ASGCT 2024: Simultaneous Five-gene Epigenetic Editing to Generate TGF-β and Adenosine-resistant Allogeneic CAR T Cells

Boston, December 10, 2023 – Chroma Medicine, Inc., (Chroma) a genomic medicine company pioneering single-dose epigenetic editing therapeutics, today presented data demonstrating the potential of its multiplex epigenetic editing platform to enhance functional allogeneic chimeric antigen receptor (CAR) T cells at the American Society of Hematology (ASH) 65th Annual Meeting in San Diego.

Allogeneic CAR T cell products offer advantages over autologous CAR T cells and have the potential to broaden access to cancer immunotherapy; however, their clinical effect remains limited by lack of durable response and challenges related to immunogenicity and graft-versus-host disease. Incorporating additional edits may help produce cells resistant to rejection—potentially improving allogeneic T cell persistence—but using editing technologies that rely on double- or single-stranded DNA breaks can result in unintended genomic changes. Chroma’s epigenetic editing technology has the potential to provide durable modulation of gene expression without cutting or nicking the DNA, making it well-suited for simultaneous targeting of multiple genes to enhance generation of persistent allogeneic CAR T cells.

“The data presented at ASH illustrate the tremendous potential of epigenetic editing to accelerate allogeneic CAR T approaches by enhancing functional allogeneic cells to avoid common genotoxic challenges observed in nuclease-based gene editing and base editing,” said Vic Myer, Ph.D., Chroma’s President and CSO. “We believe harnessing nature’s innate mechanism for gene regulation unlocks vast opportunity to efficiently, effectively, and simultaneously silence many target genes, and the data presented underscore the strength of this approach in ex vivo cell therapies.”

The poster presentation shows Chroma’s epigenetic editor in primary T cells induces durable silencing of T cell receptor and MHC class I and MHC class II expression, maintained through restimulation. The data also demonstrate that multiplex epigenetic editing of CAR T cells does not interfere with cytotoxic anti-tumor function, further highlighting the potential to create CAR T cell therapies with greater accessibility, durability, and efficacy for patients.

Details for Chroma’s poster presentation at the 2023 ASH Annual Meeting are as follows:

Title: Durable Multiplex Epigenetic Editing for Generation of Allogeneic CAR T Without Chromosomal Rearrangements
Presenter: Jamie Schafer, Ph.D., Associate Director, Ex Vivo Program Sciences, Chroma Medicine
Session: 703. Cellular Immunotherapies: Basic and Translational: Poster II
Session Date and Time: Sunday, December 10, 2023, 6:00 – 8:00p PT

The poster presentation is available on Chroma’s website.

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About Chroma Medicine

Chroma Medicine is a biotechnology company pioneering a new class of genomic medicines that harnesses epigenetics, nature’s innate mechanism for gene regulation, to deliver precise, programmable single-dose therapeutics while preserving genomic integrity. The company’s modular platform enables development of medicines that can address a wide range of complex diseases, whether they require silencing, activation, or targeting multiple genes at once. Chroma was founded by the world’s foremost experts in genomic research and is led by a veteran team of industry leaders and scientists with deep experience in genomic medicine, drug discovery, and development. For more information, please visit chromamedicine.com or follow the company on LinkedIn and X (formerly known as Twitter).

Media Contact

Lia Dangelico

Verge Scientific Communications

540.303.0180

lia.dangelico@vergescientific.com

Boston, November 11, 2023Chroma Medicine, Inc., (Chroma) a genomic medicine company pioneering single-dose epigenetic editing therapeutics, today presented new preclinical data demonstrating that a single administration of its epigenetic editor efficiently and durably lowered PCSK9 and cholesterol levels in non-human primates in a late-breaking oral presentation at the 2023 American Heart Association (AHA) Scientific Sessions, held November 11-13 in Philadelphia.

The data presented provide strong evidence for the potential of Chroma’s epigenetic editing platform to silence expression of PCSK9 in the liver and to induce a durable reduction in low-density lipoprotein-cholesterol (LDL-C) levels, a key factor for reducing risk of atherosclerotic cardiovascular disease (ASCVD), without cutting or nicking the DNA.

The PCSK9 gene actively promotes the degradation of LDL receptors, thereby reducing the ability of the liver to clear cholesterol from the blood. Genetic and pharmacologic reductions in PCSK9 levels have been shown to correlate with decreased cardiovascular events, making it an established target for prevention of ASCVD.

“We believe our epigenetic editing approach offers the potential for highly efficacious, specific, and durable silencing of PCSK9 in the liver while preserving genomic integrity and avoiding the inherent risks of editing approaches that cut or nick the DNA,” said Vic Myer, Ph.D., Chroma’s President and Chief Scientific Officer. “These results not only validate the power of our platform to effectively silence PCSK9 but also provide strong evidence of the resulting impact on key therapeutic biomarkers.”

The work details Chroma’s human PCSK9-targeting epigenetic editor, which was shown to efficiently and durably reduce PCSK9 levels in vivo through 10 months of follow up after a single administration in human transgenic mice. The data also show that the silencing was maintained in mice pre- and post- partial hepatectomy, the standard surgical model for induction of liver regeneration. In non-human primates, a significant reduction in circulating PCSK9 (80%) levels was achieved, resulting in a 58% reduction in LDL-C levels.

