Phase 3 Clinical Candidate Rilparencel Demonstrates Distinct Secretomic Signatures at Key Points in Manufacturing, Suggesting a Reduced Inflammatory and Fibrotic Profile

Background: Kidney cortical biopsy-derived rilparencel is a first-in-class autologous kidney epithelial cell platform in Phase 3 clinical trials for patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). Data from two Phase 2 studies suggests that kidney cortical injection of rilparencel may preserve organ function as measured by estimated glomerular filtration rate (eGFR). T2D and CKD are associated with inflammation and tissue fibrosis. In a small pilot proof-of-concept study, we sought to characterize how the rilparencel secretome may facilitate kidney repair and restoration. Methods: In a subset (NCT02836574) of 5 patients with T2D and CKD, conditioned-medium (CM, 24 hr) was collected from 2 stages, early and final product/rilparencel, during the manufacturing process. The CM was queried for 51 secreted inflammatory and fibrotic markers (Luminex xMAP, Intelliflex) whose expression levels were used to generate principal component analysis (PCA) plots. Results: Secretomes exhibited distinct clustering with a secretory profile of reduced levels of inflammatory and fibrotic markers in rilparencel CM vs. early-stage CM. Conclusion: This small pilot study suggests that our manufacturing process results in a product, rilparencel, that secretes reduced inflammatory and fibrotic markers, which may in part underlie its reparative and restorative activity. Secretomic profiling may also inform a potency assurance strategy for rilparencel. Funding: Commercial Support - ProKidney LLCPCA plot, based on inflammatory and fibrotic secretory markers, demonstrates distinct clusters between early-stage CM (red) and final-stage/rilparencel CM (blue).