The novel angiotensin II type 2 receptor agonist buloxibutid improves lung function in IPF compared to real-world external IPF control arms

<bold>Background:</bold> Buloxibutid (C21) is an oral, selective angiotensin II type 2 receptor agonist, which drives upstream repair pathways in idiopathic pulmonary fibrosis (IPF) that improve alveolar epithelial type 2 cell survival and surfactant production, reduces fibrosis, and resolves vascular remodeling. AIR was an open-label phase 2a trial of buloxibutid 100 mg BID in 52 treatment-naïve participants with IPF. An FVC increase from baseline by 216 mL (90% CI 37, 395) was observed at 36 weeks. Aims and Objectives: To explore the robustness of the findings in AIR, external treatment-naive matched synthetic control arms were created using real-world IPF data on the Qureight platform. <bold>Methods:</bold> Trial participants (n=48) were matched 1:1 with external controls based on FVC % predicted and FEV1/FVC. Analyses were conducted using conservative imputation for missing data (n=48) and on observed data (n=28 at week 36). <bold>Results:</bold> The mean estimated differences in FVC change from baseline to week 36 between buloxibutid and external control arms on imputed and observed data were 146.0 and 302.1 mL, respectively. <fig><object-id>erj;66/suppl_69/OA1249/F1</object-id><object-id>F1</object-id><object-id>F1</object-id><graphic></graphic></fig> <bold>Conclusions:</bold> FVC improvement during treatment with buloxibutid differed from the real-world treatment-naive FVC decline in severity matched patients. This is consistent with the proposed mechanism of action of buloxibutid, indicating its potential for IPF disease modification.