Drug Development Pipeline

Restore CFTR Function

• Ivacaftor (Kalydeco®)

  Ivacaftor (Kalydeco^®) is an oral medication that was the first drug available that targeted the underlying cause of CF – the defective CFTR protein.  Ivacaftor helps facilitate the opening of the chloride channel on the cell surface to allow chloride and sodium (salt) to move in and out of the cell. 

• Lumacaftor + ivacaftor (Orkambi®)

  Lumacaftor and ivacaftor (Orkambi^®) is a combination therapy combining lumacaftor, which is designed to fix the defective CFTR protein so that it can move to the proper place on the cell surface, with ivacaftor, which helps improve the function of the protein as a chloride channel on the cell surface.

• Tezacaftor + ivacaftor (Symdeko™)

  Tezacaftor + ivacaftor (Symdeko™) is a combination therapy combining tezacaftor, a compound designed to move the defective CFTR protein to the proper place in the airway cell surface, with ivacaftor, which helps facilitate the opening of the chloride channel on the cell surface to allow chloride and sodium (salt) to move in and out of the cell.

• VX-445 + tezacaftor + ivacaftor

  This program is testing VX-445 in combination with tezacaftor and ivacaftor. VX-445 and tezacaftor (VX-661) are new CFTR correctors. Correctors are drugs designed to fix the defective CFTR protein so that it can move to the proper place on the cell surface. Once CFTR protein reaches the cell surface, ivacaftor helps facilitate the opening of the chloride channel to allow chloride and sodium (salt) to move in and out of the cell. 

• VX-659 + tezacaftor + ivacaftor

  This program is testing VX-659 in combination with tezacaftor and ivacaftor. VX-659 and tezacaftor (VX-661) are new CFTR correctors. Correctors are drugs designed to fix the defective CFTR protein so that it can move to the proper place on the cell surface. Once CFTR protein reaches the cell surface, ivacaftor helps facilitate the opening of the chloride channel to allow chloride and sodium (salt) to move in and out of the cell.

• Ataluren

  Ataluren (Translarna™) is a novel, small molecule compound designed to enable production of a full-length and functional CFTR protein in individuals with CF who have nonsense mutations. The compound aims to help the body override a premature signal to stop production of the CFTR protein. 

• QBW251

  QBW251 is a type of CFTR Modulator called a “potentiator”. Similar to the drug ivacaftor, this drug would help to facilitate the opening of the chloride channel on the cell surface. This compound is administered through an oral pill.

• FDL169

  FDL169 is a new CFTR corrector. Correctors are drugs designed to fix and restore the function of the defective CFTR protein. The corrected CFTR then moves to the cell surface, where it functions as a chloride channel and helps maintain the right balance of fluid in the airways.

• GLPG2222

  GLPG2222 is a new CFTR corrector. Correctors are drugs designed to fix and restore the function of the defective CFTR protein. The corrected CFTR then moves to the cell surface, where it functions as a chloride channel and helps maintain the right balance of fluid in the airways.

• PTI-428

  PTI-428 is a type of CFTR modulator called an amplifier. Amplifiers increase the amount of CFTR protein in the cell. This makes more CFTR protein available for other therapies, such as ivacaftor and lumacaftor, to work on. When combined with other therapies, PTI-428 may increase CFTR function across multiple gene mutations.

• PTI-801

  PTI-801 is a new CFTR corrector. Correctors are drugs designed to fix and restore the function of the defective CFTR protein. The corrected CFTR then moves to the cell surface, where it functions as a chloride channel and helps maintain the right balance of fluid in the airways.

• PTI-808

  PTI-808 is a type of CFTR modulator called a potentiator. Potentiators help facilitate the opening of the chloride channel on the cell surface to allow chloride and sodium (salt) to move in and out of the cell.

• VX-561 (formerly CTP-656)

  VX-561 is an altered form of the potentiator ivacaftor (Kalydeco®). Potentiators are drugs that facilitate the opening of the chloride channel on the cell surface to allow chloride and sodium (salt) to move in and out of the cell. VX-561, or deuterated ivacaftor, may be more stable in the body than regular ivacaftor, which would allow it to be taken once a day.

