Proteostasis Plans New Trials of Its CFTR Protein Therapies for Cystic Fibrosis

Alice Melão, MSc avatar

by Alice Melão, MSc |

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Proteostasis plans more trials

Proteostasis Therapeutics is expecting clinical trial results on three of its cystic fibrosis therapies in the next few months, and plans to start additional trials in 2018.

CF is a genetic disease caused by mutations in the sequence of the CFTR gene, which leads to impaired activity of the CFTR protein. The disease is characterized by increased production of thick, sticky mucus that interferes with breathing and digestion.

The company is testing three therapies aimed at restoring the normal activity of functions that are abnormal due to a mutated CFTR gene.

One therapy is a CFTR protein amplifier, PTI-428. It is designed to increase the level of the immature form of the CFTR protein so there is more material for other treatments to act on.

Proteostasis is also developing a CFTR corrector, PTI-801, that will address the protein’s malfunctioning. In addition, it is developing a CFTR potentiator, PTI-808, whose aim is to improve the performance of other therapies.

“Next-generation CF therapies based on combined use of CFTR modulators are fundamental to raising the bar of disease-targeting treatment,” Meenu Chhabra, the president and CEO of Proteostasis Therapeutics, said in a press release. “The team at Proteostasis has worked determinedly to deliver three truly novel, differentiated CFTR modulators to the clinic [clinical trials], generating data on safety, tolerability, and PK [pharmacokinetics] of their combined use.” Pharmacokinetics refers to the body’s effect on a drug.

Proteostatis is conducting a Phase 2 clinical trial (NCT02718495) of the CFTR amplifier’s safety, effectiveness, and stability in about 136 adults with cystic fibrosis.

Researchers are testing PTI-428 alone and in combination with Vertex’s Orkambi (lumacaftor/ivacaftor) in a seven-day-on, seven-day-off regimen for up to 28 days. Proteostatis has completed enrolling trial participants, and expects preliminary findings by the end of 2017.

A Phase 1 clinical trial (NCT03258424) is comparing the safety and patients’ ability to tolerate a combination of PTI-428 and Vertex’s Kalydeco (ivacaftor), versus a placebo. Preliminary results are expected in the first quarter of 2018.

Researchers are also recruiting 120 cystic fibrosis patients and 60 healthy volunteers for two Phase 1 trials (NCT03140527 and NCT03140527) of PTI-801’s safety. Initial findings are expected by the end of 2017.

“Our CFTR modulators have shown synergy in vitro [in a laboratory setting] with other known and investigational CFTR modulators, creating a multiplicity of possible development pathways, including add-on therapies to marketed CFTR modulators and proprietary double and triple combinations,” Chhabra said.

“Given the potential therapeutic benefit of multiple combination options and our commitment to next-generation modulators, our combination development plan includes a PTI-801 and PTI-808 doublet and a PTI-808, PTI-801, and PTI-428 triplet,” he added.

The company is recruiting healthy volunteers to test the safety of its CFTR modulators in dual- and triple-therapy combinations. It expects to start a clinical trial evaluating a combination of PTI-801 and PTI-808 in the fourth quarter of 2017 and a trial of a triple combo therapy — PTI-801, PTI-808 and a CFTR modulator — in the first half of 2018.