Most organizations start with something genuinely promising a strong hypothesis, a compelling mechanism, an innovative platform. The misalignment creeps in later, as that science moves toward regulatory review. An endpoint hits statistical significance without showing meaningful clinical benefit. A study population is broad enough to dilute a real treatment effect into noise. A biomarker that could have guided an early go/no-go decision shows up two years too late to matter. None of this requires anyone to make an obvious mistake. It happens through a series of individually defensible choices that drift, cumulatively, away from what regulators and payers are going to ask.