Raphael Thys
Targeting ‘remnant cholesterol,’ company’s lead program is already in Phase 2 development for adults with metabolic dysfunction.
US biotech Marea Therapeutics launched this week with $190 million in investment as it aims to accelerate the development of innovative medicines for cardiometabolic diseases. The company’s approach leverages large-scale human genetics to create new treatments that address critical and genetically validated causes of these diseases. Marea’s lead program, currently in Phase 2 clinical trials, is designed to target untreated lipid and metabolic drivers of cardiovascular events in high-risk patients.
By focusing on the underlying biology of cardiometabolic disease rather than managing symptoms, Marea is targeting the inability to store excess energy safely, which leads to high rates of atherosclerotic heart disease and diabetes. A key marker for these conditions is elevated remnant cholesterol, a highly atherogenic lipid that circulates in the blood and is not effectively targeted by existing therapies.
“Marea aims to transform the way cardiometabolic diseases are treated by leveraging large-scale human genetics and expertise in adipose function and biology to pursue genetically validated targets focusing on central – but unaddressed – drivers of cardiometabolic disease risk,” said Dr Josh Lehrer, CEO of Marea. “This approach could be the next frontier for patients with cardiometabolic disease who remain at very high risk, despite currently available therapies.”
Remnant cholesterol, carried by triglyceride-rich lipoproteins, is a major driver of cardiovascular disease risk, independent of traditional risk factors like LDL cholesterol, diabetes or obesity. Marea’s lead drug MAR001 is a monoclonal antibody targeting ANGPTL4 that aims to lower remnant cholesterol by enhancing adipose tissue lipoprotein lipase (LPL) activity. The company claims its approach is backed by human genetics, which has shown that ANGPTL4 inhibition can lead to improved triglyceride distribution, insulin sensitivity, and protection against cardiovascular disease and type 2 diabetes.
Marea says that its preclinical models of MAR001 have demonstrated positive results, including reductions in triglycerides, remnant cholesterol and ectopic fat, as well as improved insulin sensitivity. The company’s strong Phase 1 results have paved the way for the current Phase 2 clinical development for adults with metabolic dysfunction.
“ANGPTL4 human genetics shows the potential to essentially reverse the adipose dysfunction responsible for the metabolic syndrome- which is not adequately treated by current therapies including weight loss and LDL cholesterol treatment,” said Dr Ethan J Weiss, CSO of Marea. “More than five million cardiovascular patients in the US alone have elevated remnant cholesterol putting them at risk for a heart attack. MAR001 has the potential to provide unique benefit to these patients by correcting the underlying adipose dysfunction leading to both elevated remnant cholesterol and metabolic dysfunction.”
The company was incubated by Third Rock Ventures and boasts an impressive list of investors including Sofinnova Investments, Forbion, Perceptive Xontogeny Venture Fund, venBio, Omega Funds, Alpha Wave Global and Surveyor Capital. The new funding will support the development of MAR001 and other pipeline programs, currently undisclosed.
“With initial clinical validation, world-class scientific founders and investors, and an experienced board and leadership team, Marea is poised to become a premier cardiometabolic disease company,” said Third Rock Ventures’ Jeffrey Tong. “We aim to accelerate a new generation of medicines, including MAR001, that treat key unaddressed drivers of cardiometabolic disease, potentially providing important new therapeutic options for millions of patients.”