PLN-74809, the company’s lead candidate, is a small molecule that selectively inhibits both alphaVβ1 and αVβ6 integrins. These proteins mediate cell adhesion and are specific for tissues implicated in fibrosis (scarring), such as epithelial tissue.
By blocking these integrins, PLN-74809 is expected to prevent the activation of TGF-beta, a pro-fibrotic molecule that controls important cellular mechanisms, including cell differentiation and growth.
Preclinical studies in animal models showed that PLN-74809 prevented the growth of fibrotic tissue in the lung by blocking TGF-beta.
The randomized, double-blind, placebo-controlled Phase 1 trial an will include about 90 healthy people. Its main goal is to evaluate the safety and tolerability of PLN-74809 after a single dose, and again after 14 days of dosing, the company reported.
The trial will also address pharmacokinetics and biomarkers associated with the activity of the αVβ6 and αVβ1 integrins. Pharmacokinetics is the study of a compound’s absorption, distribution, metabolism, and excretion in the body.
“Based on positive preclinical studies, and shortly after submitting our first investigational new drug application, Pliant’s first-in-human trial for PLN-74809 is underway and will inform further development of our novel, proprietary compound for the potential treatment of patients with idiopathic pulmonary fibrosis,” Éric Lefebvre, MD, Pliant’s chief medical officer, said in a press release.
Lefebvre added that the trial’s results will also help guide the development of PLN-74809 in other diseases where integrins and TGF-beta are crucial drivers of fibrosis, such as primary sclerosing cholangitis. This chronic, progressive disorder is characterized by inflammation and fibrosis in the bile ducts, which connect the liver to the small intestine.
PLN-74809 was designated orphan drug by the U.S. Food and Drug Administration for IPF and primary sclerosing cholangitis in August 2018. This designation provides fiscal incentives to promote investment and quicken the clinical development of possible therapies for rare diseases.
Pliant Therapeutics, a California-based company, was launched in 2016 following a financing round of $45 million raised by Third Rock Ventures. Pliant raised $62 million in a second round of financing in July 2018, which is expected to further help in the advancement of therapies for fibrotic diseases.