GluN2B

▎药明康德内容团队编辑根据中国国家药监局药品审评中心（CDE）官网，在刚刚结束的3月，有超过60款1类新药首次在中国获批临床。按照新注册分类，“1类新药”是指尚未在全球任何国家和地区获批上市的药物，它们也往往代表了药物研发领域的前沿方向。本文中就让我们来看看这些1类新药都有哪些？又有望惠及哪些患者？图片来源：123RF从药物类型来看，3月首次在中国获批临床的1类新药呈现“百花齐放”的状态，涵盖了小分子靶向药、抗体偶联药物（ADC）、单抗、双抗、三抗、核酸药物、细胞与基因疗法、多肽、分子胶、核药等诸多类型。在已披露作用机制的药物中，小分子靶向药占比最多，达30%左右。它们的靶点包括了RXRα、NR2B、KCNQ2/3、CGRP受体、PKR、S1P1、CHK1、RTK、MAT2A、KRAS G12D、IDH1/IDH2等。其次是抗体偶联药物（ADC），有7款。▲3月首次在中国获批临床的1类新药分子类型分布从疾病领域来看，在3月首次在中国获批临床的1类新药中，抗肿瘤药物有近30款，占比超过40%。其次是自身免疫及炎症性疾病，占比超过10%。此外还涵盖了罕见病、神经/精神系统疾病、代谢性疾病、心血管疾病、血液病等疾病领域。▲3月首次在中国获批临床的1类新药疾病领域分布以下将分享部分在3月获批临床的ADC疗法的基本信息，供读者参阅。欲了解更多药物的信息，请扫描下方二维码，即可获得“2024年3月首次在中国获得临床试验默示许可的1类新药”完整PDF文件。AZD9829：一种靶向CD123的抗体与阿斯利康（AstraZeneca）专有的拓扑异构酶1抑制剂（TOP1i）有效载荷连接而成的ADC。该药的主要作用机制是将TOP1i载荷递送到表达CD123的癌细胞中，导致DNA损伤和细胞凋亡。该药在中国获批临床，拟开发治疗CD123阳性恶性血液疾病。JSKN016注射液：康宁杰瑞研发的新一代双抗ADC，可同时靶向HER3和TROP2。JSKN016与肿瘤细胞表面TROP2或者HER3结合后，通过靶点介导的内吞作用进入到溶酶体中，释放出具有细胞毒性的拓扑异构酶I抑制剂 (TOPIi），进而诱导肿瘤细胞死亡。该抑制剂还可以穿透细胞膜，进入到抗原阴性的肿瘤细胞中发挥旁观者效应，两者的叠加作用可以有效抑制肿瘤细胞的生长。该药获批临床的适应症为晚期恶性实体瘤。注射用BL-M05D1：百利天恒全资子公司SystImmune开发的在研一款ADC，采用专有的Claudin18.2特异性抗体开发。由于与Claudin18.2特异性结合，BL-M05D1对包括胃癌在内的表达Claudin18.2的恶性肿瘤具有特异性。该药获批临床的适应症为局部晚期或转移性胃癌或胃食管交界处癌、胰腺癌、结直肠癌等实体瘤。SYS6023：石药集团巨石生物研发的一款单克隆抗体偶联药物，可与肿瘤表面的特异性受体结合。该药在临床前研究中对多种癌症显示出了较好的抗肿瘤作用。本次获批临床的适应症为晚期实体瘤。注射用NC18：诺灵生物自主研发的新型靶向HER2的ADC，采用了独特的Polymer linker和诺灵生物独家的AF-HEA细胞毒素，该组合展现出良好的活性、可控的旁杀效应、更好的抗耐药性。该产品获批临床的适应症为HER2阳性或表达的复发或转移的晚期实体瘤。IBI130：信达生物研发的一款靶向TROP2的ADC，此前已经在澳大利亚开展1/2期临床研究，用于治疗实体瘤。IBI129：信达生物在研的靶向B7-H3的ADC，此前已经登记开展了一项国际多中心1/2期临床试验，针对实体瘤。除了上述药物，3月还有包括CGT、抗体药物、小分子靶向疗法、多肽等在内的其它类型药物首次在中国获批临床，限于篇幅，本文不再一一介绍。希望这些新药后续临床研究顺利进行，早日造福患者！扫描下方二维码，您将可以获取“2024年3月首次在中国获得临床试验默示许可的1类新药”完整PDF文件。参考资料：[1]中国国家药监局药品审评中心（CDE）官网. From https://www.cde.org.cn/main/xxgk/listpage/4b5255eb0a84820cef4ca3e8b6bbe20c[2] 各公司官网及新闻稿本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「医药观澜」微信公众号留言联系我们。其他合作需求，请联系wuxi_media@wuxiapptec.com。免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。

SAN DIEGO, April 3, 2024 /PRNewswire/ -- Neurocrine Biosciences, Inc. (Nasdaq: NBIX) today announced that the first patient has been randomized for its Phase 2 clinical study to evaluate the efficacy, safety, and tolerability of investigational compound NBI-1070770 in adults with major depressive disorder. NBI-1070770 is a novel, selective, and orally active, negative allosteric modulator (NAM) of the NR2B subunit-containing N-methyl-D-aspartate (NMDA NR2B) receptor. "Based upon our Phase 1 first-in-human study, we are excited to bring this novel oral compound, which acts through a clinically validated mechanism of action, into clinical development as a potential treatment for major depressive disorder," said Eiry W. Roberts, M.D., Chief Medical Officer at Neurocrine Biosciences. "The selectivity of NBI-1070770 for the NMDA NR2B receptor has the potential to benefit patients who have moderate to severe depression." The NBI-1070770 Phase 2 multi-center, randomized, double-blind, placebo-controlled study will enroll approximately 72 adults and is being conducted at centers throughout the United States. The study will evaluate the safety and efficacy of NBI-1070770 in subjects with major depressive disorder compared to placebo on improving symptoms of depression as measured by the Montgomery-Åsberg Depression Rating Scale. For more information about the Phase 2 study (NBI-1070770-MDD2029), visit Clinicaltrials.gov. Neurocrine Biosciences acquired the rights to develop and commercialize NBI-1070770 from Takeda Pharmaceutical Company, Ltd. About