Seismic Therapeutic Closes $121 Million Series B Financing to Advance Immunology Pipeline Optimized by its Machine Learning Platform

Funding will advance company’s two lead programs through clinical proof-of-mechanism, as well as enable continued growth of its biologics pipeline and expansion of its IMPACT platform   

The financing brings total capital raised by the company to $222 million 

Cambridge, Mass., December 4, 2023 – Seismic Therapeutic, Inc., the machine learning immunology company, today announced that it has closed a $121 million Series B financing. The Series B was led by new investor Bessemer Venture Partners with participation from other new investors, Amgen Ventures, Codon Capital, Alexandria Venture Investments, Gaingels and GC&H, as well as existing investors, Timothy A. Springer, Lightspeed Venture Partners, Polaris Partners, Boxer Capital, GV, Samsara BioCapital, and management and founders.

Proceeds from the Series B financing will be used to advance through Phase 1 proof-of-mechanism trials with Seismic’s two lead programs: a pan‑immunoglobulin (Ig) G protease sculpting (Sc) enzyme candidate (S-1117) and a PD-1 agonist:Fc gamma receptor IIb selective Dual-cell Bidirectional (DcB) antibody candidate (S-4321). In addition, the Series B will enable the continued growth of the company’s pipeline in both the IgSc and DcB product areas, beyond the lead programs. The funding will also enable the company to further expand its proprietary machine learning-enabled IMPACT platform with the development and implementation of additional cutting-edge methods to enhance biologics drug discovery in immunology. Concurrent with the financing, Andrew Hedin, MBA, biotech and healthcare partner of Bessemer Venture Partners, will join Seismic’s board of directors.

“Seismic has made impressive achievements in a short time integrating the power of machine learning with its deep drug development expertise to create two differentiated lead programs, each offering a compelling opportunity to address unmet medical needs in autoimmune diseases in a new way,” said Mr. Hedin. “We look forward to collaborating with the Seismic team to realize the full potential of its unique approach to immunology drug development, enabled by machine learning.”

Since the company’s launch and announcement of its Series A round, Seismic has advanced two programs into IND-enabling studies. This progress resulted from Seismic’s integration of leading-edge machine learning into drug development in a specific area – biologics for immunology – powered by a diverse team of drug developers and machine learning innovators. With this approach and its IMPACT platform, Seismic has rapidly engineered novel biologics with drug-like properties using multi-parameter optimization. For its lead IgSc enzyme program, Seismic engineered novel pan-IgG proteases with reduced B cell and T cell immunogenicity and chemical liabilities while maintaining enzyme activity and stability, creating a protease therapeutic to address multiple pathogenic mechanisms in a single drug for the treatment of acute and chronic autoantibody mediated diseases. Seismic designed its lead DcB antibody program to optimize the targeting of multiple cell types that drive pathogenesis of autoimmune diseases, specifically engaging T cells via PD-1 agonism and antigen presenting cells via the inhibitory Fc gamma receptor.

“We are delighted to secure the support of such a strong syndicate of investors who believe in Seismic’s ability to pioneer a new era of immunology drug development integrating machine learning,” said Jo Viney, PhD, Founder, President and CEO of Seismic Therapeutic. “This financing enables us to continue our momentum and advance both of our exciting lead programs into the clinic. We believe the time is right to harness advances in machine learning to discover the next generation of biologics drugs to improve the lives of patients with autoimmune diseases.” 

About the IMPACT Platform
The IMPACT platform “parallelizes” interdisciplinary components of drug discovery to generate drug molecules on an unprecedented scale that are engineered to be better therapeutics to treat autoimmune diseases. Comprehensive integration of machine learning with protein engineering, structural biology and translational immunology enables the accelerated design and analysis of vast numbers of proteins and protein modifications. This parallelized process bypasses the trial and error methods of conventional biologics development, enabling simultaneous optimization for biologic function, reduced immunogenicity and developability, resulting in the creation of novel biologics with superior properties. 

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 (formerly Twitter) @Seismic_Tx.

About Bessemer Venture Partners
Bessemer Venture Partners helps entrepreneurs lay strong foundations to build and forge long-standing companies. With more than 145 IPOs and 300 portfolio companies in the enterprise, consumer and healthcare spaces, Bessemer supports founders and CEOs from their early days through every stage of growth. Bessemer’s global portfolio has included Pinterest, Shopify, Twilio, Yelp, LinkedIn, PagerDuty, DocuSign, Wix, Fiverr, and Toast and has $20 billion of assets under management. Bessemer has teams of investors and partners located in Tel Aviv, Silicon Valley, San Francisco, New York, London, Hong Kong, Boston, and Bangalore. Born from innovations in steel more than a century ago, Bessemer’s storied history has afforded its partners the opportunity to celebrate and scrutinize its best investment decisions (see Memos) and also learn from its mistakes (see Anti-Portfolio).

