anti-CD123/duocarmazine ADC BYON4413

An antibody-drug conjugate (ADC) consisting of a humanized, immunoglobulin G1 (IgG1) monoclonal antibody against the interleukin-3 (IL3)-receptor alpha chain (CD123; IL-3RA) that is site-specifically conjugated to the cleavable linker-duocarmycin payload duocarmazine (valine-citrulline-seco duocarmycin hydroxybenzamide azaindole; vc-seco-DUBA; SYD980), with potential antineoplastic activity. Upon administration of anti-CD123/duocarmazine ADC BYON4413, the antibody moiety targets and binds to the cell surface antigen CD123 expressed on tumor cells. Upon binding, internalization and cleavage of the vc linker inside the tumor cell by proteases, duocarmycin is released and binds to the minor groove of DNA. This alkylates adenine at the N3 position, and induces cell death specifically in tumor cells expressing CD123. CD123 regulates the proliferation, survival and differentiation of hematopoietic cells. CD123 is overexpressed on a variety of cancers, including myeloid leukemia, and increased expression of CD123 on leukemic stem cells is associated with poor prognosis.