Verve Therapeutics Announces Pipeline Progress and Reports Third Quarter 2024 Financial Results

Seven participants across two cohorts dosed in the Heart-2 Phase 1b clinical trial of VERVE-102 targeting PCSK9; Initial data planned for the first half of 2025

First participant dosed in the Pulse-1 Phase 1b clinical trial of VERVE-201 targeting ANGPTL3; Regulatory clearances in Australia, Canada, and the U.K.

Cash, cash equivalents, and marketable securities of $539.9 million; cash runway through 2026

BOSTON, Nov. 05, 2024 (GLOBE NEWSWIRE) -- Verve Therapeutics, a clinical-stage company developing a new class of genetic medicines for cardiovascular disease, today reported pipeline updates and financial results for the quarter ended September 30, 2024.

"In the third quarter, we made considerable progress towards our mission to develop a new class of genetic medicines where a one-time treatment leads to lifelong lowering of blood cholesterol," said Sekar Kathiresan, M.D., co-founder and chief executive officer of Verve Therapeutics. "We continue to execute on the Heart-2 clinical trial and are pleased to share that as of October 29, 2024, seven participants have been dosed. VERVE-102 has been well-tolerated, with no serious adverse events and no clinically significant laboratory abnormalities observed. We look forward to providing initial data from the Heart-2 clinical trial and an update on the PCSK9 program in the first half of 2025."

Dr. Kathiresan continued, "In addition, we are excited to announce that the first participant in the Pulse-1 Phase 1b clinical trial for our ANGPTL3 product candidate, VERVE-201, was recently dosed. With cash runway through 2026, we are well-positioned to execute additional important milestones across our pipeline and advance our early-stage programs, including our program targeting LPA. With two product candidates being tested in the clinic, we expect 2025 to be an eventful year for Verve as we develop a new approach for the treatment of cardiovascular disease."

PCSK9 Program

Enrollment Ongoing in Heart-2 Phase 1b Clinical Trial Evaluating VERVE-102

   -- 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 and durably reduces disease-driving low-density lipoprotein 
      cholesterol (LDL-C). VERVE-102 consists of messenger RNA expressing an 
      adenine base editor and an optimized guide RNA targeting the PCSK9 gene 
      identical to VERVE-101, the company's initial PCSK9 product candidate 
      that showed proof-of concept for this mechanism. However, compared to 
      VERVE-101, VERVE-102 uses a different lipid nanoparticle (LNP) delivery 
      system, which includes a different ionizable lipid and Verve's 
      proprietary GalNAc liver-targeting ligand, designed to allow the LNP to 
      access liver cells using either the low-density lipoprotein receptor 
      (LDLR) or the asialoglycoprotein receptor (ASGPR). 
   -- VERVE-102 is being evaluated in the Heart-2 open-label Phase 1b clinical 
      trial in two patient populations who require deep and durable reductions 
      of LDL-C levels in the blood: adults living with heterozygous familial 
      hypercholesterolemia (HeFH) and adults living with premature coronary 
      artery disease $(CAD.UK)$. The Heart-2 clinical trial is expected to include 
      four dose cohorts, each comprised of three to nine patients with either 
      HeFH or premature CAD. 
   -- As of October 29, 2024, dosing has been completed in seven participants 
      in the first two dose cohorts, 0.3 mg/kg and 0.45 mg/kg, in the Heart-2 
      clinical trial. VERVE-102 has been well-tolerated. No serious adverse 
      events and no clinically significant laboratory abnormalities have been 
      observed. Following the standard review from the independent data and 
      safety monitoring board (DSMB), the company expects to continue the dose 
      escalation portion of the clinical trial. 
   -- Verve recently received clearance of its Clinical Trial Applications 
      (CTAs) for the Heart-2 clinical trial in Israel and New Zealand. 
      Enrollment remains ongoing in Australia, Canada, and the U.K. 
   -- In November 2024, Verve plans to present a moderated digital poster at 
      the American Heart Association (AHA) Scientific Sessions describing the 
      design of the Heart-2 Phase 1b clinical trial. 
   -- Verve expects to provide initial data from the Heart-2 clinical trial and 
      an update on the PCSK9 program in the first half of 2025. The company 
      also plans to initiate the Phase 2 clinical trial for the PCSK9 program 
      in the second half of 2025. 

