Supplementary Figures 1 through 7 from Discovery and Optimization of HKT288, a Cadherin-6–Targeting ADC for the Treatment of Ovarian and Renal Cancers

Supplementary Figure 1. Schematic of high-content imaging-based internalization assay. Supplementary Figure 2. OVCAR3 xenografts were grown subcutaneously in NSG mice and treated with a single i.v. dose of 10 mg/kg control IgG1 or CDH6-targeting antibodies conjugated to SMCC-DM1. Supplementary Figure 3. Tumors of the PDX model HOVX2263 were grown subcutaneously in female nude mice randomized into groups of equal mean tumor volume and treated every two weeks with a 5 mg/kg i.v. dose of either IgG1-SPDB-DM4, or CDH6-targeting antibodies conjugated to SPDB-DM4. Supplementary Figure 4. Interaction analysis of anti-CDH6 antibody and CDH6 ECD protein. Supplementary Figure 5. Unenrolled NSG mice bearing OVCAR3 tumors from a separate efficacy study were allowed to grow to ~600 mm3 before being treated with either IgG1-SPDB-DM4 or CDH6-SPDB-DM4 at 8.5 mg/kg i.v. on day 34 post implant and re-dosed as indicated by arrows. Supplementary Figure 6. Representative CDH6 IHC images of the OVCAR3 subcutaneous xenograft grown in NSG mice (A), OVCAR3Luc intraperitoneal xenograft grown in SCID beige mice (B), HOVX2263 ovarian PDX subcutaneous xenograft grown in female nude mice (C), and HOVX4863 ovarian PDX subcutaneous xenograft grown in female nude mice (D). Supplementary Figure 7. (A) Correlation plot of response to HKT288 by best average response vs. CDH6 RNA expression. (B) Waterfall plot of percent best average response to CDH6-sulfoSPDB-DM4 treatment in PCT.