B32-36 IBI3002, A First-in-class Anti-IL-4RΑ/TSLP Bispecific Antibody in Patients With Mild-To-Moderate Asthma: A Randomized, Double-Blind, Placebo-Controlled, Single Dose Phase Ib Study

Abstract Rationale IBI3002 is a humanized bispecific antibody targeting interleukin-4 receptor α (IL-4Rα) involved in IL-4 and IL-13 signaling, and thymic stromal lymphopoietin (TSLP), an epithelial cell-derived cytokine implicated in multiple downstream processes in asthma pathophysiology. In preclinical studies, IBI3002 effectively suppressed airway inflammation and alleviated asthma in vivo (ATS 2025, #801). A phase Ib randomized, double-blind, placebo-controlled study (NCT06213844) was conducted to evaluate the safety, tolerability, and pharmacodynamics of IBI3002 in patients with mild-to-moderate asthma. Methods Participants with mild-to-moderate asthma, aged between 18-65 years, and an elevated Fractional exhaled Nitric Oxide (FeNO) ≥25ppb were randomized (6:2) to a single dose of 1200 mg IBI3002 or placebo, administered subcutaneously. Their asthma had to be well controlled for at least 3 months prior to randomization with stable doses of inhaled medication. Spirometer and FeNO assessments were performed pre-dose, 24h and on days (d) 8, 15, and 36. Primary endpoints were safety and tolerability through till d36, and pharmacokinetic measures were secondary endpoints. Results Eight participants were enrolled to receive 1200 mg IBI3002 (n = 6) or placebo (n = 2). The median age was 25 years (range: 20─53) and seven participants were Caucasian. The mean baseline pre-bronchodilator (pre-BD) forced expiratory volume in 1 second (FEV1) and FeNO were 3.52L and 81ppb, and 3.07L and 67ppb, in the placebo and IBI3002 groups, respectively. Two participants receiving IBI3002 reported treatment-emergent adverse events: one with presyncope and sciatica, and another with back pain and ecchymosis, of which only ecchymosis was assessed as related to treatment. All TEAEs were mild in severity. No serious adverse events were observed. None developed anti-IBI3002 antibody positivity through till d36. Compared with placebo, participants with IBI3002 showed greater improvements in pre-BD FEV1 (mean change from baseline to d36: −0.15L vs + 0.18L) and FeNO (−15ppb vs − 38ppb), as well as greater reductions in eosinophils (mean percentage change from baseline to d36: −12.50% vs − 46.53%) and immunoglobulin E (+8% vs − 13%). Conclusions IBI3002 was well tolerated and demonstrated a favorable safety profile, with preliminary signals in improving lung function and reducing airway inflammation in participants with mild-to-moderate asthma. This abstract is funded by: Innovent biologics