Safety and tolerability of a novel inhaled GATA3 mRNA targeting DNAzyme in patients with TH2-driven asthma

No major safety concerns were identified in a rigorous toxicology program for this drug candidate,6 no off-target effects were identified,7 and intranasal administration to mice resulted in rapid lung tissue distribution.8 A human whole blood assay further excluded immunotoxic effects of the novel drug candidate (see the Methods section and Figs E2 and E3 in this article's Online Repository at www.jacionline.org), and an appropriate nebulization system was identified and characterized for inhaled drug application (see the Methods section, Fig E4, and Table E1 in this article's Online Repository). The primary objective of the 3 phase I studies reported here (a first-in-human/first-in-class single-dose study in healthy subjects, a multiple-dose study in healthy subjects, and a single-dose study in asthmatic patients; Fig 1, A) was to assess the safety and tolerability of ascending doses of inhaled SB010, the active pharmaceutical ingredient of which is the GATA-3-specific DNAzyme hgd40 (for details of the drug product and active pharmaceutical ingredient, see the Methods section in this article's Online Repository).