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

Seismic Therapeutic to Participate in Upcoming Scientific Meetings

Cambridge, Mass., October 11, 2023 – Seismic Therapeutic, Inc., the machine learning immunology company, today announced that the company will participate in several upcoming scientific and industry meetings in Q4 2023, highlighting the company’s proprietary approach to applying machine learning to biologics drug discovery for immunology, and its emerging pipeline of novel therapeutics to treat dysregulated adaptive immunity.

“We look forward to sharing our progress at upcoming scientific meetings, presenting on a range of topics that describe the innovation of our IMPACT platform to usher in a new era of immunology drug development that integrates machine learning, as well as the advancement of our preclinical programs,” said John Sundy, MD, PhD, Chief Medical Officer and Head of R&D of Seismic Therapeutic. “Leveraging our IMPACT platform, we are building a pipeline of novel enzyme and antibody programs focused on addressing the unmet needs in autoimmune diseases to have a broad impact on patients.”

Details of the presentations and poster sessions by members of the Seismic team are as follows:

Thursday, October 12
QSP (Quantitative Systems Pharmacology) Summit
Presentation: Preclinical modeling of an IgG cleaving enzyme: A solution to a unique problem
Presenter: Alex Pellerin, PhD, Director of Preclinical Development
Time: 9:00 a.m. ET
Location: Cambridge, MA

Sunday, October 15
International Conference of the Inflammation Research Association
Keynote Address: New approaches for treating dysregulated adaptive immunity
Presenter: Jo Viney, PhD, President and Chief Executive Officer
Time: 6:30 p.m. MT
Location: Fort Collins, CO

Wednesday, November 15
PEGS Europe – Protein & Antibody Engineering Summit
Presentation: Integration of Machine Learning, Structural Biology, and Wet Lab Data to Augment Drug Discovery for Autoimmune Diseases
Presenter: Nathan Higginson-Scott, PhD, Chief Technology Officer
Session: Machine Learning for Protein Engineering, Part 1
Time: 5:30 p.m. Western European Time
Location: Lisbon, Portugal

Thursday, December 14 and Friday-Saturday, December 15-16
Antibody Engineering and Therapeutics
Presentation: Dual-cell Bidirectional (DcB) Antibodies for Targeting Multiple Inhibitory Pathways for Controlling Inflammation
Presenter:  Jyothsna Visweswaraiah, PhD, Director, Biotherapeutics Drug Creation
Session: Track 1, Novel Bispecifics, Multi-specifics and Therapeutic Combinations
Time: 5:45 – 6:15 p.m. PT
Poster: Design and screening of FcγRIIb selective Fc domains to enhance checkpoint agonism and treat immune mediated diseases
Author: Allison Colthart, PhD, Principal Scientist Drug Creation
Location: San Diego, CA

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 (formerly Twitter) @Seismic_Tx.

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

Seismic Therapeutic Selected as an Endpoints 11 Most Promising Biotech Startup

Cambridge, Mass., September 21, 2023 – Seismic Therapeutic, Inc., the machine learning immunology company, today announced that it has been named as one of the Endpoints 11 most promising private biotechnology companies of 2023. Seismic has been chosen by the Endpoints News editorial team because of the company’s strengths in science, leadership, financial backers and opportunity to move the dial on the development of new medicines for patients with autoimmune diseases.

“We are honored to be recognized as an Endpoints 11 company, and this serves as a testament to the hard work and dedication of our entire team,” said Jo Viney, PhD, Co-Founder, President and CEO of Seismic Therapeutic. “This recognition further energizes our Seismonauts to strive to make an impact in the biotechnology industry and in our communities. We believe that by applying machine learning to immunology biologics drug discovery we are paving the way to creating positive change in the autoimmune landscape and the lives of patients.”

The 2023 Endpoints 11 winners were announced at an awards gala held at the State Room in Boston on Wednesday, September 20, 2023.

With the company’s innovative IMPACT platform integrating machine learning with biologics drug discovery, Seismic is building a pipeline of novel enzymes and antibodies to address unmet medical needs for diseases involving humoral immunity and cell-mediated immunity, the two arms of the adaptive immune system. Within 18 months since launching, Seismic’s two lead drug programs are in IND-enabling studies, each with potential to improve the treatment landscape in autoimmune diseases:

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 (formerly Twitter) @Seismic_Tx.

 

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

Seismic Therapeutic Announces Presentation of Preclinical Data for Advancing Novel Biologics Drug Programs at the 23rd Annual Meeting of the Federation of Clinical Immunology Societies

Nine poster presentations support immunoglobin sculpting enzyme and dual-cell bidirectional antibody programs to control dysregulated adaptive immunity 

Cambridge, Mass., June 14, 2023 – Seismic Therapeutic, Inc., the machine learning immunology company, today announced nine poster presentations supporting the company’s emerging pipeline of novel biologics derived from its proprietary IMPACT platform to treat autoimmune diseases at the 23rd Annual Meeting of the Federation of Clinical Immunology Societies (FOCIS) taking place on June 20-23 in Boston, MA. Seismic’s immunoglobin (Ig) sculpting enzymes and dual-cell bidirectional (DcB) antibody programs will be highlighted in these presentations, demonstrating the design of therapeutics to address unmet medical needs for diseases involving dysregulation of humoral immunity and cell-mediated immunity, the two arms of the adaptive immune system. In particular, results from novel in vitro human assays to characterize inhibitory checkpoint receptor agonism will be presented along with activity readouts in in vivo humanized mouse models with Seismic’s lead DcB antibody program, in comparison to current benchmarks.

