Single-Course CRISPR Gene-Editing Therapy CTX310 Shows Durable Lipid Lowering

ZUG, Switzerland and BOSTON, Nov. 08, 2025 — CRISPR Therapeutics (Nasdaq: CRSP) today announced positive Phase 1 data for CTX310, an investigational in vivo CRISPR/Cas9 gene-editing therapy targeting ANGPTL3. The data, presented during a late-breaking session at the American Heart Association (AHA) Scientific Sessions and simultaneously published in The New England Journal of Medicine (NEJM), show that a single, one-time infusion of CTX310 produced significant and sustained reductions in key lipid risk factors.

At the highest dose level, CTX310 achieved:

• A mean reduction from baseline of -73% in circulating ANGPTL3 (maximum -89%).
• A mean reduction in triglycerides (TG) of -55% (maximum -84%).
• A mean reduction of low-density lipoprotein (LDL) cholesterol of -49% (maximum -87%).

These compelling results demonstrate the potential for CTX310 to deliver meaningful and sustained lipid lowering, offering a transformative therapeutic approach for severe or refractory dyslipidemia.

Mechanism and Clinical Potential

CTX310 is a breakthrough in genetic medicine, designed as an in vivo, lipid nanoparticle (LNP) delivered CRISPR/Cas9 therapy. The therapy precisely edits the ANGPTL3 gene in hepatocytes (liver cells) following a single intravenous (IV) administration. The ANGPTL3 protein regulates TG and LDL levels, both major risk factors for cardiovascular disease.

“For the first time, we’ve shown that a single-course in vivo CRISPR treatment can safely and durably lower ANGPTL3, leading to clinically meaningful reductions in triglycerides and LDL,” said Naimish Patel, M.D., Chief Medical Officer of CRISPR Therapeutics. “These data provide strong support for continued advancement of CTX310 and our broader cardiovascular gene-editing portfolio.”

Stephen J. Nicholls, lead study investigator and director of the Victorian Heart Institute, commented on the significance of the data: “Seeing a single-course treatment safely lower both LDL cholesterol and triglycerides is truly unprecedented. If these findings are confirmed in larger studies, a one-time therapy could redefine how we manage lifelong lipid disorders and help prevent cardiovascular disease.”

Safety and Trial Details

The Phase 1, open-label, dose-escalation trial evaluated single doses of CTX310 in 15 participants with various severe dyslipidemias, including HoFH, sHTG, HeFH, and mixed dyslipidemias. The participants were already on background standard-of-care therapies, yet their lipid levels remained uncontrolled.

The CRISPR/Cas9 gene-editing therapy was generally well tolerated, with no dose-limiting toxicities or serious adverse events related to the treatment. Adverse events were generally mild to moderate, reinforcing the positive safety profile and supporting the continued development of the program.

CRISPR Therapeutics is now advancing CTX310 into Phase 1b clinical trials, with a focus on prioritizing development in severe hypertriglyceridemia (sHTG) and mixed dyslipidemia.