XmAb®5574 (MOR208)

XmAb®5574/MOR208 is a monoclonal antibody in Phase 2 development by MorphoSys AG as a treatment for B-cell acute lymphoblastic leukemia (B-ALL) and non-Hodgkin lymphoma (NHL). XmAb5574 targets CD19 with its variable domain and uses our cytotoxic XmAb® Fc domain technology for superior killing of malignant B cells. Xencor discovered XmAb5574 and licensed exclusive worldwide rights for all indications to MorphoSys in 2010.

The cytotoxic XmAb Fc technology results in improved binding to the human Fc receptors FcγRIIIa and FcγRIIa, thereby enhancing recruitment of natural killer(NK) cells and other effector cells to attack the tumor. We applied further engineering to the CD19-binding variable domain of XmAb5574/MOR208 to enhance its affinity over 10-fold for human CD19.

In preclinical studies, we demonstrated that XmAb5574/MOR208 had strong, FcγR-dependent, anti-tumor activity against multiple human B-cell lymphomas in vitro and strong anti-tumor effects in mouse lymphoma models. We also demonstrated favorable half-life and potent B-cell depletion in primate models. Our completed Phase 1 multiple ascending dose clinical trial in patients with CLL demonstrated an acceptable safety profile and encouraging signs of anti-tumor activity.