Late Breaking Abstract - Efficacy Of Csj117 On Allergen-Induced Asthmatic Responses In Mild Atopic Asthma Patients

Introduction: CSJ117 is a potent neutralizing antibody fragment against human Thymic stromal lymphopoietin (TSLP), formulated as a PulmoSol™ engineered powder in hard capsules for delivery to the lungs via dry powder inhaler. Methods: In this double-blind, placebo-controlled study, 28 mild, atopic asthmatics meeting elibility criteria were randomized to receive 4mg CSJ117 (n = 15) or placebo (n = 13) inhaled daily for 12 weeks. Allergen inhalation challenge (AIC) was conducted at screening, day 42 and day 84. The primary efficacy variable was the late asthmatic response (LAR), measured 3 to 7 hours after AIC at day 84. Other outcomes included the early asthmatic response (EAR) measured within 2 hours after AIC, fractional exhaled nitric oxide (FeNO) level, and sputum eosinophils. Data were analyzed using repeated measures ANCOVA (β=10%) and one-sided tests (α=10%). Results: CSJ117 attenuated allergen-induced LAR and EAR at day 84. The time-adjusted AUC percentage decrease and the maximum decrease in FEV1 from pre-AIC were lower in the CSJ117 group compared to placebo (4.20% vs 11.38%, p = 0.008, and 9.28% vs 17.70%, P=0.029, during LAR; 12.83% vs 17.09%, P = 0.097, and 25.48% vs 30.90%, P = 0.105, during EAR). CSJ117 significantly attenuated the allergen-induced increase in % sputum eosinophils after AIC on day 84. CSJ117 significantly reduced FeNO before AIC at Day 83, but not the allergen-induced change. Conclusion: CSJ117 reduced allergen-induced bronchoconstriction and sputum eosinophilia, and pre challenge FeNO levels. These findings demonstrate CSJ117’s ability to attenuate airway inflammation in allergic asthmatics and support further studies as an inhaled anti-TSLP.