ProMIS Neurosciences, Inc.

9月8日，英国，NRG Therapeutics（“NRG”）是一家创新的神经科学公司，致力于解决线粒体功能障碍的新机制，宣布完成其超额认购的5000万英镑（6700万美元）B轮融资。（新锐！1800万美元A轮融资，开发帕金森和ALS新药） 此次融资由SV Health Investors的痴呆症发现基金（DDF）领投，该基金是一家专业风险基金，致力于投资开发或实现痴呆症新疗法的公司。其他投资者包括英国商业银行、M Ventures、诺华风险基金和Criteria Bio Ventures，以及现有的投资者Omega Funds和Brandon Capital。创始投资者Parkinson's UK通过其药物开发部门Parkinson's Virtual Biotech，仍然是一个积极和支持的投资者。 这笔资金将使NRG Therapeutics能够实现肌萎缩侧索硬化症（ALS）/运动神经元疾病（MND）的临床概念验证，同时通过1b期研究为帕金森病患者提供有意义的临床数据。 NRG主要开发候选药物NRG5051已被证明具有深刻的神经保护作用，并在帕金森病和ALS/MND的临床前模型中显著减少了神经炎症。NRG5051已完成IND enabling研究，并有望在2026年初进入首个人体临床研究。B轮融资通过ALS/MND的临床概念验证（PoC）研究为开发提供资金。 创始团队:Richard Rutter（CSO）；Neil Miller （CEO）；Grant Hawthorn（COO） NRG Therapeutics联合创始人兼首席执行官Neil Miller表示：“我很高兴欢迎我们的新投资者，并感谢我们现有的投资者给予的坚定支持。开发治疗神经系统疾病的新药非常具有挑战性，但鉴于未满足的医疗需求很高，老龄人口的患病率越来越高，人们对它的兴趣也在增加。这些新基金为通过ALS/MND的PoC推进我们的领先项目提供了现金跑道，并为包括帕金森病在内的其他适应症开发了我们的小分子候选药物组合，为越来越多的受神经退行性疾病影响的人及其家人带来了新的希望。” NRG已经鉴定出一种新的线粒体通透性转换孔（mPTP）调节因子，该调节因子对孔开放至关重要，并且易于受到小分子抑制。这一突破使NRG能够开发出一类新的小分子mPTP抑制剂，其设计目的是在口服时有效地穿透大脑。 线粒体对能量产生至关重要，特别是在黑质神经元（帕金森氏症）和运动神经元（ALS/MND）中，它们具有高能量需求，因此对线粒体健康特别敏感。帕金森病（a-突触核蛋白）和ALS/MND（TDP-43）中的病理蛋白对线粒体有毒，并导致线粒体功能障碍，这是神经退行性疾病中常见的潜在病理。抑制mPTP开放已被证明可以保护线粒体免受这种功能获得蛋白毒性的影响，并在临床前模型中保护神经元。 帕金森病是增长最快的神经退行性疾病之一，预计到2050年全球患病率将翻一番。目前还没有任何治疗方法可以减缓或阻止帕金森病的进展，现有的药物只能提供暂时的症状缓解。ALS/MND是一种罕见的、进展迅速的神经退行性疾病，其医疗需求尚未得到满足。2023年，美国FDA批准Qalsody（tofersen）作为一种基于血液生物标志物终点的罕见遗传（SOD1）形式的ALS/MND的疾病改良治疗方法。然而，大多数散发性疾病患者仍然没有得到现有药物的良好治疗。 关注下方公众号，带你看世界!

