LAUSR

The first‐in‐human phase I study for E6742, a dual toll‐like receptor (TLR) 7 and TLR8 antagonist, has been conducted to assess the safety, tolerability, and pharmacokinetics of E6742 in healthy volunteers. In a single ascending dose (SAD) study, 42 subjects received 10–800 mg of E6742 in the fasted state, as well as a 100‐mg cohort in the fed state for evaluating the effect of food. In a multiple ascending dose (MAD) study, 18 subjects received 100–400 mg of E6742 twice daily for 7 days. E6742 was rapidly absorbed with a median tmax ranging from 1.50 to 2.50 hours across dose groups under the fasted condition, and eliminated with a median t½ ranging from 2.37 to 14.4 hours. After multiple oral doses, a steady state was reached by day 7. In the SAD study, dose proportionality was observed for Cmax, AUC(0‐t), and AUC(0‐inf) values of E6742 up to 800 mg, but these values were slightly less than dose proportional at 10 mg. In the MAD study, the Cmax and AUC(0‐12h)ss of E6742 appeared to be almost dose proportionally increased between 100 and 200 mg, while these parameters showed more than a dose proportional increase at 400 mg. In addition to safety and good tolerability, this study demonstrated cytokine concentrations in cultured peripheral blood in response to E6742 were suppressed in a dose‐dependent manner. Further clinical studies targeting systemic lupus erythematosus patients are currently underway.