Interleukin-2 (IL-2) is an immune signaling protein that activates and expands certain immune cell populations, including regulatory T cells (Tregs). Tregs prevent autoimmunity by suppressing other immune cells from attacking normal tissue; however, in many autoimmune diseases, Tregs become dysregulated. An existing approach to restore normal immune activity and improve outcomes for patients has been to activate Tregs with IL-2 provided therapeutically at low doses. These regimens, however, suffer from a narrow therapeutic window, because IL-2 is a highly potent molecule that also activates the immune cell populations that Tregs are intended to suppress. An IL-2 therapy that is selective for Tregs, with an expanded therapeutic window compared to other IL-2 approaches, could have broad potential across many different autoimmune diseases.
XmAb564 is a monovalent IL-2-Fc fusion protein, engineered to selectively activate and expand Tregs for the potential treatment of patients with autoimmune diseases. XmAb564 is engineered with reduced binding affinity for IL-2’s beta receptor (IL-2Rβ, CD122) and increased binding affinity for its alpha receptor (IL-2Rα, CD25). Xencor’s XmAb® Bispecific Fc Domain additionally provides a stable protein scaffold and improves XmAb564’s pharmacologic properties, and Xencor’s Xtend™ Fc technology enhances its circulating half-life. In preclinical studies, XmAb564 was well-tolerated, promoted the selective and sustained expansion of Tregs and exhibited a favorable pharmacokinetic profile.
In April 2020, Xencor initiated a randomized, double-blind, placebo-controlled Phase 1 clinical study to evaluate the safety and tolerability of XmAb564, administered subcutaneously in healthy adult volunteers.