AstraZeneca will pay Silence Therapeutics $80 million to reenter a research field of renewed interest to the world’s largest drugmakers, announcing Wednesday a collaboration with the U.K. biotech to develop drug candidates built from strips of nucleic acid. AstraZeneca and Silence, which first partnered in 2007, will work on drug candidates that work by “silencing” genetic expression, thereby preventing the body’s cells from producing disease-causing proteins. The companies plan to look first at liver-expressed gene targets, but will explore others in the heart, kidney and lungs as well. Alnylam’s Onpattro was the first drug using RNA interference, or RNAi, to win approval in the U.S., capping a two-decade-long research journey from when the technology was first described by Andrew Fire and Craig Mello. After abandoning the field in the mid-2010s, large pharmaceutical companies are now signaling new interest via research deals and acquisitions.
AstraZeneca’s partnerships with Silence follows a flurry of collaborations and deals between large pharmas and biotechs specializing in RNAi research.
Novartis’ near-$10 billion acquisition of The Medicines Company and its cholesterol-lowering RNAi therapy inclisiran is the most notable, but Johnson & Johnson, Eli Lilly, Regeneron, Roche and Novo Nordisk have all committed sizable sums to RNAi drug development pacts as well.
Like other drugmakers, AstraZeneca was interested in RNAi years ago, but a 2007 collaboration with Silence didn’t yield any clinical candidates. The companies work then was based on a delivery technology that’s different from the one now being used, a spokesperson for Silence told BioPharma Dive.
Several of the issues that held back RNAi drug research, such as safely and effectively delivering the therapies to the right place in the body, have now been addressed, opening up new possibilities.
AstraZeneca and Silence will aim first at the liver, which is where Alnylam’s approved drugs Onpattro and Givlaari are targeted. But like other RNAi drug developers, they also aim to move to other organs as well, potentially fitting better with AstraZeneca’s prioritization of cardiovascular and respiratory research.
Over the first three years of the collaboration, AstraZeneca and Silence will work on five genetic targets. The British pharma holds an option to add five more to the partnership.
Silence will design the RNA drug candidates and get them ready for human testing. AstraZeneca will lead clinical development and has agreed to pay Silence up to $140 million in milestone payments per target should the programs advance through development.
As a result of the deal, Silence said it would prioritize its existing candidate SLN360, which is being developed for heart disease and targets a risk factor known as lipoprotein(a). The company expects to ask the Food and Drug Administration for permission to start human testing later this year.
Study of SLN124, previously the company’s lead program, will be paused, as the company decided to stop recruiting patients with beta-thalssemia and myelodysplastic syndrome due to the coronavirus outbreak. Silence said it will restart the trial when appropriate, and aims to report interim data in the first half of next year.