A Novel Inhibitor of the Classical Pathway of Complement

A novel inhibitor of the classical pathway of the complement system Abstract The classical pathway of the complement system is implicated in the pathogenesis of a number of human autoimmune diseasesincluding systemic lupus erythematosusrheumatoid arthritisalloantibody mediated transplant rejection and autoimmune hemolytic anemiaDespite a large body of literature documenting the role of the complement system in these disordersa specific inhibitor of the classical pathway has yet to be developedCold agglutinin diseaseCADis a type of autoimmune hemolytic anemiaAIHAIt is an orphan disease that accounts forof AIHA casesThe pathophysiology of CAD is driven by the classical pathway of the complement systemThe current treatment options for CAD are broadly immunosuppressive and are associated with a number of off target effectsWe have identified a human autoantibody that inhibits the classical pathway at the step of CactivationActivated Cis the first of two subunits that compose the classical pathway Cconvertasewhich is the central enzyme of the classical pathway of complementIn a number of autoimmune diseasesdysregulation of the classical pathway can lead to uncontrolled inflammation through the production of potent anaphylotoxins and other inflammatory mediatorsWe propose that an anti CMAb will be effective at inhibiting activation of the classical pathway in certain autoimmune diseasesIn particularwe propose that this therapeutic MAb could be used to treat cold agglutinin disease and potentially other complement mediated disordersIn this Phase I SBIRwe will characterize the Cinhibitory MAb and test it in proof of principle in vitro assays to demonstrate feasibility of this therapeutic strategy Project Narrative AnthroBio has identified a human antibody that inhibits complement activation via the classical pathwayWe hypothesize that this antibody can be developed into an effective treatment for certain autoimmune inflammatory diseases mediated by the classical pathway of complement