GSK to buy iTeos’ anti-TIGIT antibody for up to $2 billion

GlaxoSmithKline has agreed to buy an anti-TIGIT antibody for cancer immunotherapy from iTeos Therapeutics for $625 million upfront and up to $1.45 billion in milestone payments.

It’s the latest billion-dollar deal in the anti-TIGIT space as large drug companies look for new checkpoint inhibitors to treat the many people who do not respond to what’s currently available.

iTeos’ experimental antibody is called EOS-448. It has several functions, says Joanne Lager, the firm’s chief medical officer. One end of the antibody blocks TIGIT, a T cell immunoreceptor with Ig and ITIM domains. Normally, this molecule serves as an immune checkpoint—when it’s activated, it tells T cells to turn down their immune responsiveness. Blocking TIGIT with checkpoint inhibitors like EOS-448 allows the immune response to stay strong.

The other end of the antibody seems to activate other immune cells that have anti-tumor activity, Lager says. And the antibody seems to mediate the killing of T cells that naturally lower the volume of the immune response, she adds.

“iTeos was really trying to find a target that they thought was validated, that really could benefit those patients that don’t benefit from current checkpoint inhibitors,” Lager says. Current checkpoint inhibitors block the activity of immune-dampening molecules such as PD-1, PDL-1, and CTLA-4.

TIGIT is a popular target in cancer therapy, and pharmaceutical companies are paying big bucks for antibodies that appear to block it. In May, Bristol Myers Squibb bought Agenus’ anti-TIGIT antibody, AGEN1777, for $200 million upfront and up to $1.36 billion in future payments. A year ago, Gilead Sciences invested $375 million in Arcus Biosciences and got an option to acquire Arcus's anti-TIGIT antibody AB154 for $275 million. Gilead could also make $1.23 billion in future payments.

Earlier this year, Roche earned breakthrough therapy designation from the US Food and Drug Administration for tiragolumab, its anti-TIGIT therapy. Tiragolumab, in combination with the PDL-1 inhibitor Teqcentriq, reduced the risk of death or disease worsening by 42% in Phase 2 trials.

EOS-448 is in Phase 1 trials as a standalone treatment, but Lager says the antibody may be best used as in combination with other checkpoint inhibitors. One of the reasons why iTeos decided to partner with GSK, she says, is that GSK is developing checkpoint inhibitors that work against some of TIGIT’s binding partners. GSK has its own anti-PD-1 treatment, Jemperli, so future combination studies would be easier to take on.

“They really have a focus on this whole pathway,” Lager says.