Abstract: TH-PO0688
E-602 (Efgitasialase Alfa) Enhances Memory B Cell Depletion and Reduces Profibrotic Macrophages via Desialylation in Autoimmune Diseases
Session Information
- Glomerular Diseases: Immunopathogenesis and Targeted Therapeutics
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology
Authors
- Peng, Li, Palleon Pharmaceuticals Inc, Waltham, Massachusetts, United States
- Mehta, Hrishikesh, Palleon Pharmaceuticals Inc, Waltham, Massachusetts, United States
- Mysore, Vijayashree, Palleon Pharmaceuticals Inc, Waltham, Massachusetts, United States
- Chou, Chih Hsing, Palleon Pharmaceuticals Inc, Waltham, Massachusetts, United States
- Cao, Lizhi, Palleon Pharmaceuticals Inc, Waltham, Massachusetts, United States
- Fan, Tianrui, Shanghai Henlius Biotech Inc, Shanghai, China
- Broderick, James W, Palleon Pharmaceuticals Inc, Waltham, Massachusetts, United States
Background
Abnormal cell surface glycosylation, particularly elevated sialoglycans, have been observed in autoimmune diseases such as systemic lupus erythematosus (SLE) and membranous nephropathy. These immune-inhibitory sugar molecules help pathogenic cells, such as cancer cells and pathogenic immune cells, evade immune clearance. High sialoglycan levels on memory B cells contribute to resistance against antibody therapies. Inadequate depletion of CD27+ memory B cells has been linked to poor clinical outcomes. This study investigates E-602, an engineered human sialidase, as a novel therapeutic approach to enzymatically remove sialoglycans from pathogenic immune cells and enhance their vulnerability to clearance.
Methods
We evaluated E-602 in ADCP and CDC assays using Raji cells and primary human B cells with anti-CD20 or anti-CD19 antibodies. Its effects on CD27+ memory B cell depletion were tested in PBMCs from SLE patients. In vivo efficacy was assessed in a lymphoma mouse model, an MRL/lpr SLE model, and non-human primates (NHPs). We also studied its ability to reduce profibrotic M2-like macrophages in tumors, surrogates for inflamed tissues.
Results
E-602 enhanced ADCP and CDC with multiple B-cell-targeting antibodies. It improved anti-CD20-mediated depletion of CD27+ memory B cells by ~50% in SLE PBMCs, which are typically resistant to anti-CD20 alone. In mouse models, E-602 boosted anti-CD20 B cell depletion. In NHPs, it enhanced B cell clearance in lymph nodes, a site often resistant to depletion. Additionally, E-602 reduced profibrotic M2-like macrophages by ~90% in the tumor microenvironment, which serves as a surrogate for chronically inflamed tissues.
Conclusion
E-602’s dual mechanism targets memory B cells (drivers of autoantibody production and relapse) and M2-like macrophages (promoters of fibrosis and organ damage). By enhancing tissue-level B cell depletion and reducing profibrotic macrophages, E-602 offers a promising approach to restore immune balance. With a favorable safety profile from the completed Phase 1 GLIMMER-01 oncology trial, E-602 represents a scientifically novel, safe, and broadly applicable add-on to existing B-cell-targeting antibody therapies in a wide range of patients with autoimmune diseases.
Funding
- Commercial Support – Palleon Pharmaceuticals