GS-0321 (previously COM503) is currently in Phase 1 development
While PVRIG and TIGIT are novel targets discovered with our computational discovery platform, more recently, we have also discovered a unique and differentiated way to target a known biological pathway, the IL-18 binding protein pathway.
We identified a potential dominant immunosuppressive mechanism which is used by macrophages in tumors to escape the immune system. This is the “interleukin-18 binding protein and interleukin-18 complex”. The inflammasome-induced pro-inflammatory cytokine, interleukin-18, is present at high levels in the tumor microenvironment, where it is expected to naturally activate anti-tumor effector cells, such as T and NK cells. But IL-18 is one of the rare cytokines that is naturally blocked by an endogenous high affinity inhibitor, called IL-18 binding protein.
GS-0321 which is licensed to Gilead is a potential first-in-class, high affinity antibody which blocks the interaction between IL-18 binding protein and IL-18, thereby freeing natural IL-18 in the tumor microenvironment to inhibit cancer growth.