Pliant Therapeutics, Inc. announced that the U.S. Food and Drug Administration (FDA) has cleared the company's Investigational New Drug (IND) application for PLN-101095, an oral, small molecule, dual selective inhibitor of integrins avß8 and avß1. A Phase 1 first-in-human study evaluating PLN-101095 in patients with solid tumors that are resistant to immune checkpoint inhibitors (ICIs) is expected to initiate in the second quarter of 2023. PLN-101095 is an oral, small molecule, dual selective inhibitor of avß8 and avß1 integrins in development for the treatment of solid tumors resistant to immune checkpoint inhibitors. TGF-ß plays an important anti-inflammatory role in the tumor micro-environment, promoting fibrosis, preventing T-cell infiltration and inhibiting the release of pro-inflammatory cytokines.

Increased TGF-ß signaling is recognized as a potential cause of resistance to checkpoint inhibitors, such as anti-PD-(L)1 therapies, seen in many tumors. PLN-101095 targets avß8 and avß1 integrins expressed in the tumor microenvironment, regulating TGF-ß activation with the goal of re-sensitizing tumors to PD(L)-1 inhibitors. The Phase 1 study will assess the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary antitumor activity of PLN-101095.

Additional details will be disclosed upon trial initiation.