Use Of Payload Core Compounds To Accelerate ADC Clinical Development Timelines

Payloads are crucial in determining the effectiveness of Antibody-Drug Conjugate (ADC) drugs. While over forty natural product classes have been utilized as payloads, most ADCs that have entered the clinic incorporate derivatives of two natural products: dolastatinin 10 and maytansine. The use of these natural products in ADCs has advanced targeted cancer therapy and the development of more effective treatments.

Accessing the desired payload poses challenges for ADC developers due to the complex synthesis process, which is more labor-intensive compared to other small molecules. The use of a GMP-quality payload intermediate as a starting point for payload synthesis enables a more efficient process for research and process development chemists and chemistry, and CMC teams. These intermediate compounds are the core of the active ingredients of Dolastatin 10 and maytansine natural products. Starting the synthetic route with a core compound accelerates the synthesis process, enabling the evaluation of a wider range of compounds. This approach also shortens the synthetic route, expediting the path to clinical trials.

Novel compounds are typically synthesized in-house or with the assistance of a contract development and manufacturing organization (CDMO).