Verve Therapeutics Advances Pipeline with Focus on Gene Editing for Cardiovascular Disease
Key Insights
Verve Therapeutics anticipates initial data from the Heart-2 Phase 1b trial of VERVE-102, targeting PCSK9, in Q2 2025, including safety and efficacy data.
VERVE-301 has been nominated as the development candidate targeting the LPA gene (search), triggering a milestone payment from Eli Lilly, who will fund Phase 1 development.
The Pulse-1 Phase 1b trial for VERVE-201, which targets ANGPTL3 (search), is progressing, with an update expected in the second half of 2025.
Verve Therapeutics is making strides in developing single-course gene editing medicines for cardiovascular disease (search), with key milestones anticipated in 2025 across its pipeline. The company's approach targets major drivers of high cholesterol, including LDL-C, remnant cholesterol, and lipoprotein(a) [Lp(a)].
VERVE-102: Targeting PCSK9
Initial data from the Heart-2 Phase 1b clinical trial evaluating VERVE-102, a novel base editing medicine targeting PCSK9, is expected in the second quarter of 2025. The Heart-2 trial is an open-label study enrolling adults with heterozygous familial hypercholesterolemia (search) (HeFH) and premature coronary artery disease (search) (CAD) who require significant LDL-C reduction. The trial includes four dose cohorts.
As of October 29, 2024, seven participants in the first two dose cohorts (0.3 mg/kg and 0.45 mg/kg) have completed dosing. VERVE-102 has been well-tolerated in these participants, with no serious adverse events or clinically significant laboratory abnormalities observed. Dosing has now advanced to the third cohort at 0.6 mg/kg following a review by the independent data and safety monitoring board (DSMB) in November.
The initial data readout in Q2 2025 will include ten to twelve participants across the first three dose cohorts, with at least 28 days of follow-up. Verve plans to report demographic, safety, and efficacy data. Final data for the dose escalation portion of the Heart-2 trial is expected in the second half of 2025. Under the collaboration agreement, Eli Lilly has the option to co-develop and commercialize the PCSK9 program, with Verve retaining control in the United States and holding all rights outside the U.S. Verve expects to deliver the opt-in data package to Lilly in the second half of 2025 and plans to initiate a Phase 2 trial for the PCSK9 program in the same period.
VERVE-201: Targeting ANGPTL3
The Pulse-1 Phase 1b clinical trial for VERVE-201, a base editing medicine targeting ANGPTL3 (search), is ongoing. The first participant was dosed in November 2024. Pulse-1 is evaluating the safety and tolerability of VERVE-201 in adults with refractory hypercholesterolemia (search) (RH) who need additional LDL-C lowering despite maximally tolerated standard therapies, including PCSK9 inhibitors. Endpoints include pharmacokinetics and changes in blood ANGPTL3 protein and LDL-C levels. Verve expects to provide an update on the ANGPTL3 program in the second half of 2025.
VERVE-301: Targeting LPA
Verve has nominated VERVE-301 as its development candidate targeting the LPA gene (search). VERVE-301 employs an in vivo gene editing approach to permanently turn off the LPA gene in the liver, reducing blood lipoprotein(a) [Lp(a)] levels. Elevated Lp(a) is a genetically validated, independent risk factor for atherosclerotic cardiovascular disease (search) (ASCVD), ischemic stroke (search), thrombosis, and aortic stenosis (search). An estimated 1.4 billion people worldwide have Lp(a) concentrations above 125 nmol/L, a level associated with increased risk. Concentrations of Lp(a) are determined at birth and are not significantly affected by lifestyle changes or current lipid-lowering therapies.
Verve has an exclusive research collaboration with Eli Lilly to advance the Lp(a) program. With the nomination of VERVE-301, Verve will receive a milestone payment from Lilly. Verve will advance the program through Phase 1 clinical development, funded by Lilly, who will then be responsible for subsequent development, manufacturing, and commercialization. Verve is eligible for up to $465 million in research, development, and commercial milestones, as well as tiered royalties on global net sales. Verve also has the option to co-fund and share margins globally on the Lp(a) program after Phase 1, in lieu of milestones and royalties.
Financial Position
Verve's existing cash, cash equivalents, and marketable securities, including the milestone payment from Lilly, are expected to fund operations into mid-2027.
Sekar Kathiresan, M.D., co-founder and chief executive officer of Verve Therapeutics, stated, "Our mission is to advance a new class of in vivo gene editing medicines for cardiovascular disease (search) that target three key drivers of high cholesterol... 2025 is anticipated to bring important milestones across our pipeline."