Figure 4

Evidence of hepatotoxicity in investigative study comparing recombinant cynomolgus monkey and human Apo2L/TRAIL. (a) Study design schema. Black arrows indicate days of rhuApo2L/TRAIL or rcynoApo2L/TRAIL administration (100 mg/kg; days 1–5, 22–26, 43–47 and 64–68 (n=4–9/sex/group)); blue arrows outlined in red indicate timing of blood sampling for clinical pathology (CP) and ATA/crosslinking activity analyses; blue arrows indicate timing of blood sampling for CP analysis; red arrows indicate timing of blood sampling for ATA/crosslinking activity analyses. Blue diamonds indicate timing of physical examinations. TN, terminal necropsy; RN, recovery necropsy. (b) ALT elevations following treatment with 100 mg/kg rcynoApo2L/TRAIL. (c) ALT elevations following treatment with 100 mg/kg rhuApo2L/TRAIL. (d) Individual animal data showing the correspondence between ALT (bars), ATAs (blue triangles) and crosslinking ATAs (red circles) on study days 21, 29, 42 and 50 following treatment with 100 mg/kg rcynoApo2L/TRAIL. (e) Individual animal data showing the correspondence between ALT (bars), ATAs (blue triangles) and crosslinking ATAs (red circles) on study days 21, 29, 42 and 50 following treatment with 100 mg/kg rhuApo2L/TRAIL