S-1117 offers a new therapeutic opportunity in autoantibody-mediated diseases such as myasthenia gravis and ITP

Company plans to develop S-1117 for chronic and acute treatment of IgG autoantibody-driven diseases and expects to initiate first-in-human Phase 1 clinical trial in 1H 2025

Seismic Therapeutic, Inc., the machine learning immunology company, today announced the presentation of new preclinical data for its pan‑immunoglobulin G (IgG) sculpting enzyme candidate, S-1117, at the 66^th American Society of Hematology (ASH) Annual Meeting taking place on December 7-10 in San Diego, CA. Preclinical data for S-1117 demonstrated superior efficacy in prophylactic and therapeutic murine models of acute immune thrombocytopenia (ITP) compared to a benchmark neonatal Fc receptor (FcRN) inhibitor therapy. ITP is an autoimmune disease that causes the body to attack its own platelets, resulting in low platelet count and bleeding.

S-1117 is a novel engineered Fc-fused pan-IgG protease targeting IgG autoantibodies. Within a single molecule, S-1117 addresses multiple, clinically validated, orthogonal pathogenic mechanisms, which may result in superior clinical outcome in autoantibody-mediated disorders, such as ITP and myasthenia gravis. Seismic plans to develop S-1117 for both chronic and acute treatment of IgG autoantibody-driven diseases and expects to initiate a Phase 1 clinical trial of S-1117 in healthy volunteers in the first half of 2025.

“Enzymatic IgG degradation by S-1117 offers a new therapeutic approach to address autoantibody-mediated diseases. The new preclinical ITP mouse model data further validates the speed, depth and magnitude of the IgG reduction we can achieve in vivo with S-1117, as well as its superior activity in this setting compared to a benchmark FcRN inhibitor,” said John Sundy, MD, PhD, Chief Medical Officer and Head of R&D at Seismic Therapeutic. “These results, combined with the previously disclosed profile of S‑1117, continue to highlight its potential as a fast acting, treat-to-target drug for chronic and acute settings.”

The S-1117 preclinical data at ASH 2024 builds upon the recently-presented results from in vitro and in vivo studies, which showed that S-1117 achieved deep, rapid and sustained reduction of all IgG subclasses and was able to directly cleave circulating and immune complexed IgG, as well as the IgG B cell receptor expressed on memory B cells. S-1117 also has the potential for a convenient, small volume, subcutaneous, self-administered treatment regimen administered every 4-6 weeks.

In the efficacy studies in animal models of ITP, acute ITP was induced in mice by rabbit anti-mouse platelet serum (or RAMS) injections, and S-1117 was administered before or after RAMS injections in the prophylactic model or therapeutic model, respectively. The new efficacy data presented at ASH 2024 includes the following highlights:

• S-1117 demonstrated superior efficacy as measured by blocking platelet destruction compared to a benchmark FcRN inhibitor.
• In the prophylactic model, a single dose of S-1117 protected mice against antibody-mediated platelet destruction even with re-dosing of RAMS.
• In the therapeutic model, a single dose of S-1117 accelerated and sustained the recovery of platelet counts, maintaining efficacy even with re-dosing of RAMS.

The poster for the data presented at ASH 2024 is available here on Seismic’s website.

About Seismic Therapeutic

Seismic Therapeutic™ is a biotechnology company making a major shift in how immunology therapies are discovered and developed, enabled by machine learning. The company has a growing preclinical stage best-in-class and first-in-class biologics pipeline, derived from its integrated IMPACT platform, to control dysregulated adaptive immunity and address multiple autoimmune diseases. The company is backed by a strong syndicate of life sciences investors and is located in the Boston biotechnology hub. For more information, please visit www.seismictx.com and follow us on LinkedIn and on X @Seismic_Tx.

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