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Verve Therapeutics aims to use gene editing to address heart attacks by targeting the liver, not the heart. And it wants to make its edits inside the patient. The startups approach raises a lot of questions. Verve has some answers now, and it has raised $63 million to learn more.

The new financing announced Thursday was led by GV, the same investor that led the Cambridge, MA-based companys Series A round of funding last year. With the additional cash, Verve CEO Sekar Kathiresan says Verve could reach its first human tests of a gene-editing therapy in about three years.

High cholesterol and triglyceride levels in the blood are among the biggest risk factors for a heart attack. For some people, high levels of these types of fats are inherited. In a condition called familial hypercholesterolemia, a genetic defect makes it harder for these people to remove the bad form of cholesterol from their blood. No matter how much they do in terms of diet and exercise, they continue to have high cholesterol levels that raise the risk of a heart attack.

Low cholesterol levels can also be inherited. In rare cases, people have a genetic mutation that turns off the gene that leads to high levels of cholesterol, Kathiresan says. Verves research is built on the 15 years of genetic research that identified eight genes linked to heart health. Such research has led to the commercialization of drugs that block PCSK9, a protein that inhibits the bodys ability to clear the bad form of cholesterol. But these drugs must be taken chronically.

Gene editing is typically thought of as a way to correct a genetic mutation that causes a problem. Verve, instead, is trying to give patients a mutation that confers a benefitturning off the gene that leads to high levels of cholesterol and triglycerides. If it works, its a one-time treatment.

What youre left with is the gene turned off forever, Kathiresan says. Its durable, lifelong control of cholesterol.

The genetic alteration would be made in vivoinside the patientby messenger RNA (mRNA), which is a genetic blueprint that carries editing instructions, and a guide RNA that gets this editor to the target gene. But to make the intended edit, the two pieces of nucleic acid need to reach their destination intact. Some companies are employing viral delivery systems. Thats the approach taken by Editas Medicine (NASDAQ: EDIT) and Allergan, now a subsidiary of AbbVie (NYSE: ABBV). Their experimental in vivo gene-editing therapy for a form of Leber congenital amaurosis, an inherited form of blindness, is delivered to target cells in the eye via an engineered adeno-associated virus. In March, a Phase 1/2 study testing the experimental therapy, AGN-151587, dosed its first patient.

A gene-editing therapy delivered via an engineered virus stays in the patient for months, which increases the risk of edits beyond the intended target, Kathiresan says. Instead, Verve uses a lipid nanoparticle, which stays in the system for about 48 hours. Such particles have been shown to quickly migrate to the liver, where they are easily taken up by the cells of the organ, Kathiresan says. Once in those cells, the Verve therapy does its work to turn off the target gene.

Verve is conducting its research with two gene-editing tools, CRISPR and base editing. Kathiresan says in the past year the company has evaluated combinations of tools and targets to determine which offer the best shot at reducing cholesterol levels while posing the lowest risk. So far the company has conducted tests in mice and monkeys. Kathiresan expects Verve will select a lead candidate by the end of this year. After that, he anticipates 18 months of preclinical research to support an application seeking FDA permission to begin tests of the gene-editing therapy in humans. Kathiresan says the first clinical trial testing Verves gene-editing drug will enroll familial hypercholesterolemia patients.

To date, Verve says it has raised $123 million total. The company calls the latest financing a Series A2 round. Earlier investors ARCH Venture Partners, F-Prime Capital, and Biomatics Capital also participated. Besides adding to its initial round, the Series A2 boosted Verves valuation, Kathiresan says. The new round also adds Wellington Management and Casdin Capital, two so-called crossover investorsfirms that invest in both private and public companies.

Crossover investment is viewed as a sign a company is preparing for an IPO. Kathiresan acknowledges that his company will need to raise more cash down the road but says its too early to determine what form that financing will take. He is, however, preparing to talk more about what Verve has accomplished so far. Kathiresan is the scheduled keynote speaker on June 27 during the annual meeting of the International Society for Stem Cell Research, where he says hell discuss more details about Verves scientific findings.

Image: iStock/SergeyNivens

Frank Vinluan is an Xconomy editor based in Research Triangle Park. You can reach him at fvinluan@xconomy.com.

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Verve Therapeutics Adds $63M to Edit Heart Attack Risk Out of Genes - Xconomy