“We are thrilled to share preclinical data showing rapid advancement of our Ig sculpting enzymes and DcB antibody programs and highlighting the translational immunology capabilities within our IMPACT platform,” said Kevin Otipoby, PhD, Senior VP Immunology of Seismic Therapeutic. “There is a great need for optimized treatments of dysregulated adaptive immunity and our IMPACT platform enables us to efficiently design, optimize, and select novel biologics drug candidates to address acute and chronic autoantibody mediated diseases and cell-mediated autoimmune diseases.”

Details of the poster presentations at FOCIS 2023 are as follows:

DcB Antibody Programs

IMPACTing Autoimmunity Through Dual Targeting of Antigen Presenting Cells and T Cells via Inhibitory Receptor Agonism
Tuesday, June 20th 6:00 – 7:45 p.m.
Poster number: Tu139
Author: Stephanie Grebinoski, PhD

Identification and Characterization of Selective FcγRIIb Binders and their Potential of IMPACTing Immune-Mediated Diseases
Tuesday, June 20th 6:00 – 7:45 p.m.
Poster number: Tu133
Author: Stephen Lutz, BS

Identification and Characterization of Inhibitory Receptor Agonists for the Treatment of Autoimmune and Inflammatory Diseases
Tuesday, June 20th 6:00 – 7:45 p.m.
Poster number: Tu132
Author: Michael Cianci, MS

In vivo models supporting the identification of novel inhibitory receptor agonists for the treatment of immune-mediated diseases
Tuesday, June 20th 6:00 – 7:45 p.m.
Poster number: Tu130
Author: Minasri Borah, MS

Ig Sculpting Enzyme Programs

The Promise of Machine Learning: Using Seismic’s IMPACT Platform to Design IgG Cleaving Enzymes for Chronic Treatment of Autoimmune Diseases
Thursday, June 22nd 7:30 a.m. -.7:30 p.m.
Poster number: Th143
Author: Alex Pellerin, PhD

In Vitro Assay Development to Assess Successful Removal of T and B Cell Epitopes Through Seismic’s IMPACT Platform
Wednesday, June 21st 7:30 a.m. – 7:30 p.m.
Poster number: W138
Author: Andita Newton, MS

In Vivo PK/PD Assessment of Invisibilized IgG Cleaving Protease for Chronic Treatment of Autoimmune Diseases
Tuesday, June 20th 6:00 – 7:45 p.m.
Poster number: Tu142
Author: Liliana Sanmarco, PhD

Identifying Next Generation Ig Selective Cleaving Enzymes for Treatment of Autoimmune Diseases Using IMPACT Platform
Tuesday, June 20th 6:00 – 7:45 p.m.
Poster number: Tu134
Author: Purvi Mande, PhD

High-Throughput Western Blot for In Vitro and In Vivo Assessment of Human Ig Specific Cleaving Enzymes
Tuesday, June 20th 6:00 – 7:45 p.m.
Poster number: Tu126
Author: Nam Le, BS

In addition to the poster presentations, Ivan Mascanfroni, PhD, Senior Director of Immunology at Seismic, will chair the “Adaptive Immunity” session on Friday, June 23rd at 8 a.m.

About Dual-cell Bidirectional (DcB) Programs

Seismic’s DcB antibody approach targets dysregulated cell-mediated immunity by optimally engaging both T cells and antigen presenting cells, such as B cells, to restore homeostasis. Activating these pathways may control multiple diseases, such as multiple sclerosis, lupus and rheumatoid arthritis. DcB antibodies simultaneously engage multiple inhibitory pathways in more than one immune cell type thereby targeting and regulating both sides of the immune synapse. 

About Immunoglobulin (Ig) Sculpting Programs

Seismic’s Ig sculpting enzymes address dysregulated humoral immunity by reducing both Ig levels and antibody effector functions, which contribute to the pathogenesis of a wide range of autoimmune diseases, such as myasthenia gravis, chronic inflammatory demyelinating polyneuropathy and immune thrombocytopenia. Enzymes that specifically cleave antibodies may eliminate circulating and immune-complexed Ig, as well as cell surface B cell receptors, thereby modulating Ig-mediated autoimmunity and inflammation. 

About Seismic Therapeutic
Seismic Therapeutic is a biotechnology company integrating machine learning across the entire biologics discovery process to accelerate immunology drug development. Using its IMPACT™ platform, the company is addressing the central challenges of biologics discovery and development by fully integrating machine learning with the key elements of biologics drug discovery – structural biology, protein engineering and translational immunology – to create optimized therapies on an accelerated path to patients. Seismic Therapeutic has an emerging pipeline of novel biologics to address adaptive immune system dysregulation to treat 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 up on Twitter @Seismic_Tx and on LinkedIn. 

