Moderna 新型冠状病毒 mRNA 疫苗 mRNA-1273中期试验结果公布

Posted 2020-11-28 leezx

参考：

https://investors.modernatx.com/news-releases/news-release-details/moderna-announces-positive-interim-phase-1-data-its-mrna-vaccine

 

 

May 18, 2020 at 7:30 AM EDT 2020年5月18日美国东部时间上午7:30
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After two doses all participants evaluated to date across the 25 µg and 100 µg dose cohorts seroconverted with binding antibody levels at or above levels seen in convalescent sera

经过两次剂量后，所有参与者的血清转换为25克和100克剂量组，其结合抗体水平均达到或超过恢复期血清中的水平

mRNA-1273 elicited neutralizing antibody titer levels in all eight initial participants across the 25 µg and 100 µg dose cohorts, reaching or exceeding neutralizing antibody titers generally seen in convalescent sera

在25克和100克剂量组中，mRNA-1273在所有8名初始参与者中引起中和抗体滴度水平，达到或超过康复血清中通常见到的中和抗体滴度

mRNA-1273 was generally safe and well tolerated

Mrna-1273基本上是安全的，耐受性良好

mRNA-1273 provided full protection against viral replication in the lungs in a mouse challenge model

Mrna-1273在小鼠攻击模型中对病毒在肺部的复制提供了完全的保护

Anticipated dose for Phase 3 study between 25 µg and 100 µg; expected to start in July

第三阶段研究的预计剂量介于25克至100克之间; 预计于7月开始

Conference call to be held on Monday, May 18 at 8:30 a.m. ET

电话会议将于美国东部时间5月18日星期一上午8:30举行

CAMBRIDGE, Mass.--(BUSINESS WIRE)--May 18, 2020-- Moderna, Inc., (Nasdaq: MRNA) a clinical stage biotechnology company pioneering messenger RNA (mRNA) therapeutics and vaccines to create a new generation of transformative medicines for patients, today announced positive interim clinical data of mRNA-1273, its vaccine candidate against novel coronavirus (SARS-CoV-2), from the Phase 1 study led by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH).

2020年5月18日，马萨诸塞州坎布里奇——(商业线)—— Moderna，inc. ，(纳斯达克: MRNA)一家临床阶段的生物技术公司，开创了信使核糖核酸疗法和疫苗，为患者创造新一代的变革性药物，今天宣布了 MRNA-1273的临床数据，该公司研制的新型冠状病毒(SARS-CoV-2)候选疫苗 MRNA-1273，来自美国国家过敏与传染病研究所(NIH)领导的第一阶段研究，是 NIH 的一部分。

Immunogenicity data are currently available for the 25 µg and 100 µg dose level (ages 18-55) after two doses (day 43) and at the 250 µg level (ages 18-55) after one dose (day 29). Dose dependent increases in immunogenicity were seen across the three dose levels, and between prime and boost within the 25 µg and 100 µg dose levels. All participants ages 18-55 (n=15 per cohort) across all three dose levels seroconverted by day 15 after a single dose. At day 43, two weeks following the second dose, at the 25 µg dose level (n=15), levels of binding antibodies were at the levels seen in convalescent sera (blood samples from people who have recovered from COVID-19) tested in the same assay. At day 43, at the 100 µg dose level (n=10), levels of binding antibodies significantly exceeded the levels seen in convalescent sera. Samples are not yet available for remaining participants.

