MASP-2 (Mannan-binding lectin-associated serine protease-2) is a key serine protease in the lectin pathway of complement activation, resulting in excessive complement activation by potentiating MBL-dependent MASP-2 activation, and the deposition of MASP-2, C4b, activated C3 and C5b-9. It activates the complement system in an antibody-independent manner.

SARS-CoV-2 is a highly pathogenic human coronavirus, causing severe atypical pneumonia, COVID-19, and hyperinflammation-related syndromes. Being highly transmissible, this novel coronavirus disease has spread fast all over the world. The N proteins of SARS-CoV, SARS-CoV-2, and MERS-CoV interact with MASP-2. Therefore, MASP-2-involved complement activation may become a new target for the treatment of COVID-19.

Moreover, MASP-2 levels are elevated following HSCT (hematopoietic stem-cell transplantation) which is related to complement activation and might lead to transplant failure. Thus, MASP-2 is also a treatment target for improving the survival rate of HSCT.

Narsoplimab (OMS 721) is an anti-MASP-2 IgG4 mAb that binds MASP-2 and blocks lectin pathway activation.

From: Rambaldi A, et al. Immunobiology. 2020 Nov;225(6):152001.

Following the in vitro experiment results, Narsoplimab (100 nM, 3 h, Vero E6 cells and Vero E6 cells with SARS-CoV-2) inhibits the N protein potentiated MASP-2 deposition. In addition, Narsoplimab (10 mg/kg, i.v.) decreases the percentage of lymphocytes (Lym%) and increases the percentage of neutrophils (Neu%) in Masp2^-/- mice. Besides, Narsoplimab inhibits LP functional activity and has shown effective efficacy in the treatment of critical COVID-19 patients.

Narsoplimab also has the potential to the treatment of adult hematopoietic stem-cell transplantation–associated thrombotic microangiopathy. Studies show that Narsoplimab significantly improves laboratory thrombotic microangiopathy (TMA) markers, and results in clinical response and favorable overall survival.

All in all, Narsoplimab is a fully humanized anti-MASP-2 IgG4 monoclonal antibody. It has the potential to research hematopoietic stem-cell transplantation and SARS-CoV-2.

References:

[1] Gao T, et al. Signal Transduct Target Ther. 2022 Sep 14;7(1):318.

[2] Khaled SK, et al. J Clin Oncol. 2022 Aug 1;40(22):2447-2457.