Targeting IgG Clearance with M281: A Novel Anti-FcRn Antibody for Autoimmune Diseases

A new approach to reducing IgG antibodies, which are key contributors in various autoimmune and alloimmune diseases, has been investigated. This strategy focuses on blocking FcRn-mediated IgG recycling to enhance IgG clearance. M281, a high-affinity, effector-less IgG1 anti-FcRn monoclonal antibody, was developed and its impact on IgG recycling was studied in human cells and in vivo using transgenic mice and cynomolgus monkeys.

M281 was found to induce dose-dependent IgG clearance without depleting albumin, a critical protein in the body. It effectively inhibits IgG recycling both in vitro in endothelial cells and in vivo in the animal models. The pharmacokinetics, target occupancy, and biodistribution of M281 align with those of a typical recombinant antibody, showing rapid target inhibition and systemic clearance. M281 also showed therapeutic effects in mouse models of idiopathic thrombocytopenia purpura and collagen antibody-induced arthritis.

The results suggest that M281 could be a promising candidate for rapidly and reversibly suppressing pathogenic autoantibodies or alloantibodies in conditions such as immune cytopenias, acquired inhibitors, thrombotic states, and other related disorders. The study's findings warrant further evaluation of M281 as a potential treatment for diseases driven by IgG autoantibodies.