Seismic Therapeutic Forms Translational Medicine Advisory Board with Prominent Experts in Immunology, Rheumatology, Dermatology and Neurology

Watertown, Mass., March 18, 2025 – Seismic Therapeutic, Inc., the machine learning immunology company, today announced the formation of a Translational Medicine Advisory Board to support the company’s focus on accelerating the path to impactful, patient-centric therapies for autoimmune and inflammatory diseases. The charter members of Seismic’s Translational Medicine Advisory Board are J. Michelle Kahlenberg, MD, PhD, Gerald Nepom, MD, PhD, Kevin O’Connor, PhD, and Cornelia Weyand, MD, PhD. These distinguished experts bring decades of combined experience and leadership in their respective fields of immunology, rheumatology, dermatology and neurology and will provide strategic guidance as the company advances its pipeline of innovative medicines in clinical trials for immune-driven diseases. They are complemented by additional expert advisors in relevant specialty areas.

“We are honored to welcome this exceptional group of advisors whose expertise will contribute valuable insights as we continue to advance our innovative biologics into the clinic,” said John Sundy, MD, PhD, Chief Medical Officer and Head of R&D for Seismic Therapeutic. “Each member brings a wealth of experience from bench-to-bedside in a range of disease areas, supporting our mission to rapidly bring a new era of medicines for autoimmune and inflammatory diseases to improve outcomes for patients.”

Michelle Kahlenberg, MD, PhD, is a Professor of Internal Medicine (Rheumatology) and Dermatology and Vice Chair of Basic and Translational Research, Internal Medicine at the University of Michigan Medical School. Her clinical work is centered on the care of complicated lupus patients, including those with refractory skin disease, and her research is funded by multiple NIH and foundation awards and combines translational approaches using patient samples and murine models to uncover the mechanisms that drive lupus and other autoimmune diseases. Dr. Kahlenberg completed her BS in Biology at Denison University, her MD, PhD, and Internal Medicine training at Case Western Reserve University, and her fellowship in Rheumatology at the University of Michigan.
Gerald (Jerry) Nepom, MD, PhD, is an Affiliate Professor, Immunology, University of Washington School of Medicine, and Immune Tolerance Network Senior Advisor at Benaroya Research Institute (BRI), Center for Interventional Immunology. Nepom is a past Director of both the BRI and the NIAID-sponsored Immune Tolerance Network. His research is focused on identifying and understanding molecular and genetic mechanisms contributing to pathogenesis of autoimmune disorders and using this information to evaluate autoreactive T cell lineage and fate determination. His translational and clinical applications include development and use of immunological monitoring tools for predicting disease susceptibility and response to therapy in clinical trials, with special emphasis on type 1 diabetes. Dr. Nepom received his bachelor’s degree in Biochemistry from Harvard, and his PhD and MD from the University of Washington.
Kevin O’Connor, PhD, is a Professor of Neurology and Immunobiology at Yale School of Medicine. He earned a Bachelor of Science degree in Chemistry from the University of Massachusetts at Amherst and a PhD in Biochemistry from Tufts University. Following his doctoral studies, Dr. O’Connor completed postdoctoral training in Immunology at Harvard Medical School, where he subsequently served as an Assistant Professor for several years before joining the faculty at Yale. Dr. O’Connor’s research focuses on human translational immunology and neurology, with a particular emphasis on understanding the role of B cells and antibodies in autoimmune diseases. His laboratory investigates both the cellular and molecular mechanisms by which autoreactive B cell subsets and autoantibody isotypes initiate and sustain autoimmunity. This research is conducted through the study of human-derived specimens. These human specimens are often obtained from clinical trials of immune-modulating treatments, serving to leverage a deeper understanding of immune mechanism variability among patients. By understanding this variability, his team’s work contributes to the advancement of personalized medicine approaches in treating autoimmune disorders.
Cornelia (Connie) M. Weyand, MD, PhD, is a Professor of Medicine and Immunology at the Mayo Clinic College of Medicine and Science and the Mayo Alix School of Medicine. She is also Professor Emerita at Stanford University. Weyand’s research has focused on how immune responses deviate from host protection to tissue damage. Her primary focus has been on autoimmune diseases, specifically atherosclerotic disease and the vasculitides. Prior to her appointment at Mayo Clinic, Dr. Weyand was Chief of Rheumatology and Immunology and the Director of the Center for Translational Medicine at Stanford University and Professor of Medicine at Emory University, where she served as the Director of the Lowance Center for Human Immunology and the Division of Rheumatology. Dr. Weyand earned her MD in Germany, followed by a residency at Hannover Medical School, Germany, and a fellowship in Immunology at Stanford University.

