Antibody-drug Conjugates with Novel Kinesin Spindle Protein Inhibitor Payloads and a Tailor-made Linker Chemistry

Abstract

With the approval of meanwhile five ADCs and more than 80 ADCs in clinical trials, the ADC landscape has developed rapidly during the last decade. However, as indicated also by the large number of ADCs which failed in the clinic, it remains challenging to achieve a sufficiently large therapeutic window in cancer patients. Furthermore, the identification of ADC payload classes with a novel mode of action would increase therapeutic options and potentially help to overcome resistance. Inhibitors of kinesin spindle protein (KSP/Eg5) have raised great interest because of their high antitumor potency which, however, could not be transferred into highly efficient clinical regimens due to dose limiting side effects such as neutropenia and mucositis.