BOSTON, Mass. — Ensoma has dosed the first patient in a Phase 1/2 clinical trial evaluating EN-374, an in vivo gene insertion therapy intended to restore immune function in people with X-linked chronic granulomatous disease, a rare and severe genetic disorder.
The therapy is the first in vivo hematopoietic stem cell–directed gene insertion approach to reach clinical testing. Jim Burns, CEO of Ensoma, said the milestone marks an important step for both the company and the X-CGD community. “Dosing our first patient in this Phase 1/2 trial is a significant milestone for Ensoma and for the X-linked CGD community,” he said. “It represents the first time an in vivo HSC-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 open-label, multicenter study will assess safety, tolerability, pharmacodynamics and early signs of effectiveness. Investigators aim to determine a dose for further development by monitoring treatment-emergent and treatment-related adverse events, as well as changes in functional DHR+ neutrophils. The trial will begin with adult participants in a dose-escalation stage, followed by pediatric enrollment in a planned dose-expansion cohort. Earlier in the year, the U.S. Food and Drug Administration granted EN-374 rare pediatric disease and orphan drug designations.
X-CGD significantly weakens the immune system, leaving patients vulnerable to recurring bacterial and fungal infections that often require prolonged hospitalization. Ahmad Rayes, M.D., principal investigator and associate professor of pediatrics at the University of Utah and Intermountain Primary Children’s Hospital in Salt Lake City, said improved therapies are urgently needed. “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,” he said. “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.”
