Fig. 5. ISB 1442 shows improved tumor growth inhibition compared to daratumumab in preclinical mouse models.

A. CB17/SCID mice (N = 5) engrafted with Raji cells (CD38^high) randomized on D12 and treated intravenously immediately with ISB 1442 at 10 mg/kg weekly, daratumumab at 16 mg/kg twice weekly and PBS (vehicle). B CB17/SCID mice (N = 5) engrafted with KMS-12-BM cells (CD38 ^low) randomized on D15 and treated immediately with ISB 1442 at 10 mg/kg weekly, daratumumab at 16 mg/kg biweekly and PBS (vehicle). C CB17/SCID mice engrafted with Raji cells treated twice weekly with daratumumab at 16 mg/kg intravenously (i.v.), and ISB 1442 at 3 mg/kg both intravenously (i.v.) and subcutaneously (s.c.). D Kaplan–Meier survival curve for experiment shown in panel C excluding 3 mice taken randomly for terminal analysis from each group at D15 unless they had reached the experimental endpoint (N = 6–9), survival endpoint was deemed to be reached when animals exceeded maximum permissible tumor volume of 1000 mm³. E Trough PK samples from 21 days post randomization (3 days post last dose) of study shown in (C, D). F PK time course at 1 and 10 mg/kg doses of ISB 1442 subcutaneously (s.c.) and intravenously (i.v.) in BALB/c nude mice (N = 4). Statistical evaluation by 1-way ANOVA followed by Tukeys post hoc test on final day of experiment prior to the humane endpoint for the second mouse in any group (A–C). Log Rank (Mantel Cox) test used to evaluate significance of difference in (D). P values for tests presented on (A–C) A P = 0.0076, B P = 0.0009, C P = 0.016 (IV vs. Dara) 0.0222 (SC vs. Dara) Ns: not significant, *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001.