ASLAN Pharmaceuticals, 400 Concar Drive, San Mateo, CA, USA.
ASLAN Pharmaceuticals, 400 Concar Drive, San Mateo, CA, USA.
Clin Immunol. 2023 Aug;253:109677. doi: 10.1016/j.clim.2023.109677. Epub 2023 Jun 12.
Eblasakimab is a first-in-class monoclonal antibody under investigation for the treatment of atopic dermatitis (AD), which targets IL-13Rα1, a subunit of the Type 2 receptor complex. IL-13Rα1 stimulates phosphorylation of signal transducer and activator of transcription 6 (STAT6) to drive inflammation. This brief report investigates the mechanistic basis of eblasakimab and its effects on IL-13Rα1 signaling as part of a phase 1a, open-label, single ascending dose study. Single ascending doses of eblasakimab were administered by intravenous or subcutaneous injection to healthy male volunteers. The impact of eblasakimab on IL-13Rα1 receptor occupancy and STAT6 phosphorylation was assessed in participant blood monocytes. No serious treatment emergent adverse events were reported. Eblasakimab effectively blocked the IL-13Rα1 receptor and inhibited STAT6 phosphorylation with single doses of 3 mg/kg intravenously and 300 mg subcutaneously. Results support further clinical development of eblasakimab as a novel biologic for AD, with potential for 2- to 4-week dosing regimens.
依巴斯单抗是一种研究用于治疗特应性皮炎(AD)的首创类单克隆抗体,其靶向 2 型受体复合物的 IL-13Rα1 亚基。IL-13Rα1 刺激信号转导和转录激活因子 6(STAT6)的磷酸化,以驱动炎症。本简要报告调查了依巴斯单抗的作用机制及其作为 1a 期、开放标签、单次递增剂量研究的一部分对 IL-13Rα1 信号的影响。依巴斯单抗通过静脉或皮下注射给予健康男性志愿者单次递增剂量。在参与者的血液单核细胞中评估依巴斯单抗对 IL-13Rα1 受体占有率和 STAT6 磷酸化的影响。未报告严重的治疗相关不良事件。依巴斯单抗以 3mg/kg 静脉内和 300mg 皮下单次剂量有效阻断 IL-13Rα1 受体并抑制 STAT6 磷酸化。结果支持依巴斯单抗作为 AD 的新型生物制剂的进一步临床开发,具有 2 至 4 周给药方案的潜力。