Proteostasis to Present Early Data from Phase 1 Study of Potential CF Therapy at NACFC Meeting

Proteostasis Therapeutics announced it will present preliminary data from its ongoing Phase 1 clinical trial evaluating ascending doses of PTI-428, an oral treatment for people with cystic fibrosis (CF).

The data will be presented at the 30^th Annual North American Cystic Fibrosis Conference (NACFC 2016), taking place Oct. 27–29 in Orlando, Florida. The company will also host an analyst and investor event, providing an overview of its science and CF clinical development plans. That nighttime event, set for Oct. 27, will be webcast live on its website.

PTI-428 is a modulator of the cystic fibrosis transmembrane conductance regulator (CFTR) protein, which is defective in CF patients. The drug acts as an amplifier, meaning that it selectively increases the amount of an immature form of the CFTR protein to provide support for other CFTR modulators, like potentiators or correctors, to act upon, ultimately improving CFTR protein activity. PTI-428 is referred to as a genotype-agnostic amplifier, and it has been shown to nearly double CFTR protein activity in in vitro studies (in patient-derived human bronchial epithelial cells) when used in combination with other therapies, Proteostasis reported.

The clinical trial  (NCT02718495)  is evaluating PTI-428’s safety, tolerability, pharmacokinetics (how a drug works within the body) in about 36 CF patients with any mutations, first in three single-ascending dose groups over three days (including a placebo group) and, should a follow-up result in a positive evaluation, in three multiple-ascending dose groups, including placebo, over three days. The study, which is being done in about a dozen sites across the U.S. and in Ontario, Canada, is recruiting patients; more information is available on its clinical trials.gov website or by clicking on the trial’s identification number above.

At NACFC 2016, Proteostasis’ poster session presentations include:

• Thursday, Oct. 27 (11:15 a.m. to 1:45 p.m. ET) – “Novel CFTR Modulator Combination of Amplifier, Corrector and Potentiator Provides Advantages Over Two Corrector-Based Combinations”(#abstract 39). In this poster, Proteostasis scientists will talk about the novel amplifier class of CFTR modulators, which led to the development of a new triple-combination therapy that uses CFTR amplifiers, correctors and potentiators. Researchers report that in human bronchial epithelial (HBE) cells electrophysiology measurements, the triple combo restores the activity of mutant F508del-CFTR protein to almost normal CFTR activity levels.
• Thursday, Oct. 27 (11:15 a.m. to 01:45 p.m ET) – “A Novel Modulator of CFTR Chloride Ion Mobility with a Distinct Mutation-Specific Profile to Existing CFTR Modulators” (#abstract 67). This presentation reports on a new class of CFTR modulators with characteristics that differ from those found in known potentiators, correctors and amplifiers, and which may represent a novel mechanism for improving mutant CFTR function.
• Saturday, Oct. 29 (10:30 a.m. to 11:50 a.m. ET) – “Phase 1 Initial Results Evaluating Safety, Tolerability, PK and Biomarker Data Using PTI-428, a Novel CFTR Modulator, in Patients with Cystic Fibrosis” (#abstract 187). This presentation will discuss preliminary data from the single-ascending and multiple ascending-dose cohorts of the Phase 1 trial.

“We expect that the data being presented at NACFC will illustrate the potential of our groundbreaking approach to treat people living with cystic fibrosis, a devastating disease with few effective therapies,” Meenu Chhabra, president and chief executive officer of Proteostasis Therapeutics, said in a press release. “In addition to unveiling the interim results of our Phase I trial of PTI-428, we’re excited to discuss findings from our preclinical studies demonstrating the advantages of our planned triple combination therapy over existing treatments including Orkambi and Kalydeco, as well as the discovery of a new class of CFTR modulators to benefit patients with the F508del- mutation – the most common mutation associated with cystic fibrosis.”

The company earlier announced that it expects final data from its clinical study before the close of 2016.