Ezogabine

Results demonstrated statistically significant effects on biomarkers that predict ALS disease progression and severity Evidence of brain penetration, target engagement, and potential anti-seizure effects demonstrated through biomarkers for TMS-EMG and EEG Safety and tolerability profile consistent with previously reported results for QRL-101 QurAlis intends to advance QRL-101 into proof-of-concept studies as a potentially best-in-class treatment for both ALS and epilepsy CAMBRIDGE, Mass., March 12, 2025 /PRNewswire/ -- QurAlis Corporation ("QurAlis"), a clinical-stage biotechnology company driving scientific breakthroughs into powerful precision medicines that have the potential to alter the trajectory of neurodegenerative and neurological diseases, today announced positive topline data from QurAlis' Phase 1 proof-of-mechanism (PoM) clinical trial of QRL-101 in healthy volunteers evaluating biomarkers related to amyotrophic lateral sclerosis (ALS) and epilepsy. Topline results demonstrated a dose-dependent, statistically significant decrease in motor nerve excitability threshold tracking (mNETT) strength-duration time constant (SDTC), the co-primary endpoint of the trial related to ALS. SDTC is a well-established electrophysiological biomarker of peripheral motor excitability related to ALS, where elevation of SDTC has been clinically shown to predict faster disease progression and mortality. The decrease in SDTC observed with QRL-101 in this study was approximately 50% greater than previously reported for the Kv7 potassium channel opener ezogabine in a single-dose study in people with ALS. Additional observations for multiple secondary and exploratory endpoints related to motor nerve excitability were also significantly impacted. The clinical trial demonstrated a statistically significant impact on multiple secondary and exploratory endpoints related to epilepsy. These included transcranial magnetic stimulation electromyography (TMS-EMG) intracortical facilitation which indicates effective inhibition of cortical excitability, as well as significant increases in electroencephalography (EEG) spectral power in beta and gamma spectral bands further demonstrating cortical target engagement and brain penetration. There was minimal to no impact on the slower delta and theta EEG bands, which suggests a low potential for GABA-A receptor activation and sedation. The study did not reach statistical significance on the co-primary endpoint of TMS-EMG motor evoked potential (MEP) amplitude, another measure of corticospinal excitability. Results also demonstrated that the safety and tolerability profile of QRL-101 was consistent with previously reported study results evaluating QRL-101 to date. There were no serious adverse events or discontinuations due to adverse events reported observed in the study. "We are excited by these topline data from our biomarker study in healthy participants which suggest that QRL-101 has the potential to provide a therapeutic effect for both ALS and epilepsy," said Kasper Roet, Ph.D., CEO and co-founder of QurAlis. "Loss of Kv7.2/7.3 function from the mis-splicing of the KCNQ2 gene leading to hyperexcitability-induced