Xencor has dosed the first subject in a Phase I clinical study of an engineered Interleukin-2 (IL-2) Fc cytokine, XmAb564, for the treatment of patients with autoimmune diseases.
XmAb564 is a monovalent IL-2-Fc fusion protein that can selectively stimulate and expand regulatory T cells (Tregs) for treating autoimmune diseases.
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Tregs suppress other immune cells from attacking normal tissue, thereby avoiding autoimmunity but in the case of several autoimmune diseases, they become dysregulated.
The randomised, double-blind, placebo-controlled single ascending dose study will assess the safety, tolerability and pharmacokinetics of subcutaneously administered XmAb564 in healthy adult subjects.
Xencor senior vice-president and chief scientific officer John Desjarlais said: “We engineered XmAb564 to selectively activate and expand regulatory T cells over other immune cells by tuning the binding affinities for both IL-2’s alpha and beta receptors.
“Our modular XmAb heterodimeric Fc domain additionally provides XmAb564 with a stable protein scaffold and improves its pharmacologic properties, and we further enhanced circulating half-life by adding our Xtend Fc technology.”
XmAb564 demonstrated to be well-tolerated, stimulated the selective and sustained expansion of Tregs and showed a favourable pharmacokinetic profile in preclinical studies.
Xencor chief medical officer and senior vice-president Allen Yang said: “The goal of an IL-2 therapy for autoimmune disease is to provide sustained low-intensity activation of Tregs while avoiding the pro-inflammatory systemic activation of effector T cells.
“An IL-2 therapy that is selective for Tregs, with an expanded therapeutic window compared to other IL-2 approaches, would have broad potential across many different autoimmune diseases.”
The trial will also assess vital immunomodulatory biomarkers.
In February, Xencor and UCLA Technology Development Group had entered an agreement for developing new therapeutic antibodies, combining novel targets proposed by UCLA researchers and applying the former’s modular suite of XmAb technology platforms.
