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Company’s engineered IgE protease, designed by its IMPACT platform, targets mechanisms in allergic diseases
Preclinical in vitro and in vivo findings are supportive of advancing development candidate S-8484 into IND-enabling studies
Data is presented at the 2025 American Academy of Allergy, Asthma and Immunology (AAAAI) / World Allergy Organization (WAO) Joint Congress
Watertown, Mass., February 28, 2025 – Seismic Therapeutic, Inc., the machine learning immunology company, today announced the presentation of preclinical data for its immunoglobulin E (IgE) protease, S‑8484, demonstrating rapid and sustained degradation of IgE in plasma and on IgE B cell receptors. S‑8484 also demonstrated efficacy in animal models of allergic disease. Designed using protein structure-augmented machine learning tools developed with Seismic’s IMPACT platform, S‑8484 is the Company’s third development stage program, and its second immunoglobulin protease pipeline candidate engineered to have potent enzymatic activity with optimized therapeutic properties. The in vitro and in vivo data supporting S‑8484 are being presented at the 2025 American Academy of Allergy, Asthma and Immunology (AAAAI) / World Allergy Organization (WAO) Joint Congress taking place in San Diego, California, February 28-March 3, 2025.
“We believe we are at the forefront of an emerging field to design drugs based on bacterial proteases to address immune-driven diseases. Targeting IgE with a protease such as S‑8484 offers the unique ability to directly degrade serum IgE antibody and cleave IgE expressed on B cells therefore targeting multiple mechanisms of humoral immune dysfunction in allergic diseases to induce rapid and sustained reduction in IgE,” said Kevin Otipoby, PhD, Chief Research Officer of Seismic Therapeutic. “In developing S-8484 as an IgE protease, Seismic is advancing a novel approach to address the significant unmet need in allergic diseases, and the data that we are sharing support differentiated efficacy driven by chronic IgE degradation. We look forward to continuing our work with S‑8484 in IND-enabling studies on the path to clinical development.”
The preclinical data are being presented at AAAAI/WAO in a poster presentation, entitled “Discovery and Characterization of a Novel Engineered Fc-fused IgE Cleaving Enzyme for Treatment of IgE Mediated Diseases,” by first author Purvi Mande, PhD, Principal Scientist of Seismic Therapeutic. The poster describes preclinical studies of S‑8484 and Fc-fused IgE protease progenitor molecules that demonstrate the multiple mechanisms of action and efficacy in in vitro and in vivo studies.
Highlights from the in vitro studies include demonstration of the following therapeutic properties:
In vivo studies performed in mouse models demonstrate that an IgE protease achieved comparable efficacy to an approved anti-IgE therapy in animal models of anaphylaxis and allergy, including:
“The rapid advancement of S-8484 as an IgE protease from research through preclinical development is a testament to our ability to design and optimize protease therapeutics with our IMPACT platform, leveraging the latest advancements in structure-augmented machine learning,” said Nathan Higginson-Scott, PhD, Chief Technology Officer of Seismic Therapeutic. “We were able to overcome a selectivity challenge often inherent in naturally occurring proteases to create a molecule with high selectivity and potency for IgE from a precursor that could weakly degrade multiple isotypes. Our ability to perform multi-objective optimization also allowed us to develop a molecule with the desired biological properties and manufacturability. We are excited about the differentiated profile of S‑8484 to target IgE with the potential to address unmet need in allergic diseases.”
The poster for the data presented at AAAAI/WAO will be available here on Seismic’s website.
About S-8484
S-8484 is a novel immunoglobulin E (IgE) protease therapeutic engineered with Seismic’s IMPACT platform to achieve selective cleaving of IgE and with enhanced drug-like properties. By selectively cleaving IgE, S‑8484 is designed to eliminate IgE from circulation and on cell surfaces, to address the humoral immune dysregulation that results in allergic diseases such as food allergies, chronic rhinosinusitis with nasal polyps, and chronic spontaneous urticaria.
About Seismic Therapeutic
Seismic Therapeutic™ is a biotechnology company making a major shift in how immunology therapies are discovered and developed, enabled by our proprietary machine learning tools. The company has a growing pipeline including two clinical stage best-in-class and first-in-class biologics, derived from its integrated IMPACT platform, to control dysregulated adaptive immunity and address multiple immune-related diseases. S-1117 is a novel engineered Fc-fused pan-IgG protease targeting IgG autoantibodies, and S-4321 is a non-depleting bifunctional PD‑1: FcγRIIb‑selective agonist antibody for the treatment of autoimmune disease. Both programs will enter first-in-human studies in 2025. Seismic 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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