Pharmaceuticals

Marea Therapeutics’ Cardiometabolic Mission

Marea Therapeutics emerged this week, announcing $190M in Series A/B funding and a mission to develop “a new generation of medicines for cardiometabolic diseases” – starting with their drug candidate targeting remnant cholesterol.

Marea got its start from a tweet by UCSF cardiologist Ethan J. Weiss, MD, regarding his interest in metabolism and a protein (Angptl4) that blocks lipoprotein lipase (LPL) and regulates how the body stores fat.

  • A follow-up Twitter comment directed Dr. Weiss to a Novartis molecule that targets Angptl4, and by 2022 Weiss had co-founded Marea Therapeutics and licensed the drug candidate from Novartis.
  • Since then, Marea has assembled a solid founding team, and gained backing by some of the biggest investors in life sciences.

They have also turned that Novartis drug candidate into their lead program, MAR001, a monoclonal antibody that targets ANGPTL4, and is intended to address the untreated lipid and metabolic drivers of cardiovascular events in high-risk patients.

Marea believes that by blocking Angptl4 and altering its LPL activity, MAR001 could lower remnant cholesterol, correct adipose tissue, and bring improvements to triglyceride distribution, metabolic function, and insulin sensitivity — potentially reducing cardiovascular events. 

  • That’s different from most current cholesterol approaches that mainly target LDL reduction, but previous research has shown that remnant cholesterol carries cardiovascular risks that are independent of LDL-C, apoB, and other traditional risk factors.
  • Despite this evidence, there are currently no other available targeted therapies for remnant cholesterol reduction and improving metabolic function.

Marea still has to prove MAR001’s performance, although in its Phase 1 trial MAR001 significantly lowered remnant cholesterol levels and improved metabolic biomarkers. 

  • Results from its current Phase 1b/2a trial is due to be completed by the end of 2024, and its Phase 2b trial is scheduled to start in early 2025.

Marea’s pipeline will also extend beyond MAR001, as it develops other candidates targeting “untapped nodes driving cardiometabolic diseases.”

The Takeaway

Nothing happens fast in cardiology, and that’s especially true for brand new cholesterol and cardiometabolic approaches. That said, five million cardiovascular patients in the U.S. have elevated remnant cholesterol – and none of them are receiving remnant cholesterol treatments – so Marea’s efforts might be worth waiting for.

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