Remdesivir

人工智能（Artificial Intelligence，AI）的发展，为新药研发带来新的技术手段。AI制药（AIDD，即AI Drug Discovery）是指将NLP、深度神经网络、生成模型等AI技术与传统制药环节相结合，通过数据交叉比对、加速筛选等方式，提升新药研发效率，拓展药物创新空间的技术应用。 据数据显示：截至2023年底，全球AI制药企业数量高达897家，国内相关企业数量约为90家左右。这其中既有恒瑞医药这样的老牌药企，也有英矽智能、晶泰科技这样获得资本投资的新兴创业公司。目前全球AI药物研发企业约343家，潜在总额超过120亿美元。麦肯锡全球研究所（MGI）预计，生成式AI每年可为制药和医疗行业带来600亿至1100亿美元的经济价值。 国家发改委发布的首部生物经济五年规划——《“十四五”生物经济发展规划》，首次提出“生物经济”的概念，并对中国生物技术与信息技术的融合提出了新要求“推动生物信息产业发展，提升制药装备的自动化、数字化和智能化水平”，让行业对AI制药赛道有了更大的期待。 近日在三部门联合印发的《卫生健康行业人工智能应用场景参考指引》中，就明确指出AI可以赋能药物研发的全流程，包括智能药物研发、智能药物临床试验辅助、智能药品临床综合评价辅助。AI制药技术的应用有望缩短药物研发周期，降低成本，提高研发成功率。AI技术使得从药物设计到临床试验的全流程更加高效，为传统药物研发带来创新变革，并展现出在药物研发领域的广阔前景和巨大潜力。 智驱未来，AI制药赛道花开可期 AI制药的应用场景 AI技术可应用于药物发现、临床前研究、临床试验、药品生产和销售推广五个阶段，贯穿整个新药研发生产销售环节，其主要功能概括为三方面：探寻疾病机制、寻找对应的解决途径（蛋白靶点、信号通路、新的生物标志物等）、获取可用于抑制的生物试剂（能够满足特定属性的分子）。AI技术目前主要应用于靶点发现、先导化合物研究和化合物筛选、化合物合成、新适应症发现、晶型预测、优化临床试验设计、患者招募、药品检查、学术推广九大场景。其中，靶点发现和先导化合物研究被认为是全球AI+新药研发最具变革意义的研究领域，是企业布局的热门方向。此外，更强的关联搜索能力也是AI在药物重定向上的巨大优势。代表性案例包括： （1）2020年2月，Exscientia公司联合住友制药合作开发的针对强迫症的DSP-1181，在日本启动I期临床试验。该候选药物分子是全球首款完全由AI设计并进入临床试验的AI候选药物，整个项目从提出概念到进入临床，用时不到一年； （2）2020年2月，Benevolent.AI公司在《柳叶刀》杂志发表论文称，通过其研发的AI平台检索海量科学文献，发现巴瑞替尼或可用于治疗新冠。同年11月，FDA授予巴瑞替尼（Baricitinib）与瑞德西韦联用疗法作为行管特效药的紧急使用授权（EUA）； （3）2022年，Insilico Medicine将AlphaFold2（DeepMind公司的人工智能程序）应用于早期药物发现，成功在30天内获得了针对全新靶点CDK20的苗头化合物，CDK20抑制剂有望成为癌症，特别是肝细胞癌的创新疗法。 图. AI技术应用场景 资料来源：头豹研究院、凯莱英整理 AI制药赛道的竞争者 目前，布局AI制药赛道的企业主要分为互联网公司、AI制药企业和传统药厂三大阵营。 互联网公司进入AI制药赛道的形式主要为三种：对外投资+打造自己的相关平台+提供算力/计算框架服务。互联网公司主要以提供特定算法或框架的形式停留在产业链相对上游的部分。预测未来各类云计算平台将整合基础数据、AI研发工具以及算力，为客户提供端到端的一体化产品。 AI制药企业主要分为自研管线、自研平台、CRO/2B服务三种模式：自研管线在后期临床试验成本很高，且在相同的赛道上也可能存在竞争；自研平台领域分为专注于特定环节的特定单点软件和端到端平台两种形式，大部分软件目前仍处于市场推广与初期试用阶段；CRO/2B服务模式是目前的主要商业模式，这类模式承担着快速变现、维持现金流和验证技术实力、打开市场等多重职责。由于可以以靶点/候选化合物/候选药物等为交付结果，CRO/2B服务模式有助于初创公司将长期研发风险转移，同时有助于帮助技术平台沉淀。该模式一般采取首付款+里程碑付款的方式，单次CRO合作大多会涉及多个管线。如2022年8月17日，将人工智能用于小分子药物发现的领导者AI制药公司Atomwise宣布，已与赛诺菲签署多靶点研究合作，将利用其AtomNet®平台对多达五个药物靶点进行计算发现和研究。协议包括2000万美元的预付款，以及10亿美元的里程碑付款和分阶段特许权使用费。 传统药厂主要通过自建团队、对外投资及合作（CRO型业务合作和技术合作）这三种形式进入AI制药赛道。其中，业务合作已经成为最常见的形式，头部AI制药企业在传统药厂的合作上甚至逐渐呈现出垄断态势。以Exscientia为例，该公司已披露了和罗氏、拜耳、赛诺菲、GSK、日本住友、Evotec在内的顶级制药公司的合作。据Deep Pharma Intelligence，在44家世界头部传统药企中，已有93%的药企完成与AI制药企业的合作布局。特别是在罗氏、诺华、辉瑞等全球TOP 10药企中，与AI制药企业的合作平均达到6次以上，还形成了MELLODDY（Machine Learning Ledger Orchestration for Drug Discovery）、MLDPS（Machine Learning for Pharmaceutical Discovery and Synthesis Consortium）等由传统药企主导的大型AI制药联盟。 AI制药赛道已成投资风口 近几年来，AI技术在创新药领域的应用越来越多，将AI技术用于药物开发的创新药公司呈现出井喷式的增长，资本的持续助力成为AI药物研发赛道的重要驱动因素。Deep Pharma Intelligence（DPI）报告显示，自2016年以来，全球AI制药药物发现领域的投资金融整体呈上升态势，2021年达127.3亿美元。单轮过亿的融资已不鲜见，包括XtalPi和Insitro（均为4亿美元）、Generate Biomedicines（3.7亿美元）、Exscientia和Insilico Medicine（均为2.55亿美元）以及Arbor Biotechnologies（2.15亿美元）等。 与全球AI制药药物研发的发展趋势类似，2016-2021年的中国AI制药初创企业融资金额整体呈上升态势，2021年达到12.4亿美元。近几年来，随着政府相继出台一系列宏观政策，进一步促进了AI技术的创新成果转化，也鼓励了AI技术与产业的协同性发展。加之新冠疫情的影响推动了创新药的需求，中国AI制药的潜在市场正被逐渐打开。AI医药研发已经成为AI行业的重头戏，但在国内，AI对医药研发领域的助力尚为弱小。 图. 2016-2021全球AI制药药物发现领域投资金额 资料来源：头豹研究院 图. 2016-2021年中国AI制药初创企业融资金额 资料来源：头豹研究院 AI制药赛道已进入快速成长期，备受业界关注。随着AI技术的不断迭代及新政策的陆续出台，未来AI制药领域将会呈现更多新的突破。基于新的数据体系、计算框架、算法体系等，AI技术或将构筑制药业的新范式，助力赋能行业的创新发展。 参考资料： [1] 头豹研究院-2021年中国医药CXO（研发及生产外包服务）行业概览. [2] 头豹研究院-中国AI制药行业概览. [3] 量子位智库-AI制药深度产业报告. 