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Our PCSK9 Programs

We are developing two product candidates targeting PCSK9 – VERVE-101 and VERVE-102. These single-course treatments are designed to permanently turn off the PCSK9 gene in the liver to reduce disease-driving LDL-C.


VERVE-101, a single-course in vivo liver base editing medicine, is currently being evaluated in our Phase 1b heart-1 clinical trial in patients with high-risk heterozygous familial hypercholesterolemia (HeFH), established atherosclerotic cardiovascular disease (ASCVD), and uncontrolled LDL-C levels on oral standard-of-care therapy.

HeFH is characterized by extremely high LDL-C levels in the blood that, over time, cause plaque to build up in the arteries, resulting in reduced blood flow or blockage. This significantly increases an individual’s risk for heart attack and stroke. Inactivation of the PCSK9 gene in the liver can be effective in lowering LDL-C levels.

We believe that VERVE-101 has the potential to treat a broad population of patients and plan to take a stepwise approach for its clinical development. If our Phase 1b heart-1 clinical trial to evaluate the safety and efficacy of VERVE-101 in patients with high-risk HeFH is successful, we plan to expand into the broader HeFH population, and then ultimately target larger patient groups with established ASCVD.

Encouraging Clinical Results from heart-1  
We announced encouraging initial proof-of-concept data from the heart-1 clinical trial in November 2023. Results indicated that treatment with VERVE-101 led to dose-dependent reductions of disease-causing LDL-C in people living with HeFH, and the safety profile was consistent with the severe, advanced ASCVD patient population enrolled.

The heart-1 trial is designed to evaluate the safety and tolerability of VERVE-101, along with analyses of pharmacokinetics and pharmacodynamic reductions in blood PCSK9 protein and LDL-C. In the interim dataset, six patients were treated at sub-therapeutic doses (0.1 mg/kg [n=3] and 0.3 mg/kg [n=3]) and four patients were treated at potentially therapeutic doses (0.45 mg/kg [n=3] and 0.6 mg/kg [n=1]). Initial safety results reported were from all ten patients enrolled, and efficacy data included nine participants, as one patient who received the 0.45 mg/kg dose had not reached day 28 as of the data cut-off date of 10/16/2023.

Key findings include:

  • The two patients treated with 0.45 mg/kg of VERVE-101 had a time-averaged blood PCSK9 protein reduction of 59% and 84%. The patient treated with 0.6 mg/kg of VERVE-101 had a time-averaged blood PCSK9 protein reduction of 47%.
  • The two patients treated with 0.45 mg/kg of VERVE-101 had a time-averaged LDL-C reduction of 39% and 48%. The patient treated with 0.6 mg/kg of VERVE-101 had a time-averaged LDL-C reduction of 55%. In this single participant in the highest dose cohort, the 55% reduction in LDL-C was durable out to 180 days, with follow-up ongoing.
  • VERVE-101 was well-tolerated in the two lower dose cohorts, with no treatment-related adverse events observed. In the two higher dose cohorts, treatment-related adverse events were observed, including transient, mild or moderate infusion reactions and transient, asymptomatic increases in liver transaminases with mean bilirubin levels below the upper limit of normal.
    • Two patients experienced serious adverse events, which were each cardiovascular events in the context of severe underlying ASCVD.
    • All safety events were reviewed with the independent data and safety monitoring board who recommended continuation of study enrollment with no protocol changes required.

See full results from the interim analysis here

PCSK9 graph
LDLC graph


We are committed to solving FH by targeting PCSK9, and we are currently evaluating a second PCSK9 gene editor, VERVE-102, further increasing our odds of addressing the unmet needs of patients with FH, and ultimately, those with or at-risk of ASCVD.

VERVE-102 is a single-course in vivo liver base editing medicine that aims to inactivate PCSK9 like VERVE-101, but that is delivered via Verve’s proprietary GalNAc-LNP delivery technology. Preclinical studies in NHPs using VERVE-102 with GalNAc-LNP delivery demonstrated effective in vivo gene editing in the liver and significant PCSK9 protein reduction.

Preclinical development to support a regulatory submission for VERVE-102 began in early 2022, and Verve expects to initiate a Phase 1b clinical trial with VERVE-102 for patients with HeFH in the first half of 2024.