目前可以获得两次剂量(第43天)后25克和100克剂量水平(18-55岁)以及一次剂量(第29天)后250克水平(18-55岁)的免疫原性数据。 三种剂量水平的免疫原性呈剂量依赖性增强，25克和100克剂量水平的初始和增强之间呈剂量依赖性增强。 所有年龄在18-55岁之间的参与者(每组15人)在接受单次剂量后，于第15天血清转换所有三种剂量水平。 在第43天，第二剂量后两周，在25克剂量水平(n15) ，结合抗体水平与恢复期血清(从新型冠状病毒肺炎康复的人的血液样本)在同一分析中检测的水平相同。 在第43天，100克剂量水平(n10) ，结合抗体水平显著超过恢复期血清中的水平。 剩下的参与者还没有样品。

At this time, neutralizing antibody data are available only for the first four participants in each of the 25 µg and 100 µg dose level cohorts. Consistent with the binding antibody data, mRNA-1273 vaccination elicited neutralizing antibodies in all eight of these participants, as measured by plaque reduction neutralization (PRNT) assays against live SARS-CoV-2. The levels of neutralizing antibodies at day 43 were at or above levels generally seen in convalescent sera.

目前，中和抗体卫生组织的数据只能提供25克和100克剂量组的前4名参与者的数据。 与结合抗体数据一致的是，mRNA-1273疫苗接种在所有8个参与者中引起中和抗体，通过对活 SARS-CoV-2的斑块减少中和(PRNT)测定。 恢复期血清中和抗体水平在第43天达到或高于恢复期血清水平。

mRNA-1273 was generally safe and well tolerated, with a safety profile consistent with that seen in prior Moderna infectious disease vaccine clinical studies. The sole incidence of a grade 3 adverse event in the 25 µg and 100 µg dose cohorts was a single participant at 100 µg who experienced grade 3 erythema (redness) around the injection site. To date, the most notable adverse events were seen at the 250 µg dose level, comprising three participants with grade 3 systemic symptoms, only following the second dose. All adverse events have been transient and self-resolving. No grade 4 adverse events or serious adverse events have been reported.

Mrna-1273基本上是安全的，耐受性良好，其安全性与先前的现代传染病疫苗临床研究结果一致。 在25克和100克剂量组中，只有一名参与者在注射部位周围出现3级红斑(发红) ，发生率为100克。 迄今为止，最值得注意的不良事件发生在250克剂量水平，包括三名患有3级全身症状的参与者，仅次于第二次剂量。 所有的不良事件都是短暂的和自我解决的。 没有4级不良事件或严重不良事件的报告。

Preclinical results from a viral challenge study in mice conducted in collaboration with NIAID and its academic partners are also available. In this study, vaccination with mRNA-1273 prevented viral replication in the lungs of animals challenged with SARS-CoV-2. Neutralizing titers in Phase 1 clinical trial participants at the 25 µg and 100 µg dose levels were consistent with neutralizing titers that were protective in the mouse challenge model.

与 NIAID 及其学术伙伴合作进行的小鼠病毒挑战研究的临床前结果也可以获得。 在这项研究中，用 mRNA-1273接种疫苗可以阻止 SARS-CoV-2感染动物肺部的病毒复制。 第一阶段临床试验参与者中和滴度在25克和100克剂量水平与中和滴度一致，在小鼠挑战模型中具有保护作用。

Based on the interim Phase 1 data, the Moderna-led Phase 2 study will be amended to study two dose levels, 50 µg and 100 µg, with the aim of selecting a dose for pivotal studies. The NIAID-led Phase 1 study is being amended to include a 50 µg dose level cohort across each of the three age groups. Moderna anticipates the dose for the Phase 3 study to be between 25 µg and 100 µg and expects Phase 3 trial initiation in July, subject to finalization of the clinical trial protocol.

根据临时第一阶段的数据，现代主义领导的第二阶段研究将进行修改，以研究两个剂量水平，50克和100克，目的是选择一个关键的研究剂量。 正在对国际艾滋病署牵头的第一阶段研究进行修订，以便在三个年龄组中的每一个组中纳入50克剂量水平的队列。 现代化预计第三阶段研究的剂量将在25克至100克之间，并预计第三阶段试验将在7月开始，取决于临床试验方案的最终确定。

“These interim Phase 1 data, while early, demonstrate that vaccination with mRNA-1273 elicits an immune response of the magnitude caused by natural infection starting with a dose as low as 25 µg,” said Tal Zaks, M.D., Ph.D., Chief Medical Officer at Moderna. “When combined with the success in preventing viral replication in the lungs of a pre-clinical challenge model at a dose that elicited similar levels of neutralizing antibodies, these data substantiate our belief that mRNA-1273 has the potential to prevent COVID-19 disease and advance our ability to select a dose for pivotal trials.”

