Fig. 4: OTX-2002 exhibits combinatorial efficacy with standard of care tyrosine kinase inhibitors, lenvatinib, in HCC.

A The effect of OTX-2002 on the lenvatinib response in HCC was evaluated through in vitro dose response studies of lenvatinib with increasing concentrations of HA-tagged OTX-2002-DS evaluated in Hep 3B (left) and SK-HEP-1 (right) cells. Results are from one independent experiment (Hep 3B, n = 6 technical replicates for all treatments; SK-HEP-1, n = 6 technical replicates for lenvatinib alone and combination with 0.06 ug/mL of OTX-2002, n = 4 technical replicates for lenvatinib combination with 0.6 ug/mL of OTX-2002) and were repeated once. B–E In vivo study using Hep 3B subcutaneous tumors to test combination of OTX-2002 plus lenvatinib. Hep 3B subcutaneous (B) tumor volume (two-way ANOVA with adjusted p-values for multiple comparisons; *P = 0.0162 and ns = not signficant) and (C) area under the curve (AUC; one-way ANOVA with adjusted p-value for multiple comparisons; **P = 0.0019 and *P = 0.0493) at the noted treatment conditions. Results are from one independent experiment (n = 8 mice per group) and were repeated once. D Bodyweight changes over course of the combination study in (B). E Survival curves for combination study in (B) with mice removed when they reached an endpoint of >1000 mm³. Significance measured using Log-rank (Mantel-Cox) test comparing OTX-2002 (***P = 0.001) or lenvatinib (**P = 0.0089) single agents to combination group. For all relevant panels error bars represent mean ± standard error of the mean (SEM). Source data are provided as a Source Data file.