XLRS1

DURHAM, N.C., Oct. 10, 2024 (GLOBE NEWSWIRE) -- Atsena Therapeutics, a clinical-stage gene therapy company focused on bringing the life-changing power of genetic medicine to reverse or prevent blindness, today announced that safety and efficacy data on ATSN-201 for the treatment of X-linked retinoschisis (XLRS) will be presented during a panel discussion at the American Academy of Ophthalmology (AAO) 2024 Annual Meeting taking place October 18-21, 2024, in Chicago. ATSN-201, a best-in-class gene therapy product candidate, leverages AAV.SPR, the company’s novel spreading capsid, to achieve therapeutic levels of gene expression in photoreceptors of the central retina while avoiding the surgical risks of foveal detachment. Presentation details are as follows: Session: First-time Results of Clinical TrialsDate and Time: Friday, October 18, 2024, 4:54 - 5:33 p.m. CDTPresentation Title: Interim Safety and Efficacy of ATSN-201 Dose Escalation Study in Patients With X-linked Retinoschisis (XLRS)Presentation Time: 5:08 p.m. CDTPresenter: Christine Nichols Kay, MD, Clinical Ophthalmology Advisor, Atsena Therapeutics The safety and tolerability of ATSN-201 is being evaluated in the LIGHTHOUSE study, a Phase I/II, open-label, dose-escalation and dose-expansion clinical trial in male patients ages six and older with a clinical diagnosis of XLRS caused by mutations in the RS1 gene. Enrollment for this study is ongoing. For more information, visit ClinicalTrials.gov (Identifier: NCT05878860). ATSN-201 has received Orphan Drug and Rare Pediatric Disease designations from the U.S. Food and Drug Administration. About X-linked Retinoschisis (XLRS)XLRS is a monogenic X-linked disease caused by mutations in the RS1 gene which encodes retinoschisin, a protein secreted primarily by photoreceptors. RS1 is localized to the extracellular surface of rods, cones, and bipolar cells. XLRS is characterized by schisis, or abnormal splitting of retinal layers, which causes impaired visual acuity that is not correctable with glasses and ultimately blindness. XLRS primarily affects males and is typically diagnosed in early childhood. Approximately 30,000 males in the U.S. and EU have XLRS, for which there are currently no approved treatments. About AAV.SPRAAV.SPR, one of Atsena’s novel capsids, spreads laterally beyond the subretinal injection bleb margins to enable safe and efficient transduction of the central retina (where schisis cavities predominate in XLRS patient retinas) when injected into areas outside the macula. A preclinical study in non-human primates demonstrated that AAV.SPR promotes transgene expression well beyond bleb margins. This is in stark contrast to benchmark AAV vectors, which remain confined to those original margins. At clinically relevant doses, AAV.SPR efficiently transduces foveal cones without the need for surgical detachment and does not cause inflammation. For more information about the preclinical study and how AAV.SPR works, visit https://atsenatx.com/our-approach/laterally-spreading-aav/. About Atsena TherapeuticsAtsena Therapeutics is a clinical-stage gene therapy company developing best-in-class treatments for the reversal or prevention of blindness from inherited retinal diseases. The company’s lead program is evaluating