Ensoma Announces FDA Clearance of IND Application for First In Vivo HSC-Directed Gene Insertion Therapy

Company is Developing EN-374 as a One-Time Treatment for X-Linked Chronic Granulomatous Disease

BOSTON--(BUSINESS WIRE)--Ensoma, a genomic medicines company advancing the future of medicine through one-time, in vivo therapies, today announced U.S. Food and Drug Administration (FDA) clearance of the Investigational New Drug (IND) application for its lead program EN-374 in X-linked chronic granulomatous disease (X-CGD), a rare and severe genetic disorder.

EN-374 is a first-in-class in vivo hematopoietic stem cell (HSC)-directed therapy for X-CGD, which is caused by mutations in the CYBB gene of the NAPDH oxidase complex in neutrophils and severely compromises immune function, leaving people living with the disease vulnerable to life-threatening infections. EN-374 employs virus-like particles (VLPs) to deliver payloads that efficiently engineer HSCs for sustained expression of a CYBB transgene in neutrophils, thereby restoring function of the infection-fighting NADPH oxidase enzyme complex critical for immune defense. In preclinical studies, EN-374 demonstrated therapeutic restoration of 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 potential efficacy of EN-374 and identify a dose for further clinical development in X-CGD. Adult participants with X-CGD will be enrolled into the dose-escalation part of the trial. Following completion of the adult cohorts, pediatric participants will be enrolled in a dose-expansion cohort. Earlier this year, the FDA granted Ensoma rare pediatric disease and orphan drug designations 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.”

Beyond CGD, Ensoma is pioneering the future of precision in vivo treatment with preclinical programs in cancer and sickle cell disease.

About CGD

Chronic granulomatous disease (CGD) is a rare, severe genetic disorder that affects approximately 1 in 100,000-200,000 live births, and the median life expectancy for individuals with the condition is around 45 years. X-linked CGD (X-CGD), the most common form of the condition, comprises 60-70% of cases and is caused by CYBB gene mutations that prevent white blood cells called neutrophils from fighting infection. People with CGD are vulnerable to recurrent, severe 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 burdens. Ensoma’s lead program, EN-374, represents the first in vivo HSC-directed therapy for X-CGD, building on a mechanism that has been validated ex vivo.

About Ensoma

Ensoma is developing potentially curative medicines for genetic diseases, immune disorders and cancer through precision in vivo cellular engineering. Our platform combines class-leading proprietary base editing and high-efficiency gene integration systems with high-capacity virus-like particles (VLPs) to provide one-time, durable genetic medicines in an outpatient procedure. The delivery system is based on VLPs that preferentially bind to hematopoietic stem cells (HSCs), efficiently delivering DNA to the nucleus and de-targeting the liver. With a 35-kilobase cargo capacity, these VLPs can carry a diverse range of sophisticated genomic engineering tools capable of precise changes from single base edits to large multi-gene insertions, along with control elements for HSC-lineage cell specific expression. Ensoma is supported by top-tier investors and a passionate team committed to a bold, global vision for genomic medicines. Ensoma is based in Boston. For more information, visit ensoma.com.