Seismic Therapeutic's Novel IgE Protease S-8484 Shows Promise in Preclinical Allergic Disease Studies

• Seismic Therapeutic's S-8484, an engineered IgE protease, demonstrates rapid and sustained degradation of IgE in both plasma and B cell receptors, showing potential for treating allergic diseases.
• Preclinical studies reveal S-8484's comparable efficacy to approved anti-IgE therapy in animal models of anaphylaxis and allergy, with successful reduction of IgE-induced inflammation.
• The drug candidate, developed using Seismic's IMPACT platform with machine learning tools, shows high selectivity and potency for IgE, positioning it as a potential treatment for food allergies and chronic rhinosinusitis.

Seismic Therapeutic has unveiled promising preclinical data for S-8484, its novel immunoglobulin E (IgE) protease, demonstrating significant potential in treating allergic diseases. The findings, presented at the 2025 AAAAI/WAO Joint Congress in San Diego, showcase the drug's ability to rapidly degrade IgE in multiple contexts.

Innovative Mechanism of Action

S-8484 represents a groundbreaking approach to treating allergic conditions through direct enzymatic degradation of IgE. "We believe we are at the forefront of an emerging field to design drugs based on bacterial proteases to address immune-driven diseases," stated Kevin Otipoby, PhD, Chief Research Officer of Seismic Therapeutic. The drug's dual mechanism targets both circulating IgE and IgE expressed on B cells, potentially offering more comprehensive treatment outcomes.

Compelling Preclinical Results

Laboratory studies revealed several key therapeutic properties of S-8484:

• Rapid and selective cleavage of soluble IgE
• Concentration-dependent cleavage of IgE B cell receptors
• Reduction of high-affinity IgE Fc receptor expression on mast cells from humanized mice

In vivo testing demonstrated efficacy comparable to existing anti-IgE therapies, with notable outcomes including:

• Successful reduction of IgE-induced ear inflammation
• Quick resolution of systemic anaphylactic reactions
• Decreased serum IgE and eosinophil levels in bronchoalveolar lavage during asthma model testing

Technical Innovation and Development

The development of S-8484 showcases the capabilities of Seismic's IMPACT platform, which utilizes advanced structure-augmented machine learning. Nathan Higginson-Scott, PhD, Chief Technology Officer, emphasized how they overcame traditional selectivity challenges: "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."

Therapeutic Applications

S-8484 is being developed to address several allergic conditions with significant unmet needs, including:

• Food allergies
• Chronic rhinosinusitis with nasal polyps
• Chronic spontaneous urticaria

The drug's ability to eliminate IgE both from circulation and cell surfaces positions it as a potentially powerful tool in treating these conditions. The company is now advancing S-8484 through IND-enabling studies toward clinical development.