VERVE-102 / Eli Lilly - LARVOL DELTA

† VERVE-102, a clinical stage in vivo base editing medicine, leads to potent and precise inactivation of PCSK9 in preclinical studies (NLA 2025) - P1 | "Here we demonstrate that VERVE-102 leads to potent and precise PCSK9 inactivation in PHH and animal models and provide nonclinical proof-of-concept for LDL-C lowering. A first-in-human clinical trial of VERVE-102 (NCT06164730) is ongoing."

Preclinical • Cardiovascular • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Metabolic Disorders • PCSK9

Next Steps (GlobeNewswire) - "Verve plans to dose the first patient in the Phase 2 clinical trial of VERVE-102 in the second half of 2025, subject to regulatory clearance. With the recent clearance by the U.S. FDA of the investigational new drug (IND) application for VERVE-102, Verve expects to enroll patients at U.S. trial sites in the Phase 2 clinical trial. Verve expects its current capital position to be sufficient to fund its operations into mid-2027, which includes the completion of the Phase 2 clinical trial."

Trial completion date • Trial status • Heterozygous Familial Hypercholesterolemia

Verve Therapeutics Announces Positive Initial Data from the Heart-2 Phase 1b Clinical Trial of VERVE-102, an In Vivo Base Editing Medicine Targeting PCSK9 (GlobeNewswire) - P1b | N=36 | Heart-2 (NCT06164730) | Sponsor: Verve Therapeutics, Inc. | "Verve Therapeutics...today announced positive initial data from the Heart-2 Phase 1b clinical trial of VERVE-102. The Heart-2 Phase 1b clinical trial is evaluating patients with heterozygous familial hypercholesterolemia (HeFH) and/or premature coronary artery disease (CAD), two populations that require deep and durable reductions of low-density lipoprotein cholesterol (LDL-C) levels in the blood. Among 14 participants across three dose levels, VERVE-102 was well-tolerated, with no treatment-related serious adverse events (SAEs) and no clinically significant laboratory abnormalities observed....Verve expects to announce the final data from the dose escalation portion of the Heart-2 clinical trial, including durability data, in the second half of 2025."

P1 data • Coronary Artery Disease • Heterozygous Familial Hypercholesterolemia

Verve Therapeutics Receives U.S. FDA Fast Track Designation for VERVE-102, an In Vivo Base Editing Medicine Targeting PCSK9 (GlobeNewswire) - "Verve Therapeutics...announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation for VERVE-102 for the treatment of patient groups with hyperlipidemia and high lifetime cardiovascular risk to reduce low-density lipoprotein cholesterol (LDL-C)....In the second quarter of 2025, Verve expects to announce demographic and initial safety and efficacy data from the Heart-2 clinical trial....In addition, in the second half of 2025, Verve remains on track to report the final data for the dose escalation portion of the Heart-2 clinical trial, deliver the opt-in package for the PCSK9 program to Eli Lilly and Company (Lilly), and initiate the Phase 2 clinical trial for the PCSK9 program."

Fast track • P1 data • Cardiovascular • Heterozygous Familial Hypercholesterolemia

As part of the IND submission, Verve provided the FDA with interim clinical data from the dose-escalation portion of the ongoing Heart-2 Phase 1b clinical trial for VERVE-102. (GlobeNewswire) - P1b | N=36 | Heart-2 (NCT06164730) | Sponsor: Verve Therapeutics, Inc. | "With our ongoing Heart-2 clinical trial for VERVE-102 progressing internationally, we are excited to begin activating trial sites in the U.S. as we expect it to play a key role in our continued clinical development....Data submitted to the FDA had a cut-off date of January 10, 2025, and included participants across the first three dose cohorts (0.3 mg/kg, 0.45 mg/kg, and 0.6 mg/kg). As of the data cut-off date, VERVE-102 has been well-tolerated, with no treatment-related serious adverse events and no clinically significant laboratory abnormalities observed. In the second quarter of 2025, Verve expects to announce demographic and initial safety and efficacy data from the Heart-2 clinical trial. Enrollment in the Heart-2 clinical trial is progressing well...Verve remains on track to report the final data for the dose escalation portion of the Heart-2 clinical trial."

P1 data • Cardiovascular • Heterozygous Familial Hypercholesterolemia

Verve Therapeutics Announces Clearance of Investigational New Drug Application by the U.S. FDA for VERVE-102, an Investigational Gene Editing Medicine Designed to Durably Lower Cholesterol After a Single Dose (GlobeNewswire) - "Verve Therapeutics...today announced the clearance of its Investigational New Drug (IND) application by the U.S. Food and Drug Administration (FDA) for VERVE-102 for the treatment of patients living with heterozygous familial hypercholesterolemia (HeFH) and/or premature coronary artery disease (CAD)."

IND • Cardiovascular • Heterozygous Familial Hypercholesterolemia

Verve Therapeutics Announces Pipeline Progress and Reports Fourth Quarter and Full Year 2024 Financial Results (GlobeNewswire) - "Initial Data for the Heart-2 Phase 1b Clinical Trial Evaluating VERVE-102 Expected in the Second Quarter of 2025....Dosing has been completed or is ongoing in participants across the first three dose cohorts, 0.3 mg/kg, 0.45 mg/kg, and 0.6 mg/kg, in the Heart-2 clinical trial....Verve expects to report the final data for the dose escalation portion of the Heart-2 clinical trial and initiate the Phase 2 clinical trial for the PCSK9 program in the second half of 2025. Verve plans to deliver the opt-in data package for the PCSK9 program and receive a decision from Eli Lilly and Company (Lilly) in the second half of 2025....ANGPTL3 Program: Pulse-1 Phase 1b Clinical Trial for VERVE-201 Continues to Progress....Verve expects to provide an update on the ANGPTL3 program in the second half of 2025."

P1 data • Cardiovascular • Heterozygous Familial Hypercholesterolemia

Design of Heart-2: a phase 1b clinical trial of VERVE-102, an in vivo base editing medicine delivered by a GalNAc-LNP and targeting PCSK9 to durably lower LDL cholesterol (AHA 2024) - "Consistency of the gRNA target site suggests that potential therapeutic benefits should apply broadly across ancestries. The ongoing Heart-2 clinical trial is intended to support selection of a safe and effective dose for future clinical investigation of VERVE-102."

P1 data • Preclinical • Cardiovascular • Coronary Artery Disease • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Heterozygous Familial Hypercholesterolemia • Metabolic Disorders • ASGR • MUC4

A Study of VERVE-102 in Patients With Familial Hypercholesterolemia or Premature Coronary Artery Disease (clinicaltrials.gov) - P1 | N=36 | Recruiting | Sponsor: Verve Therapeutics, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Cardiovascular • Coronary Artery Disease • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Heart Failure • Heterozygous Familial Hypercholesterolemia • Metabolic Disorders

VERVE-101, a CRISPR base-editing therapy designed to permanently inactivate hepatic PCSK9 and reduce LDL-cholesterol. (PubMed, Expert Opin Investig Drugs) - No abstract available

Journal

A Study of VERVE-102 in Patients With Familial Hypercholesterolemia or Premature Coronary Artery Disease (clinicaltrials.gov) - P1 | N=36 | Not yet recruiting | Sponsor: Verve Therapeutics, Inc.

New P1 trial • Cardiovascular • Coronary Artery Disease • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Heart Failure • Heterozygous Familial Hypercholesterolemia • Metabolic Disorders