Chroma Medicine Presents Preclinical In Vivo Data Showing Durable Cholesterol Reduction with a PCSK9-Targeted Epigenetic Editor at the 2023 AHA Scientific Sessions

This first presentation of non-human primate (NHP) data highlights the potential of Chroma's epigenetic editors to achieve specific and robust results after a single administration, without cutting or nicking the DNA

In NHPs, Chroma's epigenetic editor achieved efficient reductions in blood PCSK9 (80%) and low-density lipoprotein (LDL) cholesterol (58%) levels that were durably maintained over the course of three months

Transgenic mouse data demonstrate near-complete (>98%) silencing of human PCSK9 with durability out to 10 months

PCSK9 silencing was durably maintained in a mouse model of partial hepatectomy

BOSTON, Nov. 11, 2023 /PRNewswire/ -- Chroma 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.

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).

SOURCE Chroma Medicine