neurodegeneration was one of the first genetic breakthroughs from human ALS motor neuron stem cell models made by our founders at Harvard. QurAlis was started to develop a best-in-class Kv7 ion channel opener for the treatment of hyperexcitability-induced disease progression in ALS, which occurs in about half of all people living with ALS. Elevated SDTC has been clinically linked to faster disease progression and mortality, underscoring the need for an effective treatment for this population." Dr. Roet continued, "The decrease in SDTC observed with QRL-101 in this study was approximately 50% greater than previously reported for the Kv7 opener ezogabine in a single-dose study in people with ALS. QRL-101 has the potential to be a promising therapeutic, especially considering the encouraging results from a previous study with ezogabine in ALS patients showing positive effects on both SDTC and the disease progression biomarker compound muscle action potential (CMAP). Further, based on the strong clinical validation of Kv7.2/7.3 ion channel openers in seizure reduction, the TMS-EMG intracortical facilitation together with the EEG data from this study suggest QRL-101 may have the potential to reduce both frequency and severity of seizures in people living with epilepsy without causing sedation. We are encouraged by these results and look forward to advancing the clinical program for QRL-101 in both ALS and epilepsy so that we can fulfill our mission of bringing much-needed precision medicine options to patients." Kv7.2/7.3 is a voltage-gated potassium channel whose role is crucial for the regulation of both neuronal excitability and membrane potential. QRL-101 is a potentially best-in-class selective Kv7.2/7.3 ion channel opener for the treatment of hyperexcitability-induced disease progression in ALS, which occurs in both sporadic and genetic forms of ALS, with the majority caused by the mis-splicing of the KCNQ2 gene in the pre-mRNA. Kv7 is also a clinically validated target to regulate the hyperexcitable state in epilepsy. In vivo and in vitro studies have demonstrated that QRL-101 is more potent in threshold track studies and exhibits the potential for fewer clinical adverse events that ezogabine, a less selective, first-generation, Kv7.2/7.3 channel opener. The Phase 1 PoM study (QRL-101-05, NCT06681441) was a randomized, double-blind, placebo-controlled, three-way crossover trial. The study was conducted at the Centre for Human Drug Research, an early-phase Contract Research Organization based in Leiden, The Netherlands. The study evaluated two dose levels of QRL-101 versus placebo in healthy volunteers, assessing: Co-primary endpoints: Motor nerve excitability (mNETT SDTC; ALS biomarker) Cortical excitability (TMS-EMG MEP amplitude; epilepsy biomarker) Secondary endpoints: Additional TMS-EMG cortical excitability measures Resting-state pharmaco-EEG Safety, tolerability, and pharmacokinetics (PK) Additional QRL-101 clinical trials include: QRL-101-01 (NCT05667779) was a first-in-human, single-ascending dose clinical trial in 88 healthy participants. In this clinical trial, QRL-101 was shown to be well tolerated. The study completed in late 2023 and results from