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Introduction and Objectives In the phase 3 WAYPOINT study ( NCT04851964), tezepelumab demonstrated efficacy for the treatment of severe chronic rhinosinusitis with nasal polyps (CRSwNP). This analysis aimed to evaluate the effects of tezepelumab on inflammatory biomarkers in patients from the overall WAYPOINT population and those with comorbid asthma.Methods Patients with CRSwNP received tezepelumab 210 mg or placebo subcutaneously every 4 weeks for 52 weeks. This pre-specified exploratory analysis assessed changes from baseline in levels of serum IL-5 and IL-13, nasal lining fluid (NLF) IgE, plasma and nasal polyp eosinophil-derived neurotoxin (EDN), and neutrophil biomarkers plasma myeloperoxidase or elastase in nasal polyp tissue.Results 122/203 tezepelumab recipients and 126/205 placebo recipients had comorbid asthma. Baseline serum and NLF thymic stromal lymphopoietin (TSLP) levels were similar between treatment arms. Tezepelumab significantly reduced levels of all biomarkers, except those associated with neutrophils, compared with placebo in the overall population and in patients with comorbid asthma ( figure 1).Abstract S161 Figure 1Changes from baseline to week 52 in nasal polyp eosinophil-derived neurotoxin (A) and neutrophil elastase (B) levels overall and among patients with comorbid asthmaConclusion Tezepelumab reduced levels of type 2 inflammatory biomarkers compared with placebo in adults with severe CRSwNP, both in the overall study population and in patients with comorbid asthma.