Immunome, Inc. (NASDAQ:IMNM), a biotechnology company focused on developing first-in-class and best-in-class targeted cancer therapies, recently presented preclinical data showing its proprietary antibody-drug conjugate (ADC) 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