Eikonoklastes Therapeutics, Inc.

CINCINNATI--(BUSINESS WIRE)-- Eikonoklastes Therapeutics, a biopharmaceutical company developing a novel gene therapy platform to discover and develop critical treatments for Amyotrophic Lateral Sclerosis (ALS) and other neurodegenerative diseases, today announced the formation of a Scientific Advisory Board (SAB) - Gene Therapy, comprised of key leaders in neurology and gene therapy development. The SAB – Gene Therapy will work cohesively with management to advance the company’s gene therapy pipeline. Eikonoklastes’s gene therapy platform is built upon the pioneering work from the lab of Dr. Brian Head, Professor of Anesthesiology at University of California, San Diego. “I am very pleased to join Eikonoklastes’ Scientific Advisory Board,” said Dame Pamela Shaw, DBE, MD. “I look forward to working with this distinguished group of industry experts to advise the Eikonoklastes team through the development of its innovative technology to address enormous unmet clinical needs.” “We are fortunate to have the support of a truly world-class group of scientific and industry thought leaders on our Scientific Advisory Board, who will offer their expertise to ensure we optimally design our development program to meet the needs of patients and rapidly advance this technology through regulatory approval to treat patients with this devastating disease,” said Bruce Halpryn, Ph.D., Board Chair and CEO of Eikonoklastes. “Each member brings unique experience in technology, manufacturing, regulatory affairs, and clinical development. This collection of unparalleled expertise will serve us well as we develop our lead candidate, ET-101, initially for ALS and expanding into several other inadequately treated neurodegenerative diseases,” said Samuel Lee, MD, MBA, MPH, President and Chief Business Officer of Eikonoklastes. The founding members of the Eikonoklastes Scientific Advisory Board – Gene Therapy are: Brian Head, PhD Research Career Scientist, VA San Diego Healthcare System Professor of Anesthesiology, University of California – San Diego Russell Lonser, MD Chairman, Department of Neurological Surgery, Ohio State University Wexner Medical Center Director, Gene Therapy Institute, Ohio State University Professor of Neuroscience, Ohio State University College of Medicine Michael O’Beirne Former Executive Director, Regulatory Strategy at Sarepta Therapeutics Vaithianathan “Palani” Palaniappan, PhD Chief Technology Officer, Pioneering Medicines at Flagship Pioneering Former Head of Global Technical Operations, Sarepta Former Global Head of Biologics and New Modality Development, Takeda Seward Rutkove, MD Chair, Department of Neurology at Beth Israel Deaconess Medical Center Professor of Neurology, Harvard Medical School Dame Pamela Shaw, DBE, MD Founder and Director, Sheffield Institute for Translational Neuroscience