Neurocrine Biosciences Neurocrine Biosciences is a leading neuroscience-focused, biopharmaceutical company with a simple purpose: to relieve suffering for people with great needs, but few options. We are dedicated to discovering and developing life-changing treatments for patients with under-addressed neurological, neuroendocrine and neuropsychiatric disorders. The company's diverse portfolio includes FDA-approved treatments for tardive dyskinesia, chorea associated with Huntington's disease, endometriosis* and uterine fibroids*, as well as a robust pipeline including multiple compounds in mid- to late-phase clinical development across our core therapeutic areas. For three decades, we have applied our unique insight into neuroscience and the interconnections between brain and body systems to treat complex conditions. We relentlessly pursue medicines to ease the burden of debilitating diseases and disorders, because you deserve brave science. For more information, visit neurocrine.com, and follow the company on LinkedIn, X (formerly Twitter), and Facebook. (*in collaboration with AbbVie) NEUROCRINE BIOSCIENCES, NEUROCRINE, and YOU DESERVE BRAVE SCIENCE are registered trademarks of Neurocrine Biosciences, Inc. The Neurocrine logo is a trademark of Neurocrine Biosciences, Inc. Forward-Looking Statement In addition to historical facts, this press release contains forward-looking statements that involve a number of risks and uncertainties. These statements include, but are not limited to, statements related to the potential benefits of NBI-1070770. Among the factors that could cause actual results to differ materially from those indicated in the forward-looking statements are: risks that clinical development activities may not be initiated or completed on time or at all, or may be delayed for regulatory, manufacturing, or other reasons, may not be successful or replicate previous clinical trial results, may fail to demonstrate that our product candidates are safe and effective, or may not be predictive of real-world results or of results in subsequent clinical trials; our future financial and operating performance; risks associated with our dependence on third parties for development, manufacturing, and commercialization activities for our products and product candidates, and our ability to manage these third parties; risks that the FDA or other regulatory authorities may make adverse decisions regarding our products or product candidates; risks that the potential benefits of the agreements with our collaboration partners may never be realized; risks that our products, and/or our product candidates may be precluded from commercialization by the proprietary or regulatory rights of third parties, or have unintended side effects, adverse reactions or incidents of misuse; risks associated with U.S. federal or state legislative or regulatory and/or policy efforts which may result in, among other things, an adverse impact on our revenues or potential revenue; risks associated with potential generic entrants for our products; and other risks described in the Company's periodic reports filed with the Securities and Exchange Commission, including without limitation the Company's annual report on Form 10-K for the year ended December 31, 2023. Neurocrine Biosciences disclaims any obligation to update the statements contained in this press release after the date hereof other than required by law. SOURCE Neurocrine Biosciences, Inc.

