Eli Lilly Puts Up $60M For In Vivo GeneEditing Med For Cardiovascular Disease
Eli Lilly already has two drug candidates in its pipeline that are designed to lower levels of a key protein that is a risk factor for cardiovascular disease, but even if these drugs eventually make it to market, they will require consistent dosing. Lilly is paying $60 million to Verve Therapeutics to help develop a preclinical gene-editing therapy that could offer patients a one-off treatment, expanding the potential for this protein's pharmacological action.
The important protein, lipoprotein (a) or lipoprotein (a), is produced in the liver and circulates in the blood in concentrations defined at birth. Diet and exercise combined with lipid-lowering medication have little effect on Lp(a) levels. Boston-based Verve aims to lower these levels with an in vivo gene therapy that turns off the gene that encodes Lp(a).
The Lilly Verver payment represents an equal distribution of cash and equity investments, according to a Verve securities filing. The deal announced Thursday requires Lilly to fund phase one clinical development research for the treatment from its partners. Since then, the Indianapolis pharmaceutical giant has been responsible for developing the program. Verve could earn $465 million in milestone payments.
“We believe there is a significant opportunity for a single use of a gene-editing drug to permanently lower Lp(a) levels in patients with atherosclerotic cardiovascular disease and elevated blood Lp(a) levels, and we are excited to join forces. Together with Lilly, a leading company In the field of cardiovascular disease, it is for patients to accelerate this program,” Verve Founder and CEO, Sekar Katrisan, said in a prepared statement.
Verve has been tested in humans for VERVE-101, an in vivo gene therapy for the treatment of high cholesterol. This temporary treatment turns off PCSK9, a gene that codes for a protein in the liver that makes it difficult to get rid of LDL cholesterol. VERVE-101 is undergoing Phase 1 trials in New Zealand and the United Kingdom, but remains under clinical control in the United States until the biotech collects more data at the request of the Food and Drug Administration. The company said it expects the first numbers from the New Zealand and UK teams in the second half of this year.
Meanwhile, Lilly followed up Lp(a) with another genetic drug. LY3819469 uses small interfering RNA to inhibit the production of apolipoprotein (a), which reduces apolipoprotein (a). This 'gene silencing' treatment has been licensed by Dicerna Pharmaceuticals, which was acquired by Novo Nordisk in 2018. LY3819469 is in phase II trials as a potential treatment for atherosclerotic cardiovascular disease.
Another Lp(a) driver currently under development by Lilly is muvalaplin (formerly LY3473329), a small molecule that the company says disrupts Lp(a) production. This molecule has also passed phase II trials in atherosclerotic cardiovascular disease.
In association with Verve, Lilly acquires another competitor in Lp(a) Pharmaceuticals. Novartis is conducting Phase III trials of pelacarsen, an anti-allergic oligonucleotide licensed from Ionis Pharmaceuticals. Amgen is in the process of researching olpaciran, a gene inhibitor drug licensed from Arrowhead Pharmaceuticals that is in late-stage clinical development. Silence Therapeutics has an Lp(a) gene ablation therapy, zerlasiran (previously SLN360). This treatment has reached Phase 2 trials, the leading biotechnology program. The company offering the most direct competition to Verve's approach is CRISPR Therapeutics, which is also developing in vivo gene-editing therapies. The CRISPR program Lp(a), CTX320, is in the earlier stage.
The Lilly/Verve Lp(a) Research Collaboration Agreement is for a period of five years. Lilly can extend the contract for another year. The deal also gives Lilly the right to add another objective to the partnership. This predetermined target is not detected. Verve said that with the $60 million in cash and Lilly's equity investment, the company expects to have cash until 2026, which is a year longer than the company projected in its first-quarter 2023 earnings report.
Photo: Hudimm, Getty Images
