Another Arcus TIGIT trial flops

Arcus’s partnership with Gilead appears to be unravelling further after the latest failure of the anti-TIGIT MAb domvanalimab. On Monday, Arcus released an SEC filing reporting the discontinuation for futility of a phase 3 study, Star-121, in first-line NSCLC. The companies also ditched the phase 2 Edge-Lung trial.

This was probably a foregone conclusion following the failure of Star-221 in gastric cancer in December, but Gilead seems to be cooling on its partner more broadly. The big biotech is understandably not opting into domvanalimab, but has also foregone option rights to other projects in Arcus’s portfolio.

Off the table now are preclinical projects against CCR6, CD89 and CD40L, all being developed in inflammation and immunology. Meanwhile, Gilead will maintain its existing time-limited options to projects including the AXL inhibitor AB801 and the anti-CD39 MAb AB598 (both in phase 1), as well as two other immunology assets, the MRGPRX2 antagonist AB102 and a TNF small molecule inhibitor.

In and out

Not mentioned was the CD73 inhibitor quemliclustat, in the phase 3 Prism-1 trial in first-line pancreatic ductal adenocarcinoma, due to read out in 2027. Gilead opted into this asset in 2021, but later said that Prism-1 would be Arcus’s sole responsibility. The only Gilead-sponsored trial that includes quemliclustat is the now-defunct Edge-Lung.

Arcus also has full rights to its now-lead project the HIF2α inhibitor casdatifan, outside Japan (where Otsuka’s Taiho has licensed the asset; it also has Japanese rights to domvanalimab). Gilead has notably declined to opt into this project in the past.

But Gilead has shown a recent appetite for big bolt ons, buying Arcellx for $7.8bn in February, and Tubulis for $3.15bn earlier this month. Gilead had earlier deals with both targets, but clearly remains unconvinced by Arcus. The smaller company’s stock closed down 6% on Monday.

Gilead and Arcus signed a 10-year partnership in 2020, and in early 2024 the big biotech doubled down with a $320m equity investment, despite various setbacks with other TIGIT projects.

The main remaining TIGIT player now is AstraZeneca, which keeps starting new pivotal trials of its contender, the anti-TIGIT x PD-1 bispecific antibody rilvegostomig, despite the target’s dire history.

Phase 3 trials of domvanalimab

Note: *AstraZeneca-sponsored trial. Source: OncologyPipeline & SEC filing.