Ensoma Announces Clearance of U.K. Clinical Trial Authorization Application for EN-374, First In Vivo HSC-Directed Gene Insertion Therapy

MHRA authorization to initiate Phase 1/2 clinical trial at U.K. sites follows first U.S. patient dosing with EN-374 for treatment of X-linked chronic granulomatous disease

BOSTON--(BUSINESS WIRE)--Ensoma, an in vivo cellular engineering company with a mission to advance the future of medicine through one-time therapies, today announced U.K. Medicines and Healthcare Products Regulatory Agency (MHRA) clearance of the clinical trial authorization (CTA) application for its lead program EN-374, an in vivo hematopoietic stem cell (HSC)-directed gene insertion therapy for the treatment of X-linked chronic granulomatous disease (X-CGD), a rare and severe genetic disorder. The company announced last week that the first U.S. patient in the multinational Phase 1/2 trial was successfully dosed with EN-374.

“This is a defining moment for Ensoma. With regulatory clearance to initiate our Phase 1/2 trial in the U.K. so quickly following successful dosing of the first patient at a U.S. site, we are well positioned to generate meaningful clinical data for our first-in-class in vivo HSC-directed therapy,” said Jim Burns, CEO of Ensoma. “These milestones underscore the potential of our technology and commitment of our team to deliver breakthrough genetic medicines to patients.”

The Phase 1/2 study is an open-label, multicenter clinical trial evaluating the safety, tolerability, pharmacodynamics and efficacy biomarkers 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 biomarkers 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 U.S. Food and Drug Administration (FDA) granted Ensoma rare pediatric disease and orphan drug designations for EN-374.

About CGD

Chronic granulomatous disease (CGD) is a rare, severe genetic disorder that affects approximately 1 in 100,000-200,000 live births worldwide, and the median life expectancy for individuals with the condition is around 45 years. X-linked CGD (X-CGD), the most common form, comprises 60-70% of cases and is caused by mutations in the CYBB gene of the NADPH oxidase complex in neutrophils. CGD severely 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 burdens.

About EN-374

EN-374 is a first-in-class in vivo hematopoietic stem cell (HSC)-directed therapy for X-CGD that employs virus-like particles (VLPs) to deliver payloads having a CYBB transgene to HSCs. Neutrophils arising from the engineered HSC then express the protein product of the CYBB transgene. In this way, EN-374 is designed to restore function of the infection-fighting NADPH oxidase enzyme complex critical for immune defense in humans having an impaired CYBB gene. In preclinical studies, EN-374 demonstrated therapeutic levels of restoration of CYBB protein expression and NADPH oxidase activity in circulating neutrophils. 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 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 potentially one-time, durable genetic medicines. In preclinical animal studies, the VLPs preferentially bind to hematopoietic stem cells (HSCs), efficiently delivering DNA to the nucleus. With a 35-kilobase cargo capacity, these VLPs can carry a diverse range of sophisticated genomic engineering tools capable of 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.