Abstract: PUB327
Using a Human Decedent Model to Elucidate the Mechanism of Action of Rilparencel, an Investigative Autologous Renal Cell Therapy for the Treatment of CKD
Session Information
Category: Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)
- 2000 Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)
Authors
- Zanoni, Francesca, NYU Langone Transplant Institute, New York, New York, United States
- Stavas, Joseph, ProKidney LLC, Winston-Salem, North Carolina, United States
- Bruce, Andrew T., ProKidney LLC, Winston-Salem, North Carolina, United States
- Culleton, Bruce F., ProKidney LLC, Winston-Salem, North Carolina, United States
- Keating, Brendan, NYU Langone Transplant Institute, New York, New York, United States
- Montgomery, Robert Avery, NYU Langone Transplant Institute, New York, New York, United States
- Conway, Anthony, ProKidney LLC, Winston-Salem, North Carolina, United States
Background
CKD is a global health burden with many patients progressing to end-stage kidney disease (ESKD). Rilparencel, an investigational autologous renal cell therapy, has shown promise in stabilizing kidney function in patients with advanced CKD in Phase 2 studies. A Phase 3 trial called REGEN-006 (NCT05099770) is underway. However, the molecular and cellular mechanisms of rilparencel are not well understood. A recent IRB-approved human decedent model was used at NYU to investigate cellular and molecular changes and deep kidney functional assessment following kidney xenotransplantation and may offer insights into the Mechanism of Action (MoA) of rilparencel.
Methods
The ProKidney-NYU Study will use this decedent model to investigate rilparencel’s MoA. Eligible brain-dead donors (>18 years, eGFR 20-60 mL/min/1.73m^2) will undergo bilateral nephrectomies with external autotransplantation into the pelvis for easy accessibility. The right kidney will be biopsied for rilparencel manufacture (Day 0) followed by cell injection into the same kidney cortex on Day 22 (Fig. 1). Serial bilateral kidney biopsies with paired urine, serum, and blood samples will be collected over 61 days. Multi-omic analyses (spatial transcriptomics, scRNA-Seq, cytometry, spatial proteomics, metabolomics, and lipidomics) will be performed from both treated (right) and control (left) kidneys.
Results
Anticipated results include comparative analyses of multi-omic gene expression, protein abundance and metabolite profiles pre- and post-treatment. Single-cell and spatial datasets will be integrated with histopathological changes. The association of molecular findings with functional clinical outcomes will be assessed throughout the study.
Conclusion
Detailed characterization of rilparencel’s MoA using advanced multi-omic analyses in a decedent model could significantly enhance our understanding of autologous renal cell therapies in CKD treatment.