Pliant Therapeutics Presents Preclinical Data in NASH and PSC at The Liver Meeting 2018

SOUTH SAN FRANCISCO, Calif., Nov. 9, 2018 /PRNewswire/ -- Pliant Therapeutics, Inc., a biotechnology company unraveling and targeting the key biological pathways driving fibrosis, today announced company scientists and research collaborators will present in vivo data highlighting Pliant's clinical product candidates in two posters at The Liver Meeting® 2018 hosted by the American Association for the Study of Liver Diseases (AASLD). Leveraging its discovery engine, Pliant is advancing small-molecule, tissue-specific integrin inhibitors that modulate transforming growth factor beta (TGF-?), a key regulator of physiological healing and pathologic fibrosis.

"Our research continues to support the potential of our approach of integrin inhibition to treat fibrosis in a variety of liver diseases, including nonalcoholic steatohepatitis and primary sclerosing cholangitis," said Scott Turner, Ph.D., vice president of translational sciences at Pliant Therapeutics. "We continue to increase our understanding of the molecular drivers of fibrotic liver diseases and evaluating these drivers in translational models to inform our selection of product candidates to take into the clinic."

Details for the two poster presentations at The Liver Meeting are as follows:

Poster Title:  Targeted Disruption of TGF-? Activation By an ?V?1 Integrin Inhibitor Significantly Reduces Liver Fibrosis in CCl4 Mouse Model (Presentation 1104)
Authors:  S. Turner, M. Decaris, G. Lee, S. Martin, C. Chen, E. Lefebvre, M. Rexhepaj, P. Kotak, L. Hooi, K.  Leftheris, J. Cha, J. Jiang, P. Andre
Date & Time:  Saturday, November 10, 2018, 2:00 p.m. to 7:30 p.m. PT
Session:  Liver Fibrogenesis and Non-Parenchymal Cell Biology
Summary:

• Few investigational compounds for nonalcoholic steatohepatitis (NASH) are directly targeting fibrosis. Pliant has identified an orally available, small-molecule compound for inhibition of ?_V?₁ mediated TGF-? activation. Given the integrin ?_V?₁ has been proposed as master regulator of TGF-? activation and hepatic fibrogenesis, Pliant tested the antifibrotic activity of ?_V?₁ inhibition in CCl₄ injured BALB/c mice.
• The study results presented by Dr. Turner demonstrated an inhibition of ?_V?₁-mediated activation of TGF-? significantly reduced CCl₄-induced liver fibrosis, warranting further evaluation.

Poster Title: A Novel Selective Small Molecule Inhibitor of avb6 Integrin Safely Prevents Pre-Established Biliary Fibrosis in Balbc.Mdr2-/- Mouse Model (Presentation 1109)
Authors:  Y. Lin, K. Vaid, P. Andre, S. Turner, J. Jiang, J. Cha, Y. Popov
Date & Time:  Saturday, November 10, 2018, 2:00 p.m. to 7:30 p.m. PT
Session:  Liver Fibrogenesis and Non-Parenchymal Cell Biology
Summary:

• Yury Popov, M.D., Ph.D., assistant professor of medicine, division of gastroenterology, Beth Israel Deaconess Medical Center at Harvard Medical School, and collaborators evaluated three novel, small molecule ?_V?₆ integrin inhibitors in a mouse model of primary sclerosing cholangitis (PSC):
• PLN-1177, a pan RGD integrin inhibitor;
• PLN-1561, an ?_V?₆/?_V?₁ dual inhibitor;
• PLN-1705, an ?_V?₆ selective inhibitor.
• All three compounds significantly reduced serum total bilirubin and inhibited biliary fibrosis as assessed both histologically and biochemically through hepatic collagen levels, with the selective inhibitors having the most potent effects.
• Pan RGD integrin inhibitors may present previously unanticipated risks of exacerbated inflammation in the setting of cholestatic liver disease.
• The study concluded that partial inhibition of ?_V?₆ is sufficient to potently reduce fibrosis, and that pan RGD integrin inhibitors may present previously unanticipated risks of exacerbated inflammation in the setting of cholestatic liver disease.

About Pliant Therapeutics
Pliant Therapeutics is a biotechnology company unraveling and targeting the key biological pathways driving fibrosis. By leveraging its powerful product discovery engine, Pliant's mission is to develop novel therapeutics that seek to halt progression of fibrotic diseases, ultimately preserving organ function. Founded by a group of seasoned experts in fibrosis biology, medicinal chemistry and translational medicine, Pliant expects to initiate clinical trials with its lead product candidate PLN-74809 in idiopathic pulmonary fibrosis in late 2018, with additional programs to advance into the clinic in 2019. For more information, please visit www.pliantrx.com.

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SOURCE Pliant Therapeutics, Inc.