Pliant Therapeutics, Inc. Reports Positive Interim Results from Phase 2a PET Imaging Clinical Trial in Patients with Idiopathic Pulmonary Fibrosis
September 07, 2021 at 07:00 am EDT
Share
Pliant Therapeutics, Inc. announced positive interim results from a Phase 2a positron emission tomography (PET) imaging-based clinical trial of PLN-74809, an oral small molecule dual selective inhibitor of avß6/avß1, in patients with idiopathic pulmonary fibrosis (IPF). Across four dose levels, all patients achieved greater than 50% target engagement after a single dose of PLN-74809. Target engagement of 50% was previously established in a Phase 1b trial as the threshold for predicted clinical anti-fibrotic effect. In addition, there was a dose- and plasma concentration-dependent response with the two highest doses approaching target saturation. The ongoing Phase 2a open-label PET imaging clinical trial is designed to evaluate avß6 target engagement levels achieved by PLN-74809 when administered across single-doses of 60 mg, 120 mg, 240 mg or 320 mg in IPF patients. The trial is also evaluating safety, tolerability and pharmacokinetics. Patients undergo a PET scan prior to dosing and at four hours post-dose to evaluate target avß6 specific engagement. Images are analyzed for regions of high fibrotic activity, which are then evaluated for target engagement. Following completion of a standard washout period, patients may consent to receive a second dose of PLN-74809 at a different dose level followed by a second post-dose PET scan.
As fibrosis is a chronic disease, proof-of-efficacy in human trials is expensive and takes years to complete. Pliant utilizes pharmacodynamic biomarkers and advanced imaging techniques, including PET, to evaluate target engagement by company product candidates over relatively short time periods and de-risk Pliant’s programs by designing clinical trials that allow the Company to show proof-of-mechanism in advance of clinical efficacy data. Interim Phase 2a PET Clinical Trial Results. Four IPF patients were administered six single doses of PLN-74809 across 60 mg, 120 mg, 240 mg or 320 mg, generating a total of six post-dose scans. PLN-74809 Demonstrated Lung Penetration, with Greater than 50% Target Engagement Achieved in the Lungs of All IPF Patients Across All Dose Cohorts: Up to 98% target engagement of PLN-74809 achieved. Greater than 50% target engagement of PLN-74809 achieved across all doses. Dose and Plasma Concentration Response Established: PLN-74809 achieved a dose response across all single-doses from 60 mg to 320 mg. Suggests target engagement levels along the entire exposure curve of PLN-74809. Supports potential anti-fibrotic activity of PLN-74809 at the doses being evaluated in the ongoing Phase 2a INTEGRIS-IPF trial. PLN-74809 Well-Tolerated Across All Doses: No serious adverse events reported.
Pliant Therapeutics, Inc. is a clinical-stage biotechnology company. The Company is focused on discovering and developing therapies for the treatment of fibrosis and related diseases. Its lead product candidate, bexotegrast (PLN-74809), is an oral, small molecule, dual selective inhibitor of αvÃ6 and αvÃ1 integrins that is in development in the lead indications for the treatment of idiopathic pulmonary fibrosis (IPF) and primary sclerosing cholangitis (PSC). The Company has initiated BEACON-IPF, a Phase 2b trial of bexotegrast in IPF. It has also developed PLN-1474, a small molecule, selective inhibitor of αvÃ1 integrin for the treatment of non-alcoholic steatohepatitis (NASH) with liver fibrosis. It has initiated a Phase 1 study for its third clinical program, PLN-101095, a small molecule, dual-selective inhibitor of αvÃ8 and αvÃ1 integrins, that is being developed for the treatment of solid tumors. The Company has a preclinical program, PLN-101325, targeting muscular dystrophies.