XmAb® Antibody Engineering Technology

Xencor’s XmAb® technology has been used to create a growing pipeline of drug candidates, and has led to an array of partnerships with biotech and pharmaceutical companies. We use our proprietary algorithms and computer models of the structure of the Fc domain to identify small structural changes with potentially large improvements in antibody function.

Subtle Changes for Dramatically Enhanced Function
Each XmAb Fc domain Xencor has developed consists of a naturally occurring Fc domain with a small number of amino acid changes, usually two, that are critical for modulating interactions with the desired receptors. XmAb drug candidates are usually more than 99.5% identical in structure and sequence to natural antibodies, but have dramatically enhanced function. We believe this conservative design allows our engineered antibodies to retain the beneficial stability, pharmacokinetics and ease of discovery of natural antibodies, as well as use well-validated methods for antibody manufacturing.

Our patented XmAb technology enables the creation of therapeutic antibody candidates that have novel interactions with the human immune and antibody regulation systems. We have identified a set of Fc domains, each of which is engineered with particular amino acid changes to augment a specific naturally-occurring antibody function based on its Fc receptor binding profile, including:

  • Immune Inhibitor Fc Domain—selective immune inhibition and rapid target clearance, targeting the receptor FcγRIIb
  • Cytotoxic Fc Domain—increased cytotoxicity, targeting the receptors FcγRIIIa on natural killer (NK) cells and FcγRIIa on other immune system cells
  • Xtend Fc Domain—extended antibody half-life, targeting the receptor FcRn on endothelial cells