ANB032, a novel BTLA agonist monoclonal antibody, reduced T cell proliferation, inflammatory cytokine secretion and prevented graft versus host disease in a mouse model

BTLA is a co-inhibitory checkpoint receptor that regulates activation of T cells, B cells and dendritic cells. The interaction of BTLA with its ligand HVEM induces inhibitory signals that regulate immune cell function. ANB032 is a novel BTLA agonist IgG4 antibody that does not compete with the binding of BTLA to HVEM. Upon binding to BTLA, and simultaneous Fc receptor engagement to an opposing cell, ANB032 induced inhibitory signaling, reduced T cell proliferation and reduced inflammatory cytokine secretion. In vitro, ANB032 reduced Th1, Th2, Th17 and Th22 inflammatory cytokine secretion from atopic dermatitis patient derived PBMCs. To determine the efficacy and the immune regulatory effects of ANB032, we ran an experiment comparing it to reference BTLA agonist antibodies in a human xenograft GvHD mouse model. Compared to the reference antibodies, ANB032 demonstrated superior in vivo efficacy on key endpoints, including improved survival, body weight maintenance, reduced human T cell expansion and reduced plasma inflammatory cytokines. ANB032 demonstrated, both in vitro and in vivo, the potential therapeutic benefit that BTLA agonism may provide in the treatment of autoimmune or inflammatory diseases and is being evaluated in an ongoing Phase 2 study in atopic dermatitis (NCT05935085).