全球AI制药行业现状——机遇与挑战并存 近两年，AI技术在各领域大放异彩，赢得全球各界的目光，点燃全球追捧AI研发的热潮。AI技术辅助新药研发，作为医疗AI中市场潜力巨大的细分领域，也获得全球制药企业的青睐，目前已有800余家知名药企，其中不乏500强老牌巨头，如阿斯利康、强生等都在AI制药领域推进多个创新合作项目。国内而言，也有近百家企业，包括恒瑞医药、石药集团等传统药企，纷纷跨领域与AI创新公司开展合作，通过战略合作、股权投资等不同形式积极拥抱AI。 2010年到2021年间，全球由AI参与的药物研发项目数量从6个增长到158个，2022年全球有近41家AI制药企业、80条药物管线成功进入临床阶段，其中41条推进到Ⅰ期，超过了总数的一半；Ⅱ期项目超过29个之多，都充分彰显了AI在临床应用中可观的推进速度。 据Research And Markets数据显示，2022年全球AI制药市场规模为10.4亿美元，预计2026年市场规模将达到29.94亿美元，年平均复合增长率高达30%。国内方面，AI药物研发行业起步稍晚，业内预计，2023年市场规模将达到4.14亿元。 图.2022年-2026年全球AI制药市场规模及增速 来源：根据公开资料整理 AI制药之所以引发全球热潮，最大的优势是有望降低新药研发成本。AI制药可定义为一种以医药大数据为学习研究土壤，运用NLP、CV、知识图谱、机器学习、深度学习等AI技术参与制药过程，以计算、预测、寻找合适的、新兴的有机物化学反应、潜在药物分子并观察药物临床效果的技术手段。因此，AI制药可通过自然语言处理、机器学习及大数据等人工智能技术，提高优化新药研发的效率及质量，降低临床失败概率及研发成本。 一般而言，传统的药物创新研发遵循着“倒摩尔定律”，即大约每九年，药物研发的成本会翻倍。Pharma projects 数据显示，全球的新药研发成本由2010年的11.9亿美元上升至2020年的25.1亿美元。但AI技术完全逆而行之，凭借数据和算法模型建立的优势，有助于避免研发过程中的人为因素干扰，有望缩短药物早期发现所需时间，显著节约成本。据统计，使用AI技术能够将药物发现时间缩短40%，药物临床试验时间节约50%-60%，同时将临床新药研发的成功率从12%提高到约14%，总体上达到减少药物研发成本的目的。 目前，AI制药主要应用于靶点发现、化合物合成、化合物筛选、药物晶型预测、患者招募、药物重定向与临床试验设计优化等场景。AI制药企业布局的领域中，近一半都是从事早期药物开发，其次是数据处理、临床开发、端到端药物开发、临床前发展和药物再利用等。从AI制药参与的临床适应症方向来看，肿瘤、免疫学、神经病学领域占比最大，分别为37%、21%和14%。 图. AI制药参与的临床适应症分布 图. AI制药企业布局领域分布 来源：观知海内 梳理AI制药全产业链，上游为人工智能技术和生物医疗设备等，前者包括芯片、服务器硬件设备、数据收集和处理平台、云计算平台等，后者包括冷冻电镜、自动化实验室等设备；中游为药物研发过程的全环节，包括靶点发现、老药新用、化合物筛选、分子设计以及优化、晶型预测、ADMET预测、临床前实验结果预测等领域，产品类型主要包括小分子药物、大分子药物、新药研发、细胞基因疗法等；下游客户包括CXO在内的药物制造开发企业。 凭借全球东风，AI制药相关初创公司近两年大量涌现，并成功获得资本青睐。数据显示，2022年全球AI制药赛道相关融资总事件达144起，同比增长87%，总金额为62.02亿美元，同比增长36%。其中，中国43起。 2023年全球AI+药物研发相关融资总事件达104件，总金额为36亿美元。其中美国的AI药物研发融资事件为48起，中国32起，其他国家和地区为24起，投融资活动仍然主要活跃在中国、美国和欧洲（欧洲则集中在英国）。中国的投融资活动则主要集中于珠三角、京津冀以及长三角等医药产业较为发达的地区。 图. 全球AI制药企业融资事件数量 来源：根据公开资料整理 虽然AI制药前景一片光明 ，但我们也要注意当下存在的潜在问题：AI黑盒算法存在安全风险，时至今日仍有原理不够透明、运行机制无法解释的弊端。 AI算法的黑盒问题产生的原因是深度学习等主流算法模型内部结构复杂，运行过程自主性强、人工无法干预，所以在数据输入、模型训练、结果输出等方面存在用户无法真实了解其内部工作原理的问题，导致结果也不能完全掌控。 另一方面，深度学习的特点是基于大量数据及模型训练，而药物开发、疾病诊断及治疗计划领域的数据质量具有诸多问题，如各医疗机构、实验室生成数据的实验条件和记录数据的格式或注释往往不相同，存在数值不一致、数据缺失、误差等问题，难以被计算机统一识别，加之医药领域普遍存在“数据孤岛”，大多数高质量和核心数据掌握在少数企业中，保密性极强，公开可能性较小，制约了“AI+医药”行业的整体发展。 总体而言，AI制药处于挑战与机遇并存的局面，不仅考验技术创新，也对行业合作、数据共享、伦理规范提出了更高层次的要求，期待AI制药领域的难题能及早一一破解，迎来真正的行业大爆发。   References   参考资料 1.https://baijiahao.baidu.com/s?id=1800375985631400000 2.https://baijiahao.baidu.com/s?id=1785700983659122271&wfr=spider&for=pc 3.https://www.sohu.com/a/769025314_260616 4.https://www.163.com/dy/article/IVVF1A3L05198SOQ.html END 来源 | 凯莱英Asymchem，等 声明：文章资料来源于网络，如涉及内容、版权和其它问题，请联系 ehs_pharma@163.com 及时处理！文章内容为作者个人观点,并不代表本公众号赞同或支持其观点。如果转载，请注明来源及作者。 点分享 点收藏 点在看 点点赞

SHELTON, CT / ACCESSWIRE / December 23, 2024 / NanoViricides, Inc. (NYSE American:NNVC) (the "Company"), says that its broad-spectrum antiviral drug candidate NV-387 is the best weapon to fight a potential bird flu pandemic because the mercurial H5N1 Influenza A virus would not be able to escape the drug."Despite all changes, the H5N1 Influenza A virus should remain susceptible to NV-387 because NV-387 mimics the very essential host-side feature that H5N1 continues to use even as it changes," said Anil R. Diwan, Ph.D., President and Executive Chairman of the Company, adding "This drug puts us in a great position to be able to fight a bird flu pandemic