F2G Ltd.

【噬纪家园】 × 知噬分子 2026年3月 16 第 151 期 一周要闻抢先看 【行业进展】噬菌体疗法公司BiomX启动高层重组；法国启动国家噬菌体治疗研究平台；世卫组织发布新抗生素研发目标框架；全球抗生素研发管线持续缩减；印度启动国家计划强化生物医药研发；噬菌体衍生抗菌药SAL200公布新研究数据 【科研进展】细菌Schlafen蛋白通过tRNA切割介导抗噬菌体防御；VI型CRISPR-Cas13条件免疫调控噬菌体命运；CRISPR毒素双保险提升工程菌生物封闭；噬菌体调控细菌代谢驱动克罗恩病炎症；携带转座元件的质粒驱动染色体基因失活加速耐药进化 01 行业进展 噬菌体疗法公司BiomX启动高层重组 开发噬菌体疗法的临床阶段生物技术公司 BiomX近日宣布进行管理层调整，任命 Michael Oster 为首席执行官(CEO)，同时任命 David Rokach 为首席财务官(CFO)。公司表示，此次人事变动旨在推动下一阶段战略执行和资本市场发展。BiomX专注于开发针对特定细菌感染的 噬菌体疗法，通过利用能够感染并杀灭细菌的病毒来治疗慢性感染和耐药菌相关疾病。新任CEO Michael Oster拥有企业战略和并购经验，而David Rokach拥有超过20年的金融和投资管理经验，将负责公司的财务战略和资本市场事务。公司希望通过新的管理团队，加速其噬菌体治疗管线的发展。 原文链接 https://www.biotimes.co.kr/news/articleView.html?idxno=30187 法国启动国家噬菌体治疗研究平台 法国国家研究署(ANR，Agence Nationale de la Recherche)在“France 2030抗生素耐药研究计划”中提出，将建设法国公共噬菌体治疗研究平台，以加速应对抗生素耐药问题。该计划属于国家级抗微生物耐药（AMR）研究框架，重点支持抗生素创新、耐药监测以及替代疗法研发。文件指出，噬菌体疗法利用专门感染细菌的病毒来杀灭病原菌，被认为是对抗耐药感染的重要补充技术。该平台将整合研究机构、医院和产业资源，推动临床研究、监管规范和生产能力建设，从而加速噬菌体治疗在法国乃至欧洲的应用 原文链接 https://anr.fr/fileadmin/aap/2025/france2030-aap-ppr-antibioresistance-2025-Webinaire-09032026.pdf 世卫组织发布新抗生素研发目标框架 世界卫生组织(WHO)近日发布三项新的抗菌药物“目标产品概况”（Target Product Profile，TPP），为新型抗生素研发提供明确方向。该框架重点针对三类高风险感染：多重耐药革兰阴性菌导致的严重感染、免疫抑制或重症患者中的耐药革兰阳性菌感染，以及细菌性脑膜炎。TPP文件详细提出未来抗生素应具备的关键特征，包括疗效、安全性、药代动力学、可及性及价格可负担性等指标。WHO表示，这些指南旨在帮助研究机构和制药企业优先开发应对全球抗菌药物耐药威胁的创新抗生素。 原文链接 https://www.who.int/news/item/11-03-2026-who-releases-new-target-product-profiles-for-urgently-needed-antibiotics 噬菌体衍生抗菌药SAL200 公布新研究数据 韩国生物医药公司 iNtRON Biotechnology近日在瑞士举行的 AMR Conference 2026 上公布其抗感染候选药物 SAL200(Tonabacase)的最新研究数据。SAL200是一种来源于噬菌体的重组抗菌蛋白，属于内溶素(Endolysin)类药物，通过直接裂解细菌细胞壁实现快速杀菌，与传统抗生素抑制细菌代谢的机制不同。研究显示，该药物对多重耐药菌如耐甲氧西林金黄色葡萄球菌(MRSA)和耐万古霉素菌株(VRSA)具有显著杀菌活性。在兔感染性心内膜炎模型中，SAL200可将心脏瓣膜以及肾脏、脾脏等器官中的细菌数量降低至检测下限以下，表现出接近“完全灭菌”的效果。SAL200目前已完成1期和2a期临床研究，正继续推进用于感染性心内膜炎和菌血症的治疗开发。 原文链接 https://intodeworld.com/board/board.php?bbsid=notice&idx=116 全球抗生素研发管线持续缩减 日前，Access to Medicine Foundation发布的《2026抗微生物耐药基准报告》（AMR Benchmark）显示，全球大型制药企业的抗菌药物研发管线在过去五年下降约35%，从92个项目减少至60个。尽管整体研发投入下降，但报告仍发现7个具有创新潜力的后期抗生素项目，来自GSK、Otsuka、Shionogi、BioVersys、F2G、Innoviva和Venatorx等公司。这些药物主要针对多重耐药细菌感染，被认为可能改变未来抗感染治疗格局。报告指出，持续推进抗生素研发并改善药物可及性，是应对全球耐药菌威胁的关键。 原文链接 https://wellcome.org/insights/articles/2026-amr-benchmark-pockets-progress-some-companies-show-tide-can-be-turned-there 印度启动国家计划强化生物医药研发 印度政府近日宣布推进“BioPharma Shakti”计划，以加强本国生物医药研发与生产能力。该计划由印度生物技术部推动，重点支持疫苗、生物制药及高价值药物开发，同时强化产业基础设施和创新能力。政府表示，该计划将促进本土企业和研究机构合作，加速新药研发和产业化，提升印度在全球生物医药供应链中的地位。