[Translation] A Phase I clinical trial to evaluate the safety, tolerability, pharmacokinetic characteristics and explore the dosing of CG001 in healthy people/PNH patients

Part 1（健康人剂量递增阶段）主要研究目的：评估健康人接受 CG001 注射后的安全性和耐受性；次要研究目的：评估健康人接受 CG001 注射后的药代动力学（PK）特征；评估健康人接受 CG001 注射后的免疫原性；探索性目的：探索健康人接受 CG001 注射后的药效/免疫学标志物。 Part 2（PNH患者剂量递增阶段）主要研究目的：评估 PNH 患者接受 CG001 注射后的安全性和耐受性；次要研究目的：评估 PNH 患者接受 CG001 注射后的 PK 特征；评估 PNH 患者接受 CG001 注射后的免疫原性；初步评估 PNH 患者接受 CG001 注射后的有效性；探索性目的：探索PNH患者接受CG001注射后的药效/免疫学标志物。

[Translation]

Part 1 (healthy subjects dose escalation phase) Main study objectives: evaluate the safety and tolerability of CG001 after injection in healthy subjects; Secondary study objectives: evaluate the pharmacokinetic (PK) characteristics of CG001 after injection in healthy subjects; evaluate the immunogenicity of CG001 after injection in healthy subjects; Exploratory objectives: explore the pharmacodynamic/immunological markers of CG001 after injection in healthy subjects. Part 2 (PNH patients dose escalation phase) Main study objectives: evaluate the safety and tolerability of CG001 after injection in PNH patients; Secondary study objectives: evaluate the PK characteristics of CG001 after injection in PNH patients; evaluate the immunogenicity of CG001 after injection in PNH patients; preliminarily evaluate the effectiveness of CG001 after injection in PNH patients; Exploratory objectives: explore the pharmacodynamic/immunological markers of CG001 after injection in PNH patients.

Start Date11 Apr 2022

Sponsor / Collaborator

Shanghai Kangjing Bioscience Co. Ltd.

100 Clinical Results associated with CG-001(ComGen)

100 Translational Medicine associated with CG-001(ComGen)

100 Patents (Medical) associated with CG-001(ComGen)

Literatures (Medical) associated with CG-001(ComGen)

13 Aug 2024·Blood Advances

CG001, a C3b-targeted complement inhibitor, blocks 3 complement pathways: development and preclinical evaluation

Article

Author: Wang, Pilin ; Li, Luying ; Chen, Jianfeng ; Xu, Ting ; Han, Bing ; Li, Ling ; Yu, Jie ; Dong, Yanrong ; Shen, Shupei ; Ding, Peipei ; Lv, Xinyue ; Hu, Weiguo

AbstractExcessively 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) x2, termed CG001, that could potently block all 3 complement pathways. Complement receptor of the immunoglobulin superfamily (CRIg) and factor H (FH) bind to distinct sites in C3b and synergistically inhibit complement activation. CRIg occupancy in C3b prevents the recruitment of C3 and C5 substrates, whereas 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 alternative pathways–induced hemolytic mouse and classical pathways–induced mesangial proliferative glomerulonephritis 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.

01 Nov 2014·The FASEB JournalQ2 · BIOLOGY

A novel CRIg‐targeted complement inhibitor protects cells from complement damage

Q2 · BIOLOGY

Article

Author: He, Guangsheng ; Zhang, Xin ; Wang, Yingwei ; Hu, Weiguo ; Chen, Suning ; Du, Yiqun ; Wu, Qian ; Wang, Wenjuan ; Teng, Xiaoyan ; Qiao, Qian ; Guo, Lin ; Lu, Renquan ; Wang, Na

The inappropriate activation of complement may contribute to various immune diseases. The alternative pathway (AP) predominates during complement activation regardless of the initiating pathways. Hence, the main AP regulator factor H (FH) holds great potential as an attractive therapeutic intervention. In addition, complement receptor of the immunoglobulin superfamily (CRIg) has been demonstrated to inhibit AP and, more notably, still specifically binds to C3b/iC3b. We thus developed novel CRIg-targeted complement inhibitors by connecting the functional domains of CRIg and FH, which we termed CRIg-FH and CRIg-L-FH. CRIg-L-FH, slightly more potent than CRIg-FH, considerably inhibited both AP- and also classical pathway (CP)-mediated hemolysis and successfully eliminated the deposition of C3b/iC3b. Kinetic analysis further revealed that the binding affinity constant (KD) of CRIg/FH was in the micromolar range, consistent with its long-lasting binding to complement-attacked cells. CRIg-L-FH efficiently protected aberrant erythrocytes of patients with paroxysmal nocturnal hemoglobinuria (PNH) from AP- and CP-mediated complement damage (IC50 was 22.43 and 64.69 nM, respectively). Moreover, CRIg-L-FH was found to inhibit complement activation induced by the anti-Thy1 antibody in a mesangioproliferative glomerulonephritis (MPGN) rat model. Hence, CRIg-L-FH protects glomerular mesangial cells (GMCs) from complement-mediated injury and proliferative lesions. These findings strongly suggest that CRIg/FH is a potential therapeutic drug candidate for a range of complement-mediated diseases.

Frontiers in ImmunologyQ2 · MEDICINE

A Targeted Complement Inhibitor CRIg/FH Protects Against Experimental Autoimmune Myasthenia Gravis in Rats via Immune Modulation

Q2 · MEDICINE

ArticleOA

Author: Zhao, Chongbo ; Song, Jie ; Xi, Jianying ; Hu, Weiguo ; Yan, Chong ; Li, Ling ; Luo, Sushan ; Ding, Peipei ; Zhao, Rui

Antibody-induced complement activation may cause injury of the neuromuscular junction (NMJ) and is thus considered as a primary pathogenic factor in human myasthenia gravis (MG) and animal models of experimental autoimmune myasthenia gravis (EAMG). In this study, we tested whether CRIg/FH, a targeted complement inhibitor, could attenuate NMJ injury in rat MG models. We first demonstrated that CRIg/FH could inhibit complement-dependent cytotoxicity on human rhabdomyosarcoma TE671 cells induced by MG patient-derived IgGin vitro. Furthermore, we investigated the therapeutic effect of CRIg/FH in a passive and an active EAMG rodent model. In both models, administration of CRIg/FH could significantly reduce the complement-mediated end-plate damage and suppress the development of EAMG. In the active EAMG model, we also found that CRIg/FH treatment remarkably reduced the serum concentration of autoantibodies and of the cytokines including IFN-γ, IL-2, IL-6, and IL-17, and upregulated the percentage of Treg cells in the spleen, which was further verifiedin vitro. Therefore, our findings indicate that CRIg/FH may hold the potential for the treatment of MGviaimmune modulation.

100 Deals associated with CG-001(ComGen)

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Glomerulonephritis, Membranoproliferative	NDA/BLA	China	Fudan University	01 Nov 2014
Hemoglobinuria, Paroxysmal	Phase 1	China	Shanghai Kangjing Bioscience Co. Ltd.	11 Apr 2022
Autoimmune Diseases	Preclinical	China	Shanghai Kangjing Biomedical Technology Co., Ltd.	30 Jan 2022
Myasthenia Gravis	Preclinical	China	Fudan University	26 Jan 2022

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