VANCOUVER, British Columbia, March 27, 2024 (GLOBE NEWSWIRE) -- Algernon Pharmaceuticals Inc. (the “Company” or “Algernon”) (CSE: AGN) (FRANKFURT: AGW0) (OTCQB: AGNPF), a Canadian clinical stage pharmaceutical development company, is pleased to announce that it has closed on its agreement with Seyltx Inc. (“Seyltx”), a privately owned U.S. based drug development company, for the acquisition of Algernon’s NP-120 (“Ifenprodil”) research program for the purchase price of USD $2M cash and a 20% common share equity position in Seyltx. The Company previously announced on November 22, 2003 that it had signed a Letter of Intent with Seyltx, to acquire Algernon’s Ifenprodil research program. Ifenprodil is an N-methyl-D-aspartate (“NMDA”) receptor antagonist specifically targeting the NMDA type subunit 2B (GluN2B), which prevents glutamate signaling. Ifenprodil is one of Algernon’s lead research programs and represents a novel first-in-class potential treatment for chronic cough. It is thought to interfere with central signalling in the brain, suppressing the urge to cough. “There are multiple converging lines of evidence that define GluN2B as the master regulator of the cough reflex in the deep brain, including human clinical data with the allosteric inhibitor Ifenprodil in the hardest to treat cough population, those with underlying idiopathic pulmonary fibrosis, illustrating dramatic reductions in cough counts. This human efficacy data is complemented by an extensive safety package that de-risks the final phases of clinical development,” said Dietrich A. Stephan, Ph.D. co-founder and CEO of Seyltx. “I have great respect for the Algernon team who have done an outstanding job at maturing the program to this point, and we look forward to completing the clinical development of this exciting agent for a common and debilitating condition.” Seyltx plans to initiate an Ifenprodil multi-center Phase 2b placebo-controlled chronic cough study in CY2024. Algernon’s clinical management team will be available to provide support, oversight, and management of the study. “We are very pleased to have closed this transaction with Seyltx,” said Christopher J. Moreau, Algernon’s Chief Executive Officer. “We believe that Ifenprodil, a first in class potential treatment for chronic cough could outperform all other drugs that have been clinically investigated to date. We look forward to working with Seyltx as they advance Ifenprodil into the Phase 2b clinical trial.” In connection with the transaction, Maxim Group LLC was paid a transaction advisory services fee pursuant to an agreement with Algernon whereby Maxim was retained to identify and evaluate potential M&A and strategic opportunities. Algernon’s Phase 2a Study Data Algernon’s decision to advance to a Phase 2b cough study was based on positive data previously reported from the Company’s proof of concept Phase 2a study of idiopathic pulmonary fibrosis (“IPF”) and chronic cough, where Ifenprodil showed a significant reduction in cough count. Patients with IPF are usually excluded from trials in refractory chronic cough (“RCC”), and cough in this population is regarded as extremely difficult to treat. Key Data: The geometric mean 24-hour cough counts were reduced by 32.0% at 4 weeks(p = 0.023) and 39.5% at 12 weeks (p = 0.001) compared to baselineThe geometric mean awake cough counts were reduced by 30.2% at 4 weeks(p = 0.038) and 37.4% at 12 weeks (p = 0.002) compared to baselineAlgernon previously announced on January 14, 2022, that it had received positive feedback from the U.S. Food and Drug Administration at its pre-Investigational New Drug (pre-IND) meeting for its investigation of Ifenprodil solely for the treatment of chronic cough. About Chronic Cough Chronic cough is defined as a cough lasting for more than eight weeks in duration and in the United States cough continues to be one of the most common reasons that adults consult medical doctors. Some cases of chronic cough are so debilitating that quality of life is severely impacted leading