Eli Lilly’s pipeline already includes two drug candidates designed to reduce levels of a key protein that’s a cardiovascular disease risk factor, but even if those medicines eventually reach the market, they’ll require chronic dosing. Lilly is expanding its prospects for pharmacologically addressing this protein, paying $60 million to share in the development of a preclinical gene-editing therapy from Verve Therapeutics with potential to offer patients a one-time treatment.

The protein of interest, lipoprotein (a) or Lp(a), is produced in the liver and circulates in the blood at concentrations that are determined by birth. Diet and exercise along with lipid-lowering drugs have little impact on Lp(a) levels. Boston-based Verve aims to reduce those levels with an in vivo gene-editing therapy that inactivates the gene that codes for Lp(a).

Lilly’s payment to Verve is an equal split of cash and an equity investment, according to a Verve securities filing. The deal announced Thursday calls for Lilly to fund its partner’s research for the therapy through Phase 1 clinical development. After that point, the Indianapolis-based pharma giant is responsible for further development of the program. Verve could earn up to $465 million in milestone payments.

“In patients with established [atherosclerotic cardiovascular disease] and elevated blood Lp(a), we believe there is a substantial opportunity for a single-course gene-editing medicine to permanently lower Lp(a) levels, and we are thrilled to have joined forces with Lilly, an industry leader in cardiometabolic disease, to accelerate this program toward patients,” Verve co-founder and CEO Sekar Kathiresan said in a prepared statement.

Verve has already reached human testing with VERVE-101, an in vivo gene-editing therapy for high cholesterol. This one-time treatment turns off PCSK9, a gene that codes for a liver protein that makes it more difficult for the body to clear LDL cholesterol. VERVE-101 is in Phase 1 testing in New Zealand and the U.K. but remains under a clinical hold in the U.S. while the biotech gathers additional information requested by the FDA. The company has said it expects preliminary data from the New Zealand and U.K. cohorts in the second half of this year.

Meanwhile, Lilly has been pursuing Lp(a) with another genetic medicine. LY3819469 uses small interfering RNA to block the production of apolipoprotein(a), which in turn reduces levels of Lp(a). This “gene silencing” therapy was in-licensed in 2018 from Dicerna Pharmaceuticals, which has since been acquired by Novo Nordisk. LY3819469 is currently in Phase 2 testing as a potential treatment for atherosclerotic cardiovascular disease.

The other Lp(a) program in Lilly’s pipeline is muvalaplin (formerly LY3473329), a small molecule that the company says works by disrupting Lp(a) formation. This molecule has also reached Phase 2 testing in atherosclerotic cardiovascular disease.

By partnering with Verve, Lilly gains another contender in the field of drugs aiming to address Lp(a). Novartis has reached Phase 3 testing with pelacarsen, an antisense oligonucleotide licensed from Ionis Pharmaceuticals. Amgen is in the hunt with olpasiran, a gene-silencing drug licensed from Arrowhead Pharmaceuticals that has reached late-stage clinical development. Silence Therapeutics has its own gene-silencing Lp(a) therapy, zerlasiran (formerly SLN360). That therapy, the biotech’s lead program, has reached Phase 2 testing. The company posing the most direct competition to Verve’s approach is CRISPR Therapeutics, which is also developing an in vivo gene-editing therapy. CRISPR’s Lp(a) program, CTX320, is preclinical.

The Lilly/Verve research collaboration agreement in Lp(a) spans five years. Lilly may extend the pact for one additional year. The deal also gives Lilly the right to add an additional target to the collaboration. That pre-determined target was not disclosed. With the $60 million cash payment and equity investment from Lilly, Verve says it expects its cash should last into 2026, about one year beyond what the company had estimated in its report of first quarter 2023 financial results.

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