Abstract: FR-PO0822
Selective T-Cell Engagement for Deep B-Cell Depletion in Primary Membranous Nephropathy (pMN): Scientific Rationale and Trial Design for CLEAR-AbKD
Session Information
- Glomerular Diseases: Practice and New Concepts Shaping Modern Care
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
Authors
- Woollard, Kevin, AstraZeneca R&D Cambridge, Cambridge, England, United Kingdom
- Schaffner, Hannah, AstraZeneca R&D Cambridge, Cambridge, England, United Kingdom
- Hu, Ping, AstraZeneca R&D Cambridge, Cambridge, England, United Kingdom
- Moore, Kristi, AstraZeneca R&D Cambridge, Cambridge, England, United Kingdom
- Padmakumar, Swathi, AstraZeneca R&D Cambridge, Cambridge, England, United Kingdom
- Golan, Karin, AstraZeneca R&D Cambridge, Cambridge, England, United Kingdom
- Davenport, Kathleen, AstraZeneca R&D Cambridge, Cambridge, England, United Kingdom
- Hofherr, Alexis, AstraZeneca R&D Cambridge, Cambridge, England, United Kingdom
Background
pMN is an autoimmune disease commonly caused by autoantibodies to podocyte phospholipase A2 receptors (PLA2R), leading to nephrotic-range proteinuria and risk of progressive loss of kidney function. Current therapies for high-risk disease (e.g. cyclophosphamide, calcineurin inhibitors, or anti-CD20 antibodies) can induce remission but are limited by toxicity, incomplete B cell depletion, and frequent relapse. CD20-directed therapy may not fully eliminate pathogenic B cell populations, including subsets with tissue residence or CD20low/- phenotypes. Recent clinical evidence in severe autoimmune diseases suggests that deep B cell depletion may enable sustained disease control after a limited treatment course.
Methods
In oncology, CD19-targeted T-cell engager (TCE) therapies have achieved rapid and profound B cell depletion with a manageable safety profile. Surovatamig is a CD19×CD3 bispecific TCE (in late-stage clinical development for B cell malignancies) designed to recruit cytotoxic T cells to eliminate CD19+ B cells, thereby depleting a broader spectrum of pathogenic B cell populations than CD20 directed agents (including memory B cells and plasmablasts). Preclinical studies show surovatamig eliminates CD19+ patient B cells while its lower affinity CD3-binding arm limits T cell overactivation and cytokine release. In a rat model of pMN, we further confirmed disease contribution of tissue-resident B cells.
Results
CLEAR-AbKD is an open-label, proof-of-concept Phase 2 trial evaluating a short course of surovatamig in adults with relapsing or treatment-resistant pMN (N=34). Key objectives include safety, pharmacokinetics, B cell depletion, anti PLA2R antibody levels, proteinuria, and kidney function. Risk-mitigation measures are in place to manage known toxicities of TCEs (including cytokine release and infection risk). Patients will be followed for two years to evaluate the durability of clinical response
Conclusion
CD19-directed T-cell engagement targets the immunopathogenic source of pMN. By eliminating circulating, tissue-resident, and anti-CD20-refractory B cell clones, surovatamig may achieve deeper and more durable remission while reducing cumulative immunosuppression. The CLEAR-AbKD trial will provide initial data on the feasibility, safety, and immunological impact of this approach in pMN.
Funding
- Commercial Support – AstraZeneca