AZD5492

AZD5492 is a trispecific, CD8-guided T cell-engaging antibody developed for the treatment of B-cell malignancies, including chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), large B-cell lymphoma, follicular lymphoma, and mantle cell lymphoma. It is an asymmetric monoclonal IgG1 antibody that contains two Fab binding domains targeting CD20 on B cells and VHH binding domains for both the T cell receptor (TCR) and the CD8 co-receptor. This design enables preferential engagement of CD8+ T cells to form an artificial immunological synapse with CD20+ target cells, leading to targeted B cell killing while reducing activation of CD4+ T cells and associated cytokine release. Preclinical studies have shown potent anti-tumor efficacy with reduced systemic cytokine production compared to conventional bispecific antibodies. AZD5492 is administered subcutaneously and is currently in Phase 1/2 clinical trials for relapsed or refractory B-cell malignancies as well as early-phase studies in autoimmune diseases such as systemic lupus erythematosus (SLE) and idiopathic inflammatory myopathies (IIM)[1][5][6][7].