Post-hoc biomarker analysis in participants with IPF receiving bexotegrast over 12-weeks in INTEGRIS-IPF

<bold>Rationale:</bold> Biomarkers of early therapeutic response are needed to inform drug development in idiopathic pulmonary fibrosis (IPF). Here we used proteomic screening to assess longitudinal changes in plasma protein levels in participants with IPF receiving bexotegrast, a dual-selective inhibitor of TGF-β-activating integrins α_Vβ₆ and α_Vβ₁ shown to reduce forced vital capacity (FVC) decline in participants with IPF over 12 weeks (Wuyts, W. et al. ERS Int Conf 2023, #42463), to identify candidate biomarkers of therapeutic response. <bold>Methods:</bold> Plasma samples from INTEGRIS-IPF (<ext-link>NCT04396756</ext-link>) collected at baseline, Week 4 and Week 12 were analyzed by Olink Explore 384 Inflammation panel. Pairwise comparisons and mixed effects model for repeated measures (MMRM) were used to assess differences in protein levels at baseline, between treatment groups across time, and to correlate protein levels with % predicted FVC (FVCpp). <bold>Results:</bold> Pairwise comparison of plasma proteins showed minimal differences between bexotegrast and placebo groups at baseline, with a downward shift in most proteins observed with bexotegrast relative to placebo at Weeks 4 and 12. MMRM analysis showed a significant difference in change from baseline for 13 proteins for bexotegrast (320 mg QD) vs placebo (FDR<0.05), with approximate dose-dependent differences observed for ITGB6, MMP10, PLAUR, and SPON1. Nine proteins were also found to significantly associate with longitudinal changes in FVCpp (FDR<0.05). <bold>Conclusions:</bold> Thirteen candidate biomarkers of early therapeutic response were identified in participants with IPF receiving bexotegrast. Further biomarker analyses are planned in the enrolling Phase 2b BEACON-IPF study (<ext-link>NCT06097260</ext-link>).