Cohort 2 fully enrolled; enrollment and dosing now underway for Cohort 3 (final dose level); No cases of amyloid-related imaging abnormalities (ARIA) observed to date; The trial, expected to enroll 128 patients, remains on track to report 6-month interim data in Q2 2026 and final 12-month top-line results in Q4 2026. Sept. 03, 2025 -- ProMIS Neurosciences, Inc. (Nasdaq: PMN), a clinical-stage biotechnology company developing next-generation therapies for Alzheimer’s disease (AD) and other neurodegenerative disorders, today announced that the independent Data and Safety Monitoring Board (DSMB) for its ongoing PRECISE-AD Phase 1b clinical trial has unanimously recommended that the Company proceed to the third and final dose escalation cohort in this trial of PMN310 for the treatment of AD. The recommendation followed a review of available safety data through Cohort 2, which has now been fully enrolled, with no cases of amyloid-related imaging abnormalities (ARIA) observed to date. Enrollment of patients into Cohort 3 is now underway, keeping the Company on track to deliver 6-month interim data in the second quarter of 2026 and final 12-month top-line results in the fourth quarter of 2026. “The DSMB’s recommendation to proceed with the planned escalation to the final dose cohort underscores the steady progress of our Phase 1b program and keeps us firmly on track toward our planned interim and top-line data readouts in 2026,” said Neil Warma, President and CEO of ProMIS Neurosciences. “Together with the recent FDA Fast Track designation for PMN310, this achievement highlights the momentum we are building as we advance through clinical development. “Unlike therapies directed at amyloid plaque, which continue to be associated with safety concerns, PMN310 is engineered to avoid plaque and precisely target only toxic oligomers, the amyloid species most closely linked to neuronal damage and disease progression. The favorable safety profile observed to date highlights this differentiated strategy and reinforces the potential of PMN310 to meet a critical unmet need in Alzheimer’s disease.” “The safety profile observed with PMN310 to date is encouraging and consistent with its design as a highly selective antibody targeting toxic oligomers,” said Larry Altstiel, M.D., Ph.D., Chief Medical Officer of ProMIS Neurosciences. “By potentially avoiding plaque and monomer binding, we believe PMN310 may reduce off-target effects and focus therapeutic activity on the molecular species most implicated in disease progression. As we enter the final cohort, we look forward to assessing a comprehensive biomarker panel, including pTau217, pTau243, neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), Abeta42/40 ratios and synaptic integrity markers such as SNAP25 and neurogranin, to provide critical insights into target engagement, neuronal injury, and potential disease-modifying effects. Importantly, this trial is