Istradefylline

CALGARY, Alberta , Oct. 19, 2026 (GLOBE NEWSWIRE) -- Marvel Biosciences Corp. (TSXV: MRVL | OTCQB: MBCOF) , and its wholly-owned subsidiary, Marvel Biotechnology Inc. (collectively the “Company” or “Marvel”), a drug discovery company developing novel therapeutics for autism spectrum disorder (“ASD”) and related neurodevelopmental disorders, is pleased to announce that it has selected CMAX as the Phase I clinical site to test its lead drug candidate MB-204, an important step in the Company’s preparations to advance its lead patented drug candidate toward first-in-human clinical evaluation. CMAX Clinical Research is an independent clinical research facility, based in Adelaide, Australia. CMAX has been established as a Phase I unit since December 1993, making it the longest-running in Australia and, since establishment, has consistently maintained world class standards with a total commitment to providing excellence and quality in all areas of clinical service. CMAX is also one of Australia’s most modern Phase I clinical facilities, adjacent to Adelaide’s Biomed City. The facility offers 78 ‐ bed capacity for in ‐ house stays and conducts >40 studies per year. The CMAX site specialises in Phase I – FTIH, SAD/MAD, first time in patients, BA/BE, PK/PD and Proof-Of-Concept studies. CMAX has conducted >600 studies since the unit was established. Marvel’s preparations for clinical development are supported by a growing body of preclinical research evaluating MB-204 across multiple genetically distinct models of neurodevelopmental disorders. The Company has reported behavioural and cognitive improvements in mouse models associated with Rett syndrome (Mecp2), Fragile X syndrome (Fmr1) and autism spectrum disorder (Oprm1), alongside preliminary findings from a Shank3 mouse model associated with Phelan-McDermid syndrome. In its August 2026 Fragile X study, Marvel reported statistically significant improvements in recognition memory at both tested doses and persistent effects on selected endpoints following treatment cessation (refer to press release dated August 5, 2026 ) . Preliminary Shank3 findings also indicated improvements across multiple behavioural measures, although final statistical analyses and additional endpoints remained pending at the time of that announcement (refer to press release dated October 8, 2026 ). “We are pleased to be working with CMAX and Novotech as our clinical partners for the Phase I trial of MB-204”, commented Dr. Mark Williams, Chief Science Officer of Marvel Biosciences . “We look forward to navigating the ethics approval and regulatory process with both groups to start clinical testing.” The selection of CMAX represents an important operational step in Marvel’s preparations to advance MB-204 toward first-in-human clinical evaluation. As previously disclosed, the Company is planning a Phase I program beginning with a single ascending dose (SAD) study designed to evaluate the candidate’s initial safety, tolerability and pharmacokinetic pro humans. The planned study is also expected to assess potential biomarkers and selected cognitive endpoints, with findings intended to inform the design of a subsequent multiple ascending dose (MAD) study. Initiation of the trial remains subject to applicable regulatory and ethics approvals and completion of the necessary clinical preparations. About Marvel Biosciences Corp. Marvel Biosciences Corp. (TSXV:MRVL | OTCQB:MBCOF), and