This workshop examines one of the central tensions in ADC development, asking how potent is too potent. It explores whether increasing payload potency truly expands the therapeutic window or simply shifts toxicity into new and sometimes less predictable profiles. Through case based discussion, the session will analyze how DAR optimization, site specific conjugation, linker selection and payload characteristics collectively shape safety, efficacy and clinical usability

• Examine how payload permeability, linker stability and intracellular release location collectively determine safety margins and clinical feasibility
• Challenge the assumption that extreme payload potency is always required for ADC success, tracing where this paradigm originated and when it no longer holds
• Discuss trade‑offs between payload potency, off‑target toxicity, dosing flexibility, and clinical tolerability
• Explore practical strategies to balance potency, dosing flexibility and tolerability including mechanism selective payload design and refined conjugation approaches to improve therapeutic index