Proteostasis Dismisses 13 Researchers, Shifts R&D Focus to Potential Cystic Fibrosis Therapies

Patrícia Silva, PhD avatar

by Patrícia Silva, PhD |

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Proteostasis Therapeutics is eliminating 13 research positions in order to save $3 million as it “readjusts priorities to focus resources on researching and developing” its cystic fibrosis (CF) programs, including clinical trials for PTI-428, PTI-801 and PTI-808 small molecules.

The R&D shift also includes its discovery-stage program in unfolded protein response (UPR), conducted in collaboration with Astellas Pharma.

As such, the Cambridge, Massachusetts-based company says it will reduce its research staff from 46 percent of the total workforce to 34 percent. About $200,000 of the money the company saves by dismissing those employees will be used to fund the CF clinical program, it said.

“The prioritization of our resources is meant to reflect our conviction that the CF and UPR programs remain the biggest potential drivers of value for Proteostasis and our stakeholders,” Proteostasis President and CEO Meenu Chhabra said in a press release. “A streamlined research organization will give us the financial flexibility to make judicious investments in our assets with the largest potential return for the company and for the patients we seek to benefit.”

She added: “We would like to thank our departing colleagues for their dedication to Proteostasis’ mission of discovering and developing groundbreaking therapies to treat diseases caused by an imbalance in the proteostasis network. Their efforts have contributed to the realization of the potential of our platform.”

CF is caused by a genetic mutation known as the cystic fibrosis transmembrane conductance regulator (CFTR). This generates a faulty version of the CFTR protein.

PTI-428 is a CFTR amplifier, meaning it increases the amount of an immature form of the CFTR protein, making more protein available for other agents to act on it. PTI-801, a new-generation CFTR corrector, addresses problems in the faulty protein. PTI-808 is a CFTR potentiator, meaning it improves the performance of other CFTR-targeting therapies.

The three therapies are designed to improve the activity of cells with a defective CFTR gene and restore the cells’ normal transport of chloride. That reduces the thickness of mucus, typical in CF, which interferes with proper breathing and digestion.

PTI-428 is being studied in a Phase 1/2 trial (NCT02718495) for its safety, tolerability and pharmacokinetics. In the study’s Phase 1 portion of the study, the drug has been shown to be safe and well-tolerated, with only mild or moderate side effects reported.

Proteostasis is now enrolling patients in the study’s Phase 2 portion, with preliminary results expected in the fourth quarter of 2017.

PTI-801 will be studied in a Phase 1/2 trial by the end of 2017. This trial has the support of the Cystic Fibrosis Foundation Therapeutics Development Network Protocol Review Committee as well as the European Cystic Fibrosis Society Clinical Trial Network.

Regarding PTI-808, the U.S. Food and Drug Administration (FDA) has approved the company’s investigational new drug application. Proteostasis is now about to start a Phase 1 study on the drug’s safety and pharmacokinetics in healthy volunteers.

If PTI-428 and PTI-801 prove effective, Proteostasis will launch a clinical trial to evaluate combinations of all three agents by year’s end. That study will cover CF patients with the F508del mutation in the CFTR gene.


“Our company was founded on the scientific premise that small molecules can restore the balance in the proteostasis network and have therapeutic applications in multiple genetic, degenerative and metabolic diseases,” Chhabra said. “As we move forward, our focus will be in continuing the clinical development of the CF pipeline and advancing the understanding of the underlying biology of our novel CFTR modulators.”