Verve Therapeutics (VERV) Stifel 2024 Healthcare Conference summary

Pipeline overview and strategy

• Focus on gene editing medicines for cardiovascular disease, aiming for one-time, permanent cholesterol reduction via liver-targeted base editing.

• Lead programs target PCSK9 (Verve-101, Verve-102), ANGPTL3 (Verve-201), and Lp(a), with Verve-102 and Verve-201 in clinical trials and Lp(a) in preclinical development.

• Verve-102 has dosed seven patients across two dose levels, with phase I data expected in the first half of next year.

• Verve-201 dosed its first patient, expanding the clinical pipeline.

Clinical trial updates and safety

• Verve-101 and Verve-102 share the same gene editing cargo but differ in lipid nanoparticle composition, with 102 designed to improve safety.

• Verve-101 showed durable LDL reductions up to 60% at 18 months but had liver safety issues linked to the nanoparticle, not the editing cargo.

• Verve-102 has not shown similar safety abnormalities in the first seven patients, and dose escalation is ongoing.

• Heart-2 trial uses a flexible, adaptive dose design, referencing dose ranges from similar programs.

Efficacy and patient populations

• Efficacy is measured by both PCSK9 protein reduction and LDL lowering, with established relationships between the two.

• Heart-2 trial enrolls more moderate patients, excluding those with severe coronary blockages via CT angiogram.

• Target populations include HeFH and premature CAD, aiming for lifelong LDL reduction as a functional cure.

• LDL reduction is expected to be >40% for HeFH and >50% for ASCVD, matching or exceeding current therapies.