Proteostasis Therapeutics' Double and Triple-Combo CF Drugs Possible Threat to Vertex Dominance


Boston-based Proteostasis Therapeutics announced positive preliminary data from its ongoing Phase I clinical trial of PTI-808 and PTI-801 in cystic fibrosis (CF). Despite it being an early-stage trial and preliminary data, company shares exploded upward by 301 percent, with more than 44 million shares trading hands.

Proteostasis announced positive data from three doublet cohorts. PTI-801 is a third-generation CF transmembrane conductance regulator (CFTR) corrector. PT-808 is a novel CFTR potentiator. A third drug, PTI-428, is a novel CFTR amplifier. The clinical trials are evaluating the safety, tolerability and pharmacokinetics of the drugs in combination against placebo. The endpoints were based on changes in sweat chloride (SC) concentrations and in percent predicted FEV1.

“Doublet combinations, the current standard of care for many CF patients, are the benchmark for current treatment in cystic fibrosis,” said Carsten Schwarz, Head, Adult Cystic Fibrosis Centre, Lung-Transplantation Program, and Endoscopy Unit, Department of Pediatric Pneumology and Immunology, Charite, Berlin University Medical Center, in a statement. “These data are the first results seen using an entirely new CF doublet, compare favorably to the standard of care, and demonstrate the potential of next-generation CFTR modulators to further improve outcomes in this disease. I look forward to results from the fourth dosing cohort and to understanding the potential of another novel combination, PTI-801, PTI-808 and PTI-428.”

The combination therapies hit all of their primary endpoints. There was at least a 6 percent improvement in ppFEV1, exceeding the efficacy observed with current dual CFTR modulator therapy.

Proteostasis also indicated that the first dose cohort of its proprietary triplet combination of PTI-801, PTI-808 and PTI-428 is expecting preliminary data in the fourth quarter of this year. Complete data from the doublet and triplet cohorts are expected in the first quarter of 2019.

Also, the company has completed studies of PTI-8801 and PTI-428 in patients on the background of Vertex Pharmaceuticals’ Orkambi (lumacaftor/ivacaftor). There is an ongoing trial of the doublet PTI-808 and PTI-801, and the PTI triplet, PTI-808, PTI-801, and PTI-428. It is also running separate studies of PTI-801 and PTI-428 in CF patients on background Vertex’s Symdeko (tezacaftor/ivacaftor and ivacaftor). It expects a read-out in the first quarter of 2019.

“We’ve taken a significant step forward in demonstrating the potential value of our proprietary combinations with this doublet data, and as our data package builds out across both doublet and triplet programs, we remain committed to bringing more choices in CFTR modulator combinations to the CF community,” stated Meenu Chhabra, president and chief executive officer of Proteostasis. “Critically, these data represent the first clinical results using only PTI-developed candidates, eliminating the known shortcomings and the noise that comes from add-on studies with existing standards of care. This marks the growth of a second branch in our development strategy, one focused on proprietary combinations, while corroborating the biologic activity and dose responses observed in our past add-on studies. The next several months include data milestones for the Company that will illuminate key next steps in both of these strategies: alternatives-to-standards-of-care and add-on-to-standards-of-care.”

A dominant player in the CF market, Vertex Pharmaceuticals, had a stock dip at the news, but appears to be recovering. In a note to investors, Brian Abrahams, an analyst with RBC, said that any drop in Vertex after the Proteostasis news means it “will be a buying opportunity” for investors and that it is an “incremental negative” for Vertex. But, if the early-stage data are confirmed or if a larger pharma company partners with Proteostasis, Proteostasis could be a serious threat.

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