Marea Therapeutics Advances ANGPTL4 Antibody to Phase 2b After Promising Cholesterol Reduction Results

Marea Therapeutics, a San Francisco-based biotech company, has reported encouraging results from its phase 2a trial of MAR001, an antibody targeting ANGPTL4. The study demonstrated significant reductions in remnant cholesterol and triglycerides, paving the way for an imminent phase 2b trial.

MAR001 Shows Promising Efficacy in Lipid Reduction

In a randomized trial involving 55 participants with high triglyceride levels, MAR001 exhibited potent lipid-lowering effects:

• Remnant cholesterol decreased by 37.4% to 52.5% compared to placebo after 12 weeks of treatment
• Triglycerides showed placebo-adjusted reductions of up to 52.7%
• A subgroup of patients with significantly elevated triglyceride levels experienced even more pronounced effects, with placebo-adjusted mean reductions in remnant cholesterol and triglycerides of up to 66% and 64%, respectively

The study evaluated three different doses of MAR001 administered every two weeks, with the highest doses producing the most substantial lipid reductions.

Safety Profile and Historical Context

MAR001 demonstrated a favorable safety profile in the phase 2a trial:

• The antibody was generally well-tolerated, with no clinically significant findings
• No elevated systemic inflammatory biomarkers were observed
• MRI assessments showed no changes in mesenteric lymph node (MLN) size or local inflammation

These safety outcomes are particularly noteworthy given the historical challenges associated with targeting ANGPTL4. Previous attempts by other companies, including Regeneron and Novartis, encountered setbacks due to adverse effects observed in animal studies, such as intestinal injury and lipid accumulation in MLNs.

Marea's Progress and Industry Landscape

Marea Therapeutics, which emerged last year with $190 million in funding, is positioning itself at the forefront of ANGPTL4-targeted therapies. The company plans to initiate a phase 2b trial by mid-2025, building on the positive results from this recent study.

While Marea leads the charge in antibody-based approaches, other companies are exploring alternative methods to target ANGPTL4. Lipigon Pharmaceuticals, for instance, is currently conducting a phase 2 trial of an antisense oligonucleotide designed to inhibit ANGPTL4 production.

As Marea Therapeutics advances its promising candidate, the pharmaceutical industry watches closely, recognizing the potential impact of ANGPTL4 inhibition on cardiovascular risk management and lipid metabolism disorders.