Abstract: SA-PO0270
Potent Bispecific Antibody Inhibiting Activation of Complement Alternative Pathway and Lectin Pathway for lgAN Therapy
Session Information
- Pharmacology
November 08, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)
- 2000 Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)
Authors
- Liu, Dongzhou, Huadong Medicine Company Limited, Hangzhou, Zhejiang, China
- Li, Jiarong, Huadong Medicine Company Limited, Hangzhou, Zhejiang, China
- Wang, Linli, Huadong Medicine Company Limited, Hangzhou, Zhejiang, China
- Dai, Shanshan, Sanyou Biopharmaceuticals Co., Ltd, Shanghai City, Shanghai, China
- Cai, Minxuan, Huadong Medicine Company Limited, Hangzhou, Zhejiang, China
- Pan, Hao, Huadong Medicine Company Limited, Hangzhou, Zhejiang, China
- Guo, Liubin, Huadong Medicine Company Limited, Hangzhou, Zhejiang, China
- Lv, Yaxuan, Sanyou Biopharmaceuticals Co., Ltd, Shanghai City, Shanghai, China
- Cao, Yiming, Huadong Medicine Company Limited, Hangzhou, Zhejiang, China
- Wei, Qingli, Huadong Medicine Company Limited, Hangzhou, Zhejiang, China
- Wu, Yadong, Huadong Medicine Company Limited, Hangzhou, Zhejiang, China
- Lang, Guojun, Sanyou Biopharmaceuticals Co., Ltd, Shanghai City, Shanghai, China
Background
Complement activation is crucial in pathogenesis of IgA nephropathy (IgAN). Iptacopan, an oral inhibitor targeting Factor B(CFB) to inhibit complement alternative pathway (AP) has secured FDA approval, and several complement lectin pathway (LP) inhibitors are also currently undergoing clinical trials for IgAN. We developed a bispecific antibody targeting to CFB and mannose binding lectin associated serine protease 2 (MASP2) to block AP and LP simultaneously. This innovative therapeutic candidate aims to explore enhanced efficacy, prolonged pharmacokinetics, and improved safety.
Methods
The CFB and MASP2 BsAb were generated via animal immunization, antibody screening, humanization, and affinity maturation. Human & cynomolgus C5b9 deposition inhibition assay was used for evaluate inhibition on AP and LP in vitro. In a nephritis model utilizing humanized CFB mice, the differences in U-ALB and UACR levels were assessed among single- and dual-target biologics. Additionally, a single-dose study in rhesus monkeys was conducted to evaluate the pharmacokinetics and safety of BsAb with distinct Fc engineering.
Results
The active bispecific antibody block AP and LP activation in vitro was developed, displayed remarkable effects in reducing U-ALB and UACR levels(81.0%) in nephritis mice model, which is significantly superior to the single- target mAbs(33.4% & 45.5%) and mAb combination(62.7%) , highlighting the advantages of dual-pathway therapeutic strategy. Moreover, BsAb exhibited excellent PK in NHP, characterized by an in vivo half-life ~85 hours.
Conclusion
A bispecific antibody targeting CFB and MASP2 with potent inhibitory against activation of complement AP and LP was obtained, and it demonstrated superior in vivo efficacy compared to single-target bio-molecules and their combination. Furthermore, the selected PCC candidate present favorable pharmacokinetics and safety profiles, supporting the potential as a first-in-class therapy for IgAN and other glomerulonephritide diseases. IND-enabling studies are conducted.
Funding
- Commercial Support – Huadong Medicine Pharmaceutical Co., Ltd；Sanyou Biopharmaceuticals Co., Ltd