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.

波士顿--（商业新闻短讯）--Ensoma是一家基因组药物公司，通过一次性体内治疗促进医学的未来，能够精确和持久地设计造血系统，今天公布了其针对遗传，免疫和肿瘤疾病的三个领先项目。这些创新项目利用Ensoma的体内造血干细胞（HSC）工程平台，旨在解决慢性肉芽肿性疾病（CGD），镰状细胞病（SCD）和实体瘤的关键未满足需求。

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的体内HSC工程方法有可能大大改善患者获得治疗的机会，并大大减轻治疗负担。。

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.

Ensoma的体内HSC工程平台将现成的传递系统与先进的基因工程工具包结合在一起，为各种疾病提供持久和变革的治疗。该递送系统基于病毒样颗粒（VLP），其优先结合HSC，有效地将DNA递送至细胞核并去靶向肝脏。

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.

这些VLP具有35千碱基的货运能力，携带各种复杂的基因组工程工具，能够进行精确的变化，从单碱基编辑到大型多基因插入。重要的是，该平台利用造血干细胞作为工程细胞的自我更新库，提供持久的治疗，改善患者对遗传和免疫疾病以及肿瘤学的获取和结果。

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..

Ensoma的主要项目是针对患有X连锁CGD（X-CGD）的个体，这种疾病严重损害免疫功能，使患者容易受到威胁生命的感染。X-CGD是该病最常见的形式，影响60-70%的CGD患者。。

“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.

Ensoma首席执行官吉姆·伯恩斯（JimBurns）表示：“科学和医学已经证明，通过骨髓移植和体外HSC靶向基因治疗，基于HSC的疗法具有治疗效果，但获得这些治疗的机会有限，给患者和医疗保健系统带来了沉重负担。”。

“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.”.

“在Ensoma，我们相信体内HSC工程的时机已经到来。我们在X-CGD中的概念验证数据证明了我们对CGD的体内方法，并将我们定位于2025年上半年的IND申请，这将使其成为第一个在人体中测试的体内HSC定向疗法。我们正在通过镰状细胞病和实体瘤的临床前项目跟踪CGD，强调我们致力于通过精确的体内治疗来推进医学的未来。”。

Ensoma will present key preclinical data at the Society for Immunotherapy of Cancer (SITC) 39th Annual Meeting and the 66th 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..

Ensoma将在癌症免疫治疗学会（SITC）第39届年会和第66届美国血液学会（ASH）年会上展示关键的临床前数据，突出其体内HSC工程平台在推进CGD，SCD和实体瘤治疗方面的潜力。以下是调查结果和演示细节的摘要。。

Chronic Granulomatous Disease:

慢性肉芽肿性疾病：

Key Findings from ASH:

ASH的主要发现：

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.

将在ASH年会上提交的临床前数据将突出Ensoma创新的体内基因疗法EN-374的概念验证，该疗法旨在治疗X-CGD。X-CGD是由突变的CYBB基因引起的，该基因阻止称为中性粒细胞的白细胞产生功能性NADPH氧化酶，NADPH氧化酶是一种对抗细菌和真菌感染的重要蛋白质。

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.

Ensoma的新方法利用VLP有效地设计HSC，以在中性粒细胞中持续表达CYBB转基因，恢复对免疫防御至关重要的NADPH氧化酶复合物的功能。该研究证明了小鼠循环中性粒细胞中CYBB蛋白表达和NADPH氧化酶活性的治疗性恢复，达到了显示为X-CGD患者带来有意义的临床益处的水平。

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..

这项研究将EN-374定位为一种开创性的疗法，可解决未满足的医疗需求，并有可能扩大针对遗传，免疫和肿瘤疾病的HSC定向基因疗法的使用范围。。

Presentation Details:

演示详细信息：

Title: In Vivo Hematopoietic Stem Cell Engineering Restores the Function of NADPH Enzyme Complex in X-Linked Chronic Granulomatous Disease Model in Mice

标题：体内造血干细胞工程在小鼠X连锁慢性肉芽肿疾病模型中恢复NADPH酶复合物的功能

Abstract: 801

摘要：801

Poster Presentation Time/Date: 5:30-7:30 p.m. PT, Saturday, Dec. 7

海报展示时间/日期：12月7日星期六下午5:30-7:30

Location: San Diego Convention Center, Halls G-H

地点：圣地亚哥会议中心G-H厅

Presenter: Sravya Kattula, Ph.D., Ensoma

出席者：Sravya Kattula，博士，恩索马

Sickle Cell Disease:

镰状细胞病：

Key Findings from ASH:

ASH的主要发现：

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.

