Dose-dependent rescue of neurological phenotypes, including epileptic seizures, motor deficits, and cognitive impairments, with long-lasting effects in adult mice

剂量依赖性挽救神经表型，包括癫痫发作，运动缺陷和认知障碍，对成年小鼠产生长期影响

Capsida poster will also show new data with its next-generation gene therapy showing significant brain-wide expression of STXBP1 protein and liver detargeting after a single IV infusion

Capsida海报还将展示其下一代基因疗法的新数据，显示单次静脉输注后STXBP1蛋白在大脑中的广泛表达和肝脏的去靶向性

Wholly owned program is first in class and currently in IND-enabling studies to support initiation of clinical trials in first half of 2025

全资拥有的项目是一流的，目前在IND中，使研究能够支持2025年上半年开始临床试验

THOUSAND OAKS, Calif., May 7, 2024 /PRNewswire/ -- Capsida Biotherapeutics ('Capsida') today announced new preclinical data supporting the potential of Capsida's gene therapy candidate, CAP-002, to achieve levels of gene supplementation necessary to correct neurological phenotypes associated with genetic epilepsy due to syntaxin-binding protein 1 (STXBP1) mutations..

加利福尼亚州千橡，2024年5月7日/PRNewswire/-Capsida Biotherapeutics（“Capsida”）今天宣布了新的临床前数据，支持Capsida基因治疗候选物CAP-002的潜力，以达到必要的基因补充水平，以纠正由于语法结合蛋白1（STXBP1）突变引起的与遗传性癫痫相关的神经表型。。

Gene therapy for genetic epilepsy due to STXBP1 mutations has not been previously possible because earlier generation adeno-associated viruses (AAVs) or wild-type AAVs could not achieve the level of widespread neuronal transduction required to modify the disease. CAP-002 is a first-in-class next-generation intravenous (IV)-administered gene therapy that achieves brain-wide neuronal expression while simultaneously detargeting the liver.

由于STXBP1突变导致的遗传性癫痫的基因治疗以前是不可能的，因为早期的腺相关病毒（AAV）或野生型AAV无法达到改变疾病所需的广泛神经元转导水平。CAP-002是一流的下一代静脉注射（IV）基因疗法，可实现全脑神经元表达，同时使肝脏失去靶向性。

Capsida's wholly owned program is currently in IND-enabling studies and is expected to enter the clinic in the first half of 2025..

Capsida全资拥有的项目目前正在进行IND启用研究，预计将于2025年上半年进入诊所。。

The first presentation, co-authored with Mingshan Xue, Ph.D., Associate Professor, Department of Neuroscience, Department of Molecular and Human Genetics at Baylor College of Medicine and the Cain Foundation Laboratories, Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital is entitled, 'AAV Gene Therapy Corrects Neurological Phenotypes with Clinically Relevant Doses in a Mouse Model of STXBP1-Related Developmental and Epileptic Encephalopathy.' The study found that IV administration of the gene encoding STXBP1 in adult mice lacking one functional copy of the STXBP1 gene rescues key phenotypic defects in a dose-dependent manner and does so with long-lasting effects.

第一篇报告由贝勒医学院神经科学系副教授、分子与人类遗传学系副教授薛明山博士和德克萨斯州儿童医院Jan和Dan Duncan神经学研究所Cain Foundation实验室共同撰写，标题为“AAV基因疗法在STXBP1相关发育性和癫痫性脑病小鼠模型中用临床相关剂量纠正神经表型”该研究发现，在缺乏STXBP1基因功能拷贝的成年小鼠中静脉注射编码STXBP1的基因可以剂量依赖性地挽救关键的表型缺陷，并具有持久的作用。

Capsida and Baylor observed that the dose-dependent rescue of neurological phenotypes, including epileptic seizures, motor deficits, and cognitive impairments, was dependent on supplementation of STXBP1 in neurons throughout the brain and at levels not achievable by wild-type serotypes, such as AAV9..

