Therapy Areas: Autoimmune
Xencor Touts Phase 1a Clinical Data for XmAb564
9 November 2022 - - US-based clinical-stage biopharmaceutical company Xencor, Inc. (NASDAQ: XNCR) has released topline clinical data from its Phase 1a single-dose, healthy volunteer study of XmAb564, in development for patients with autoimmune diseases, the company said.

XmAb564 is a wholly owned, monovalent interleukin-2 Fc fusion protein (IL-2-Fc), engineered with dramatically lowered potency and heightened binding affinity for the IL-2 alpha receptor, resulting in selective activation of regulatory T cells (Tregs).

Tregs combat autoimmunity by suppressing other immune cells from attacking normal tissue; however, in many autoimmune diseases, Tregs become dysregulated.

The Phase 1 single ascending-dose study of XmAb564 was designed to characterize its safety, tolerability and pharmacokinetics in healthy volunteers, and the study included an analysis of key immunomodulatory biomarkers.

The study enrolled 48 subjects, with six dose-level cohorts each randomizing six subjects to XmAb564 and two subjects to placebo. Single doses ranged from 0.003 mg/kg to 0.065 mg/kg.

XmAb564 was well-tolerated across all dose levels. Adverse events were Grade 1 or Grade 2 and resolved without intervention, and no serious AEs were observed.

The most common AE was injection site reaction. Laboratory tests indicated some subjects had transient increases in eosinophils, though no eosinophil-related AEs were observed.

This laboratory increase may be related to the mechanism of action of CD25-targeting IL-2 drug candidates.

Dose-dependent and selective expansion of CD25bright and total Tregs was observed throughout the study.

The expansion of CD25bright Tregs with at least 10-fold increases over baseline began at the third dose level and reached a 117-fold increase over baseline at the highest dose. Total Tregs increased 8-fold over baseline at the highest dose.

An important metric for selectivity, the ratio of Tregs to conventional T cells (which include effector T cells) increased consistently in a dose-dependent manner, with a ratio of 0.14 at the highest dose compared to