should it happen."WHO has stated "Available virus sequences from human cases [of H5 infection] have shown some genetic markers that may reduce susceptibility to neuraminidase inhibitors (antiviral medicines such as oseltamivir) [NAIs] or endonuclease inhibitors (such as baloxavir marboxil) [PBIs]" in their updated public health assessment of recent Influenza A H5 infections, dated December 20, 2024[1].NAIs and PBIs[2] are the only classes of drugs that currently exist for influenza treatment, and as the virus evolves, they are very likely to be rendered ineffective in the field, since already strains with reduced susceptibility are circulating.While the US Government has already sourced and stockpiled two different H5N1 vaccines, the Biden administration has currently no plans to authorize their use.Influenza viruses change far more rapidly than SARS-CoV-2 ever did in the COVID-19 pandemic[3]. At least one mutation in the H5 coat protein would be required for efficient infection of humans, and a few more changes that would still be required for rapid human-to-human transmission, in order for the H5N1 virus to turn into a pandemic virus; changes that have not happened yet.Nevertheless, any currently designed H5N1 vaccines are unlikely to be of much use, or possibly very limited use, from public health perspective to protect from a potential pandemic strain of H5N1 that has not appeared yet.In any case, vaccine against a rapidly changing virus is a game of chasing a rapidly moving target, as we have all learned from the experience during the COVID-19 pandemic[4].It is thus clear that a drug that the virus cannot escape is the only appropriate tool to fight a potential pandemic.We have already developed such a drug. NV-387 is a broad-spectrum antiviral that mimics the very host-side features that the virus continues to require no matter how much it changes in the field. It is highly unlikely that a susceptible virus would escape such a drug.The ultra-broad antiviral spectrum of NV-387, which encompasses a large number of diverse kinds of viruses including COVID, RSV, Influenza and even Orthopoxviruses (i.e. MPox, Smallpox), further substantiates that it is unlikely that a susceptible virus would escape this drug.What is more, NV-387 has demonstrated substantially superior activity to existing influenza drugs in a lethal lung infection animal study, as we have previously reported (reproduced below):Survival Lifespan of Lethally Infected Mice - Lung Infection with Influenza A H3N2TreatmentSurvival, DaysIncrease in Survival, DaysIncrease in Survival, %NV-387, Oral15788%Oseltamivir, Oral10225%Peramivir, I.V.11338%Baloxivir, Oral11338%Vehicle800%In this animal study, we also found that NV-387 treatment led to significant lung protection in the infected animals: lung destroying immune cell infiltration was substantially reduced, and the amount of mucus in the lungs was also substantially reduced, indicating that NV-387 protected the lungs and the animal from advancing into pneumonia.We believe that any H5N1 highly pathogenic virus is likely to be even more susceptible to NV-387 than the seasonal H3N2 influenza A virus. This is because