CFF’s Therapeutics Development Arm Endorses Trial of PTI-428, Symdeko Combo

The Therapeutics Development Network (TDN) of the Cystic Fibrosis Foundation has endorsed Proteostasis Therapeutics‘ trial assessing PTI-428 in combination with Symdeko (tezacaftor/ivacaftor) as a treatment for cystic fibrosis (CF).

The Phase 2 trial will assess the safety, tolerability and pharmacokinetics of multiple doses of PTI-428 over a 28-day period in CF patients receiving a background therapy of Symdeko (developed by Vertex Pharmaceuticals). Results of the study are expected in 2019.

PTI-428 is an amplifier of the cystic fibrosis transmembrane conductance regulator (CFTR, the protein that is defective in CF patients).

The drug is intended to augment the activity of other medications, such as Symdeko and Orkambi that modulate the activity of CFTR. PTI-428 has the potential to be effective in several types of gene mutations in the CFTR gene that cause CF.

In December, Proteostasis announced the results of a 28-day study in CF subjects on background Orkambi therapy. Results showed that PTI-428 improved lung function, measured as percent predicted of forced expiratory volume in 1 second (ppFEV1). The improvement was 5.2 percentage points from baseline compared to Orkambi alone.

“Amplifiers have the potential to provide benefit across various mutation classes and across complementary background therapies, including correctors and potentiators,” Jennifer Taylor-Cousar, MD, of National Jewish Health in Denver, said in a press release.

Taylor-Cousar is a lead investigator for the PTI-428 study in CF patients on Symdeko therapy.

PTI-428 is designed to stabilize a system in the body called the proteostasis network (PN). The PN ensures that every protein within a cell will reach its final destination correctly folded and functional, or to be degraded and cleared to prevent damage.

Disease, genetic mutations, environmental factors, and aging can cause an imbalance in the PN, which can lead to a decrease in protein quality control that contributes to disease.

“In in vitro studies of PTI-428, our amplifier complements marketed agents such as ivacaftor, lumacaftor and tezacaftor. This Phase 2 study is the next stepping stone within the broader development path for PTI-428 as an add-on to current CFTR modulator therapies as well as future options which could have Symdeko components as their backbone,” said Meenu Chhabra, president and CEO of Proteostasis.

“We believe PTI-428 holds the promise of improving treatment efficacy for currently underserved segments of the CF population, as well as for those who have experienced a decline in lung function over time while on Orkambi,” Chhabra said. “We are grateful and humbled to receive TDN endorsement for this latest study of PTI-428 and we plan to start dosing CF patients in the third quarter of this year.

“We aim to share initial results in early 2019. This study will allow us to broaden the planned pivotal trial next year that includes subjects on either Orkambi or Symdeko background therapy,” Chhabra added.

TDN has also endorsed clinical trials of Proteostasis’ CF drug PTI-801, and the company’s triple combination of PTI-428, PTI-801, and PTI-808.