Neurotrophic factor-producing mesenchymal stem cell therapy (BrainStorm Cell Therapeutics)

Memorandum of Understanding has been signed NEW YORK, Nov. 11, 2024 /PRNewswire/ -- BrainStorm Cell Therapeutics Inc. (NASDAQ: BCLI), a leading developer of cellular therapies for neurodegenerative diseases, today announced that it has entered into a Memorandum of Understanding (MOU) with Pluri Inc. (NASDAQ: PLUR) through its wholly owned subsidiary ("Pluri"), an established global leader in the development and manufacturing of cell-based therapeutics, to manufacture NurOwn® for use in BrainStorm's planned Phase 3b trial in amyotrophic lateral sclerosis (ALS). This MOU enables BrainStorm to begin transfer of its manufacturing technology and start producing NurOwn at Pluri's manufacturing facility upon finalizing the binding definitive agreement. Under the terms of the proposed agreement, Pluri will provide GMP-compliant manufacturing of NurOwn at its facilities in Israel. This collaboration aims to fulfill essential supply requirements of NurOwn® as BrainStorm advances its Phase 3b clinical trial. Additionally, the two companies are exploring options for manufacturing to support potential future commercial distribution, pending approval of NurOwn. "Pluri has become a recognized leader in GMP-compliant clinical manufacturing of cell-based products, known for their exceptional quality standards and strict regulatory compliance," said Haro Hartounian, PhD, Chief Operating Officer at BrainStorm. "Pluri will offer manufacturing capacity to support our Phase 3b clinical trials, in addition to our existing development and clinical manufacturing activities at The Center for Advanced Cellular Therapies (I-ACT) in Israel. We believe that having Pluri's clinical manufacturing facility near BrainStorm's manufacturing and R&D teams will strengthen communication and foster a highly productive collaboration." Chaim Lebovits, President and CEO of Brainstorm, added, "The Phase 3b clinical trial marks a critical step toward potential regulatory approval of NurOwn, "This MOU with Pluri creates a strong foundation to meet the clinical supply requirements of NurOwn®. The proposed agreement also offers the prospect of establishing an attractive supply arrangement that aligns well with our strategic priorities as we prepare for the operational and financial commitments of the Phase 3b trial." Yaky Yanay, CEO and President of Pluri commented, "We applaud BrainStorm for their commitment to developing a novel cell therapy for ALS. We are eager to utilize our proprietary knowledge, long years of experience and manufacturing capabilities to support their mission of bringing hope to patients and families impacted by this devastating disease." The Phase 3b trial has been designed to enroll up to approximately 200 participants with ALS. It will be conducted in two parts: In Part A, participants will receive 3 doses of NurOwn or placebo for 24 weeks. This will be followed by an open label period, during which patients from both arms will receive 3 doses NurOwn for another 24 weeks (Part B). The primary efficacy endpoint will be a comparison of change in ALSFRS-R from baseline to week-24 (i.e. at the end of Part A) for NurOwn vs. placebo. Successful completion of Part A of the double-blind Phase 3b study will position BrainStorm to submit a Biologics License Application (BLA) for regulatory approval, potentially accelerating the path to market. BrainStorm plans to hold a conference call for investors later in Q4 2024, during which it will provide further updates on the NurOwn Phase 3 clinical