Ensoma announced that the FDA has cleared its IND application for EN-374, the company’s lead program targeting X-linked chronic granulomatous disease (X-CGD), a rare genetic disorder.
EN-374 is designed as a one-time, in vivo hematopoietic stem cell (HSC)-directed therapy for X-CGD. X-CGD is caused by mutations in the CYBB gene that affect the NADPH oxidase enzyme complex in neutrophils, severely impairing immune function and leaving affected individuals vulnerable to life-threatening infections. EN-374 uses virus-like particles (VLPs) to deliver genetic payloads directly into HSCs in vivo, enabling sustained expression of a functional CYBB transgene in neutrophils. The therapeutic goal is to restore NADPH oxidase enzyme complex activity and immune function.
In preclinical studies, Ensoma reports that EN-374 successfully restored CYBB protein expression and NADPH oxidase activity in circulating neutrophils.
“The FDA’s clearance of our EN-374 IND is a pivotal moment for Ensoma that further establishes our unique in vivo HSC engineering platform and brings us one step closer to meaningfully improving outcomes for people living with X-CGD and other chronic diseases,” said Jim Burns, CEO of Ensoma. “We have completed all manufacturing activities for EN-374, through which we have successfully demonstrated reproducibility and scalability, and anticipate initiating our Phase 1/2 clinical trial in Q4 2025. We are excited to explore the potential of EN-374 to offer a simpler, more accessible approach to restoring immune function in X-CGD than HSC transplantation or ex vivo therapies.”
The planned Phase 1/2 clinical trial will assess the safety and potential efficacy of EN-374 and identify appropriate dosing for further clinical development in X-CGD. Initially, adult participants with X-CGD will be enrolled in a dose-escalation stage of the study. Upon completion of adult dosing, pediatric participants will enter a subsequent dose-expansion cohort. Earlier this year, the FDA granted rare pediatric disease and orphan drug designations to EN-374.
“One of the strengths of our platform is its modular nature – we can evaluate multiple products for a family of diseases in a single clinical trial by inserting different genes to address the various genetic forms of CGD, for example. This exciting approach should enable greater efficiency in the clinic and facilitate the regulatory process,” said Robert Peters, Ph.D., chief scientific officer of Ensoma. “Our EN-374 program will support a greater understanding of our technology’s broad applicability and also validate its potential to develop future HSC-directed, one-time medicines for other genetic diseases, cancer and immunologic conditions.”
Beyond CGD, Ensoma is developing additional preclinical programs targeting cancer and sickle cell disease, utilizing the same precision in vivo cellular engineering approach.
