SOUTH SAN FRANCISCO, Calif., March 28, 2019 /PRNewswire/ -- Pliant Therapeutics, Inc., a biotechnology company focused on discovering, developing and commercializing treatments for fibrotic diseases, today announced the presentation of in vivo data highlighting product candidate PLN-1474 for fibrotic liver diseases in an oral presentation at The International Liver Congress™ 2019 hosted by the European Association for the Study of the Liver (EASL). Pliant is advancing towards human studies its small-molecule selective inhibitor of the integrin αvβ1 to decrease the activation of transforming growth factor beta (TGF-β), a key regulator of pathologic fibrosis. The company's PLN-1474 program is targeting late-stage liver fibrosis (i.e., F3/F4) associated with nonalcoholic steatohepatitis (NASH).
"Up to now, only modest improvements in liver fibrosis stage or severity have been reported with investigational compounds evaluated in patients with nonalcoholic steatohepatitis. We believe that directly targeting the TGF-β activation pathway via integrin inhibition holds the potential to provide more clinically meaningful antifibrotic benefits and ultimately prevent disease progression to cirrhosis and liver-related complications," said Éric Lefebvre, M.D., chief medical officer of Pliant Therapeutics. "Our research continues to generate compelling preclinical evidence that supports PLN-1474 as a clinical candidate and validates our approach of αvβ1 integrin inhibition to treat advanced liver fibrosis associated with NASH. We look forward to advancing PLN-1474 into the clinic and plan to submit an investigational new drug application in the fourth quarter of this year."
Details for the oral presentation at The International Liver Congress are as follows:
Poster Title: Targeted Disruption of TGF-β Activation By an αvβ1 Integrin Inhibitor Significantly Reduces Liver Fibrosis in CCl4 Mice and Human NASH Liver Slices (PS-091)
Johanna Schaub, Martin Decaris, Maureen Reilly, Gail Lee, Shamra Martin, Vikram Rao, Chun Chen, Megi Rexhepaj, Perna Kotak, Lisa Hooi, Katerina Leftheris, Jake Cha, Irene Lepist, Patrick Andre, Scott Turner
Date & Time: Friday, April 12, 2019, 16:30 p.m. - 16:45 p.m. CET
Session: Liver Fibrosis
- In previous studies, Pliant's selective small molecule inhibitor showed efficacy in the CCl4 mouse models of fibrosis and suggested a prominent role of αvβ1 in TGF-β activation in liver fibrosis.
- In further in vivo studies, inhibition of αvβ1 was evaluated in a model of precision cut liver slices from CCl4-treated mice and explanted human cirrhotic liver tissue.
- The study results, presented by Scott Turner, Ph.D., vice president of translational sciences at Pliant Therapeutics, demonstrate a significant reduction in SMAD3 phosphorylation (a marker of TGF-β activation), fibrotic gene expression and liver collagen content.
About Pliant Therapeutics
Pliant Therapeutics is a clinical stage biotechnology company targeting the key biological pathways driving fibrosis. Pliant has leveraged its powerful product discovery engine to develop a portfolio of novel therapeutics that seek to halt progression of multiple life-threatening fibrotic diseases. The company's lead product candidate, PLN-74809, is a selective inhibitor of αvβ1 and αvβ6 integrin receptors that play a key role in multiple fibrotic pathways. PLN-74809 has received Orphan Designation from the FDA in both idiopathic pulmonary fibrosis and primary sclerosing cholangitis, and is being studied in an ongoing Phase 1 clinical trial. Pliant's second product candidate, PLN-1474, is a selective inhibitor of αvβ1, targeting late-stage liver fibrosis and is currently in IND-enabling studies. For more information, please visit www.pliantrx.com.
SOURCE Pliant Therapeutics, Inc.