program. About NurOwn® The NurOwn® technology platform (autologous MSC-NTF cells) represents a promising investigational therapeutic approach to targeting disease pathways important in neurodegenerative disorders. MSC-NTF cells are harvested from each person with ALS and are manufactured using an innovative and proprietary process, to secrete neurotrophic factors to target specific neurodegenerative diseases. The lead program for NurOwn is for the treatment of ALS. BrainStorm's long-term commitment to ALS is demonstrated in preclinical research and a series of clinical studies, all of which have been published in peer-reviewed journals. The NurOwn clinical program has generated valuable insights into the pathology of ALS, as well as disease progression and treatment. Since the initial Phase 3 readout, BrainStorm has shared the full dataset through rigorous peer-reviewed analysis, including: quantification of Floor Effect, which had been noted, but never before explored in depth; evaluation of multiple pre-specified biomarkers, collected at seven different points across 20 weeks during the trial, allowing a longitudinal view; and analysis of genetic data, which represents one of the first ALS trials to prospectively invoke pharmacogenomic analysis of clinical outcome, offering great promise for the development of future treatments for ALS. About Pluri Inc. Pluri™ is pushing the boundaries of science and engineering to create cell-based products for commercial use and is pioneering a biotech revolution that promotes global well-being and sustainability. The Company's technology platform, a patented and validated state-of-the-art 3D cell expansion system, advances novel cell-based solutions for a range of challenges— from medicine and climate change to food scarcity, animal cruelty and beyond. PluriCDMO™ offers CDMO services to companies from early preclinical development, through late-stage clinical trials and commercialization, with a mission to deliver high-quality, essential therapies to patients. . Pluri establishes partnerships that leverage the Company's proprietary 3D cell-based technology across various industries that require effective, mass cell production. To learn more, visit us at or follow Pluri on LinkedIn and X (formerly known as Twitter). About 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. 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. 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). Notice Regarding Forward-Looking Statements This press release contains "forward-looking statements" that are subject to substantial risks and uncertainties, including statements regarding meetings with the U.S. Food and Drug Administration (FDA), Special Protocol Assessment (SPA), ADCOM meeting related to NurOwn, the timing of a PDUFA action date for the BLA for NurOwn, the clinical development of NurOwn as a therapy for the treatment of ALS, the future availability of NurOwn to patients, and the future success of BrainStorm. All statements, other than statements of historical fact, contained in this press release are forward-looking statements. Forward-looking statements contained in this press release may be identified by the use of words such as "anticipate," "believe," "contemplate," "could," "estimate," "expect," "intend," "seek," "may," "might," "plan," "potential," "predict," "project," "target," "aim," "should," "will" "would," or the negative of these words or other similar expressions, although not all forward-looking statements contain these words. Forward-looking statements are based on BrainStorm's current expectations and are