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Computing checkpoints

Compugen takes the plunge into clinical development with a mAb against a new checkpoint

After 25 years as a discovery company, Compugen Ltd. is about to enter the clinic for the first time with a first-in-class mAb against a new checkpoint target. The target’s expression on adaptive immune cells, and its ligand’s expression on PD-L1-negative tumors, could allow COM701 to work where PD-1 inhibitors don’t.

COM701 is a mAb against PVRIG. Compugen discovered PVRIG, along with the checkpoint proteins ILDR2 and TIGIT, using bioinformatics to search the genome for new members of the B7/CD28 family of immune regulators.

The B7/CD28 family includes the checkpoint proteins PD-1 and PD-L1. But unlike PD-1, PVRIG, ILDR2 and TIGIT inhibit NK cells in addition to T cells. Some companies have pegged inhibition of NK cells as a key feature of next-wave checkpoints because doing so could unleash a multipronged immune attack on the tumor (see “NK Cell Check-In”).

Based on expression of PVRIG’s ligand PVRL2, Compugen plans to

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