Proteostasis Therapeutics will present an update on its cystic fibrosis (CF) clinical programs — which include an amplifier, a corrector, and a potentiator of the CFTR gene — at the upcoming 41st European Cystic Fibrosis Society (ECFS) Conference, June 6-9 in Belgrade, Serbia.
In two presentations, the company will cover the most recent advances made in the development of PTI-428, PTI-801, and PTI-808.
The presentation, “Proteostasis: new study results/development pipeline,” will be given by Geoffrey S. Gilmartin, MD, chief development officer of Proteostasis.
Patrick Flume, MD, professor of medicine and pediatrics at the Medical University of South Carolina, will present the latest clinical data on PTI-428 in the presentation, “Phase 2 initial results evaluating PTI-428, a novel CFTR amplifier, in patients with cystic fibrosis.”
PTI-428 is being developed to increase the amount of the cystic fibrosis transmembrane conductance regulator (CFTR) — the protein that is defective in CF patients. When combined with other CFTR modulators, such as Vertex’s Orkambi (lumacaftor/ivacaftor) and Symdeko (tezacaftor/ivacaftor), it may improve treatment effectiveness and patient outcomes.
Results from a 28-day Phase 2 trial in CF patients receiving Orkambi revealed that the addition of PTI-428 to the treatment plan improved by 5.2 percentage points their mean predicted forced expiratory volume in 1 second (ppFEV1; a measure of lung function), compared to Orkambi alone.
Supported by the trial’s positive data, Proteostasis expects to start in the third quarter of 2018 a Phase 2 trial to test PTI-428’s efficacy and safety in combination with Symdeko, and is also planning a global Phase 3 program for PTI-428.
Currently, the company is recruiting CF patients in the U.K. for a Phase 1 trial (NCT03500263) to evaluate the safety and early efficacy of PTI-428 in combination with PTI-808 (a CFTR potentiator) and PTI-801 (a CFTR corrector). This trial was endorsed by the Cystic Fibrosis Foundation’s Therapeutics Development Network (TDN).
In April, the U.S. Food and Drug Administration granted Fast Track Designation to the triple combo treatment program.
PTI-801 is a third generation CFTR corrector that is currently being tested in a 14-day Phase 1 trial (NCT03140527) in CF patients undergoing treatment with Orkambi. The trial is currently enrolling participants. For more information, visit the clinical trial web page here.
Preliminary data collected from four patients who were treated with 100 mg of PTI-801 once a day, and who completed the pre-established 14 days of treatment, showed mean absolute improvements in ppFEV1 of about 4 percentage points from baseline.
Proteostasis expects to report additional data from this study in the second quarter of 2018, according to a press release.
PTI-808 is the company’s new CFTR potentiator that is being tested in combination with PTI-801 and PTI-428. Initial safety and tolerability data showed that the drug has an acceptable profile, with only mild or moderate adverse events being reported in healthy volunteers.
Interim data from initial testing of co-administration of PTI-428, PTI-808, and PTI-801 in 20 healthy volunteers revealed that these therapies, when combined, continued to be safe. No serious safety issues or clinically meaningful drug-drug interactions associated with the combo treatment were reported.