Professor of Neurology, University of Sheffield Mark Tuszynski, MD, PhD Director, UC San Diego Translational Neuroscience Institute Distinguished Professor of Neuroscience, University of California – San Diego About Eikonoklastes Therapeutics Eikonoklastes Therapeutics is a biotech company rapidly developing a pipeline of disruptive new treatments for today’s most challenging diseases. The company’s 1st-in-class gene therapy (ET-101) has been engineered to overexpress Caveolin-1, which organizes and regulates synaptic receptors essential for neuromuscular signaling and function. Eikonoklastes is also advancing a new generation of tissue factor (TF) therapies (ET-201) for the treatment of Triple Negative Breast Cancer and other oncology indications. To learn more, visit

关键词肌萎缩侧索硬化症；Qalsody；研究进展肌萎缩侧索硬化症（ALS），俗称“渐冻症”，是一种渐进和致命的神经退行性疾病，由来自大脑和脊髓的运动神经元缺失引起，可导致四肢、躯干、胸部、腹部肌肉逐渐无力并萎缩，从而影响运动、交流、吞咽和呼吸功能，最终致死。据统计，全球范围内每10000人中大约有6-9个ALS患者，且患病率逐年增长。目前，ALS发病机制并不十分明确。据2023年3月英国谢菲尔德大学谢菲尔德转化神经科学研究所Pamela J. Shaw团队在Nature Reviews Drug Discovery期刊上发表的文章，ALS发病与遗传、氧化应激、兴奋性毒性、神经炎症反应、线粒体功能紊乱、DNA和RNA损伤、蛋白稳态受损、轴突损伤等有关，这些因素相互作用导致患者出现运动神经元损伤。复杂的发病机制导致ALS药物研发十分困难，目前全球获批治疗ALS的药物非常有限，已获批的药物包括利鲁唑、依达拉奉、Relyvrio和Qalsody。利鲁唑是是第一个获FDA和欧盟批准用于治疗ALS的药物。作为神经保护剂，利鲁唑可改善病人生存状态，但却无法阻止ALS病情的发展，目前已获批的剂型包括片剂、口腔膜剂和混悬剂。依达拉奉是一种脑保护剂（自由基清除剂），为期6个月的临床试验证明其能够减缓ALS相关的日常功能衰退。目前，已获批的剂型有静脉注射剂（如Radicava）和口服混悬剂（如Radicava ORS）。Relyvrio是苯丁酸钠(PB)和牛磺酸二醇(TURSO)组成的复方制剂，其靶向ALS和其他神经退行性疾病中的内质网和线粒体依赖性神经元退行性变通路，减少神经元死亡和功能障碍，可显著减缓ALS疾病进展和延长生存期。2022年，Relyvrio先后在加拿大和美国被批准用于治疗成人ALS。Qalsody（tofersen）是Ionis研发的一种反义寡核苷酸（ASO)药物，它能够与编码SOD1的 mRNA结合，被核糖核酸酶RNase-H降解，从而减少突变SOD1蛋白的生成。2023年4月，Qalsody被FDA批准用于治疗超氧化物歧化酶1 (SOD1)突变所致的ALS。此外，目前全球还有多款在研ALS新疗法，详见下表。在研ALS疗法药物类型多样，涉及间充质干细胞疗法、基因疗法（ASO疗法和腺相关病毒（AAV）介导基因疗法）、Treg细胞疗法等，且有多款进入临床后期。全球部分在研ALS药物来源：公开资料01干细胞疗法干细胞疗法可以通过多种途径进行神经损伤修复，具有治疗ALS等多种中枢神经系统疾病潜力。过去十几年，ALS干细胞疗法的开发和临床转化取得了巨大的成就，据不完全统计，clinicaltrials官网登记的干细胞治疗ALS的临床研究数量超过40项。其中间充质干细胞作为能够保护运动神经元（MN）、分化为多种神经细胞类型、调节免疫细胞作用和减少中枢神经系统（CNS）炎症的细胞而脱颖而出。据悉，Corestem公司的间充质干细胞疗法NeuroNata-R已于2014在韩国获有条件批准用于治疗ALS，目前NeuroNata-R 联合利鲁唑治疗ALS的3期临床试验正在进行中。此外，Brainstorm公司的间充质干细胞疗法NurOwn®进展也较快。2020年11月，Brainstorm宣布NurOwn®在治疗ALS的3期临床试验中未能达到主要终点指标和关键次要终点，不过NurOwn®在病情较轻的患者组中产生了具有临床意义的作用。2022年11月，FDA在未对NurOwn®的BLA进行审查情况下就否决了其上市申请。02基因疗法自1993年发现第一个ALS致病基因，迄今为止，已有近30个基因被证实与ALS的发病相关，最常见的致病基因突变主要包括SOD1、TARDBP、FUS、OPTN、SQSTM1、DAO、DCTN1、VAPB、SIGMAR1、GRN、C9orf72等。近30年来，全球多款治疗ALS的基因疗法已进入临床试验阶段。在研ALS基因疗法包括反义寡核苷酸（ASO）疗法、腺相关病毒（AAV）介导的基因沉默/传递等多种创新疗法，其中首款治疗ALS的ASO药物Qalsody已于今年4月在美国获批。此外，ASO疗法中的ION363进展也较快，目前已进入3期临床。ION363是一种针对FUS RNA的反义药物，可减少FUS蛋白的产生。在FUS-ALS小鼠模型中，反义介导的突变FUS蛋白的还原可防止运动神经元丢失。通过针对FUS-ALS的根本原因，ION363具有减少或预防FUS-ALS患者疾病进展的潜力。2021年4月，ION363治疗FUS突变ALS患者的3期临床试验启动。WAVELife Sciences开发WVE-004是的一款针对C9orf72基因突变导致的ALS和额颞叶痴呆（FTD）的ASO药物，旨在选择性靶向含有与C9orf72基因相关的六核苷酸重复扩增（G4C2）的转录变体，从而保留C9orf72蛋白。C9orf72中的G4C2扩增是ALS和FTD散发性和遗传性形式的最常见遗传原因之一。