its wholly-owned subsidiary, Marvel Biotechnology Inc., is a Calgary-based pharmaceutical development biotechnology company entering Phase 1 clinical stage. The Company is developing MB-204, a novel fluorinated derivative of the approved anti-Parkinson’s drug Istradefylline, the only clinically approved adenosine A2a antagonist. A significant and growing body of scientific evidence suggests drugs that block the adenosine A2a receptor, such as MB-204, could be useful in treating other neurological diseases such as autism, depression and Alzheimer’s Disease. The Company is actively investigating its potential in addressing other neurodevelopmental disorders, such as Rett Syndrome and Fragile X Syndrome, to expand its therapeutic reach. Contact Information: Marvel Biosciences Corp. J. Roderick (Rod) Matheson, Chief Executive Officer Email: rod@marvelbiosciences.com Dr. Mark Williams, President and Chief Science Officer Email: mark@marvelbiosciences.com Tel: 403 770 2469 Website: | Twitter/X | LinkedIn Neither the TSX Venture Exchange nor its Regulation Services Provider (as that term is defined in the policies of the TSXV) accepts responsibility for the adequacy or accuracy of this press release. All information contained in this news release with respect to the Company and its subsidiary,(collectively, the "Parties") were supplied by Marvel, respectively, for inclusion herein and each parties' directors and officers have relied on each other for any information concerning such Party. This news release may contain forward-looking statements and other statements that are not historical facts. Forward-looking statements are often identified by terms such as "will", "may", "should", "anticipate", "expects" and similar expressions. All statements other than statements of historical fact, included in this release, including, without limitation, statements regarding the future plans and objectives of the Company are forward-looking statements that involve risks and uncertainties. There can be no assurance that such statements will prove to be accurate and actual results and future events could differ materially from those anticipated in such statements. Important factors that could cause actual results to differ materially from the expectations of the Company and include other risks detailed from time to time in the filings made by the Company under securities regulations. The reader is cautioned that assumptions used in the preparation of any forward-looking information may prove to be incorrect. Events or circumstances may cause actual results to differ materially from those predicted, as a result of numerous known and unknown risks, uncertainties, and other factors, many of which are beyond the control of the Company. As a result, the Company cannot guarantee that the above events on the terms will occur and within the time disclosed herein or at all. The reader is cautioned not to place undue reliance on any forward-looking information. Such information, although considered reasonable by management at the time of preparation, may prove to be incorrect and actual results may differ materially from those anticipated. Forward-looking statements contained in this news release are expressly qualified by this cautionary statement. The forward-looking statements contained in this news release are made as of the date of this news release and the Company will update or revise publicly any of the included forward-looking statements as expressly required by Canadian securities law.

