Abstract 4397: Development of antibody-drug conjugate technology based on novel linkers & DNA alkylating duocarmycin derivatives

Antibody-Drug Conjugation (ADC) is gaining momentum as a next generation antibody therapeutics approach in oncology. Tumor specific delivery of the cell-killing agent maximizes the agent9s potency while avoiding damage to healthy tissue resulting in a high therapeutic window. Syntarga9s Potent Payload Technology comprises the combination of highly potent DNA-alkylating duocarmycin derivatives and suitable linker technologies. Duocarmycin analogs and the CC-1065 derivatives represent a class of highly potent, cell-killing, DNA-alkylating, minor groove binding agents. This class is suitable to target solid tumors and has not been associated with Multi-Drug Resistance (MDR). Strong in vivo Proof of Concept with Potent Payload ADCs has been obtained against multiple targets. In human tumor xenograft models, substantial efficacies have been obtained based on single dose treatments, with minimal or absent side effects. We discuss applicability and several other aspects of multiple, validated Potent Payload-based Antibody-Drug Conjugates (ADCs). Latest results of preclinical development progress (in vivo efficacy, safety, etc.) will be presented, including drug potencies, linker stability and therapeutic window aspects for ADCs directed against HER2. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4397.