Scribe Therapeutics has announced promising in vivo data for its CRISPR-based therapies targeting cardiometabolic diseases. The company's X-Editor (XE) gene editing technology and Epigenetic Long-Term X-Repressor (ELXR) epigenetic modifying technology have demonstrated significant reductions in LDL-C, apolipoprotein C-III (APOC3), and triglyceride levels in preclinical studies. These findings, presented at the American Heart Association (AHA) Scientific Sessions 2024, suggest a potential new approach to treating conditions such as atherosclerotic cardiovascular disease (ASCVD) and hypertriglyceridemia.
CRISPR-Based Technologies Target Key Lipid Regulators
Scribe's technologies focus on proprotein convertase subtilisin/kexin type 9 (PCSK9) and apolipoprotein C-III (APOC3), key regulators of lipid metabolism. The XE gene editing technology achieved long-term LDL-C reduction of up to 55% for at least a year in non-human primates, with no identified off-target effects. In a parallel approach, Scribe’s ELXR epigenetic silencing technology demonstrated sustained LDL-C reduction of up to 67% in non-human primates for nearly six months.
"At AHA, we presented data that validate both of these technologies and their potential to empower patients—including millions suffering from cardiometabolic disease—to rewrite their future," said Benjamin Oakes, PhD, co-founder of Scribe Therapeutics. "Our latest data are proof that the future of medicine is here. The technologies Scribe has developed are opening new doors to safe genetic medicines that will allow physicians, patients, and other drug developers to choose the method best suitable to treat their target disease."
Addressing Unmet Needs in Cardiometabolic Disease
Cardiovascular disease remains a leading cause of death worldwide, and dyslipidemia affects a significant portion of the adult population in the U.S. Current standard-of-care therapies often suffer from poor patient adherence, highlighting the need for improved treatment options. Scribe's therapies aim to address this unmet need by providing durable, potentially one-time treatments that can significantly reduce lipid levels.
STX-1150 and STX-1400 Show Preclinical Efficacy
Scribe highlighted work from three programs at AHA 2024. New data for STX1150, an engineered CasX-based epigenetic silencer targeting PCSK9 to lower LDL-C levels, were presented. A single dose of STX1150 demonstrated sustained LDL-C reduction of up to 67% in NHPs for nearly six months. The company also presented new data for STX1400, a CRISPR XE gene editing therapy that targets the apolipoprotein C-III (APOC3) gene for the treatment of hypertriglyceridemia in familial chylomicronemia syndrome (FCS) and severe hypertriglyceridemia (sHTG) patients. The company demonstrated that STX1400 reduced APOC3 and triglyceride levels by more than 90% in vivo with the XE gene editing technology in mice.
Next Steps
Scribe Therapeutics anticipates further updates in 2025 as it continues to advance its CRISPR-based therapies toward clinical development. The company's focus on engineering CRISPR technologies for improved potency and specificity aims to create safer and more effective genetic medicines for a range of cardiometabolic diseases.
