Drug Development Pipeline

Restore CFTR Function

• Elexacaftor + tezacaftor + ivacaftor (Trikafta™)

  Elexacaftor + tezacaftor + ivacaftor (Trikafta™) is a combination therapy combining three CFTR modulators. Elexacaftor and tezacaftor are CFTR correctors, a type of modulator designed to fix the defective CFTR protein so that it can move to the proper place on the cell surface. Ivacaftor is a potentiator. Once CFTR protein reaches the cell surface, potentiators help facilitate the opening of the chloride channel to allow chloride and sodium (salt) to move in and out of the cell. 

• 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.

• 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. 

• VX-659 + tezacaftor + ivacaftor

  This program tested VX-659 in combination with tezacaftor and ivacaftor. VX-659 and tezacaftor (VX-661) are 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-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.

• 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.

• ABBV-2222 (formerly GLPG2222)

  ABBV-2222 (formerly GLPG2222) is a type of CFTR modulator called a 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.

• ABBV-3067

  ABBV-3067 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. 

• ELX-02

  ELX-02 is a compound designed to restore CFTR function in 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. ELX-02 is intended allow lung cells to override these premature stop signals and make full-length, functional CFTR protein.

• FDL169

  FDL169 is a 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 (alone and in combination)

  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-428 is currently being studied both alone as well as in combination with two other CFTR modulators, PTI-801 and PTI-808.

• PTI-801 (alone and in combination)

  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-801 is currently being studied both alone as well as in combination with two other CFTR modulators, PTI-428 and PTI-808.

• PTI-808 (alone and in combination)

  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.

  PTI-808 is currently being studied both alone as well as in combination with two other CFTR modulators, PTI-801 and PTI-428.

• VX-121

  VX-121 is a 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.

• 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. 

• 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.

• 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. 

• Spirovant Sciences

  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.