Verve Therapeutics (VERV) Barclays 27th Annual Global Healthcare Conference summary

Company overview and technology

• Focused on developing a one-time gene editing therapy for lifelong cholesterol lowering to prevent heart attacks.

• Uses in vivo base editing to turn off cholesterol-raising genes in the liver via a single intravenous infusion.

• Targets include PCSK9, ANGPTL3, and LPA, chosen for strong human genetic validation.

• Chose base editing over standard CRISPR-Cas9 for improved safety, avoiding DNA cuts and potential translocations.

• Technology and delivery platform are designed to be flexible and adaptable.

Lipid nanoparticle (LNP) delivery evolution

• Two products, VERVE-101 and VERVE-102, use the same gene editing cargo but different LNP compositions.

• VERVE-101 showed strong efficacy and durability but had transient liver and platelet lab abnormalities, leading to a study pause.

• VERVE-102 uses a next-gen LNP with a safer ionizable lipid, also used by Intellia, and a proprietary GalNAc ligand for improved liver targeting.

• Preclinical and early clinical data suggest VERVE-102 avoids the lab abnormalities seen with VERVE-101.

• GalNAc addition aims to equalize efficacy in patients with LDL receptor mutations by enabling alternative liver cell entry.

Clinical development and upcoming data

• Phase I study of VERVE-102 is ongoing in HeFH and premature coronary artery disease patients, with data expected in Q2.

• Three dose cohorts (0.3, 0.45, 0.6 mg/kg) are being tested, with at least 10-12 patients and 28 days of follow-up per patient.

• Safety and efficacy endpoints include LDL and PCSK9 reduction, aiming for inclisiran-like benchmarks (40-50% LDL, 60-70% PCSK9 reduction).

• No treatment-related serious adverse events or significant lab abnormalities observed as of mid-February.

• Dose escalation will continue to a fourth cohort to define maximal effect and safety margin.