目前， WVE-004正在进行一项针对42名与C9ORF72相关的ALS或FTD患者的1/2期安全性研究。AAV介导的ALS基因疗法进展相对较慢，其中Apic Bio开发APB-102由重组AAVrh10载体组成，该载体表达微核糖核酸（miRNA），旨在敲低SOD1的表达，目的是减缓或潜在逆转SOD1突变患者ALS的进展，目前已进入1/2期临床。Eikonoklastes Therapeutics的ET-101（SynCav1）是由加州大学圣地亚哥分校Brian Head博士实验室首创，用于过表达Caveolin-1的一种AAV9基因疗法，Caveolin-1可以组织和调节神经肌肉信号传导和功能所必需的突触受体。研究结果显示，增加Caveolin-1可以对神经细胞产生保护作用，使神经细胞可以补偿潜在疾病引起的神经退行性过程，并且使得细胞保持健康并提高其功能性。2022年12月，ET-101获得FDA孤儿药认定，用于治疗散发性和家族性ALS。03其他药物Treg细胞疗法也被开发用于治疗ALS，如ALS001。ALS001是一种自体的Treg细胞疗法，已被FDA授予的孤儿药资格。其1期临床结果表明，ALS001能够对神经起到保护作用，减缓ALS的进展。此外，Atibuclimab、Tegoprubart（AT-1501）等单抗也开发用于治疗ALS。其中Atibuclimab是一款靶向CD14的单克隆抗体，由小鼠可变区和人类IgG4 Fc区组成，可调节感染和损伤引发的致病性炎症反应。2021年1月，FDA授予Atibuclimab治疗ALS的孤儿药资格。Tegoprubart是一种靶向CD40L单抗，可阻断CD40L通路的激活，在ALS的临床前动物模型显示，CD40L通路可以改善肌肉功能、延缓疾病进展和提高存活率。在健康志愿者和患有ALS的成人开展的1a/1b期单次递增剂量试验显示，Tegoprubart在所有剂量下都表现出良好的耐受性，并显示出良好的安全性。而且，Tegoprubart在整个剂量范围内显示出线性剂量比例，半衰期长达26天。已公布的Tegoprubart治疗ALS的2a期临床试验结果显示：Tegoprubart表现出良好的耐受性，以及降低炎症相关生物标志物水平的作用。总结肌萎缩侧索硬化症(ALS)被WHO列为与艾滋病、癌症、白血病、类风湿等并列的五大绝症之一，然而目前该领域获批药物有限，ALS患者3年和5年死亡率分别为50%和80%。随着研究的深入，基因疗法、细胞疗法等药物治疗ALS的潜力已显现，期待未来有更好的ALS疗法获批上市，造福广大ALS患者。END👇关注药渡数据媒体矩阵

AAV Manufacturing Partnership to Advance Eikonoklastes’ Novel Gene Therapy for Amyotrophic Lateral Sclerosis (ALS) CINCINNATI & COLUMBUS, Ohio--(BUSINESS WIRE)-- Eikonoklastes Therapeutics, a preclinical biotech company developing treatments for today’s most challenging diseases, and Forge Biologics, a gene therapy-focused contract development and manufacturing organization, today announced a manufacturing partnership that will advance Eikonoklastes’ AAV-based gene therapy, ET-101, into clinical trials for the treatment of patients with amyotrophic lateral sclerosis (ALS). This press release features multimedia. View the full release here: Forge will provide adeno-associated viral (AAV) process development and manufacturing services for ET-101. Eikonoklastes will utilize Forge’s platform process including its proprietary HEK 293 suspension Ignition Cells™ and pEMBR™ adenovirus helper plasmid. All development and AAV manufacturing activities will occur at the Hearth, Forge’s 200,000 square foot gene therapy facility in Columbus, Ohio. “Eikonoklastes is conducting promising research into treating patients with ALS, and we are honored to work together with them during this critical phase of development to help ET-101 enter clinical trials,” said Timothy J. Miller, Ph.D., CEO, President, and Co-Founder of Forge Biologics. “Our primary goal is to deliver the AAV resources, scale, technology, and expertise for our partners to help patients living with diseases like ALS with no known cure.” ALS is a rare neurological disease with significant socioeconomic impact, whose patients are desperate for novel, safe and effective therapies. ALS is the lead indication for Eikonoklastes’ ET-101, which has just received Orphan Drug Designation from the FDA—an important