MAR-001

Marea's approach "could be the next frontier for patients with cardiometabolic disease who remain at very high risk," said CEO Josh Lehrer, M.D. Marea Therapeutics has emerged with $190 million, a mid-stage clinical program and a plan to harness genetics and pioneer “the next frontier” of cardiometabolic medicines. Marea was incubated by Third Rock Ventures, a healthcare VC that led the San Francisco-based biotech’s series A. The $190 million is the sum of a combined series A and B, with the latter round steered by Sofinnova Investments, and co-led by Forbion, Perceptive Xontogeny Venture Fund and venBio, according to a June 18 release. The money will be funneled into phase 2 activities for lead program MAR001, a monoclonal antibody (mAb) designed to inhibit ANGPTL4, a protein highly expressed in body fat. Preclinical models found that MAR001 reduced triglycerides, remnant cholesterol and ectopic fat, while improving insulin sensitivity, according to Marea. The mAb is delivered by subcutaneous injection. “In a phase 1 trial, a single dose of MAR001 significantly lowered remnant cholesterol levels and improved metabolic biomarkers,” Maha Katabi, Ph.D., Marea board member and general partner at Sofinnova Investments, said in the release. The results come from Marea’s ongoing phase 1b/2a that has an estimated enrollment of 48 participants with metabolic dysfunction. The trial is nearly fully enrolled, with the phase 2a component ongoing, a Marea spokesperson told Fierce Biotech.  The biotech also plans to launch a phase 2b trial assessing MAR001 for metabolic dysfunction in the beginning of next year, according to the spokesperson. Besides lowering remnant cholesterol and improving metabolic function, the therapy is designed to reduce cardiovascular events for high-risk patients. Currently, there aren’t any approved targeted therapies for lowering remnant cholesterol and boosting metabolic performance, according to the company. “More than five million cardiovascular patients in the U.S. alone have elevated remnant cholesterol, putting them at risk for a heart attack,” Ethan Weiss, M.D., co-founder and chief scientific officer of Marea, said in the release. “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.” Marea’s three other co-founders are Charles Homcy, M.D., a partner emeritus for Third Rock Ventures; Sir Stephen O’Rahilly, M.D., professor at the University of Cambridge; and Joshua Rabinowitz, M.D., Ph.D., professor at Princeton University. Heading up the Marea mission is CEO Josh Lehrer, M.D., who has been in the top spot since October 2023, according to his LinkedIn profile. Before Marea, Lehrer led Graphite Bio (now merged with LENZ Therapeutics) and previously spent more than six years in various leadership roles at Global Blood Therapeutics. “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 CEO Lehrer in the release. “This approach could be the next frontier for patients with cardiometabolic disease who remain at very high risk, despite currently available therapies.” Other members of Marea’s management include Christine Garrett, Ph.D., as chief strategy officer; Mark Joing as chief development operations officer; and Ethan Weiss, M.D., scientific founder and chief scientific officer. The biotech is also working on a pipeline of undisclosed additional candidates targeting other cardiometabolic diseases, a group of common conditions that includes heart attack, diabetes, stroke and metabolic dysfunction-associated steatohepatitis (MASH).   

Marea Therapeutics announced its launch on Tuesday with $190 million in funding to develop drugs targeting genetically validated causes of cardiometabolic diseases. The firm – incubated by Third Rock Ventures – has backing from a number of high-profile investors, including Sofinnova Investments, Forbion, Perceptive Xontogeny Venture Fund and venBio.The startup’s lead programme, dubbed MAR001, is in Phase II development to address the lipid and metabolic drivers of cardiovascular events in high-risk patients. The drug targets ANGPTL4, inhibition of which can preferentially augment adipose tissue lipoprotein lipase (LPL) activity to lower remnant cholesterol, improve adipose tissue and metabolic function, and reduce cardiovascular events.Marea noted that MAR001 has demonstrated “strong” results in Phase I and is currently in mid-stage development for adults with metabolic dysfunction. “In a Phase I trial, a single dose of MAR001 significantly lowered remnant cholesterol levels and improved metabolic biomarkers,” remarked Maha Katabi, general partner at Sofinnova.More to come.