Moderna 首席医疗官 Tal Zaks 医学博士博士说: “这些初步的第一阶段数据表明，使用 mRNA-1273接种疫苗会引起免疫反应，其程度与自然感染开始剂量低至25克所引起的免疫反应相当。”。 “结合临床前接种模型成功阻止病毒在肺部复制的剂量引起相似水平的中和抗体，这些数据证实了我们的信念，即 mRNA-1273具有预防新型冠状病毒肺炎病的潜力，并提高我们为关键试验选择剂量的能力。”

“With today’s positive interim Phase 1 data and the positive data in the mouse challenge model, the Moderna team continues to focus on moving as fast as safely possible to start our pivotal Phase 3 study in July and, if successful, file a BLA,” said Stéphane Bancel, Chief Executive Officer at Moderna. “We are investing to scale up manufacturing so we can maximize the number of doses we can produce to help protect as many people as we can from SARS-CoV-2.”

“有了今天积极的中期第一阶段数据和老鼠挑战模型的积极数据，Moderna 团队继续集中于尽快安全地开始我们关键的第三阶段研究在七月，如果成功的话，提交一份 BLA，” Moderna 的首席执行官 st phane Bancel 说。 “我们正在投资扩大生产规模，这样我们就能最大限度地生产疫苗，以帮助保护尽可能多的人免受 SARS-CoV-2的感染。”

Funding from the Biomedical Advanced Research and Development Authority (BARDA), a division of the Office of the Assistant Secretary for Preparedness and Response (ASPR) within the U.S. Department of Health and Human Services (HHS), supported the planning for the Phase 2 and Phase 3 studies of mRNA-1273 and will also support the execution of these studies, as well as the scale-up of mRNA-1273 manufacturing both at the Company’s facilities and that of its strategic collaborator, Lonza Ltd.

美国卫生和公众服务部负责准备和反应的助理秘书办公室下属的生物医学高级研究和发展管理局卫生研究所提供的资金支持了 mRNA-1273的第二阶段和第三阶段研究的计划，并将支持这些研究的实施，以及扩大 mRNA-1273在该公司设施和其战略合作者 Lonza 有限公司的生产规模。

Conference Call and Webcast Information

电话会议及网上广播资料

Moderna will host a live conference call and webcast at 8:30 a.m. ET on Monday, May 18, 2020. To access the live conference call, please dial 866-922-5184 (domestic) or 409-937-8950 (international) and refer to conference ID 2186342. A webcast of the call will also be available under “Events and Presentations” in the Investors section of the Moderna website at investors.modernatx.com. The archived webcast will be available on Moderna’s website approximately two hours after the conference call.

现代版将在2020年5月18日星期一美国东部时间上午8:30主持电话会议和网络直播。 要进入现场电话会议，请拨打866-922-5184(国内)或409-937-8950(国际)并参阅会议 ID 2186342。 此次电话会议的网络直播也将在 Moderna 网站的投资者部分的“活动和演示”栏目下面的 Investors.modernatx.com 中提供。 存档的网络广播将在电话会议后大约两个小时在 Moderna 的网站上提供。

About mRNA-1273

关于 mRNA-1273

mRNA-1273 is an mRNA vaccine against SARS-CoV-2 encoding for a prefusion stabilized form of the Spike (S) protein, which was selected by Moderna in collaboration with investigators from Vaccine Research Center (VRC) at the National Institute of Allergy and Infectious Diseases (NIAID), a part of the NIH. The first clinical batch, which was funded by the Coalition for Epidemic Preparedness Innovations, was completed on February 7, 2020 and underwent analytical testing; it was shipped to NIH on February 24, 42 days from sequence selection. The first participant in the NIAID-led Phase 1 study of mRNA-1273 was dosed on March 16, 63 days from sequence selection to Phase 1 study dosing.

