NovelMed intends to develop a humanized anti-Bb antibody as a prophylactic treatment for inflammatory responses associated with hemodialysis. During this procedure, blood contacts the artificial surfaces of the dialyzer, activating the alternative complement pathway (AP). AP activation causes cellular activation and production of inflammatory mediators with potent inflammatory properties. When a patient with chronic kidney disease undergoes repeated dialysis procedures, these inflammatory mediators accumulate and cause persistent secondary organ damage over time. We have shown that Bikaciomab prevents AP activation, cellular activation and production of inflammatory mediators in whole blood circulating through the hemodialyzer. Bikaciomab has a unique mechanism of action as this antibody binds C3 and C5 convertase and neutralizes their proteolytic activity required for the propagation of the alternative complement pathway. This approach appears to be clinically viable given large number of indications where such a drug can be tested and used. The proposed therapeutic strategy is a single drug strategy that effectively prevents an array of inflammatory mediators known to generate potent inflammation. Recent publication underlines the role of complement for the treatment of inflammatory response due to hemodialysis. Murine anti-Bb has been humanized using recombinant engineering. The monoclonal demonstrates high affinity, target selectivity and is ready to be tested in the dialysis system. Now that the humanized antibody is available, its further development as a clinically viable product is proposed for renal disorders. The scientific, regulatory, safety and business development team has been established to conduct the proposed studies.
This proposal supports development of humanized Bikaciomab that is a selective inhibitor of the alternative pathway to prevent the onset of inflammation in dialysis patients. The inflammation associated with hemodialysis can be followed by devastating tissue and organ damage. According to National Kidney and Urologic Diseases Information Clearinghouse, more than half a million Americans require ongoing hemodialysis. Among hemodialysis patients in the U.S, inflammation associated with the procedure it is a leading cause of morbidity, mortality and steep health care costs. If successful, humanized Bikaciomab would address a critical unmet medical need for patients requiring hemodialysis. Such a treatment could save lives, livelihoods, and incalculable costs in health care and all the indirect costs associated with the devastating inflammation based side effects of hemodialysis.