EDP-1908

关注并星标CPHI制药在线11月30日，美国FDA批准辉凌制药的RBX2660上市，用于降低18岁以上成年人艰难梭菌感染（CDI）后的复发，商品名为Rebyota，这也是FDA批准的首款粪便微生物疗法。攻克抗生素耐药，微生物疗法迎来里程碑式进展艰难梭菌(C. difficile) 是一种可导致CDI的细菌，CDI是一种潜在的危及生命的疾病，可导致腹泻和严重的结肠炎症。在美国，CDI导致每年15000–30000人死亡相关。艰难梭菌感染经常成为复发恶性循环的开始，给患者和医疗系统造成沉重负担。据估计，高达35%的CDI病例在初次诊断后会复发，复发者发生进一步感染的风险显著升高。首次复发后，高达65%的患者可能会再次复发。艰难梭菌反复感染的一个核心原因便是，肠道微生物菌群遭到破坏。众所周知，肠道含有数百万微生物菌群。某些情况下，如服用抗生素治疗感染，可能会改变肠道内微生物的平衡，使艰难梭菌繁殖并释放毒素，进而导致腹泻、腹痛、发烧，甚至器官衰竭和死亡。从CDI恢复后，患者可能会发生多次再感染，这种情况即为复发性CDI。对于CDI复发的患者，目前临床上的治疗选择极为有限。此时，Rebyota便应运而生。Rebyota由符合要求的捐赠的人类粪便制成。其通过单剂量直肠给药的方式，促进患者肠道菌群的恢复，从而防止艰难梭菌感染的进一步发生。11月7日，辉凌制药公布了Rebyota的III期临床试验数据。该研究纳入了267例受试者，接受了盲法治疗（n=180，Rebyota；n=67，安慰剂），主要终点是治疗成功，定义为在完成研究治疗后8周内没有出现CDI腹泻。结果显示，Rebyota在8周时治疗成功率为70.6%，而安慰剂组为 57.5%。Rebyota在标准抗生素治疗后，降低复发CDI方面优于安慰剂的概率为99.1%。超过90%治疗成功的研究参与者在6个月内没有 CDI 复发。Rebyota不良反应多为轻到中度的消化道反应，且无治疗相关的严重不良事件发生。不过，FDA也在官网披露，辉凌制药虽然对捐赠者和捐赠的粪便进行过可传播病原体的检测，但由于Rebyota由人类粪便制成，可能存在传播疾病的风险。此外，Rebyota可能含有食物过敏原；该产品因食物过敏原而引起不良反应的可能性尚不清楚。尽管如此，Rebyota的获批仍给微生物治疗领域注入了一针强心剂。因为，全球数十家公司都未曾在这一领域做出有治疗意义的临床结果。因此，FDA生物制品评估与研究中心主任Peter Marks博士对此表示：“Rebyota的获批对复发性CDI患者来说是一大进步。复发性CDI影响个人的生活质量，也可能危及生命。今天的获批是一个重要的里程碑，作为FDA批准的第一个粪便微生物产品，它为预防复发性CDI提供了新选择。”国内外有哪些玩家在布局？近年来，越来越多的科学研究已证明肠道微生物的诸多作用。美国政府在奥巴马时代就开始资助使用肠道微生物来治疗人类疾病。在政策的推动下，除了Seres、Evelo、Finch等一大批微生物制药明星企业已经在舞台上崭露头角，辉瑞、罗氏、辉凌等跨国制药巨头也纷纷布局微生态制药赛道。其中微生物明星公司Seres Therapeutics曾于10月26日宣布，FDA已接受其在研口服微生物疗法SER-109的生物制品许可申请（BLA），用于预防复发性艰难梭菌感染rCDI，预计于2023年4月26日前完成审查。SER-109由多种厚壁菌门菌种的纯化细菌孢子组成。在两项III期研究中（ECOSPOR III和ECOSPOR IV），试验结果显示，ECOSPOR III研究在8周时，SER-109减少CDI复发的效力优于安慰剂，治疗8周后的持续临床反应率约为88%，而安慰剂组为60%。在ECOSPOR IV试验中，第8周时，有91.3%接受SER-109治疗的受试者展现出持续性的临床疗效，与ECOSPOR III试验中观察到的88%的治疗效率一致。Evelo是一家通过识别针对小肠免疫细胞的特定单克隆菌株，引导全身免疫反应，从而治疗癌症、炎症性等疾病的公司。癌症免疫疗法和微生物组的结合让这家公司成立之初便备受关注。另外，Evelo利用细胞在小肠中的重要作用，开发了一个综合平台，识别微生物的单个菌株，并将其开发为针对小肠细胞的药物。而这一部分小肠细胞往往具有明确的药理特性。基于这个平台，Evelo开发出一系列的候选产品。比如治疗癌症疾病的主要候选产品EDP1503以及针对炎症性疾病的主要候选产品EDP1815，以及Evelo在肿瘤学中领先的微生物细胞外囊泡临床候选产品EDP1908等。Finch是一家临床阶段生物医药公司，专注于使用粪便移植的微生物组研发新型疗法。公司产品管线由专有的Human-First平台驱动，使用反向翻译来识别营养不良的疾病，并设计针对这些疾病的微生物组疗法。利用机器学习和分子表征技术，Finch能够确定微生物组破坏导致疾病的条件，并揭示与成功临床结果相关的关键动态。基于公司专有平台，Finch研发出了针对炎症性肠病 (IBD)的微生物疗法FIN-524和FIN-525（曾获武田合作共同开发，后被武田退回），以及一种口服的微生物组胶囊CP101，该产品旨在提供完整的功能性微生物组，以持久地修复community-level营养不良。把视野拉回国内，目前未知君生物、慕恩生物、知易生物等皆有布局。未知君生物深圳未知君生物科技有限公司（简称未知君生物）成立于2017年，是国内行业专注于肠道微生物治疗的AI制药公司，拥有先进完备的微生物药物研发平台。未知君把肠道微生态视作系统性的对象，通过数据建模、机器学习的方法去找出哪些菌与疾病治疗间存在因果关系，找到以后再定向地把这些菌分离出来，最后成药。其研发的代号为XBI-302的粪菌移植药物，获得了FDA的新药临床试验（IND）批准，可正式进入治疗急性移植物抗宿主病的临床试验阶段，这是中国微生态制药企业首次获FDA批准的IND申请，标志着中国制药企业正式开拓出一条国内微生态药物向FDA递交审批的完整路径，实现了粪菌移植从治疗形式向药物形态的转化。慕恩生物慕恩（广州）生物科技有限公司（简称慕恩生物），是国内专注于将微生物资源商业化的创新型生物技术公司，已搭建起了从发现、筛选、改造微生物到应用微生物的完整微生物组产业化技术体系。公司建立了生物多样性与全球规模数一数二的肠道微生物、植物微生物菌种库和基因库，发现、保存和鉴定了超18万株具有自主知识产权的微生物菌株。其研发的活菌生物药MNC-168可通过提升抗肿瘤功能与肿瘤免疫疗法的响应力，能够多靶点激活机体中免疫激活型抗原呈递细胞-树突细胞、M1巨噬细胞、IFN-γ+阳性辅助型CD4+ T淋巴细胞与IFN-γ+阳性毒杀型CD8+T淋巴细胞等免疫细胞，同时能显著上调IL-1β、TNF-α、IFN-γ、CXCL9与CXCL10与等抗肿瘤活性免疫细胞因子与趋化因子。通过长期作用于肠道粘膜微环境，重新激活免疫系统的抗肿瘤能力，从而达到治疗多种恶性实体瘤的目的。目前，MNC-168单药在晚期恶性实体瘤受试者中的安全性、耐受性、药代动力学特征及初步有效性I期临床研究，于11月8日完成中国受试者的首次用药。知易生物广州知易生物科技有限公司（简称知易生物），是中国活体生物药（LBPs）与二代益生菌研发公司。拥有微生物与致病菌谱、新功能菌株分离与靶标确定、新活菌药物、活性成分药物开发的完整技术体系，以及从发现、临床前到NDA的产业化平台。2019年11月，知易生物的原创新药SK08活菌散获批进入临床，目前处于针对腹泻型肠易激综合征（IBS-D）的II期临床试验阶段。