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.

Media Contact
Kathryn Morris, The Yates Network
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kathryn@theyatesnetwork.com

Investor Contact
Emiley Demick, Precision AQ (formerly Stern IR)
212-362-1200
emiley.demick@precisionaq.com

Seismic Therapeutic Doses First Cohort in Phase 1 Clinical Trial of S-1117, a Novel Pan IgG Protease Therapy for Antibody-Mediated Diseases

Clinical trial will assess safety, tolerability and reduction in immunoglobin G (IgG)

Plans to develop S-1117 for treatment of wide array of IgG autoantibody-driven diseases, such as myasthenia gravis, chronic inflammatory demyelinating polyneuropathy, and immune thrombocytopenia

Watertown, Mass., March 11, 2025 – Seismic Therapeutic, Inc., the machine learning immunology company, today announced the dosing of the first healthy subject cohort in a Phase 1 clinical trial of S‑1117, a novel engineered Fc-fused pan-immunoglobin G (IgG) protease targeting IgG autoantibodies for the treatment of autoimmune diseases. The study will build on preclinical evidence of S‑1117’s rapid, deep, and sustained reduction of IgG levels, cleavage of the B cell receptor on memory B cells, and elimination of IgG effector function. Seismic has also shown biological activity in multiple in vivo models demonstrating S‑1117’s potential for chronic and acute treatment of IgG autoantibody-driven diseases, such as myasthenia gravis, chronic inflammatory demyelinating polyneuropathy, and immune thrombocytopenia.

“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, on track to enter the clinic by mid-year, and S-8484, an IgE protease, which has entered IND-enabling studies.”

The Phase 1 study is a randomized, placebo-controlled, double-blind clinical trial to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of S‑1117 in healthy subjects. Key pharmacodynamic markers include the measurement of the speed and depth of IgG reduction and cleavage of the B cell receptor on memory B cells. The study will be conducted in two parts, a single ascending dose stage followed by a multiple ascending dose stage. Seismic intends to investigate S‑1117 as a chronic and acute treatment, used in a treat-to-target approach that can be tailored to a patient’s disease activity for a wide array of IgG autoantibody-driven diseases.

Further details about the S-1117 Phase 1 clinical trial can be found on ClinicalTrials.gov (NCT06828393).

“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. 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,” said John Sundy, MD, PhD, Chief Medical Officer and Head of R&D at Seismic Therapeutic. “We believe this broad approach has the potential to drive deeper responses and offer improved clinical outcomes for patients with autoimmune diseases.”

About S-1117
S‑1117 is a novel engineered Fc-fused pan-IgG protease targeting IgG autoantibodies engineered with Seismic’s IMPACT platform to selectively cleave IgG and have enhanced drug-like properties. S‑1117 is designed to address multiple, clinically validated, orthogonal pathogenic mechanisms within a single molecule, which may result in superior clinical outcomes in disorders such as myasthenia gravis, chronic inflammatory demyelinating polyneuropathy, and immune thrombocytopenia. Seismic plans to develop S‑1117 for chronic and acute treatment of IgG autoantibody-driven diseases.

