Th118 - ANB032, a BTLA (B and T Cell Lymphocyte Attenuator) Checkpoint Receptor Agonist, Modulates Dendritic Cell (DC) Maturation and Function

German Muench – AnaptysBio; Eric Hare – AnaptysBio; Pejman Soroosh – AnaptysBio; Stephen Parmley – AnaptysBio; Paul Lizzul – AnaptysBio; Martin Dahl – AnaptysBio

Abstract Text: BTLA is a co-inhibitory checkpoint receptor that regulates T cell, B cell, and DC function. The interaction of BTLA with its ligand, HVEM, induces inhibitory signals that regulate immune cell function. ANB032, an investigational non-depleting BTLA agonist antibody, does not compete with the binding of BTLA to HVEM. Previous in vitro studies demonstrated that 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 (Th1, Th2, Th17, Th22). Although the expression of BTLA on subsets of DCs has been reported, BTLA’s role in modulating DC maturation and function has not been thoroughly investigated. To address the functional role of BTLA on DCs, an LPS-mediated maturation assay with monocyte-derived DCs was performed to confirm that mature DCs highly express BTLA. ANB032 reduced HLA-DR expression, co-stimulatory molecule expression, and inhibited inflammatory cytokine production from DCs challenged with LPS. When co-cultured with allogenic naïve T cells, ANB032-treated DCs increased the generation of Foxp3+ Tregs and decreased production of Th1 and Th2 cytokines. Therefore, BTLA agonism by ANB032 inhibits a broad range of immune cells and modulates DC function, while inducing Tregs, and potentially restoring immune balance, which may provide therapeutic value in the treatment of autoimmune and inflammatory disease. ANB032 is currently being studied in a Phase 2 clinical trial in atopic dermatitis (NCT05935085).