Characterization of ABBV-319. (A) Analysis of CD19 and NR3C1 gene expression in normal tissues using GTEx data sets. (B) Analysis of CD19 and NR3C1 gene expression across different cancer indications using Aster ORIEN data sets. (C) Analysis of CD19 and NR3C1 gene expression in patients that are treatment naïve or post–R-CHOP treatment using Aster ORIEN data sets. Statistical analysis with Wilcoxon test. ns, not significant. (D) Structure of the GRM linker drug. (E) Fold change in GRE activity compared with the untreated control after treatment of K562 GRE reporter cells with prednisolone, dexamethasone, and GRM payload for 24 hours. Mean ± standard error of the mean (SEM) are depicted. (F) Summary of EC₅₀ for prednisolone, dexamethasone, and GRM payload across 20 glucocorticoid-sensitive cell lines. Each dot represents the log(EC₅₀) of a cell line and the median log(EC₅₀) is displayed. (G) Imaging analysis of CD19 localization after treatment of KARPAS422 with an Alexa Fluor 647-labeled ABBV-319 for the indicated time. Brightfield, LysoTracker (green), CD19 (red), and merged images are displayed. (H) The fold change in GRE activity relative to the untreated control after treating K562-GRE reporter cells with ABBV-319 for 24 hours. (I) Percentage viability of SU-DHL-6 cells relative to the untreated control after treatment with GRM payload, isotype-GRM ADC, and ABBV-319 for 5 days. (J) EC₅₀ of ABBV-319 across a panel of malignant B-cell lines with a range of E_max from supplemental Table 2. # denotes double-hit lymphoma (DHL) and ∗ denotes triple-hit lymphoma (THL) based on published annotations.²¹