FDA clears Ensoma IND for first in vivo HSC-directed gene insertion therapy

Ensoma announced the U.S. FDA clearance of the investigational new drug (IND) application for its lead program, an in vivo hematopoietic stem cell (HSC)-directed therapy for X-linked chronic granulomatous disease (X-CGD), a rare and severe genetic disorder.

X-CGD is caused by mutations in the CYBB gene of the NAPDH oxidase complex in neutrophils and severely compromises immune function, leaving people living with the disease vulnerable to life-threatening infections. Ensoma’s therapy, EN-374, employs virus-like particles (VLPs) to deliver payloads that efficiently engineer HSCs for sustained expression of a CYBB transgene in neutrophils, thereby restoring function of the infection-fighting NADPH oxidase enzyme complex critical for immune defense.

In preclinical studies, EN-374 demonstrated therapeutic restoration of CYBB protein expression and NADPH oxidase activity in circulating neutrophils. “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,” said Jim Burns, Ensoma CEO.

“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,” said Burns.