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Kathryn Morris, The Yates Network LLC
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Seismic Therapeutic Presents Preclinical Data on S-8484, Its Novel IgE Protease, for Treatment of Allergic Diseases

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:

Potent, rapid and highly selective cleavage of soluble IgE.
Concentration-dependent cleavage of IgE B cell receptor.
Concentration-dependent reduction of expression of the high-affinity IgE Fc receptor, on bone marrow-derived mast cells from humanized mice.

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:

Reduction in IgE-induced ear inflammation when dosed systemically, supporting good tissue penetration.
Rapid resolution of systemic anaphylactic reaction in a therapeutic mouse model.
Reduction of serum IgE and eosinophils in bronchoalveolar lavage (BAL) in rat allergen-induced asthma model.

“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.

Media Contact
Kathryn Morris, The Yates Network LLC
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kathryn@theyatesnetwork.com

Investor Contact
Emiley Demick, Precision AQ
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emiley.demick@precisionaq.com

Seismic Therapeutic Presents New Preclinical Efficacy Data for S-1117 in Prophylactic and Therapeutic Animal Models of Immune Thrombocytopenia (ITP) at 66th ASH Annual Meeting

S-1117 offers a new therapeutic opportunity in autoantibody-mediated diseases such as myasthenia gravis and ITP

Company plans to develop S-1117 for chronic and acute treatment of IgG autoantibody-driven diseases and expects to initiate first-in-human Phase 1 clinical trial in 1H 2025

Watertown, Mass., December 9, 2024 – Seismic Therapeutic, Inc., the machine learning immunology company, today announced the presentation of new preclinical data for its pan‑immunoglobulin G (IgG) sculpting enzyme candidate, S-1117, at the 66^th American Society of Hematology (ASH) Annual Meeting taking place on December 7-10 in San Diego, CA. Preclinical data for S-1117 demonstrated superior efficacy in prophylactic and therapeutic murine models of acute immune thrombocytopenia (ITP) compared to a benchmark neonatal Fc receptor (FcRN) inhibitor therapy. ITP is an autoimmune disease that causes the body to attack its own platelets, resulting in low platelet count and bleeding.

S-1117 is a novel engineered Fc-fused pan-IgG protease targeting IgG autoantibodies. Within a single molecule, S-1117 addresses multiple, clinically validated, orthogonal pathogenic mechanisms, which may result in superior clinical outcome in autoantibody-mediated disorders, such as ITP and myasthenia gravis. Seismic plans to develop S-1117 for both chronic and acute treatment of IgG autoantibody-driven diseases and expects to initiate a Phase 1 clinical trial of S-1117 in healthy volunteers in the first half of 2025.

“Enzymatic IgG degradation by S-1117 offers a new therapeutic approach to address autoantibody-mediated diseases. The new preclinical ITP mouse model data further validates the speed, depth and magnitude of the IgG reduction we can achieve in vivo with S-1117, as well as its superior activity in this setting compared to a benchmark FcRN inhibitor,” said John Sundy, MD, PhD, Chief Medical Officer and Head of R&D at Seismic Therapeutic. “These results, combined with the previously disclosed profile of S‑1117, continue to highlight its potential as a fast acting, treat-to-target drug for chronic and acute settings.”

The S-1117 preclinical data at ASH 2024 builds upon the recently-presented results from in vitro and in vivo studies, which showed that S-1117 achieved deep, rapid and sustained reduction of all IgG subclasses and was able to directly cleave circulating and immune complexed IgG, as well as the IgG B cell receptor expressed on memory B cells. S-1117 also has the potential for a convenient, small volume, subcutaneous, self-administered treatment regimen administered every 4-6 weeks.

