Late Breaking Abstract - Early improvement in asthma small airway dysfunction after one dose of SAR443765, a novel bispecific anti-thymic stromal lymphopoietin/anti-IL-13 nanobody molecule

Introduction: SAR443765 is a novel anti-thymic stromal lymphopoietin (TSLP)/anti-IL-13 engineered antibody (nanobody molecule) shown to significantly and rapidly reduce FeNO in patients with mild-to-moderate asthma after one dose.¹ Combined TSLP/IL-13 blockade is expected to improve lung function, particularly small airway dysfunction, which have been shown to correlate with poor disease control and type 2 inflammation. Aims/Objectives: To assess the effects of SAR443765 in asthma. Methods: In a Phase 1 randomized, controlled study (NCT05366764), 36 patients with mild-to-moderate asthma received one subcutaneous SAR443765 400 mg dose. Lung physiology was assessed via spirometry and forced oscillometry technique for up to 57 days. Results: Rapid FEV₁ improvement was observed after a single dose of SAR443765 (maximal at Day 8 and largely maintained to Day 57), reflected in reduced respiratory resistance at 5Hz. Positive SAR443765 effects were also observed in forced expiratory flow at 25%–75%, oscillometry resistance heterogeneity (R5-20), and reactance area (AX), particularly in patients with impaired baseline lung function, consistent with improvement in small airway dysfunction. Conclusions: A single dose of the novel anti-TSLP/anti-IL-13 biologic nanobody molecule SAR443765 improved lung function and small airway dysfunction in asthma. These effects surpass those reported for monovalent IL-13 or TSLP pathway targeting and suggest potential for superior effects in patients with asthma. Study and medical writing funded by Sanofi ¹Deiteren et al. ATS 2023.