designed to enroll 128 patients, providing a robust dataset across biomarkers, safety outcomes such as ARIA, and clinical measures that will inform the next phase of development.” PMN310 is a humanized IgG1 antibody directed toward toxic amyloid-beta oligomers (AβOs) that are believed to be a major driver of AD. The DSMB recommended continuation of the trial as planned without any modification and provided clearance to continue the trial and proceed to the next and final dosing level, going from the 10 mg/kg dose of PMN310 in the second cohort to the 20mg/kg dose for the final cohort. The DSMB based its review on cumulative safety data for all patients in the current and prior cohort. Neil Warma, President and CEO of ProMIS Neurosciences, will discuss our clinical progress along with other corporate updates at the upcoming H.C. Wainwright 27th Annual Global Investment Conference, taking place in New York, New York on September 10, 2025, at 12:30 p.m. Eastern Time. The webcast of the presentation may be accessed by visiting the Events page of the Company’s website at www.promisneurosciences.com, and will be available for at least 30 days following the event. ProMIS Neurosciences is a clinical-stage biotechnology company committed to the discovery and development of therapeutic antibodies and vaccines selective for toxic oligomers associated with the development and progression of neurodegenerative and other misfolded protein diseases. The Company’s proprietary target discovery engine, EpiSelect™, has been shown to predict novel targets known as Disease Specific Epitopes (DSEs) on the molecular surface of misfolded proteins that cause neurodegenerative and other misfolded protein diseases, including Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), multiple system atrophy (MSA), and Parkinson’s Disease (PD). ProMIS has offices in Cambridge, Massachusetts (USA) and Toronto, Ontario (CAN). PMN310, the Company’s lead product candidate for the treatment of AD, is a humanized monoclonal antibody that has been designed to selectively target only the toxic oligomers, avoiding plaque, thereby potentially reducing or eliminating ARIA liability. In addition, because PMN310 may not be limited by off-target binding or side effects, PMN310 could potentially offer an improved efficacy profile over other amyloid-directed antibody therapeutics. PMN310 was granted Fast Track designation by the U.S. Food and Drug Administration in July 2025. Based on the encouraging results from the Phase 1a trial (NCT06105528) of PMN310, ProMIS initiated PRECISE-AD, a Phase 1b clinical trial in AD patients. PRECISE-AD (NCT06750432) is a randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability and pharmacokinetics (PK) of multiple ascending doses (5, 10, 20 mg/kg) of intravenous PMN310 in patients with Mild Cognitive Impairment due to AD and mild AD (Stage 3 and Stage 4 AD). PRECISE-AD will be the first study to