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AstraZeneca puts $55M into Accent as pharmas continue push to drug RNA

AstraZeneca will pay privately held Accent Therapeutics $55 million in a deal to develop cancer drugs that target enzymes which can modify RNA molecules.Lexington, Massachusetts-based Accent will handle the early research and development work under the deal, before handing those responsibilities off to AstraZeneca after Phase 1 testing. The biotech could receive up to $1.1 billion in additional cash from AstraZeneca, though those dollars are tied to various milestones.Accent is one member of a group of companies that are using chemical-based drugs to target RNA. It’s at least the third such company to form a partnership with a large drugmaker, following similar pacts featuring Arrakis Therapeutics and Skyhawk Therapeutics.

Interfering with RNA — the molecules that turn genetic instructions into proteins — comes with great promise, because it gives drugmakers a way to try to control the expression of specific genes. But doing so with small molecules has long only been achieved accidentally, and is thought to be a tough task because RNA molecules constantly shapeshift and move freely inside cells.

Other methods of disrupting RNA sequences — such as the approaches used by Alnylam Pharmaceuticals and Ionis Pharmaceuticals — emerged first. After years of ups and downs, both companies have brought to market drugs to treat transthyretin amyloidosis, spinal muscular atrophy, and other diseases, over the past few years.

Their progress validated new ways to develop medicines and led to a flurry of deals between RNA drug developers and pharmaceutical companies, which have shown renewed interest after abandoning the field years ago. AstraZeneca is among them: in March, it put $80 million into Silence Therapeutics to develop RNA-based drugs for heart, kidney, lung and other diseases.

Now, however, increasing understanding about RNA biology has also led to a new group of venture-backed startups that aim to use chemical-based compounds to drug RNA. A number of them, including Accent, Arrakis, Skyhawk, Gotham Therapeutics and Expansion Therapeutics, have started up and raised cash from venture firms since 2017.

Though these privately held startups are much earlier in their work than the likes of Alnylam and Ionis, pharmaceutical companies have already shown interest. In April, Roche paid $190 million to start a wide-ranging deal with Arrakis. Skyhawk is working with Merck & Co., Biogen and others.

Accent is specifically focused on cancer therapies, and even more narrowly, drugging enzymes that modify RNA molecules. RNAs use these enzymes to make chemical changes to alter their structure and function, which, in turn, affects how much of a particular protein they produce.

Accent aims to find and selectively block enzymes that might, for instance, lead to the production of proteins that drive tumor growth. A 2018 paper published in Nature Reviews Drug Discovery — co-authored by Accent president and chief scientific officer Bob Copeland — highlights some of the RNA-modifying enzymes believed to be implicated in cancer. Among them is an enzyme, METTL3/14, that Accent is pursuing as a potential drug target for the blood cancer acute myeloid leukemia.

Accent will conduct the initial research and development for any drug prospects that emerge from the deal, and hand things off to AstraZeneca following Phase 1 testing. Accent will get the option to split U.S. rights, as well as the costs of development, of each program afterwards. AstraZeneca does get the exclusive option to grab worldwide rights to two Accent programs, however.