Mrna-1273是一种针对 SARS-CoV-2编码的 s 蛋白预融合稳定形式的 mRNA 疫苗，该疫苗是由 Moderna 与美国国家过敏与传染病研究所疫苗研究中心(VRC)的研究人员合作选择的，该研究所是 NIH 的一部分。 第一批由流行病防范创新联盟资助的临床试验于2020年2月7日完成，并进行了分析测试; 它于2月24日运抵 NIH，距序列选择还有42天。 国际艾滋病研究所领导的 mRNA-1273第一阶段研究的第一位参与者于3月16日服药，从序列选择到第一阶段研究服药共63天。

On May 6, the U.S. Food and Drug Administration (FDA) completed its review of the Company’s Investigational New Drug (IND) application for mRNA-1273 allowing it to proceed to a Phase 2 study, which is expected to begin shortly. On May 12, the FDA granted mRNA-1273 Fast Track designation. Moderna is finalizing the protocol for a Phase 3 study, expected to begin in July 2020. A summary of the company’s work to date on SARS-CoV-2 can be found here.

5月6日，美国食品和药物管理局(FDA)完成了对该公司关于 mRNA-1273的研究新药(IND)申请的审查，允许该公司进入第二阶段研究，预计不久将开始。 5月12日，FDA 批准了 mRNA-1273快速通道认证。 现代化正在为第三阶段研究敲定方案，预计于2020年7月开始。 该公司迄今为止在 SARS-CoV-2方面的工作摘要可以在这里找到。

About Moderna’s Prophylactic Vaccines Modality

关于现代人预防性疫苗的形式

Moderna scientists designed the company’s prophylactic vaccines modality to prevent infectious diseases. More than 1,400 participants have been enrolled in Moderna’s infectious disease vaccine clinical studies under health authorities in the U.S., Europe and Australia. Clinical data demonstrate that Moderna’s proprietary vaccine technology has been generally well-tolerated and can elicit durable immune responses to viral antigens. Based on clinical experience across Phase 1 studies, the company designated prophylactic vaccines a core modality and is working to accelerate the development of its vaccine pipeline.

现代科学家设计了该公司的预防性疫苗模式来预防传染病。 在美国、欧洲和澳大利亚的卫生当局的监督下，超过1400名参与者参加了 Moderna 的传染病疫苗临床研究。 临床数据表明，Moderna 的专利疫苗技术一般耐受良好，能够引起病毒抗原的持久免疫反应。 根据第一阶段研究的临床经验，该公司将预防性疫苗指定为核心模式，并正在努力加速其疫苗管道的开发。

The potential advantages of an mRNA approach to prophylactic vaccines include the ability to combine multiple mRNAs into a single vaccine, rapid discovery to respond to emerging pandemic threats and manufacturing agility derived from the platform nature of mRNA vaccine design and production. Moderna has built a fully integrated manufacturing plant which enables the promise of the technology platform.

预防性疫苗的信使核糖核酸方法的潜在优势包括将多个信使核糖核酸结合成单一疫苗的能力，对新出现的大流行威胁作出反应的快速发现，以及来自信使核糖核酸疫苗设计和生产平台性质的制造灵活。 现代化已经建立了一个完全集成的制造工厂，使承诺的技术平台。

Moderna currently has nine development candidates in its prophylactic vaccines modality, including:

现代社会目前在预防性疫苗方面有九个候选研发对象，包括:

Vaccines against respiratory infections

呼吸道感染疫苗

Respiratory syncytial virus (RSV) vaccine for older adults (mRNA-1777 and mRNA-1172 or V172 with Merck) 针对老年人的人类唿吸道合胞病毒(RSV)疫苗(mRNA-1777和 mRNA-1172或默克公司的 V172)
RSV vaccine for young children (mRNA-1345) 儿童呼吸道合胞病毒疫苗(mRNA-1345)
Human metapneumovirus (hMPV) and parainfluenza virus type 3 (PIV3) vaccine (mRNA-1653) 人类偏肺病毒及副流感三型病毒疫苗(mRNA-1653)
Novel coronavirus (SARS-CoV-2) vaccine (mRNA-1273) 新型冠状病毒(SARS-CoV-2)疫苗(mRNA-1273)
Influenza H7N9 (mRNA-1851) H7n9流感病毒(mRNA-1851)
Vaccines against infections transmitted from mother to baby

预防母婴传播感染的疫苗

Cytomegalovirus (CMV) vaccine (mRNA-1647) 巨细胞病毒(CMV)疫苗(mRNA-1647)
Zika vaccine (mRNA-1893 with BARDA) 寨卡病毒疫苗(mRNA-1893与 BARDA)
Vaccines against highly prevalent viral infections

针对高度流行病毒感染的疫苗

Epstein-Barr virus (EBV) vaccine (mRNA-1189) 人类疱疹病毒第四型疫苗(mRNA-1189)
To date, Moderna has demonstrated positive Phase 1 data readouts for seven prophylactic vaccines (H10N8, H7N9, RSV, chikungunya virus, hMPV/PIV3, CMV and Zika). Moderna’s CMV vaccine is currently in a Phase 2 dose-confirmation study. Moderna’s investigational Zika vaccine (mRNA-1893), currently in a Phase 1 study, was granted FDA Fast Track designation in August 2019.

迄今为止，Moderna 已证实7种预防性疫苗(H10N8、 H7N9、 RSV、基孔肯雅病毒、 hmpv / piv3、 CMV 和寨卡病毒)的1期数据显示为阳性。 现代人巨细胞病毒疫苗目前正在进行第二阶段剂量确认研究。 现代人正在研究的寨卡疫苗(mRNA-1893) ，目前处于第一阶段研究中，在2019年8月被 FDA 授予快速通道称号。

About Moderna

关于 Moderna

Moderna is advancing messenger RNA (mRNA) science to create a new class of transformative medicines for patients. mRNA medicines are designed to direct the body’s cells to produce intracellular, membrane or secreted proteins that can have a therapeutic or preventive benefit and have the potential to address a broad spectrum of diseases. The company’s platform builds on continuous advances in basic and applied mRNA science, delivery technology and manufacturing, providing Moderna the capability to pursue in parallel a robust pipeline of new development candidates. Moderna is developing therapeutics and vaccines for infectious diseases, immuno-oncology, rare diseases and cardiovascular diseases, independently and with strategic collaborators.

现代人正在推进信使核糖核酸(mRNA)科学，为患者创造一种新的转化药物。 信使核糖核酸药物旨在引导人体细胞产生细胞内、细胞膜或分泌的蛋白质，这些蛋白质具有治疗或预防作用，并有可能治疗广泛的疾病。 该公司的平台建立在基础和应用信使核糖核酸科学、传递技术和制造领域不断进步的基础上，为现代人提供了并行开发新开发候选产品的能力。 现代人正在独立并与战略合作者开发传染病、免疫肿瘤学、罕见疾病和心血管疾病的治疗学和疫苗。

Headquartered in Cambridge, Mass., Moderna currently has strategic alliances for development programs with AstraZeneca PLC and Merck & Co., Inc., as well as the Defense Advanced Research Projects Agency (DARPA), an agency of the U.S. Department of Defense, and the Biomedical Advanced Research and Development Authority (BARDA), a division of the Office of the Assistant Secretary for Preparedness and Response (ASPR) within the U.S. Department of Health and Human Services (HHS). Moderna has been ranked in the top ten of Science’s list of top biopharma industry employers for the past five years. To learn more, visit www.modernatx.com.