examine the effects of a monoclonal antibody directed solely against AβO on biomarkers associated with AD pathology and clinical outcomes. Safety will be a primary outcome of the study with particular emphasis on assessing whether, as a non-plaque binder, PMN310 may have a reduced risk of ARIA. The study is powered to provide 95% confidence for detection of ARIA. The study has been designed with a sample size intended to provide sufficient power to provide meaningful insight into effects of PMN310 on biomarkers and clinical outcomes. Toxic misfolded proteins underlie the pathogenesis of neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Generation of therapeutic antibodies selectively targeting only disease-misfolded protein isoforms, while sparing normal or irrelevant isoforms of the same protein, has not yet been successfully achieved by conventional immunization strategies. ProMIS Neurosciences has developed a computational platform (EpiSelectTM) to identify conformational epitopes that are uniquely exposed on toxic misfolded proteins, which can then be used to generate misfolding-specific antibodies or vaccine formulations. Application of the ProMIS platform produced PMN310, a clinical stage, humanized monoclonal antibody candidate that has been shown to be highly selective for toxic amyloid-beta oligomers (AβO) without significant reactivity with amyloid-beta monomers or fibrils, thereby avoiding target distraction by these more abundant species, and potentially reducing the risk of brain edema and microhemorrhages associated with the targeting of vascular/parenchymal amyloid. Similarly, specific epitopes for alpha-synuclein toxic oligomers/soluble fibrils that drive synucleinopathies, and for pathogenic TDP-43 in ALS and FTD have been identified and lead candidate antibodies generated. The precise conformation of these epitopes has been translated into vaccines inducing an antibody response selective for pathogenic molecular species in preclinical mouse vaccination studies The content above comes from the network. if any infringement, please contact us to modify.

GRIN Therapeutics于2025年5月宣布完成1.4亿美元D轮融资，并与意大利制药巨头Angelini Pharma达成独家合作，获得5000万美元预付款、最高5.2亿美元里程碑付款及销售分成。 随后，公司正式启动radiprodil的全球Ⅲ期临床试验，radiprodil是针对神经发育障碍（GRIN-NDD）的负向别构调节剂，即将迈向上市冲刺。 若试验达到预设终点（如癫痫发作频率显著降低、临床整体印象量表评分改善），将推动FDA和EMA缩短审评周期，甚至可能基于“未满足医疗需求”授予优先审评，使药物提前1-2年进入市场，抢占全球首个GRIN-NDD疗法的先发优势。 目前GRIN Therapeutics的重点方向是Honeycomb试验（核心管线radiprodil）与Astroscape试验（适应症拓展）。以下是这两个板块的整体速览表： 两大实验基本情况概览 01 Honeycomb试验： 解决神经发育障碍患者特异性难题 GRIN Therapeutics的核心产品radiprodil是一款选择性靶向N-甲基-D-天冬氨酸受体亚型2B（GluN2B）的负向别构调节剂，主要针对GRIN-NDD。 GRIN-NDD是由GRIN基因功能获得性突变（GoF）导致GluN2B亚基过度激活，引发NMDA受体（N-methyl-D-aspartate，一种谷氨酸受体）异常信号传导，最终导致癫痫、发育迟缓等多系统症状的罕见病。 突变基因主要包括GRIN1、GRIN2A、GRIN2B、GRIN2D四种基因突变类型。患者普遍面临发育迟缓、智力障碍及药物难治性癫痫等多重困扰。 美国CDC（CentersforDiseaseControlandPrevention：美国疾病控制与预防中心）资助的研究显示，新生儿中GRIN-NDD总体发病率为3.2~5.45例/10万活产，其中GRIN2B突变占比最高（5.91例/10万），GRIN2A最低（3.23例/10万）。 