编者按：自上世纪60年代左旋多巴问世以来，多巴胺替代策略一直是帕金森病治疗的支柱。然而随着治疗需求的提升，帕金森病领域始终在等待新机制疗法的到来。日前，FDA官网显示，艾伯维（AbbVie）的D1/D5受体部分激动剂Juvmo（tavapadon）获FDA批准上市，用于治疗成人帕金森病，也为帕金森病治疗增加了通过选择性调节D1/D5受体发挥作用的新选择。与此同时，行业仍在探索更多治疗路径，例如腺苷A2A受体拮抗剂、LRRK2靶向疗法、抗α-突触核蛋白疗法等，帕金森病研发版图正持续拓宽。 不过，在中枢神经系统（CNS）疾病药物研发中，始终面临着复杂的病理机制与血脑屏障等各类生物学挑战。针对行业需求，药明康德生物学业务平台（WuXi Biology）构建了覆盖药效评估、安全性评价与转化研究的一体化CNS药物发现支持体系，可为全球合作伙伴提供从早期机制验证到候选分子推进的系统性解决方案。药明康德药物代谢与动力学部（DMPK）围绕CNS构建了覆盖体外筛选、体内评价与机制解析的一体化药代动力学研究策略，助力全球合作伙伴加速CNS候选药物从靶点验证走向临床转化。 此次获批的Juvmo（tavapadon）的特别之处，不仅意味着帕金森病患者多了一种新的多巴胺受体激动剂选择，更在于它终于走通了一条过去被默认"行不通"的路：D1样受体。 D1样受体是多巴胺受体家族的重要亚类，包括D1和D5受体，早在30多年前就被认为是帕金森病治疗的潜力靶点。但在漫长的时间里，靶向D1样受体的策略却进展缓慢。为什么一个重要的靶点会沉寂这么多年？Tavapadon又是怎么把它重新激活的？ 图片来源：123RF 被“冷落”三十年的靶点 上世纪六十年代，左旋多巴的出现为帕金森病患者带来了革命性的改善。作为多巴胺前体，它能为患者补充缺失的多巴胺信号，显著缓解运动症状。但长期使用后，患者会逐渐出现运动波动以及药物诱导的异动症。 这些结果让科学家意识到， 单纯给大脑"补多巴胺"并非终极策略，如果能精准激活多巴胺系统的特定受体，或许能更精细地调控运动信号。 理论上，D1样受体（包括D1、D5亚型）是理想候选者。其中，D1受体主要表达于纹状体直接通路神经元，其激活与促进运动相关。早在上世纪八九十年代，多个靶向D1样受体的完全激动剂进入了研发阶段，它们在动物模型里确实能改善运动功能，但一进入人体就暴露出问题：有些分子口服生物利用度差、需要注射给药；有些虽可口服，却伴随低血压、运动障碍等安全性问题。 这些挫折使D1样受体药物开发一度降温，早期完全激动剂面临的药代和耐受性问题成为主要开发瓶颈。 这个曾被寄予厚望的靶点，随后进入了一段长达近三十年的"冷板凳"期。 但在主流判断之外，仍有一些科学家没有放弃对D1样受体的探索。随着对受体药理学理解的加深，他们推测问题或许并不出在受体本身，而是出在"完全激动剂"这个策略上。 完全激动剂的作用方式，像是一脚把油门踩到底，它让D1受体被过度激活，信号过强，疗效和副作用之间几乎没有缓冲区。 但要如何解决这一问题呢？ 图片来源：123RF 打通被低估的路径 ▲Tavapadon分子结构（图片来源：PubChem） 原理上， 它是一个高选择性的D1/D5受体部分激动剂，即对D1/D5受体的亲和力远高于其他多巴胺受体亚型，但激活受体的强度又低于内源性多巴胺。这相当于把"油门"精确调到既能改善运动、又不至于把受体推到过度激活、快速脱敏的位置。 为了弥补早期完全激动剂的缺陷，团队还把它打磨成适合长期用药的形式，让它可口服、支持一天一次给药；同时，其开发也意在改善早期D1/D5完全激动剂所面临的低血压等耐受性问题。这些设计上的进展，意味着部分激动剂策略不仅在理论上行得通，也可能比老一代分子更契合临床长期用药的实际需求。 2018年，辉瑞与贝恩资本合作成立了专注于CNS药物研发的Cerevel Therapeutics，让一支专门聚焦中枢神经系统的团队来推进这个"机制独特、具有治疗潜力"的分子。Tavapadon随之进入Cerevel管线，并启动了关键的TEMPO系列3期临床试验。 接力推动tavapadon走向前台 2023年12月，艾伯维宣布以约87亿美元收购Cerevel，作为对神经科学管线的一次前瞻性布局，tavapadon也在其中。2024年4月，TEMPO-3试验率先显示， 在接受左旋多巴治疗并出现运动波动的中晚期帕金森病患者中，作为左旋多巴辅助治疗，tavapadon可显著增加无令人困扰的异动症的ON时间，并减少OFF时间。 同年8月，艾伯维完成对Cerevel的收购，而就在这之后的数月，TEMPO-1与TEMPO-2也相继传来捷报，两个试验均达到主要终点。作为早期帕金森病的单药治疗时，tavapadon的症状评分较安慰剂组取得统计学显著改善。TEMPO系列3期试验的接连成功，为D1/D5选择性部分激动策略提供了更系统的临床证据。 2025年9月，艾伯维向美国FDA提交tavapadon的新药申请，并推动其最终获批。回望来路，从早期辉瑞提出的突破性思路，到Cerevel的临床试验开展，再到艾伯维推进FDA申报并最终获得批准， 这场跨越三家公司的产业接力，终于将这款新药稳稳送到了患者面前。Tavapadon不仅为帕金森病治疗带来了一款新机制的药物选择，更将一个坐了三十多年冷板凳的老靶点，推到了具有治疗意义的前台。 图片来源：123RF 更多方向助力帕金森病治疗 Tavapadon的成功验证了D1/D5通路的治疗价值，但帕金森病药物研发的版图远不止于此，行业正从多个维度寻找更多能惠及患者的新疗法。 多巴胺能系统之外，非多巴胺能靶点也是重要的探索方向。腺苷A2A受体拮抗剂通过非多巴胺能机制调节基底节间接通路，是其中较为成熟的一条路线，Kyowa Kirin的istradefylline已获批用于帕金森病的辅助治疗，新一代A2A拮抗剂仍在临床探索中。 此外，LRRK2靶向疗法代表了另一条思路。LRRK2基因突变是家族性帕金森病最常见的遗传病因之一，在散发患者中也被观察到通路活性异常，因此靶向LRRK2有望从机制层面延缓疾病进展。今年3月，Arvinas公布了其LRRK2蛋白降解剂ARV-102的1期临床数据： 在帕金森病患者中，ARV-102在所有给药剂量下均可在第14天实现脑脊液LRRK2水平约50%或以上的降低，并持续维持至第28天。 从控制症状走向延缓疾病进展，是帕金森病研发中的重要目标之一。靶向α-突触核蛋白是备受关注的疾病修饰治疗方向之一，除被动抗体外，主动免疫策略也在推进。AC Immune的在研疫苗ACI-7104在早期帕金森病患者中开展的2期VacSYn试验取得积极的中期结果，100%的受试者产生了针对目标抗原的免疫应答，并在药效学、靶点结合等多项指标上达成预设目标。这也代表着主动免疫策略在临床试验中显示出延缓帕金森病进展的潜力。 一体化平台赋能全球CNS新药研发 Tavapadon的研发历程体现了CNS新药从分子设计到临床开发所经历的漫长链条，它也表明CNS新药研发是一场漫长的接力赛，每一棒都需要跨越大量专业关卡。 一款CNS药物从靶点验证到抵达患者，需要回答一连串问题：能否穿透血脑屏障，在脑内达到足够的游离药物浓度？能否精准作用且足够安全？ 正是基于这样的行业需求，药明康德围绕CNS药物研发构建了从靶点验证到临床转化的系统性赋能能力。 在中枢神经系统疾病药物研发中，复杂的病理机制与血脑屏障等生物学挑战，使得临床前阶段对模型预测性与转化能力提出更高要求。药明康德生物学业务平台（WuXi Biology）构建了覆盖药效评估、安全性评价与转化研究的一体化CNS药物发现支持体系，可为全球合作伙伴提供从早期机制验证到候选分子推进的系统性解决方案。平台依托完善的体内药理学能力，建立了涵盖神经退行性疾病（如阿尔茨海默病、帕金森病、ALS）、精神疾病、癫痫、多发性硬化及脑卒中等在内的多维动物模型体系，并结合学习记忆、社会行为、成瘾行为及疼痛相关功能学评价，实现对认知与神经功能的综合分析。 