QRL-101-01 supported a tolerable dose range for subsequent studies. QRL-101-03 (NCT06532396) is a randomized, double-blind, placebo-controlled, multiple-ascending dose clinical trial evaluating the safety, tolerability, and PK of QRL-101 in up to 60 healthy participants. QRL-101-04 (NCT06714396) is a Phase 1 PoM single-dose, placebo-controlled clinical trial designed to evaluate the safety and tolerability of QRL-101 in people living with ALS. QRL-101-04 is expected to enroll approximately 12 participants with ALS and will evaluate the impact of QRL-101 on mNETT. QRL-101-06 is a Phase 1 randomized, open-label, single dose, cross-over study to evaluate the PK of three formulations of QRL-101 in a fasted condition or in the presence of a high fat meal in healthy participants. More information about the QRL-101 clinical trials can be found at . About QurAlis Corporation At QurAlis, we are neuro pioneers on a quest to cure, boldly seeking to translate scientific breakthroughs into powerful precision medicines. We work collaboratively with a relentless pursuit of knowledge, precise attention to craft, and compassion to discover and develop medicines that have the potential to transform the lives of people living with neurodegenerative and neurological diseases. QurAlis is the leader in development of precision therapies for amyotrophic lateral sclerosis (ALS). In addition to ALS, QurAlis is advancing a robust precision medicine pipeline to bring effective disease-modifying therapeutics to patients suffering from severe diseases defined by genetics and clinical biomarkers. For more information, please visit or follow us on X @QurAlisCo or LinkedIn. SOURCE QurAlis WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

内容介绍 本书归纳和综述了新药的化学合成路线。覆盖范围为近5年美国FDA批准上市的新分子实体药共109个。针对每一个药物，本书给出了药物简介，药物化学结构信息，产品上市信息，药品专利保护和市场独占权保护信息，化学全合成路线和参考文献等。这些合成路线大多是目前制药工业中正在使用的化学合成工艺，有较高的实用性和学术价值。对参与反应的起始原料、中间体、反应产物都给出了详细的化学结构。每一步化学合成反应都给出了重要的化学试剂、催化剂、所使用的溶剂、合成反应条件及文献出处等。本书的特点是：作者从浩如烟海的科技文献中，精心挑选出最新、最有实用价值的合成方法，汇编成化学合成路线图，内容简洁，深入浅出，逻辑性强，容易理解，以最少的篇幅表达最多的技术信息，可帮助读者很快找到他们需要的药物合成方法及最可靠的原始科学论文。  读者对象：  1.任何从事与化学合成、药物合成、精细化工相关专业的科研人员、企业管理人员。 2.有机化学专业、药学专业、生物制药专业等大专院校的高年级学生、研究生、教师及科研人员。 3.从事客户委托的药物原料与药物中间体合成的科研人员、企业管理人员。 编辑推荐 对于制药企业而言,一个好的药物全合成路线, 可以大大缩短生产周期,简化生产工艺,降低生产成本,节约能源,减少或消除对环境的化学污染与排放。本书为了顺应我国近年来生物制药及医药工业飞速发展的潮流编写的，详细介绍了近五年美国FDA批准上市的所有（109个）新分子实体药的化学全合成路线。这些全合成路线多数是国外制药厂目前正在使用的工艺，其经济效益及社会效益都是极为显著，因此本书既有较高的科学价值又有很大的实用性。 作者简介 陈清奇，旅美药学家和化学家，担任美国MedKoo生物医药科研公司总裁，同时兼任美国数家生物制药公司的技术顾问，中国国内数个大学的客座教授。研究领域为药物化学，纳米医学体外诊断技术。 书籍目录        Abiraterone Acetate（醋酸阿比特龙）001        Aclidinium Bromide（阿克利溴铵）006        Afatinib（阿法替尼）009        Alcaftadine（阿卡他定）014        Alogliptin（阿格列汀）017        Apixaban（阿哌沙班）022        Apremilast（阿普斯特）028        Avanafil（阿伐那非）033        Axitinib（阿西替尼）038        Azilsartan Kamedoxomil（阿齐沙坦酯钾盐）044        Bazedoxifene（巴多昔芬）048        Bedaquiline（贝达喹啉）053        Belinostat（贝利司他）060        Boceprevir（波西普韦）064        Bosutinib（博舒替尼）071        Cabozantinib（卡博替尼）075        Canagliflozin（卡格列净）078        Carfilzomib（卡非佐米）083        Ceftaroline Fosamil（头孢洛林酯）087        Ceftolozane（噻呋特啰嗪）094        Ceritinib（色瑞替尼）098        Clobazam（氯巴占）101        Cobicistat（可比司他）104        