ATSN-201 in an ongoing Phase I/II clinical trial for X-linked retinoschisis (XLRS), a genetic condition affecting boys and men that is typically diagnosed in childhood and leads to blindness later in life. Another ongoing Phase I/II clinical trial is evaluating ATSN-101 for Leber congenital amaurosis type 1 (LCA1), one of the most common causes of blindness in children. Atsena’s pipeline is powered by novel adeno-associated virus (AAV) technology tailored to overcome the hurdles presented by inherited retinal diseases. Founded by pioneers in ocular gene therapy, Atsena is led by an experienced team dedicated to addressing the needs of patients with vision loss. For more information, please visit https://atsenatx.com/. Media Contact:Tony Plohoros6 Degrees(908) 591-2839tplohoros@6degreespr.com Business Contact:info@atsenatx.com

Marks second FDA designation for ATSN-201, which previously received Rare Pediatric Disease designationDURHAM, N.C., Sept. 17, 2024 (GLOBE NEWSWIRE) -- Atsena Therapeutics, a clinical-stage gene therapy company focused on bringing the life-changing power of genetic medicine to reverse or prevent blindness, today announced that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation for ATSN-201 for the treatment of X-linked retinoschisis (XLRS). ATSN-201, a best-in-class gene therapy product candidate, leverages AAV.SPR, the company’s novel spreading capsid, to achieve therapeutic levels of gene expression in photoreceptors of the central retina while avoiding the surgical risks of foveal detachment. “We are honored to receive the FDA’s Orphan Drug Designation for ATSN-201, which was also recently granted Rare Pediatric Disease designation. These designations mark a significant inflection point for the potential of this ocular gene therapy in an inherited retinal disease that currently has no available treatments,” said Patrick Ritschel, Chief Executive Officer of Atsena Therapeutics. “The Atsena team is passionate and committed to our ongoing work on the XLRS program. We look forward to bringing hope to patients affected by this rare disease and are confident these designations will expedite our path forward.” The FDA grants Orphan Drug Designation to drugs and biologics that are intended for safe and effective treatment, diagnosis or prevention of rare diseases or disorders that affect fewer than 200,000 people in the U.S. Orphan Drug Designation provides certain incentives, such as tax credits toward the cost of clinical trials upon approval and prescription drug user fee waivers. If a product receives Orphan Drug Status from the FDA, that product is entitled to seven years of market exclusivity for the disease in which it has Orphan Drug designation, which is independent from intellectual property protection. Currently, there are no approved treatments for XLRS, which is typically diagnosed in early childhood and affects approximately 30,000 males in the U.S. and EU. The safety and tolerability of ATSN-201 is currently being evaluated in the LIGHTHOUSE study, a Phase I/II, open-label, dose-escalation and dose-expansion clinical trial in male patients ages six and older with a clinical diagnosis of XLRS caused by mutations in the RS1 gene. Enrollment for this study is ongoing. For more information, visit