In the efficacy studies in animal models of ITP, acute ITP was induced in mice by rabbit anti-mouse platelet serum (or RAMS) injections, and S-1117 was administered before or after RAMS injections in the prophylactic model or therapeutic model, respectively. The new efficacy data presented at ASH 2024 includes the following highlights:

S-1117 demonstrated superior efficacy as measured by blocking platelet destruction compared to a benchmark FcRN inhibitor.
In the prophylactic model, a single dose of S-1117 protected mice against antibody-mediated platelet destruction even with re-dosing of RAMS.
In the therapeutic model, a single dose of S-1117 accelerated and sustained the recovery of platelet counts, maintaining efficacy even with re-dosing of RAMS.

The poster for the data presented at ASH 2024 is available here on Seismic’s website.

About Seismic Therapeutic

Seismic Therapeutic™ is a 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.

Media Contact
Kathryn Morris, The Yates Network
914-204-6412
kathryn@theyatesnetwork.com

Investor Contact
Emiley Demick, Precision AQ
212-362-1200
emiley.demick@precisionaq.com

Seismic Therapeutic Presents New Preclinical Data for S-4321, a Next Generation PD 1:FcγRIIb-Selective Bifunctional Agonist Antibody for the Treatment of Autoimmune Disease, at ACR Convergence 2024

Novel dual-cell bidirectional antibody engages two independent inhibitory receptors on multiple cell types in a single molecule

S-4321 is a low affinity PD-1 agonist with selective and functional FcγRIIb binding, without cell depleting activity

New preclinical data support differentiated profile, demonstrate induction of regulatory T cells and activity in a murine model of graft versus host disease

Company expects to initiate Phase 1 clinical trial of S-4321 in 1H 2025

Watertown, Mass., November 18, 2024 – Seismic Therapeutic, Inc., the machine learning immunology company, today announced the presentation of new data for S-4321, its next generation PD‑1: FcγRIIb‑selective bifunctional agonist antibody for the treatment of autoimmune disease, at ACR Convergence 2024, the annual meeting of the American College of Rheumatology, taking place in Washington, DC, on November 14-19, 2024. Based on the promising preclinical results, Seismic plans to initiate a Phase 1 clinical trial of S-4321 in healthy volunteers in the first half of 2025.

The presentation at ACR Convergence 2024 shows preclinical results supporting the mechanism of action of S-4321 and progress towards the clinic. S-4321 was designed using the Company’s IMPACT platform to agonize the inhibitory PD-1 receptor on T cells in the similar manner as its natural ligand, and to selectively bind and agonize the inhibitory FcγRIIb receptor on B cells/antigen presenting cells (APCs) without causing PD-1 expressing cell depletion.

Highlights of the poster presentation entitled, “S-4321, a novel dual-cell bidirectional PD-1:FcγRIIb selective agonist antibody for the treatment of autoimmune disease,” include:

Optimized Fab antibody domain with low affinity PD-1 binding achieved prolonged PD-1 agonism without causing PD-1 target depletion or IL-2 production, maintaining “the brakes” on activated T effector cells.
Machine learning-designed Fc antibody domain showed selective binding to the inhibitory FcγRIIb receptor over other FcγRs, avoiding the production of proinflammatory cytokines which may blunt efficacy and depletion of PD-1+ cells, including regulatory T cells (Tregs) which are needed for immune homeostasis. Moreover, the proprietary Fc domain in S-4321 agonizes FcγRIIb, adding B cell/APC inhibition in combination with PD-1 mediated T effector cell inhibition.
S-4321 promoted the induction of Tregs and inhibits graft versus host disease (GvHD) progression in a murine model.
Non-human primate studies demonstrated dose-proportional exposure and ~70% bioavailability of S-4321 with subcutaneous dosing, supporting the potential for a convenient self-administered regimen.

“We deliberately designed S-4321 as a novel bifunctional antibody with optimal agonism of both PD-1 and FcγRIIb inhibitory receptors in a single molecule,” said John Sundy, MD, PhD, Chief Medical Officer and Head of R&D at Seismic Therapeutic. “We believe the distinct profile of S-4321 will translate into superior drug activity and clinical benefit in a number of prevalent autoimmune diseases. We look forward to entering the clinic in healthy volunteers in the first half of 2025, where we will assess biomarkers of PD-1 agonist activity that are enabled by S‑4321’s differentiated mechanism.”

