The advent of many creative and innovative therapeutic platforms such as antibody-drug conjugates (ADC), bispecific proteins as T cell engagers (BiTEs, DARTs, BisAbs, etc), scFv, CAR-T and many others have provided a plethora of new potential therapeutic options for patients.  While these new innovative platforms may show great promise for patients they also present unique development challenges to the biopharm industry, especially in the areas of constructing and executing a preclinical safety program that will help to understand and mitigate the safety risks, determination of the starting dose in first-in-human trials of these very potent agents, understanding how target and disease burden play a role in patient selection and safety assessment and ultimately, how all of this is taken into account by Health Authorities around the world.