX-561 program was granted Fast Track and Orphan Drug Designations from the U.S. Food and Drug Administration for the treatment of cystic fibrosis.

ALYFTREK (Vanza triple) (vanzacaftor/tezacaftor/deutivacaftor)

Ivacaftor is a potentiator of the CFTR protein. The CFTR protein is a chloride channel present at the surface of epithelial cells in multiple organs. Ivacaftor facilitates increased chloride transport by potentiating the channel-open probability (or gating) of the G551D-CFTR protein. In vitro, ivacaftor increased CFTR-mediated transepithelial current (IT) in rodent cells expressing G551D-CFTR protein following addition of a cyclic adenosine monophosphate (cAMP) agonist with an EC50 of 100 ± 47 nM; however, ivacaftor did not increase IT in the absence of cAMP agonist. Ivacaftor also increased IT in human bronchial epithelial cells expressing G551D-CFTR protein following addition of a cAMP agonist with an EC50 of 236 nM. Ivacaftor increased the open probability of G551D-CFTR protein in single channel patch clamp experiments using membrane patches from rodent cells expressing G551D-CFTR protein by 10-fold versus untreated cells after addition of PKA and ATP.

KALYDECO® (ivacaftor)

Acute pain

Pain

VX-548 is an oral, selective NaV1.8 inhibitor that has completed Phase 1 studies in healthy volunteers. Based on a favorable pharmacokinetic, safety and tolerability profile, it was advanced to Phase 2 studies in 2021.
NaV1.8 is a voltage-gated sodium channel that plays a critical role in pain signaling in the peripheral nervous system. NaV1.8 is a genetically validated novel target for the treatment of pain, and Vertex has previously demonstrated clinical proof-of-concept with a small molecule investigational treatment targeting NaV1.8 in multiple pain indications including acute pain, neuropathic pain and musculoskeletal pain.
Vertex’s approach is to selectively inhibit NaV1.8 using small molecules with the objective of creating a new class of medicines that have the potential to provide superior relief of acute pain without the limitations of opioids, including their addictive potential. VX-548 is the most recent molecule to enter clinical development from Vertex’s portfolio of NaV1.8 inhibitors.

JOURNAVX™ (suzetrigine) (VX-548)  

Tezacaftor facilitates the cellular processing and trafficking of normal and select mutant forms of CFTR (including F508del-CFTR) to increase the amount of mature CFTR protein delivered to the cell surface. Ivacaftor is a CFTR potentiator that facilitates increased chloride transport by potentiating the channel-open probability (or gating) of the CFTR protein at the cell surface. For ivacaftor to function CFTR protein must be present at the cell surface. Ivacaftor can potentiate the CFTR protein delivered to the cell surface by tezacaftor, leading to a further enhancement of chloride transport than either agent alone. The combined effect of tezacaftor and ivacaftor is increased quantity and function of CFTR at the cell surface, resulting in increases in chloride transport. CFTR Chloride Transport Assay in Fisher Rat Thyroid (FRT) cells expressing mutant CFTR The chloride transport response of mutant CFTR protein to tezacaftor/ivacaftor was determined in Ussing chamber electrophysiology studies using a panel of FRT cell lines transfected with individual CFTR mutations. The FRT assay was conducted in ivacaftor-responsive mutations and F508del. Tezacaftor/ivacaftor increased chloride transport in FRT cells expressing CFTR mutations that result in CFTR protein being delivered to the cell surface. The minimum response threshold was designated as a net increase of at least 10% of untreated normal over baseline. The tezacaftor/ivacaftor incubation resulted in either similar or increased chloride transport compared to ivacaftor alone. In vitro data may not accurately predict added clinical benefit of SYMDEKO (tezacaftor/ivacaftor combination) over KALYDECO (ivacaftor) alone for individual mutations. In addition, the magnitude of the net change over baseline in CFTR-mediated chloride transport is not correlated with the magnitude of clinical response for individual mutations.

SYMDEKO® (tezacaftor/ivacaftor and ivacaftor)

Sickle cell disease

CTX001 is an investigational, autologous, ex vivo CRISPR/Cas9 gene-edited therapy that is being evaluated for patients suffering from TDT or severe SCD, in which a patient’s hematopoietic stem cells are edited to produce high levels of fetal hemoglobin (HbF; hemoglobin F) in red blood cells. HbF is a form of the oxygen-carrying hemoglobin that is naturally present at birth, which then switches to the adult form of hemoglobin. The elevation of HbF by CTX001 has the potential to alleviate or eliminate transfusion requirements for patients with TDT and reduce or eliminate painful and debilitating sickle crises for patients with SCD. Earlier results from these ongoing trials were published as a Brief Report in The New England Journal of Medicine in January of 2021.

CASGEVY™ (exagamglogene autotemcel) (exa-cel) (CTX001)

TRIKAFTA® (elexacaftor/tezacaftor/ivacaftor and ivacaftor) 

KALYDECO® (ivacaftor) 

Beta thalessemia

APOL1-Mediated Kidney Disease

Kidney disease

Inaxaplin (VX-147)

Diabetic peripheral neuropathy

IgA nephropathy

Povetacicept

Lumbosacral radiculopathy

VX-993

Autosomal Dominant Polycystic Kidney Disease

Genetic disorder

VX-407 is a first-in-class small molecule corrector that is designed to treat ADPKD in patients with a subset of PKD1 variants, estimated at ~25,000 (or ~10%) of the overall ~250,000 ADPKD patient population, by correcting defective PC1 folding to restore function. In doing so, the aim is to stop growth of kidney cysts and reduce kidney volume, thereby preventing progression to kidney failure.

VX-407

Type 1 diabetes

VX-880 is an investigational allogeneic stem cell-derived, fully differentiated, insulin-producing islet cell therapy manufactured using proprietary technology. VX-880 is being evaluated for patients who have T1D with impaired hypoglycemic awareness and severe hypoglycemia. VX-880 has the potential to restore the body’s ability to regulate glucose levels by restoring pancreatic islet cell function, including glucose responsive insulin production. VX-880 is delivered by an infusion into the hepatic portal vein and requires chronic immunosuppressive therapy to protect the islet cells from immune rejection.

Zimislecel (VX-880)

VX-522

Glomerular diseases

VX-993 (IV formulation)

Severe alpha-1 antitrypsin deficiency

VX-864, a first-generation AAT corrector, to assess the impact of longer-term treatment on polymer clearance from the liver, as well as the resultant levels of functional AAT (fAAT) in the plasma. Vertex is working to address the underlying genetic cause of alpha-1 antitrypsin (AAT) deficiency by developing novel small molecule correctors of Z-AAT protein folding, with a goal of increasing the secretion of functional AAT into the blood and addressing both the lung and the liver aspects of AAT deficiency.

VX-864

VX-264 uses the same stem cell-derived, fully differentiated islets from the VX-880 program, which are encapsulated in a novel device designed to shield the cells from the body’s immune system and obviate the need for immunosuppressive therapy.

Vertex Pharmaceuticals Incorporated

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