在ASH年会上，Ensoma还将展示令人信服的临床前数据，证明其全资单剂量截短的Gro-Beta（tGROβ），EN-145（以前称为MGTA-145）与plerixafor联合用于动员原始HSC的安全性和有效性。SCD小鼠模型。这种创新方法解决了当前动员方案的局限性，特别是粒细胞集落刺激因子（G-CSF）的使用，这在SCD患者中是禁忌的。

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.

在SCD小鼠模型中，EN-145和plerixafor的组合动员的长期HSC比单独的plerixafor多6倍，显着提高了基因治疗的HSC产量。对人源化NBSGW小鼠的研究进一步证明了人CD34+细胞的快速有效动员，以及优越的转导效率，这意味着Ensoma的VLP在将遗传物质传递到靶细胞中方面更有效，从而确保具有治疗潜力的修饰细胞百分比更高。

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..

这些发现突出了EN-145在SCD中强大的替代HSC动员方案中的潜在用途，为改善离体和体内基因治疗的结果铺平了道路。。

Presentation Details:

演示详细信息：

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

标题：单剂量tGROβ（EN-145）/Plerixafor可安全有效地动员小鼠模型中的原始HSC，用于镰状细胞病的体内基因治疗

Abstract: 4770

摘要：4770

Poster Presentation Time/Date: 6-8 p.m. PT, Monday, Dec. 9

海报展示时间/日期：12月9日星期一下午6-8点

Location: San Diego Convention Center, Halls G-H

地点：圣地亚哥会议中心G-H厅

Presenter: Courtney Mercadante, Ph.D., Ensoma

主持人：Courtney Mercadante，博士，恩索马

Solid Tumors:

实体瘤：

Key Findings from SITC:

SITC的主要发现：

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.

将在2024年国际癌症研究中心（SITC）上提交的临床前数据将突出Ensoma多谱系CAR免疫细胞体内工程新平台的变革潜力，为克服实体瘤治疗中的重大挑战提供了一种新方法。与血液系统恶性肿瘤不同，实体瘤呈现出复杂的微环境，限制了当前疗法的使用，并使免疫细胞浸润和功效复杂化。

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.

Ensoma的VLP靶向CD46阳性细胞，包括HSC和成熟免疫细胞，以实现有效转导并产生持久的抗肿瘤反应。在具有免疫能力的小鼠中，在几天内施用编码抗HER2 CAR的VLP产生CAR+骨髓（M），NK和T细胞，然后长期HSC更新多谱系效应子。

Upon challenge with HER2+ tumors, these engineered immune cells effectively controlled tumor growth, indicating robust and durable anti-tumor activity..

在受到HER2+肿瘤的攻击后，这些工程化的免疫细胞有效地控制了肿瘤的生长，表明其具有强大而持久的抗肿瘤活性。。

Presentation Details:

演示详细信息：

Title: In vivo VLP-based engineering generates multi-lineage CAR-immune cells that mediate potent and durable anti-tumor activity

标题：基于体内VLP的工程产生多谱系CAR免疫细胞，介导有效且持久的抗肿瘤活性

Abstract: 1098

摘要：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

海报展示时间/日期：11月7日星期四下午3:30-5:00和11月9日星期六上午9:00-8:30

Location: Grand Ballroom AB - George R. Brown Convention Center

地点：大宴会厅AB-乔治·R·布朗会议中心

Presenter: Corinne Decker, Ph.D., Ensoma

主持人：科琳·戴克（CorinneDecker），恩萨马（Ensoma）博士

'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.

Ensoma首席科学官罗伯特·彼得斯（RobertPeters）博士说：“在Ensoma，我们致力于解决遗传驱动疾病的关键未满足需求，这反映在我们领先项目的有希望的临床前数据中，包括慢性肉芽肿疾病，我们正在开创恢复免疫功能的创新解决方案。”。

“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.

“我们的VLP能够运送大型复杂货物，创造了前所未有的能力来设计体内多谱系免疫反应。除了启动我们在X-CGD中的第一个临床计划并证明我们平台的安全性和有效性之外，我们2025年的重点是在继续创新我们的技术的同时推进两个开发候选人。

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.'.

我们还积极探索合作伙伴关系，以进一步扩大我们开创性平台的潜力。总之，我们的目标是改变基因组医学的格局，并改善患有这些挑战性疾病的患者的预后。”。

About Ensoma

关于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.

Ensoma正在通过精确的体内细胞工程开发治疗药物。我们的平台将一流的专有基础编辑和高效基因整合系统与高容量病毒样颗粒（VLP）相结合，以简单的门诊程序提供一次性和持久的基因药物。

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..

我们专注于造血干细胞（HSC）的体内工程，以解决遗传疾病，免疫疾病和癌症。Ensoma得到了顶级投资者和一支充满激情的团队的支持，他们致力于为基因组药物提供大胆的全球愿景。Ensoma总部位于波士顿。。。