The poster for the data presented at ACR is available here on Seismic’s website.

At ACR Convergence 2024, Seismic also presented a poster on its second program preparing to initiate clinical development, S-1117, an engineered pan-IgG protease suitable for chronic administration, for the treatment of autoantibody-mediated diseases. The poster for the data presented at ACR is available here on Seismic’s website.

About Seismic Therapeutic
Seismic Therapeutic™ is a 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.

Media Contact
Kathryn Morris, The Yates Network
914-204-6412
kathryn@theyatesnetwork.com

Investor Contact
Emiley Demick, Precision AQ
212-362-1200
emiley.demick@precisionaq.com

Seismic Therapeutic to Participate in Upcoming Investor Conferences

Watertown, Mass., November 7, 2024 – Seismic Therapeutic, Inc., the machine learning immunology company, today announced that company management will participate in the following investor conferences:

Guggenheim’s Inaugural Healthcare Innovation Conference
Date: Wednesday, November 13, 2024
Location: Boston, MA
Format: Jo Viney, Ph.D., Founder, President and CEO, will be a speaker at the panel presentation titled, “Immunology & Inflammation: Cutting-Edge Technologies Driving the Next Wave of Biotech Breakthroughs”

Stifel Healthcare Conference 2024
Date: Tuesday, November 19, 2024
Location: New York, NY
Format: Company presentation and 1×1 meetings

Jefferies London Healthcare Conference
Date: Tuesday, November 19 – Thursday, November 21, 2024
Location: London, England, UK
Format: 1×1 meetings

Piper Sandler 36^th Annual Healthcare Conference
Date: Wednesday, December 4, 2024
Location: New York, NY
Format: Company presentation and 1×1 meetings

Wells Fargo Virtual Private Biotech Symposium
Date: Thursday, December 12, 2024
Location: Virtual
Format: 1×1 meetings

Media Contact
Kathryn Morris, The Yates Network
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Emiley Demick, Precision AQ
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Seismic Therapeutic Presents Data Demonstrating Key Capabilities and Broad Utility of Its Machine Learning-enabled IMPACT Platform to Create Novel Biologic Medicines

IMPACT platform deployed to design Company’s lead drug candidates, S-1117 and S-4321, which are on track to enter the clinic in 1H 2025

New data indicate platform’s potential to create additional novel biologics beyond pan-IgG proteases and agonist antibodies

Watertown, Mass., November 6, 2024 – Seismic Therapeutic, Inc., the machine learning immunology company, today announced the presentation of data supporting the broad ability of its IMPACT platform to create novel biologic medicines. The data show how the IMPACT platform was leveraged to design S-1117, an engineered pan-IgG protease suitable for chronic administration and one of the Company’s lead programs, and support its generalizability to create additional biologic modalities beyond pan-IgG proteases. These data on the enhanced capabilities of the IMPACT platform are being highlighted in an invited talk today at the 16^th PEGS Europe Protein and Antibody Engineering Summit (PEGS Europe 2024) in Barcelona, Spain.

Seismic’s IMPACT platform integrates machine learning with structural biology, protein engineering, and translational immunology for parallel, multi-property optimization of novel biologic therapies. The Company has built proprietary machine learning algorithms to simultaneously improve developability, modulate function, and minimize immunogenicity to enable the accelerated creation of biotherapeutics.

“We’re very excited to present new data on selected enhancements to Seismic’s IMPACT platform that demonstrate the benefits of integrating machine learning into the drug creation process to rapidly design and optimize novel drug-like protein therapeutics,” said Nathan Higginson-Scott, PhD, Chief Technology Officer at Seismic Therapeutic. “A key component of our approach is the ability to predict and remove both T and B cell epitopes beyond current state-of-the-art techniques, while maintaining other key attributes required to design biologic drugs.”

