MAR001 Cuts Remnant Cholesterol, Triglycerides by 50% in Phase 2a Trial

A novel cholesterol-lowering drug may offer a new approach to reducing cardiovascular risk in patients with elevated triglycerides and remnant cholesterol, beyond the reach of traditional therapies.1

In late-breaking data announced by Marea Therapeutics on May 7, 2025, and presented at the 93rd European Atherosclerosis Society (EAS) Congress, MAR001—a first-in-class monoclonal antibody targeting ANGPTL4—reduced remnant cholesterol and triglycerides by more than 50% compared with placebo at 12 weeks.

“ASCVD patients with elevated remnant cholesterol remain at an increased risk for major adverse cardiovascular events (MACE) despite best available standard of care therapies,” said Ethan Weiss, MD, chief scientific officer of Marea Therapeutics.1 “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.”

Remnant cholesterol drives cardiovascular risk independently of LDL-C, diabetes, or obesity—yet no therapies specifically target it to improve metabolic health.2

Developed by Marea Therapeutics to lower the risk of MACE in adults with established ASCVD and elevated triglyceride and remnant cholesterol levels, MAR001 reduced triglycerides, remnant cholesterol, and ectopic fat, and improved insulin sensitivity in preclinical data.1

The randomized, double-blind, placebo-controlled Phase 2a trial measured the safety and tolerability of multiple MAR001 doses in individuals with elevated triglycerides and remnant cholesterol. Secondary outcome measures included MAR001 serum concentration at various timepoints and the effect of MAR001 on triglyceride and remnant cholesterol metabolism at 12 weeks of treatment.

Overall, 55 participants with fasting triglycerides ≥152 and ≤496 mg/dL, marking hypertriglyceridemia, were randomly assigned to receive every 2 weeks (Q2W) MAR001 or placebo. Among the population, 10 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.

At 12 weeks, placebo-adjusted mean reductions showed the highest dose of MAR001 cut remnant cholesterol by up to 52.5% and triglycerides by 52.7%. In participants with baseline triglycerides ≥200 mg/dL, these reductions reached 66.0% and 64.0%, respectively.

Safety analyses showed MAR001 was well-tolerated, with no clinically significant findings—no systemic inflammation, MLN enlargement, or local inflammatory changes. Deaths or serious adverse events were not identified in any arm, nor were adverse events linked to study drug discontinuation.

Citing the clinically meaningful reductions in remnant cholesterol and triglycerides in Phase 2a, Marea Therapeutics announced plans to propel MAR001 into Phase 2b clinical development in the second quarter of this year.

“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 ASCVD in high-risk patients,” said Josh Lehrer, MD, chief executive officer of Marea Therapeutics.1 “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.”

References

1. Klass S. Marea Therapeutics presents positive data from phase 2a clinical trial of MAR001, being developed for cardiovascular disease, in late-breaking oral session at the 93rd eas Congress. Marea Therapeutics. May 7, 2025. Accessed May 8, 2025. https://www.mareatx.com/press-releases/marea-therapeutics-presents-positive-data-from-phase-2a-clinical-trial-of-mar001-being-developed-for-cardiovascular-disease-in-late-breaking-oral-session-at-the-93rd-eas-congress/.

2. Huh JH, Han KD, Cho YK, et al. Remnant cholesterol and the risk of cardiovascular disease in type 2 diabetes: a nationwide longitudinal cohort study. Cardiovasc Diabetol. 2022;21(1):228. Published 2022 Nov 2. doi:10.1186/s12933-022-01667-6