另外用于化疗相关性腹泻（CID）的SK10也已进入IND阶段。同时，知易生物管线上的多个源自微生物组的新型药物也正在快速有序地推进中。 随着人体微生物组研究的深入，人们越来越注意到，多数疾病的发生和发展跟人体微生物关系密切。如今，人体微生态已被证实与多种慢性疾病密切相关，如肥胖症、炎症性肠病、糖尿病、代谢综合征、动脉粥样硬化、非酒精性脂肪性肝病等。于是在近几年，微生态菌群在全球范围内获得了前所未有的关注。 目前在全球范围内，有超过 50多家企业，纷纷布局肠道微生物相关的活菌药物，其中90%左右在美国，相对而言国内的活菌药物处于滞后状态。市场分析认为，到2026年全球微生态药物市场空间有望达到100亿美元。无论是在国内还是国外，这一赛道仍处于刚起步阶段，是名副其实的朝阳产业。当前胃肠道疾患和胃肠道感染依然是微生物治疗的主要潜在临床适应症。如何在其他领域体现肠道微生物的疗效依然有着巨大的想象空间。参考来源：1、https://www.businesswire.com/news/home/20221026005415/en/Seres-Therapeutics-Announces-FDA-Acceptance-of-Biologics-License-Application-for-Investigational-Microbiome-Therapeutic-SER-109-for-Recurrent-C.-Difficile-Infection-for-Priority-Review；2、Dizman, N., Meza, L., Bergerot, P. et al. Nivolumab plus ipilimumab with or without live bacterial supplementation in metastatic renal cell carcinoma: a randomized phase 1 trial. Nat Med (2022). https://doi.org/10.1038/s41591-022-01694-6；3、Sepich-Poore GD. , Zitvogel L., Straussman R., Hasty J., Wargo JA., Knight R. The microbiome and human cancer. Science (2021). https://doi.org/10.1126/science.abc4552;4、Lin CS., Jiang X., Li B., Xian Y. et al., Preclinical monotherapeutic and anti-PD-1 synergistic anti-tumor efficacy of MNC-168, a novel human-derived live biotherapeutic product. 2021 ASCO Annual Meeting (e14581). Journal of Clinical Oncology (2021). https://ascopubs.org/doi/abs/10.1200/JCO.2021.39.15_suppl.e14581.【企业推荐】来源：CPHI制药在线声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。投稿邮箱：Kelly.Xiao@imsinoexpo.com▼更多制药资讯，请关注CPHI制药在线▼点击阅读原文，进入智药研习社~

CAMBRIDGE, Mass., June 03, 2021 (GLOBE NEWSWIRE) -- Evelo Biosciences, Inc. (Nasdaq: EVLO), a clinical stage biotechnology company developing a new modality of orally delivered medicines, announced that given accelerating growth to later-stage development and the anticipated hiring and expansion of the Leadership Team, the Evelo Board of Directors has approved an inducement equity plan. On June 1, 2021, Luca Scavo commenced his services as Evelo’s Chief Financial Officer. In connection with the commencement of Mr. Scavo’s employment, the Company issued to Mr. Scavo an option to purchase 300,000 shares of the Company’s common stock with a per share exercise price of $14.24 the closing trading price of the Company’s common stock on the Nasdaq Global Select Market on June 1, 2021, and 4,545 restricted stock units. The stock option and restricted stock units were granted pursuant to the Company’s 2021 Employment Inducement Award Plan and were approved by the Company’s Board of Directors. The stock option vests (subject to Mr. Scavo’s continued service to the Company through the applicable vesting dates) 25% on June 1, 2022, and in 36 substantially equal monthly installments over the three years thereafter and has a ten-year term. The restricted stock units vest in full upon Mr. Scavo’s completion of three years of service on June 1, 2024. The stock option and restricted stock units were granted under Rule 5635(c)(4) of the Nasdaq Listing Rules as an inducement material to Mr. Scavo’s entering into employment with the Company. About Evelo BiosciencesEvelo Biosciences is a clinical stage biotechnology