Selegiline

Currently enrolling randomized, double-blind, placebo-controlled, dose-finding, Phase 2 clinical trial to evaluate the safety and efficacy of KDS2010 in patients with Alzheimer’s disease with mild cognitive impairment and mild dementia is currently recruiting in South Korea in 114 patients and U.S. cohort will be added in 2025.KDS2010 (Tisolagiline) is a new reversible selective monoamine oxidase B (MAO-B) inhibitor being studied for its potential in treating neurodegenerative diseases like Alzheimer's disease.Apart from its role as a MAO-B inhibitor, it also influences astrocytic GABA inhibition.In neurodegenerative diseases like Alzheimer’s, altered GABAergic activity and dysfunction in astrocytic regulation of neurotransmitter systems contribute to cognitive decline and neuroinflammation.A highly selective and reversible MAO-B inhibitor, KDS2010 overcomes the disadvantages of the irreversible MAO-B inhibition.Long-term treatment with KDS2010 significantly attenuates increased astrocytic GABA levels and astrogliosis, enhances synaptic transmission, and improves learning and memory in APP/PS1 mice.1KDS2010 pharmacokinetics, lack of food effect, safety and dose selection have been characterized in Single Ascending Dose and Multiple Ascending Dose Phase 1 clinical trials with 88 healthy young adults and elderly subjects and between Korean and Western population, demonstrating favorable safety and tolerability and adequate pharmacokinetics for once-daily dosing.Per Health Care analyst reports 2023, Alzheimer’s global drug market size is expected to rise above $15 billion by 2030 in the eight major markets, as new drugs show promise and are being launched with FDA approval to slow cognitive decline.2 PALO ALTO, Calif., Dec. 11, 2024 (GLOBE NEWSWIRE) -- Scilex Bio, a controlling interest of joint venture by Scilex Holding Company (Nasdaq: SCLX, “Scilex” or “Company”) with IPMC Company, a representative company of the Bio Innovation Consortium (“IPMC”) which holds the exclusive rights to NeuroBiogen Company’s (“NB”) KDS2010 global license, announced that KDS2010 (Tisolagiline) is a new reversible selective monoamine oxidase B (MAO-B) inhibitor being studied for its potential in treating neurodegenerative diseases like Alzheimer's disease (AD). Apart from its role as a MAO-B inhibitor, it also influences astrocytic GABA inhibition. “Current treatments in development for Alzheimer’s Disease are mostly injectable antibodies or peptides targeting amyloid, tau or neuroinflammation. Advancement of a small molecule with great potential to improve cognitive function that can be delivered with once-daily oral dosing holds promise for people living with Alzheimer's disease,” said Richard Lipton, MD., Professor of Neurology at the Albert Einstein College of Medicine. GABA (gamma-aminobutyric acid) is the primary inhibitory neurotransmitter in the brain, playing a key role in regulating neuronal activity and maintaining balance between excitation and inhibition. Astrocytes, a type of glial cell in the brain, have been shown to be involved in the regulation of GABA activity. In neurodegenerative diseases like Alzheimer’s, altered GABAergic activity and dysfunction in astrocytic regulation of neurotransmitter systems contribute to cognitive decline and neuroinflammation. By inhibiting astrocytic GABA signaling, KDS2010 helps to reduce neuroinflammation and normalize the balance between excitatory and inhibitory signals in the brain, potentially leading to enhancing cognitive function in Alzheimer's disease. Mechanistically, reactive astrocytes precipitate pathological hallmarks of Alzheimer’s disease via hydrogen peroxide (H2O2) production. KDS2010 blocks MAO-B-dependent aberrant GABA/ H2O2 production in reactive astrocytes and eliminates neuronal inhibition, neuroinflammation, and neurodegeneration, while enhancing neuroregeneration.3 In the dentate gyrus of mouse models of AD, the released GABA reduces spike probability of granule cells by acting on presynaptic GABA receptors. Suppressing GABA production in reactive astrocytes restores the impaired spike probability, synaptic plasticity, and learning and memory in mice. In the postmortem brain of individuals with AD, astrocytic GABA and MAO-B are significantly upregulated. Selective inhibition of astrocytic GABA synthesis and release is a new therapeutic strategy for treating memory impairment in AD.4 Clinically, short-term treatment with known irreversible MAO-B inhibitors, such as selegiline, improves cognitive deficits in AD patients, long-term treatments have shown disappointing results. Interestingly, prolonged treatment with selegiline fails to reduce aberrant astrocytic GABA levels and rescue memory impairment in APP/PS1 mice, an animal model of AD, because of increased activity in compensatory genes for a GABA-synthesizing enzyme, diamine oxidase (DAO). A highly selective and reversible MAO-B inhibitor, KDS2010 overcomes the disadvantages of the irreversible MAO-B inhibition. Long-term treatment with