Abstract: FR-PO0660
WAL0921, an Anti-Soluble Urokinase Plasminogen Activator Receptor (suPAR) Monoclonal IgG1 Antibody, Is Safe and Well Tolerated in a Phase 1 Single Ascending Dose (SAD) Study and Reduces Circulating suPAR in Healthy Participants
Session Information
- Glomerular Diseases: Clinical, Outcomes, and Therapeutics Research - ANCA/FSGS
October 23, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Author
- Duncan, Alexander Robert, Walden Biosciences Inc., Cambridge, Massachusetts, United States
Background
Worldwide, more than 800 million people are estimated to have chronic kidney disease (CKD) that includes proteinuric glomerular kidney disease (GKD) such as focal segmental glomerulosclerosis (FSGS), IgA nephropathy (IgAN), and primary membranous nephropathy (PMN). Current therapeutics targeting GKD are aimed at symptom and sign management and do not sufficiently address disease progression and management. There remains a high need for disease-modifying treatment options given the multitude of adverse effects that have been associated with immunosuppressive therapies.
A causative, pathological role for high levels of circulating suPAR, and increased expression of cell surface uPAR, on podocyte physiology resulting in structural damage to podocytes and their effacement has been described in GKD. Removal or neutralization of suPAR by WAL0921 may be a promising pharmacological approach for the treatment of GKD. WAL0921 is an anti-suPAR monoclonal IgG1 antibody being developed to therapeutically target and treat proteinuric GKD induced and/or exacerbated by the uPAR-suPAR system.
Methods
In vitro assays, in vivo models, and non-human primate (NHP) toxicity studies supported a first-in-human study. WAL0921-01 is a single-center, randomized, double-blind, placebo-controlled SAD study to evaluate the safety, tolerability, PK, and PD of WAL0921 in healthy subjects.
Results
In vitro data show that WAL0921 binds suPAR and uPAR with high potency, blocks suPAR induced increase in Src kinase phosphorylation in podocytes, and doesn’t impair endogenous homeostatic interactions of suPAR/uPAR system with vitronectin and uPA. In vivo, WAL0921 robustly lowers nephrotoxic serum induced albuminuria in rodents while demonstrating a clean safety profile, dose-dependent exposure as well as target engagement preclinically in GLP, NHP, repeat dose toxicity studies and clinically in healthy human subjects in the completed Phase 1 study (WAL0921-01).
Conclusion
WAL0921 is safe and well tolerated in human subjects at all evaluated doses, and allowed the determination of dose levels in the ongoing Phase 2 safety and efficacy study in patients with GKD.
Funding
- Commercial Support – Walden Biosciences