BOSTON, Mass., May 8, 2026
Ensoma announced the presentation of initial clinical safety data from the first participant dosed in its ongoing Phase 1/2 clinical trial evaluating EN-374, the company’s investigational in vivo hematopoietic stem cell (HSC) engineering therapy for X-linked chronic granulomatous disease (X-CGD). The data are being presented at the American Society of Gene & Cell Therapy (ASGCT) 29th Annual Meeting in Boston and represent what the company describes as the first reported clinical experience using an in vivo HSC-directed gene insertion therapy in humans. According to Ensoma, the early clinical findings demonstrated that treatment with EN-374 was generally well tolerated in the first patient treated, with no serious adverse events or dose-limiting toxicities observed during initial follow-up.
The company believes the program represents a major advancement in the emerging field of in vivo cellular engineering, where therapeutic immune and blood cells are genetically modified directly within the patient’s body rather than through traditional ex vivo manufacturing approaches. In addition to the EN-374 clinical presentation, Ensoma also unveiled updated preclinical oncology data highlighting the ability of its proprietary virus-like particle (VLP) platform to generate multiplexed CAR-engineered macrophages, NK cells, and T cells in vivo capable of controlling HER2-positive solid tumors in animal models.
Initial EN-374 Clinical Data Support In Vivo HSC Engineering Strategy
The oral presentation at ASGCT 2026 detailed initial findings from the first participant enrolled in the EN-374-101 Phase 1/2 clinical trial for X-CGD, a rare inherited immunodeficiency disorder caused by mutations in the CYBB gene that impair the function of the NADPH oxidase enzyme complex critical for infection control. Patients with X-CGD experience recurrent severe bacterial and fungal infections due to defective neutrophil activity, and current curative treatment options remain limited primarily to allogeneic stem cell transplantation. Ensoma’s EN-374 therapy is designed to genetically engineer hematopoietic stem cells directly inside the patient using virus-like particles carrying a functional CYBB transgene payload.
The goal is to generate a continuous internal source of corrected immune cells capable of restoring normal immune defense. According to the company, treatment in the first patient included HSC mobilization, gene therapy infusion, short-course immune prophylaxis, and three cycles of enrichment therapy, all of which were well tolerated. Reported adverse events were low-grade, with no serious safety concerns identified during early follow-up. The study remains ongoing, and the company stated that additional follow-up evaluating potential clinical efficacy biomarkers and therapeutic activity will be reported later as the trial progresses.
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Preclinical Oncology Data Highlight Multiplexed Immune Cell Engineering
Beyond its rare disease gene therapy program, Ensoma also presented updated preclinical oncology findings demonstrating the broader capabilities of its in vivo engineering platform. A poster presentation showcased preclinical data involving the generation of multiplexed CAR-engineered macrophages (CAR-M), natural killer cells (CAR-NK), and T cells (CAR-T) directly within the body using lineage-restricted regulatory elements. In HER2-positive solid tumor models, the company reported significant tumor control and prolonged survival compared with untreated controls. Importantly, investigators observed preserved normal hematopoiesis and immune cell differentiation following HSC engineering, supporting the possibility of generating multiple anti-cancer immune cell populations without disrupting normal bone marrow function.
The company believes this multi-lineage approach may offer advantages over conventional single-cell-type immunotherapies, particularly in difficult-to-treat solid tumors where immune suppression and tumor heterogeneity remain major barriers to therapeutic success. Ensoma also presented additional preclinical research involving engineered helper-dependent adenoviral capsids designed to evade pre-existing neutralizing antibodies, a common limitation in viral gene delivery systems. According to the company, the optimized HDAdGen2 vector demonstrated improved resistance to anti-Ad5 neutralizing antibodies while maintaining efficient gene delivery both in vitro and in vivo.
Ensoma Expands Position in Next-Generation Genomic Medicines
Ensoma is positioning itself within the rapidly growing genomic medicine sector focused on developing potentially curative one-time therapies using in vivo genetic engineering technologies. Unlike conventional ex vivo gene therapies that require stem cell harvesting, laboratory modification, and reinfusion, Ensoma’s platform is designed to directly target hematopoietic stem cells inside the body using high-capacity virus-like particles capable of delivering complex gene editing payloads.
The company’s proprietary VLP system supports cargo capacities of up to 35 kilobases, enabling delivery of sophisticated genomic engineering tools ranging from single-base editing to large multi-gene insertions. Company executives stated that the early EN-374 clinical findings represent an important milestone for the field of in vivo HSC engineering and may validate a fundamentally new therapeutic approach for treating genetic diseases, immune disorders, and cancer. As clinical development continues, investors and researchers are closely monitoring whether in vivo HSC-directed therapies can achieve durable therapeutic benefits while simplifying manufacturing and expanding accessibility compared with traditional cell therapy approaches. Ensoma believes its platform could eventually support scalable one-time treatments across a broad range of diseases driven by immune dysfunction and genetic abnormalities.
Source: Ensoma press release
