Pliant Therapeutics announced that its lead therapy candidate PLN-74809 was designated an orphan drug by the U.S. Food and Drug Administration (FDA), an act that helps to advance its development as a possible treatment of idiopathic pulmonary fibrosis (IPF).
Pliant intends to move PLN-74809 into clinical trials in IPF patients early in 2019.
Orphan designation provides companies exploring possible therapies for rare disease with fiscal incentives that are meant to promote investment in them, and to possibly speed their arrival in the clinic.
“Achieving this important regulatory milestone provides Pliant an early vote of confidence as we prepare our investigational new drug application and plan the first-in-human trials for PLN-74809,” Éric Lefebvre, chief medical officer of Pliant, said in a company press release.
“We are eager to initiate clinical development of this product candidate early next year as a potential treatment option for patients with IPF,” Lefebvre added.
Pliant’s product pipeline focuses on tissue-specific inhibitors to treat a range of fibrotic diseases affecting different organs, including the lungs (IPF) and liver (non-alcoholic steatohepatitis, cirrhosis, and primary sclerosing cholangitis).
The company’s approach consists in developing inhibitors that target two key players of the fibrotic process — integrins, proteins that mediate cell adhesion, and TGF-β signaling, a major regulator of physiological healing and disease-related fibrosis.
Its lead compound, PLN-74809, is a small molecule that works as a dual selective inhibitor of the αVβ1 and αVβ6 integrins.
By modulating integrins specific to tissues implicated in fibrosis, such as epithelial tissue, the compound aims to blocks the activation of TGF-β, preventing the growth of fibrotic tissue within organs.
Preclinical studies in animal models of disease that were treated with PLN-74809 showed promise. The treatment was seen to regulate the activity of integrins which, in turn, selectively blocked the action of TGF-β, preventing the growth of scar tissue within the lungs and liver.
This strategy, targeting TGF-β in a tissue-specific manner, offers advantages over targeting TGF-β broadly, Pliant states. It maximizes the products therapeutic effects while avoiding systemic side effects.
The company is also developing selective inhibitors of a cellular process called epithelial-to-mesenchymal-transition (EMT), a main driver of inappropriate tissue scarring (fibrosis).
Pliant is a California-based biotech start-up, founded by experts in fibrosis biology and medicinal chemistry. It was launched in 2016 following a financing round of $45 million raised by Third Rock Ventures.