all High-Path Avian Influenza A viruses are known to possess a poly-basic site that is much longer than the corresponding sequence in seasonal influenza viruses. The virus uses this poly-basic site to bind to sulfated proteoglycans prior to entry into cells. NV-387 displays a copious amount ligands that mimic this sulfated structure, which is how this drug (NV-387) entraps the virus. Thus a longer poly-basic site would be expected to cause a stronger interaction between the H5N1 High Path viruses and NV-387 in contrast to the interaction between NV-387 and seasonal influenza viruses.NV-387 has completed a Phase I human clinical trial with no reported adverse events and no drop-outs, indicating excellent safety and tolerability. We are now preparing for a Phase II clinical trial for the treatment of MPox which is currently an epidemic in Central Africa. We are also working on a Phase II clinical trial of NV-387 for the treatment of respiratory virus infections (including Influenza viruses, Coronaviruses, and RSV, among others).Thus we believe that we are in a strong position to combat a potential bird flu pandemic, being one of very few companies globally that is developing a broad-spectrum antiviral drug with the promise that viruses would be highly unlikely to escape the drug.[1] https://www.who.int/publications/m/item/updated-joint-fao-who-woah-assessment-of-recent-influenza-a(h5n1)-virus-events-in-animals-and-people_dec2024[2] NAIs = Neuraminidase inhibitors. These include Oseltamivir (Tamiflu®), Peramivir (Rapivab®), Zanamivir (Relenza®). They inhibit the exit of the virus particle from cell after the virus has already replicated into copious quantities inside the cell. PBIs = Viral Polymerase (B) inhibitors. Currently only Baloxavir (Xofluza) is licensed. They inhibit the production of new copies of viral genomic RNA. However, resistant virus to baloxavir was created in patients treated with baloxavir in its clinical trial itself. Further, the toxicity of this drug limits its use to a single dose.[3] Influenza viruses change very rapidly because they have many more tools to change themselves compared to other viruses. Firstly, an influenza virus is made up of eight separate segments of RNA, that it can simply swap with other influenza viruses (called "Re-assortment"). Secondly, segments of RNA can hop from one RNA to another (Called "Recombination"), and thirdly, single point mutations occur all the time across the entire RNA, because the virus lacks "proof-reading" capability (i.e. ability to ensure that the RNA is copied correctly).[4] The COVID vaccines did not protect the vaccinated from getting sick, and they did not even stop the vaccinated from transmitting the virus to others. The benefit of vaccination is thought to be in persons with other morbidities who would have been likely to contract severe disease from infection with hospitalization and possible death. However, the vaccines always lagged behind in time, developed against a strain that was already overtaken by a different one in the field even before rollout of the vaccine.About NanoViricidesNanoViricides, Inc. (the "Company") (www.nanoviricides.com) is