Ionis gets into gene editing

Ionis already has a pipeline bursting at the seams with antisense projects – some more successful than others. But the company clearly believes it has capacity for more, today announcing a gene editing collaboration with Metagenomi worth $80m up front.

Ionis refutes any notion that its scope is already too broad, or that the deal might cause it to lose focus. “Gene editing is a natural extension of antisense,” the group’s chief executive, Brett Monia, tells Evaluate Vantage, adding the tie-up is a “key step” towards Ionis becoming “the leader in genetic medicines”.

Mr Monia calls Metagenomi an “established and experienced leader” in gene editing. The private group is not quite as well known as the likes of Crispr Therapeutics and Intellia, however; its main claim to fame so far is hooking Moderna as a partner around a year ago.

Like many other recent gene editing deals, Ionis’s latest foray has not broken the bank. Perhaps more importantly, the move gives it a foothold in a technology that threatens to disrupt its core business.

Crispr and liver first

Metagenomi is developing various gene editing technologies, including Crispr nucleases, base editing and Crispr-associated transposases (Casts). The last two, it says, could allow the integration of large DNA fragments, an ambitious goal in gene editing.

The deal covers four unnamed targets and could be expanded to include four more, and initially work will take a well-trodden path: Crispr nucleases for liver targets. Specifically, Mr Monia says: “We will focus on targets and disease areas where Ionis has already made substantial investments, but we will also work on novel targets.”

The groups will also explore targets outside the liver, and future work might use the other gene editing modalities, adds Brian Thomas, Metagenomi’s chief executive.

As for its efforts in Crispr, Metagenomi is testing nucleases that it claims are differentiated from the Crispr/Cas9 system that has become ubiquitous. Mr Thomas says the group will only advance novel systems that are “equal to or better than” the incumbents. The chief exec highlights Metagenomi’s “ultra-small” nucleases, which could be more easily packaged up than Cas9 – an approach also being taken by Mammoth Biosciences.

He also points to the company’s large variety of PAM sequences, an essential part of Crispr targeting.

Metagenomi’s in-house projects are all at a very early stage, but buy in from Moderna and now Ionis will go some way to validating its approach.

Under threat?

Ionis, meanwhile, seems to be facing up to the fact that antisense, a cutting-edge technology not all that long ago, could be under threat from gene therapy and editing.

This was exemplified over the weekend with further data on Intellia’s hereditary angioedema project NTLA-2002 at the American College of Allergy, Asthma & Immunology meeting. Ionis is also active in this disease.

The prospect of a once-and-done therapy holds an obvious appeal over a chronically dosed antisense injection. But there are still big question marks over the long-term safety and durability of gene therapy and editing – not to mention the cost of such approaches.

The next few years should shed some light on how this battle might evolve. At least Ionis now has an insurance policy.