Results From a First-in-Human Study of BNZ-1, a Selective Multicytokine Inhibitor Targeting Members of the Common Gamma (γc) Family of Cytokines

J Clin Pharmacol. 2020 Feb;60(2):264-273. doi: 10.1002/jcph.1522. Epub 2019 Aug 29.


Pathologic roles of interleukin (IL)-2, IL-9, and IL-15, have been implicated in multiple T-cell malignancies and autoimmune diseases. BNZ-1 is a selective and simultaneous inhibitor of IL-2, IL-9, and IL-15, which targets the common gamma chain signaling receptor subunit. In this first-in-human study, 18 healthy adults (n = 3/cohort) received an intravenous dose of 0.2, 0.4, 0.8, 1.6, 3.2, or 6.4 mg/kg infused over ≤5 minutes on day 1 and were followed for 30 days for safety and pharmacokinetic/pharmacodynamic sample collection. No dose-limiting toxicities, infusion reactions, or serious or severe treatment-emergent adverse events were observed. Headache was the only treatment-emergent adverse event in >1 subject (n = 3). Peak and total BNZ-1 exposure was generally dose proportional, with a terminal elimination half-life of ∼5 days. Pharmacodynamic effects of BNZ-1 on regulatory T cells (Tregs, IL-2), natural killer (NK) cells (IL-15) and CD8 central memory T cells (Tcm, IL-15) were measured by flow cytometry and used to demonstrate target engagement. For Tregs, 0.2 mg/kg was an inactive dose, while a maximum ∼50% to 60% decrease from baseline was observed on day 4 after doses of 0.4 to 1.6 mg/kg, and higher doses produced an 80% to 93% decrease from baseline on day 15. Similar pharmacodynamic trends were observed for natural killer cells and CD8 Tcm, although decreases in CD8 Tcm were more prolonged. These subpopulations returned to/toward baseline by day 31. T cells (total, CD4, and CD8), B cells, and monocytes were unchanged throughout. These preliminary results suggest that BNZ-1 safely and selectively inhibits IL-2 and IL-15, which results in robust, reversible immunomodulation.

Keywords: Interleukin-15; common gamma cytokines; interleukin-2; natural killer cells; regulatory T cells.

Publication types

  • Clinical Trial, Phase I

MeSH terms

  • Adult
  • B-Lymphocytes / drug effects
  • Female
  • Healthy Volunteers
  • Humans
  • Infusions, Intravenous
  • Interleukin Receptor Common gamma Subunit / metabolism*
  • Interleukin-15 / antagonists & inhibitors*
  • Interleukin-2 / antagonists & inhibitors*
  • Interleukin-9 / antagonists & inhibitors*
  • Killer Cells, Natural / drug effects
  • Male
  • Peptides / administration & dosage
  • Peptides / adverse effects*
  • Peptides / pharmacokinetics*
  • T-Lymphocytes / drug effects


  • IL15 protein, human
  • IL2 protein, human
  • IL9 protein, human
  • Interleukin Receptor Common gamma Subunit
  • Interleukin-15
  • Interleukin-2
  • Interleukin-9
  • Peptides