a clinical stage company that is creating special purpose nanomaterials for antiviral therapy. The Company's novel nanoviricide™ class of drug candidates and the nanoviricide™ technology are based on intellectual property, technology and proprietary know-how of TheraCour Pharma, Inc. The Company has a Memorandum of Understanding with TheraCour for the development of drugs based on these technologies for all antiviral infections. The MoU does not include cancer and similar diseases that may have viral origin but require different kinds of treatments.The Company has obtained broad, exclusive, sub-licensable, field licenses to drugs developed in several licensed fields from TheraCour Pharma, Inc. The Company's business model is based on licensing technology from TheraCour Pharma Inc. for specific application verticals of specific viruses, as established at its foundation in 2005.Our lead drug candidate is NV-387, a broad-spectrum antiviral drug that we plan to develop as a treatment of RSV, COVID, Long COVID, Influenza, and other respiratory viral infections, as well as MPOX/Smallpox infections. Our other advanced drug candidate is NV-HHV-1 for the treatment of Shingles. The Company cannot project an exact date for filing an IND for any of its drugs because of dependence on a number of external collaborators and consultants. The Company is currently focused on advancing NV-387 into Phase II human clinical trials.NV-CoV-2 (API NV-387) is our nanoviricide drug candidate for COVID-19 that does not encapsulate remdesivir. NV-CoV-2-R is our other drug candidate for COVID-19 that is made up of NV-387 with remdesivir encapsulated within its polymeric micelles. The Company believes that since remdesivir is already US FDA approved, our drug candidate encapsulating remdesivir is likely to be an approvable drug, if safety is comparable. Remdesivir is developed by Gilead. The Company has developed both of its own drug candidates NV-CoV-2 and NV-CoV-2-R independently.The Company is also developing drugs against a number of viral diseases including oral and genital Herpes, viral diseases of the eye including EKC and herpes keratitis, H1N1 swine flu, H5N1 bird flu, seasonal Influenza, HIV, Hepatitis C, Rabies, Dengue fever, and Ebola virus, among others. NanoViricides' platform technology and programs are based on the TheraCour® nanomedicine technology of TheraCour, which TheraCour licenses from AllExcel. NanoViricides holds a worldwide exclusive perpetual license to this technology for several drugs with specific targeting mechanisms in perpetuity for the treatment of the following human viral diseases: Human Immunodeficiency Virus (HIV/AIDS), Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), Rabies, Herpes Simplex Virus (HSV-1 and HSV-2), Varicella-Zoster Virus (VZV), Influenza and Asian Bird Flu Virus, Dengue viruses, Japanese Encephalitis virus, West Nile Virus, Ebola/Marburg viruses, and certain Coronaviruses. The Company intends to obtain a license for RSV, Poxviruses, and/or Enteroviruses if the initial research is successful. As is customary, the Company must state the risk factor that the path to typical drug development of any