The Sting is dead; long live the Sting

Given the previous failures of Sting agonists, yesterday’s move by GSK for Mersana’s XMT-2056 came as a surprise. But a look at the pipeline shows that Mersana is not alone in continuing to pursue this once-hot mechanism.

These contenders will have to hope that they can improve on the lacklustre efficacy that hit Merck & Co, and partners Novartis and Aduro; and some groups are taking interesting approaches to try and do just that.

As easy as ADC?

GSK already had a conventional small-molecule Sting agonist in the shape of GSK3745417. Yesterday’s deal gave it an option over an antibody-drug conjugate targeting Her2 that has a Sting agonist payload. XMT-2056 is still preclinical, making GSK’s $100m up-front payment all the more remarkable.

Of projects that have already reached the clinic, only Takeda appears to be trying something similar. The Japanese group’s TAK-500 is an ADC hitting CCR2, a chemokine linked with various cancers, and delivering TAK-676, a Sting agonist that is also being trialled separately.

Codiak Biosciences is another company taking a novel tack: its exoSTING comprises exosomes loaded with a small-molecule Sting agonist, designed to allow delivery directly to antigen-presenting cells. The company reckons exoSTING is a hundredfold more potent than free Sting agonists while avoiding systemic exposure.

Codiak reported phase 1/2 single-agent data in June, and plans to take the agent into phase 2 in bladder cancer next year.

Free Sting

There are also plenty of groups continuing to look at free Sting. Of these, F-Star, which recently agreed to be bought by China’s Sino Bio, claims that its candidate, SB 11285, is differentiated from the first generation as it is intravenously delivered, rather than being injected directly into a patient’s tumour. This, the group says, will allow treatment of hard-to-reach cancers.

F-Star is due to report further data from a dose-escalation trial this year; whether SB 11285 will be a priority for the group’s new owner is anybody’s guess. The project originally came from Spring Bank, with which F-Star merged in 2020.

Aside from GSK and Takeda, some other big players still have an interest in Sting, including Bristol Myers Squibb, via its 2017 purchase of IFM Therapeutics. However, Abbvie has gone quiet on MAVU-104, the preclinical asset its picked up with Mavupharma in 2019.

GSK’s latest foray into this mechanism shows that there could be life here, but this story could still have a sting in its tail.

This table has been updated to include IMSA101.