Source: Fierce Biotech by Nick Paul Taylor

GlaxoSmithKline is paying iTeos Therapeutics $625 million upfront for rights to phase 1 anti-TIGIT monoclonal antibody EOS-448. The deal sets GSK up to challenge Bristol Myers Squibb, Gilead Sciences, Merck and Roche for the red-hot corner of the immuno-oncology market. 

Interest in TIGIT has exploded over the past 18 months, with Merck and Roche quickly expanding their clinical development programs and Bristol Myers and Gilead striking big deals to buy their way into the race. Now, GSK has put together a still-bigger upfront to land EOS-448, paying more initially than Bristol Myers and Gilead combined.

The $625 million upfront secures GSK the right to co-commercialize and evenly split the profits from EOS-448 in the U.S. Elsewhere, GSK has an exclusive license and will pay iTeos tiered royalties. GSK is on the hook for up to $1.45 billion in milestones.

EOS-448 is currently in a phase 1 dose-finding trial in patients with advanced solid tumors. Earlier this year, iTeos reported a partial response in a Keytruda-refractory, BRAF-mutant melanoma patient who received EOS-448 as a monotherapy. ITeos responded to the early data by stepping up its plans to run combination clinical trials and by looking into partnerships that could expand development. 

The involvement of GSK will facilitate the expansion of EOS-448 development. A randomized clinical trial of EOS-448 in combination with GSK’s PD-1 checkpoint inhibitor Jemperli is set to start next year. GSK also highlighted its phase 1 anti-CD96 candidate GSK’608 and preclinical anti-PVRIG GSK’562 prospect as assets it will explore in “various novel combinations, including doublets and triplets.”

ITeos is trailing the front-runners in the TIGIT race, but GSK sees the breadth of its own pipeline as a potential differentiator. “Since GSK validated the role of CD226 axis targets as important in oncology, it has been strategically building a carefully constructed set of assets to target this network of checkpoint inhibitors. The addition of EOS-448 results in GSK being the only company with antibodies targeting all three known checkpoints,” the Big Pharma wrote in a statement. 

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 potential to expand the pool of patients who respond well to immuno-oncology agents has led to a flurry of TIGIT deals and activities. Merck and Roche are advancing multifront clinical programs that could deliver pivotal data, while Gilead paid Arcus Biosciences $175 million upfront, in part to pick up an option on phase 2 anti-TIGIT candidate AB154, and Bristol Myers handed Agenus $200 million for a preclinical drug against the target. Along the way, iTeos rode the wave of interest in TIGIT to a $200 million IPO. 

With GSK nabbing EOS-448, the pool of available anti-TIGIT antibodies has thinned further. The list of other companies with TIGIT candidates in the clinic includes BeiGene, Compugen, Mereo BioPharma, Merck KGaA and Seagen.