Seismic Therapeutic Shares New Preclinical Data on S-1117 for Autoantibody-Mediated Diseases at MGFA Session, AANEM Meeting

Seismic Therapeutic, Inc., a company specializing in machine learning and immunology, recently unveiled new preclinical data for its investigational enzyme, S-1117, at the Myasthenia Gravis Foundation of America (MGFA) Scientific Session during the American Association of Neuromuscular and Electrodiagnostic Medicine (AANEM) 2024 annual meeting in Savannah, Georgia. S-1117 is an innovative Fc-fused pan-IgG protease that targets IgG autoantibodies, which are implicated in various chronic and acute autoantibody-mediated diseases, such as myasthenia gravis (MG), a persistent neuromuscular autoimmune disorder. The company aims to begin a Phase 1 clinical trial involving healthy volunteers in the first half of 2025.

"S-1117 presents a unique ability to address multiple pathogenic mechanisms within a single molecule, and we believe this multi-faceted approach could drive deeper responses and enhance clinical outcomes for MG patients, as well as others with autoantibody-mediated diseases," commented John Sundy, MD, PhD, Chief Medical Officer and Head of Research & Development at Seismic Therapeutic. "Despite advances in treatments, a substantial proportion of MG patients do not achieve remission or low disease activity with currently available therapies. We believe S-1117 could offer significant advantages over existing options and eagerly anticipate moving forward with first-in-human Phase 1 clinical trials next year."

The preclinical data presented at AANEM revealed that S-1117 achieved a profound, swift, and sustained reduction of all IgG subclasses. S-1117 also demonstrated its ability to directly cleave circulating and immune-complexed IgG, as well as the IgG B cell receptor on memory B cells. Additionally, current pharmacokinetic (PK) and pharmacodynamic (PD) modeling for S-1117 indicates the potential for a small volume, subcutaneous, self-administered treatment regimen every four to six weeks.

Key findings from the presentation included:
- In vitro studies showed that S-1117 cleaved soluble IgG from both healthy volunteers and MG patients.
- S-1117 cleaved all IgG subclasses, including IgG3, in plasma samples from healthy individuals and MG patients.
- The magnitude of soluble IgG cleavage in vitro from MG patients was similar to that from healthy volunteers.
- S-1117 cleaved preformed immune complexes and the B cell receptor.

In vivo studies using rabbit and mouse models demonstrated rapid, deep, and sustained IgG reduction and cleavage of the B cell receptor within hours after both intravenous and subcutaneous administration. Projections of human PK and PD through quantitative systems pharmacology (QSP) modeling for S-1117 suggest that low chronic doses administered infrequently can achieve significant IgG reductions of 90% or more. The modeling further supports the potential for a subcutaneous, self-administered treatment regimen to maintain therapeutic IgG reduction levels with doses as low as <1mg/kg administered monthly. Given its rapid onset of action, S-1117 is also anticipated to be applicable to acute conditions, such as MG crisis.

Seismic Therapeutic is utilizing machine learning to pioneer new immunology therapies. The company has an expanding pipeline of preclinical stage biologics, derived from its integrated IMPACT platform, aimed at managing dysregulated adaptive immunity and addressing multiple autoimmune diseases. Seismic Therapeutic is supported by a strong syndicate of life sciences investors and is located in the Boston biotechnology hub.