Pharmacokinetics, pharmacodynamics, and safety of HE009, a novel selective S1P1 receptor modulator, in healthy Chinese subjects

HE009, a novel selective sphingosine-1-phosphate receptor-1 (S1P1) modulator, was evaluated in healthy Chinese subjects to assess its pharmacokinetics, pharmacodynamics, and safety profile. This randomized, placebo-controlled phase I study comprised single ascending dose (SAD, 0.05–4.0 mg), multiple ascending dose (MAD, 0.5–3.0 mg), dose titration, and food effect components. HE009 exhibited dose-proportional exposure, with T_maxof 4–6 h and t_1/2 of 16–24 h, supporting once-daily dosing. Steady-state was achieved by day 7 with minimal accumulation (1.7–2.0 fold). A clear concentration-effect relationship was observed, with maximum lymphocyte count reductions of 58% (SAD) and 70–80% (MAD). Notably, HE009 demonstrated a favorable cardiac safety profile, with transient, asymptomatic bradycardia mitigated by dose titration. No events related to hypertension were observed during the study period. These findings suggest HE009 offers potential advantages in efficacy, safety, and dosing flexibility compared to existing S1P receptor modulators for treating autoimmune disorders like systemic lupus erythematosus. The trial was registered on the Chinese Clinical Trial Registry, (Identifier No. ChiCTR2200066345), Registered December 1, 2022.