KDS2010 significantly attenuates increased astrocytic GABA levels and astrogliosis, enhances synaptic transmission, and improves learning and memory in APP/PS1 mice.1 KDS2010 pharmacokinetics, lack of food effect, safety and dose selection have been characterized in Single Ascending Dose and Multiple Ascending Dose Phase 1 clinical trials with 88 healthy young adults and elderly subjects and between Korean and Western populations, demonstrating favorable safety and tolerability and adequate pharmacokinetics for once-daily dosing. A Randomized, Double-Blind, Placebo-Controlled, Dose-Finding, Phase 2 Clinical Trial to Evaluate the Safety and Efficacy of KDS2010 in Patients with Alzheimer’s Disease with Mild Cognitive Impairment and Mild Dementia is currently recruiting in South Korea in 114 patients and U.S. cohort will be added in 2025. For more information on Scilex Holding Company, refer to www.scilexholding.com For more information on Semnur Pharmaceuticals, refer to www.semnurpharma.com For more information on Scilex Holding Company Sustainability Report, refer to www.scilexholding.com/investors/sustainability For more information on ZTlido®, including Full Prescribing Information, refer to www.ztlido.com. For more information on ELYXYB®, including Full Prescribing Information, refer to www.elyxyb.com. For more information on Gloperba®, including Full Prescribing Information, refer to www.gloperba.com. https://www.facebook.com/scilex.pharm https://www.linkedin.com/company/scilex-holding-company/ info@scilexholding.com About Scilex Holding Company Scilex Holding Company is an innovative revenue-generating company focused on acquiring, developing and commercializing the treatment for neurodegenerative and cardiometabolic diseases, and non-opioid pain management products for the treatment of acute and chronic pain. Scilex targets indications with high unmet needs and large market opportunities with non-opioid therapies for the treatment of patients with acute and chronic pain and are dedicated to advancing and improving patient outcomes. Scilex’s commercial products include: (i) ZTlido® (lidocaine topical system) 1.8%, a prescription lidocaine topical product approved by the U.S. Food and Drug Administration (the “FDA”) for the relief of neuropathic pain associated with postherpetic neuralgia, which is a form of post-shingles nerve pain; (ii) ELYXYB®, a potential first-line treatment and the only FDA-approved, ready-to-use oral solution for the acute treatment of migraine, with or without aura, in adults; and (iii) Gloperba®, the first and only liquid oral version of the anti-gout medicine colchicine indicated for the prophylaxis of painful gout flares in adults. In addition, Scilex has three product candidates: (i) SP-102 (10 mg, dexamethasone sodium phosphate viscous gel) (“SEMDEXA™” or “SP-102”), a novel, viscous gel formulation of a widely used corticosteroid for epidural injections to treat lumbosacral radicular pain, or sciatica, for which Scilex has completed a Phase 3 study and was granted Fast Track status from the FDA in 2017; (ii) SP-103 (lidocaine topical system) 5.4%, (“SP-103”), a next-generation, triple-strength formulation of ZTlido, for the treatment of acute pain and for which Scilex has recently completed a Phase 2 trial in acute low back pain. SP-103 has been granted Fast Track status from the FDA in low back pain; and (iii) SP-104 (4.5 mg, low-dose naltrexone hydrochloride delayed-release capsules) (“SP-104”), a novel low-dose delayed-release naltrexone hydrochloride being developed for the treatment of fibromyalgia, for which Phase 1 trials were completed in the second quarter of 2022. Scilex Holding Company is headquartered in Palo Alto, California. For more information on Scilex Holding Company, refer to www.scilexholding.com About Semnur Pharmaceuticals, Inc. Semnur Pharmaceuticals, Inc. (“Semnur”) is a clinical-late stage specialty pharmaceutical company focused on the development and commercialization of novel non-opioid pain therapies. Semnur’s lead program, SP-102 (SEMDEXA™), is the first non-opioid novel gel formulation administered epidurally in development for patients with moderate to severe chronic radicular pain/sciatica. Semnur Pharmaceuticals, Inc. is headquartered in Palo Alto, California. For more information on Semnur Pharmaceuticals, refer to www.semnurpharma.com About Scilex Bio Scilex Holding Company and IPMC Company, a representative company of the Bio Innovation Consortium (“BOIC”), which holds the exclusive rights to NeuroBiogen Company’s (“NB”) KDS2010 global license, formed a joint venture, Scilex Bio, to develop and commercialize a next-generation reversible MAO-B Inhibitor, a novel inhibitor of aberrant GABA production in reactive astrocytes for the treatment of obesity and neurodegenerative diseases including Alzheimer’s disease. About IPMC IPMC is a private biopharmaceutical company focused on the development of new medicines for the treatment of cardiometabolic and neurodegenerative diseases. Forward-Looking