A specialty pharma company at the Phase II/III transition faced an existential enrollment math problem: 420 patients required, 12,000 diagnosed in the US, thirty-six months to enroll, and three-and-a-half years of cash runway. Synthetic phenotyping and trial design modeling identified a patient enrichment strategy that reduced the projected Phase III enrollment requirement by 34% — saving an estimated eighteen months and $90M in trial execution costs. The company preserved its independence instead of diluting founders' equity by 60%.