Development and characterization of narsoplimab, a selective MASP-2 inhibitor, for the treatment of lectin-pathway-mediated disorders.

ABSTRACT:

Introduction

Overactivation of the lectin pathway of complement plays a pathogenic role in a broad range of immune-mediated and inflammatory disorders; mannan-binding lectin-associated serine protease-2 (MASP-2) is the key effector enzyme of the lectin pathway. We developed a fully human monoclonal antibody, narsoplimab, to bind to MASP-2 and specifically inhibit lectin pathway activation. Herein, we describe the preclinical characterization of narsoplimab that supports its evaluation in clinical trials.

Methods and results

ELISA binding studies demonstrated that narsoplimab interacted with both zymogen and enzymatically active forms of human MASP-2 with high affinity (K_D 0.062 and 0.089 nM, respectively) and a selectivity ratio of >5,000-fold relative to closely

SUBMITTER: Dudler T 

PROVIDER: S-EPMC10663225 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature