Cholesterol risks persist; Marea Therapeutics secures $190M to tackle it

Heart disease prevention saw a significant breakthrough with the advent of statins during the 1980s and 1990s. This was further enhanced by the introduction of PCSK9 inhibitors in the early 2000s, providing doctors with even more effective cholesterol-lowering options. Despite these advancements, there remains a segment of the population that continues to face high cardiovascular risks even when treated with these drugs in conjunction with optimal contemporary care. Ethan Weiss, a cardiologist from the University of California, San Francisco, highlighted this issue, noting that some individuals still exhibit significantly elevated risks.

Pharmaceutical companies have been delving into various methods to mitigate this risk by targeting new biological pathways and experimenting with innovative technologies. Marea Therapeutics, a new venture spearheaded by Weiss, entered this arena on Tuesday with a launch backed by $190 million in funding. The company aims to develop a monoclonal antibody that targets remnant cholesterol to bolster heart health.

Marea Therapeutics faces stiff competition in this field. Novartis launched a PCSK9-targeting injection in 2021, joining existing treatments from Amgen, Sanofi, and Regeneron, which have demonstrated the capability to reduce LDL cholesterol by 50% to 60% when used in conjunction with statins. Marea, however, is focusing on individuals who remain at risk due to high levels of remnant cholesterol—essentially the cholesterol that remains after accounting for HDL and LDL levels. Over the past decade, research has increasingly identified remnant cholesterol as a critical marker for cardiovascular risk assessment.

Marea's lead drug candidate, MAR001, aims to address this issue by targeting the ANGPTL4 protein, which plays a role in regulating triglycerides, lipid metabolism, and insulin sensitivity. The drug was licensed from Novartis, and Marea anticipates completing Phase 1b/2a trials by the end of the year. According to genetic studies cited by Marea, loss of ANGPTL4 function has been linked with the reduction of remnant cholesterol and a decreased risk of heart disease. Josh Lehrer, Marea’s CEO, described this genetic validation as a “perfect storm” of evidence supporting their approach. Lehrer, who has a background in gene therapy and was mentored by Weiss during his residency at UCSF, previously served as the CEO of Graphite Bio.

Apart from MAR001, Marea Therapeutics has several other undisclosed projects in its development pipeline. The company was incubated by Third Rock Ventures, a prominent biotech investment firm, which led Marea’s Series A funding round. The Series B round was spearheaded by Sofinnova Investments, with contributions from Forbion, Perceptive Xontogeny Venture Fund, and venBio. Combined, these funding rounds amassed the $190 million announced by the company on Tuesday.

The founding team of Marea includes Weiss as the chief scientific officer, along with Third Rock’s Charles Homcy, and academic experts Stephen O'Rahilly from the University of Cambridge and Joshua Ravinowitz from Princeton University. The executive team is further strengthened by Christine Garrett as chief strategy officer and Mark Joing as chief development operations officer.

With substantial financial backing and a strong leadership team, Marea Therapeutics is positioned as one of the most promising new entrants in the cardiovascular drug development sector. It joins other innovative companies like Verve Therapeutics, which is exploring gene-editing strategies to treat heart disease.