Single-Dose VERVE-102 Cuts LDL Up to 62%, Showing Clean Safety Profile

1. Liver-Targeted Delivery: The active components are packaged inside a proprietary GalNAc lipid nanoparticle (LNP). The GalNAc ligand acts like a homing signal, directing the LNP specifically to receptors on hepatocytes (liver cells) .
2. Genetic Editing Machinery: Inside the nanoparticle are two key molecules: an mRNA blue-print for an adenine base editor, and a guide RNA .
3. Precise DNA Correction: Once inside the liver cell, the guide RNA navigates the base editor directly to the PCSK9 gene. The editor then chemically converts one specific DNA base pair (an A•T to a G•C). This minuscule change introduces a premature "stop" signal in the gene, effectively rendering it permanently inactive .

By mimicking a naturally occurring human genetic variant that provides lifelong protection from heart disease, VERVE-102 is designed to be a truly one-and-done therapy .

Phase 1b Heart-2 Trial: The Data

In May 2026, Eli Lilly announced the full results from the Heart-2 trial, which enrolled 35 adults with heterozygous familial hypercholesterolemia (HeFH) or premature coronary artery disease—conditions that carry high cardiovascular risk .

Participants received a single infusion across multiple dosing cohorts. The key findings showed dose-dependent and durable efficacy:

• PCSK9 Protein Reduction: Dose-dependent mean reductions ranged from 51% to 88%. At the highest dose, PCSK9 levels dropped by up to 88% .
• LDL Cholesterol Reduction: The therapy lowered LDL-C by up to 62% across the trial. In the 0.6 mg/kg dosing cohort specifically, the mean reduction was 53%, with individual patients achieving a maximum reduction of 69% .
• Durability: Critically, these reductions were sustained for up to 18 months of follow-up, supporting the therapy's potential to deliver a lifelong effect after a single course of treatment .

Safety First: A Clean Profile

The safety data were perhaps as important as the efficacy. Verve's first-generation candidate, VERVE-101, produced promising cholesterol cuts but was paused due to liver safety concerns at higher doses . VERVE-102, using an upgraded LNP delivery system, appears to have solved that problem.

In the Heart-2 trial, VERVE-102 was well-tolerated at all dose levels. Investigators reported:

• No treatment-related serious adverse events (SAEs) or dose-limiting toxicities .
• No clinically significant changes in liver enzymes (ALT/AST), bilirubin, or platelets, which were key safety watchpoints after the previous program .

One participant experienced a Grade 2 infusion-related reaction with transient symptoms that resolved with standard acetaminophen treatment . The consistent safety profile across low and high doses removes a significant hurdle for the program's advancement.

What's Next for VERVE-102?

VERVE-102's path to the clinic is accelerating through a series of strategic milestones:

• Phase 2 is Underway: Verve had previously dosed its first Phase 2 patient in the second half of 2025. The positive Phase 1b data will inform the optimal dose selection for these pivotal trials .
• FDA Fast Track: The U.S. FDA granted Fast Track designation in April 2025 for treating patient groups with hyperlipidemia and high cardiovascular risk. This allows for more frequent FDA meetings and a potentially accelerated rolling review of a future Biologics License Application (BLA) .
• Eli Lilly's Option: Under its partnership with Verve, Eli Lilly holds rights to lead development and commercialization. The companies jointly announced the Phase 1b data, signaling a coordinated push forward, though a formal opt-in decision had not been declared at the time of the results .

VERVE-102 is the lead candidate in a broader pipeline of single-course gene editors targeting the root genetic causes of cardiovascular disease, including therapies for ANGPTL3 and Lp(a) .