Authors:

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

Background:

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.

Conclusions:

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.