Ensoma, an in vivo cellular engineering company with a mission to advance the future of medicine through one-time therapies, today announced the presentation of initial clinical data from the first participant dosed in its Phase 1/2 trial of EN-374 for the treatment of X-linked chronic granulomatous disease (X-CGD) at the American Society of Gene & Cell Therapy (ASGCT) 29th Annual Meeting, taking place May 11-15 in Boston. The data represent the first reported clinical experience with in vivo hematopoietic stem cell (HSC)-directed therapy, from which the patient has the potential to create a continuous source of therapeutic immune and blood cells to treat disease.
“We are excited to discuss encouraging initial safety data from the first participant in our Phase 1/2 clinical trial of EN-374 for X-CGD, the first-ever in vivo HSC gene insertion therapy in the clinic. While these are early data from a single participant, they mark an important first step in evaluating a new approach to engineering hematopoietic stem cells directly in vivo, and we look forward to continuing to assess safety and potential markers of clinical activity as the study progresses,” said Jim Burns, CEO of Ensoma. “Additional ASGCT presentations include promising developments with both Ensoma’s viral vector technology and our approach to producing cancer-killing immune cells. Together, these data advance our goal of bringing the power of in vivo HSC engineering to patients and treating genetic diseases and cancer with a potentially continuous supply of engineered immune and blood cells.”
Oral Presentations:
Title: First in vivo hematopoietic stem cell (HSC) gene addition clinical trial: Initial results from EN-374-101 in X-linked chronic granulomatous disease (X-CGD)
Presentation Date/Time: Friday, May 15, 8:00-9:45 a.m. ET
Location: Westin Seaport Commonwealth Ballroom ABC (Concourse level)
Presenter: Ahmad Rayes, M.D., University of Utah
Key Highlights:
- Treatment, including HSC mobilization, gene therapy infusion, short-course immune prophylaxis and three cycles of enrichment, was well tolerated
- Adverse events (AEs) were all low-grade. There were no serious AEs or dose-limiting toxicities
- Follow-up to assess potential efficacy is ongoing and will be reported at a later date
Title: Discovery and development of engineered neutralizing antibody-evading helper-dependent adenovirus capsids as candidates for in vivo gene therapy
Presentation Date/Time: Wednesday, May 13, 11:15-11:30 a.m. ET
Location: Westin Seaport Commonwealth Ballroom ABC (Concourse Level)
Presenter: Marcin Maziarz, Ph.D., Ensoma
Data Summary:
- Engineered series of hexon-modified helper-dependent adenovirus (HDAd) capsids designed to evade pre-existing Ad5 neutralizing antibodies (NAbs), a known barrier to gene delivery
- Identified an optimized capsid variant (HDAdGen2) that demonstrated evasion of NAbs in human sera
- HDAdGen2 maintained transduction efficiency comparable to the standard HDAd5/35++ vector in vitro and in vivo
- Findings suggest potential to improve gene delivery in patients with pre-existing immunity to Ad5
- Supports continued advancement of optimized capsids for in vivo gene therapy applications
Poster Presentation:
Title: An in vivo engineered and lineage-restricted multiplexed CAR-M, -NK, and -T cell therapy mounts robust solid tumor control in pre-clinical models
Poster Presentation Date/Time: Wednesday, May 13, 5:00-6:30 p.m. ET
Location: MCEC Exhibit and Poster Hall (Halls B2-C, Exhibit level)
Presenter: Yiwen Zhao, Ph.D., Ensoma
Data Summary:
- Designed lineage-restricted regulatory elements to drive CAR expression selectively in myeloid, NK and T cell populations
- Observed durable HER2+ tumor control and prolonged survival in treated animals compared to controls in preclinical models
- Maintained normal hematopoiesis and immune cell differentiation following HSC engineering
- Supports potential of a multi-lineage, in vivo-generated cell therapy approach for solid tumors
Additionally, Drew Dietz, M.D., Vice President and Head of Clinical Research & Development at Ensoma, will speak during a scientific symposia session. Details are as follows:
Title: Adenoviral vectors and in vivo selection: Designing clinical strategies for durable benefit
Session Date/Time: Friday, May 15, 11:07-11:33 a.m. ET
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. In preclinical studies, EN-374 demonstrated therapeutic levels of restoration of CYBB gene 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. The Phase 1/2 study is an open-label, multicenter clinical trial in the US and UK 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.
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.
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