pharmaceutical product is extremely lengthy and requires substantial capital. As with any drug development efforts by any company, there can be no assurance at this time that any of the Company's pharmaceutical candidates would show sufficient effectiveness and safety for human clinical development. Further, there can be no assurance at this time that successful results against coronavirus in our lab will lead to successful clinical trials or a successful pharmaceutical product.This press release contains forward-looking statements that reflect the Company's current expectation regarding future events. Actual events could differ materially and substantially from those projected herein and depend on a number of factors. Certain statements in this release, and other written or oral statements made by NanoViricides, Inc. are "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. You should not place undue reliance on forward-looking statements since they involve known and unknown risks, uncertainties and other factors which are, in some cases, beyond the Company's control and which could, and likely will, materially affect actual results, levels of activity, performance or achievements. The Company assumes no obligation to publicly update or revise these forward-looking statements for any reason, or to update the reasons actual results could differ materially from those anticipated in these forward-looking statements, even if new information becomes available in the future. Important factors that could cause actual results to differ materially from the company's expectations include, but are not limited to, those factors that are disclosed under the heading "Risk Factors" and elsewhere in documents filed by the company from time to time with the United States Securities and Exchange Commission and other regulatory authorities. Although it is not possible to predict or identify all such factors, they may include the following: demonstration and proof of principle in preclinical trials that a nanoviricide is safe and effective; successful development of our product candidates; our ability to seek and obtain regulatory approvals, including with respect to the indications we are seeking; the successful commercialization of our product candidates; and market acceptance of our products.The phrases "safety", "effectiveness" and equivalent phrases as used in this press release refer to research findings including clinical trials as the customary research usage and do not indicate evaluation of safety or effectiveness by the US FDA.FDA refers to US Food and Drug Administration. IND application refers to "Investigational New Drug" application. cGMP refers to current Good Manufacturing Practices. CMC refers to "Chemistry, Manufacture, and Controls". CHMP refers to the Committee for Medicinal Products for Human Use, which is the European Medicines Agency's (EMA) committee responsible for human medicines. API stands for "Active Pharmaceutical Ingredient". WHO is the World Health Organization. R&D refers to Research and Development.Contact:NanoViricides, Inc.[email protected]Public Relations Contact:[email protected]SOURCE: NanoViricides, Inc.