Abstract: FR-PO1156
Phase 3 Clinical Candidate Rilparencel Demonstrates Weak Association with Renal Epithelial Senescence-Associated Secretory Phenotype
Session Information
- CKD: Kidney Function and Extrarenal Complications
October 25, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2302 CKD (Non-Dialysis): Clinical, Outcomes, and Trials
Authors
- Rohlfing, Mark A., ProKidney LLC, Morrisville, North Carolina, United States
- Greenawalt, Ashley, ProKidney LLC, Morrisville, North Carolina, United States
- Bauer, Brooke, ProKidney LLC, Morrisville, North Carolina, United States
- Bruce, Andrew T., ProKidney LLC, Morrisville, North Carolina, United States
- Justewicz, Dominic Mark, ProKidney LLC, Morrisville, North Carolina, United States
Background
CKD is associated with an enhanced senescence-associated secretory phenotype (SASP) and high inflammation, which can induce senescence. This study evaluated the renal epithelial SASP of rilparencel. Biopsy-derived rilparencel is a first-in-class autologous renal epithelial cell product in Phase 3 clinical trials for patients with T2D and CKD. Data from two Phase 2 clinical trials suggest that cortical administration of rilparencel potentially stabilizes estimated glomerular filtration rate (eGFR).
Methods
rilparencel manufactured from kidney biopsies of each of 5 patients with T2D and CKD (NCT02836574) was submitted for scRNA-seq, and 52 differentially expressed genes (DEGs) were evaluated for this study. Additionally, for each patient, proteins secreted by rilparencel were compared to proteins secreted from a manufacturing precursor to rilparencel (Intelliflex). Fifty-one secreted proteins and 52 DEGs were seeded into the SASP atlas, a proteomic analysis of renal epithelial cells 10 days post-irradiation (PMID:31945054), to determine if any are associated with a renal epithelial SASP. As comparison, IGFBP2 and CXCL8, senescence markers known to be elevated in CKD, were used as positive controls.
Results
Of the secreted proteins and DEGs associated with rilparencel, only PTER (a DEG) was identified as being secreted by renal epithelial cells according to the SASP atlas. The SASP atlas reports that PTER protein expression is approximately 2-fold less than IGFBP2 and CXCL8, which serve as positive SASP controls for comparison (A). Additionally, rilparencel secretes reduced levels of proinflammatory cytokines compared to an earlier stage in the product manufacture (B), which also suggests a reduced senescence phenotype.
Conclusion
Our proprietary manufacturing process generates a renal epithelial cell-based product (rilparencel) from renal cortex tissue with a low SASP, which may in part underlie its therapeutic activity in the clinic.
Funding
- Commercial Support – ProKidney LLC