P-173 - MP1032 - a novel anti-inflammatory drug- ameliorates the progression of autoimmune diseases

Abstract

Inflammatory autoimmune diseases such as rheumatoid arthritis (RA), multiple sclerosis (MS), and psoriasis are a major health burden. A dysregulated redox system with excessive production of reactive oxygen species (ROS) is thought to play a central role in disease progression as these oxygen species facilitate the production of proinflammatory cytokines. MP1032 belongs to a new class of anti-inflammatory drugs that act as potent ROS scavengers. A unique feature of this compound class is that the scavenging activity is dynamically regulated by an intracellular feedback loop. Scavenging activity increases with increased inflammatory activation of innate immune cells and ceases at physiological, non-inflammatory activation states. Using ultra-weak photon emission imaging, ROS scavenging activity of MP1032 was demonstrated in mice directly at the site of inflammation. In adjuvant-induced RA, this effect was accompanied by markedly reduced serum levels of IL-6 and TNFα and reduced arthritic scores in MP1032-treated rats. MP1032 also ameliorated disease progression in models of MS. In a human Phase IIa trial, MP1032 demonstrated good clinical efficacy and safety in moderate psoriasis, highlighting the potential of redox-based therapies in chronic inflammatory and autoimmune diseases.