总部位于马萨诸塞州坎布里奇的现代化公司目前与阿斯利康公司、默克公司、美国国防部下属的国防高级研究计划局以及美国卫生与公众服务部负责准备和反应的助理国务卿办公室下属的美国生物医学高级研究和发展管理局研究与发展部建立了战略联盟。 在过去的五年里，现代版一直在《科学》杂志的顶级生物制药行业雇主名单上排名前十。 欲了解更多信息，请访问 www.modernatx.com。

Forward Looking Statement

前瞻性声明

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including regarding the Company’s development of a potential vaccine against the novel coronavirus, the parameters and timing of the Phase 1 and planned Phase 2 and 3 studies of mRNA-1273, the Company’s investment in manufacturing, and the Company’s intentions regarding vaccine dose production. In some cases, forward-looking statements can be identified by terminology such as “will,” “may,” “should,” “could”, “expects,” “intends,” “plans,” “aims,” “anticipates,” “believes,” “estimates,” “predicts,” “potential,” “continue,” or the negative of these terms or other comparable terminology, although not all forward-looking statements contain these words. The forward-looking statements in this press release are neither promises nor guarantees, and you should not place undue reliance on these forward-looking statements because they involve known and unknown risks, uncertainties, and other factors, many of which are beyond Moderna’s control and which could cause actual results to differ materially from those expressed or implied by these forward-looking statements. These risks, uncertainties, and other factors include, among others: the fact that there has never been a commercial product utilizing mRNA technology approved for use; the fact that the rapid response technology in use by Moderna is still being developed and implemented; the fact that the safety and efficacy of mRNA-1273 has not yet been established; potential adverse impacts due to the global COVID-19 pandemic such as delays in regulatory review, manufacturing and supply chain interruptions, adverse effects on healthcare systems and disruption of the global economy; and those other risks and uncertainties described under the heading “Risk Factors” in Moderna’s most recent Quarterly Report on Form 10-Q filed with the U.S. Securities and Exchange Commission (SEC) and in subsequent filings made by Moderna with the SEC, which are available on the SEC’s website at www.sec.gov. Except as required by law, Moderna disclaims any intention or responsibility for updating or revising any forward-looking statements contained in this press release in the event of new information, future developments or otherwise. These forward-looking statements are based on Moderna’s current expectations and speak only as of the date hereof.

本新闻稿载有经修订的1995年《私人证券诉讼改革法》含义范围内的前瞻性声明，包括关于该公司开发新型冠状病毒潜在疫苗、第一阶段的参数和时间以及计划中的 mRNA-1273第二和第三阶段研究、该公司对制造业的投资以及该公司关于疫苗剂量生产的意图。 在某些情况下，前瞻性陈述可以通过诸如“ will”、“ may”、“ should”、“ could”、“ expects”、“ plants”、“ aims”、“ expected”、“ believes”、“ estimates”、“ predicts”、“ potential”、“ continue”或这些术语的否定或其他类似术语等术语来确定，尽管并非所有前瞻性陈述都包含这些词语。 这份新闻稿中的前瞻性声明既不是承诺也不是保证，你不应过分依赖这些前瞻性声明，因为它们涉及已知和未知的风险、不确定性和其他因素，其中许多是 Moderna 无法控制的，可能导致实际结果与这些前瞻性声明所表达或暗示的结果有重大差异。 这些风险、不确定性和其他因素包括: 从来没有一种商业产品使用获准使用的信使核糖核酸技术; Moderna 使用的快速反应技术仍在开发和实施; 全球新型冠状病毒肺炎大流行可能造成的不利影响，例如监管审查延误、制造和供应链中断、对医疗系统的不利影响和全球经济中断，以及 Moderna 最近提交美国的表格10-Q 季度报告中”风险因素”标题下所描述的其他风险和不确定性。 美国证券交易委员会(SEC)以及 Moderna 随后向 SEC 提交的备案文件(可在 SEC 网站 www.SEC. gov 查阅)中查阅。 除法律规定外，现代版不打算或不负责在出现新的信息、未来发展或其他情况时更新或修订本新闻稿所载的任何前瞻性声明。 这些具有前瞻性的声明是基于 Moderna 当前的期望，并且仅在此日期发表。

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