EN-374 / Ensoma - LARVOL DELTA

Study of EN-374 Gene Therapy in Participants With X-Linked Chronic Granulomatous Disease (clinicaltrials.gov) - P1/2 | N=15 | Active, not recruiting | Sponsor: Ensoma | Recruiting ➔ Active, not recruiting

Enrollment closed • Gene Therapies • Immunology • Primary Immunodeficiency • CYBB

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) (ASGCT 2026) - P1/2 | "Treatment consists of: HSC mobilization with GCSF and plerixafor; EN-374 gene therapy administration with short course (<24 hours) immune prophylaxis including dexamethasone, anakinra and tocilizumab; and then in vivo selective enrichment to expand the amount of gene modified cells using temozolomide (TMZ) and O6BG. Conclusion In this first ever experience with in vivo HSC gene addition therapy, the treatment course of mobilization, gene therapy infusion, short course immune prophylaxis, and enrichment was well tolerated by the first participant. Additional participants are under evaluation and up-to-date data on all participants will be presented."

Late-breaking abstract • Preclinical • Bone Marrow Transplantation • Gene Therapies • Genetic Disorders • Graft versus Host Disease • Immunology • Infectious Disease • Musculoskeletal Pain • Primary Immunodeficiency • CD34 • CTSG • CYBB

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

New P1/2 trial • Genetic Disorders

In Vivo Hematopoietic Stem Cell Engineering Restores the Function of NADPH Enzyme Complex in X-Linked Chronic Granulomatous Disease Model Mice (ASH 2024) - "In an in vivo study, CD46tg/CYBB KO mouse HSCs were first mobilized from the bone marrow to peripheral circulation by granulocyte colony stimulating factor and plerixafor...Gene-modified HSCs in the peripheral circulation homed back to the bone marrow and, via the selectable MGMT-P140K marker, were enriched by administration of O6BG and temozolomide...This study sets the foundation for the first in vivo HSC gene therapy to reach the clinic and can be applied to a range of genetic disorders which thus far have only been addressed with ex vivo gene therapies that involve significant patient burden and manufacturing limitations. Thus, this VLP-based, off-the-shelf therapy has the potential to dramatically broaden the patient populations that can benefit from HSC-directed gene therapies."

Preclinical • Gene Therapies • Genetic Disorders • Graft versus Host Disease • Immunology • Infectious Disease • Primary Immunodeficiency • Transplant Rejection • CD46 • CYBB • ITGAM • MGMT

Study of EN-374 Gene Therapy in Participants With X-Linked Chronic Granulomatous Disease (clinicaltrials.gov) - P1/2 | N=15 | Recruiting | Sponsor: Ensoma | Not yet recruiting ➔ Recruiting

Enrollment open • Gene Therapies • Immunology • Primary Immunodeficiency

Novel In Vivo Gene Therapy Approach to Hematopoietic Stem Cell (HSC) Engineering Creates Durable HSC-Derived Neutrophils to Treat X-Linked Chronic Granulomatous Disease (ASGCT 2025) - "Unmodified HSCs are then depleted by O6-benzylguanine (O6BG) and single dose temozolomide (TMZ), at less than conventional regimens, while gene-modified HSCs are protected from the toxic effects of TMZ and enriched to achieve therapeutic levels of gene marking. Additionally, with a scalable, suspension-based manufacturing process, our VLPs can support large patient populations at low cost, and this study sets the foundation for the first VLP-based, off-the-shelf in vivo HSC gene therapy to be studied in a XCGD clinical trial. Our technology has the potential to be applied to a wide range of genetic disorders which thus far have only been addressed with allogeneic-HSC transplants and ex vivo gene therapies Disease Focus of Abstract:Rare Diseases"

Gene therapy • Preclinical • Gene Therapies • Genetic Disorders • Graft versus Host Disease • Immunology • Infectious Disease • Primary Immunodeficiency • Rare Diseases • Transplant Rejection • CD46 • CYBB

Ensoma Announces FDA Clearance of IND Application for First In Vivo HSC-Directed Gene Insertion Therapy (Businesswire) - "Ensoma...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....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."

IND • New P1/2 trial • Genetic Disorders

Ensoma to Present Preclinical Data and Manufacturing Advancements for In Vivo HSC Engineering Platform to Treat Cancer, Immune Disorders and Genetic Diseases at ASGCT 28th Annual Meeting (Businesswire) - "Ensoma...announced it will present preclinical data and manufacturing advancements at the American Society of Gene & Cell Therapy (ASGCT) 28th Annual Meeting, hosted May 13-17 in New Orleans. The company’s poster presentations will highlight key programs that leverage its in vivo HSC engineering platform."

Preclinical • Genetic Disorders • Oncology

Study of EN-374 Gene Therapy in Participants with X-Linked Chronic Granulomatous Disease (clinicaltrials.gov) - P1/2 | N=15 | Not yet recruiting | Sponsor: Ensoma

New P1/2 trial • Gene Therapies • Immunology • Primary Immunodeficiency

Ensoma Receives Rare Pediatric Disease and Orphan Drug Designations for EN-374 for Treatment of Chronic Granulomatous Disease (Businesswire) - "Ensoma...today announced the U.S. Food and Drug Administration (FDA) has granted both rare pediatric disease and orphan drug designations to the company’s lead program, EN-374, for the treatment of X-linked chronic granulomatous disease (X-CGD). Ensoma anticipates it will submit an investigational new drug application (IND) for EN-374 in the first half of 2025."

FDA event • IND • Orphan drug • Genetic Disorders