Novel engineered Fc-fused pan-IgG protease demonstrates deep, rapid and sustained reduction of IgG levels and ability to address multiple pathogenic mechanisms as a single drug molecule
Preclinical data supports potential for S-1117’s multi-mechanistic action to address unmet need in myasthenia gravis
Company expects to initiate first-in-human Phase 1 clinical trial of S-1117 in 1H 2025
WATERTOWN, Mass.--(BUSINESS WIRE)--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 Myasthenia Gravis Foundation of America (MGFA) Scientific Session at the American Association of Neuromuscular and Electrodiagnostic Medicine (AANEM) 2024 annual meeting in Savannah, Georgia.
S-1117 is a novel engineered Fc-fused pan-IgG protease targeting IgG autoantibodies that play a key role in the pathogenesis of a range of chronic and acute autoantibody mediated diseases, including myasthenia gravis (MG), a chronic neuromuscular autoimmune disorder. Seismic plans to initiate a Phase 1 clinical trial of S-1117 in healthy volunteers in the first half of 2025.
“S-1117 has shown the unique ability to target multiple orthogonal pathogenic mechanisms within a single molecule, and we believe this multi-mechanistic approach has the potential to drive deeper responses and offer improved clinical outcomes for MG patients, as well as for patients with other autoantibody-mediated diseases,” said John Sundy, MD, PhD, Chief Medical Officer and Head of R&D at Seismic Therapeutic. “Despite recent treatment advancements, there remains a significant opportunity to address the large proportion of MG patients who do not achieve remission or low disease activity with currently approved therapies. We believe S‑1117 can offer advantages over existing treatment options and look forward to advancing S‑1117 into first-in-human Phase 1 clinical studies in the first half of next year.”
The S-1117 preclinical data presented at AANEM showed deep, rapid and sustained reduction of all IgG subclasses. S-1117 also demonstrated the ability to directly cleave circulating and immune complexed IgG, as well as the IgG B cell receptor expressed on memory B cells. Moreover, current S-1117 PK/PD modeling indicates the potential for a convenient small volume, subcutaneous, self-administered treatment regimen administered every 4-6 weeks.
Highlights of the Presentation
In vitro, S-1117 was shown to cleave soluble forms of IgG from healthy volunteers and MG patients. The results support additional key attributes of S-1117:
- Cleaves all IgG subclasses, including IgG3, in plasma of healthy individuals and MG patients;
- Achieves a magnitude of soluble IgG cleavage in vitro from MG patients similar to healthy volunteers; and
- Cleaves preformed immune complexes, which drive injury to tissues, as well as the B cell receptor.
In vivo studies performed with S-1117 in rabbit and mouse models showed rapid, deep and sustained IgG reduction and demonstrated 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 indicate that infrequent chronic low doses can achieve titratable IgG reductions of 90% or greater. PK/PD modeling further supports the potential for a subcutaneous, self-administered treatment regimen to achieve therapeutic levels of IgG reduction at doses as low as <1mg/kg of drug administered monthly. In addition, given the rapid onset of action, S-1117 is predicted to be applied to acute conditions, such as MG crisis.
The poster for the data presented at AANEM 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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