AstraZeneca takes a chance on the STING pathway with F-star
After a slew of Big Pharma companies and biotechs walked away from the STING pathway in the last few years, AstraZeneca is approaching the field with a new bet on the drug class’ next generation.
The British drugmaker is teaming up with F-star Therapeutics on a slate of preclinical STING inhibitor compounds, the companies announced Thursday morning. It’s a modest sum as these things go, with $12 million upfront and over $300 million in milestones, plus single-digit royalties.
STING plays a central role in regulating how the immune system recognizes foreign invaders, F-star CEO Eliot Forster tells Endpoints News, and companies have for years been looking at ways to either stimulate or inhibit the pathway to treat diseases. Researchers can agonize the pathway to try to treat cancer — getting the immune system to attack tumors — or inhibit it in conditions like rheumatoid arthritis to tamp down on immune responses gone haywire.
F-star had been working on both sides of the STING coin, and already has a slate of STING agonists in the clinic. These weren’t for sale, Forster says, and AstraZeneca is getting only the preclinical STING inhibitors for yet-to-be disclosed targets. It’s a slate of candidates that F-star had been looking to partner out from the start, and AstraZeneca will take over full development with an exclusive global license.
The pathway has run up against several issues in the past, particularly on the agonist side of things. Aduro’s high-profile stumbles dealt in part with a STING agonist program for cancer, which Novartis walked away from in 2019. And after Chinook acquired Aduro, it too dumped the last of the STING agonist candidates earlier this year.
There was also a cGAS-STING inhibitor where Aduro partnered with Eli Lilly, which ended up auctioned off once Aduro began cutting bait. The deals proved costly for the Big Pharmas, as Novartis had teed up $250 million upfront with $500 million in milestones, while Lilly fronted $12 million in cash and promised up to $620 million in milestones.
Nimbus Therapeutics also pivoted away from its STING programs in June 2020 as it built out partnerships with Gilead and Celgene prior to the Bristol Myers Squibb acquisition.
But Forster said the STING agonist programs F-star is retaining are representative of the next generation of the class, and that the inhibitors licensed out Thursday were informed by similar emerging research. Whereas the old STING agonists for cancer could only be injected directly into the tumor, leading to a host of problems, the clinical candidates F-star kept are re-engineered to be given through an IV.
“The centrality of the STING pathway to the immune response in both directions is key,” Forster said. “That’s why the whole industry has been interested in it for the past decade … The first generation was a good go, but the second generation drugs are really getting to that druggability point where we can begin to manipulate the pathway.”