Pro-disease stability
CFTR Modulators

#CForward Our goal is to develop drugs that restore CFTR activity and to provide more disease-modifying options for people with CF.

CFTR MODULATORS

Our CFTR Modulators

Potentiator DIROCAFTOR (or PTI-808)
  • Potentiators improve chloride transport by increasing the opening time of the CFTR channels at the cell surface.
  • Potentiators bind to the CFTR channel and improve gating so the channel stays open for longer.
  • Increased opening time enables higher outflow of chloride ions, which increases the amount of water outside the cell, hydrating the body’s airways, intestines, and other organ systems.
  • Improved hydration helps thin the built-up mucus that causes complications in people with CF.
  • Potentiators have the possibility to treat people with CF gating and conductance mutations.
Corrector POSENACAFTOR (or PTI-801)
  • Correctors enhance the folding and stability of mutated CFTR proteins so that they can reach the cell surface and stay there longer.
  • The activity of the mutated CFTR protein that reaches the cell surface can be further enhanced by the addition of a potentiator.
  • Corrector/potentiator combinations synergize to bring more CFTR protein to the cell surface and enhance the opening time of the CFTR channel.
  • Corrector/potentiator combinations have the potential to treat people with CF with one or two copies of the F508del mutation.
Amplifier NESOLICAFTOR (or PTI-428)
  • Amplifiers selectively increase the amount of newly synthesized CFTR protein in the cell, regardless of the specific CFTR mutation.
  • Amplifiers act during translation of CFTR from mRNA into protein.
  • This leads to additional CFTR protein for correctors to properly fold and transport to the cell surface where potentiators keep the CFTR channel open for longer.
  • The only amplifier in clinical development in CF is nesolicaftor, which is being studied in combination with our corrector and potentiator in people with CF with at least one F508del mutation.
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PIPELINE

Our CFTR Modulator pipeline

We are developing CFTR modulator combinations for people with CF who have the F508del mutation or have rare mutations.

CHOICES trial – ongoing ex vivo study in patient-derived organoids, clinical portion to start in the second half of 2020