subject to inherent uncertainties, risks and assumptions that are difficult to predict. These potential risks and uncertainties include, without limitation, management's ability to successfully achieve its goals, BrainStorm's ability to raise additional capital, BrainStorm's ability to continue as a going concern, prospects for future regulatory approval of NurOwn, whether BrainStorm's future interactions with the FDA will have productive outcomes, and other factors detailed in BrainStorm's annual report on Form 10-K and quarterly reports on Form 10-Q available at . These factors should be considered carefully, and readers should not place undue reliance on BrainStorm's forward-looking statements. The forward-looking statements contained in this press release are based on the beliefs, expectations, and opinions of management as of the date of this press release. We do not assume any obligation to update forward-looking statements to reflect actual results or assumptions if circumstances or management's beliefs, expectations or opinions should change, unless otherwise required by law. Although we believe that the expectations reflected in the forward-looking statements are reasonable, we cannot guarantee future results, levels of activity, performance, or achievements. CONTACTS Media: Lisa Guiterman Phone: +1 202-330-3431 [email protected] IR: Michael Wood Phone: +1 646-597-6983 [email protected] Logo: SOURCE BrainStorm Cell Therapeutics Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

▎药明康德内容团队编辑 近期，全球细胞和基因疗法（CGT）领域迎来系列进展。Abeona Therapeutics公司向美国FDA重新提交了其自体细胞基因疗法prademagene zamikeracel（pz-cel）的生物制品许可申请（BLA），用于治疗隐性营养不良性大疱性表皮松解症（RDEB）。用于治疗肌萎缩侧索硬化（ALS）的在研细胞疗法debamestrocel公布了积极的扩展研究结果，与外部匹配的对照组相比具有统计学上显著的生存优势。多款用于治疗阿尔茨海默病（AD）的候选CGT疗法公布亮眼早期临床试验数据。临床试验结果本文将节选其中部分重要进展做简单介绍，仅供读者参阅。 图片来源：123RF ———✦研发进展✦——— ◇ Abeona Therapeutics公司宣布已向美国FDA重新提交了其自体细胞基因疗法pz-cel的BLA，作为隐性营养不良性大疱性表皮松解症患者的一种潜在新疗法。Pz-cel是由患者的自身皮肤细胞经过基因校正后扩增形成的角质细胞片，这些皮肤细胞的基因组中整合了一个功能正常的COL7A1基因以表达胶原蛋白VII，这种蛋白质是形成将表皮连接到真皮的锚纤维所需的。该候选疗法可通过外科手术来覆盖伤口区域，实现持续的伤口愈合和疼痛减轻。此前，pz-cel已获得美国FDA授予的再生医学先进疗法认定、突破性疗法认定、孤儿药资格及罕见儿科疾病认定。 ◇ BrainStorm Cell Therapeutics公司公布了其用于治疗ALS的在研细胞疗法debamestrocel的扩展研究结果。研究结果显示，在扩展使用项目（EAP）的最后一次随访中，10名受试者中有9人存活。生存曲线显示debamestrocel组与外部匹配对照组相比，具有统计学上显著的生存优势，其中debamestrocel组的中位生存时间为46.6个月，而匹配对照组为41.1个月。此外，在6名在3期临床试验期间已接受debamestrocel的患者中，观察到神经丝轻链（NfL）水平持续下降。相比之下，在3期试验中接受安慰剂的患者组中，中位NfL水平增加了37%，表明神经退行性病变加重。然而，这些患者在EAP中接受debamestrocel治疗后，大多数人的NfL水平趋于稳定。 Debamestrocel来源于ALS患者自身骨髓的间充质干细胞，这些细胞在体外进行扩增和分化，并且通过该公司独有的技术刺激分泌高水平的多种神经营养因子。这些分化的细胞在输注回到患者体内后，可能激活神经保护和免疫调节信号通路，从而减轻ALS患者的症状。 ◇ Lexeo Therapeutics公司公布了其用于治疗载脂蛋白E4（APOE4）基因纯合子型阿尔茨海默病的候选基因疗法LX1001的1/2期临床试验数据。结果显示，所有15名接受LX1001治疗的轻度认知障碍（MCI）或轻度或中度AD患者的神经保护性APOE2蛋白表达量呈剂量依赖性增加，12个月后仍具有持续性。大多数受试者的淀粉样病理学趋于稳定，超过三分之二患者的脑脊液（CFS）tau生物标志物（包括CSF T-tau、P-tau181、P-tau2172和P-tau2312）与基线和自然病史相比持续减少。此外，LX1001的安全性良好，没有报告淀粉样蛋白相关成像异常（ARIA）。 LX1001是一种基于AAVrh10的候选基因疗法，用于治疗APOE4基因纯合子型阿尔茨海默病患者。APOE4是APOE基因的一个等位基因，APOE4纯合子个体患阿尔茨海默病的风险大约是普通人群的15倍。而APOE2等位基因纯合子个体患阿尔茨海默病的风险比普通人群低40%。LX1001旨在在APOE4纯合子患者的中枢神经系统中表达具有保护作用的APOE2基因，潜在减缓或阻止阿尔茨海默病的进展。此前，LX1001已被美国FDA授予快速通道资格。 ◇ NKGen Biotech公司公布了其自体增强型自然杀伤（NK）细胞疗法troculeucel用于治疗中度AD的1/2a期临床试验中的1期临床数据。初步结果显示，在给予迄今为止最高剂量（60亿细胞）的冷冻保存的troculeucel的情况下，troculeucel表现出非常高的安全性，没有不良反应。在接受最高剂量治疗的前3名受试者中，100%患者的认知功能稳定或有所改善，并且其中两名受试者在接受仅三个月的治疗后，从中度疾病阶段显著好转至轻度认知障碍。 Troculeucel（SNK01）是一款自体、非基因工程改造的NK细胞产品，它具有增强的细胞毒性，活化受体表达率超过90%，可从任何供体中稳定生产。该候选疗法能够有效降低AD患者CSF中的α-突触核蛋白（α-syn）水平，该蛋白的升高被认为与认知能力下降有关。 ◇ Regeneration Biomedical公司公布了其用于治疗轻度至中度AD患者的自体Wnt激活脂肪来源干细胞（RB-ADSC）的1期临床试验结果。结果显示，该疗法的耐受性良好。第12周时，患者的P-tau和β淀粉样蛋白的水平有所下降。3名受试者中有2名的简易精神状态量表（MMSE）结果显示其认知功能有改善的趋势。 