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

Seismic Therapeutic Announces Presentation of Preclinical Data Demonstrating Advances in Novel Biologics Discovery at the PEGS Boston Summit

Application of IMPACT platform to optimize antibody and enzyme therapeutics through parallelization and invisibilization to develop novel protein therapeutics

Cambridge, Mass., May 11, 2023 – Seismic Therapeutic, Inc., the machine learning immunology company, today announced the presentation of preclinical data that describe the application of the company’s IMPACT platform at PEGS Boston 2023, taking place on May 15-19. The three poster presentations outline how Seismic’s IMPACT platform enables the parallel optimization of multiple parameters, including predicting and removing B and T cell epitopes, augmenting drug-like properties and retaining protein function, to create novel drug candidates across the immunoglobin (Ig) sculpting enzymes and dual-cell bidirectional (DcB) antibody product areas. Seismic is designing novel biologics derived from the IMPACT platform to address unmet medical needs for diseases involving humoral immunity and cell-mediated immunity, the two arms of the adaptive immune system.

“We are pleased to share the advancements of our efforts in biologics discovery uniquely enabled by our IMPACT platform,” said Nathan Higginson-Scott, PhD, Chief Technology Officer and Senior VP Drug Creation of Seismic Therapeutic. “With our parallelized processes we can bypass the trial and error methods of conventional biologics development, enabling simultaneous optimization for biologic function, reduced immunogenicity and augmented developability, resulting in the creation of novel enzyme and antibody therapeutics for the treatment of autoimmune diseases.”

Details of the poster presentations at PEGS Boston 2023 are as follows:

Development and deimmunization of protein therapeutics by machine learning
Session C1C: Machine Learning Approaches for Protein Engineering
Poster number: P212
Author: Nathan Rollins, PhD

Identifying Ig selective proteases for treatment of autoimmune disease using the IMPACT platform
Session C6C: Characterization for Novel Biotherapeutics
Poster number: P211
Author: Jung-Eun (June) Shin, PhD

Discovery and characterization of FcgRIIb specific mAbs
Session C1B: Engineering Antibodies
Poster number: P213
Author: Elliott Wittenberg, BS

About Immunoglobulin (Ig) Sculpting Programs
Seismic’s Ig sculpting enzymes address dysregulated humoral immunity by reducing both Ig levels and antibody effector functions, which contribute to the pathogenesis of a wide range of autoimmune diseases, such as myasthenia gravis, chronic inflammatory demyelinating polyneuropathy and immune thrombocytopenia. Enzymes that specifically cleave antibodies may eliminate circulating and immune-complexed Ig, as well as cell surface B cell receptors, thereby modulating Ig-mediated autoimmunity and inflammation. 

About Dual-cell Bidirectional (DcB) Programs
Seismic’s DcB antibody approach targets dysregulated cell-mediated immunity by optimally engaging both T cells and antigen presenting cells, such as B cells, to restore homeostasis. Activating these pathways may control multiple diseases, such as multiple sclerosis, lupus and rheumatoid arthritis. DcB antibodies simultaneously engage multiple inhibitory pathways in more than one immune cell type thereby targeting and regulating both sides of the immune synapse. 

About Seismic Therapeutic
Seismic Therapeutic is a biotechnology company integrating machine learning across the entire biologics discovery process to accelerate immunology drug development. Using its IMPACT platform, the company is addressing the central challenges of biologics discovery and development by fully integrating machine learning with the key elements of biologics drug discovery – structural biology, protein engineering and translational immunology – to create optimized therapies on an accelerated path to patients. Seismic Therapeutic has an emerging pipeline of novel biologics to address adaptive immune system dysregulation to treat 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 Twitter @Seismic_Tx and on LinkedIn. 

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

 

Seismic Therapeutic Announces Presentation of Preclinical Data for Immunoglobin Sculpting Enzyme and Dual-Cell Bidirectional Antibody Programs at IMMUNOLOGY 2023

Demonstrates the application of the IMPACT platform to design novel protein therapeutics  

Seven poster presentations and two oral presentations support discovery, optimization, and characterization of Ig sculpting enzymes and dual-cell bidirectional antibody programs to control dysregulated adaptive immunity 

Cambridge, Mass., May 9, 2023 – Seismic Therapeutic, Inc., the machine learning immunology company, today announced seven poster presentations and two oral presentations supporting the company’s emerging pipeline of immunoglobin (Ig) sculpting enzymes and dual-cell bidirectional (DcB) antibody programs at IMMUNOLOGY 2023, the annual meeting of the American Association of Immunologists (AAI) taking place on May 11-15 in Washington, D.C. Seismic is designing novel biologics derived from the company’s proprietary IMPACT platform to address unmet medical needs for diseases involving humoral immunity and cell-mediated immunity, the two arms of the adaptive immune system.

