Pliant Therapeutics completes trial of PLN-74809 to treat in IPF

28th June 2019 (Last Updated June 28th, 2019 00:00)

Clinical stage biopharmaceutical company Pliant Therapeutics has completed a Phase 1b clinical trial of PLN-74809, an oral small-molecule dual selective inhibitor of tissue-specific αvß6 and αvß1 integrins to treat idiopathic pulmonary fibrosis (IPF), and primary sclerosing cholangitis (PSC).

Pliant Therapeutics completes trial of PLN-74809 to treat in IPF
Clubbing of the fingers in patients suffering with idiopathic pulmonary fibrosis problem. Credit: IPFeditor

Clinical stage biopharmaceutical company Pliant Therapeutics has completed a Phase Ib clinical trial of PLN-74809, an oral small-molecule dual selective inhibitor of tissue-specific αvß6 and αvß1 integrins to treat idiopathic pulmonary fibrosis (IPF) and primary sclerosing cholangitis (PSC).

PLN-74809 was found to prevent activation of TGF-β by up to 70% in alveolar macrophages gathered from healthy volunteers through a dose and exposure-dependent approach.

Furthermore, PLN-74809 was found to be well tolerated, reporting only mild adverse events, and with no drug-related adverse events.

In this randomised, double-blind, placebo-controlled trial of PLN-74809, the company analysed 20mg and 40mg doses of the drug against placebo administered over seven days in 18 healthy volunteers. The trial indicated evidence of on-target biological activity in humans.

The trial was intended to analyse PLN-74809’s ability to cut down TGF-β activation in the lungs of healthy volunteers as measured through relative pSMAD2 levels in alveolar macrophages gathered through bronchioalveolar lavage.

Besides evaluating safety and pharmacokinetics, the trail identified target plasma concentrations for preventing TGF-b activation in the lungs.

This trial will guide once-daily dose selection and trial design as Pliant proceeds into Phase IIa trials in patients with IPF.

Participants who exceeded the target plasma exposure levels after seven days of dosing saw ≥50% reductions in TGF-β activation compared to pre-treatment levels.

Pliant Therapeutics chief medical officer Éric Lefebvre said: “We’re pleased to report that PLN-74809 has shown human proof-of-mechanism by inhibiting TGF-β activation in the lungs of healthy volunteers.

“By inhibiting this critical molecular driver of fibrosis, we believe PLN-74809 may disrupt the fibrosis pathway and affect disease progression in patients with IPF. The compound continues to display a favourable safety, tolerability and pharmacokinetic profile. We plan to initiate our Phase IIa programme in IPF patients in the second half of 2019.”

The Phase Ia trials found the drug to be well tolerated, with a half-life potentially supporting once-daily dosage.

The company also expects to analyse PLN-74809 in other fibrotic diseases with unmet clinical needs, including in PSC, a chronic progressive disorder characterised by inflammation and fibrosis of the bile ducts in the liver.