Abstract: TH-PO0822
Model-Based Assessment of Clinical Responses to A Proliferation-Inducing Ligand (APRIL) Blockade Informing Development of the Anti-APRIL Monoclonal Antibody JADE101 in IgAN
Session Information
- Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)
- 1900 Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)
Authors
- Gufford, Brandon T., Jade Biosciences, San Francisco, California, United States
- DeVries, Todd, Jade Biosciences, San Francisco, California, United States
- Tong, Vincent W., Jade Biosciences, San Francisco, California, United States
- Lewis, Sandy, Jade Biosciences, San Francisco, California, United States
- Li, Li, Jade Biosciences, San Francisco, California, United States
- Filbert, Erin L., Jade Biosciences, San Francisco, California, United States
- King, Andrew J., Jade Biosciences, San Francisco, California, United States
Background
IgA nephropathy (IgAN) is an autoimmune kidney disease characterized by mesangial deposition of immune complexes containing IgA and Gd-IgA1. Therapeutics blocking A proliferation-inducing ligand (APRIL) have demonstrated disease modifying potential in IgAN by reducing IgA, Gd-IgA1 and proteinuria, ultimately stabilizing kidney function. JADE101 is a novel APRIL neutralizing monoclonal antibody (mAb) designed with high affinity and extended half-life. Biomarker responses to APRIL inhibition can be integrated using pharmacokinetic (PK) and pharmacodynamic (PD) models to predict anticipated clinical responses in IgAN informing development of APRIL targeted therapies.
Methods
Population-based clinical PKPD models were used to integrate data from the JADE101 development program with publicly available clinical data in healthy volunteers and patients with IgAN, including studies of anti-APRIL mAbs and dual APRIL/BAFF inhibitors. Model-based simulations were used to predict PD outcomes supporting dose regimen selection targeting biomarker responses relevant to IgAN drug development. Predicted outcomes were compared to observed data to assess robustness of the modeling framework.
Results
PK models incorporating target-mediated drug disposition, a hallmark of APRIL-targeted therapies, adequately described serum disposition. Serum concentrations linked to direct and indirect effect PD models enabled semi-mechanistic description of anti-APRIL effects on circulating free APRIL and key immunoglobulins (IgA, IgG) relevant to therapeutic effects and safety of APRIL-targeted therapies. Population-based simulations provided data-driven assessment of inter-individual variability and potential impact on clinical responses. The PKPD modeling framework robustly captured observed clinical data in IgAN patients, informing dose regimen selection of novel anti-APRIL therapeutics.
Conclusion
Integration of rich biomarker datasets across molecules/clinical trial phases provides a quantitative framework to predict potential clinical responses to APRIL-blockade. This framework supports dose and dose interval selection anticipated to drive targeted biomarker responses associated with clinical benefit in patients with IgAN. The model-informed drug development approach underpins JADE101 development as a potentially disease modifying therapy in IgAN with convenient, infrequent dosing.
Funding
- Commercial Support – Jade Biosciences