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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 .

药时代：拥抱创新！拥抱未来！2023年5月，在生物医药领域，有2家公司通过IPO上市，但以其他方式上市的医药公司数量依旧维持在高位：其中4家公司宣布与SPAC合并上市，另有4家公司进行反向并购上市。一、IPO上市5月，有2家医药公司采用IPO形式上市，数量上比4月多1家，但仍处于历史低位，生物医药IPO市场依然不景气。1、Acelyrin(NASDAQ:SLRN)5月5日，Acelyrin在纳斯达克交易所上市，发行价定在区间顶格，为每股18美元，同时将发行规模从895万股扩大至3000万股，募集金额达5.4亿美元，是自2021年2月上市的Sana (NASDAQ:SANA)（5.88亿美元）之后，又一家募集金额超过5亿美元的Biotech公司，二者相隔达26个月之久。Acelyrin成立于2020年12月，由Horizon Therapeutics（被安进以260亿美元收购）的前研发负责人Shao-Lee Lin和前首席商务官Robert F. Carey共同创立。Acelyrin采取了对外买入研发管线的策略，寻找并购买具有市场前景的潜在颠覆性药物，试图复制Horizon的爆款药物Tepezza的成功故事。公司目前的在研管线全部都是从外部买入：Izokibep：一款白细胞介素 17A (IL-17A) 抑制剂，可以特异性结合IL-17A的两个亚基以及血清中的白蛋白，对靶点的亲和力高，分子量仅为单抗的十分之一，可以通过皮下注射，达到传统单抗静脉给药的吸收水平，同时还拥有不输于单抗的半衰期，在皮肤、关节等组织器官领域有着独特优势。目前处于治疗银屑病关节炎 (PsA) 、化脓性汗腺炎（HS）和葡萄膜炎的2b/3期临床试验阶段，治疗中轴型脊柱关节炎 (AxSpA)的试验也进入了临床2期。Izokibep此前发布了治疗银屑病关节炎的积极二期数据，有成为IL-17靶点的BIC产品的潜力。该药物最初是由Affibody公司研发，Acelyrin于2021年11月以2500万美元首付款和3亿美元里程碑付款的价格，引进了Izokibep的部分权益。而此前的2020年5月，国内的创响生物也引进Izokibep在大中华区、韩国的独家开发和商业化权利，以及日本外亚太地区的临床开发权利。Lonigutamab ：一款皮下给药的抗IGF-1R单抗药物，通过靶向IGF-1R的一个独特表位，可以增加疗效的持久性和耐受性，目前正在开展甲状腺眼病的临床1期试验。该药物由Acelyrin于2023年，以收购ValenzaBio公司的形式获得。SLRN-517：一种靶向 c-KIT 的全人源IgG1单克隆抗体，目前处于IND申报阶段。该药物由Acelyrin于2023年，以收购ValenzaBio公司的形式获得。Acelyrin是近些年为数不多的在一级市场屡创融资记录的Biotech公司。自成立以来，Acelyrin共完成了3轮融资，总融资金额达到5.58亿美元。上市后，公司股价首日暴涨30.56%。无论是IPO的定价、发行规模，还是首日涨幅，均显示出市场对公司的高度热情。Acelyrin从成立到上市，仅有短短25个月，累计获得10.98亿美元的融资，且完成在纳斯达克上市，不仅融资规模上，而且在上市速度上，都是Biotech行业所罕见，尤其是在过去一年多时间的Biotech行业下行阶段，更加难能可贵。Acelyrin获得资本市场追捧的原因主要是：热门靶点的晚期管线。白细胞介素17(IL-17)是由活化的T细胞分泌的促炎细胞因子，在免疫系统中发挥多种调节功能，与银屑病、强直性脊柱炎、牙周炎等自身免疫性疾病的发生相关。在IL-17靶点的药物中，已有Taltz、Cosentyx、Bimekizumab等多款药物获批，其中礼来的Taltz和诺华的Cosentyx分别在2022年实现了24.82亿美元和47.88亿美元的销售收入，是妥妥的blockbuster的存在。在Taltz和Cosentyx的后继追赶者中，资本市场也给与了高度期待。6月20日，礼来宣布以24亿美元的价格收购了DICE Therapeutics，DICE的主打药物便是处于临床二期的口服IL-17抑制剂DC-806。2022年4月，以合并SPAC上市的MoonLake(NASDAQ:MLTX)，其主打药物Sonelokimab是靶向IL-17的三抗药物，具有挑战Cosentyx的潜力，吸引了BVF、Cormorant、RTW等知名Biotech投资机构的投资，近一年涨幅达156.29%，是2022年以来表现最好的De-SPAC医药公司。优秀的创始人组合。Acelyrin的CEO Shao-Lee Lin、首席医学官Paul Peloso 、总裁Robert F. Carey等均来自于Horizon Therapeutics。其中Shao-Lee Lin曾担任Horizon的研发负责人，主导了甲状腺眼药Tepezza研发；Robert Carey曾在摩根大通担任生命健康领域的负责人，主导的融资金额超过100亿美元。Acelyrin的创始投资机构Westlake Village BioPartners由前安进公司研发主管Sean Harper和Beth Seidenberg 博士创立，与学术界、资本界的关系密切。