CRISPR Therapeutics (CRSP) Corporate presentation summary

Background and rationale

• ANGPTL3 regulates lipid metabolism by inhibiting lipoprotein and endothelial lipase, making it a promising target for cardiovascular risk reduction.

• Poor adherence to lipid-lowering drugs limits current therapies; a one-time gene-editing approach could overcome this.

• CRISPR-Cas9 enables precise, targeted loss-of-function mutations in hepatocytes to mimic protective natural variants.

Study design and participants

• Phase 1a, multicenter, open-label, single-ascending dose trial with 15 participants having HoFH, HeFH, severe hypertriglyceridemia, or mixed dyslipidemia.

• Doses ranged from 0.1 to 0.8 mg/kg of CTX310, administered intravenously.

• Median age was 53 years; 87% male; 40% had clinical ASCVD; mean LDL-C was 155 mg/dL.

Efficacy results

• At 12 months, ANGPTL3 levels dropped up to 79% at the highest dose.

• LDL cholesterol reduced by up to 53% and triglycerides by up to 48% at 12 months for the highest dose.

• Apolipoprotein B and non-HDL cholesterol also showed significant reductions at higher doses.

• Triglyceride-rich lipoprotein cholesterol decreased by up to 72% at the highest dose.