Late Breaking Abstract - Bexotegrast reduces type 1 collagen deposition in participants with idiopathic pulmonary fibrosis (IPF) after 12 weeks of therapy

<bold>Background:</bold> Bexotegrast (BEXO, PLN-74809) is an oral, once-daily, dual-selective inhibitor of α_vβ₆ and α_vβ₁ integrins in development for treatment of IPF (BEACON-IPF; <ext-link>NCT06097260</ext-link>). <bold>Objectives:</bold> We report 12-week results in the first interventional Phase 2a study (<ext-link>NCT05621252</ext-link>) evaluating type 1 collagen deposition in the lungs of participants (pts) with IPF. <bold>Methods:</bold> Pts were randomized to BEXO 160 mg or placebo (PBO) for 12 weeks and underwent positron emission tomography (PET) with ⁶⁸Ga-CBP8, a type 1 collagen probe, and dynamic contrast enhanced magnetic resonance imaging (DCE-MRI). Safety, FVC, cough severity and biomarkers were assessed. <bold>Results:</bold> Ten pts were randomized: BEXO 160 mg (n=7) and PBO (n=3). At Week 12, BEXO had a reduction in the mean (SE) ⁶⁸Ga-CBP8 lung standardized uptake values (SUVs) from baseline vs an increase from baseline with PBO (−0.015 [0.038] vs 0.074 [0.068]); larger changes occurred in the subpleural regions for BEXO (−0.051 [0.056]) vs PBO (0.128 [0.079]). Changes in DCE-MRI peak enhancement and washout rates mirrored SUV changes. BEXO increased mean (SE) FVC vs a decrease with PBO over 12 weeks (difference BEXO vs PBO: 106 [90.4] mL). BEXO was well tolerated, and no discontinuations, serious AEs or deaths were reported. BEXO decreased cough severity at all timepoints; antifibrotic effects were observed in circulating biomarkers of collagen synthesis (PRO-C3) and IPF progression (ITGB6). <bold>Conclusions:</bold> ⁶⁸Ga-CBP8 PET detected clear antifibrotic effects and potential lung remodeling with BEXO. BEXO improved FVC, biomarkers of fibrosis, and cough severity, suggesting its potential for disease modification.