Seismic Therapeutic Presents Preclinical Data on S-1117, its Novel Pan-IgG Protease Addressing Multiple Pathogenic Mechanisms in Autoimmune Disease, at American Academy of Neurology (AAN) 2024

Seismic Therapeutic, Inc., the machine learning immunology company, today announced the presentation of preclinical data for its pan?immunoglobulin G (IgG) sculpting enzyme candidate, S-1117, at the American Academy of Neurology (AAN) 2024 annual meeting in Denver. The poster presentation titled, "Preclinical Pharmacology of S-1117, a Novel Engineered Fc-fused IgG Cleaving Enzyme, for Chronic Treatment of Autoantibody-mediated Diseases," features preclinical in vitro and in vivo results supporting the differentiated therapeutic profile of S-1117.

S-1117 is a novel engineered pan-IgG protease targeting IgG autoantibodies that have an important role in the pathogenesis of a range of chronic and acute autoantibody mediated diseases, including the chronic neuromuscular autoimmune disorder, myasthenia gravis.

"Given our pan-IgG sculpting enzyme's ability to address multiple pathogenic mechanisms as a single drug agent, it has the potential to achieve improved clinical outcomes compared to current therapeutic approaches in chronic autoantibody-mediated diseases," said Kevin Otipoby, PhD, Chief Research Officer of Seismic Therapeutic. "With the polypharmacology that is possible with S-1117, we aim to overcome existing treatment limitations and achieve higher rates of remission for patients with chronic autoantibody mediated diseases. We are excited to continue to advance S-1117 towards first-in-human clinical studies."

The preclinical data presented at AAN describe results across a variety of measures that support the differentiated profile of S-1117 compared to therapeutic benchmarks in chronic autoantibody-mediated diseases. S-1117 addresses multiple mechanisms of autoimmunity, as shown by the preclinical results that demonstrated rapid and deep lowering of IgG and immune complex levels, reducing IgG effector functions, and cleaving the antigen B?cell receptor (BCR) on memory B cells.

In vitro studies demonstrated S-1117's ability to cleave soluble and membrane-bound forms of IgG, including the BCR, and to reduce tissue-damaging IgG effector functions:

• S-1117 cleaved soluble IgG and the antigen BCR on memory B cells with comparable potency and demonstrated the ability of S-1117 to degrade immune complex in tissues and in circulation.
• S-1117 reduced IgG effector functions, significantly reducing antibody-dependent cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) of peripheral blood mononuclear cells (PBMCs).

In vivo studies performed in mouse models with S-1117 or Fc-fused pan-IgG protease progenitor molecule demonstrated the compound's ability to lower pathogenic IgG and immune complex levels:

• A murine pharmacokinetic/pharmacodynamic model showed rapid, deep and sustained reduction of IgG levels.
• A murine nephritis model showed reduced complement and immune complex deposition, as well as reduced proteinuria, blood urea nitrogen and renal pathology.

About Seismic Therapeutic
Seismic Therapeutictm 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.