这一罕见病群体正在逐步扩大，早期发病地域主要集中在欧美，后期也逐渐向东方国家蔓延。2021年，北京儿童医院研究报告显示有11例中国患儿为新生突变。 但现有疗法仅能缓解症状，无法触及NMDA过度激活的核心病理机制，缺乏特异性药物。 在临床实践中，医生主要通过抗癫痫药物控制癫痫发作，例如使用苯二氮䓬类药物或丙戊酸，但这类药物对GRIN-NDD患者有效性的差异显著，部分患者可能需要超常规剂量才能缓解症状，但过多剂量容易对患者造成一定负面影响（如记忆力下降、造成肝脏代谢负担等）。 此外，抗癫痫药物虽能部分控制癫痫发作，但对认知障碍、肌张力异常等症状几乎无效，且长期使用可能引发镇静、认知抑制等副作用。 radiprodil的独特之处就在于，它能够选择性抑制GluN2B过度激活的作用机制，在临床前研究中已被证实能有效调节突触传递异常。 adiprodil Phase1b 在Radiprodil Phase1b/2a的Honeycomb试验中，Radiprodil在治疗GRIN相关神经发育障碍（GRIN-NDD）患者时，行为量表评估（包括CGI-C和ABC-C）显示了积极的改善趋势。 在所有参与试验的患者中（包括癫痫和非癫痫队列），CGI-C和ABC-C均显示临床改善：护理人员和临床医生报告患者行为症状（如情绪调节、社交互动、刻板行为）的减轻。改善与癫痫发作减少无关，表明Radiprodil可能直接缓解神经发育障碍的核心行为问题。 FDA基于此授予突破性疗法认定，明确其“实质性优于现有对症治疗”的定位，标志着该试验不仅验证了靶点有效性，更将GRIN-NDD从“无药可治”推向“对因治疗”的新阶段。 02 Astroscape实验： 高表达共性机制推进多适应症管线拓展 GRIN Therapeutics的管线布局展现出鲜明的“靶点中心化，多适应症拓展”特征。 除上文针对GRIN-NDD的核心管线外，公司现已启动Astroscape试验。 该试验是GRIN Therapeutics开展的概念验证篮子试验，针对结节性硬化症（TSC）和局灶性皮质发育不良Ⅱ型（FCDⅡ型）患者。 Astroscape研究 这些群体普遍存在“现有药物无法控制癫痫（或长期失效）”的问题，因此研究基于“TSC和FCD患者脑皮层NR2B（GluN2B）亚基过度表达，驱动NMDA受体异常激活引发癫痫”的机制来探索radiprodil的疗效与安全性。 该试验与GRIN-NDD核心管线（Honeycomb试验）形成“靶点验证→跨适应症延伸”的协同，加速药物在脑健康领域的突破。 这一拓展能够实现源于团队发现TSC和FCD病变脑组织中均存在GluN2B的过度表达，与GRIN-NDD的病理机制具有同源性。 此外，基于TSC和FCD病变组织中GluN2B高表达的共性机制，公司于2024年10月启动GRIN Therapeutics Astroscape试验（Phase1b/2a），评估radiprodil对难治性癫痫的疗效。 ● Tuberous sclerosis complex（TSC，机制同源拓展） 机制：TSC患者病变组织中NR2B（GluN2B）亚基过表达，导致NMDAR介导的兴奋性突触过度激活，驱动难治性癫痫。 阶段：处于PoC（概念验证）早期，2024年10月启动Astroscape试验（1b/2a），已入组30例患者（20例TSC、10例FCD）。试验采用“剂量爬坡+开放扩展”设计，允许患者进入长期延伸研究。 ● Focal cortical dysplasia（FCDII型，机制同源拓展） 机制：FCDⅡ型患者皮质发育异常区存在NR2B过表达，与TSC共享“NMDAR兴奋性失衡”病理，因此与TSC共线开发（同属Astroscape试验队列）。 阶段：同TSC处于PoC早期，依托Astroscape试验同步评估。FCD作为儿童难治性癫痫的核心病因（占药物难治性癫痫的20%），若验证有效，将覆盖更广泛的“结构异常性癫痫”群体。 ● Other DEEs（发育性癫痫脑病，疾病谱延伸） 机制：针对更广泛的NMDAR功能失调（非突变型，如表达异常、调控异常）导致的发育性癫痫脑病（DEEs），涵盖West综合征、Dravet综合征等。 阶段：目前处于概念探索后期，通过与约翰霍普金斯医院等机构合作，筛选NMDAR功能异常生物标志物匹配的患者，计划2026年启动探索性PoC试验。 Other DEEs GRIN整体的管线布局体现了“精准靶点×机制延伸”的逻辑，既规避了单一适应症的市场局限，又通过共享临床前数据降低研发成本。 随着Ⅲ期临床试验的启动，radiprodil正从“罕见病创新药”向“神经发育疾病平台型药物”迈进。 管线开发情况 03 1.4亿美元D轮融资， 康奈尔医学院临床经验加持 2025年5月，GRIN Therapeutics完成1.4亿美元D轮融资，意大利百年药企（始于1920年）Angelini Pharma不仅注入6500万美元战略投资，更通过独家合作获得radiprodil在北美以外地区的开发与商业化权利。 该合作条款包括5000万美元预付款、最高5.2亿美元里程碑付款及销售分成。这一合作模式既解决了全球化商业化的资源需求，又通过产业资本的注入强化了研发底气。 Angelini Pharma在神经罕见病与脑健康领域深耕数十年（如布局Angelman综合征疗法），能凭借欧洲及新兴市场的渠道、患者资源，有利于加速radiprodil在北美以外的临床推进与市场开拓。 而黑石生命科学（Blackstone Life Sciences）作为长期投资者，在D轮中注资7500万美元，并通过2亿美元的资本承诺为公司提供全周期支持，这种“财务投资+产业赋能”的模式，加速了radiprodil从临床到上市的转化效率。 在融资层面的亮眼表现，本质上是资本对GRIN Therapeutics技术价值与团队实力的双重认可。 总裁兼CEO Bruce Leuchter医生是威尔康奈尔医学院临床神经精神科主任。此外，他还具备丰富的药企运营经验，曾在高盛、瑞信等机构负责生物科技股权研究与并购。 首席医学官MichaelA.Panzara深耕神经发育疾病临床研究，主导了关键临床试验的设计与监管沟通。 而2025年6月新加入董事会的神经科学专家GailFarfel博士，更以其在ProMIS Neurosciences等企业积累的商业化经验，为公司提供战略指导。 目前，radiprodil先后获得FDA突破性疗法认定（基于Honeycomb试验中癫痫发作的显著改善）、孤儿药资格，以及欧盟EMA的优先药物（PRIME）认定。这些资质不仅提供了加速审批通道，更凸显了监管机构对其“解决重大未满足医疗需求”的认可，有望抢占全球首个GRIN-NDD疗法的先发优势。 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。文中如果涉及企业信息和数据，均由受访者向分析师提供并确认。 动脉网，未来医疗服务平台