HC74

**HC74** is a proprietary novel topoisomerase I inhibitor payload designed for antibody-drug conjugates (ADCs), developed by Immunome, Inc. It exhibits enhanced potency (IC50=5nM vs. 20nM for deruxtecan across 89 cancer cell lines), high membrane permeability enabling robust bystander activity, faster hepatocyte clearance, superior permeability, and reduced efflux compared to deruxtecan. HC74 overcomes resistance mechanisms including efflux transporters (ABCC1, ABCB1), doxorubicin/vincristine resistance, and target heterogeneity, showing efficacy in preclinical models of mantle cell lymphoma, triple-negative breast cancer, colorectal cancer (refractory to trastuzumab-DXd/irinotecan), non-small cell lung cancer, and acquired resistance models.