Immunome presents preclinical data on ADC payload HC74

Immunome (IMNM) presented preclinical data showing its proprietary antibody-drug conjugate payload HC74 overcomes multiple mechanisms of ADC resistance, including payload efflux and target heterogeneity. HC74 is a novel topoisomerase I inhibitor that serves as the payload in IM-1021, a ROR1-targeted ADC currently in a Phase 1 trial for solid and liquid tumors, and as the payload in several preclinical candidates within the Immunome pipeline. The data were presented on Oct. 23, 2025, in a poster entitled “HC74, a novel topoisomerase I inhibitor payload for antibody-drug conjugates that overcomes multi-drug resistance” at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in Boston. Highlights of the poster include: Over-expression of drug efflux transporters such as ABCC1 and ABCB1 drives primary and acquired resistance to approved ADC payloads and standard chemotherapies but not to HC74; HC74 exhibits high membrane permeability, leading to enhanced cytotoxicity and robust bystander activity; ADCs incorporating HC74 show meaningful efficacy in multiple preclinical tumor models, including: Colorectal cancer refractory to trastuzumab-DXd and irinotecan; Models with acquired resistance to trastuzumab-DXd; Non-small cell lung cancer with heterogenous target expression. “HC74 is designed to overcome key limitations of existing ADC payloads,” said CSO Jack Higgins. “Clinical data show high levels of efflux transporters and target heterogeneity can reduce ADC efficacy. We believe HC74’s ability to overcome those resistance mechanisms supports its potential as a best-in-class payload. We look forward to advancing IM-1021 and our broader HC74 pipeline.”