MAR001, a first-in-class monoclonal antibody targeting ANGPTL4, demonstrated approximately 53% placebo-adjusted mean reduction in remnant cholesterol and placebo-adjusted mean reduction in triglycerides at 12 weeks

Approximately 65% placebo-adjusted mean reduction in remnant cholesterol and triglycerides in participants with greater triglyceride elevation at baseline (≥200 mg/dl)

MAR001 was generally well tolerated; Phase 2b study expected to initiate in second quarter of 2025

Second oral presentation at EAS describes association of remnant cholesterol levels with major cardiovascular events in patients with atherosclerotic cardiovascular disease, underscoring potential of MAR001 to become an important new therapeutic option

Marea Therapeutics, Inc., a clinical-stage biotechnology company harnessing the latest advances in human genetics to develop first-in-class, next-generation medicines for cardioendocrine diseases, today presented positive data from a Phase 2a clinical trial of MAR001 in a late-breaking oral session at the 93rd European Atherosclerosis Society (EAS) Congress being held May 4-7, 2025 in Glasgow, UK. MAR001 is a first-in-class monoclonal antibody that targets ANGPTL4, a protein that is highly expressed in adipose tissue.

“We are very excited by these data from our Phase 2a study, which demonstrate the strong potential of MAR001 to address the most important unaddressed lipid and metabolic drivers of atherosclerotic cardiovascular disease in high-risk patients,” said Josh Lehrer, M.D., M.Phil., FACC, chief executive officer of Marea. “We look forward to advancing MAR001 into Phase 2b development for treating residual cardiovascular risk in patients who remain at highest risk despite aggressive standard of care therapies.”

“Atherosclerotic cardiovascular disease patients with elevated remnant cholesterol remain at an increased risk for major adverse cardiovascular events despite best available standard of care therapies,” said Ethan Weiss, M.D., chief scientific officer of Marea. “These data clearly validate the ability of MAR001 to significantly lower remnant cholesterol and triglycerides by inhibiting ANGPTL4, supporting genetic findings and expected translation to substantial cardiovascular disease risk reduction. We believe MAR001 has the potential to become an important new therapeutic option for patients.”

Presentation Highlights:

• The primary objective of Marea’s randomized, double-blind, placebo-controlled Phase 2a clinical trial was to characterize the safety and tolerability of multiple doses of MAR001 in participants with elevated triglycerides and remnant cholesterol.
• Secondary objectives were to describe the serum concentration of MAR001 at selected timepoints and to characterize the effect of MAR001 on triglyceride and remnant cholesterol metabolism following 12 weeks of treatment.
• The study enrolled 55 participants with hypertriglyceridemia (fasting TGs ≥151 and ≤496 mg/dL) randomized to Q2W MAR001 or placebo (blinded, 2:1 MAR001:Placebo). Ten participants were randomized to the 150 mg MAR001 arm, nine to the 300 mg MAR001 arm, 17 to the 450 mg MAR001 arm, and 19 to placebo.
• MAR001 demonstrated up to a 52.5% placebo-adjusted mean reduction in remnant cholesterol and up to a 52.7% placebo-adjusted mean reduction in triglycerides at 12 weeks.
• In participants with significantly elevated triglyceride levels at baseline (≥200 mg/dL), MAR001 demonstrated up to a 66.0% placebo-adjusted mean reduction in remnant cholesterol and up to a 64.0% placebo-adjusted mean reduction in triglycerides at Week 12.
• MAR001 was generally well tolerated, with no clinically significant findings, and no findings of elevated systemic inflammatory biomarkers or changes in mesenteric lymph node (MLN) size or local inflammation as assessed by MRI. There were no deaths or serious adverse events in any arm, and no adverse events with MAR001 leading to study drug discontinuation.

Table 1: Mean Placebo-Adjusted Reductions in Remnant Cholesterol and Triglyceride (TG) at 12 Weeks

Presentation Details:

Title: A Novel ANGPTL4 Inhibitory Antibody Safely Lowers Plasma Triglycerides and Remnant Cholesterol in Humans

Abstract Number: 1320

Session Title: Late Breaker Session: Clinical

Session Date and Time: Wednesday, May 7, 2025, 11:00 a.m. – 12:30 p.m. BST

Title: Real-world Analysis of the Association of Remnant Cholesterol Levels with Major Cardiovascular Events in Patients with Atherosclerotic Cardiovascular Disease

Abstract Number: 1314

Session Title: SaaG Session: Epidemiology: From Prevention to Prognosis

Session Date and Time: Tuesday, May 6, 2025, 2:35 p.m. – 3:35 p.m. BST

About Remnant Cholesterol

Remnant cholesterol is carried by triglyceride-rich lipoproteins, is highly atherogenic, and drives cardiovascular events independent of classical risk factors like LDL cholesterol, diabetes or obesity. There are currently no available targeted therapies to lower remnant cholesterol and improve metabolic function.

About MAR001

MAR001 is a first-in-class monoclonal antibody that targets ANGPTL4, a protein that is highly expressed in adipose tissue. By inhibiting ANGPTL4 and thereby augmenting lipoprotein lipase (LPL) activity, MAR001 is designed to lower remnant cholesterol and improve adipose tissue function. Human genetic data has identified ANGPTL4 as a highly promising therapeutic target because loss of function alleles leads to lower remnant cholesterol, improved adipose distribution, improved insulin sensitivity, lower triglyceride levels, and protection from cardiovascular disease and type 2 diabetes.

MAR001 is being developed to reduce the risk of major adverse cardiovascular events (MACE) in adults with established atherosclerotic cardiovascular disease (ASCVD) plus elevated triglycerides and remnant cholesterol.

Preclinical models with MAR001 demonstrated reduction in triglycerides, remnant cholesterol and ectopic fat, and improved insulin sensitivity. Results from a Phase 2a study of MAR001 demonstrated clinically meaningful reductions in remnant cholesterol and triglycerides. Marea plans to advance MAR001 into Phase 2b clinical development in the second quarter of 2025.

About Marea Therapeutics

Marea Therapeutics is a clinical-stage biotechnology company harnessing the latest advances in human genetics to develop first-in-class, next-generation medicines for cardioendocrine diseases. The company’s lead therapy, MAR001, is in Phase 2 clinical development for adults with metabolic dysfunction and high risk for cardiovascular disease. The company is also advancing MAR002 for the treatment of acromegaly. To learn more, please visit www.mareatx.com and follow us on LinkedIn and X.

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