regulatory milestone reflecting the compelling data underlying the ET-101 program and its potential as a first-in-class treatment option for both familial and sporadic ALS. “We are excited to advance ET-101, our novel treatment for neurodegenerative diseases, towards a first-in-human clinical trial in ALS patients. Partnering our AAV manufacturing with Forge will further our ability to advance into clinical trials,” said Bruce Halpryn, Ph.D., Chair, CEO, and Co-Founder of Eikonoklastes Therapeutics. “With their end-to-end platform supporting AAV therapies, Forge is accelerating our development to reach patients suffering from ALS.” About Amyotrophic Lateral Sclerosis (ALS) ALS, also known as Lou Gehrig’s Disease, is a rare, progressive, debilitating, and universally fatal neurodegenerative disease affecting the motor neurons connecting the brain and spinal cord. Degeneration of these neurons leads to paralysis as the brain loses its ability to control muscle movement. Most people with ALS succumb to respiratory failure, usually within three to five years from when symptoms first appear. An estimated 10 percent of ALS is familial and caused by genetic mutations that are inherited. The 90%+ of sporadic ALS may be due to a combination of environment and genetic risk factors. There is currently no cure for either familial or sporadic ALS. About Eikonoklastes Therapeutics Eikonoklastes Therapeutics is a preclinical biotech company rapidly developing a pipeline of disruptive new treatments for today’s most challenging diseases. The company’s 1st-in-class gene therapy (ET-101) has been engineered to overexpress Caveolin-1, which organizes and regulates synaptic receptors essential for neuromuscular signaling and function. Eikonoklastes is also advancing a new generation of tissue factor (TF) therapies (ET-201) for the treatment of Triple Negative Breast Cancer and other oncology indications. To learn more, visit About Forge Biologics Forge Biologics is a hybrid gene therapy contract manufacturing and clinical-stage therapeutics development company. Forge’s mission is to enable access to life changing gene therapies and help bring them from idea to reality. Forge’s 200,000 square foot facility utilizes 20 cGMP suites in Columbus, Ohio, the Hearth, to serve as its headquarters. The Hearth is a custom-designed cGMP facility dedicated to AAV manufacturing and hosts scalable, end-to-end manufacturing services. Offerings include process and analytical development, plasmid DNA manufacturing, viral vector manufacturing, final fill, as well as regulatory consulting support to accelerate gene therapy programs from preclinical through clinical and commercial stage manufacturing. By taking a patients-first approach, Forge aims to accelerate the timelines of these transformative medicines for those who need them the most. To learn more, visit .