ABSTRACT D‐2570 selectively binds to the pseudokinase domain of tyrosine kinase 2, which mediates the downstream cytokine signaling pathways involved in immune regulation. The safety, tolerability, pharmacokinetics, and pharmacodynamics of D‐2570 were evaluated in a randomized, double‐blind, placebo‐controlled phase I study conducted in healthy Chinese subjects. The study consisted of three parts: single ascending dose (D‐2570: 3–48 mg once daily) study, multiple ascending dose (D‐2570: 6–36 mg once daily for 10 days) study, and food effect (D‐2570: 9 mg) study. D‐2570 was rapidly absorbed, with peak plasma concentration at around 4 h and exposure increased sub‐proportional across the dose groups. Following multiple dosing, mean terminal elimination half‐lives at steady state ranged from 22.22 to 33.86 h, with modest area under curve accumulation (1.74‐ to 2.08‐fold) showing no dose dependence. A high‐fat meal increased area under the concentration time curve from time zero extrapolated to infinite time and maximum plasma concentration by 33% and 15% for the 9‐mg dose, with no significant effect on median time to maximum concentration. The inhibitory effect of D‐2570 on the release of interferon‐gamma induced by interleukin‐12/interleukin‐18 increased dose‐dependently in the range of 6–36 mg. No deaths or serious treatment‐emergent adverse events occurred, and all the adverse events were Grade 1 or 2 in severity. D‐2570 was well tolerated in healthy Chinese subjects, and its pharmacokinetic profile was characterized. These results provide the rationale for dose selection in future clinical trials and support advancing D‐2570 as a potential treatment option for autoimmune diseases mediated by tyrosine kinase 2. Trial Registration: Chinadrugtrials.org.cn (CTR20222168)
Wang et al. (2026) studied this question.