Disease Modifying Biologics for Rheumatoid Arthritis

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DESCRIPTION (provided by applicant): Nearly 70 million people in the US suffer from arthritis related conditions[1, 2]. Of these, rheumatoid arthritis (RA) cases constitute approximately 3 million. RA is a chronic systemic inflammatory disease that primarily results in erosive destruction of articular joints with additional variable extra-articular effects. The growing elderly population coupled with the prevalence of RA in the elderly age group (up to a third of cases) highlights the critical need to develop effective treatment options to reduce the health care burden of the US in the coming couple of decades. NovelMed has developed a potent anti-arthritic pharmaceutical agent YalcioMab that specifically blocks the activation of the alternative complement pathway. This compound prevents TNF-1 (tumor necrosis factor 1) production by monocytes; effectively inhibits inflammation and joint destruction in an animal model of RA; and exhibits a good safety profile in initial studies. This Fast Track application proposes to further develop YalcioMab as a potent anti-arthritic agent through 1) evaluation of its efficacy in prophylactic and therapeutic models of rabbit models of antigen-induced arthritis (AIA); 2) characterization and in vivo testing of its chimeric version c-YalcioMab; and 3) production, characterization, in vivo and toxicological evaluation of its humanized version h-YalcioMab. NovelMed expects that following this important research, h-YalcioMab will be ready as a product for pre-clinical IND (investigational new drug) work. Based on the preliminary results obtained so far, NovelMed projects that h-YalcioMab treatment will be more specific than current drugs, infliximab (RemicadeTM) and Enbrel, which also target basal levels of TNF-1 in the human body. NovelMed has filed patent applications protecting YalcioMab and its analogs and has exclusive rights on the new biologic. NovelMed is supported by funds from the NIH and a couple of investors, and is a fully equipped drug discovery company focusing on biological agents. Overall, the proposed work is in the direction of a cost-effective, efficacious and safe therapeutic agent for preventing joint destruction in RA patients through regulation of a specific complement- mediated inflammatory response. PUBLIC HEALTH RELEVANCE: Rheumatoid arthritis (RA) affects nearly 3 million individuals in the US, yet no effective and safe treatment is available. Current therapies for rheumatoid arthritis (RA), which primarily target inflammation, are not effective in all patients. NovelMed has developed a potent anti-arthritic pharmaceutical agent that shows excellent results in limited animal model studies. NovelMed's therapeutic agent prevents activation of neutrophils, monocytes and platelets, which together drive inflammation and joint destruction associated with RA. This application proposes to develop the pharmaceutical agent through in vitro and in vivo studies so as to file an IND application with the FDA in the near future.