A new startup wants to edit out the world’s biggest killer. Prominent cardiologist and geneticist Sekar Kathiresan is heading up a new company, Verve Therapeutics, that will develop gene-altering medicine to prevent heart attacks. Heart disease is the leading cause of death in the US and worldwide.
“Imagine an injection, once in life, that safely confers enduring protection against heart attack in adults,” said Kathiresan, the director of the Center for Genomic Medicine at Massachusetts General Hospital. He is stepping down from his posts at the hospital, the Broad Institute, and Harvard Medical School to run Verve full time in July.
Backed by $58.5 million in venture cash, Verve’s big idea is to use gene editing to give people DNA mutations that have been found to protect the heart health of the people born with them. There are seven that are well understood, including PCSK9. They each play a role in the production of “bad” cholesterol or triglycerides; high levels of either are known risk factors for heart disease. Verve has rights to develop treatments based upon them, Kathiresan said: “Our approach is to mimic those naturally occurring protective mutations.”
The Cambridge, MA-based firm’s first goal is to treat people who have had a heart attack, are at high risk of more, and don’t have treatment options. For example, people with the inherited condition familial hypercholesteremia might not be helped by statins, the longtime standard of care for high cholesterol. (Although it seems a surprisingly low number of them haven’t tried statins.)
One in 250 Americans have familial hypercholesterolemia, with the most severe cases sometimes dying before adulthood, according to the American Heart Association.
They have a relatively new option known as PCSK9 inhibitors, approved in 2015, but Verve believes the limitations of those drugs—initial high costs that have forced their makers to reduce prices, and the need to inject them regularly for a lifetime—will open to the door to a one-time genetic fix.
Verve intends to start with these patients and, if all goes well, move into broader patient populations.
To test its cutting-edge heart medicine in humans—potentially a much wider swath of people—Verve will have to convince regulators that it is safe. And if it does well in clinical trials, Verve will still face competition. In addition to PCSK9-blocking drugs, drug developers such as Esperion Therapeutics (NASDAQ: ESPR) and The Medicines Co. (NASDAQ: MDCO) could have new cholesterol-lowering drugs on the market within a couple years.
Verve executives think they’ll avoid some of the risk of drug development because the protective genes have been deeply studied. “We know the targets are relevant from the human experience,” said Burt Adelman, Verve cofounder and chairman and a former R&D chief at Biogen (NASDAQ: BIIB). “People who have these risk genes naturally knocked out have no associated abnormalities. We’re starting out with the right biology and with some of the safety risks already understood.”
Verve will produce medicines that alter one gene at a time, but Kathiresan declined to say which genes are at the top of the company’s list.
The company’s chief scientific advisor, Kiran Musunuru of the Perelman School of Medicine at the University of Pennsylvania, has spent years exploring the positive effects of silencing the PCSK9 gene. PCSK9 plays a key role in the production of LDL cholesterol—the bad kind of cholesterol.
The company’s strategy highlights how quickly the gene editing field has moved into human medicine. Instead of building its own capabilities in-house, Verve is licensing different CRISPR-based editing technologies from the Broad Institute, Editas Medicine (NASDAQ: EDIT), and Beam Therapeutics. Beam CEO John Evans is also affiliated with ARCH Venture Partners, which is a Verve investor, but Verve officials insist that they are not beholden to any one approach, such as the “base editing” Beam is advancing.
“We are strategy-agnostic,” said Verve board member Anthony Philippakis, the Broad’s chief data officer and a partner at GV, the investment arm of Alphabet. GV led Verve’s Series A round.
As with all genetic medicines, delivery of the therapeutic parts into cells is a big hurdle—one that many companies are working on. To change the production of cholesterol and triglycerides, the two disease-causing lipids, Verve will have to aim its therapeutic arrows not at heart cells, but at the liver where most lipids are produced. The company has licensed delivery technology from Verily, another Alphabet entity, and from Beam as well.