Another day, another deal for Dicerna, which yesterday unveiled a substantial collaboration with the diabetes giant Novo Nordisk, only weeks after the ink had dried on a hepatitis B pact with Roche. With big drug developers comfortable enough with RNA-based technologies to start committing substantial amounts of money, companies with research platforms are benefiting.
The RNA approach has been “derisked” by large programmes like The Medicine Company’s inclisiran, while concerns such as off-target toxicities are not as great as they once were, Marcus Schindler, head of Novo’s drug discovery, told Vantage. He believes that the biggest challenge facing the Dicerna collaboration will be finding novel targets that are relevant to the cardio-metabolic conditions in focus.
“We have extremely high confidence that once we have found a target that is truly expressed in hepatocytes, [Dicerna] will be able to knock them down. That’s not what we’re worried about. The burden is on the biology,” he said.
Novo is increasing its efforts in big data, genomics and bioinformatics to find new targets, Mr Schindler said. The deal will see up to 30 liver cell targets investigated, in diseases from Nash to diabetes and obesity, as well as rare conditions.
Terms of the transaction include a $175m up-front fee for Dicerna and a $50m equity investment from Novo – struck at a substantial premium to the RNAi specialist’s recent share price – as well as $75m over three years to help fund discovery and development. Milestones will also be due on any project taken forward.
Dicerna’s technology generates therapies designed to silence disease-driving genes in the liver. Mr Schindler said that because the company’s technology was “highly tuned” to hepatocytes, he hoped to see projects with minimal systemic exposure and good tolerability emerging. Clinical work should commence in two to three years.
The deal is certainly typical of Novo in that it is very early stage, though it represents the company’s first move into RNA. The Danish company has shown an interest in more novel technologies recently: last year it struck a genome editing collaboration with Bluebird Bio, in haemophilia, and Mr Schindler said Novo remained interested in adding “novel treatment modalities”.
Access to Dicerna’s platform will bring the ability to address intracellular targets, which are particularly relevant in many cardio-metabolic conditions. The company’s existing peptide platforms largely focus on extracellular or secreted proteins, though he argued that the technologies did not sit in completely different worlds.
“We are still talking about injectables, a field we are extremely well versed in, and nucleotide chemistry is not so far away from peptide chemistry,” he said. “But this gives us a lot more tools to ... address the biological targets of relevance.”
While this collaboration is a small step for Novo, it represents something much larger for Dicerna, which climbed 11% on the news yesterday to close at a four-and-a-half year high. The deal is its fifth and most extensive to date, and the extra cash leaves the company very well financed – with around $750m in the bank analysts reckon Dicerna should easily have enough to fund the launch of its in-house rare disease project DCR-PHXC, on which pivotal data should emerge later next year.
This sort of validation has been a long time coming for Dicerna, which floated in 2014 before it had even got a project in the clinic, and promptly saw its share price triple. That exuberance was short lived, however; the high-risk RNAi space has taken years to prove its worth. RNAi is still far from mainstream, of course, but collaborations with typically cautious developers like Novo will do much to move the technology in that general direction.