Safety and tolerability of bexotegrast in Phase 2 trials of idiopathic pulmonary fibrosis (IPF) and primary sclerosing cholangitis (PSC)

<bold>Background:</bold> Bexotegrast (BEXO), an oral, once-daily, dual-selective inhibitor of integrins αvβ6 and αvβ1, has been studied in >700 participants from Phase 1 and Phase 2 trials in IPF and PSC <bold>Objectives:</bold> We report integrated safety and tolerability results from Phase 2 trials in IPF (INTEGRIS-IPF; <ext-link>NCT04396756</ext-link>) and PSC (INTEGRIS-PSC; <ext-link>NCT04480840</ext-link>) in which BEXO was administered for ≥12 weeks. <bold>Methods:</bold> Participants with IPF or PSC received BEXO 40 mg, 80 mg, 160 mg, 320 mg or placebo (PBO). We report safety and tolerability data (≤40 weeks in the 320-mg arm) and adverse event (AE) frequency and severity. <bold>Results:</bold> The IPF safety population (BEXO, n=88; PBO, n=31) was 84% male and 97% White, with a median (range) age of 71.6 (54-87) years. The PSC safety population (BEXO, n=90; PBO, n=30) was 69% male and 87% White, with a median (range) age of 45.2 (18-71) years. The most common AEs (BEXO/PBO) were diarrhea (12.8%/6.6%), fatigue (10.6%/9.8%), nausea (6.1%/4.9%), COVID-19 (6.1%/4.9%) and headache (5.0%/9.8%). Most diarrhea events were mild or moderate and occurred in participants with IPF treated with BEXO and nintedanib, which is associated with diarrhea. Seven (3.9%) and 3 (4.9%) BEXO- and PBO-treated participants had serious AEs (SAEs); none were related to BEXO. One death occurred in the IPF trial and was considered unrelated to BEXO. There was no overall dose relationship for any AEs in IPF or PSC. <bold>Conclusions:</bold> Bexotegrast was generally well tolerated in Phase 2 trials ≥12 weeks, with no related SAEs. Most AEs were mild to moderate, and discontinuation rates were low. Late-stage evaluation is currently underway in the BEACON-IPF study (<ext-link>NCT06097260</ext-link>).