• Cavosonstat (N91115)

  Cavosonstat (N91115) is a compound that modulates the function of the defective CFTR protein and decreases inflammation in the lung. Cavosonstat is the first of a new class of compounds that increase levels of an important signaling molecule in the body, called S-nitrosoglutathione or GSNO. Levels of GSNO have been shown to be decreased in people with CF. These novel compounds have been shown to increase the amount of CFTR protein that reaches the cell surface and to stabilize CFTR protein so that its function can be improved. 

   

• Riociguat

  Riociguat is a novel therapy that stimulates sGC, an enzyme in the cardiopulmonary system and the receptor for nitric oxide (NO). Preclinical data has shown evidence that riociguat can result in improved function of the CFTR protein as a chloride channel, moving salt and fluids in and out of cells.

   

• VX-152 + tezacaftor + ivacaftor

  This program is testing VX-152 in combination with tezacaftor and ivacaftor. VX-152 and tezacaftor (VX-661) are new CFTR correctors. Correctors are drugs designed to fix the defective CFTR protein so that it can move to the proper place on the cell surface. Once CFTR protein reaches the cell surface, ivacaftor helps facilitate the opening of the chloride channel to allow chloride and sodium (salt) to move in and out of the cell.

• VX-440 + tezacaftor + ivacaftor

  This program is testing VX-440 in combination with tezacaftor and ivacaftor. VX-440 and tezacaftor (VX-661) are new CFTR correctors. Correctors are drugs designed to fix the defective CFTR protein so that it can move to the proper place on the cell surface. Once CFTR protein reaches the cell surface, ivacaftor helps facilitate the opening of the chloride channel to allow chloride and sodium (salt) to move in and out of the cell.

• Eluforsen (QR-010)

  Eluforsen (QR-010) is an oligonucleotide designed to repair CFTR-encoded mRNA, which could result in a normal CFTR protein in people who have one or two copies of the F508del mutation. It is delivered via inhalation.

• MRT5005

  MRT5005 is a new drug designed to restore CFTR function by delivering correct copies of CFTR-encoded mRNA to the lungs. mRNA is a molecule that contains genetic instructions to make proteins. Delivery of CFTR-encoded mRNA would allow the lung cells to create normally functioning CFTR protein, regardless of an individual’s specific CFTR gene mutation. This drug is delivered via inhalation.

• Arcturus

  This program is developing a potential inhaled therapy to deliver normal CFTR messenger RNA to the lungs. Delivery of CFTR-encoded mRNA would allow the lung cells to create normally functioning CFTR protein, regardless of an individual’s specific CFTR gene mutation. 

• Editas

  This program is exploring ways to correct common and rare mutations in the CFTR gene using CRISPR/Cas approaches. These technologies aim to edit DNA so that the genetic defect that leads to a faulty CFTR protein is fixed. 

• Genzyme/Sanofi

  This program is working to identify new therapies designed to fix the defective CFTR protein in people who have the F508del mutation. 

• Icagen

  This program is working to identify potential therapies for people with CF who have nonsense mutations. Nonsense mutations (also known as “x” or “stop” mutations) in the CFTR gene cause the production of CFTR protein to stop prematurely. Overriding these premature stop signals would allow full-length, functional CFTR protein to be made.

• Pfizer

  This program is working to identify new therapies designed to fix the defective CFTR protein in people who have the F508del mutation.

• Reata

  This program is working to expand the number of therapies designed to fix the defective CFTR protein in people who have the F508del mutation. 

• ReCode Therapeutics

  This program is developing suppressor tRNA delivery to treat nonsense mutations. Nonsense mutations (also known as “x” or “stop” mutations) in the CFTR gene cause the production of CFTR protein to stop prematurely. Delivery of suppressor tRNA would allow lung cells to override these premature stop signals and make full-length, functional CFTR protein.

• Southern Research Institutes

  This program is working to identify potential therapies for nonsense mutations in the cystic fibrosis-causing gene. 

• Talee Bio

  This program is working to advance inhaled adeno-associated virus (AAV) delivery of the CFTR gene to the lungs. This would allow the lung cells to create normally functioning CFTR protein, regardless of an individual’s specific CFTR gene mutation. 

• 4D Molecular Therapeutics

  This program is working to advance inhaled adeno-associated virus (AAV) delivery of the CFTR gene to the lungs. This would allow the lung cells to create normally functioning CFTR protein, regardless of an individual’s specific CFTR gene mutation.