Enhertu®/DS-8201, an ADC targeting HER2, has been extensively utilized in the treatment of various tumor types. This includes HER2-positive and HER2-low expressing breast cancer, HER2-mutated non-small cell lung cancer, and HER2-positive gastric cancer. Despite its significant success as a breakthrough therapy, there is still a considerable unmet clinical need in patients with HER2-low expression and those who develop secondary resistance.
The dual targeting of EGFR and HER2 is a promising approach to address these challenges, as both are oncogenes that are widely co-expressed in tumors. In response, we have developed the candidate, an EGFR x HER2 bispecific ADC. This novel ADC features a highly stable yet cleavable linker and a potent topoisomerase 1 inhibitor as the payload.
In comparison to DS-8201, the candidate has shown superior in vitro plasma stability and stronger tumor cell binding and internalization activity. It also demonstrates potent direct cytotoxic and bystander killing effects on tumor cells. In multiple mouse CDX models, the candidate has exhibited significantly better in vivo antitumor effects than DS-8201.
These findings indicate that the candidate holds substantial therapeutic potential across a range of tumor types. These include urothelial carcinoma, lung cancer, gastric cancer, colorectal cancer, ovarian cancer, and breast cancer.
To summarize, the candidate has competitive advantages: (1) Better efficacy than single-target ADCs; (2) Overcoming tumor heterogeneity and drug resistance; (3) Lower off-target toxicity due to a stable linker; (4) Therapeutic potential in multiple types of solid tumors.
If you are interested in this candidate, please contact DrugTimes BD Team at BD@drugtimes.cn.
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