NEW YORK, April 9, 2024 /PRNewswire/ -- BrainStorm Cell Therapeutics Inc. (NASDAQ: BCLI), a leading developer of adult stem cell therapeutics for neurodegenerative diseases, today announced that it received written agreement from the U.S. Food and Drug Administration (FDA), under a Special Protocol Assessment (SPA), on the design for a Phase 3b trial of NurOwn® in amyotrophic lateral sclerosis (ALS)..

2024年4月9日，纽约/PRNewswire/--BrainStorm Cell Therapeutics Inc.（纳斯达克股票代码：BCLI），一家针对神经退行性疾病的成人干细胞疗法的领先开发商，今天宣布，根据一项特别方案评估（SPA），它收到了美国食品和药物管理局（FDA）关于NurOwn®肌萎缩侧索硬化症（ALS）3b期试验设计的书面协议。。

The SPA agreement with the FDA validates the clinical trial protocol and statistical analysis of the planned Phase 3b trial of NurOwn, demonstrating their adequacy for addressing objectives that support a future BLA (Biologics License Application) in ALS.

与FDA的SPA协议验证了NurOwn计划的3b期临床试验的临床试验方案和统计分析，证明了它们足以解决支持ALS未来BLA（生物制剂许可证申请）的目标。

'We are pleased to have reached an agreement with the FDA on key elements of the Phase 3b trial design that provides a potential path forward towards obtaining regulatory approval,' said Chaim Lebovits, President and Chief Executive Officer of BrainStorm. 'We believe that having this SPA in place will help de-risk certain regulatory aspects of the NurOwn clinical program.

BrainStorm总裁兼首席执行官夏姆·勒博维茨（ChaimLebovits）说，我们很高兴与FDA就3b期试验设计的关键要素达成协议，为获得监管部门的批准提供了潜在的途径我们相信，拥有这个SPA将有助于降低NurOwn临床计划某些监管方面的风险。

BrainStorm's ultimate goal is to provide a new treatment option that can help patients afflicted with ALS, and we believe that the SPA potentially brings us one step closer to this goal. We appreciate the Agency's engagement and guidance during the SPA process and look forward to moving forward with the study.'.

头脑风暴的最终目标是提供一种新的治疗选择，可以帮助患有ALS的患者，我们相信SPA可能会使我们离这一目标更近一步。我们感谢该机构在SPA过程中的参与和指导，并期待着推进这项研究。”。

BrainStorm anticipates commencement of the Phase 3b study in 2024, after reviewing the protocol with investigators, securing study site Institutional Review Board approvals, and engaging with appropriate members of the ALS community.

头脑风暴预计在2024年开始3b期研究，与研究人员一起审查方案，获得研究现场机构审查委员会的批准，并与ALS社区的适当成员接触。

Stacy Lindborg, Co-CEO of BrainStorm, commented, 'We have worked with leading neurologists, scientists, and members of the ALS community to create a robust study designed to evaluate the effectiveness and safety of NurOwn. This trial builds on valuable insights from our earlier studies and will enroll people living with ALS who are earlier in the course of their disease.

BrainStorm联合首席执行官斯泰西·林德伯格（StacyLindborg）评论道：“我们与领先的神经科医生、科学家和ALS社区成员合作，创建了一项强有力的研究，旨在评估NurOwn的有效性和安全性。这项试验建立在我们早期研究的宝贵见解的基础上，将招募病程较早的ALS患者。

Based on the evidence generated on NurOwn to date, we have a trial that we're optimistic will be positive. Over the past year, we've assembled an excellent team in clinical development that is highly qualified to execute this trial with excellence. We've been parallel processing to enable us to deliver the first dose in the trial in 2024, and we're anxious to get started.'.

根据迄今为止在纽隆产生的证据，我们有一个试验，我们乐观地认为将是积极的。在过去的一年中，我们组建了一支优秀的临床开发团队，该团队非常有资格出色地执行这项试验。我们一直在进行并行处理，以使我们能够在2024年的试验中提供第一剂，我们渴望开始。”。

The Phase 3b trial (Study BCT-006-US) will be a two-part, multicenter, study designed to assess the efficacy and safety of NurOwn in patients with ALS. The entry criteria will enroll participants earlier in the course of their disease, having the onset of ALS symptoms, including limb weakness, within the prior 24 months, all ALSFRS-R items 2 at Screening, and upright slow vital capacity >=65% of predicted for gender, height and age.

3b期试验（研究BCT-006-US）将是一项分为两部分的多中心研究，旨在评估NurOwn对ALS患者的疗效和安全性。入选标准将在疾病早期招募参与者，在前24个月内出现ALS症状，包括肢体无力，所有ALSFRS-R项目筛查时为2，直立缓慢肺活量>=性别，身高和年龄预测值的65%。

Patients will also be allowed to receive concomitant treatment of an approved standard of care..

患者也将被允许接受经批准的护理标准的伴随治疗。。

Part-A is a double blind, placebo-controlled period of 24 weeks duration. Up to approximately 200 patients are planned to be enrolled and randomized 1:1 to NurOwn or placebo treatment groups. There will be a screening period of six to nine weeks, during which eligible participants will undergo a single bone marrow aspiration procedure to procure the mesenchymal stem cells (MSCs) that will be used to manufacture each participant's NurOwn treatment for the duration of the trial.

