Table I.

Cellular characterization of PRN473 confirms selectivity and limited off-target effects

TargetCell Type and AssayIC50 ± SD (nM)
On-target activity
 BTKB cell: Ramos occupancy30 ± 15
 FcγRMonocyte: IgG activation76 ± 40
 FcεRBasophil: IgE activation in human whole blood1130 ± 510
 FcεRMast: IgE degranulation and β-hexosaminidase release89
 FcεRMast: IgE degranulation and histamine release175
 BCRB cell: human whole blood activation274 ± 95
 BTKBTK occupancy in human whole blood364 ± 112
Off-target activity
 TCRT cell: T cell activation in human whole blood>7900
 EGFRCellular reporter assay> 5000
 CytotoxicityHCT-116 cells>20,000
  • PRN473 target specificity (measured by IC50 levels) was determined using cells selected based on the presence/absence of BTK, BCR, FcR, and non–BTK-related functions. Results of cell-based target specificity assays showed that PRN473 inhibits B cell activation and Fc receptor signaling, demonstrates durable BTK inhibition, shows an absence of cytotoxic effects, and has limited functional effects on T cells and other non–BTK-dependent cellular pathways.