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BOSTON--( BUSINESS WIRE )--Ensoma, a genomic medicines company advancing the future of medicine through one-time, in vivo treatments capable of precisely and durably engineering the hematopoietic system, today unveiled its three lead programs targeting genetic, immune and oncological diseases. These innovative programs leverage Ensoma’s in vivo hematopoietic stem cell (HSC) engineering platform and aim to address critical unmet needs in chronic granulomatous disease (CGD), sickle cell disease (SCD) and solid tumors. Ensoma’s in vivo HSC engineering approach has the potential to offer greatly improved patient access to therapy and a vastly reduced treatment burden. Ensoma’s in vivo HSC engineering platform combines an off-the-shelf delivery system with an advanced gene engineering toolkit that, together, offer durable and transformative therapies across a range of diseases. The delivery system is based on virus-like particles (VLPs) that preferentially bind to HSCs, efficiently deliver DNA to the nucleus and de-target the liver. With a 35-kilobase cargo capacity, these VLPs carry a diverse range of sophisticated genomic engineering tools capable of precise changes, from single base edits up to large multi-gene insertions. Importantly, the platform leverages HSCs as a self-renewing reservoir of engineered cells, providing durable therapies with improved patient access and outcomes across genetic and immune disorders, as well as oncology. Ensoma’s lead program is for individuals living with X-linked CGD (X-CGD), a condition that severely compromises immune function and leaves patients vulnerable to life-threatening infections. X-CGD is the most common form of the condition, affecting 60-70% of CGD patients. “Science and medicine have shown the curative impact of HSC-based therapies through bone marrow transplantation and ex vivo HSC-targeted gene therapy, but access to these treatments is limited and comes with significant burden for the patient and the healthcare system,” said Jim Burns, CEO of Ensoma. “At Ensoma, we believe the time for in vivo HSC engineering has come. Our proof-of-concept data in X-CGD demonstrate our in vivo approach for CGD and position us for an IND filing in the first half of 2025, which would make it the first in vivo HSC-directed therapy to be tested in humans. We are following CGD with preclinical programs in sickle cell disease and solid tumors, underscoring our dedication to advancing the future of medicine through precision in vivo treatment.” Ensoma will present key preclinical data at the Society for Immunotherapy of Cancer (SITC) 39th Annual Meeting and the 66 th American Society of Hematology (ASH) Annual Meeting, highlighting the potential of its in vivo HSC engineering platform in advancing treatments for CGD, SCD and solid tumors. Below is a summary of the findings and presentation details. Chronic Granulomatous Disease: Key Findings from ASH: Preclinical data to be presented at the ASH Annual Meeting will highlight proof-of-concept for Ensoma's innovative in vivo gene therapy, EN-374, designed to treat X-CGD. X-CGD is caused by a mutant CYBB gene that prevents white blood cells called neutrophils from producing functional NADPH oxidase, a protein important for fighting bacterial and fungal infections. Ensoma’s novel approach employs VLPs to efficiently engineer HSCs for sustained expression of a CYBB transgene in neutrophils, restoring function of the NADPH oxidase enzyme complex critical for immune defense. The study demonstrated therapeutic restoration of CYBB protein expression and NADPH oxidase activity in murine circulating neutrophils, achieving levels shown to confer meaningful clinical benefits for X-CGD patients. This research positions EN-374 as a pioneering therapy that addresses an unmet medical need and offers the potential to expand access to HSC-directed gene therapies for genetic, immune and oncological disorders. Presentation Details: Title : In Vivo Hematopoietic Stem Cell Engineering Restores the Function of NADPH Enzyme Complex in X-Linked Chronic Granulomatous Disease Model in Mice Abstract: 801 Poster Presentation Time/Date: 5:30-7:30 p.m. PT, Saturday, Dec. 7 Location: San Diego Convention Center, Halls G-H Presenter: