Ensoma, an in vivo cellular engineering company with a mission to advance the future of medicine through one-time therapies, announced that the first patient has been dosed in the company’s Phase 1/2 clinical trial of EN-374. EN-374 is an in vivohematopoietic stem cell (HSC)-directed gene insertion therapy for the treatment of X-linked chronic granulomatous disease (X-CGD), a rare and severe genetic disorder.

“Dosing our first patient in this Phase 1/2 trial is a significant milestone for Ensoma and for the X-linked CGD community,” said Jim Burns, CEO of Ensoma. “It represents the first time an in vivoHSC-directed gene insertion therapy has been evaluated in a patient, opening the door to a potentially simpler approach to addressing the root cause of this life-threatening disease. EN-374 is designed as a one-time treatment to restore immune function in patients who currently face a lifelong burden of severe infections, repeated hospitalizations and limited therapeutic options. The results of this study would also provide both clinical proof of concept for our platform and readthrough to our programs in oncology and sickle cell disease, as well other potential indications. We are deeply grateful to the patients, families, clinicians, hospitals and advocacy partners supporting the study.”

The Phase 1/2 study is an open-label, multicenter clinical trial evaluating the safety, tolerability, pharmacodynamics and preliminary efficacy of EN-374, with the goal of identifying a dose for further clinical development in X-CGD. Key safety endpoints include the incidence of treatment-emergent, treatment-related and serious adverse events, while efficacy endpoints include changes in functional DHR+ neutrophils and the proportion of participants reaching predefined DHR+ neutrophil thresholds (≥10–50%). Adult participants with X-CGD will be enrolled in the dose-escalation portion of the trial. Following completion of the adult cohorts, pediatric participants would be enrolled in a dose-expansion cohort. Earlier this year, the FDA granted Ensoma rare pediatric disease and orphan drug designations for EN-374.

“People living with X-CGD are highly susceptible to recurrent, life-threatening bacterial and fungal infections, which can be severe and accompanied by lengthy hospitalizations,” said Ahmad Rayes, M.D., principal investigator and associate professor of pediatrics in the Pediatric Immunology and Hematopoietic Cell Transplantation/Cellular Therapy Program at the University of Utah and Intermountain Primary Children’s Hospital in Salt Lake City. “Current treatment options may reduce infection risk but often fall short of meaningful immune restoration, particularly for children. Evaluating an in vivo HSC-directed gene insertion therapy offers real hope to families who have been waiting for safer, more accessible and more durable solutions.”