RB-ADSC是Wnt激活的脂肪源性干细胞，取自患者自身的脂肪组织。采集后，干细胞在体外进行培养和扩增，筛选出Wnt表达的干细胞，然后通过植入位于头皮下，可直接进入大脑的一个侧脑室的Ommaya储存器重新输回患者体内。 ◇ 中国国家药监局药品审评中心（CDE）官网公示，石药集团的嵌合抗原受体（CAR）-T细胞注射液SYS6020获得一项新的临床试验默示许可，拟开发治疗难治性全身型重症肌无力。公开资料显示，SYS6020为一款基于mRNA-脂质纳米颗粒（LNP）的CAR-T细胞注射液，也是石药集团布局的首个细胞治疗在研产品。SYS6020通过表达可特异性识别BCMA抗原的CAR，进而靶向识别患者体内BCMA阳性的细胞并对其进行杀灭，从而达到治疗目的。今年6月，SYS6020在中国首次获批临床，拟开发治疗复发或难治性多发性骨髓瘤。8月，SYS6020治疗系统性红斑狼疮（SLE）适应症获批临床，本次是该产品再次获得自身免疫疾病IND许可。 ◇ CDE官网公示，由艺妙神州全资子公司再妙生物与阳光诺和合作开发的CAR-T药物ZM001注射液获批临床，拟开发治疗SLE。根据新闻稿，ZM001通过特异性清除SLE患者体内的B细胞，抑制体内自身抗体的产生，缓解脏器中免疫复合物的沉积，并能够使机体重建正常的B细胞，进而缓解红斑狼疮症状，并维持长期疗效，是一种潜在的中度和重度SLE治疗药物。在此前进行的临床前研究中，ZM001展现出了清除B细胞快速且持续性的疗效，以及极低的严重不良反应发生率。 ◇ 普罗凯融生物申报的1类新药MSCohi-O镜片获批临床，拟开发治疗慢性眼部移植物抗宿主病（coGVHD）。根据普罗凯融生物公开资料介绍，这是其开发的负载间充质干细胞的高透氧水凝胶镜片。其核心创新性是解决脐带间充质干细胞自身无法停留在眼表的瓶颈障碍，实现稳定的眼表局部给药，从机理上治疗免疫相关的眼科疾病。该产品此前已经获得美国FDA授予孤儿药资料，用于治疗oGVHD。移植物抗宿主病是一种多系统疾病，其中眼部移植物抗宿主病会严重影响患者的视力，干预不及时还会导致患者失明。 ◇ 华道生物1类新药HD004细胞获批临床，拟用于治疗CLDN18.2表达阳性的晚期实体瘤伴恶性腹腔积液。根据华道生物公开资料，这是华道生物研发的靶向CLDN18.2的自体CAR-T产品。HD004细胞通过腹腔内灌注给药方式更直接靶向腹腔中的肿瘤细胞以发挥抗肿瘤作用，可以一定程度克服实体瘤CAR-T疗法障碍，提高CAR-T细胞运输和肿瘤浸润效率，在肿瘤局部停留时间延长，并且降低了脱靶效应带来的风险。 ▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放 参考资料（可上下滑动查看） [1] Lexeo Therapeutics Announces Positive Interim Data for LX1001, First-Ever Gene Therapy to Impact the Underlying Genetic Cause of APOE4-Associated Alzheimer’s Disease, at the Clinical Trials on Alzheimer’s Disease (CTAD) Conference. Retrieved November 1, 2024, from https://ir.lexeotx.com/news-releases/news-release-details/lexeo-therapeutics-announces-positive-interim-data-lx1001-first [2] NKGen Biotech Presents Phase 1/2a Troculeucel Data in Alzheimer’s Disease at the 17th Annual Clinical Trials on Alzheimer’s Disease (CTAD) Conference. Retrieved November 1, 2024, from https://www.globenewswire.com/news-release/2024/10/29/2970775/0/en/NKGen-Biotech-Presents-Phase-1-2a-Troculeucel-Data-in-Alzheimer-s-Disease-at-the-17th-Annual-Clinical-Trials-on-Alzheimer-s-Disease-CTAD-Conference.html [3] Regeneration Biomedical Presents Data on First Cohort from an Ongoing Phase I Clinical Trial of Stem Cell Therapy Delivered Directly into the Brains of Patients with Alzheimer’s Disease. Retrieved November 1, 2024, from https://www.globenewswire.com/news-release/2024/10/29/2970530/0/en/Regeneration-Biomedical-Presents-Data-on-First-Cohort-from-an-Ongoing-Phase-I-Clinical-Trial-of-Stem-Cell-Therapy-Delivered-Directly-into-the-Brains-of-Patients-with-Alzheimer-s-Di.html [4] Abeona Therapeutics® Completes Pz-cel Biologics License Application Resubmission to U.S. Food and Drug Administration. Retrieved November 1, 2024, from https://www.globenewswire.com/news-release/2024/10/29/2970698/0/en/Abeona-Therapeutics-Completes-Pz-cel-Biologics-License-Application-Resubmission-to-U-S-Food-and-Drug-Administration.html [5] BrainStorm Cell Therapeutics Presented Positive Survival Data from NurOwn® Expanded Access Program at 2024 Annual NEALS Meeting. Retrieved October 28, 2024, from https://www.prnewswire.com/news-releases/brainstorm-cell-therapeutics-presented-positive-survival-data-from-nurown-expanded-access-program-at-2024-annual-neals-meeting-302288404.html [6] 自愿公告 - 首款基於mRNA-LNP的CAR-T细胞注射液(SYS6020)再获新适应症临床试验批准. Retrieved October 25, 2024, from http://www.cninfo.com.cn/new/disclosure/detail?stockCode=01093&announcementId=1221524554&orgId=gshk0001093&announcementTime=2024-10-25 [7] 进军自免 | 艺妙神州治疗系统性红斑狼疮的CAR-T药物获得临床试验通知书. Retrieved October 29, 2024, from  https://mp.weixin.qq.com/s/x8WT9y2BSVT-o26Luzfl3A 免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。 版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。 分享，点赞，在看，聚焦全球生物医药健康创新