Identifying next generation Ig selective cleaving enzymes for treatment of autoimmune diseases using IMPACT platform

Abstract Dysregulated humoral immune mechanisms result in immunoglobulin production that is pathogenic and contributes to a wide range of autoimmune diseases transplant rejection. Proteases derived from human pathogens can specifically cleave these immunoglobulins (Ig) potentially eliminate circulating, cell-surface immune-complex Ig classes modulate Ig-mediated autoimmunity inflammation, providing novel opportunity treat antibody-mediated diseases. We describe here the discovery, generation, functional characterization specific proteases. These proteases were identified using Seismic Therapeutic’s IMPACT platform tested for their ability intact subclasses isotypes high-throughput CE-SDS cleavage assay. Additionally, we found enzymes soluble cell bound blood, dramatically reducing effector function. believe subclass isotype cleaving will provide an develop targeted therapies various where autoantibodies are key drivers disease. In addition, they be better tolerated compared current therapeutic interventions such as plasma exchange other immunosuppressive therapies.