与此同时，WuXi Biology通过脑电图监测、受体占有率分析、生物标志物检测及PK/PD关联研究，对疗效、安全性及靶点作用进行多终点整合评估，支持小分子、生物大分子及新型疗法的开发。依托AAALAC认证动物设施与标准化实验体系，平台能够将疾病模型数据与转化科学紧密结合，提高临床预测性与研发效率，帮助合作伙伴降低CNS项目早期风险，加速创新疗法迈向临床阶段。 针对药物"入脑并维持暴露"的核心挑战，药明康德药物代谢与动力学部（DMPK）围绕CNS构建了覆盖体外筛选、体内评价与机制解析的一体化药代动力学研究策略。针对血脑屏障（BBB）这一关键生物屏障对药物分布的严格限制，药明康德DMPK建立了系统化的分级评估体系：在早期阶段，通过平行人工膜渗透模型（PAMPA）、MDR1-MDCK细胞模型等高通量体外模型，结合转运体研究与理化性质分析，快速筛选具备脑渗透潜力的候选分子。在体内阶段，利用原位脑灌注与脑微透析等先进技术，实时定量检测药物在血浆、脑组织及脑脊液中的分布与游离浓度，精准计算脑-血浆未结合分配系数（Kp,uu）等关键参数，揭示真实脑暴露水平。 同时，药明康德DMPK将药代数据与基于生理学的药代动力学模型（PBPK）、结构优化及转运机制研究相结合，支持从分子设计到临床转化的跨尺度决策。依托这一"分层筛选+多模型验证+机制驱动优化"的综合能力，药明康德DMPK能够帮助客户系统性提升CNS候选药物的脑暴露预测准确性，加速突破血脑屏障带来的研发瓶颈，推动创新疗法更高效地迈向临床。 帕金森病乃至更广泛的CNS疾病领域，仍有许多未被满足的治疗需求。从靶点的重新认识，到分子设计策略的迭代，再到临床开发的高效推进，每一步突破，都依赖于科学认知的提升与研发能力的持续积累。未来，药明康德将持续以一体化研发赋能平台，助力全球合作伙伴的CNS新药研发过程，让更多创新疗法更快抵达患者身边。 After 30 Years of Being Underestimated, This Approach Finally Has an FDA-Approved Drug Since the introduction of levodopa in the 1960s, dopamine replacement strategies have remained a cornerstone of Parkinson’s disease treatment. Yet as treatment needs have evolved, the field has continued to seek therapies with novel mechanisms. The FDA recently approved AbbVie’s D1/D5 receptor partial agonist Juvmo (tavapadon) for the treatment of Parkinson’s disease in adults, adding a new treatment option that selectively modulates D1/D5 receptor signaling.At the same time, the industry continues to explore other therapeutic approaches, including adenosine A2A receptor antagonists, LRRK2-targeted therapies, and therapies targeting α-synuclein, further broadening the Parkinson’s disease R&D landscape. Drug discovery for central nervous system (CNS) diseases, however, continues to face major biological challenges, including complex disease mechanisms and the blood-brain barrier. To address these industry needs, WuXi Biology, a business unit of WuXi AppTec, has built an integrated CNS drug discovery support system spanning efficacy assessment, safety evaluation, and translational research, providing global clients with systematic solutions from early mechanism validation to candidate advancement. WuXi AppTec DMPK has established an integrated pharmacokinetic research strategy around CNS that covers in vitro screening, in vivo evaluation, and mechanistic analysis, enabling global clients to accelerate the path from target validation to late-stage research for CNS drug candidates. The significance of the newly approved Juvmo (tavapadon) goes beyond giving people with Parkinson’s disease another dopamine receptor agonist option. It also represents progress along a therapeutic path that had long been regarded as difficult to pursue successfully: targeting D1-like receptors. D1-like receptors are an important subclass of the dopamine receptor family and include the D1 and D5 receptors. They were recognized more than 30 years ago as potential therapeutic targets in Parkinson’s disease, yet drug development against these receptors progressed slowly for decades. Why did such an important target remain on the sidelines for so long? And how did tavapadon bring this approach back into focus? Image source: 123RF A Target Sidelined for Three Decades The introduction of levodopa in the 1960s transformed the treatment of Parkinson’s disease. As a dopamine precursor, levodopa helps restore deficient dopaminergic signaling and can substantially improve motor symptoms. With long-term treatment, however, many patients gradually develop motor fluctuations and drug-induced