Sravya Kattula, Ph.D., Ensoma Sickle Cell Disease: Key Findings from ASH: At the ASH Annual Meeting, Ensoma will also showcase compelling preclinical data demonstrating the safety and efficacy of its wholly owned single-dose truncated Gro-Beta (tGROβ), EN-145 (formerly MGTA-145), combined with plerixafor for mobilizing primitive HSCs in mouse models of SCD. This innovative approach addresses the limitations of current mobilization regimens, particularly the use of granulocyte colony-stimulating factor (G-CSF), which is contraindicated in SCD patients. In a SCD mouse model, the combination of EN-145 and plerixafor mobilized six-fold more long-term HSCs than plerixafor alone, significantly enhancing HSC yield for gene therapies. Studies in humanized NBSGW mice further demonstrated rapid and effective mobilization of human CD34+ cells, along with superior transduction efficiency—meaning that Ensoma’s VLPs were more effective at delivering the genetic material into the target cells, ensuring a higher percentage of modified cells with therapeutic potential. These findings highlight EN-145's potential use in a robust alternative HSC mobilization regimen in SCD, paving the way for improved outcomes in both ex vivo and in vivo gene therapies. Presentation Details: Title: Single Dose of tGROβ (EN-145)/Plerixafor Safely and Effectively Mobilizes Primitive HSCs in Mouse Models for In Vivo Gene Therapy of Sickle Cell Disease Abstract: 4770 Poster Presentation Time/Date: 6-8 p.m. PT, Monday, Dec. 9 Location: San Diego Convention Center, Halls G-H Presenter: Courtney Mercadante, Ph.D., Ensoma Solid Tumors: Key Findings from SITC: Preclinical data to be presented at SITC 2024 will highlight the transformative potential of Ensoma’s novel platform for in vivo engineering of multi-lineage CAR-immune cells, offering a new approach to overcoming the significant challenges in solid tumor therapies. Solid tumors, unlike hematological malignancies, present a complex microenvironment that limits access for current therapies and complicates immune cell infiltration and efficacy. Ensoma’s VLPs target CD46-positive cells, including both HSCs and mature immune cells, to enable efficient transduction and generate durable anti-tumor responses. In immune-competent mice, administration of VLPs encoding an anti-HER2 CAR generated CAR+ myeloid (M), NK and T cells within just a few days, followed by long-term HSC renewal of multi-lineage effectors. Upon challenge with HER2+ tumors, these engineered immune cells effectively controlled tumor growth, indicating robust and durable anti-tumor activity. Presentation Details: Title: In vivo VLP-based engineering generates multi-lineage CAR-immune cells that mediate potent and durable anti-tumor activity Abstract: 1098 Poster Presentation Time/Date: 3:30-5 p.m. CT, Thursday, Nov. 7 & 9 a.m. – 8:30 p.m. CT, Saturday, Nov. 9 Location: Grand Ballroom AB - George R. Brown Convention Center Presenter: Corinne Decker, Ph.D., Ensoma "At Ensoma, our commitment to addressing critical unmet needs in genetically driven diseases is reflected in the promising preclinical data from our lead programs, including for chronic granulomatous disease, where we are pioneering innovative solutions to restore immune function,” said Robert Peters, Ph.D., chief scientific officer of Ensoma. “Our VLPs enable the delivery of large, complex cargo, creating the unprecedented ability to engineer multi-lineage immune responses in vivo . Beyond initiating our first clinical program in X-CGD and demonstrating the safety and efficacy of our platform, our focus for 2025 is to progress two development candidates while continuing to innovate our technology. We are also actively exploring partnerships that can further expand the potential of our groundbreaking platform. Together, we aim to transform the landscape of genomic medicine and improve outcomes for patients suffering from these challenging conditions." About Ensoma Ensoma is developing curative medicines 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 and durable genetic medicines in a simple outpatient procedure. We are focused on in vivo engineering of hematopoietic stem cells (HSCs) to address genetic diseases, immune disorders and cancer. 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 .