<h4>Introduction</h4>Opaganib is a first-in-class oral sphingolipid metabolism inhibitor that inhibits sphingosinekinase 2 (SphK2) and dihydroceramide desaturase (DES) and that has a demonstrated safety and preliminary anti-cancer activity signal in a Phase I study.<h4>Methods</h4>In this phase II trial, patients with metastatic castration-resistant prostate cancer who had disease progression on novel hormonal agents (NHAs) abiraterone or enzalutamide were enrolled and treated with opaganib while continuing their NHA. The gene discussed is SPHK2; the disease is cancer.