2. Academic Validation
  3. CG001, a C3b-targeted complement inhibitor blocks three complement pathways: development and preclinical evaluation

CG001, a C3b-targeted complement inhibitor blocks three complement pathways: development and preclinical evaluation

  • Blood Adv. 2024 Jun 12:bloodadvances.2024012874. doi: 10.1182/bloodadvances.2024012874.
Ling Li 1,  Peipei Ding 2,  Yanrong Dong 3,  Shupei Shen 4,  Xinyue Lv 5,  Jie Yu 6,  Luying Li 5,  Jianfeng Chen 7,  Pilin Wang 8,  Bing Han 9,  Ting Xu 8,  Weiguo Hu 10
Affiliations

Affiliations

  • 1 Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
  • 2 Fudan University.
  • 3 Suzhou Alphamab Co. Ltd., Jiangsu, China.
  • 4 Peking Union Medical College Hospital, Chinese Academy of Medical Science,Beijing, Beijing, China.
  • 5 ComGen Pharmaceutical Co. Ltd., China.
  • 6 ComGen Pharmaceutical Co. Ltd., Shanghai, China.
  • 7 Fudan University Shanghai Cancer Center, Shanghai, China.
  • 8 Alphamab Co. Ltd., Jiangsu, China.
  • 9 Peking Union Medical Colleague Hospital, Beijing, China.
  • 10 Shanghai Medical College, Fudan University, Shanghai, China.
PMID: 38865712 DOI: 10.1182/bloodadvances.2024012874
Abstract

Excessively activated or dysregulated complement activation may contribute to the pathogenesis of a wide range of human diseases, thus leading to a surge in complement inhibitors. Herein, we developed a human-derived and antibody-like C3b-targeted fusion protein (CRIg-FH-Fc) *2, termed CG001, that could potently block all three complement pathways. CRIg and FH bind to distinct sites in C3b and synergistically inhibit complement activation. CRIg occupancy in C3b prevents the recruitment of C3 and C5 substrates, while FH occupancy in C3b accelerates the decay of C3/C5 convertases and promotes the Factor I-mediated degradation and inactivation of C3b. CG001 also showed therapeutic effects in AP-induced hemolytic mouse and CP-induced MsPGN rat models. In the pharmacological/toxicological evaluation in rats and cynomolgus monkeys, CG001 displayed an antibody-like pharmacokinetic profile, a convincing complement inhibitory effect, and no observable toxic effects. Therefore, CG001 holds substantial potential for human clinical studies.

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