Proteostasis Therapeutics Initiates Global Cystic Fibrosis Phase 2 Study

Proteostasis Therapeutics announced that the first patient has been dosed in the Company's 28-day, Phase 2 study evaluating its proprietary cystic fibrosis transmembrane conductance regulator (CFTR) modulator combinations in F508del homozygous and heterozygous CF subjects.

Initiation of the 28-day Phase 2 study follows the positive results of the 14-day Phase 1 clinical studies of PTI's proprietary doublet (PTI-808 and PTI-801) and triplet (PTI-808, PTI-801 and PTI-428) combinations. The previous studies demonstrated a favorable safety and tolerability profile for the combinations, as well as statistically significant improvement in percent predicted FEV1 (ppFEV1) and sweat chloride concentration that was superior to the current CFTR modulator standard of care for F508del homozygous patients. The ongoing Phase 2 trial will explore efficacy over a longer duration and in additional genotypes including subjects heterozygous for the F508del mutation with PTI's doublet and triplet combinations. Dose selection (600 mg of PTI-801 and 300 mg or PTI-808, with or without 10 mg PTI-428) was based on the totality of dose range finding data from approximately 250 CF subjects studied thus far.

"Despite the inclusion of CF subjects colonized with bacteria associated with a more rapid decline in lung function, our doublet and triplet studies have delivered a compelling signal of ppFEV1 improvement," said Geoffrey Gilmartin, M.D., M.M.Sc., Chief Medical Officer of Proteostasis. "By focusing on European centers, our next stage in development will target the recruitment of patients comparable to those used in other CFTR modulator combination studies which, together with optimal dose levels and longer treatment duration, could potentially further enhance the magnitude of pulmonary benefit."

Proteostasis' Phase 2, global, multicenter, randomized, placebo-controlled study is expected to enroll up to 30 F508del homozygous patients and up to 30 F508del heterozygous patients. Study endpoints include safety, changes in sweat chloride concentration and changes in ppFEV1. Data from the study are expected in the first quarter of 2020. 

PTI-428 is an investigational CFTR amplifier in development for the treatment of CF in patients with at least one F508del mutation in the CFTR gene, as part of PTI's proprietary triple combination regimen that includes PTI-808, a novel potentiator, and PTI-801, a third-generation CFTR corrector. PTI-801 has Fast Track Designation from the U.S. Food and Drug Administration (FDA).  In May 2019, PTI-428 received Orphan Drug Designation (ODD) from the European Commission (EC).  In addition to ODD from the EC, PTI-428 has ODD, Breakthrough Therapy Designation and Fast Track Designation from the FDA.

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