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

Original application of the IMPACT platform, using a combination of in silico design and wet lab validation, to design S-1117, an engineered pan-IgG protease variant to reduce both T cell epitopes to prevent de novo anti-drug antibodies (ADA) generation and B cell epitopes to reduce pre-existing ADA binding and support chronic dosing, while retaining its activity and stability
New application of the IMPACT platform in which Seismic has shown the first example of engineering a protease’s specificity, applying the Company’s multi-objective optimization capabilities to create a selective IgE protease, using a combination of in silico design and wet lab validation, from a protease with both IgG and IgE cleaving properties in a single round of designs, while improving the activity and stability
In silico sequence design and fitness evaluation indicating that Seismic’s machine learning framework can, in a generalizable way, eliminate immunogenic T cell epitopes across a broad range of additional protein drug modalities, in particular non-protease enzymes and non-monoclonal antibodies, while maintaining their potency with high confidence

“Application of our IMPACT platform to new protein therapeutics for diseases of the immune system has enabled us to make rapid inroads into the design and development of our lead drug candidates – S-1117 , as well as S-4321, a dual-cell bidirectional PD-1 antibody agonist – that are on track to enter the clinic in the first half of 2025,” said John Sundy, MD, PhD, Chief Medical Officer and Head of R&D at Seismic Therapeutic. “These data show how we are strengthening our IMPACT platform to serve as our product engine, creating a range of biologic therapies designed to address diseases more effectively by optimizing for function, minimizing immunogenicity, and enhancing drug-like properties of biologic therapies.”

About Seismic Therapeutic
Seismic Therapeutic™ is a biotechnology company making a major shift in how immunology therapies are created 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.

Media Contact
Kathryn Morris, The Yates Network
914-204-6412
kathryn@theyatesnetwork.com

Investor Contact
Emiley Demick, Precision AQ
212-362-1200
emiley.demick@precisionaq.com

Seismic Therapeutic Announces Presentations at Upcoming Scientific and Medical Conferences

Watertown, Mass., November 5, 2024 – Seismic Therapeutic, Inc., the machine learning immunology company, today announced the company’s participation in four upcoming scientific and medical conferences, presenting on Seismic’s emerging pipeline of novel therapeutics to treat autoimmune and inflammatory diseases, as well as its proprietary IMPACT platform that applies machine learning to biologics drug discovery.

Details of Seismic’s presentations and poster sessions are as follows:

IMPACT platform presentation:

November 5-7: PEGS Europe Protein & Antibody Engineering Summit, Barcelona, Spain

Presentation Title: Machine learning for multi-objective optimization of bacterial proteases that degrade pathogenic immunoglobulins
Session: Machine Learning Approaches for Protein Engineering: Part 1
Date: Wednesday, November 6
Time: 6:45 p.m. CET
Presenter: Ryan Peckner, PhD, Director, Head of Machine Learning

Pipeline program presentations:

November 14-19: American College of Rheumatology (ACR) Convergence, Washington, DC

Poster Title: Preclinical polypharmacology of S-1117, a novel engineered Fc-fused IgG degrading enzyme, for chronic treatment of autoantibody-mediated diseases
Session: B Cell Biology & Targets in Autoimmune & Inflammatory Disease
Date: Saturday, November 16
Time: 10:30 a.m. ET
Presenter: Julia Manasson, MD, Medical Director, Clinical & Translational Medicine

Poster Title: S-4321, a novel dual-cell bidirectional PD-1:FcγRIIb selective agonist antibody for the treatment of autoimmune disease
Session: T Cell Biology & Targets in Autoimmune & Inflammatory Disease
Date: Monday, November 18
Time: 10:30 a.m. ET
Presenter: Julia Manasson, MD, Medical Director, Clinical & Translational Medicine