Seismic’s Ig sculpting enzymes address dysregulated humoral immunity by reducing both Ig levels and antibody effector functions, which contribute to the pathogenesis of a wide range of autoimmune diseases, such as myasthenia gravis, chronic inflammatory demyelinating polyneuropathy and immune thrombocytopenia. Enzymes that specifically cleave antibodies may eliminate circulating and immune-complexed Ig, as well as cell surface B cell receptors, thereby modulating Ig-mediated autoimmunity and inflammation. The presentations demonstrate the application of the IMPACT platform to reduce immunogenicity while retaining the function of novel Ig sculpting enzymes for the acute and chronic treatment of autoantibody-driven diseases.

Seismic’s DcB antibody approach targets dysregulated cell-mediated immunity by optimally engaging both T cells and antigen presenting cells (APCs), such as B cells to restore homeostasis. Activating these pathways may control multiple diseases, such as multiple sclerosis, lupus and rheumatoid arthritis. The presentations demonstrate the application of IMPACT platform to identify and optimize novel antibody molecules that simultaneously engage multiple inhibitory pathways in more than one immune cell type, thereby targeting and regulating both sides of the immune synapse.

“We are excited by the meaningful progress of our growing pipeline of novel biologics to treat humoral and cell-mediated autoimmune diseases,” said John Sundy, MD, PhD, Chief Medical Officer and Head of R&D of Seismic Therapeutic. “Our lead Ig sculpting program, a pan-IgG protease, is suitable for the treatment of acute and chronic autoantibody mediated diseases. We are also applying our insights to design additional Ig sculpting enzymes that are selective for IgG subclasses and other Ig isotypes. We are advancing our lead DcB antibody program which agonizes an inhibitory checkpoint receptor on T cells and selectively engages the inhibitory Fc receptor FcγRIIb on B cells/APCs to restore homeostasis in cell-mediated autoimmune diseases.”

Details of the poster presentations at IMMUNOLOGY 2023 are as follows:

Ig Sculpting Enzyme Programs

Identifying next generation Ig selective cleaving enzymes for treatment of autoimmune diseases using IMPACT platform

Sunday, May 14th 2:30-3:45 p.m.
Poster Board Number: P900
Author: Purvi Mande, PhD

The promise of machine learning: using Seismic’s IMPACT platform to design a class of IgG cleaving enzymes with drug like properties and reduced immunogenicity for the chronic treatment of autoimmune diseases

Friday, May 12th 2:30-3:45 p.m.
Poster Board Number: P969
Author: Alex Pellerin, PhD

In vitro assay development to assess successful removal of T and B cell epitopes through Seismic’s IMPACT platform

Friday, May 12th 2:30-3:45 p.m.
Poster Board Number: P972
Author: Andita Newton, B.S.

In vivo PK/PD assessment of invisibilized IgG cleaving protease for chronic treatment of autoimmune diseases

Sunday, May 14th 2:30-3:45 p.m.
Poster Board Number: P764
Author: Liliana Sanmarco, PhD

High-throughput Western Blot for in vitro and in vivo assessment of human Ig specific cleaving enzymes

Sunday, May 14th 2:30-3:45 p.m.
Poster Board Number: P767
Author: Nam Le, B.S.

DcB Antibody Programs

IMPACTing autoimmunity through dual targeting of antigen presenting cells and T cells via inhibitory receptor agonism

Saturday, May 13th 2:30-3:45 p.m.
Poster Board Number: P428
Author: Stephanie Grebinoski, PhD

Identification and characterization of selective FcγRIIb binders and their potential of IMPACTing immune-mediated diseases

Sunday, May 14th 2:30-3:45 p.m.
Poster Board Number: P769
Author: Stephen Lutz, B.S.

Details of the oral presentations at IMMUNOLOGY 2023 are as follows:

About the IMPACT Platform

The IMPACT platform “parallelizes” interdisciplinary components of drug discovery to generate drug molecules on an unprecedented scale that are engineered to be better therapeutics to treat autoimmune diseases. Comprehensive integration of machine learning with protein engineering, structural biology and translational immunology enables the accelerated design and analysis of vast numbers of proteins and protein modifications. This parallelized process bypasses the trial and error methods of conventional biologics development, enabling simultaneous optimization for biologic function, reduced immunogenicity and developability, resulting in the creation of novel biologics with superior properties.

About Seismic Therapeutic
Seismic Therapeutic is a biotechnology company integrating machine learning across the entire biologics discovery process to accelerate immunology drug development. Using its IMPACT platform, the company is addressing the central challenges of biologics discovery and development by fully integrating machine learning with the key elements of biologics drug discovery – structural biology, protein engineering and translational immunology – to create optimized therapies on an accelerated path to patients. Seismic Therapeutic has an emerging pipeline of novel biologics to address adaptive immune system dysregulation to treat 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 Twitter @Seismic_Tx and on LinkedIn.

