Seismic Therapeutic Advances Novel IgG Protease S-1117 into Phase 1 Clinical Trial for Autoimmune Diseases

• Seismic Therapeutic has dosed the first cohort of healthy participants in a Phase 1 trial of S-1117, a novel pan-IgG protease designed to target autoantibodies in multiple autoimmune conditions.
• The randomized, double-blind trial will evaluate S-1117's safety, pharmacokinetics, and ability to rapidly reduce IgG levels and cleave B cell receptors on memory B cells.
• S-1117, developed using Seismic's machine learning IMPACT platform, shows potential for treating conditions including myasthenia gravis, chronic inflammatory demyelinating polyneuropathy, and immune thrombocytopenia.

Seismic Therapeutic has initiated dosing in the first cohort of healthy participants for its Phase 1 clinical trial of S-1117, marking the company's transition to a clinical-stage biotechnology firm. The novel engineered Fc-fused pan-immunoglobulin G (IgG) protease targets IgG autoantibodies implicated in various autoimmune diseases.

The randomized, placebo-controlled, double-blind trial will assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of S-1117. Key pharmacodynamic markers include measuring the speed and depth of IgG reduction and cleavage of the B cell receptor on memory B cells.

"The start of our first-in-human study of S‑1117 marks a significant milestone for Seismic as we transition to a clinical-stage company," said Jo Viney, PhD, Chief Executive Officer of Seismic Therapeutic. "S‑1117 validates our founding belief that we have the potential to create transformative medicines by leveraging machine learning through our IMPACT platform, guided by the best minds in immunology to discover novel biologics."

Trial Design and Development Strategy

The Phase 1 study will proceed in two stages, beginning with a single ascending dose portion followed by a multiple ascending dose evaluation. This structured approach will help establish the optimal dosing regimen for future clinical development.

Seismic intends to investigate S-1117 as both a chronic and acute treatment using a "treat-to-target" approach that can be tailored to individual patient disease activity. This strategy could potentially allow for personalized treatment protocols based on the severity and manifestation of autoimmune conditions.

John Sundy, MD, PhD, Chief Medical Officer and Head of R&D at Seismic Therapeutic, explained the rationale behind S-1117's development: "We designed S‑1117 with a differentiated profile as a novel pan-IgG protease with the ability to address multiple pathogenic mechanisms at the root of IgG autoantibody-driven diseases. Our IMPACT platform enabled us to create a molecule deimmunized for T and B cell epitopes that is suitable for chronic dosing."

Dr. Sundy also highlighted the manufacturing achievements: "We demonstrated successful large-scale GMP manufacturing with a formulation that enables convenient subcutaneous dosing. We believe this broad approach has the potential to drive deeper responses and offer improved clinical outcomes for patients with autoimmune diseases."

Therapeutic Potential and Target Indications

S-1117 has demonstrated biological activity in multiple in vivo models, suggesting potential efficacy for both chronic and acute treatment of IgG autoantibody-driven diseases. The company is particularly focused on three key indications:

1. Myasthenia gravis - a neuromuscular disorder characterized by weakness and rapid fatigue of voluntary muscles
2. Chronic inflammatory demyelinating polyneuropathy - a neurological disorder causing progressive weakness and impaired sensory function
3. Immune thrombocytopenia - an autoimmune bleeding disorder characterized by abnormally low platelet counts

The therapeutic approach of S-1117 is designed to address multiple, clinically validated pathogenic mechanisms within a single molecule. By selectively cleaving IgG and exhibiting improved drug-like properties, S-1117 may potentially offer superior clinical outcomes compared to existing therapies.

The IMPACT Platform and Pipeline Expansion

S-1117 was developed using Seismic's proprietary IMPACT platform, which integrates machine learning with immunology expertise to discover novel biologics. This approach has enabled the company to build a growing pipeline of potential best-in-class and first-in-class biologics for autoimmune diseases.

Beyond S-1117, Seismic is advancing two additional drug candidates: S‑4321, a PD-1 Fcγ RIIb bifunctional agonist expected to enter clinical trials by mid-year, and S-8484, an IgE protease that has entered IND-enabling studies.

The Massachusetts-based company is backed by a strong syndicate of life sciences investors and is positioning itself as a leader in applying machine learning to immunology drug discovery.

Further details about the S-1117 Phase 1 clinical trial can be found on ClinicalTrials.gov (NCT06828393).