Seismic Therapeutic Showcases IMPACT Platform's Machine Learning Abilities for Novel Biologic Medicines

Seismic Therapeutic, Inc., based in Watertown, Massachusetts, has unveiled new data showcasing the broad capabilities of its IMPACT platform in developing innovative biologic medicines. The data illustrate the platform's application in designing S-1117, a pan-IgG protease geared for chronic administration, which is among the company's leading programs. They also underscore the platform's potential to create various biologic modalities besides pan-IgG proteases. These advancements are being presented at the 16th PEGS Europe Protein and Antibody Engineering Summit in Barcelona, Spain.

The IMPACT platform of Seismic Therapeutic combines machine learning with structural biology, protein engineering, and translational immunology. This integration facilitates the parallel optimization of multiple properties in novel biologic therapies. The company has developed unique machine learning algorithms that enhance developability, modulate function, and reduce immunogenicity, thereby speeding up the creation of biotherapeutics.

Nathan Higginson-Scott, PhD, Chief Technology Officer at Seismic Therapeutic, expressed enthusiasm about presenting the enhancements to the IMPACT platform. He highlighted the advantages of incorporating machine learning into the drug development process, which allows for rapid design and optimization of innovative drug-like protein therapeutics. A significant aspect of their approach is the capability to predict and eliminate both T and B cell epitopes, surpassing current techniques while preserving crucial attributes required for designing biologic drugs.

The presentation at PEGS Europe 2024 by Ryan Peckner, PhD, Director and Head of Machine Learning at Seismic Therapeutic, includes key highlights:

1. The original application of the IMPACT platform involved using a combination of in silico design and wet lab validation to create S-1117. This engineered pan-IgG protease variant was designed to reduce both T cell epitopes, to prevent the generation of new anti-drug antibodies (ADA), and B cell epitopes, to decrease binding of pre-existing ADAs. This supports chronic dosing while maintaining activity and stability.

2. A new application of the IMPACT platform demonstrated the first instance of engineering a protease’s specificity. Seismic used its multi-objective optimization capabilities to create a selective IgE protease by transforming a protease with both IgG and IgE cleaving properties in a single round of designs, while enhancing activity and stability.

3. In silico sequence design and fitness evaluation showed that Seismic’s machine learning framework can, in a generalizable manner, eliminate immunogenic T cell epitopes across a wide range of protein drug modalities, especially non-protease enzymes and non-monoclonal antibodies, while retaining their potency with high confidence.

John Sundy, MD, PhD, Chief Medical Officer and Head of R&D at Seismic Therapeutic, noted that applying the IMPACT platform to new protein therapeutics for immune system diseases has accelerated the design and development of their lead drug candidates, S-1117 and S-4321, a dual-cell bidirectional PD-1 antibody agonist. These candidates are on track to enter clinical trials in the first half of 2025. The data demonstrate how the company is enhancing its IMPACT platform to act as a product engine, creating a variety of biologic therapies aimed at addressing diseases more effectively by optimizing function, reducing immunogenicity, and improving the drug-like properties of biologic therapies.

Seismic Therapeutic is a biotechnology company revolutionizing the creation and development of immunology therapies through machine learning. The company has a growing preclinical pipeline of best-in-class and first-in-class biologics, derived from its integrated IMPACT platform, aimed at controlling dysregulated adaptive immunity and addressing multiple autoimmune diseases. Based in the Boston biotechnology hub, Seismic Therapeutic is supported by a strong syndicate of life sciences investors.