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

 

Founder Q&A with Jeff Ravetch, MD, PhD

Jeff Ravetch, MD, PhD

Theresa and Eugene Lang Professor, Rockefeller University
Head, Leonard Wagner Laboratory of Molecular Genetics and Immunology

 

 

 


Challenge: Autoimmune diseases driven by multiple immune cell types

The pathology of many autoimmune diseases derives from interactions of multiple cell types including T cells and B cells/antigen presenting cells (APCs). Clinical evidence has shown that inhibitory checkpoint receptor antagonists can result in autoimmunity, suggesting that agonism may restore immune homeostasis.

New drug discovery approaches for autoimmune diseases

Seismic integrates machine learning with structural biology, protein engineering, and translational immunology to develop Dual Cell Bidirectional antibodies which simultaneously target multiple inhibitory pathways in more than one cell type to restore immune homeostasis in these diseases. These bidirectional antibodies agonize T cell checkpoint inhibitors, bind, and signal through, Fc receptors on APCs/B cells to prevent production of pro inflammatory cytokines and potentially inhibit pathogenic T cell, B cell and APC activity.

Expert perspective: Jeffrey V. Ravetch, MD, PhD

Dr. Jeffrey Ravetch is an academic founder of Seismic and a leading expert in the cell surface receptors that bind the Fc region of antibodies (FcR) and the mechanisms by which these receptors enable antibodies to mediate diverse biological activities. His work established the novel structural basis for Fc domain functional diversity and the pre-eminence of FcR pathways in host defense, inflammation and tolerance, describing novel signaling pathways to account for the paradoxical roles of antibodies as both promoting and suppressing inflammation. His work has been widely extended into clinical applications for the treatment of neoplastic, inflammatory, and infectious diseases.

In this installment of our Founders Q&A Series, Seismic’s Business Development Associate Rebecca Goydel, PhD, spoke with Dr. Ravetch about his work in immunology and Fc receptors, which offers expert insight into Seismic’s innovative approach to dysregulated cell-mediated immunity.

Rebecca Goydel:

Your work has changed the way we look at Fc receptors. How has the field evolved over the years to support the important role of Fc receptors in drug development? 

Jeff Ravetch:

We continue to broaden the way the field looks at the Fc region of antibodies in general. For many years, the biological activity of an antibody has been attributed primarily to the Fab portion which has specificity for binding, while the Fc region of the antibody confers pharmacokinetic properties such as half life.

Historically, there has been a lot of resistance to the notion that the Fc domain is an integral part of the biological activity of the antibody.

If we jump ahead to 2000, that’s when the first antibodies emerged as therapeutics, in particular for oncology. They were developed based on their in vitro activities to arrest tumor growth. The presumption was that they worked by binding to a target that had specific cellular responses. It turns out from my lab’s studies back in 2000, that the activity for those antibodies was actually driven by cytotoxic capacity through the Fc, and that was Fc receptor driven. This understanding was the genesis of our interest in how therapeutic antibodies depend on Fc engagement.

It wasn’t until 2013 that the first antibodies with modified Fc to engage individual Fc receptors with some specificity were approved. Today, there are about half dozen Fc engineered antibodies with selective Fc receptor binding for enhanced FcR activity, and another half dozen or so where Fc modifications are made to reduce Fc receptor binding to reduce toxicity. That’s a good start. Now there’s a momentum in drug development, where anyone starting an antibody program considers both ends of the molecule. It has taken us twenty years to get to the point where it’s established to some degree. There’s still a lot to do and a great deal of opportunity.

Now that the Fc region is recognized as a key component for the biological activity of therapeutic antibodies, how readily is it being incorporated in drug development?

Indeed, Fc modification is now recognized as important in antibody drug development. But, there are still many areas to further understand the complexity of the Fc and Fc receptors.  Throughout my career, I’ve focused on defining the role that the Fc region plays in biological processes that are antibody driven. It is complicated because there’s not one type of Fc region and Fc receptor, but multiple types of each.  The combinatorial possibilities of those two components leads to hundreds of different Fc structures. How many of them are biologically relevant? What do they do? How are they regulated? Generally, there have been a few limited sets of mutations used to manipulate Fc activity, but they broadly impact Fc receptors.  We still need to move the needle when it comes to stimulating Fc receptors selectively since they have different functions. This leaves a lot of room for improved therapies to be discovered and fill the large gap in this space.

Specifically, FcγRIIB is unique among Fcγ receptors, it has inhibitory activity and is the most abundantly expressed Fc receptor. It is present on almost all cell types that are involved in immune reactions and its level of expression is there to prevent inappropriate cellular activation, so it is well regulated. This makes it a useful target for therapies in the inflammation space. We know this balance of stimulating inhibitory receptor engagement is really key and if we can shift the equilibrium towards the inhibitory receptor, we have a chance at suppressing these inflammatory responses. Seismic’s Dual Cell Bidirectional program aims to address inhibitory receptor agonism by favoring FcγRIIB binding over its close relative FcγRIIA while agonizing inhibitory checkpoint receptors on T cells with the other end of the molecule to treat autoimmune diseases.