December 7-10: American Society of Hematology (ASH) Annual Meeting, San Diego, CA

Poster Title: Preclinical polypharmacology of S-1117, a novel engineered Fc-fused IgG degrading enzyme, for chronic treatment of autoantibody-mediated diseases
Session: 311. Disorders of Platelet Number or Function: Clinical and Epidemiological: Poster II
Publication Number: 2562
Date: Sunday, December 8
Time: 6:00 p.m. PT
Presenter: Julia Manasson, MD, Medical Director, Clinical & Translational Medicine

December 15-19 – Antibody Engineering and Therapeutics Conference, San Diego, CA

Presentation Title: Dual Cell Bidirectional Antibodies for Treating Autoimmunity
Session: Main Conference
Date: Wednesday, December 18
Time: 11:00 a.m. PT
Presenter: Jyothsna Visweswaraiah, PhD, Director, Head of Biotherapeutics

In addition to the presentation, Dr. Visweswaraiah will serve as co-chair for the “Forward and reverse translation medicine” session on Monday, December 16 at 2:25 p.m. PT.

Poster Title: Engineering and development of an IgG degrading enzyme therapeutic using the IMPACT platform
Presenter: Allison Colthart, PhD, Principal Scientist Drug Creation

Poster Title: Discovery and Characterization an FcgRIIb-Selective PD-1 Agonist for the Treatment of Autoimmunity
Presenter: Colin Lipper, PhD, Senior Scientist, Drug Creation

Media Contact
Kathryn Morris, The Yates Network
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kathryn@theyatesnetwork.com

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Emiley Demick, Precision AQ
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emiley.demick@precisionaq.com

Seismic Therapeutic Presents New Preclinical Data on S-1117 in Autoantibody-Mediated Diseases Including Myasthenia Gravis at MGFA Scientific Session at AANEM Annual Meeting

Novel engineered Fc-fused pan-IgG protease demonstrates deep, rapid and sustained reduction of IgG levels and ability to address multiple pathogenic mechanisms as a single drug molecule

Preclinical data supports potential for S-1117’s multi-mechanistic action to address unmet need in myasthenia gravis

Company expects to initiate first-in-human Phase 1 clinical trial of S-1117 in 1H 2025

Watertown, Mass., October 15, 2024 – Seismic Therapeutic, Inc., the machine learning immunology company, today announced the presentation of new preclinical data for its pan‑immunoglobulin G (IgG) sculpting enzyme candidate, S-1117, at the Myasthenia Gravis Foundation of America (MGFA) Scientific Session at the American Association of Neuromuscular and Electrodiagnostic Medicine (AANEM) 2024 annual meeting in Savannah, Georgia.

S-1117 is a novel engineered Fc-fused pan-IgG protease targeting IgG autoantibodies that play a key role in the pathogenesis of a range of chronic and acute autoantibody mediated diseases, including myasthenia gravis (MG), a chronic neuromuscular autoimmune disorder. Seismic plans to initiate a Phase 1 clinical trial of S-1117 in healthy volunteers in the first half of 2025.

“S-1117 has shown the unique ability to target multiple orthogonal pathogenic mechanisms within a single molecule, and we believe this multi-mechanistic approach has the potential to drive deeper responses and offer improved clinical outcomes for MG patients, as well as for patients with other autoantibody-mediated diseases,” said John Sundy, MD, PhD, Chief Medical Officer and Head of R&D at Seismic Therapeutic. “Despite recent treatment advancements, there remains a significant opportunity to address the large proportion of MG patients who do not achieve remission or low disease activity with currently approved therapies. We believe S‑1117 can offer advantages over existing treatment options and look forward to advancing S‑1117 into first-in-human Phase 1 clinical studies in the first half of next year.”

