Exatecan is a semisynthetic derivative of the camptothecin class of compounds. It inhibits topoisomerase I (TOP1), leading to DNA damage and ultimately triggering apoptosis. Exatecan derivatives have been incorporated into next-generation antibody–drug conjugates (ADCs), such as Deruxtecan (DXd). DXd has the same core structure as Exatecan, with a cleavable tetrapeptide linker composed of glycine–glycine–phenylalanine–glycine (GGFG).
Trastuzumab deruxtecan (brand name Enhertu), developed by Daiichi Sankyo in collaboration with AstraZeneca, is the first FDA-approved ADC using the Exatecan derivative payload. It was approved in 2020 for the treatment of HER2-positive metastatic breast cancer and later expanded to HER2-low breast cancer and other HER2-expressing solid tumors. The ADC has an average drug-to-antibody ratio (DAR) of approximately 8.
The AqT®-Exatecan (CM81314) drug asset is currently available for partner evaluation using site-specific labeling with a releasable VC-PAB linker. This drug asset enables the efficient loading of up to eight drug molecules per antibody with minimal aggregation.