Seralutinib shows significant anti-fibrotic effects: evidence from patient-derived models

Background : Fibrosis contributes to both pulmonary vascular and parenchymal remodeling in pulmonary hypertension (PH) and interstitial lung disease (ILD). Seralutinib is a potent inhaled PDGFRα/ß, CSF1R and c-KIT kinase inhibitor in clinical development for PAH and PH-ILD. In the phase 2 TORREY study (NCT04456998) in Group 1 PH patients, seralutinib decreased circulating fibrotic biomarkers, including collagen 1a1. Objective : To test whether seralutinib inhibits established fibrosis in idiopathic pulmonary fibrosis (IPF) patient-derived precision-cut lung slices (PCLS) and lung fibroblasts (HLF). Methods : PCLS from two IPF patient donors were cultured and treated for 4 days with vehicle, seralutinib (0.1-10μM), or nintedanib (1μM). Supernatants were collected and pro-fibrotic markers evaluated. The antifibrotic effect was also studied in IPF patient-derived lung fibroblasts with the same treatments. Statistical significance was determined by one-way ANOVA with nominal p