Ensoma, a US-based in vivo cellular engineering company developing therapies with a one-time treatment regimen, has recently dosed the first patient in its Phase I/II clinical trial of EN-374. The Phase I/II study, carried out in the US, is an open-label, multicentre clinical trial evaluating the safety, tolerability, pharmacodynamics and preliminary efficacy of EN-374, to identify the dose level for further clinical evaluation in participants with X-linked chronic granulomatous disease (X-CGD). The results of this study should also provide both clinical proof of concept for the company’s platform and an outlook for its programmes in oncology and sickle cell disease, as well other potential indications.
The US Food and Drug Administration had already granted rare paediatric disease and orphan drug designations for EN-374 in February 2025 and the regulatory clearance to initiate another Phase I/II trial in the United Kingdom was communicated by Ensoma in December 2025.
CGD is a rare, severe genetic disorder that compromises immune function and leaves those with the disease vulnerable to recurrent bacterial and fungal infections, often leading to chronic and life-threatening dysregulated inflammation and serious complications. Current treatments, including antibiotics, antifungals, interferon gamma and allogeneic stem cell transplantation, offer limited benefit and/or come with significant side effects. X-CDG, the most common form of the disease, is caused by mutations in the CYBB gene of the NAPDH oxidase complex in neutrophils. EN-374 uses the Sleeping Beauty transposase SB100X to insert an intact CYBB gene into the genome of haematopoietic stem cells. SB100X was developed by Zsuzsanna Izsvák and Zoltan Ivics at the Max Delbrück Center in Berlin. The Sleeping Beauty system is a key genome editing technology for the transfer of large payloads, particularly into haematopoietic stem cells and T cells. With Ascenion’s support, Ensoma licensed SB100X from the Max Delbrück Center for the development of first-in-class in-vivo gene therapies.
Further information:
Ensoma's press release 1
Ensoma's press release 2
