Chroma Medicine Presents Preclinical In Vivo Data Demonstrating Best-in-Class Potency and Durable Cholesterol Reduction with a PCSK9-Targeted Epigenetic Editor at the 2024 ESC Congress

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Sep 03, 2024, 07:00 ET

New NHP data indicate robust silencing at clinically relevant dose levels and highlight potential best-in-class potency achievable with Chroma's epigenetic editors

Chroma's epigenetic editor achieved efficient and durable reductions in blood PCSK9 (84%) and LDL-cholesterol (68%) following a single 1.0 mg/kg dose

Potential for life-long durability supported by mechanistic data confirming robust and stable CpG methylation at the PCSK9 locus in NHPs

BOSTON, Sept. 3, 2024 /PRNewswire/ -- Chroma Medicine, Inc., (Chroma) a genomic medicine company pioneering single-course epigenetic editing therapeutics, presented new preclinical data demonstrating the potency, durability, and specificity of its PCSK9-targeted epigenetic editor in an oral presentation at the 2024 European Society of Cardiology Congress, held August 30-September 2 in London.

The data showcase the potential best-in-class potency achievable in NHPs with Chroma's optimized epigenetic editors. They also indicate the company's epigenetic editing platform can effectively silence expression of PCSK9 in the liver, inducing durable reductions in low-density lipoprotein-cholesterol (LDL-C) levels 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. This can result in chronically elevated blood levels of LDL-C and lead to increased risk for early onset atherosclerotic cardiovascular disease (ASCVD). Genetic and pharmacologic reductions in PCSK9 levels have been shown to correlate with decreased cardiovascular events, making it an established and compelling target for prevention of ASCVD.

"These results underscore the successful optimization and development of a highly potent, durable, and specific PCSK9-targeted therapeutic," said Catherine Stehman-Breen, M.D., Chroma's Chief Executive Officer. "By demonstrating potency at clinically relevant doses, we have achieved a key requirement for successful translation of a lipid nanoparticle-delivered genomic medicine into an efficacious and well-tolerated therapeutic, supporting continued advancement toward clinical studies."

Data from the presentation demonstrate best-in-class potency, with Chroma's human PCSK9-targeting epigenetic editor reaching saturating pharmacology at 1.0 mg/kg in NHPs. A significant reduction in circulating PCSK9 (84%) levels was achieved, resulting in a 68% reduction in LDL-C levels, maintained out to three months. Additional data show that the company's epigenetic editor efficiently and durably reduced PCSK9 levels in vivo for one year after a single administration in human transgenic mice. The silencing was maintained in mice pre- and post-partial hepatectomy, the standard surgical model for induction of liver regeneration.

"We believe single-course therapies are crucial in the creation of genomic medicines that can disrupt the current treatment paradigm for lowering LDL-cholesterol and reduce the risk of serious cardiovascular disease," said Jenny Marlowe, Ph.D., Chroma's Chief Development Officer. "These data presented at ESC confirm the potential of our epigenetic editing platform to produce a highly potent therapeutic that can bring the promise of better treatment options within reach."

Find the presentation on the Chroma website here.

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 harness epigenetics, nature's innate mechanism for gene regulation, to deliver precise, programmable single-course 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 us on LinkedIn and X.

SOURCE Chroma Medicine