Abstract: TH-PO0396
Translational Preclinical Evaluation of GenSci136, a Long-Acting Dual B-Cell-Activating Factor (BAFF)/A Proliferation-Inducing Ligand (APRIL) Inhibitor, in Experimental Lupus Nephritis
Session Information
- Glomerular Diseases: Autoimmune Diseases
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology
Author
- Qu, Bo, Changchun GeneScience Pharmaceutical Co., Ltd.,, Shanghai, China
Group or Team Name
- GenSci136 Research & Development Group
Background
Lupus nephritis (LN) is a severe manifestation of systemic lupus erythematosus driven by immune-complex deposition, complement activation, and progressive renal injury. Dysregulated B-cell activation and autoantibody production are central to LN pathogenesis. BAFF and APRIL support B-cell survival, differentiation, and plasma-cell maintenance and are associated with LN activity. We evaluated GenSci136, a long-acting dual BAFF/APRIL inhibitor, in preclinical models of LN and immune-complex–mediated renal injury.
Methods
BAFF/APRIL pathway inhibition was assessed using luciferase reporter assays and primary human B-cell activation/differentiation assays. In vivo efficacy was evaluated in human BAFF transgenic mice, a BAFF-driven autoimmune glomerulopathy model, treated once weekly with subcutaneous GenSci136 at multiple doses. Efficacy was further tested in MRL/MpJ-Faslpr/J mice treated twice weekly for 14 weeks. Renal function, UACR, histopathology, glomerular immune-complex deposition, circulating immunoglobulins, and autoantibodies were assessed. Exploratory PK/PD analyses were conducted after single subcutaneous dosing in cynomolgus monkeys.
Results
GenSci136 potently inhibited BAFF/APRIL-mediated BAFF-R, TACI, and BCMA signaling. In primary human B-cell assays, GenSci136 suppressed class-switched memory B-cell expansion, plasma-cell differentiation, and immunoglobulin secretion. In hBAFF transgenic mice, GenSci136 dose-dependently reduced circulating IgA, IgG, and anti-dsDNA antibodies, decreased glomerular IgA deposition, and improved renal histopathology. In MRL/lpr mice, GenSci136 reduced anti-dsDNA antibodies, improved serum creatinine and blood urea nitrogen, decreased UACR, and attenuated glomerular injury and mesangial expansion, with reduced renal IgG deposition. In cynomolgus monkeys, single-dose GenSci136 showed sustained systemic exposure and longer mean residence time than telitacicept, with prolonged reductions in IgM, IgA, and IgG.
Conclusion
GenSci136 suppresses pathogenic humoral immunity and mitigates immune-complex–mediated renal injury across complementary preclinical models. Its sustained pharmacologic activity supports further clinical development for LN and other immune-complex–mediated kidney diseases.
Funding
- Commercial Support – Changchun GeneScience Pharmaceutical Co., Ltd.,