Seismic Therapeutic Starts Phase 1 Trial of S-1117 for Antibody-Mediated Diseases
Seismic Therapeutic, Inc., a machine learning-driven immunology company, has announced a significant milestone in its journey toward developing transformative therapies for autoimmune diseases. The company has dosed the first cohort of healthy subjects in its Phase 1 clinical trial of S-1117, a novel engineered Fc-fused pan-immunoglobulin G (IgG) protease designed to target IgG autoantibodies. S-1117 is being evaluated for its potential to provide both chronic and acute treatment options for IgG autoantibody-driven conditions such as myasthenia gravis, chronic inflammatory demyelinating polyneuropathy, and immune thrombocytopenia.
This first-in-human study builds upon strong preclinical evidence that S-1117 can rapidly, deeply, and sustainably reduce IgG levels. Additionally, it has demonstrated the ability to cleave the B cell receptor on memory B cells and eliminate IgG effector functions. These mechanisms position S-1117 as a promising candidate for treating autoimmune diseases by addressing the underlying pathology at multiple levels.
“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. 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,” said Jo Viney, PhD, Chief Executive Officer of Seismic Therapeutic. “The strength of our approach is reinforced by our two additional drug candidates, S-4321, a PD-1 FcγRIIb bifunctional agonist, which remains on track to enter the clinic by mid-year, and S-8484, an IgE protease, which has now entered IND-enabling studies.”
About the Phase 1 Clinical Trial
The Phase 1 clinical trial of S-1117 is a randomized, placebo-controlled, double-blind study designed to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of the drug candidate in healthy subjects. Key pharmacodynamic markers being assessed include the rate and extent of IgG reduction, as well as the cleavage of the B cell receptor on memory B cells. The study will be conducted in two stages: an initial single ascending dose (SAD) stage, followed by a multiple ascending dose (MAD) stage.
Seismic intends to explore S-1117’s potential as both a chronic and acute treatment, implementing a treat-to-target approach that allows dosing to be tailored to a patient’s disease activity. This strategy aims to offer a personalized approach to managing IgG autoantibody-driven diseases, potentially improving patient outcomes and treatment efficacy.
Further details about the Phase 1 trial of S-1117 can be accessed on ClinicalTrials.gov under the identifier NCT06828393.
The Science Behind S-1117
S-1117 has been engineered with a differentiated profile as a novel pan-IgG protease. The therapy is designed to address multiple pathogenic mechanisms associated with IgG autoantibody-driven diseases, providing a multifaceted approach to treatment. Leveraging its proprietary IMPACT platform, Seismic has developed S-1117 as a molecule that is deimmunized for T and B cell epitopes, making it suitable for chronic administration without inducing an unwanted immune response.
Additionally, Seismic has demonstrated successful large-scale Good Manufacturing Practice (GMP) production of S-1117. The drug is formulated for subcutaneous administration, providing a convenient dosing option that enhances patient accessibility and adherence.
“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,” said John Sundy, MD, PhD, Chief Medical Officer and Head of R&D at Seismic Therapeutic. “Our IMPACT platform enabled us to create a molecule deimmunized for T and B cell epitopes that is suitable for chronic dosing. We also 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.”
Expanding Seismic’s Pipeline
Seismic’s clinical advancement of S-1117 underscores the company’s broader commitment to addressing key unmet needs in immunology. The company’s pipeline includes multiple promising candidates aimed at modulating the immune system and providing innovative solutions for patients with autoimmune diseases:
- S-4321: A PD-1 FcγRIIb bifunctional agonist, designed to selectively enhance regulatory pathways within the immune system. The candidate remains on track to enter clinical trials by mid-year.
- S-8484: An IgE protease that has now entered IND-enabling studies, with the goal of addressing IgE-mediated allergic and autoimmune conditions.
These additional candidates reinforce Seismic’s strategy of developing biologics that can be precisely engineered to regulate immune responses, leveraging cutting-edge advancements in machine learning and immunology.
The Future of IgG Autoantibody-Driven Disease Treatment
Autoimmune diseases driven by IgG autoantibodies present significant treatment challenges, as current therapies often provide only partial relief and come with the risk of immunosuppression. By targeting IgG autoantibodies at their source, Seismic aims to deliver a more effective and safer therapeutic approach. The successful development of S-1117 could open the door for future therapies that take advantage of protease-based mechanisms to selectively target disease-driving antibodies while preserving overall immune function.
As Seismic Therapeutic moves forward with its clinical program, the company remains committed to advancing the frontiers of immunology, bringing AI-powered drug discovery together with rigorous scientific research to develop the next generation of precision medicines for autoimmune diseases.
