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Proteostasis Begins Dosing in Phase 2 Trial of 3 CF Investigational Therapies

The first patient has been dosed in a Phase 2 clinical trial testing Proteostasis Therapeutics‘s combinations of three investigational therapies for cystic fibrosis (CF), the company announced.

The three treatments under investigation are all designed to fix the defective CFTR protein due to mutations in the CFTR gene, which is the cause of CF. The compounds under investigation are PTI-428, which is an amplifier; PTI-801, which is a corrector; and PTI-808, which is a potentiator.

The therapies are being tested in double (PTI-808 and PTI-801), and triple (PTI-808, PTI-801, and PTI-428) combinations.

In a previous Phase 1 study (NCT03500263), the triple combination therapy was shown to have an acceptable safety and tolerability profile. It also led to a statistically significant reduction in sweat chloride levels, and improvements in lung function, as assessed by ppFEV1 (percent predicted forced expiratory volume in one second), after 14 days of treatment.

The new Phase 2 study (NCT03251092) will assess the treatments’ effectiveness in 180 patients treated for a longer period (28 days). It also will include more patient genotypes, namely individuals with either one copy (heterozygous) or two copies (homozygous) of the F508del mutation in the CFTR gene, with 30 individuals of each genotype expected to be included.

Dosing for the Phase 2 study is based on previous data. Patients will be treated with 600 mg of PTI-801 and 300 mg of PTI-808, with or without 10 mg PTI-428 for the double and triple combinations, or with a placebo, as appropriate. The study’s goals include the treatments’ safety profiles, as well as lung function (as measured by ppFEV1), and sweat chloride concentration.

“Our doublet and triplet studies have delivered a compelling signal of ppFEV1 improvement,” Geoffrey Gilmartin, MD, chief medical officer of Proteostasis, said in a press release.

“By focusing on European centers, our next stage in development will target the recruitment of patients comparable to those used in other CFTR modulator combination studies which, together with optimal dose levels and longer treatment duration, could potentially further enhance the magnitude of pulmonary benefit,” Gilmartin said.

Results from the Phase 2 trial are expected to be reported in the beginning of 2020. Visit this link for more information about the trial, which is recruiting at 37 locations in the U.S. and Europe.


Marisa, a science writer, holds an MS in Cellular and Molecular Pathology from the University of Pittsburgh, where she studied novel genetic drivers of ovarian cancer. She specializes in cancer biology, immunology, and genetics. Marisa began working with BioNews in 2018, and has written about science and health for SelfHacked and the Genetics Society of America. She also writes/composes musicals and coaches the University of Pittsburgh fencing club.

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