Late Breaking Abstract - Efficacy of a monoclonal antibody against IL-25 in human allergic asthma: an open-label, single-arm, phase Ic study

Background: Interleukin-25 (IL-25) is a key upstream regulator of type 2 immunity. XKH001, an anti-IL-25 neutralizing antibody, has shown significant therapeutic effects in murine asthma models. Methods: This open-label, single-arm, phase Ic study enrolled 12 patients with mild allergic asthma. Participants underwent methacholine challenge testing and received subcutaneous injections of XKH001 every four weeks. Results: Among patients with moderate-to-severe baseline airway hyperresponsiveness (AHR), XKH001 treatment increased the methacholine PD20-forced expiratory volume in 1 second (FEV1), indicating improvement in AHR. Treatment also significantly reduced eosinophils, TARC, and eotaxin levels in induced sputum. Notably, patients with higher baseline AHR exhibited greater reductions in peripheral blood eosinophils, eotaxin, and IL-8. Conclusions: This study provides the first clinical evidence supporting IL-25 as a therapeutic target in patients with moderate-to-severe asthma. erj;66/suppl_69/PA5681/TB1 T1 TB1 Table 1. Demographic and Clinical Characteristics of the Patients at Baseline Characteristic XKH001(N=12) Age — yr 31.80 ± 9.81 Male sex — no. (%) 6 (50.0) Duration of asthma —yr 11.46±12.98 FEV1 — Percent of predicted value 87.11 ± 10.26 Methacholine PD20 — mg 0.30±0.29 Sputum eosinophils — % 6.86±12.13 Blood eosinophils — ×109/liter 0.38±0.24 erj;66/suppl_69/PA5681/F1 F1 F1