The S-1117 preclinical data presented at AANEM showed deep, rapid and sustained reduction of all IgG subclasses. S-1117 also demonstrated the ability to directly cleave circulating and immune complexed IgG, as well as the IgG B cell receptor expressed on memory B cells. Moreover, current S-1117 PK/PD modeling indicates the potential for a convenient small volume, subcutaneous, self-administered treatment regimen administered every 4-6 weeks.

Highlights of the Presentation

In vitro, S-1117 was shown to cleave soluble forms of IgG from healthy volunteers and MG patients. The results support additional key attributes of S-1117:

Cleaves all IgG subclasses, including IgG3, in plasma of healthy individuals and MG patients;
Achieves a magnitude of soluble IgG cleavage in vitro from MG patients similar to healthy volunteers; and
Cleaves preformed immune complexes, which drive injury to tissues, as well as the B cell receptor.

In vivo studies performed with S-1117 in rabbit and mouse models showed rapid, deep and sustained IgG reduction and demonstrated cleavage of the B cell receptor within hours after both intravenous and subcutaneous administration.

Projections of human PK and PD through quantitative systems pharmacology (QSP) modeling for S-1117 indicate that infrequent chronic low doses can achieve titratable IgG reductions of 90% or greater. PK/PD modeling further supports the potential for a subcutaneous, self-administered treatment regimen to achieve therapeutic levels of IgG reduction at doses as low as <1mg/kg of drug administered monthly. In addition, given the rapid onset of action, S-1117 is predicted to be applied to acute conditions, such as MG crisis.

The poster for the data presented at AANEM is available here on Seismic’s website.

Media Contact
Kathryn Morris, The Yates Network
914-204-6412
kathryn@theyatesnetwork.com

Investor Contact
Emiley Demick, Precision AQ
212-362-1200
emiley.demick@precisionaq.com

Seismic Therapeutic Announces Participation at Upcoming October Scientific and Medical Conferences

Watertown, Mass., September 30, 2024 – Seismic Therapeutic, Inc., the machine learning immunology company, today announced the company’s participation in three upcoming scientific and medical conferences, presenting on Seismic’s emerging pipeline of novel therapeutics to treat rare and prevalent autoimmune diseases, as well as its proprietary IMPACT platform that applies machine learning to biologics drug discovery.

Details of Seismic’s presentations and poster sessions are as follows:

October 3-4: Biologics US, San Diego, CA
Presentation Title: Structure empowered IMPACT platform in the discovery & development of Immunoglobulin Sculpting (IgSc) enzyme & Dual-cell Bidirectional (DcB) antibody drugs for immunological diseases
Session: Track 1: Computational Tools, AI/ML-Guided Engineering
Date: Friday, October 4
Time: 2:15 p.m. PT
Presenter: Yi Xing, PhD, Senior Director, Head of Structural Biology

October 15-18: Myasthenia Gravis Foundation of America Scientific Session at American Association of Neuromuscular & Electrodiagnostic Medicine Annual Meeting, Savannah, GA
Presentation Title: Preclinical pharmacology of S-1117, a novel engineered Fc-fused IgG cleaving enzyme, for chronic treatment of autoantibody-mediated diseases including Myasthenia Gravis
Session: Therapeutics
Date: Tuesday, October 15
Time: 10:10 a.m. ET
Presenter: Julia Manasson, MD, Medical Director, Clinical & Translational Medicine

October 15-18: CHI Immunogenicity & Bioassay Summit, Washington, DC
Presentation Title: Machine learning for deimmunization and multi-objective optimization of biologics
Session: Immunogenicity Prediction & Control – Deimmunization, Developability, and Machine Learning
Date: Friday, October 18
Time: 3:35 p.m. ET
Presenter: Ryan Peckner, PhD, Director, Head of Machine Learning

Media Contact
Kathryn Morris, The Yates Network
914-204-6412
kathryn@theyatesnetwork.com

Investor Contact
Emiley Demick, Precision AQ
212-362-1200
emiley.demick@precisionaq.com