A部分是一个持续24周的双盲安慰剂对照期。计划招募大约200名患者，并以1:1的比例随机分配到NurOwn或安慰剂治疗组。筛选期为六至九周，在此期间，符合条件的参与者将接受一次骨髓穿刺手术，以获得间充质干细胞（MSCs），用于在试验期间制造每个参与者的NurOwn治疗。

Patients will then be randomized 1:1 and treated with NurOwn or placebo via three repeated intrathecal injections, once every eight weeks. All eligible patients who complete Part-A will have the option of entering Part-B, open-label extension period of 24 weeks duration, where all participants will receive three repeated intrathecal injections of NurOwn, once every eight weeks..

然后将患者以1:1的比例随机分组，每八周一次，通过三次重复鞘内注射用NurOwn或安慰剂治疗。所有符合条件的完成A部分的患者都可以选择进入B部分，开放标签延长期为24周，所有参与者将每八周接受三次重复鞘内注射NurOwn。。

The primary efficacy endpoint is the change in the Revised Amyotrophic Lateral Sclerosis Functional Rating (ALSFRS-R) total score from baseline to Week 24. Primary inference from the trial will be based on a p-value from the combined assessment of function and survival (CAFS) to account for mortality observed in the trial.

主要疗效终点是修订后的肌萎缩侧索硬化功能评分（ALSFRS-R）总分从基线到第24周的变化。试验的主要推断将基于功能和生存综合评估（CAFS）的p值，以解释试验中观察到的死亡率。

Cerebrospinal Fluid (CSF) and blood samples will be collected for analysis of biomarkers of neuroinflammation, neurodegeneration, and neuroprotection. An independent Data Monitoring Committee (DMC) will monitor the safety of the trial participants..

将收集脑脊液（CSF）和血液样本，用于分析神经炎症，神经变性和神经保护的生物标志物。一个独立的数据监测委员会（DMC）将监测试验参与者的安全。。

Special Protocol Assessment

特别议定书评估

A Special Protocol Assessment (SPA) is a process in which drug developers may ask to meet with the FDA to reach an agreement on the design and size of certain clinical trials to determine if they adequately address scientific and regulatory requirements for a study that could support marketing approval.

特别方案评估（SPA）是一个过程，在这个过程中，药物开发人员可能会要求与FDA会面，就某些临床试验的设计和规模达成协议，以确定它们是否充分满足可能支持上市批准的研究的科学和监管要求。

A SPA agreement indicates concurrence by FDA with the adequacy and acceptability of specific critical elements of overall protocol design for a study intended to support a future marketing application. These elements are critical to ensuring that the trial conducted under the protocol can be considered an adequate and well-controlled study that can support marketing approval.

SPA协议表明FDA同意总体方案设计的特定关键要素的充分性和可接受性，以支持未来的营销应用。这些因素对于确保根据协议进行的试验可以被认为是一项充分且控制良好的研究，可以支持营销批准至关重要。

Feedback on these issues provides the greatest benefit to companies in planning late-phase development strategy. A SPA agreement does not indicate FDA concurrence on every protocol detail..

对这些问题的反馈为公司规划后期发展战略提供了最大的好处。SPA协议并不表示FDA同意每个协议细节。。

About BrainStorm Cell Therapeutics Inc.

关于BrainStorm Cell Therapeutics Inc。

BrainStorm Cell Therapeutics Inc. is a leading developer of innovative autologous adult stem cell therapeutics for debilitating neurodegenerative diseases. BrainStorm holds the rights to clinical development and commercialization of the NurOwn® technology platform used to produce autologous MSC-NTF cells through an exclusive, worldwide licensing agreement.

BrainStorm Cell Therapeutics Inc.是用于衰弱神经退行性疾病的创新性自体成体干细胞疗法的领先开发商。BrainStorm拥有通过独家全球许可协议生产自体MSC-NTF细胞的NurOwn®技术平台的临床开发和商业化权利。

Autologous MSC-NTF cells have received Orphan Drug designation status from the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of amyotrophic lateral sclerosis (ALS). BrainStorm has completed a Phase 3 trial in ALS (NCT03280056); this trial investigated the safety and efficacy of repeat-administration of autologous MSC-NTF cells and was supported by a grant from the California Institute for Regenerative Medicine (CIRM CLIN2-0989), and another grant from the ALS Association and I AM ALS.

自体MSC-NTF细胞已获得美国食品和药物管理局（FDA）和欧洲药品管理局（EMA）的孤儿药物指定状态，用于治疗肌萎缩侧索硬化症（ALS）。头脑风暴已完成ALS的3期试验（NCT03280056）；该试验研究了重复施用自体MSC-NTF细胞的安全性和有效性，并得到了加利福尼亚再生医学研究所（CIRM CLIN2-0989）的资助，以及ALS协会和我是ALS的另一笔资助。

BrainStorm completed under an investigational new drug application a Phase 2 open-label multicenter trial (NCT03799718) of autologous MSC-NTF cells in progressive MS and was supported by a grant from the National MS Society (NMSS)..

头脑风暴在一项研究性新药申请下完成了一项进行性MS中自体MSC-NTF细胞的2期开放标签多中心试验（NCT03799718），并得到了美国国家MS学会（NMSS）的资助。