dyskinesia. These limitations prompted researchers to consider whether simply “adding dopamine” to the brain was sufficient as a long-term strategy. More selective activation of specific receptors within the dopamine system could, in principle, enable finer control of motor signaling. D1-like receptors, including the D1 and D5 subtypes, emerged as attractive candidates. In particular, D1 receptors are predominantly expressed on neurons in the striatal direct pathway, where their activation is associated with the facilitation of movement. As early as the 1980s and 1990s, several full agonists targeting D1-like receptors entered development. Although some improved motor function in animal models, substantial challenges emerged in humans. Some compounds had poor oral bioavailability and required injection, while others could be given orally but were associated with hypotension, motor disturbances, and other tolerability or safety concerns. These setbacks caused enthusiasm for D1-like receptor drug development to decline. Pharmacokinetic and tolerability limitations associated with early full agonists became major development barriers, leaving this once-promising target on the sidelines for nearly three decades. Still, some researchers continued to explore D1-like receptor pharmacology. As understanding of receptor signaling advanced, they began to consider whether the problem lay not with the receptor itself, but with the full-agonist strategy. A full agonist can be compared to pressing an accelerator all the way down: strong receptor activation can drive an intense biological response, leaving relatively little room between the desired pharmacological effect and unwanted effects. So how could that problem be addressed? Image source: 123RF Unlocking an Underestimated Pathway Pharmacologically, tavapadon is a highly selective D1/D5 receptor partial agonist. It has substantially greater affinity for D1/D5 receptors than for other dopamine receptor subtypes, while producing less receptor activation than a full agonist.Conceptually, this is more like adjusting the accelerator to an appropriate level rather than pressing it fully down—providing sufficient receptor activation to improve motor function while reducing the risk of excessive stimulation. The molecule was also optimized for chronic treatment, including oral administration and once-daily dosing. Its development was intended in part to address tolerability issues, such as hypotension, that had limited earlier D1/D5 full agonists. These advances suggested that partial agonism could offer not only a pharmacologically viable approach, but also one better suited to the practical requirements of long-term treatment. ▲The molecular structure of tavapadon (Image source：PubChem) In 2018, Pfizer and Bain Capital established Cerevel Therapeutics, a company focused on CNS drug development, creating a dedicated organization to advance this mechanistically differentiated molecule. Tavapadon subsequently became part of Cerevel’s pipeline and entered the pivotal TEMPO Phase 3 clinical development program. A Relay Effort Brings Tavapadon to the Forefront In April 2024, the TEMPO-3 trial reported positive results in patients with more advanced Parkinson’s disease who were receiving levodopa and experiencing motor fluctuations. As an adjunct to levodopa, tavapadon significantly increased “ON” time without troublesome dyskinesia and reduced “OFF” time.返回搜狐，查看更多