Mechanism of Action

ENHERTU is a specifically engineered HER2-directed antibody-drug
conjugate (ADC)3,4

HER2-directed mAb3

  • Provides targeted
    delivery of cytotoxic
    agent3,4
  • Consists of the same
    amino acid sequence
    as trastuzumab5

Topoisomerase I inhibitor payload3,4,a

  • Highly potent payload is an exatecan derivative, known as DXd, with a short systemic half-life3,5
  • 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 effect3,5,6

Tumor-selective cleavable linker3-5,a

  • Attaches payload to the antibody3
  • Linker-payload is stable in plasma4,5
  • Linker selectively cleaved by enzymes that are upregulated in tumor cells3,5

ENHERTU has a homogeneous and high
drug-to-antibody ratio of ~8 molecules of
cytotoxic agent per antibody3-5,a,b

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

bADCs are a mixture of molecules in which the DAR is variable. Homogeneity of DAR refers to a mixture where there is low variability of DAR; the payload number per antibody falls into a narrow range.5

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DAR, drug-to-antibody ratio; DNA, deoxyribonucleic acid; HER2, human epidermal growth factor receptor 2; mAb, monoclonal antibody.