LQ036 is an inhalable homogeneous bivalent anti IL-4R? single domain antibody. Phase I single-ascending dose (SAD) and multiple-ascending dose (MAD) study were conducted in healthy volunteers to evaluate the safety, tolerance, pharmacokinetics (PK) and systemic IL-4R? target engagement of LQ036. In SAD study, LQ036 was delivered by oral inhalation with a nebulizer at 5 different doses (1mg, 4mg, 10mg, 20mg and 40mg). And in MAD study, LQ036 was inhaled at 3 different doses (4mg, 10mg and 20mg), once daily for 10 days.

LQ036 was found to be safe and well tolerated when orally delivered at all dose groups. No treatment-related serious adverse events were reported in this study. Moreover, there were no treatment related anti-LQ036 antibodies found in the serum of all participants. Systemic LQ036 exposure was found dose-dependently from ?4mg, with the peak systemic exposure occurring between 6.2-8.5 hours post inhalation. Systemic LQ036 was cleared quickly by the renal infiltration, with mean T1/2 about 7 hours. Otherwise, circulating LQ036 engagement was determined ex vivo by inhibition of IL-4 stimulated pSTAT6 in whole blood, with an obvious whole blood pSTAT6 level inhibition lasting for 48 hours from delivered dose ?4mg. And near complete inhibition of whole blood pSTAT6 level was found at 40mg dose cohorts. Considering the clinical validated corelation between whole blood pSTAT6 level and FeNO value, it would reasonable to conclude that LQ036 would greatly inhibit the FeNO in asthma patients. The overall profile of LQ036 illustrates its suitability for development as a promising inhaled therapy for the treatment of asthma.