Checkpoint antagonists have emerged as an important class of immunotherapies in the last 10 years. What is your perspective of how the Fc and or Fc receptor binding fits in the landscape of current therapies? 

This is an area that my lab is actively involved in. We’ve developed a flow chart for how one goes about developing an antibody that’s targeting a checkpoint receptor. Most checkpoint targets have both inhibitory as well as activating activity. What becomes a more important component? Is it blocking an inhibitory signal or agonizing a stimulatory pathway?

It’s tricky because there are different Fc requirements for antibodies targeting those two pathways, and that’s where choosing the right clinical model and indication becomes critical. For agonist pathways, we’ve begun to realize that antibodies are not terrific when it comes to cross-linking receptors, which is key for almost all receptor agonists. You need to have some way of bringing together multiple receptors (multimerizing) for the desired activity, and that’s where the Fc can be very valuable. And that’s of course one of the facets of Seismic’s Dual Cell Bidirectional product area, whereby engaging an Fc receptor, it can act as a scaffold to allow for multimerization.

What excites you the most about the work being done at Seismic? 

Tim Springer called me and said he was starting a company that would be looking at pathways that impact the interaction of antibody Fc regions and Fc receptors, either to remove receptor engagement or optimize inhibitory receptor engagement. I thought that was a fabulous idea. When I was introduced to the team that was being assembled for this new company called Seismic, it was clear this was a group of people who knew what they were doing. I got the sense that this is a different model for a biotech company – one that’s built on the science, with an appreciation for the realities of getting across the finish line, so that was quite exciting.

The company’s work in engaging an inhibitory Fc receptor to act as a scaffold, allowing for multimerization, along with modulating the immune synapse between B and T cells, is really exciting and breaking new ground. For example, if you multimerize an inhibitory PD-1 antibody, you can create a stronger inhibitory signal. You can use an antibody with a modified Fc to accomplish this. The more exciting concept is that you can combine inhibitory activities from both the Fc receptor and checkpoint inhibitor pathways, and perhaps get an even greater inhibitory response with a bidirectional strategy, which is exactly what Seismic is working on.

Seismic is leveraging machine learning to accelerate drug discovery. From your perspective, how will machine learning contribute to and improve drug development in the area of immunology?

Historically, the way we used to do our optimization for Fc was basically trial and error. We had some receptors, we had some Fc variants, and we mixed and matched. We had no way of optimizing. When we hit upon something that worked, we said good enough, we’ll use it. But that’s obviously an older approach. Machine learning offers some very interesting possibilities and Seismic is leveraging this. We’ve started adopting machine learning in my own lab now too as we develop reagents that will specifically recognize various glycoforms of an IgG Fc and exploring how to take those glycoforms and manipulate them in ways that would be potentially therapeutic.

Machine learning is a powerful tool, and Seismic is deploying it strategically to move drug development in important new directions. The goal is to generate the correct immune synapse.  In the case of Seismic, this includes desired checkpoint inhibitor agonism on T cells with the right Fcs included to target FcγRIIB receptors on B cells. Machine learning can aid in this to avoid the traditional trial and error. It’s an area that is ripe for rethinking and machine learning can contribute to future innovation.

 

 

Seismic Therapeutic Appoints Melanie Manning as Chief People Officer

Cambridge, Mass., March 27, 2023 – Seismic Therapeutic, Inc., a biotechnology company using machine learning for immunology drug development, announced today that Melanie Manning has joined the company as Chief People Officer. She is an experienced and versatile human resources (HR) leader with more than 20 years of experience supporting business plans and developing programs to fully engage talent in multiple industries, including at biopharmaceutical companies Novartis and Biogen.

“Melanie joins us at a key time as Seismic plans for our transition from a discovery stage to a preclinical and eventual clinical organization, and I’m thrilled to welcome her to the team,” said Jo Viney, PhD, Co-Founder, President and CEO of Seismic Therapeutic. “She has an outstanding track record of enacting progressive HR programs, as well as the experience to implement additional creative strategies by which Seismic can continue to attract, retain, and develop talent. Moreover, her insights will be invaluable in further strengthening our culture as we fulfill our vision to build an exceptional organization that creates next generation immunology drugs for patients.”

“I’m excited to join Seismic and build on the company’s amazing workplace culture, commitment to community engagement, and diversity, equity, inclusion, and belonging,” Manning said. “I am dedicated and honored to help achieve the company’s strategic goals by building relationships, fostering trust and helping employees to be their best authentic selves. I look forward to working collaboratively with every Seismonaut to continue to cultivate what makes Seismic a special place to work, promoting innovation and creativity to develop new immunology biologics medicines enabled by machine learning.”

Before joining Seismic, Manning held leadership positions at Enspira HR Consulting, where she served as Vice President, Human Capital, acting as primary contact for HR advisory client engagements. Prior to Enspira, she was Chief Human Resources Officer for non-profit organization Upstream USA. Previously, she served as Head of Human Resources for the Infectious Diseases division of Novartis Institutes for BioMedical Research (NIBR).  Before her tenure at Novartis, Manning served as Associate Director, Human Resources at Biogen. Earlier in her career, she held several human resources positions for divisions of Fidelity Investments, which included HR business partner and Center of Excellence program office roles. She has a Masters degree in Human Relations and a BA from the University of Oklahoma and completed Intensive Studies in French Literature and Civilization at Université de Clermont-Ferrand, France.