ClinicalTrials.gov (Identifier: NCT05878860). About X-linked Retinoschisis (XLRS)XLRS is a monogenic X-linked disease caused by mutations in the RS1 gene which encodes retinoschisin, a protein secreted primarily by photoreceptors. RS1 is localized to the extracellular surface of rods, cones, and bipolar cells. XLRS is characterized by schisis, or abnormal splitting of retinal layers, which causes impaired visual acuity that is not correctable with glasses and leads to progressive vision loss and ultimately blindness. XLRS primarily affects males and is typically diagnosed in early childhood. Approximately 30,000 males in the U.S. and EU have XLRS, for which there are currently no approved treatments. About AAV.SPRAAV.SPR, one of Atsena’s novel capsids, spreads laterally beyond the subretinal injection site to enable safe and efficient transduction of the central retina (where schisis cavities predominate in XLRS patient retinas) when injected into areas outside the macula. A preclinical study in non-human primates demonstrated that AAV.SPR promotes transgene expression well beyond subretinal injection bleb margins. This is in stark contrast to benchmark AAV vectors, which remain confined to the original bleb margins. At clinically relevant doses, AAV.SPR efficiently transduces foveal cones without the need for surgical detachment and does not cause inflammation. For more information about the preclinical study and how AAV.SPR works, visit https://atsenatx.com/our-approach/laterally-spreading-aav/. About Atsena TherapeuticsAtsena Therapeutics is a clinical-stage gene therapy company developing best-in-class treatments for the reversal or prevention of blindness from inherited retinal diseases. The company’s lead program is evaluating ATSN-201 in an ongoing Phase I/II clinical trial for X-linked retinoschisis (XLRS), a progressive genetic condition affecting boys and men that is typically diagnosed in childhood. Another ongoing Phase I/II clinical trial is evaluating ATSN-101 for Leber congenital amaurosis type 1 (LCA1), one of the most common causes of blindness in children. Atsena’s pipeline is powered by novel adeno-associated virus (AAV) technology tailored to overcome the hurdles presented by inherited retinal diseases. Founded by pioneers in ocular gene therapy, Atsena is led by an experienced team dedicated to addressing the needs of patients with vision loss. For more information, please visit https://atsenatx.com/. Media Contact:Tony Plohoros6 Degrees(908) 591-2839tplohoros@6degreespr.com Business Contact:info@atsenatx.com

据Mordor Intelligence数据，2024年全球基因治疗市场规模预计为71.8亿美元，预计到2029年将达到246.7亿美元，在预测期内（2024-2029年）复合年增长率为28%。基因治疗为许多疾病的治疗开辟了一条新途径。基因治疗药物可通过DNA、RNA或者核糖核蛋白（RNP）的形式存在，这其中关键的技术是如何将它们递送到细胞内。尽管基因治疗领域依然吸金，安全、精准、有效的递送工具依然是该领域最难解决的问题之一。 目前基因治疗多聚焦在遗传疾病，随着研发投入的增加和技术的进步，基因治疗拓展到更大市场的常见疾病中。值得一提的是，在2017年后新成立的多家专注基因治疗的公司，专注于开发基因治疗递送工具的并不多，因诺惟康走在了前列。2024年7月，旗下基于自研递送载体的IVB103注射液收到FDA的IND许可，标志着因诺惟康成为一家进入临床阶段的生物技术公司，也是因诺惟康基因递送工具开发的一个里程碑。 创立初期围绕AAV搭建技术平台，瞄准眼科领域“给药难”痛点 因诺惟康创始人王成博士本科毕业于清华大学，后赴哥伦比亚大学深造，师从美国科学院院士、HHMI研究员Stephen Goff，专攻病毒学与分子生物学方向并获得博士学位。2015年毕业后他加入再生元（Regeneron）制药，成为再生元病毒载体部门的的初创科学家之一，投身于基因治疗与细胞治疗领域的前沿探索，负责早期细胞和基因治疗的技术平台的搭建和管线产品布局。期间他领导确定了再生元在基因递送工具开发的方向，推动了多款产品的药物结构确定，最快的已经进入到临床3期实验。 在积累了行业经验后，王成萌生了回国创业的念头，然而鉴于对国内环境的不熟悉，他先在凯风创投担任了一段时间的生物医药早期投资顾问。