YH004 is a novel humanized antibody targeting 4-1BB, a member of the tumor necrosis factor receptor superfamily, on the surface of immune cells, using a unique IgG1 subtype. 4-1BB is mainly expressed in T cells, DC cells, monocytes, B cells, mast cells, NK cells and neutrophils. As a 4-1BB agonist, YH004 can induce immune cell proliferation and cytokine expression to activate the body's immune response. In vivo preclinical experiments in mice showed that the single-drug and combined drug efficacies of YH004 were significantly better than those of the control. A large number of preclinical and clinical data have demonstrated the great potential of targeting 4-1BB for cancer immunotherapy, but the hepatotoxicity caused by 4-1BB agonists has hindered its further clinical development. In vitro functional analysis of YH004 showed that its binding affinity to human andmonkey 4-1BB was equivalent, and no hepatotoxicity of YH004 was observed in in vivo toxicity tests of cynomolgous monkeys. We have obtained CTN approval from the TGA in June 2021 and are initiating the Phase I
clinical study in Australia.