Pliant Therapeutics Raises $100M to Develop Therapies for Fibrotic Diseases

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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financing PLN-74809

Pliant Therapeutics has raised $100 million in Series C financing that will support the clinical development of PLN-74809, a candidate therapy for idiopathic pulmonary fibrosis (IPF) and primary sclerosing cholangitis (PSC), a liver disease characterized by progressive inflammation and fibrosis of the bile ducts.

The funding will also be used to support ongoing drug discovery research projects for other fibrotic diseases.

The company previously raised $45 million in Series A, and $62 million in Series B financing.

Specifically, Pliant is focused on the development of fibrotic tissue-specific inhibitors of integrins and of the TGF-beta pathway. Integrins are a class of proteins involved in the adhesion of cells to each other and to a substrate, and have been suggested as drivers in fibrosis development. TGF-beta is a key regulator of physiological healing and fibrosis.

Pliant’s lead candidate, PLN-74809, is a small molecule capable of inhibiting both the αvβ1 and αvβ6 integrins, and subsequently block the activation of the TGF-beta pathway.

Pre-clinical studies showed that inhibition of TGF-beta activation by PLN-74809 prevents and/or possibly reverses the growth of fibrotic tissue within the lung and liver.

In a previous Phase 1a study, results showed that the therapy was well-tolerated in healthy volunteers receiving 10 to 75 mg of PLN-74809, with its stability in the body potentially supporting once-daily dosing.

In a following Phase 1b study, researchers compared two PLN-74809 doses — 20 mg and 40 mg — to a placebo, given over seven days to 18 healthy volunteers. Results showed that all participants who achieved the targeted blood exposure levels of PLN-74809 after seven days experienced a 50% or greater reduction in TGF-beta activation compared to before the treatment. As for safety, only mild adverse events were observed, and no treatment-related side effects were reported.

A Phase 2a trial (NCT04072315) will test PLN-74809 in different dosing schemes — single dose, seven-day dosing, and 28-day dosing — in patients with IPF. The trial will be conducted at Stanford Medical Center and is currently looking for participants. More information is available on the trial’s page here.

PLN-74809 was granted orphan drug designation by the U.S. Food and Drug Administration in August 2018 for the treatment of IPF. Orphan designation provides companies exploring therapies for rare diseases with fiscal incentives that are meant to promote investment in them, and to possibly speed their arrival to patients.

The investment in Series C financing was led by Novartis, with the support of multiple new investors, including Redmile Group, Farallon Capital Management, Cormorant Asset Management, Surveyor Capital, and Logos Capital joining the round as new investors. Previous investors participating in the financing included Eventide Asset ManagementCowen Healthcare Investments, Schroder Adveq, Menlo Ventures, S-Cubed Capital, Agent Capital, and undisclosed institutional investors.

“Our team is proud to have the support and strategic expertise provided by this group of world-class investors to help us achieve our vision of developing transformative medicines for patients living with devastating fibrotic diseases,” Bernard Coulie, MD, PhD, president and CEO of Pliant Therapeutics, said in a press release.

“This financing will support the continued clinical development of our lead product candidate in IPF and PSC, as well as our continued strategy to build our pipeline of proprietary product candidates for a wide range of other fibrotic diseases,” he  said.