期间，国内基因治疗初创企业成为吸金大户，并在产品层面逐步缩小与海外的差距。但在创新基因递送工具的研发上，国外仍占据领先地位，而国内企业则处于追赶阶段。他还指出了基因治疗领域一个普遍存在的问题：由于当前递送工具效率低下，往往需要加大剂量使用，而这容易引发严重的免疫反应，甚至导致患者死亡。 这一认知促使王成及团队致力于提升递送工具的效率和安全性。2021年，有了国内市场积累的王成创立了公司，并与合伙人一起将公司命名为INNOVEC（即因诺惟康），也这是“Innovative Vector for Gene Therapy”的缩写，直接体现了其致力于革新基因递送工具、推动基因治疗技术进步的初心。 因诺惟康目前坐落于聚焦细胞治疗、基因治疗、合成生物学、AI医疗等前沿产业领域的海星医药健康创新园。海星医药健康创新园由海淀区国资背景的海新域城市更新集团运营，不仅为生物医药产业提供了高标准的空间载体与产业服务，更布局了“孵化+办公”、“研发实验”至“中试”的全链条产业生态。通过其独特的“一中心、五平台”综合服务体系，辅以完善的物业与配套支持，海星医药健康创新园为因诺惟康等众多高新技术企业构建了覆盖全生命周期的成长沃土。此外，这一运营方式加速了科技成果的转化效率并逐步构建起了具有特色的医药健康产业生态圈,为园区内企业的成长提供了不可或缺的滋养与支持。 目前，基因递送工具主要分为两类：病毒载体，比如腺相关病毒（AAV）、慢病毒（LV）；非病毒载体，比如纳米脂质体（LNP）。RNA在细胞质当中就可以发挥作用，LNP可以直接把RNA送到细胞质，是高效的递送载体；DNA必须到细胞核中才能实现功能，目前为止病毒载体还是递送DNA入细胞核的最有效的工具。因诺惟康选择围绕AAV搭建平台，因为AAV致病性极低，而且能够长期待在不分裂的细胞当中，适合用于感染视网膜、大脑、肌肉、心脏等大部分人体组织和器官。 在适应症的选择上，王成团队决定首先从眼科领域入手。眼科作为局部注射治疗的代表领域，尽管看似简单，但在将基因递送工具有效送达眼睛内特定细胞时仍面临诸多挑战：对于常见眼病的治疗，需要开发更加简便的给药方式，如玻璃体内给药，以扩大治疗可及性，然而，传统基因递送工具在玻璃体内给药时对视网膜的感染效率有限，因此，他们致力于对现有载体进行改造升级，以提高其在视网膜的感染效率，从而满足临床需求。 EASI-AAV平台剑指 基因治疗递送技术开发难题 当前，因诺惟康已围绕AAV载体和眼科基因治疗领域的诸多痛点问题，搭建了EASI-AAV平台，旨在让所有AAV技术和产品开发变得更容易（easy）。 AAV是微小病毒科（parvoviridae）家族的成员之一，是一类直径约20-26nm，含有4.7kb左右的线状单链DNA，无法自主复制，无包膜的微小病毒。研究中采用的重组腺相关病毒载体（rAAV）是在非致病的野生型AAV基础上改造而成的基因载体，由于其种类多样、免疫原性低、致病性极低、宿主细胞范围广、体内表达基因时间长等，被视为最有前途的基因研究和基因治疗载体之一。 但是目前的腺相关病毒都在小鼠或NHP上开发，存在着从动物到人转化率低的问题，组织靶向性，感染效率，免疫反应等问题最为突出，加之AAV本身包装容量有限，生产成本高等问题，AAV作为基因治疗工具急需技术创新。为此，因诺惟康的策略之一是通过改造病毒载体，使其能够识别并利用特定细胞表面的受体，从而实现精准的组织靶向。 此外，公司在技术平台EASI-AAV下，还延伸出了EASI-FIND、EASI-Expand和EASI-Stable等技术。EASI-FIND是因诺惟康根据“从人到人”的理念——从人出发，以AI为驱动，开发适用于人体的AAV递送载体。传统的AAV开发都是从动物身上做起，所开发载体往往在人体身上的感染效率低，或者是不能感染相应的组织，因为病毒感染的物种差异性很大。而EASI-FIND旨在用简单的方式开发组织靶向性的新型AAV，突破动物到人转化的障碍。EASI-Expand和EASI-Stable则专注解决AAV包装容量和生产过程复杂等问题。 以眼内给药的AAV为例，传统载体无论是玻璃体内注射还是视网膜下注射，都比较难到达双极细胞和感光细胞，而因诺惟康基于EASI-AAV平台开发的玻璃体注射的载体，正好能够比较有效地感染双极细胞和感光细胞。王成专门提到：“在选择这个适应症的时候，我们会去特别考量，两种细胞上面有哪些基因缺陷会导致疾病。” 此外，因诺惟康全人源核酸递送系统（hVLP）也处于对载体进行靶向性改造的在研状态。hVLP是全部用人的蛋白组成核酸递送系统，可以使递送系统具有病毒载体系统的效率和易于改造，非病毒系统的可重复递送等优点。据悉，目前因诺惟康完成系统的初步验证，并且提交专利申请。 FDA授予新载体 开发项目的首个IND批件 值得一提的是，自2021年公司成立，并启动实验以来，因诺惟康团队在短短三年内便取得了成果。2024年7月26日，因诺惟康IVB103注射液提前收到FDA的新药临床试验（IND）许可，可正式进入临床试验阶段。这也是FDA授予的新载体开发项目的首个IND批件，展现了其高效的执行力和研发速度。 IVB103注射液是在因诺惟康自主研发的新型载体基础上开发的一款可玻璃体内给药的治疗新生血管性年龄相关性黄斑变性（nAMD）的药物。王成提到：“临床前数据显示IVB103优于国际在研的同类先进产品，具有“best in class”的潜力。在Information Request中，FDA对IVB103的CMC仅有一个问题，Non-clinical无问题，这显示出因诺惟康自主研发的载体具有良好的安全性和成药性，也成为公司提前收到FDA的IND许可的先决条件。” 因诺惟康的另一重磅管线IVB102是在公司自主研发的新型载体基础上开发的一款治疗X连锁视网膜劈裂（XLRS）的药物。2024年初，IVB102注射液先后获得美国食品药品监督管理局（FDA）授予儿科罕见病药物资格认（RPDD）和罕见病药物资格（ODD）认证。临床前研究中，IVB102注射液在模型动物体内也已显示出惊人的疗效。在给予IVB102注射液治疗后4-8周，视网膜劈裂所产生的囊腔基本消失。给药16-24w后，小鼠视觉电生理信号恢复到与野生型小鼠相当水平，显著优于全球同类产品。XLRS属于X染色体隐性遗传视网膜疾病的一种，患病率约为1/15000-1/30000以男性发病为主，呈现家族遗传的特征。该病最早可从两三岁发病，会出现不同程度的视力受损，表现为视网膜内层劈裂、黄斑劈裂所致轮辐装改变和周边视网膜劈裂，视网膜电图（ERG）呈负波形，b波振幅显著下降，可并发玻璃体出血和视网膜脱离，“等待失明”似乎已成为患者可预见的命运。RS1是迄今为止发现的唯一XLRS致病基因，但目前国内外均没有针对XLRS的有效治疗手段。目前IVB102注射液在北京协和医院开展研究者发起的临床实验，睢瑞芳教授担任主要研究者。该实验已经完成低中高剂量全部患者入组。受试者给药后状况良好，无严重不良事件发生。初步有效性观察显示，患者在中央视网膜厚度，视力及静态视野方面有显著改善。 而在谈及推进管线进展时，王成强调，这一过程不仅是技术的验证过程，更是提升技术价值的关键步骤。公司正在推进与高校和医院的研究团队合作。他期待在临床取得成功后，能吸引更多企业和研究单位利用因诺惟康的递送技术开展合作，满足更多的科研和临床需求。 如果有高校和医院的研究团队想要与因诺惟康合作，请联系动脉网。 如果您想对接文章中提到的项目，或您的项目想被动脉网报道，或者发布融资新闻，请与我们联系；也可加入动脉网行业社群，结交更多志同道合的好友。 近 期 推 荐 声明：动脉网所刊载内容之知识产权为动脉网及相关权利人专属所有或持有。未经许可，禁止进行转载、摘编、复制及建立镜像等任何使用。 动脉网，未来医疗服务平台