Capsida和Baylor观察到，包括癫痫发作，运动缺陷和认知障碍在内的神经表型的剂量依赖性挽救取决于在整个大脑的神经元中补充STXBP1，并且其水平是野生型血清型（例如AAV9）无法达到的。。

These data will be featured in an oral presentation today at the American Society of Gene & Cell Therapy (ASGCT) 2024 Annual Meeting, taking place May 7-11, 2024 in Baltimore, MD and virtually. Wu Chen, Ph.D., Instructor, Department of Neuroscience, Baylor College of Medicine, will deliver the oral presentation (abstract 38) at 3:00-3:15 PM ET as part of the Neurologic Diseases I Session (location: Ballroom 4, Baltimore Convention Center)..

这些数据将在今天于2024年5月7日至11日在马里兰州巴尔的摩举行的美国基因与细胞治疗学会（ASGCT）2024年年会上进行口头介绍。贝勒医学院神经科学系讲师Wu Chen博士将于美国东部时间下午3:00-3:15进行口头报告（摘要38），作为神经疾病I课程的一部分（地点：巴尔的摩会议中心舞厅4）。。

Dr. Xue commented, 'This study built upon our previous proof-of-concept study and represents a significant advancement in our understanding of the therapeutic potential of engineered AAV gene supplementation therapy in the treatment of genetic epilepsy and developmental disorders due to STXBP1 mutations.

薛博士评论道：“这项研究建立在我们之前的概念验证研究的基础上，代表了我们对工程化AAV基因补充疗法在治疗STXBP1突变引起的遗传性癫痫和发育障碍方面的治疗潜力的理解的重大进步。

These data are encouraging and emphasize the potential for CAP-002 to meaningfully improve outcomes in patients with this disease.'.

这些数据令人鼓舞，并强调CAP-002有可能有意义地改善这种疾病患者的预后。”。

On Wednesday, May 8, 2024, Capsida will also present new data in a poster presentation entitled, 'CAP-002: Systemic AAV Gene Therapy with Next Generation Capsids for Treatment of STXBP1 Encephalopathy' (abstract 504). The data show that a single IV infusion of CAP-002 results in brain-wide STXBP1 gene expression and is capable of transducing up to 70% of neurons at therapeutically relevant doses in non-human primates (NHPs).

2024年5月8日星期三，Capsida还将在题为“CAP-002：用下一代衣壳进行系统性AAV基因治疗以治疗STXBP1脑病”的海报演示中提供新数据（摘要504）。数据显示，单次IV输注CAP-002会导致全脑STXBP1基因表达，并且能够在非人灵长类动物（NHP）中以治疗相关剂量转导多达70%的神经元。

This level of gene expression raises neuronal STXBP1 protein to levels comparable to those that reversed disease phenotype in the mouse model. CAP-002 had no clinical pathology, histopathology, or immunogenicity findings..

这种基因表达水平将神经元STXBP1蛋白提高到与小鼠模型中逆转疾病表型的水平相当的水平。CAP-002没有临床病理学，组织病理学或免疫原性发现。。

'These data demonstrate that our STXBP1 program effectively crosses the blood-brain barrier in NHPs following IV delivery and achieves breakthrough levels of widespread brain transduction and STXBP1 protein expression needed to achieve disease-modifying impact as demonstrated in the mouse model data,' said Capsida's Chief Scientific Officer Susan Catalano, Ph.D.

Capsida首席科学官苏珊·卡塔拉诺（SusanCatalano）博士说：“这些数据表明，我们的STXBP1程序在静脉注射后有效地穿过了NHP中的血脑屏障，并达到了突破性水平的广泛脑转导和STXBP1蛋白表达，以达到小鼠模型数据所证明的疾病缓解效果。”。

'Coupled with significant detargeting of the liver compared to AAV9, CAP-002 holds the promise of effectively reversing disease and does so via less-invasive IV administration. We look forward to advancing our STXBP1 program into clinical development in the first half of 2025, so that we can bring this disease-modifying treatment option to people suffering from this devastating disease.'.

