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Preclinical results demonstrate that immunoglobin G (IgG) cleaving enzymes can address the primary pathogenic mechanism in myasthenia gravis, an autoimmune disorder, by degrading immunoglobulins in circulation and in immune complexes, thereby eliminating complement deposition
Findings also reveal the role of immunoglobin M (IgM) in activation of the complement system in myasthenia gravis disease pathology
Publication in Proceedings of the National Academy of Sciences results from a collaboration between Seismic and academic investigators
Watertown, Mass., October 21, 2025 – Seismic Therapeutic, Inc., the machine learning immunology company, today announced the publication of data on the activity of its engineered pan-immunoglobin enzymes in myasthenia gravis, an autoantibody-driven disease in the Proceedings of the National Academy of Sciences (PNAS). The article is titled “Therapeutic IgG and IgM-specific proteases disarm the acetylcholine receptor autoantibodies that drive myasthenia gravis pathology.”
The research is part of an ongoing multi-year collaboration between Seismic and Yale University and was led by Kevin O’Connor, Ph.D., Professor of Neurology and Immunobiology at Yale School of Medicine and an internationally recognized expert in B cell-mediated autoimmune diseases.
The published experiments investigated the cleavage of anti-acetylcholine receptor (AChR) autoantibodies and three pathogenic mechanisms that contribute to myasthenia gravis, including activation of the complement system—a primary driver of structural damage at the neuromuscular junction. Results showed how Seismic’s engineered pan-immunoglobin G (IgG) enzymes cleaved pathogenic AChR autoantibodies in both circulation and as part of immune complexes, effectively inhibiting complement activation.
The study also demonstrated that AChR-IgM is also a significant driver of complement deposition in myasthenia gravis, acting alone or synergistically with IgG in distinct patient subsets. These pathogenic effects were fully blocked by an IgM-specific protease engineered by Seismic.
“These data demonstrate the power of our platform to engineer proteases that can uniquely target mechanisms underlying disease pathology,” said John Sundy, Chief Medical Officer & Head of Research and Development at Seismic Therapeutic. “We are proud to partner with Dr. O’Connor and his team at Yale to advance the scientific understanding of myasthenia gravis, and how our Ig-targeted enzymes may enable a more comprehensive approach to treating the pathogenic mechanisms that drive autoantibody-mediated diseases.”
The publication in PNAS can be accessed via this link.
About Seismic Therapeutic
Seismic Therapeutic™ is a clinical-stage biotechnology company making a major shift in how immunology therapies are discovered and developed, enabled by machine learning. The company has a growing preclinical stage best-in-class and first-in-class biologics pipeline, derived from its integrated IMPACT platform, to control dysregulated adaptive immunity and address multiple autoimmune diseases. The company 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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