Marea Therapeutics Debuts with $190M to Boost Cardiometabolic Medicines

Marea Therapeutics, headquartered in South San Francisco, California, and incubated by Third Rock Ventures, has emerged as a pioneering clinical-stage biotechnology firm aiming to revolutionize treatments for cardiometabolic diseases. With a substantial financial backing of $190 million from Series A and B rounds, the company is poised to advance its clinical-stage pipeline of innovative therapies. The Series A round was spearheaded by Third Rock Ventures, while the Series B round saw leadership from Sofinnova Investments, co-leadership from Forbion and Perceptive Xontogeny Venture Fund, and participation from investors such as Alpha Wave Global, Omega Funds, and Surveyor Capital (a Citadel company).

The primary focus of Marea Therapeutics is on leveraging large-scale human genetics to address critical, unaddressed, and genetically validated causes of cardiometabolic diseases. MAR001, the company's lead program, is a first-in-class ANGPTL4 inhibitor currently in Phase 2 clinical development. This therapeutic candidate aims to target untreated lipid and metabolic drivers of cardiovascular events in high-risk patients.

"Marea is committed to transforming the treatment landscape for cardiometabolic diseases by targeting genetically validated causes of these conditions," stated Josh Lehrer, CEO of Marea. Lehrer emphasized that despite available therapies, many patients remain at high risk, and Marea's approach could represent a significant advancement for these individuals. Jeffrey Tong, a board member and partner at Third Rock Ventures, also underscored the potential of Marea to become a leading cardiometabolic disease company, given its strong scientific foundation and experienced leadership team.

The therapeutic focus of Marea's lead program, MAR001, is on ANGPTL4, a protein highly expressed in adipose tissue. By inhibiting ANGPTL4, MAR001 aims to enhance adipose tissue lipoprotein lipase (LPL) activity, thus reducing remnant cholesterol, improving metabolic functions, and decreasing cardiovascular events. Remnant cholesterol, carried by triglyceride-rich lipoproteins, is identified as highly atherogenic and contributes to cardiovascular incidents independent of traditional risk factors such as LDL cholesterol, diabetes, or obesity. Currently, no targeted therapies exist to lower remnant cholesterol and improve metabolic functions.

Human genetics has highlighted ANGPTL4 as a promising target for therapeutic intervention. Loss of function alleles of ANGPTL4 have been associated with remnant cholesterol clearance, improved triglyceride distribution, better insulin sensitivity, and protection against both cardiovascular disease and type 2 diabetes through an adipose-specific mechanism. Preclinical models of MAR001 demonstrated a reduction in triglycerides, remnant cholesterol, ectopic fat, and enhanced insulin sensitivity. Phase 1 results showed significant promise, leading to the ongoing Phase 2 clinical trials for adults with metabolic dysfunction.

Ethan J. Weiss, co-founder and Chief Scientific Officer of Marea, remarked on the potential of ANGPTL4 human genetics to correct adipose dysfunction, a core issue in metabolic syndrome inadequately addressed by current treatments. Over five million cardiovascular patients in the U.S. alone are at risk due to elevated remnant cholesterol levels. According to Maha Katabi, General Partner at Sofinnova Investments, MAR001 could offer unique benefits by addressing the underlying causes of metabolic dysfunction.

Marea Therapeutics is also advancing additional candidates targeting untapped mechanisms driving cardiometabolic diseases. The company's executive team comprises experts in human genetics, adipocyte biology, and cardiometabolic disease drug development. Notable figures include Charles Homcy, Sir Stephen O’Rahilly, Joshua Rabinowitz, and Ethan J. Weiss. The management team features Christine Garrett, Mark Joing, and Josh Lehrer. The board of directors includes industry veterans such as Ted Love, Antoine Boulanger, Jung Choi, Chris Garabedian, Maha Katabi, Aaron Royston, and Jeffrey Tong.

In summary, Marea Therapeutics is well-positioned to make significant strides in the field of cardiometabolic diseases by advancing its innovative therapies, with MAR001 leading the charge. The company's strategic focus and distinguished team offer promising prospects for addressing unmet medical needs in this critical area of healthcare.