Crizotinib（克里唑蒂尼）112        Dabigatran Etexilate Mesylate（甲磺酸达比加群酯）118        Dabrafenib（达拉菲尼）123        Dapagliflozin（达格列净）127        Dasabuvir（达沙布韦）132        Deferiprone（去铁酮）136        Dienogest（地诺孕素）138        Dolutegravir（度鲁特韦）141        Droxidopa（屈昔多巴）145        Efinaconazole（艾氟康唑）149        Eliglustat（依利格鲁司特）152        Elvitegravir（埃替格韦）155        Empagliflozin（依帕列净）161        Enzalutamide（恩杂鲁胺）166        Eribulin Mesylate（甲磺酸艾日布林）168        Eslicarbazepine Acetate（艾利西平醋酸酯）175        Estradiol Valerate（雌二醇戊酸酯）180        Ezogabine（依佐加滨）185        Finafloxacin（非那沙星）193        Fingolimod Hydrochloride（盐酸芬戈莫德）197        Florbetapir F 18（氟比他匹）205        Flutemetamol F 18（富特米他）211        Gabapentin Enacarbil（加巴喷丁恩那卡比）214        Gadobutrol（钆布醇）218        Gadoterate Meglumine（钆特酸葡甲胺）224        Ibrutinib（依鲁替尼）227        Icatibant（艾替班特）232        Idelalisib（艾代拉里斯）234        Indacaterol （茚达特罗）236        Ingenol Mebutate（巨大戟醇甲基丁烯酸酯）240        Ioflupane 123I（碘[123I]氟潘）242        Ivacaftor（依瓦卡特）247        Ledipasvir（雷迪帕韦）250        Linaclotide（利那洛肽）259        Linagliptin（利拉利汀）261        Lomitapide（洛美他派）267        Lorcaserin（氯卡色林）270        Lucinactant（芦西纳坦）274        Luliconazole（卢立康唑）276        Lurasidone（鲁拉西酮）279        Macitentan（马西替坦）283        Miltefosine（米替福新）286        Mipomersen Sodium（米泊美生钠）290        Mirabegron（米拉贝隆）292        Naloxegol（纳罗克格）296        Netupitant（奈妥吡坦）299        Nintedanib（尼达尼布）303        Olaparib（奥拉帕尼）307        Olodaterol（奥达特罗）311        Omacetaxine Mepesuccinate（高三尖杉酯碱）315        Ombitasvir（艾姆伯韦）319        Ospemifene（奥培米芬）323        Paritaprevir（帕瑞它韦）327        Pasireotide（帕瑞肽）331        Peramivir（帕拉米韦）333        Perampanel（吡仑帕奈）337        Pirfenidone（吡非尼酮）343        Pomalidomide（泊马度胺）345        Ponatinib（泊那替尼）351        Regorafenib（瑞戈非尼）355        Rilpivirine（利匹韦林）357        Riociguat（利奥西呱）366        Rivaroxaban（利伐沙班）370        Roflumilast（罗氟司特）378        Ruxolitinib（鲁索替尼）384        Simeprevir（司美匹韦）388        Sofosbuvir（索非布韦）396        Suvorexant（苏沃雷生）401        Tafluprost（他氟前列腺素）405        Tasimelteon（他司美琼）409        Tavaborole（它瓦波罗）413        Tedizolid Phosphate（磷酸特地唑胺）415        Telaprevir（替拉瑞韦）418        Teriflunomide（特立氟胺）426        Ticagrelor（替格瑞洛）430        Tofacitinib（托法替尼）438        Trametinib（曲美替尼）443        Umeclidinium（芜地溴铵）447        Vandetanib（凡德他尼）450        Vemurafenib（威罗菲尼）456        Vilanterol（维兰特罗）460        Vilazodone Hydrochloride（盐酸维拉佐酮）463        Vismodegib（维莫德吉）468        Vorapaxar（沃拉帕沙）470        Vortioxetine（沃替西汀）473        附录1本书使用的期刊名称缩写表477        附录2专利文献代码481        附录3美国药品专利中的用途代码定义484        附录4美国药品市场独占权代码定义530        附录5美国FDA于2010—2014批准上市的药物名单563        英文索引607        中文索引611        CAS登记号索引613 下载方式 现在，这份资料分享给大家。小编在公众号设置了自动回复功能，在公众号后台回复关键词：新药全合成 ●书籍分享||有机氧化反应原理与应用 ●书籍分享||有机卤化反应原理及应用 ●推荐合成书籍【有机缩合反应原理与应用】 ●推荐合成书籍【有机环合反应原理与应用】 ●书籍分享||有机还原反应原理与应用 ●ChemDraw使用让你从化学菜鸟变成老鸟 ●干货分享||有机合成: 策略与控制 ●干货分享||有机合成工艺研发-副反应抑制法 ●基础有机化学(邢其毅)第3、4版教材+习题解析 ●ChemDrawV20最新版详细安装图文教程 ●干货分享||核磁共振二维谱 ●书籍分享||全合成中的经典:更多的目标、战略和方法 ●书籍分享||实用药物化学 ●书籍分享||基于模仿创新的小分子药物发明 ●书籍分享||制药工艺开发-目前的化学与工程挑战 ●书籍分享||手性合成:不对称反应及其应用(第5版) ●书籍分享||新药研发案例研究--明星药物如何从实验室走向市场 ●书籍分享||英汉·汉英化学化工词汇 ●书籍分享||有机化学结构与功能（第四版） ●书籍分享||过渡金属有机化学(原著第6版） ●重磅书籍分享||不对称催化基础 ●书籍分享||药物设计学-唐赟