Heart disease prevention was revolutionized by the introduction of statins in the 1980s and 1990s. The arrival of PCSK9 inhibitors two decades later added even more powerful cholesterol-lowering drugs to physicians’ armamentarium.
For some people, though, such medicines aren’t enough. “If you look within the population of people who've got [PCSK9 inhibitors] on top of the optimal care that you can get in a contemporary setting, there are still people who look like they have really increased risk,” said Ethan Weiss, a cardiologist at the University of California, San Francisco.
Drugmakers have explored different ways to reduce that risk, probing new targets and testing new technologies. Weiss’ new startup, Marea Therapeutics, officially joined the hunt Tuesday, launching with $190 million to develop a monoclonal antibody designed to reduce “remnant” cholesterol and improve heart health.
The bar will be high. Novartis, which was the source of Marea’s lead prospect, brought a PCSK9-targeting shot to market in 2021, adding to existing PCSK9 treatments from Amgen, Sanofi and Regeneron. The drugs can lower LDL, or “bad,” cholesterol by 50% to 60% on top of statin therapy.
Marea plans to focus on the subset of people who remain at risk due to remnant cholesterol, which is essentially what persists after subtracting HDL and LDL cholesterol from total counts. Studies published over the past decade have pointed to remnant cholesterol as another biomarker for gauging cardiovascular risk.
Marea’s drug, dubbed MAR001, targets a protein called ANGPTL4, which regulates triglycerides, lipid metabolism and insulin sensitivity. Marea licensed MAR001 from Novartis and expects a Phase 1b/2a trial of the drug to be completed by the end of the year.
According to Marea, genetics studies have shown that loss of ANGPTL4 function was associated with clearance of remnant cholesterol and protection from heart disease.
“It's almost like a perfect storm in having this degree of genetic validation," said Josh Lehrer, Marea’s CEO. Lehrer, who was mentored by Weiss as a resident at UCSF in the early 2000s, previously was CEO of gene therapy developer Graphite Bio.
In addition to MAR001, Marea also has a number of unnamed programs in its pipeline.
The startup was incubated by longtime biotech investor Third Rock Ventures, which led its Series A financing. Sofinnova Investments led Marea’s Series B financing and the two rounds together totaled the $190 million in funding the company announced Tuesday.
Forbion, Perceptive Xontogeny Venture Fund and venBio co-led the Series B, in which Third Rock and several other funds participated.
Weiss, now Marea’s chief scientific officer, co-founded the company with Third Rock's Charles Homcy, as well as professors Stephen O'Rahilly at the University of Cambridge and Joshua Ravinowitz at Princeton University. Joining Weiss and Lehrer in the c-suite are Christine Garrett as chief strategy officer and Mark Joing as chief development operations officer.
Marea’s funding and backing make it among the most notable cardiovascular drugmakers to launch in recent years. Verve Therapeutics is another, having raised significant funds to develop gene editing treatments for heart disease.