Analyses of Heart-1 Phase 1b Clinical Trial of VERVE-101

   -- Verve recently reported updated durability data from the Heart-1 clinical 
      trial of VERVE-101 at the European Society of Gene and Cell Therapy 
      (ESGCT) 2024 Congress and the American Society of Nephrology Kidney Week 
      2024 Meeting. Mean, time-averaged PCSK9 protein reductions of greater 
      than 60% were observed in each of the two higher dose cohorts (0.45 mg/kg 
      and 0.6 mg/kg), and mean, time-averaged LDL-C reductions of 42% at 0.45 
      mg/kg (n=6) and time-averaged LDL-C reduction of 57% at 0.6 mg/kg (n=1) 
      were observed. In the single participant in the highest dose cohort, 
      LDL-C reduction has now been sustained out to 18 months after the single 
      dose. No new treatment related adverse events have been reported since 
      March 2024. Verve believes that these new durability data further support 
      the potential of once-and-done gene editing medicines for the treatment 
      of cardiovascular disease. 
   -- Verve has completed a series of nonclinical studies as part of its 
      investigation into the previously disclosed laboratory abnormalities 
      observed with VERVE-101. In order to isolate the role of the LNP and 
      determine whether the laboratory abnormalities observed in the Heart-1 
      clinical trial were due to the LNP delivery system, these studies used a 
      version of VERVE-101 with a non-targeting guide RNA designed to preclude 
      base editing. Data from these studies continue to support Verve's 
      understanding that the LNP in VERVE-101 is likely the primary driver of 
      the laboratory abnormalities observed in the Heart-1 clinical trial. The 
      Heart-1 clinical trial will remain paused during the dose escalation 
      portion of the Heart-2 clinical trial evaluating VERVE-102. 

ANGPTL3 Program

First Participant Dosed with VERVE-201 in the Pulse-1 Phase 1b Clinical Trial

   -- VERVE-201 is a novel, investigational gene editing medicine designed to 
      be a single course treatment that permanently turns off the ANGPTL3 gene 
      in the liver to reduce disease-driving LDL-C as well as remnant 
      cholesterol and utilizes Verve's proprietary GalNAc-LNP delivery 
      technology. VERVE-201 is being developed in two patient populations: 
      patients with refractory hypercholesterolemia $(RH)$, defined as those who 
      are unable to achieve adequate LDL-C reduction with maximally tolerated 
      standard of care therapies, potentially including PCSK9 inhibitors, and 
      patients living with homozygous familial hypercholesterolemia (HoFH), a 
      rare and often fatal inherited cause of premature ASCVD characterized by 
      extremely high blood LDL-C. The aim of this medicine is to reduce the 
      heavy treatment burden associated with available therapies, including the 
      requirement for multiple oral, injectable, and intravenous infusions, 
      often administered over decades. 
   -- Verve announced today that the first participant has been dosed with 
      VERVE-201 in its Pulse-1 Phase 1b clinical trial.The Pulse-1 clinical 
      trial is designed to evaluate the safety and tolerability of VERVE-201 
      administration in adult patients with RH who require additional lowering 
      of LDL-C despite treatment with maximally tolerated standard of care 
      therapies, potentially including PCSK9 inhibitors. Endpoints also include 
      pharmacokinetics and changes in blood ANGPTL3 protein and LDL-C levels. 
      The Pulse-1 clinical trial is a single-ascending dose study that has an 
      adaptive design. The Pulse-1 clinical trial is expected to include four 
      dose cohorts each comprised of three to nine patients with RH. 
   -- Verve recently received regulatory clearances to initiate the Pulse-1 
      clinical trial in Australia, Canada, and the U.K. 

Upcoming Investor Events

Verve plans to participate in fireside chats during the following upcoming investor events:

   -- Guggenheim's Inaugural Healthcare Innovation Conference, November 11 at 
      4:00 PM ET, Boston, MA 
 
   -- Stifel 2024 Healthcare Conference, November 18 at 3:00 PM ET, New York, 
      NY 
 
   -- Jefferies London Healthcare Conference, November 20 at 4:00 PM GMT, 
      London, UK 

Upcoming Medical Meeting Presentations

Verve plans to present a moderated digital poster at the American Heart Association (AHA) Scientific Sessions in Chicago, IL. Details of the poster session are as follows:

Title: 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

Session: Genomic Therapies for Cardiovascular Disease

Date and Time: November 16 at 10:35 AM CT

Third Quarter 2024 Financial Results

Cash Position: Verve ended the third quarter of 2024 with $539.9 million in cash, cash equivalents, and marketable securities. Verve expects its capital position to be sufficient to fund its operations through 2026.

(MORE TO FOLLOW) Dow Jones Newswires

November 05, 2024 07:00 ET (12:00 GMT)