Abnormal function of the adaptive immune system drives a diverse set of chronic and acute autoimmune diseases. At Seismic, we are building a pipeline of novel biologics derived from our IMPACT platform focused on addressing the unmet need in dysregulated adaptive immunity to have a broad impact on patients.

We have emerging best-in-class and first-in-class enzyme and antibody programs across two drug product areas modulating the two arms of the adaptive immune system, humoral immunity and cell-mediated immunity. For diseases of humoral immunity driven by autoantibodies that recognize one’s own tissues, we are discovering and developing multiple types of immunoglobulin sculpting (IgSc) enzyme therapeutics that modify different pathogenic Ig, starting with Ig proteases. For diseases of cell-mediated immunity characterized by inappropriately activated T cells, we are discovering and developing Dual-cell Bidirectional (DcB) antibody therapies which activate multiple inhibitory pathways in more than one cell type to regulate both sides of the immune cell synapse.

IgSc enzymes

Disease Treatment Challenge

Pathogenic antibodies cause a diverse set of autoimmune diseases, such as myasthenia gravis, chronic inflammatory demyelinating polyneuropathy and immune thrombocytopenia. Our Ig sculpting enzymes are designed to modify, reduce or eliminate these pathogenic antibodies and are optimized as therapeutics via our IMPACT platform.

Lead Drug Program

Our lead IgSc program, a novel engineered pan-IgG protease, is suitable for the treatment of acute and chronic autoantibody mediated diseases. Our protease addresses multiple pathogenic mechanisms in a single drug, hypothesized to result in superior clinical outcomes. Our pan-IgG protease lowers IgG and immune complex levels, reduces antibody effector functions such as complement fixation, and cleaves the antigen receptor on self-reactive memory B cells, thereby modulating Ig-mediated autoimmunity and inflammation. Utilizing the IMPACT platform we generated novel pan-IgG proteases with reduced B and T cell immunogenicity and chemical liabilities while maintaining enzyme activity and stability.

Broad Pipeline Opportunities

We are applying our insights to design additional Ig sculpting enzymes that are selective for IgG subclasses and other Ig isotypes.

DcB antibodies

Disease Treatment Challenge

Pathogenesis of autoimmune diseases derives from interactions of multiple cell types including T cells and antigen presenting cells, as is seen in systemic lupus erythematosus, multiple sclerosis, rheumatoid arthritis, and many other diseases. Our Dual-cell Bidirectional (DcB) antibody therapies are optimized via our IMPACT platform to engage simultaneously T cells and antigen presenting cells, such as B cells, to restore immune homeostasis and potentially promote disease remission.

Lead Drug Program

Our lead DcB antibody program agonizes PD-1, a well-known inhibitory checkpoint receptor on T cells, and selectively engages the inhibitory Fc gamma receptor, FcγRIIb, on B cells and other antigen presenting cells. In preclinical assays we observed enhanced PD-1 agonism as well as reduced pro-inflammatory cytokine production with PD-1 DcB antibody candidates containing a novel FcγRIIb-selective Fc domain. We believe that targeting both sides of the cell-cell synapse will drive greater efficacy than PD-1 agonists.

Broad Pipeline Opportunities

We are applying our insights from our lead DcB program to design additional DcB antibodies that target different checkpoint receptors.