to depression, anxiety, urinary incontinence, dysphonia, sleep interruption, vomiting, and even rib fractures further adding to the decay in socio-familial dynamics. Chronic cough is believed to be the result of a hypersensitivity of the cough reflex within the neuronal circuitry that governs the urge to cough, wherein one or more aspects that regulate cough are over-active to stimulus, triggering a cough at abnormal levels. Trials of cough suppressants (“Antitussives”) have shown differences in response that may reflect differing pathological processes driving cough in different patients. Experimental Antitussives (like gefapixant and camlipixant) often only engage a single receptor, while the overall cough response is governed by multiple receptors triggered by a large variety of stimuli. A compound like Ifenprodil, acting centrally in the brain where all peripheral messages are sent and coordinated, may achieve a better outcome than what has been achieved by others in clinical trials. Chronic Cough Market According to Data Bridge Market Research analyses, the global chronic cough market was valued at USD $6.15B in 2021 and is projected to grow up to USD $11.38B by 2029. Merck & Co. obtained the rights to gefapixant, a P2X3 receptor antagonist, as the lead asset in the acquisition of Afferent Pharmaceuticals in 2016. At the time, gefapixant had interim data from a Phase 2b study in RCC. The deal was worth up to USD $1.25 billion. Bellus Health, which was advancing camlipixant, its own novel P2X3 receptor antagonist, closed a deal on June 16, 2023 with GSK plc which bought all the outstanding shares in Bellus for USD $14.75 per share in cash with a total deal value estimated at USD $2 billion, confirming the need for better therapies for chronic cough. About NP-120 (Ifenprodil) NP-120 selectively inhibits GluN2B receptors which diminish excitability of neurons and prevent the relaying of information along neuronal circuitry, including the cough reflex. NP-120 may also inhibit the neuroplastic enhancement of central and peripheral cough response neurons. About Seyltx Inc. Seyltx is a clinical-stage pharmaceutical company focused on addressing refractory chronic cough by modulating the master switch of the cough reflex in the brain. Refractory chronic cough is a common disorder estimated to affect between 4-5 million individuals in the United States alone, for which there exist no effective therapies. About Algernon Pharmaceuticals Inc. Algernon Pharmaceuticals is a Canadian clinical stage drug development company investigating multiple drugs for unmet global medical needs. Algernon Pharmaceuticals has active research programs for chronic kidney disease and is the parent company of a private subsidiary called Algernon NeuroScience, that is advancing a psychedelic program investigating a proprietary form of DMT for stroke and traumatic brain injury. CONTACT INFORMATION Christopher J. MoreauCEOAlgernon Pharmaceuticals Inc.604.398.4175 ext 701info@algernonpharmaceuticals.com investors@algernonpharmaceuticals.com www.algernonpharmaceuticals.com Neither the Canadian Securities Exchange nor its Market Regulator (as that term is defined in the policies of the Canadian Securities Exchange) accepts responsibility for the adequacy or accuracy of this release. CAUTIONARY DISCLAIMER STATEMENT: No Securities Exchange has reviewed nor accepts responsibility for the adequacy or accuracy of the content of this news release. This news release contains forward-looking statements relating to product development, licensing, commercialization and regulatory compliance issues 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 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 Company’s expectations include the failure to satisfy the conditions of the relevant securities exchange(s) and other risks detailed from time to time in the filings made by the Company with 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. 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 applicable law.