M5542 / EMD Serono - LARVOL DELTA

M5542, a bifunctional fusion protein targeting CD80, CD86, and OX40L that modulates excessive T-cell activity: a preclinical proof-of-concept study. (PubMed, Front Immunol) - "M5542, single-agent comparators CTLA-4Ig (abatacept), anti-OX40L, and both single agents in combination were tested for their ability to inhibit proinflammatory cytokine production in a mixed lymphocyte reaction of activated monocyte-derived dendritic cells and T cells from healthy donors or peripheral blood mononuclear cells from individuals with SLE. In this preclinical study, the bifunctional M5542 blocked CD28 and OX40-mediated T-cell inflammation with greater immunomodulatory activity than monofunctional agents and in some assays comparable to or better than the combination of the monofunctional agents. These findings support further evaluation of M5542 in T-cell-driven autoimmune disease settings."

Journal • Preclinical • Glomerulonephritis • Graft versus Host Disease • Immunology • Inflammation • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Systemic Lupus Erythematosus • CD80 • CD86 • IFNG • TNFSF4

M5542: A Potent CD80, CD86, and OX40L Antagonist Fusion Molecule for the Treatment of Autoimmune Diseases (ACR Convergence 2024) - "To explore whether dual pathway blockade is superior to single pathway blockade, we investigated the in vitro potency and in vivo efficacy of M5542, a novel CD80, CD86, and OX40L antagonist, and a bi-functional fusion molecule that blocks the CD28 and OX40 pathways to inhibit T-cell activation and function, thereby curbing inflammation in autoimmune diseases. M5542, single agent comparators abatacept (CTLA4Ig) and anti-OX40L, or the combination thereof were tested for their ability to inhibit proinflammatory cytokine production in a mixed lymphocyte reaction (MLR) of activated monocyte-derived dendritic cells (MDDCs) and T-cells from healthy donors or SLE peripheral blood mononuclear cells (PBMCs). M5542 effectively blocked CD28 and OX40 mediated T-cell activation and reduced T-cell driven inflammation, demonstrating promise in treating autoimmune diseases."

Graft versus Host Disease • Immunology • Inflammation • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus • CD80 • CD86 • IFNG • IL6 • TNFA • TNFSF4