Supplementary Figures 1 through 10 and Supplementary Tables 1 through 3 from MM-141, an IGF-IR– and ErbB3-Directed Bispecific Antibody, Overcomes Network Adaptations That Limit Activity of IGF-IR Inhibitors

PDF - 711K, Supplemental Figure S1. Schematic representation of components of IGF-1R/ErbB3 merged mechanistic signaling model. Supplemental Table S1. Mean ligand-stimulated pAKT (S473) levels (A) or simulated levels (B) in BxPC-3, AdRr and MCF7 cells that were used to generate 3D contour plots in Figure 1A. Supplemental Figure S2. Western blots used to generate bar graphs in Figures 1, 3, & 4. Supplemental Figure S3. MM-141 is selective for IGF-1R and ErbB3, and is cross-reactive to relevant toxicology species. Supplemental Table S2. MM-141 is more potent than monospecific antibodies at inhibition of single ligand-induced pAKT (Ser473) signaling. Supplemental Figure S4. MM-141 does not promote basal signaling. Supplemental Figure S5. Generation of isogenic BxPC-3 cell lines with stable knockdown of IGF-1R or ErbB3. Supplemental Table S3. Mean pAKT (S473) levels in engineered BxPC-3 cells that were used to generate 3D contour plots in Figure 3A. Supplemental Figure S6. MM-141 maintains activity over a broad range of receptor profiles. Supplemental Figure S7. Mechanistic model can recapitulate signal inhibition properties of MM-141. Supplemental Figure S8. Pharmacokinetic properties of MM-141. Supplemental Figure S9. MM-141 controls gemcitabine-induced network adaptation. Supplemental Figure S10. MM-141 controls expression of IGF-1R and ErbB3-interacting RTKs.