Ensoma nabs IND from the FDA for first in-vivo HSC-directed gene insertion therapy
With FDA approval secured, Ensoma prepares to advance its groundbreaking in vivo therapy into clinical trials targeting X-CGD patients.
Ensoma announced that the FDA has cleared its IND application for EN-374, a potential gene insertion therapy for X-Linked Chronic Granulomatous Disease (X-CGD).
The condition is caused by mutations in the CYBB gene, which is part of the NADPH oxidase complex found in neutrophils.
These mutations severely compromise immune function, leaving individuals highly susceptible to life-threatening infections. EN-374 uses virus-like particles (VLPs) to deliver genetic material directly to HSCs, enabling these cells to sustainably produce a functional CYBB transgene in neutrophils. This approach aims to restore the NADPH oxidase enzyme complex, which is crucial for the immune system’s ability to fight infections. The company reports that in preclinical research, EN-374 effectively 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 Phase 1/2 clinical trial will evaluate the safety and preliminary efficacy of EN-374 in adults with X-CGD and identify an appropriate dose for further clinical development. The trial will initially enroll adult participants in a dose-escalation phase, followed by pediatric patients in a subsequent dose-expansion cohort. Earlier this year, Ensoma received rare pediatric disease and orphan drug designations from the FDA for 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.”