About Seismic Therapeutic
Seismic Therapeutic is a biotechnology company integrating machine learning across the entire biologics discovery process to accelerate immunology drug development. Using its IMPACT™ platform, the company is addressing the central challenges of biologics discovery and development by fully integrating machine learning with the key elements of biologics drug discovery – structural biology, protein engineering and translational immunology – to create optimized therapies on an accelerated path to patients. Seismic Therapeutic has an emerging pipeline of novel biologics to treat adaptive immune system dysregulation to treat 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.

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

Seismic Therapeutic Selected for BioSpace’s NextGen Class of 2023

Cambridge, Mass., January 4, 2023 – Seismic Therapeutic, Inc., a biotechnology company advancing machine learning for immunology drug development, announced today it has been selected for BioSpace’s NextGen “Class of 2023” featuring the 25 most promising new life sciences companies in North America that launched between September 2021 and September 2022 with a Series A funding.

“At a time when there is so much exciting scientific innovation in the biopharma industry, we are honored to be recognized as one of the most promising New Life Science Companies on the BioSpace NextGen Class of 2023 List,” said Jo Viney, PhD, CEO of Seismic Therapeutic. As we start the new year, I and our growing, dedicated team of Seismonauts are energized to continue to rapidly advance our pipeline of innovative immunology therapies derived from our IMPACT platform.”

BioSpace has been recognizing the most exciting startups in biotech and pharma for the past nine years in its NextGen list. Organizations across all therapeutic areas are considered, and 25 companies were selected this year. BioSpace’s editorial team analyzed multiple components as determining factors: finance, collaborations, pipeline, growth potential and innovation.

The complete NextGen “Class of 2023” list can be viewed on BioSpace.

About BioSpace

BioSpace is the digital hub for life science news and jobs. We provide essential insights, opportunities and tools to connect innovative organizations and talented professionals who advance health and quality of life across the globe. Learn more and subscribe at www.biospace.com

About Seismic Therapeutic
Seismic Therapeutic is a biotechnology company integrating machine learning across the entire biologics discovery process to accelerate immunology drug development. Using its IMPACT™ platform, the company is addressing the central challenges of biologics discovery and development by fully integrating machine learning with the key elements of biologics drug discovery – structural biology, protein engineering and translational immunology – to create optimized therapies on an accelerated path to patients. Seismic Therapeutic has an emerging pipeline of novel biologics to treat adaptive immune system dysregulation to treat 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.

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

Seismic Therapeutic Named Emerging Company of the Year in Life Sciences at 2022 NEVY Awards

Cambridge, Mass., December 9, 2022 – Seismic Therapeutic, Inc., a biotechnology company advancing machine learning for immunology drug development, announced today the company was selected as the Emerging Company of the Year in Life Sciences by the New England Venture Capital Association (NEVCA) in its 10th annual NEVY Awards, which recognizes and celebrates the top innovators, investors and companies in the region.

“We are thrilled to be named Emerging Company of the Year in Life Sciences and thank the New England Venture Capital Association for recognizing our vision and momentum,” said Jo Viney, PhD, CEO of Seismic Therapeutic. “We look ahead with excitement as our dynamic team works to advance our IMPACT platform to develop innovative immunology therapies that make a difference for patients.”

Seismic Therapeutic representatives received the award on December 8th at the annual celebratory event at the House of Blues in Boston. The NEVYs honor both early- and late-stage companies, as well as the venture capitalists who support them, and cover a broad spectrum of the region’s thriving industry clusters, including technology, life sciences, healthcare and medtech.

About the New England Venture Capital Association
The New England Venture Capital Association (NEVCA) works toward a collaborative, inclusive, and prosperous innovation ecosystem. Through unique programs, critical policy work, and dynamic local events and regional marketing, the NEVCA invests in the entrepreneurial ecosystem on behalf of the VC community. VCs are only as successful as the entrepreneurs in whom they invest and the environments in which those investments grow. We don’t just host events: we act as a network, catalyst, and resource for the innovation economy, from celebrations to education; legislative advocacy to workforce development. Follow @NewEnglandVC on Twitter, or check out www.newenglandvc.org.

About Seismic Therapeutic
Seismic Therapeutic is a biotechnology company integrating machine learning across the entire biologics discovery process to accelerate immunology drug development. Using its IMPACT™ platform, the company is addressing the central challenges of biologics discovery and development by fully integrating machine learning with the key elements of biologics drug discovery – structural biology, protein engineering and translational immunology – to create optimized therapies on an accelerated path to patients. Seismic Therapeutic has an emerging pipeline of novel biologics to treat adaptive immune system dysregulation to treat 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.

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

 
 

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