Statements This press release and any statements made for and during any presentation or meeting concerning the matters discussed in this press release contain forward-looking statements related to Scilex and its subsidiaries and are subject to risks and uncertainties that could cause actual results to differ materially from those projected. Forward-looking statements include statements regarding the Scilex and its subsidiaries, including but not limited to, statements regarding the terms of the potential licensing transaction, statements regarding KDS2010 and the potential efficacy and preclinical results, the potential for KDS2010 to be an innovative new treatment for obesity and Alzheimer’s disease benefitting people living with neurodegenerative and cardiometabolic diseases, the potential market size and growth opportunity for the weight loss and Alzheimer’s global drug market, the Company’s outlook, goals and expectations for 2024, and the Company’s development and commercialization plans. Although each of Scilex and its subsidiaries believes that it has a reasonable basis for each forward-looking statement contained in this press release, each of Scilex and its subsidiaries caution you that these statements are based on a combination of facts and factors currently known and projections of the future, which are inherently uncertain. Risks and uncertainties that could cause actual results of Scilex to differ materially and adversely from those expressed in our forward-looking statements, include, but are not limited to: the inability of the parties to consummate the licensing transaction for any reason, including any failure to satisfy or waive any closing conditions; changes in the structure, timing and completion of the proposed transaction between Scilex and NeuroBiogen; the ability of the parties to achieve the benefits of the proposed licensing transaction, risks related to the outcome of any legal proceedings that may be instituted against the parties following the announcement of the proposed licensing transaction; risks associated with the unpredictability of trading markets; general economic, political and business conditions; the risk that the potential product candidates that Scilex or Scilex Bio develops may not progress through clinical development or receive required regulatory approvals within expected timelines or at all; risks relating to uncertainty regarding the regulatory pathway for Scilex’s and Scilex Bio’s product candidates; the risk that Scilex and Scilex Bio will be unable to successfully market or gain market acceptance of its product candidates; the risk that Scilex’s product candidates may not be beneficial to patients or successfully commercialized; the risk that Scilex has overestimated the size of the target patient population, their willingness to try new therapies and the willingness of physicians to prescribe these therapies; risks that the outcome of the trials and studies for SP-102, SP-103 or SP-104 may not be successful or reflect positive outcomes; risks that the prior results of the clinical and investigator-initiated trials of SP-102 (SEMDEXA™), SP-103 or SP-104 may not be replicated; regulatory and intellectual property risks; and other risks and uncertainties indicated from time to time and other risks described in Scilex’s most recent periodic reports filed with the SEC, including its Annual Reports on Form 10-K for the year ended December 31, 2023 and subsequent Quarterly Reports on Form 10-Q that the Company has filed or may file, including the risk factors set forth in those filings. Investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this release, and Scilex undertakes no obligation to update any forward-looking statement in this press release except as may be required by law. Contacts: Investors and MediaScilex Holding Company 960 San Antonio RoadPalo Alto, CA 94303Office: (650) 516-4310 Email: investorrelations@scilexholding.com Website: www.scilexholding.com Investors and MediaDenali Capital Acquisition Corp. 437 Madison Avenue, 27th FloorNew York, NY 10022 References Jong-Hyun Park, et al. Science Advances. 2019 Mar 20;5(3):eaav0316www.ihealthcareanalyst.com/global-alzheimers-disease-market/Heejung Chun, et al. Nature Neuroscience 2020 Dec;23(12):1555-1566Seonmi Jo, et al. Nature Medicine. 2014 August ; 20(8): 886–896. doi:10.1038/nm.3639 SEMDEXA™ (SP-102) is a trademark owned by Semnur Pharmaceuticals, Inc., a wholly-owned subsidiary of Scilex Holding Company. A proprietary name review by the FDA is planned. ZTlido® is a registered trademark owned by Scilex Pharmaceuticals Inc., a wholly-owned subsidiary of Scilex Holding Company. Gloperba® is the subject of an exclusive, transferable license to Scilex Holding Company to use the registered trademark. ELYXYB® is a registered trademark owned by Scilex Holding Company. Scilex Bio™ is a trademark owned by Scilex Holding Company. All other trademarks are the property of their respective owners. © 2024 Scilex Holding Company All Rights Reserved.

