創勝集團 - 全整合型國際化生物制藥公司
創勝集團, 生物藥, 抗體, 藥物研發
24 Jun, 2022
Di Sun1, Linlin Mao1, Xinlai Yao1, Fei Chen1,Taotao Zhu1, Shuang Lu1, Lulu Hong2, Wei Tang2, Steven Yu1, Yi Gu1, Xueming Qian1
1Suzhou Transcenta Therapeutics Co., Limited, Suzhou, China;
2HJB (Hangzhou)Co., Limited, Hangzhou, China
MASP2, mannose-binding protein-associated serine protease 2, is a key enzyme in the lectin pathway initiation of complement activation. Studies have shown that lectin pathway activation contributes to multiple human diseases such as immunoglobulin A nephropathy (IgAN), hematopoietic stem-cell transplantation–associated thrombotic microangiopathy (HSCT-TMA). Therefore, inhibition of MASP2 might be a potential treatment approach for diseases related to lectin pathway activation. TST004 is a humanized IgG4 anti-MASP2 antibody. Here we report the in vitro characterization of TST004, as well as in vivo pharmacokinetic (PK) and pharmacodynamic (PD) and safety profiles in cynomolgus monkeys.
TST004 demonstrated potent and selective in vitro and in vivo activities for the MASP2 dependent lectin complement pathway. TST004 displayed excellent tolerability and safety profiles in non-human primate (NHP). The sustained and dose-dependent reduction of serum C4c level upon TST004 dosing provides a PD signal for MASP2 dependent complement pathway inhibition. These data warrant further evaluation of the potential utility of TST004 in blocking MASP2 dependent diseases.