“与AAV9相比，CAP-002具有显着的肝脏去靶向性，有望有效逆转疾病，并通过微创IV给药来实现。我们期待着在2025年上半年将STXBP1计划推进临床开发，以便我们能够为患有这种毁灭性疾病的人带来这种改变疾病的治疗选择。”。

About Genetic Epilepsy Due to STXBP1 Mutations

关于STXBP1突变引起的遗传性癫痫

Genetic epilepsy caused by mutations in the syntaxin-binding protein 1 (STXBP1) gene is a devastating developmental and epileptic encephalopathy estimated to affect one in 30,000 children born each year globally. It is associated with severe developmental delay and intellectual disability, treatment-resistant seizures, and sudden unexpected death in epilepsy (SUDEP).

由语法结合蛋白1（STXBP1）基因突变引起的遗传性癫痫是一种破坏性的发育性和癫痫性脑病，估计在全球每年出生的30000名儿童中就有一名受到影响。它与严重的发育迟缓和智力残疾，难治性癫痫发作以及癫痫猝死（SUDEP）有关。

The STXBP1 protein is present in every neuron in the brain and is essential for normal neurotransmission. There are no disease-modifying therapies for this disorder..

STXBP1蛋白存在于大脑的每个神经元中，对于正常的神经传递至关重要。这种疾病没有缓解疾病的疗法。。

About CAP-002: Capsida's Program for Genetic Epilepsy Due to STXBP1 Mutations

关于CAP-002：Capsida针对STXBP1突变引起的遗传性癫痫的计划

CAP-002 is a wholly owned first-in-class next-generation intravenous (IV)-administered gene therapy that achieves brain-wide neuronal expression of the syntaxin-binding protein 1 (STXBP1) protein after a single infusion, with significant liver detargeting. Capsida is developing CAP-002 for the treatment of genetic epilepsy caused by mutations in the STXBP1 gene.

CAP-002是全资拥有的一流的下一代静脉注射（IV）基因疗法，可在单次输注后实现突触结合蛋白1（STXBP1）蛋白的全脑神经元表达，并具有明显的肝脏去靶向性。Capsida正在开发CAP-002，用于治疗由STXBP1基因突变引起的遗传性癫痫。

CAP-002 is currently in IND-enabling studies and is expected to enter the clinic in the first half of 2025..

CAP-002目前正在进行IND启用研究，预计将于2025年上半年进入诊所。。

About Capsida Biotherapeutics

关于辣椒生物治疗学

Capsida Biotherapeutics is a fully integrated gene therapy company with a central nervous system (CNS) pipeline consisting of disease modifying and potentially curative treatments for rare and more common diseases across all ages. Capsida's intravenously (IV) administered gene therapies utilize proprietary engineered capsids that enable high transduction levels to desired tissues and cells, while limiting tropism to non-target organs, such as the liver.

Capsida Biotherapeutics是一家完全集成的基因治疗公司，拥有中枢神经系统（CNS）管道，包括针对所有年龄段的罕见和更常见疾病的疾病缓解和潜在治疗方法。Capsida静脉内（IV）给药的基因疗法利用专有的工程衣壳，使其能够高水平转导至所需的组织和细胞，同时限制向非靶器官（如肝脏）的趋向性。

Capsida has three wholly owned programs, including potential best-in-class treatments for genetic epilepsy due to STXBP1 mutations and Parkinson's disease associated with GBA mutations, both of which are in IND-enabling studies. In addition to its wholly owned programs, the Company has validating CNS partnerships with AbbVie, Lilly, CRISPR Therapeutics, and the AbbVie partnership was expanded to include ophthalmology disorders.

Capsida拥有三个全资项目，包括针对STXBP1突变引起的遗传性癫痫和与GBA突变相关的帕金森氏病的潜在最佳治疗方案，这两个项目均处于IND支持研究中。除了全资拥有的项目外，该公司还与AbbVie，Lilly，CRISPR Therapeutics建立了CNS合作伙伴关系，AbbVie合作伙伴关系扩大到包括眼科疾病。

Capsida was founded in 2019 by lead investors Versant Ventures and Westlake Village BioPartners and originated from groundbreaking research in the laboratory of Viviana Gradinaru, Ph.D., a neuroscience professor at Caltech. Visit us at www.capsida.com..

Capsida由主要投资者Versant Ventures和Westlake Village BioPartners于2019年成立，起源于加州理工学院神经科学教授Viviana Gradinaru博士实验室的开创性研究。请访问www.capsida.com。。

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来源辣椒生物治疗剂