AZD5492 (AstraZeneca)

AZD5492 is an asymmetric, trispecific monoclonal IgG1 antibody developed by AstraZeneca for the treatment of various B-cell malignancies, including relapsed or refractory chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), and non-Hodgkin lymphomas such as large B-cell lymphoma, follicular lymphoma, and mantle cell lymphoma. Engineered using the proprietary Target Induced T-cell Activating Nanobody (TITAN) platform, AZD5492 acts as a CD8-selective, CD20xCD3 T-cell engager. It features two Fab binding domains for CD20, one VHH domain for the T-cell receptor (TCR/CD3), and one VHH domain for the CD8 co-receptor. This design allows for the preferential engagement and activation of CD8+ cytotoxic T cells, leading to the formation of an artificial immunological synapse with CD20+ target B cells and subsequent target cell lysis. The drug is administered subcutaneously and is currently undergoing Phase I/II clinical evaluation.