PLN-104

PLN-104 is a selective small molecule inhibitor of integrin alpha-V beta-1 (αVβ1), developed by Pliant Therapeutics. It is designed to target the TGF-β signaling pathway by preventing the αVβ1-mediated activation of latent TGF-β, which is a key driver of stromal reprogramming, immunosuppression, and fibrogenesis in the tumor microenvironment. In preclinical studies, particularly in patient-derived models of metastatic pancreatic ductal adenocarcinoma (PDA), PLN-104 has demonstrated significant anti-tumor activity, both as a monotherapy and in combination with standard-of-care chemotherapies like gemcitabine and nab-paclitaxel (Abraxane). By selectively blocking αVβ1, the drug aims to disrupt the pro-tumorigenic crosstalk between malignant and stromal cells, potentially overcoming resistance to immunotherapy and reducing metastatic spread in aggressive cancers.