AACR 2023: A First-In-Class Anti-HER2/TROP2 Bispecific Antibody-Drug Conjugate (YH012) Exhibits Potent Anti-Tumor Efficacy

AACR 2023: A First-In-Class Anti-HER2/TROP2 Bispecific Antibody-Drug Conjugate (YH012) Exhibits Potent Anti-Tumor Efficacy

Conclusions

  • HER2 and TROP2 are co-expressed in a wide range of tumor types. Of note, TROP2 was also expressed in many HER2-low solid tumors, such as HER2-low breast cancers, suggesting broad therapeutic indications of YH012.
  • YH012 demonstrated superior internalization compared to its parental monospecific Abs.
  • YH012 was shown to increase tumor cell specificity and minimize side effects in normal cells.
  • YH012 showed increased anti-tumor activity in both HER2-high and HER2-low CDX and PDX models, as well as durable efficacy than benchmarks, indicating that YH012 has strong therapeutic potential, especially in HER2-low expressing cancers.
  • By targeting dual TAAs, YH012 has the potential to increase tumor specificity and potency, reduce toxicity, and overcome tumor heterogeneity.
  • The backbone of YH012 molecule is constructed using RenLite plus knobs-into-holes technology, offering excellent BsAb assembly efficiency, good physicochemical properties and CMC developability.

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