凭借创始人和投资人的行业经验和资源，Acelyrin有能力去把握Biotech行业的趋势，有机会去实现潜力药物的收购，以及推进药物的实验和商业化。二、反向并购上市（Reverse Merger）5月，共有4家生物医药公司宣布或完成了反向并购上市。1、Magenta Therapeutics(NASDAQ:MGTA)5月3日，Magenta Therapeutics宣布与Dianthus Therapeucs以全股票交易的形式完成合并,预计将于2023年第三季度完成，合并后的公司预计将在纳斯达克交易，股票代码为“DNTH”。合并的同时，Dianthus Therapeucs进行一笔7000万美元的融资，投资方包括富达、Venrock Healthcare Capital、5AM Ventures、Wedbush、Avidity Partners等机构。Dianthus Therapeutics是一家新一代补体疗法研发公司，采用半衰期延长技术进行修饰，对活性补体蛋白具有高选择性，有潜力实现以更低的剂量水平和更低频率给药，为严重自身免疫性疾病的患者研发变革性药物。Dianthus目前主要的管线DNTH103是一款靶向C1s补体的抑制剂，采取皮下注射且低频率的给药方式，具有改善严重自身免疫性疾病患者生活的潜力。DNTH103后续研发的催化剂较多，今年底计划发布临床一期数据，2024年一季度启动重症肌无力的临床2期试验，以及两项针对其他神经系统疾病临床2期试验，2024年下半年发布计划发布治疗Cold Agglutinin疾病的数据。2022年4月，Dianthus Therapeucs完成了1亿美元的A轮融资，由5AM Ventures, Avidity Partners, 富达领投，Venrock Healthcare Capital、 Fairmount、Tellus BioVentures跟投。Dianthus的CEO Garcia拥有25年的Biotech从业经历，此前曾担任Zealand Pharma的高级副总裁；首席医疗官Simrat Randhawa博士拥有超过20年的临床实践经验，曾担任Aurinia Pharmaceuticals临床和医疗事务高级副总裁。选择卖壳的Magenta Therapeutics是一家旨在开发干细胞移植疗法用于血癌、遗传病和自身免疫性疾病患者的公司，曾经在一级市场也是备受追捧的明星项目，累计完成了1.52亿美元的融资，并于2018年6月IPO上市，融资规模达1亿美元。上市之后，得益于早期不错的数据，Magenta又完成了多次增发融资：2019年5月，以每股13.25美元的价格完成了5630万美元的融资；2020年6月，以每股8美元完成了6000万美元的融资；2021年5月，以每股9美元的价格完成了8640万美元的融资；参与增发的投资者中，不乏Deep Track Capital, TCG X, Great Point, OrbiMed, Janus Henderson等知名机构。在合作方面，也得到了诺华、Beam Therapeutics、Bluebird Bio等公司认可，然而2021年以来，Magenta的研发难言顺利：2021年7月，MGTA-117在急性髓系白血病（AML）和骨髓增生异常综合征（MDS）患者中的1/2期临床试验的IND申请遭到FDA的临床暂停，虽然后来暂停解除，但股价却再也没有回到之前的位置；2022年4月，Magenta宣布裁员，并暂停MGTA-145 (CXCR2激动剂) 的临床试验，用以将其现金储备延长至2024年第二季度；2022年12月，公司发布了MGTA-117治疗AML的I/II期剂量递增试验数据，出现多例安全性事件，公司股价当日暴跌52%；今年1月，Magenta宣布MGTA-117在治疗AML和MDS的I/II期剂量递增试验中，出现了一例患者死亡，暂停了相关临床研究。2月2日，Magenta宣布寻求出售公司/管线等战略选择，计划裁员84%，受到此消息影响，公司股价当日暴涨51.66%，侧面反应出股东们认为公司应该暂停意义不大的管线研发，选择其他可以实现股东价值最大化的途径。三、SPAC上市5月，有4家生物医药公司宣布与SPAC合并上市，不仅数量上比4月少了近50%，而且4家拟合并的生物医药公司质地均为一般，尚未凸显较大的投资价值。欢迎加入美股滚雪球的知识星球，查看我们的行业分享以及每周更新的多个投资机会：一、我们专注的领域1、美股生物医药股投资（核心领域，优势明显）；2、中概股、美股云计算板块、美股互联网板块投资（重点领域，擅长中长线）；3、美股IPO、次新股、SPAC、ETF投资（关注领域，水平中等）；二、我们提供的服务1、每日：医药板块速评（包括板块走势、持仓标的动态、新列入观察标的情况）、每天交易机会提示（不限于医药股）；2、每周：至少推荐一只值得交易的标的分析、建仓价格和仓位建议等；3、每周：白马股、成长股、短期交易股、烟蒂股、次新股等五大类，七小类关注标的名单定期更新；4、每季：核心标的和重点观察标的季报更新；5、不定期投资逻辑分享，如逆向并购概念股、SPAC公司、中概股打新等；封面图来源：123rf精彩推荐专利悬崖之后，有哪些商机？打败了降糖这个BOSS后，礼来Tirzepatide的「中国人群」数据还有哪些隐藏彩蛋？乘风破浪，聚力同行！——「博腾药物开发者论坛」成功举办！GLP-1赛道爆火！2023年都发生了哪些大事？面临的挑战有哪些？点击阅读原文，与药时代一起快乐学习！