Positive Interim Results From Phase 2a Trial of Investigational IPF Treatment

Pliant Therapeutics announced positive interim results from an ongoing phase 2a open-label positron emission tomography (PET) imaging clinical trial to evaluate the potential of PLN-74809 in patients with idiopathic pulmonary fibrosis (IPF).

PLN-74809 is an oral small molecule that allows for dual selective inhibition of α_vβ₆/α_vβ₁. PLN-74809 achieved α_vβ₆ target engagement up to 98% in the lungs of IPF patients after administration of a single dose. Overall, target engagement was greater than 50%, the threshold for predicted clinical antifibrotic effect previously established in a phase 1b trial.

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Éric Lefebvre, MD, chief medical officer of Pliant Therapeutics, stated, “We believe the high target engagement levels seen after the administration of just a single dose illustrate the potential of PLN-74809 to show a potent antifibrotic effect in our longer-term clinical trials.”

The study authors observed a PLN-74809 dose response across all single doses from 60 mg to 320 mg, suggesting target engagement along the entire exposure curve. Response to PLN-74809 was dose- and plasma concentration-dependent with the 2 highest doses administered, 240 mg and 320 mg. No serious adverse events were reported across all doses.

“These data represent a significant step forward in our understanding of the potential antifibrotic activity of PLN-74809 and support the selected doses in our ongoing 12-week Phase 2a INTEGRIS-IPF trial,” Lefebvre said.

In the trial reported on, patients with IPF are given PLN-74809 single doses of 60 mg, 120 mg, 240 mg, or 320 mg to evaluate α_vβ₆ target engagement levels, safety, tolerability, and pharmacokinetics. PET scans, performed prior to PLN-74809 dosing, 4 hours postdosing, and after a second dose are used to investigate regions of high fibrotic activity for target engagement.

Reference

Pliant Therapeutics reports positive interim results from phase 2a PET imaging clinical trial in patients with idiopathic pulmonary fibrosis. News release. Pliant Therapeutics, Inc.; September 7, 2021.