Late Breaking Abstract - Sustained suppression of type 2 inflammatory biomarkers in asthma with APG808, a half-life extended anti-IL-4Rα monoclonal antibody

Introduction: APG808 is a novel anti-IL-4Rα monoclonal antibody that inhibits IL-13- and IL-4-mediated signaling. Findings from a first-in-human study in healthy volunteers demonstrated safety and tolerability of APG808 across dose groups and optimized pharmacokinetics of APG808 with potential for dosing once every 6 to 8 weeks. Aim: To evaluate the safety of multiple doses of APG808 and the effect on type 2 (T2) inflammatory biomarkers in asthma. Methods: This phase 1b, multiple-dose, randomized, double-blind, proof-of-mechanism study included 22 participants with mild-to-moderate asthma and baseline elevated fractional exhaled nitric oxide (FeNO; ≥25 ppb), a marker of airway inflammation. Participants were randomized 3:1 to receive subcutaneous APG808 600 mg or placebo on days 1 and 29. Safety, FeNO and other pharmacodynamic biomarkers were assessed at multiple timepoints. Results: Through 12 weeks of available follow-up, multiple doses of APG808 were well-tolerated in participants with asthma. There were no severe adverse events. Multiple doses of APG808 resulted in rapid suppression of FeNO, with maximal reduction from baseline of 53%, and maintained >30 ppb reduction from baseline through week 12. APG808 treatment led to rapid and near-complete suppression of pSTAT6 and reduction of TARC through week 12. Conclusion: In a multiple-dose study in participants with mild-to-moderate asthma, APG808 demonstrated a favorable safety profile consistent with the anti-IL-4Rα class. The optimized PK profile, together with durable suppression of FeNO, a T2 biomarker associated with asthma exacerbations, supports continued clinical development of APG808.