BGB-A445 is a humanized non-ligand blocking agonistic OX40 monoclonal antibody with high affinity for OX40. It activates the downstream NF-κB pathway, inducing activation, proliferation, and survival of immune cells. BGB-A445 significantly depletes regulatory T cells in a dose-dependent manner via antibody-dependent cellular cytotoxicity (ADCC). In the MC38 mouse model, BGB-A445 demonstrates potent, dose-dependent antitumor efficacy and is applicable in cancer studies, such as colorectal adenocarcinoma.

BGB-A445 binds tightly to overexpressed OX40 on cell surfaces in a dose-dependent manner, with an EC50 of 0.219 µg/mL in HuT78 cells and 0.157 µg/mL in primary human CD4-positive T cells. It induces dendritic cell maturation by upregulating the levels of CD83 and CD86 when used at concentrations of 0-10 µg/mL for 48 hours. Furthermore, BGB-A445 enhances IL-2 production in HuT78/OX40 cells and primary CD4-positive T cells in a dose-dependent manner, with an EC50 of 0.059 µg/mL at concentrations ranging from 0.0001-10 µg/mL over a 48-hour period. Overnight exposure to BGB-A445 (0.001-10 µg/mL) induces antibody-dependent cellular cytotoxicity against tumor regulatory T cells with high OX40 levels and expression percentages. Additionally, it increases the percentage of CD8-positive cells in T cells within PBMCs while decreasing the percentage of regulatory T cells.

BGB-A445, administered intraperitoneally at 0.3-10 mg/kg weekly for 2 to 4 weeks, demonstrates significant anti-tumor activity in genetically identical mouse models MC38, CT26WT, and PAN02, while also enhancing effector T cell proliferation in a dose-dependent manner.