The transition from preclinical to clinical testing is a pivotal moment in drug development. It’s also one of the most challenging development milestones, beset by unknown risks, unexpected data and potential regulatory hurdles to overcome. Therefore, proper planning for first-in-human (FIH) studies is critical, since missteps in trial design, CMC, or regulatory planning can cost millions and stall drug development timelines. Accordingly, it is important to apply practical strategies proven to move molecules efficiently through early clinical assessment, including innovative single ascending dose/multiple ascending dose (SAD/MAD) designs, diverse patient recruitment tactics and fundamentally sound CMC approaches. Doing so can help drug developers avoid common development pitfalls and confidently pursue a fast-tracked path to proof-of-concept (PoC) validation.