The INTEGRIS-IPF clinical trial evaluated the safety, tolerability, and efficacy of bexotegrast (PLN-74809) in patients with idiopathic pulmonary fibrosis (IPF). Bexotegrast is an oral, once-daily investigational drug designed to block the activation of transforming growth factor β (TGF-β) by preventing integrins αvβ6 and αvβ1 from binding to the arginine-glycine-aspartate sequence of latent TGF-β. The Phase-2a, multicenter, randomized, double-blind, placebo-controlled trial included participants with IPF who were randomized to receive bexotegrast at doses of 40 mg, 80 mg, 160 mg, or 320 mg, or placebo, with or without background IPF therapy (pirfenidone or nintedanib). The primary endpoint was the incidence of treatment-emergent adverse events (TEAEs), while exploratory efficacy endpoints included changes in forced vital capacity (FVC), quantitative lung fibrosis (QLF) extent (%), and changes in fibrosis-related biomarkers. Key findings included: - Bexotegrast was well tolerated, with similar rates of TEAEs in the pooled bexotegrast and placebo groups (69.7% vs. 67.7%, respectively). - Diarrhea was the most common TEAE, primarily observed in participants receiving nintedanib background therapy. - Participants treated with bexotegrast experienced a reduction in FVC decline over 12 weeks compared to those receiving placebo, with or without background therapy. - A dose-dependent antifibrotic effect was observed, as indicated by QLF imaging and decreases in fibrosis-associated biomarkers (ITGB6 and PRO-C3). The study concluded that bexotegrast demonstrated a favorable safety and tolerability profile up to 12 weeks, with exploratory analyses suggesting an antifibrotic effect. Further studies are needed to confirm these findings and evaluate the long-term benefits of bexotegrast in treating IPF.The INTEGRIS-IPF clinical trial evaluated the safety, tolerability, and efficacy of bexotegrast (PLN-74809) in patients with idiopathic pulmonary fibrosis (IPF). Bexotegrast is an oral, once-daily investigational drug designed to block the activation of transforming growth factor β (TGF-β) by preventing integrins αvβ6 and αvβ1 from binding to the arginine-glycine-aspartate sequence of latent TGF-β. The Phase-2a, multicenter, randomized, double-blind, placebo-controlled trial included participants with IPF who were randomized to receive bexotegrast at doses of 40 mg, 80 mg, 160 mg, or 320 mg, or placebo, with or without background IPF therapy (pirfenidone or nintedanib). The primary endpoint was the incidence of treatment-emergent adverse events (TEAEs), while exploratory efficacy endpoints included changes in forced vital capacity (FVC), quantitative lung fibrosis (QLF) extent (%), and changes in fibrosis-related biomarkers. Key findings included: - Bexotegrast was well tolerated, with similar rates of TEAEs in the pooled bexotegrast and placebo groups (69.7% vs. 67.7%, respectively). - Diarrhea was the most common TEAE, primarily observed in participants receiving nintedanib background therapy. - Participants treated with bexotegrast experienced a reduction in FVC decline over 12 weeks compared to those receiving placebo, with or without background therapy. - A dose-dependent antifibrotic effect was observed, as indicated by QLF imaging and decreases in fibrosis-associated biomarkers (ITGB6 and PRO-C3). The study concluded that bexotegrast demonstrated a favorable safety and tolerability profile up to 12 weeks, with exploratory analyses suggesting an antifibrotic effect. Further studies are needed to confirm these findings and evaluate the long-term benefits of bexotegrast in treating IPF.