Entered into a Phase 1 clinical trial for the treatment of acute myeloid leukemia (AML) and other CD123-expressing hematologic malignancies in 2016.

XmAb14045 is a tumor-targeted antibody that contains both a CD123 binding domain and a cytotoxic T-cell binding domain (CD3). An XmAb Bispecific Fc domain serves as the scaffold for these two antigen binding domains and confers long circulating half-life, stability and ease of manufacture on XmAb14045. CD123 is highly expressed on AML cells and leukemic stem cells, and is associated with poorer prognosis in AML patients.  Engagement of CD3 by XmAb14045 activates T cells for highly potent and targeted killing of CD123-expressing tumor cells.

The structural stability and modularity enabled by the XmAb Bispecific Fc domain allowed the tuning of XmAb14045’s potency to balance anti-tumor activity with the reduction of immune toxicity that can result from T-cell activation.