Verve Therapeutics, announced that the first patient has been dosed with VERVE-102 in the Heart-2 Phase 1b clinical trial. The Heart-2 trial is enrolling adult patients with heterozygous familial hypercholesterolemia (HeFH) or premature coronary artery disease (CAD), two patient populations who require deep reductions of low-density lipoprotein cholesterol (LDL-C) levels in the blood for an extended period of time. Patients living with HeFH have an inherited disorder characterized by elevated blood levels of LDL-C starting early in life.

Patients living with premature CAD experience cholesterol-driven blockage of coronary arteries early in life and are at high risk of further complications. A lack of durable control of LDL-C levels in both HeFH and premature CAD patients carries high lifetime risks for cardiovascular events, including heart attack and sudden death. VERVE-102 is a novel, investigational gene editing medicine designed to be a single course treatment that permanently turns off the PCSK9 gene in the liver to reduce disease-driving LDL-C. VERVE-102 consists of messenger RNA expressing an adenine base editor and an optimized guide RNA targeting the PCSK9 gene.

In addition, VERVE-102 uses a proprietary GalNAc-LNP delivery technology which allows lipid nanoparticles to access and deliver the gene editing medicine to liver cells using either the asialoglycoprotein receptor (ASGPR) or the low-density lipoprotein receptor (LDLR). Heart-2 is an open-label Phase 1b clinical trial designed to evaluate the safety and tolerability of VERVE-102 administration in adult patients with HeFH or premature CAD who require additional lowering of LDL-C. Endpoints also include pharmacokinetics and changes in blood PCSK9 protein and LDL-C levels. The trial is a single-ascending dose study that has an adaptive design.

Heart-2 is expected to include four dose cohorts each comprised of three to nine patients with either HeFH or premature CAD. HeFH is diagnosed based on high LDL-C levels, a personal or family history of ASCVD, physical exam features, and/or mutations identified in certain genes. Premature CAD is defined as evidence of ASCVD occurring in men aged 50 years old or women 60 years old.

Clinical Trial Applications for the Heart-2 trial have been cleared in Canada and the United Kingdom.