SOUTH SAN FRANCISCO, Calif., Oct. 31, 2019 /PRNewswire/ -- Pliant Therapeutics, Inc., a clinical stage biopharmaceutical company focused on discovering and developing novel therapies for the treatment of fibrosis, today announced that company scientists and research collaborators will present data highlighting Pliant's lead product candidate PLN-74809 at The Liver Meeting® 2019 hosted by the American Association for the Study of Liver Diseases (AASLD). Pliant is evaluating PLN-74809 in fibrotic diseases with unmet clinical needs, including primary sclerosing cholangitis, a chronic progressive disorder characterized by inflammation and fibrosis of the bile ducts in the liver, and idiopathic pulmonary fibrosis.
"Pliant's preclinical research in sophisticated translational models using human tissue samples from patients with advanced cholestatic liver disease undergoing transplantation continues to validate our integrin-targeting approach to block TGF-β activation in the liver and the resulting cascade that drives fibrosis and the building of scar tissue," said Scott Turner, Ph.D., vice president of translational sciences at Pliant Therapeutics. "Our goal is to advance PLN-74809 into Phase 2a clinical trials for the treatment of primary sclerosing cholangitis in the first half of 2020, leveraging the safety data from over 80 study participants treated with PLN-74809 to date."
Details for the poster presentation at The Liver Meeting are as follows:
Poster Title: PLN-74809 A Dual αvβ6 αvβ1 Integrin Inhibitor Inhibits Fibrosis in Precision Cut Liver Tissue from PSC and PBC Patients and the MDR2 Knock Out Mouse (Abstract #1308)
Authors: S. Turner, M. Decaris, S. Ho, C. Chen and J. Schaub
Session: PBC/PSC and Other Cholestatic Diseases
Date & Time: Saturday, November 9, 2019, 2:00 p.m. ET
Location: Hynes Convention Center, Hall B
- In in vivo studies evaluating PLN-74809, the expression of αVβ6 and αVβ1 was examined in human tissue samples explanted from patients with primary sclerosing cholangitis (PSC) or primary biliary cholangitis (PBC). In addition, the inhibition of αVβ6 and αvβ1 was evaluated in MDR2 knockout mice.
- The study results demonstrate that inhibition of αVβ6 and αVβ1-mediated activation of transforming growth factor beta (TGF-β) reduced collagen gene expression in liver tissue, as well as TGF-β signaling, hepatic collagen and serum bilirubin levels in MDR2 knockout mice. The dual inhibition of the integrins significantly reduced liver fibrosis in the PSC and PBC models.
Pliant's PLN-74809 is being developed for the treatment of patients with idiopathic pulmonary fibrosis and primary sclerosing cholangitis. The orally available small molecule is designed as a dual selective inhibitor of the tissue-specific αVβ6 and αVβ1 integrins. Inhibiting these two integrins is expected to decrease the activation of TGF-β, a putative master regulator of fibrosis. Demonstrating human proof-of-biological mechanism in a Phase 1b clinical trial, PLN-74809 was shown to inhibit TGF-β activation by up to 70% in alveolar macrophages collected from healthy volunteers. The effect was observed in a dose- and exposure-dependent manner. PLN-74809 was also shown to be well tolerated and well absorbed orally, with a half-life potentially supporting once-daily dosing. PLN-74809 has initiated Phase 2a trials in patients suffering from IPF.
About Pliant Therapeutics
Pliant Therapeutics is a clinical stage biopharmaceutical company focused on discovering and developing novel therapies for the treatment of fibrosis. Pliant seeks to slow or halt the progression of multiple life-threatening fibrotic diseases by developing targeted treatments. The company's lead product candidate, PLN-74809, is designed to be a selective inhibitor of αvβ1 and αvβ6 integrins that play a key role in multiple fibrotic pathways. PLN-74809 has received Orphan Drug Designation from the U.S. Food and Drug Administration in both idiopathic pulmonary fibrosis (IPF) and primary sclerosing cholangitis (PSC), has completed Phase 1b testing. Pliant's second product candidate, PLN-1474, is designed to be an oral, small molecule selective inhibitor of αvβ1, targeting late-stage liver fibrosis and is partnered with Novartis. For more information, please visit www.pliantrx.com.
SOURCE Pliant Therapeutics, Inc.