Leveraging large-scale human genetics to advance clinical-stage pipeline of first-in-class treatments that target critical, unaddressed and genetically validated causes of cardiometabolic diseases

Lead program, MAR001, is a first-in-class ANGPTL4 inhibitor in Phase 2 clinical development aiming to address the untreated lipid and metabolic drivers of cardiovascular events in high-risk patients

Company incubated by Third Rock Ventures with distinguished scientific founders and leading investor syndicate including Sofinnova Investments, Forbion, Perceptive Xontogeny Venture Fund, venBio, Omega Funds, Alpha Wave Global and Surveyor Capital (a Citadel company)

Marea Therapeutics, a clinical-stage biotechnology company incubated by Third Rock Ventures to develop a new generation of medicines for cardiometabolic diseases, launched today with $190 million in combined Series A and B financings. The Series A round was led by Third Rock Ventures and the Series B round was led by Sofinnova Investments and co-led by Forbion, Perceptive Xontogeny Venture Fund and venBio, with the participation of Alpha Wave Global, Omega Funds, Surveyor Capital (a Citadel company) and founding investor Third Rock Ventures. This financing will fund the company’s MAR001 Phase 2 development plan and further progression of additional pipeline programs.

“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 Josh Lehrer, M.D., M.Phil., FACC, chief executive officer of Marea. “This approach could be the next frontier for patients with cardiometabolic disease who remain at very high risk, despite currently available therapies.”

“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 Jeffrey Tong, Ph.D., board member and partner, Third Rock Ventures. “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.”

Targeting Cardiometabolic Diseases at their Source

Marea’s lead program, MAR001, is a monoclonal antibody that targets ANGPTL4, a protein that is highly expressed in adipose tissue. By inhibiting ANGPTL4 and thereby preferentially augmenting adipose tissue lipoprotein lipase (LPL) activity, MAR001 aims to lower remnant cholesterol, improve adipose tissue and metabolic function, and reduce cardiovascular events. Remnant cholesterol is carried by triglyceride-rich lipoproteins, is highly atherogenic, and drives cardiovascular events independent of classical risk factors like LDL cholesterol, diabetes or obesity1. There are currently no available targeted therapies to lower remnant cholesterol and improve metabolic function.

Human genetics has demonstrated ANGPTL4 as a highly promising therapeutic target to lower remnant cholesterol with loss of function alleles leading to remnant cholesterol clearance, improved triglyceride distribution, improved insulin sensitivity, and protection from both cardiovascular disease and type 2 diabetes all via an adipose specific mechanism.

Preclinical models with MAR001 demonstrated reduction in triglycerides, remnant cholesterol and ectopic fat (storage of triglycerides in tissues other than adipose tissue), and improved insulin sensitivity. MAR001 has demonstrated strong Phase 1 results and is in 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. More than five million cardiovascular patients in the U.S. alone have elevated remnant cholesterol putting them at risk for a heart attack,” said Ethan J. Weiss, M.D., co-founder and chief scientific officer of Marea. “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.”

“In a Phase 1 trial, a single dose of MAR001 significantly lowered remnant cholesterol levels and improved metabolic biomarkers. We are very excited about this compound’s potential,” said Maha Katabi, Ph.D., general partner, Sofinnova Investments. “Led by renowned experts in genetics and cardiometabolic diseases, Marea is well positioned to advance MAR001 and other pipeline programs, potentially unlocking a new era in cardiovascular care.”

Marea is also advancing a pipeline of additional candidates aimed to address additional untapped nodes driving cardiometabolic diseases.

Management and Organization

Marea is led by a dynamic team of scientists and company builders with deep know-how and experience in human genetics, adipocyte biology and cardiometabolic disease drug development.

Marea founders include:

  • Charles Homcy, M.D., partner emeritus, Third Rock Ventures
  • Sir Stephen O’Rahilly, M.D., FRS, professor of clinical biochemistry and medicine, University of Cambridge
  • Joshua Rabinowitz, M.D., Ph.D., professor of chemistry & integrative genomics, Princeton University
  • Ethan J. Weiss, M.D., chief scientific officer

Marea management team members include:

  • Christine Garrett, Ph.D., chief strategy officer
  • Mark Joing, MBA, chief development operations officer
  • Josh Lehrer, M.D., M.Phil., FACC, chief executive officer
  • Ethan J. Weiss, M.D., scientific founder and chief scientific officer

Marea board members include:

  • Ted Love, M.D., chairman, former president and chief executive officer of Global Blood Therapeutics (acquired by Pfizer) and chairman, Biotechnology Innovation Organization (BIO)
  • Antoine Boulanger, Ph.D., principal, Forbion
  • Jung Choi, MBA, entrepreneur in residence, Third Rock Ventures
  • Chris Garabedian, venture portfolio manager, Perceptive Advisors
  • Maha Katabi, Ph.D., general partner, Sofinnova Investments
  • Josh Lehrer, M.D., M.Phil., FACC, chief executive officer
  • Aaron Royston, M.D., managing partner, venBio
  • Jeffrey Tong, Ph.D., partner, Third Rock Ventures

“With its focused scientific approach and differentiated first-in-class development programs, Marea has the potential to become a leading company in the cardiometabolic disease space,” said Dr. Love. “I am thrilled to partner with this talented board and management team to advance MAR001 and other programs for patients who are in need of breakthrough cardiometabolic disease therapies.”

About Marea

Marea Therapeutics is a clinical-stage biotechnology company harnessing the latest advances in human genetics to develop first-in-class, next-generation medicines for cardiometabolic diseases. The company’s lead program, MAR001, is in Phase 2 clinical development to lower remnant cholesterol in adults with metabolic dysfunction and high risk for cardiovascular disease. Marea is led by a dynamic team of scientists and company builders with deep know-how and experience in cardiometabolic diseases, human genetics and adipocyte biology. To learn more, please visit www.mareatx.com and follow us on LinkedIn and X.

1 https://doi.org/10.1161/CIRCIMAGING.121.012615Circulation: Cardiovascular Imaging. 2021;14:e012615

Media: 1AB Katie Engleman katie@1abmedia.com

Investors: 1AB Steve Klass steve@1abmedia.com