Ensoma Launches Trio of Programs Using In Vivo Stem Cell Engineering for Genetic, Immune, and Cancer Diseases

Ensoma, a pioneering genomic medicines company based in Boston, is making significant strides in the field of medicine with its innovative in vivo treatments. These therapies aim to precisely and sustainably engineer the hematopoietic system, targeting genetic, immune, and oncological diseases. The company's three primary programs focus on chronic granulomatous disease (CGD), sickle cell disease (SCD), and solid tumors, addressing critical unmet medical needs.

The core of Ensoma's approach is its in vivo hematopoietic stem cell (HSC) engineering platform. This platform combines an off-the-shelf delivery system with a sophisticated gene engineering toolkit to offer durable and transformative therapies across various diseases. The delivery system utilizes virus-like particles (VLPs) that preferentially bind to HSCs, efficiently deliver DNA to the nucleus, and de-target the liver. With a substantial cargo capacity of 35 kilobases, these VLPs can carry a wide array of genomic engineering tools, enabling precise genetic modifications ranging from single base edits to large multi-gene insertions. Leveraging HSCs as a self-renewing source of engineered cells, the platform provides durable therapies with improved accessibility and outcomes for patients with genetic and immune disorders, as well as oncology.

One of Ensoma's lead programs targets individuals with X-linked chronic granulomatous disease (X-CGD), the most common form of CGD, which severely weakens immune function and increases susceptibility to life-threatening infections. X-CGD affects 60-70% of CGD patients. The traditional treatments for CGD, such as bone marrow transplantation and ex vivo HSC-targeted gene therapy, are limited by accessibility and significant burden for patients and healthcare systems. Ensoma's in vivo HSC engineering offers a promising alternative. Proof-of-concept data for X-CGD demonstrate the potential of this approach, positioning Ensoma for an Investigational New Drug (IND) filing in the first half of 2025.

Ensoma’s second program focuses on sickle cell disease (SCD), which currently has limited mobilization regimens, especially since the use of granulocyte colony-stimulating factor (G-CSF) is contraindicated for SCD patients. At the American Society of Hematology (ASH) Annual Meeting, Ensoma will present data showcasing the safety and efficacy of its single-dose truncated Gro-Beta (tGROβ), EN-145 (formerly MGTA-145), combined with plerixafor for mobilizing primitive HSCs in mouse models of SCD. The combination of EN-145 and plerixafor significantly enhances HSC yield for gene therapies, addressing the limitations of current regimens. Studies in humanized mice models also demonstrate rapid and effective mobilization of human CD34+ cells, indicating a robust alternative for HSC mobilization in SCD.

The third program targets solid tumors, which pose a complex challenge due to their microenvironment that limits access for current therapies and complicates immune cell infiltration and efficacy. Ensoma's VLPs, which target CD46-positive cells including HSCs and mature immune cells, enable efficient transduction and generate durable anti-tumor responses. Preclinical data to be presented at SITC 2024 demonstrate the platform's ability to generate multi-lineage CAR-immune cells, offering a new approach to solid tumors. In immune-competent mice, administration of VLPs encoding an anti-HER2 CAR generated CAR+ myeloid, NK, and T cells, leading to long-term HSC renewal and effective tumor control upon challenge with HER2+ tumors.

Ensoma's commitment to addressing critical unmet needs in genetically driven diseases is reflected in its promising preclinical data. The company aims to advance the future of medicine through precision in vivo treatments, with a focus on initiating clinical programs and continuing technological innovation. Ensoma is also exploring partnerships to expand the potential of its groundbreaking platform, striving to transform the landscape of genomic medicine and improve outcomes for patients with challenging conditions.