12 月 2 日，NMPA 官网显示，Zambon/精鼎医药的甲磺酸沙非胺片获批上市，作为辅助疗法，治疗接受稳定剂量的左旋多巴（L-dopa）治疗的运动波动的特发性帕金森病（受理号：JXHS2200034/35）。 截图来源：NMPA 官网 帕金森病（PD）是一种常见的中老年神经系统退行性疾病，主要发病因素包括神经元损害和多巴胺水平下降、遗传因素、环境因素、氧化应激和炎症、线粒体功能障碍、α-突触核蛋白沉积、免疫系统异常。  据公开数据，目前我国帕金森病患者人数超过 300 万人，约占全球 50%。65 岁以上发病率约为 1.7%。随着人口老龄化进程不断加快，预计到 2030 年我国帕金森病患者将达 500 万，将给社会及患者家庭带来极大的医疗及经济负担。 左旋多巴是临床最常用的帕金森病治疗药物，但长期使用易引发运动并发症，其中运动波动是帕金森病治疗过程中最常见的运动并发症，也是帕金森病患者致残的主要原因。 甲磺酸沙非胺（Safinamide）抑制单胺氧化酶 B (MAO-B)，选择性比 MAO-A 高 1000 倍以上，通过阻断多巴胺的分解代谢来抑制 MAO-B 活性，被认为会导致多巴胺水平增加，并随后增加大脑中的多巴胺能活动。在临床研究中，在剂量> 20 mg 时测量到 MAO-B 的完全抑制（>90%）。 原研沙非胺由意大利制药公司 Newron 和赞邦（Zambon）共同研发，2015 年 2 月在欧洲获得批准，2017 年 3 月被 FDA 批准作为附加治疗药物，用于治疗正在服用左旋多巴/卡比多巴且出现「关闭」状态的帕金森患者，商品名 Xadago。 2022 年 11 月 8 日，发表在 CNS Drugs 上的评价沙非胺作为辅助疗法，用于接受稳定剂量左旋多巴治疗的、出现运动波动的特发性帕金森病的中国患者的疗效和安全性的 III 期临床（XINDI 研究）结果显示：在第 16 周，沙非胺组和安慰剂组之间平均每日总「关」期时间变化的差异为 1.10 小时 (p < 0.0001)。且从第 2 周开始，沙非胺组每日总「关」期时间的变化就体现了明显优势，提示沙非胺胺可在短期内起效。 除了改善「关」期时间外，沙非胺组在延长「开」期时间，改善 UPDRS、CG I 和 PDQ-39 评分方面相较于安慰剂均有显著优势，疗效明确。 安全性方面，沙非胺安全性良好，两组患者的不良事件或严重不良事件无显著差异。 原研沙非胺国内获批上市将为帕金森病患者提供新选择，同时进一步加剧国内 MAO-B 抑制剂市场竞争。 据 Insight 数据库，此前国内已批准两款 MAO 抑制剂，即司来吉兰和雷沙吉兰。  其中司来吉兰是第一代选择性、不可逆 MAO-B 抑制剂，选择性较第二代和第三代 MAO-B 抑制剂差，其原研药「咪多吡」（Eldepryl）来自芬兰奥利安集团（Orion Corporation），目前国内多家企业取得其仿制药生产批件。 雷沙吉兰是第二代 MAO-B 抑制剂，比司来吉兰功效强 5～10 倍，副作用小，且具有一定的神经保护作用。原研雷沙吉兰由丹麦灵北公司和以色列梯瓦公司研发，2017 年 5 月在国内获批，目前国内有 10 家企业取得其仿制药生产批件，其中齐鲁制药于 2021 年取得首仿生产批件。 此外，目前国内还有一款在研 MAO-B 抑制剂，即东阳光药业的 HEC122505MsOH。该药是一种高效能、高选择性 MAO-B 可逆抑制剂，临床上拟与左旋多巴合用治疗帕金森病，目前处于 I 期临床。 封面来源：企业 Logo 免责声明：本文仅作信息分享，不代表 Insight 立场和观点，也不作治疗方案推荐和介绍。如有需求，请咨询和联系正规医疗机构。 编辑：vvy PR 稿对接：微信 insightxb 投稿：微信 insightxb；邮箱 insight@dxy.cn 多样化功能、可溯源数据…… Insight 数据库网页版等你体验 点击阅读原文，立刻解锁！