MAR001 lowers triglycerides without worsening glycaemic control in Phase 2b TYDAL-TIMI 78 trial

Marea Therapeutics, a subsidiary of Lisata Therapeutics, has announced that MAR001 met all objectives in Part A of the Phase 2b TYDAL-TIMI 78 trial. MAR001 is a potential first-in-class monoclonal antibody that targets angiopoietin-like protein 4 (ANGPTL4). The results were presented as a late-breaking clinical trial at the American Heart Association (AHA) Scientific Sessions 2026 and published at the same time in The New England Journal of Medicine.

Part A was randomised, double-blind and placebo-controlled. It enrolled 235 adults with elevated triglycerides and remnant cholesterol, who received subcutaneous MAR001 (300 mg, 450 mg or 900 mg) or placebo every four weeks for 24 weeks.

Key results

• Primary endpoint met at every dose. Placebo-adjusted reductions in fasting triglycerides at Week 12 were 39.1%, 40.9% and 45.5% at 300 mg, 450 mg and 900 mg, respectively (p<0.001 for all doses). The reductions were sustained through Week 24.
• Greater lowering at higher baseline levels. In participants with baseline triglycerides of ≥300 mg/dL, placebo-adjusted reductions were 52.8%, 53.7% and 57.2%. In those with triglycerides of ≥500 mg/dL, reductions from baseline reached up to 72.2%.
• Normalisation. At Week 12, 31.0%, 35.1% and 51.7% of participants on 300 mg, 450 mg and 900 mg reached normal triglyceride levels (<150 mg/dL), compared with 3.4% on placebo.
• Remnant cholesterol. Placebo-adjusted reductions ranged from 37.3% to 40.8% across the three doses (p<0.001).

Safety

Treatment-emergent adverse events occurred in 69.5% of participants on MAR001 and 77.6% on placebo. Serious adverse events occurred in 2.8% and 6.9%, and injection-site reactions in 14.1% and 19.0%, respectively. There were no cases of pancreatitis, no deaths, and no worsening of HbA1c or other markers of glucose homeostasis.

Glycaemic control is a key consideration because up to 70% of people with severe hypertriglyceridemia (sHTG) also have type 2 diabetes. sHTG substantially increases the risk of acute pancreatitis, so new treatments need to lower triglycerides without adding to the metabolic and cardiovascular risk many patients already carry.

ANGPTL4 is highly expressed in adipose tissue. Inhibiting it boosts lipoprotein lipase activity. Human genetic data show that people with loss-of-function variants in ANGPTL4 have lower triglycerides, better insulin sensitivity and protection from cardiovascular disease and type 2 diabetes.

“The TYDAL-TIMI 78 Part A results provide important clinical evidence supporting ANGPTL4 inhibition as a promising new approach to treating hypertriglyceridemia,” said Michelle L. O’Donoghue, MD, MPH, of Brigham and Women’s Hospital and the TIMI Study Group.

Marea has started enrolling Part B, which will randomise approximately 100 participants with sHTG (fasting triglycerides 450–2,000 mg/dL) 1:1 to MAR001 or placebo. The company is also developing MAR005, a half-life-extended version of MAR001, as its planned Phase 3 candidate.