ESMO: GSK keeps the faith in anti-TIGIT plans; it's 'not always about being first'

Four months after the latest trial failure for Roche’s tiragolumab, GSK is still pushing ahead with its own anti-TIGIT inhibitor, bullish that plenty of opportunities remain for the next-gen therapy.

“One thing that we’ve learned is it’s not always about being first,” Hesham Abdullah, head of global oncology development at GSK, told Fierce Biotech in an interview on the opening morning of the European Society for Medical Oncology (ESMO) annual congress.

TIGIT is an immunosuppressive mediator found on immune cells in the microenvironment of many tumors. Merck and Roche have shown adding anti-TIGIT antibodies to PD-1/L1 checkpoint inhibitors results in a higher response rate and longer progression-free survival than the approved drugs alone, at least in early- and mid-phase clinical trials. 

The result has been a scramble to get in on the action for this potential new checkpoint inhibitor, with a Fierce Biotech tally in May showing that more than $6 billion has been invested by big pharmas into anti-TIGIT assets. GSK topped the list, thanks to its June 2021 deal with iTeos for an anti-TIGIT called EOS-448 that totaled more than $2 billion in potential value—over $600 million of which came in upfront cash.

With that level of down payment, it's hardly surprising if the British big pharma isn't rushing to dump its investment over another company’s TIGIT troubles. But Abdullah still acknowledges the concern across the industry when Roche reported in May that tiragolumab had failed to improve progression-free survival in patients with non-small cell lung cancer when compared to Tecentriq alone.

In fact, within hours of Roche's announcement, iTeos said that both it and GSK were figuring out how to proceed with their own trials of EOS-448 as a result of the news. 

“I think everyone was a bit disappointed, of course, seeing that the Skyscraper-01 study didn’t necessarily deliver a benefit,” Abdullah says. 

Despite the two companies' pause for thought, Abdullah remains undeterred and GSK is forging ahead with its plans for EOS-448, now rechristened GSK4428859. The company has a phase 1 trial testing the anti-TIGIT in combination with the company’s investigational anti-CD96 med and the approved anti-PD-1 drug Jemperli. GSK is already generating safety data on that trial, Abdullah said, which the company is slated to present at ESMO on Saturday. 

But more than anything, Abdullah feels that for new checkpoint inhibitors like anti-TIGITs to really take off, the industry will need to locate more selective biomarkers to identify the patient populations who would benefit most. It's in this area where GSK is well positioned to lead the charge, he said.