Mechanism of Action

ENHERTU is a specifically engineered HER2-directed antibody-drug
conjugate (ADC)1,2

HER2-targeted antibody-drug conjugate

HER2-directed mAb1

  • Provides targeted
    delivery of cytotoxic agent1,2
  • Consists of the same
    amino acid sequence
    as trastuzumab3
HER2-targeted antibody-drug conjugate

Topoisomerase I inhibitor payload1,2,a

  • Highly potent payload is an exatecan derivative, known as DXd, with a short systemic half-life1,3
  • Upon release, membrane-permeable payload causes DNA damage and cell death, resulting in destruction of HER2+ tumor cells and surrounding cells of variable HER2 expression, known as the bystander antitumor effect1,3,4

Tumor-selective cleavable linker1-3,4,a

  • Attaches payload to the antibody1
  • Linker-payload is stable in plasma2,3
  • Linker selectively cleaved by enzymes that are upregulated in tumor cells1,3

ENHERTU has a homogeneous and high
drug-to-antibody ratio of ~8 molecules of
cytotoxic agent per antibody1-3,a

aBased on in vitro and in vivo non-clinical studies. The clinical relevance of these features is under investigation.

DNA, deoxyribonucleic acid; HER2, human epidermal growth factor receptor 2; mAb, monoclonal antibody.

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