Ionis Pharmaceuticals has formed an alliance with gene editing startup Metagenomi in a bid to branch out beyond the RNA-based drugs it’s known for.
Ionis is paying $80 million up front, and promising an unspecified total of downstream payments, to Metagenomi, a young drugmaker launched in 2019 by scientists from the University of California, Berkeley. The two companies aim to jointly develop medicines for up to four genetic targets, and Ionis could add four more to the deal if certain milestones are hit. All of those drug prospects will be “in vivo” medicines, meaning they would edit genes inside the body.
The alliance represents the first foray into gene editing for Ionis, a more than three-decade old company known for its expertise developing RNA-targeting medicines known as antisense oligonucleotides.
Ionis has used that approach to develop three marketed medicines, among them the spinal muscular atrophy treatment Spinraza that’s now sold by Biogen. It also has a pipeline of drugs for several other diseases and a lengthy list of partnerships.
Yet antisense-based medicines are limited. They’re largely constrained to disease targets in the liver and must be given chronically to maintain their effectiveness. In some cases, antisense therapies have also had trouble matching the potency or safety of medicines made with RNA interference, a similar RNA-based technology.
Developing DNA editing medicines, then, is the “next logical step” for the company, said CEO Brett Monia, in an email. “Much of what we have learned and created is directly applicable to DNA therapeutics,” he said.
In diseases where a mutated gene produces a harmful protein, DNA editing drugs can drive down expression more deeply than antisense and, at least potentially, offer the prospect of a “one and done treatment,” he said. Gene editing can also help turn on expression in “loss of function” conditions where genes aren’t producing a key protein.
To develop those drugs, Ionis is teaming with Metagenomi, a member of a growing list of startups that’s formed in recent years with plans to improve on CRISPR gene editing technology. Metagenomi is mining microbial DNA to find new CRISPR-based enzymes capable of editing genes, and, since January, has raised $175 million in private funding and formed a partnership with Moderna to help back its work. The company’s pipeline includes preclinical treatments for hemophilia, cystic fibrosis and cancer.
The two companies aren’t disclosing what diseases they intend to go after. But they’re starting with targets in the liver, and conditions for which “Ionis has already made substantial investments” before moving elsewhere, according to Monia. They’ll also work together on different ways to deliver medicines to the liver and get to novel targets in other tissues, said Metagenomi CEO Brian Thomas.