What You Need to Know About Pliant

Published: Jan 24, 2017

What You Need to Know About Pliant Therapeutics
January 9, 2017
By Mark Terry, BioSpace.com Breaking News Staff

Pliant Therapeutics focuses on discovering, developing and marketing therapies for fibrotic diseases.

The company uses integrin biology and TGF-beta modulation. Pliant’s science is based on the work of Dean Sheppard, professor of medicine and chief of the Division of Pulmonary, Critical Care, Allergy and Sleep at the University of California, San Francisco (UCSF); Bill DeGrado, professor in the Department of Pharmaceutical Chemistry at UCSF; Hall Chapman, professor of medicine, Division of Pulmonary, Critical Care, Allergy and Sleep, also at UCSF; and Bradley Backes, associate professor in the UCSF Department of Medicine.

The company will be developing a therapy to stop and potentially reverse idiopathic pulmonary fibrosis (IPF). The mechanism of the disease is still unidentified, but it causes thickening and scarring of connective tissue in the lungs.

Sheppard and his fellow scientific co-founders’ research focuses on a family of protein receptors called integrins. Integrins have a significant function in excessive signal activation of TGF-beta.

Working with genetic “knock-out” mice, Sheppard and his team managed to delete all members of the integrin family, called alpha V, which resulted in the prevention of fibrosis in the lungs, liver and kidneys. Further research has been able to selectively target a subset of TGF-beta activity without shutting everything down.

“We and others are trying to identify targets that can stop the progression of fibrosis,” Bernard Coulie, chief executive officer of Pliant, told Forbes. “It may be possible even to reverse it, to regress the fibrosis. Not only do we think we can maintain a patient with a certain amount of lung function, but we may be able to help them improve. That’s our goal.”

Company Leadership
Bernard Couliechief executive officer. Prior to joining Pliant, Coulie was the chief executive officer, chief medical officer and co-founder of ActoGeniX, which was acquired by Intrexon in February 2015. Before ActoGeniX, he held positions at Johnson & Johnson Pharmaceutical Research and Development Europe .

Hans Hullchief business officer. Previously the interim chief executive officer of
Avalanche Biotechnologies , Hull was the chief executive of Orothobond prior to Avalanche.

David Morgansvice president of drug discovery and early development. Before joining Pliant, Morgans served as a consultant for the biopharma industry. Prior to consulting, he had various executive roles at

Patrick Andrevice president of biology. Prior to Pliant, Andre was principal scientist at
Merck Sharpe & Dohme . Before that, he held various positions at Portola Pharmaceuticals .

Randall Halcombvice president of medicinal chemistry. Halcomb was vice president of chemistry at Igenica Biotherapeutics prior to joining Pliant. Before that he held various research positions at
Gilead Sciences most recently as director of medicinal chemistry.

Richard Gasterdirector of translational medicine. Gaster joined
Third Rock Ventures to work on new company formation and due diligence, where he focused on Pliant. Before joining Third Rock he was a resident physician in Harvard’s Plastic and Reconstructive Surgery program.

Company Financing
Pliant launched with $45 million in Series A financing from Third Rock Ventures.

The company is developing small molecule inhibitors that target integrins known to play a key role in TGF-beta activation in disease tissues. It is also developing small molecule inhibitors known to modulate epithelial-to-mesenchymal transition.

Market Competition
Foster City, Calif.-based Gilead Sciences (GILD) recently ended a mid-stage trial of an experimental IPF drug last month after a data-monitoring committee concluded it wasn’t effective. Also, InterMune , acquired by Roche in the fall of 2014, markets one of the only two IPF treatments approved by the U.S. Food and Drug Administration (FDA), Esbriet. Boehringer Ingelheim markets the second drug, Ofev.

Scholar Rock is working to develop compounds that modulate TGF-beta signaling. Morphic Rock is working to develop compounds that target integrins.

What to Look For
The company is currently pursuing drug development programs for a range of fibrotic diseases, focusing on tissue-specific integrin modulation and EMT inhibition. In the next three to find years, Pliant hopes to have at least two programs in clinical phase development targeting fibrotic diseases.

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