Boston — Ensoma, a biotechnology company focused on one-time in vivo genomic therapies, has received clearance from the U.S. Food and Drug Administration (FDA) to begin clinical trials for EN-374, its lead therapeutic candidate targeting X-linked chronic granulomatous disease (X-CGD).
X-CGD is a rare genetic disorder caused by mutations in the CYBB gene, which impair the immune system’s ability to fight infections. Ensoma’s investigational therapy, EN-374, is the first in vivo hematopoietic stem cell (HSC)-directed gene insertion treatment designed for the condition. Unlike traditional ex vivo gene therapies or stem cell transplants, EN-374 delivers its therapeutic payload using virus-like particles (VLPs) that directly target HSCs within the body, aiming to restore immune function through sustained expression of the CYBB gene in neutrophils.
“This FDA clearance marks a pivotal milestone for Ensoma and validates the potential of our in vivo HSC engineering platform,” said Jim Burns, CEO of Ensoma. “We’re excited to move toward clinical evaluation and explore a simpler, more accessible treatment option for people living with X-CGD.”
The company plans to launch a Phase 1/2 clinical trial in the fourth quarter of 2025. The trial will begin with a dose-escalation study in adult participants, followed by a dose-expansion cohort involving pediatric patients. The FDA has already granted EN-374 both rare pediatric disease and orphan drug designations, underscoring the urgent need for effective therapies in this area.
In preclinical studies, EN-374 showed promising results, demonstrating restored CYBB protein expression and NADPH oxidase activity in circulating neutrophils—key indicators of immune function. Ensoma has completed manufacturing for the program, confirming its reproducibility and scalability.
Robert Peters, Ph.D., chief scientific officer at Ensoma, highlighted the flexibility of the company’s platform. “One of the unique advantages of our modular system is the ability to target a range of genetic variants within a disease family like CGD by inserting different therapeutic genes. This design could make trials more efficient and accelerate regulatory approval.”
In addition to X-CGD, Ensoma is advancing preclinical programs aimed at treating cancer and sickle cell disease, positioning itself at the forefront of next-generation genomic medicine.
