Lilly signs up Verve to take on Novartis and Amgen

Nov 03, 2023

A month after signing a collaboration with Scribe, Lilly is putting another bet on in vivo gene editing. This time the partner is Verve Therapeutics, and the target is Lp(a), a cardiovascular avenue also being pursued by the likes of Novartis and Amgen.

Verve gets $60m in cash and equity up front and can also stay focused on its more advanced programmes. The group could soon have a decision to make on its two lead projects, which both target PCSK9; its chief executive, Sekar Kathiresan, confirmed during a webinar with Evaluate Vantage yesterday that Verve would only take one of these into phase 3.

Lp(a) not so little

Under today’s deal, which also includes up to $465m in milestones, Verve will be responsible for development through phase 1 – though costs will be covered by Lilly – and Lilly for subsequent development.

While Verve’s lead programmes use base editing technology licensed from Beam Therapeutics, the Lp(a) project employs a novel editor, according to Verve’s website. A deal between Verve and Vertex last year in liver disease was also outside the base editing sphere, Kathiresan previously confirmed.

With the Lp(a) project still at the research stage, Verve and Lilly have a long way to go. But they could eventually end up competing with Novartis and Amgen, which both have phase 3 assets against this target.

Novartis looks to be in the lead, with the Horizon trial of its Ionis-originated contender, pelacarsen, set to read out in 2025. Amgen’s Ocean(a) study of olpasiran, licensed from Arrowhead, has a primary completion date in 2026. Others in the space include Silence Therapeutics and Crispr Therapeutics; the latter could rival Lilly and Verve in the once-and-done stakes.

There can be only one

In the nearer term, Verve has a decision looming on its two lead projects, which both target PCSK9: VERVE-101, which is already in an ex-US clinical trial, and VERVE-102, which the group unveiled during its recent first-quarter results.

The emergence of VERVE-102 raised questions about VERVE-101, which has not had a smooth development path so far.

During yesterday's Vantage webinar, Verve’s Kathiresan, said: “Ultimately, we want to choose one of the two to take forward into phase 3.” The decision would be guided by human clinical data, he added.

Like approved PCSK9 inhibitors, both assets are designed to lower cholesterol. Verve aims to provide a once-and-done treatment by permanently turning off the PCSK9 gene in the liver, an approach that could address poor compliance with existing therapies.

As for which Verve asset might ultimately win out, VERVE-102 has some potential advantages, Kathiresan said. While VERVE-101 is delivered via a regular lipid nanoparticle (LNP), the company has added a targeting ligand, Galnac, to the LNP used in VERVE-102.

Galnac targets the asialoglycoprotein (ASGPR) receptor, which is highly expressed on liver cells; its use could improve specificity with VERVE-102. In addition, the project “could be a bit more potent, because this LNP can get into hepatocytes through two different receptors – the LDL receptor or the ASGPR receptor – in contrast to a standard LNP which only gets in through one receptor.” The LDL receptor is known to mediate LNP uptake, Verve says.

This will need to be proven in the clinic. Verve plans to take VERVE-102 into phase 1 in the first half of 2024.

Another potential factor in Verve’s decision is that the Galnac-LNP formulation used in VERVE-102 is wholly owned, while the LNP used in VERVE-101 is licensed from Acuitas.

US hold

As for VERVE-101, the project is still on clinical hold in the US, although patients in the UK and New Zealand are being dosed as part of the Heart-1 trial. Initial results are due in the second half of this year.

Verve plans to include human data in its response to the FDA, with Kathiseran saying this is something the agency has asked for, but the timeline is unclear. “[The FDA] said: When you’re ready to submit your response, please provide whatever clinical data you have available from New Zealand and the UK at the time.”

A replay of the Vantage webinar, as well as our report on gene editing featuring an interview with Verve, are both available as free downloads.