DSP-0390: A Comprehensive Analysis of an Investigational Emopamil-Binding Protein Inhibitor for the Treatment of High-Grade Glioma

Executive Summary

This report provides a comprehensive analysis of the investigational therapeutic agent DSP-0390, a novel, orally administered small molecule being developed by Sumitomo Pharma Oncology, Inc. An initial query for "EBP-22" was determined to refer to this specific drug, an Emopamil-Binding Protein (EBP) inhibitor that received significant regulatory attention in 2022. DSP-0390 is being evaluated for the treatment of high-grade glioma (HGG), a group of aggressive brain tumors with a dire prognosis and a profound unmet medical need, particularly in the recurrent setting where no standard of care exists.

The therapeutic rationale for DSP-0390 is predicated on a unique and compelling biological vulnerability. The central nervous system (CNS) is isolated from peripheral cholesterol by the blood-brain barrier, making brain cells entirely dependent on de novo cholesterol biosynthesis. Glioblastoma (GBM), the most aggressive HGG, exhibits a metabolic reprogramming characterized by an "addiction" to cholesterol, which is required for rapid cell proliferation. DSP-0390 targets EBP, a critical enzyme in this biosynthesis pathway. By inhibiting EBP, the drug is hypothesized to selectively induce cytotoxicity in hyperproliferative glioma cells by starving them of essential cholesterol, while potentially sparing peripheral tissues that can source cholesterol from circulation.