These studies also show a clearer link between Chroma’s PCSK9 epigenetic editor’s molecular action of CpG methylation and PCSK9 silencing. Application of the company’s epigenetic editor was found to be highly correlated with targeted CpG methylation at the PSCK9 locus in vivo and durable through tissue regeneration in the partial hepatectomy model.

“Developing single-dose therapies is a crucial step for disrupting the current treatment paradigm for lowering LDL-cholesterol and reducing the risk of serious cardiovascular disease,” said Catherine Stehman-Breen, M.D., Chroma’s Chief Executive Officer. “Data presented today signal the potential of our epigenetic editing platform to deliver precise and durable gene regulation by leveraging the cell’s natural mechanism, bringing us another step closer to delivering better therapies to patients.”

Details for Chroma’s presentation at the 2023 AHA Scientific Sessions are as follows:

Title: A Single Administration of an Epigenetic Editor Targeting Human PCSK9 Robustly and Durably Lowers Cholesterol In Vivo
Presenter: Frederic Tremblay, Ph.D., Vice President, Head of In Vivo Programs, Chroma Medicine
Date and Time: Saturday, November 11, 2023, 9:45 – 9:55a ET
Session: Late Breaking Basic Science Abstract Oral Session

The presentation will be available on the Chroma website following the meeting.

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About ASCVD

Chronically elevated blood levels of low-density lipoprotein-cholesterol (LDL-C) can lead to increased risk for early onset atherosclerotic cardiovascular disease (ASCVD), heart attack, and stroke. ASCVD is the leading cause of death in the United States and globally. Current therapeutic interventions often fail to lower LDL-C below designated therapeutic thresholds and require frequent dosing, leading to treatment adherence challenges. The PCSK9 gene actively promotes the degradation of LDL receptors, which are responsible for clearing LDL-C from the blood, thereby reducing the ability of the liver to clear cholesterol from the blood. Genetic and pharmacologic reductions in PCSK9 have been associated with decreased LDL-C levels and reduced risk for cardiovascular events. Chroma is advancing an in vivo epigenetic editing therapeutic designed to effectively and durably silence the PCSK9 gene without cutting or nicking the DNA, resulting in decreased PCSK9 protein levels and leading to lower LDL-C levels and reduced risk of ASCVD.

About Chroma Medicine

Chroma Medicine is a biotechnology company pioneering a new class of genomic medicines that harnesses epigenetics, nature’s innate mechanism for gene regulation, to deliver precise, programmable single-dose therapeutics while preserving genomic integrity. The company’s modular platform is designed to enable the development of medicines that address a wide range of complex diseases, whether they require silencing, activation, or targeting multiple genes at once. Chroma was founded by experts in genomic research and is led by a veteran team of industry leaders and scientists with deep experience in genomic medicine, drug discovery, and development. For more information, please visit chromamedicine.com or follow the company on LinkedIn and X (formerly known as Twitter).

Media Contact

Lia Dangelico

Verge Scientific Communications

540.303.0180


Boston, MA, November 2, 2023 – Chroma Medicine, Inc., (Chroma) a genomic medicine company pioneering single-dose epigenetic editing therapeutics, today announced that it will present a poster demonstrating the potential of its multiplex epigenetic editing platform at the American Society of Hematology (ASH) 65th Annual Meeting, taking place December 9-12, 2023, in San Diego, CA.

The ASH abstract contains data showing the potential of multiplex epigenetic editing to produce functional allogeneic CAR T cells that do not exhibit a graft-versus-host-disease (GVHD) response, resist CD8+ and CD4+ T cell alloresponses, and resist the NK missing-self response normally consequent of reduced MHC class I expression, without introduction of genotoxic events.

Details of the poster presentation are:

Title: Durable Multiplex Epigenetic Editing for Generation of Allogeneic CAR T without Chromosomal Rearrangements
Presenter: Jamie Schafer, Ph.D., Associate Director, Ex Vivo Program Sciences, Chroma Medicine
Session: 703. Cellular Immunotherapies: Basic and Translational: Poster II
Session Date and Time: Sunday, December 10, 2023, 6:00-8:00 PM

The full abstract is available through the ASH conference website.

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About Chroma Medicine

Chroma Medicine is a biotechnology company pioneering a new class of genomic medicines that harnesses epigenetics, nature’s innate mechanism for gene regulation, to deliver precise, programmable single-dose therapeutics while preserving genomic integrity. The company’s modular platform enables development of medicines that can address a wide range of complex diseases, whether they require silencing, activation, or targeting multiple genes at once. Chroma was founded by the world’s foremost experts in genomic research and is led by a veteran team of industry leaders and scientists with deep experience in genomic medicine, drug discovery, and development. For more information, please visit chromamedicine.com or follow the company on LinkedIn and X (formerly known as Twitter).

Media Contact

Lia Dangelico

Verge Scientific Communications

540.303.0180

ldangelico@vergescientific.com