Imagine replacing the arsenal of drugs we use to treat heart disease with a single injection. That’s what Verve Therapeutics wants to do. And to get there, the startup is launching with $58.5 million, access to gene-editing technology from the likes of the Broad Institute and Beam Therapeutics and longtime cardiologist and geneticist Sekar Kathiresan at its helm.
Verve aims to create new treatments that edit the human genome to permanently lower a person’s risk of coronary artery disease (CAD), which can ultimately lead to a heart attack. The Cambridge, Massachusetts-based biotech’s work is based on research—including some out of Kathiresan’s lab—showing that people born with certain genetic mutations seem to be protected from CAD.
“What we found is two things. One is that some people born with protein mutations are healthy and remarkably resistant to heart attacks,” Kathiresan told FierceBiotech. “Second—if you carry DNA variants that lower LDL or bad cholesterol and triglycerides, you basically won’t get a heart attack. Verve is launched with the goal of translating these findings into treatments.”
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This treatment would edit an adult’s genome to mimic these naturally occurring mutations and bring about the same effect of lowering LDL cholesterol throughout a person’s life, thereby reducing the risk of heart attack, Kathiresan said. His lab has identified seven genes where loss-of-function mutations—mutations that “break” those genes, in Kathiresan’s words—protect people from heart attacks. Verve is studying those genes and will be prioritizing which ones it wants to target over the “next little bit.” Then, it will test its approach in animal studies.
Verve figures mimicking mutations that already exist in healthy people reduces the risks of gene editing.
“By editing a gene that we know naturally occurs in a deleted state, we can say to some degree that mother nature has already conducted part of the safety experiment. The absence of the gene is not associated with any other abnormality,” said Burt Adelman, M.D., a co-founder of Verve and chairman of its board.
“It’s kind of like nature’s phase one,” Kathiresan added.
The company starts life with a $58.5 million series A, garnered from GV, Arch Venture Partners, F-Prime Capital and Biometrics Capital. It’s licensed CRISPR-Cas9 and Cas12 technology from the Broad Institute and Harvard University and has inked partnerships with Verily and the base-editing startup Beam Therapeutics. This way, Verve will have multiple types of gene editing to draw on and will also develop the best delivery vehicles for its treatments.
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“Heart attack remains the leading killer in the world—it's rising in prevalence worldwide—and the current approach is largely chronic care. It’s not really changing that reality,” Kathiresan said.
Verve is hoping a one-time gene-editing injection could eliminate the hurdles facing cholesterol-lowering statins and other medicines, namely, poor adherence, high costs and limited access, especially in developing countries.
“Cholesterol-lowering treatments have been an important advance for many patients at risk of coronary artery disease,” Adelman said in a statement. “However, as the disease’s prevalence rises in low- and middle-income countries, the current treatment model of daily pills or monthly injections over a lifetime must evolve if we are to effectively protect millions of people from disability or death due to coronary artery disease.”
Verve will focus first on the most vulnerable patients, after which it will turn its sights to larger patient populations.
“We have a stepwise approach to clinical development. The first and most important step is to focus on adults with life-threatening coronary artery disease, who have inadequate or no available therapies … Once we establish the safety and efficacy of this adult genome editing, we will broaden our clinical focus to include progressively larger populations at risk for disease,” Kathiresan said.
“The ultimate vision would be to broaden out from that initial group to those at higher risk based on their genetic makeup,” he said. Much further down the road, this might mean offering the gene-editing treatment to any adult whose genetics show they are at risk of CAD even if they don't have symptoms.