The broader/commercial impact of this Small Business Innovation Research (SBIR) Phase I project is the creation of a drug that allows for the specific depletion of a subclass of human antibodies (IgG4) that cause several different human diseases. Current treatments that deplete human antibodies do it without regard to antibody subclass, leading to a broadly suppressed immune system. In addition, there are over 10 IgG4-related diseases where the role of IgG4 is thought to be important but not the source of the disease. These include thrombotic thrombocytopenic purpura, pemphigus vulgaris and pemphigus foliaceus, anti-muscle-specific kinase myasthenia gravis, and primary membranous nephropathy. The proposed drug would allow the entire field to investigate the role of IgG4 in a specific disease. The mechanism by which the candidate drug proposes to deplete IgG4 could be leveraged to modify serum IgG4 with other similar drugs. Thus, the candidate drug would serve as a proof of concept for a mechanism that promises the drugmaker the ability to recombine endogenous serum IgG4 with additional drugs and modifications. These will have broad implications in a series of diseases ranging from IgG4s immunosuppressive role in oncology to anti-drug-antibodies that block the effect of many medicines. The proposed project supports the creation of a drug that will recombine with endogenous pathogenic IgG4s leading to their rapid depletion. One Fab Arm Exchange Therapeutic (FAET) has alrea