company developing orally delivered medicines that act on the small intestinal axis, SINTAX™, to have systemic therapeutic effects. SINTAX plays a central role in governing the immune, metabolic, and neurological systems. Evelo currently has four product candidates in development: EDP1815, EDP1867, and EDP2939 for the treatment of inflammatory diseases and EDP1908 for the treatment of cancer. Evelo is advancing additional product candidates in other disease areas. For more information, please visit  and engage with Evelo on LinkedIn. Forward Looking StatementsThis press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including statements concerning the development of our product candidates and the promise and potential impact of our product candidates. These forward-looking statements are based on management's current expectations. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, the following: the impact of the COVID-19 pandemic on our operations, including our preclinical studies and clinical trials, and the continuity of our business; we have incurred significant losses, are not currently profitable and may never become profitable; our need for additional funding; our limited operating history; our unproven approach to therapeutic intervention; the lengthy, expensive, and uncertain process of clinical drug development, including potential delays in regulatory approval; our reliance on third parties and collaborators to expand our microbial library, conduct our clinical trials, manufacture our product candidates, and develop and commercialize our product candidates, if approved; our lack of experience in manufacturing, selling, marketing, and distributing our product candidates; failure to compete successfully against other drug companies; protection of our proprietary technology and the confidentiality of our trade secrets; potential lawsuits for, or claims of, infringement of third-party intellectual property or challenges to the ownership of our intellectual property; our patents being found invalid or unenforceable; risks associated with international operations; our ability to retain key personnel and to manage our growth; the potential volatility of our common stock; our management and principal stockholders have the ability to control or significantly influence our business; costs and resources of operating as a public company; unfavorable or no analyst research or reports; and securities class action litigation against us. These and other important factors discussed under the caption "Risk Factors" in our Quarterly Report on Form 10-Q for the three months ended March 31, 2021 and our other reports filed with the SEC could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent management's estimates as of the date of this press release. While we may elect to update such forward-looking statements at some point in the future, except as required by law, we disclaim any obligation to do so, even if subsequent events cause our views to change. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date of this press release. ContactJessica Cotrone, 978-760-5622jcotrone@evelobio.com