Developing novel therapies for cystic fibrosis


Seeking to restore protein function in CFTR-mutated cells

Cystic fibrosis (CF) is a life-limiting autosomal recessive disorder that affects 70,000 individuals worldwide. Improvement in disease management protocols and approval of new drugs that treat CF symptoms have extended life expectancy—some CF patients now live beyond 40 years. However, CF remains an incurable disease that leads to premature death.

  • A mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene has been identified as responsible for the clinical manifestations of the disease. The gene’s protein product is named CFTR
  • The class of CFTR modulators known as correctors and potentiators are currently used in patients with select mutations

Exploiting the DRT™ platform to discover novel therapies for CF

Our proprietary DRT™ (Disease-Relevant Translation) platform utilizes pertinent phenotypic assays and disease-relevant models to identify molecules that act on the protein homeostasis pathways within the cell to elicit higher CFTR mediated chloride currents, thereby helping to restore CFTR function in CFTR-mutated cells.

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Developing a new triple combination therapy in the treatment of CF

Proteostasis Therapeutics is developing a new triple-combination CF therapy comprised of 3 agents discovered utilizing our proprietary DRT™ platform. Currently in preclinical development, the triple-combination therapy includes:

  • PTI-428, an investigational CFTR amplifier
    • Our most advanced clinical candidate is PTI-428, a first-in-class CFTR amplifier, that showed in vitro increase in CFTR protein levels across genotypes.
  • PTI-801, an investigational CFTR corrector
    • PTI-801 is a new generation CFTR corrector currently in clinical development  that showed superior in vitro efficacy and synergy with known correctors
  • PTI-808, an investigational CFTR potentiator in preclinical development
    • PTI-808, a CFTR potentiator, enhanced the function of mutated F508del CFTR in vitro and restored it to almost normal levels when combined with PTI-428 and PTI-801

The cystic fibrosis program is fully owned by Proteostasis Therapeutics, Inc.