Pliant Therapeutics has successfully completed a Phase 1 clinical study assessing its investigational therapy PLN-74809 for idiopathic pulmonary fibrosis (IPF), with results supporting further clinical development of the compound.
PLN-74809 is an oral small molecule that selectively inhibits integrins (signaling receptors) called αVβ6 and αVβ1. Results from earlier preclinical studies in animal models showed that inhibition of integrins by PLN-74809 blocked the activation of the profibrotic signaling-molecule TGF-β in the lung, and prevented the growth of fibrotic (scar) tissue.
The randomized, double-blind, placebo-controlled Phase 1 trial showed the therapy’s good bioavailability (its absorbance) and pharmacokinetics (route inside the body) in 71 healthy volunteers, treated with 10 to 75 mg of PLN-74809, administered once daily for 14 days.
Results also showed that PLN-74809 was well-tolerated, and that its long half-life supported a once-daily dosing regimen.
“Less than six months after initiating our first-in-human study evaluating PLN-74809, we’re pleased to report that the compound has a favorable safety, tolerability and pharmacokinetic profile, which warrants advancing it to the next stage of development,” Éric Lefebvre, MD, chief medical officer of Pliant Therapeutics, said in a press release.
“We are now progressing with Phase 1b evaluation of PLN-74809 to assess its effects on TGF-β activation … and plan to initiate our Phase 2a program in IPF patients in the second half of 2019,” Lefebvre added.
One of the presentations highlights research sponsored by Pliant, which supports measuring αVβ6 integrin for non-invasive diagnosis, prognosis, and assessment of interstitial lung disease, such as IPF. In other presentations, researchers will show the impact of PLN-74809 on fibrosis in both mouse and human tissue models of IPF.
The U.S. Food and Drug Administration designated PLN-74809 an orphan drug in August last year to advance and speed the inhibitor’s development as a potential treatment for IPF. Pliant also expects to test the small molecule in other diseases associated with fibrosis, including primary sclerosing cholangitis, a chronic progressive disorder in the liver.