Proteostasis reports Phase 1 results from CFTR modulators
Proteostasis Therapeutics announced results from Phase 1 clinical studies of its proprietary cystic fibrosis transmembrane conductance regulator modulators: PTI-801, a third-generation CFTR corrector; PTI-808, a novel CFTR potentiator; and PTI-428, a novel CFTR amplifier. This comprehensive data set includes efficacy and safety data from 14-day studies of PTI's proprietary combination therapy, as well as separate studies of PTI-801 over 14 days and PTI-428 over 28 days as add-on treatments to background tezacaftor/ivacaftor therapy, in CF subjects. Endpoints including safety, changes in sweat chloride concentration and in percent predicted FEV1 were assessed and evaluated. In a per protocol analysis, a PTI-801 dose-dependent improvement in ppFEV1 and SC concentration was observed across cohorts. Further, improvement in ppFEV1 did not reach a plateau by day 14, unlike the response profile in the company's previously reported mid-dose doublet and in reported results from non-PTI triple combinations, a finding that affirms PTI's plan for longer duration studies. Based on the totality of data, the company will be launching three new Phase 2, 28-day studies in CF subjects with at least one F508del mutation. The studies will employ entry criteria comparable to those used in other CFTR modulator combination studies. They will include a placebo controlled, triple and double combination trial in up to 30 patients exploring PTI-801 and PTI-808 with or without PTI-428 over a 28-day treatment period. PTI's CFTR modulators will also be evaluated in a homogeneous population over a longer duration. These studies will provide insight on the magnitude of PTI-428 contribution to efficacy.