Vibecotamab (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 vibecotamab. CD123 is highly expressed on AML cells and leukemic stem cells, and is associated with poorer prognosis in AML patients. Engagement of CD3 by vibecotamab 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 vibecotamab’s potency to balance anti-tumor activity with the reduction of immune toxicity that can result from T-cell activation.