Senior Scientist 2 Seismic Therapeutic Brookline, Massachusetts, United States
Disclosure(s):
Liliana Sanmarco, PhD: No relevant disclosure to display
Introduction/Rationale: IgM is a multifunctional immunoglobin that acts as the first line of defense against systemic pathogens. IgM’s multimeric structure, together with its complement binding ability, makes IgM a highly potent inflammation driver. The presence of autoreactive IgM antibodies causing complement dependent damage has been described in inflammatory and autoimmune conditions such as Cold Agglutinin Disease (CAD) and Multifocal Motor Neuropathy (MMN) . For this reason, the development of IgM autoantibodies degrading therapy represents an attractive approach.
Methods: Employing Seismic’s IMPACT platform and evolutionary screening, we identified several novel and selective IgM proteases. Discovered proteases cleave soluble IgM in plasma and the IgM BCR in B cells from healthy individuals.
Results: CAD is an autoimmune hemolytic anemia, caused by IgM autoantibodies that bind to red blood cells (RBC), causing agglutination and activate complement cascade resulting in RBC death. Seismic’s IgM protease cleaves RBC bound IgM, preventing agglutination in whole blood from CAD donors, an unmet need not targeted by current approved treatment. In addition, IgM cleavage reduced cold-induced complement deposition on RBC from CAD patients.
Conclusion: Further engineering and optimization with our IMPACT Platform for the novel proteases is currently under way.
