Big Pharma is working to carve out an early lead in TIGIT, a potential third immune checkpoint that could deliver billions in sales. Roche has led the way, but tiny biotech Arcus is putting forward its own candidate alongside their own big-name partners – and after a mid-point check-in, the company turns positive with very little to show.
In a cryptic update, Arcus said its anti-TIGIT drug, domvanalimab, has shown “encouraging clinical activity” in an open-label Phase II study testing the drug alongside investigational PD-1 therapy, and in a clinical trial. triple therapy comprising these two drugs and the double adenosine A2a / A2b receptor antagonist etrumadenant, in metastatic non-small cell lung cancer.
Arcus appeared to show a benefit in overall response rate, but Arcus would only say that domvanalimab results were encouraging in patients with elevated PD- (L) 1 expression. Actual figures were not available and it is impossible to know if the drug even tends to be effective. Truist analysts earlier this week said Arcus previously indicated that an ORR above 50% for the TIGIT / PD-1 combo was the target.
Arcus’ PD-1, dubbed zimberelimab, for its part showed activity comparable to that of other PD-1s marketed as part of a monotherapy regimen, said biotechnology, again insufficient to determine the ‘efficiency. For the triplet arm, Arcus didn’t add anything beyond the encouraging activity mark – analysts at Truist said it was not clear what the ORR Arcus benchmark was aiming for there.
Biotechnology said the safety profiles of the three drugs were consistent with other trials but provided no data. Meanwhile, efficacy data is not yet mature enough to determine significance, and the primary endpoint of PFS has not been met, Arcus said.
Arcus’ Phase II test for its anti-TIGIT and an upcoming Phase III program have been closely watched as more major drugmakers race for the third immune checkpoint target approved after PD-1 and CTLA4.
As Truist notes, an ORR greater than 50% for domvanalimab is a key benchmark given that Roche’s own anti-TIGIT achieved an ORR of 66% in its own Phase II test combined with anti-PD- 1 Tecentriq versus an ORR of 24% for Tecentriq as monotherapy. alone in the same population of high-expressing PD- (L) 1 NSCLC patients. An ORR of 15 percentage points or more for the TIGIT-PD-1 combo versus PD-1 monotherapy would be considered a win, the analysts wrote.
Arcus said it plans to present full interim data at an upcoming medical meeting, but did not specify which one.
Domvanalimab is part of a collaboration with Gilead signed in May 2020 with $ 375 million in cash and equity for expanded access to the Arcus pipeline. The anti-TIGIT is one of a group of opt-in programs, which Truist says could fetch between $ 200 million and $ 300 million in cash if Gilead likes what he sees.
Meanwhile, there is also a collaboration between AstraZeneca and Arcus to combine Imfinzi with domvanalimab, with a registration trial expected to start earlier this year.
More and more drugmakers have sought to crash into this space after Roche’s good results. As recently as last week, GlaxoSmithKline disbursed $ 625 million in initial cash to license the iTeos anti-TIGIT drug EOS-448, which recently read Phase I data showing a single confirmed partial response on monotherapy. This deal is worth an additional $ 1.45 billion in future stages.
Bristol Myers Squibb made an equally strong entry into space last month, handing out $ 200 million upfront for rights to Agenus’ preclinical bispecific antibody that targets TIGIT and another undisclosed target. This pact was worth an additional $ 1.36 billion in milestones.