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已发表论文
一种长效抗人 MASP-2 抗体的表征用于治疗补体相关疾病
Authors Han X , Yang C, Wang Z, Fan K, Liu K, Ye H, Zhang W, Zhang J, Hu X , Lin H, Liao C
Received 13 February 2025
Accepted for publication 7 November 2025
Published 19 November 2025 Volume 2025:18 Pages 16247—16260
DOI https://doi.org/10.2147/JIR.S522657
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Professor Ning Quan
Xiangli Han,1,2,* Changyong Yang,1,2,* Zhijun Wang,1,2,* Ke Fan,1,2 Kaili Liu,1,2 Hao Ye,1,2 Wei Zhang,1,2 Jiawei Zhang,1,2 Xiaotong Hu,1,2 Hongda Lin,1,2 Cheng Liao1,2
1Shanghai Shengdi Pharmaceutical Co., Ltd, Shanghai, 200100, People’s Republic of China; 2Jiangsu Hengrui Pharmaceuticals Co., Ltd, Lianyungang, Jiangsu, 222000, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Cheng Liao, Jiangsu Hengrui Pharmaceuticals Co., Ltd, Lianyungang, Jiangsu, 222000, People’s Republic of China, Tel/Fax +86 021-61063826, Email cheng.liao@hengrui.com
Purpose: The complement system is an important component of the innate immune system, which is essential for orchestrating host defense and regulating inflammation. However, overactivation of the complement system plays a pathogenic role in the onset and progression of various inflammatory diseases and rare diseases. Central to the lectin pathway (LP) among three complement activation routes, dysregulation of mannan-binding lectin-associated serine protease-2 (MASP-2) is associated with conditions ranging from IgA nephropathy (IgAN) to hematopoietic stem cell transplantation-associated thrombotic microangiopathy (HSCT-TMA). Thus, we tend to develop an anti-MASP-2 antibody to treat relevant diseases.
Methods: Herein, we developed SHR-2010, a novel fully humanized monoclonal antibody targeting MASP-2. SHR-2010 was generated through mouse immunization with recombinant human MASP-2 protein. The binding affinities of SHR-2010 were determined using surface plasmon resonance (SPR). Then, a mouse surrogate antibody ER011-11165 was developed and subsequently evaluated in the lipopolysaccharide (LPS)-induced acute kidney injury murine model. Additionally, the pharmacokinetic (PK), pharmacodynamics (PD) and safety profiles of SHR-2010 were conducted in monkeys.
Results: SHR-2010 exhibited strong inhibition of lectin pathway activation in human and rhesus serum. Administration of ER011-11165 significantly mitigated LPS-induced nephrotoxicity in acute kidney injury mouse model. PK profiling in non-human primates (NHPs) revealed high subcutaneous bioavailability and long half-life of SHR-2010, supporting a potential subcutaneous administration route and long dosing interval in clinic. Notably, PD markers demonstrated sustained LP inhibition, with 65.8– 80.1% inhibitory effect on serum LP persisting for 408 hours following a single intravenous dose of 5 mg/kg SHR-2010. The nonclinical toxicology evaluation demonstrated that SHR-2010 exhibits a proper safety profile.
Conclusion: Preclinical studies demonstrated that SHR-2010 exhibited superior pharmacokinetics and sustained lectin pathway inhibition compared to OMS721. When coupled with optimized trial design strategies, SHR-2010 could be a promising therapeutic candidate for lectin pathway-driven diseases, including IgAN.
Keywords: MASP-2, IgA nephropathy, lectin pathway, long-acting
1Shanghai Shengdi Pharmaceutical Co., Ltd, Shanghai, 200100, People’s Republic of China; 2Jiangsu Hengrui Pharmaceuticals Co., Ltd, Lianyungang, Jiangsu, 222000, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Cheng Liao, Jiangsu Hengrui Pharmaceuticals Co., Ltd, Lianyungang, Jiangsu, 222000, People’s Republic of China, Tel/Fax +86 021-61063826, Email cheng.liao@hengrui.com
Purpose: The complement system is an important component of the innate immune system, which is essential for orchestrating host defense and regulating inflammation. However, overactivation of the complement system plays a pathogenic role in the onset and progression of various inflammatory diseases and rare diseases. Central to the lectin pathway (LP) among three complement activation routes, dysregulation of mannan-binding lectin-associated serine protease-2 (MASP-2) is associated with conditions ranging from IgA nephropathy (IgAN) to hematopoietic stem cell transplantation-associated thrombotic microangiopathy (HSCT-TMA). Thus, we tend to develop an anti-MASP-2 antibody to treat relevant diseases.
Methods: Herein, we developed SHR-2010, a novel fully humanized monoclonal antibody targeting MASP-2. SHR-2010 was generated through mouse immunization with recombinant human MASP-2 protein. The binding affinities of SHR-2010 were determined using surface plasmon resonance (SPR). Then, a mouse surrogate antibody ER011-11165 was developed and subsequently evaluated in the lipopolysaccharide (LPS)-induced acute kidney injury murine model. Additionally, the pharmacokinetic (PK), pharmacodynamics (PD) and safety profiles of SHR-2010 were conducted in monkeys.
Results: SHR-2010 exhibited strong inhibition of lectin pathway activation in human and rhesus serum. Administration of ER011-11165 significantly mitigated LPS-induced nephrotoxicity in acute kidney injury mouse model. PK profiling in non-human primates (NHPs) revealed high subcutaneous bioavailability and long half-life of SHR-2010, supporting a potential subcutaneous administration route and long dosing interval in clinic. Notably, PD markers demonstrated sustained LP inhibition, with 65.8– 80.1% inhibitory effect on serum LP persisting for 408 hours following a single intravenous dose of 5 mg/kg SHR-2010. The nonclinical toxicology evaluation demonstrated that SHR-2010 exhibits a proper safety profile.
Conclusion: Preclinical studies demonstrated that SHR-2010 exhibited superior pharmacokinetics and sustained lectin pathway inhibition compared to OMS721. When coupled with optimized trial design strategies, SHR-2010 could be a promising therapeutic candidate for lectin pathway-driven diseases, including IgAN.
Keywords: MASP-2, IgA nephropathy, lectin pathway, long-acting