Introduction/Background: Biomarker-defined clusters of severe asthma patients were previously identified via hierarchical cluster analysis; a cluster of older females with low-to-medium Type 2 (T2) biomarkers was characterized (Denton, E. et al. J Allergy Clin Immunol Pract 2021;9:2680-8.e7). Aims and Objectives: To describe biomarker-defined clusters (blood eosinophil counts [BEC], FeNO, and serum IgE [IgE]) in severe asthma patients, and characterize T2-low asthma using a model-based approach to clustering. Methods: Patients in the International Severe Asthma Registry (ISAR) with biomarker data were included, regardless of biologic use. A Gaussian finite mixture model was used to perform cluster analyses using BEC, FeNO and IgE standardized by z score. The prespecified thresholds for low biomarkers were BEC <300cells/µL, FeNO <25ppb and IgE <75 IU/mL. Results: Of 4459 patients, five clusters were identified. Cluster 1 had females with low T2 biomarkers. Cluster 2 had high BEC and FeNO; Cluster 3, triple T2 biomarker high; Cluster 4, high BEC; Cluster 5, high IgE. Figure: Median (IQR) biomarker levels and characteristics of clusters. Conclusions: In line with previous findings, a cluster with females and low biomarkers suggested low T2 involvement. The other 4 clusters varied in biomarker elevations, highlighting the complexity of T2 inflammatory involvement in severe asthma.