虽然计划涵盖多个生物医药领域，但其中的抗感染药物与抗菌药物研发被认为是重要组成部分，有望增强应对抗菌药物耐药问题的能力。 原文链接 https://www.pib.gov.in/PressReleseDetailm.aspx?PRID=2239829®=3&lang=2 02 科研进展 No.1  Nat Microbiol Artem Nemudryi  团队 细菌Schlafen蛋白通过tRNA切割介导抗噬菌体防御 近日，来自佛罗里达大学的Artem Nemudryi团队系统揭示了细菌Schlafen蛋白在抗噬菌体免疫中的关键作用。Schlafen蛋白最早在哺乳动物中被发现，是一类可通过切割转运RNA(transfer RNA,tRNA)抑制蛋白质翻译、限制病毒复制的抗病毒因子，但其在原核生物中的功能长期不清。研究人员通过基因组分析鉴定出5930个原核Schlafen同源蛋白，其中约69.6%位于细菌防御基因簇附近，提示其可能参与抗噬菌体免疫。功能实验显示，部分pSlfn系统能够显著抑制噬菌体感染，该系统并不会完全阻断噬菌体感染，而是通过降低噬菌体复制效率来限制病毒扩增。机制上，RorSlfn5通过免疫球蛋白样结构域(Ig-like domain)识别噬菌体尾部装配伴侣蛋白(tail assembly chaperone,T5.142)，激活其核糖核酸酶活性，随后特异切割细菌和噬菌体tRNA的反密码子臂(anticodon arm)，从而抑制翻译并限制病毒复制。该研究首次证明Schlafen蛋白是一类广泛存在的细菌抗噬菌体效应器，并揭示了tRNA靶向抗病毒机制在细菌与人类先天免疫中的深度进化保守性，为理解跨生命域的抗病毒策略提供了重要线索。 doi: 10.1038/s41564-026-02277-8 No.2  Nat Microbiol Alexander J. Meeske 团队 VI型CRISPR-Cas13条件免疫调控噬菌体命运 近日，来自华盛顿大学的Alexander J. Meeske团队揭示了VI型CRISPR系统(type VI-A CRISPR)中Cas13核酸酶调控温和噬菌体生命周期的关键机制。传统观点认为CRISPR免疫会阻止噬菌体整合为前噬菌体，但研究人员在李斯特菌Listeria seeligeri中发现，Cas13通过“条件激活”(conditional activation)机制在不同感染阶段产生差异化免疫反应。实验表明，当Cas13识别到裂解阶段高表达的噬菌体RNA时，会触发非特异性RNA降解并抑制病毒复制，从而显著减少噬菌体斑块形成并阻断裂解感染；而在溶原形成阶段，由于靶RNA表达水平低于激活阈值，Cas13保持不活化状态，使噬菌体能够顺利整合进入宿主染色体形成前噬菌体。进一步实验显示，在DNA损伤诱导前噬菌体进入裂解周期时，Cas13被短暂激活，显著降低释放的噬菌体颗粒数量，同时促进前噬菌体重新整合回宿主attB位点，从而避免细胞裂解并维持溶原状态。此外，在含多个前噬菌体的polylysogeny体系中，Cas13仅特异抑制被crRNA靶向的噬菌体，而不会影响其他前噬菌体诱导。该研究首次揭示Cas13能够通过RNA层面的条件性免疫精细调控噬菌体生命周期，使细菌在限制裂解感染的同时保留潜在有益的前噬菌体，为理解CRISPR免疫系统与病毒长期共存的进化策略提供了重要机制。 doi: 10.1038/s41564-026-02288-5 No.3  Nucleic Acids Res 李明/刘宏伟/赵会伟 团队 CRISPR与毒素系统构建高稳定工程菌自杀开关 近日，来自中国科学院微生物研究所的Zhao H团队开发出一种用于工程菌安全控制的新型生物封闭策略ATTACH(Associate toxin–antitoxin with CRISPR-Cas to harness engineered microbes)。工程菌在医疗、肠道诊断及工业发酵中具有广泛应用，但其意外逃逸可能带来潜在生物安全风险。为解决这一问题，研究人员将CRISPR自杀程序与毒素-抗毒素系统(toxin–antitoxin,TA)结合，构建出一种“双保险”杀菌开关。该系统利用CRISPR调控毒素模块(CRISPR-regulated toxin–antitoxin,CreTA)使细菌依赖CRISPR系统存活，同时通过I-F型CRISPR-Cas系统中的Cas3核酸酶(Cas3 nuclease)和靶向必需基因groL的引导RNA触发染色体降解，从而快速杀死细胞。实验结果显示，ATTACH系统在诱导条件下可将细菌存活率降低至10^-8.6，达到NIH推荐的生物安全阈值(<10^-8)，并将逃逸突变率降至约10^-6，相比传统CRISPR自杀系统提高约1000倍安全性。进一步优化后，研究团队构建了单质粒、无需抗生素维持的ATTACH装置，并证实其在小鼠肠道环境中同样能够稳定发挥作用，同时对细菌生长和番茄红素(lycopene)生产几乎无影响。该研究为工程菌的安全应用提供了一种高稳定、可扩展的生物封闭技术。 doi: 10.1093/nar/gkag213 No.4   Cell Host Microbe 左涛 团队 噬菌体调控细菌代谢驱动克罗恩病炎症 近日，来自中山大学的左涛团队系统解析了肠道病毒组在克罗恩病(Crohn’s disease, CD)炎症差异中的关键作用。研究人员对208名受试者(103例CD患者、105名健康对照)进行肠黏膜病毒组、细菌组及代谢组联合分析，首次提出人类肠道存在两种病毒组类型(virome enterotype)：E1和E2。结果显示，CD患者中82%属于E2型，而健康人群中E1比例更高，提示病毒组结构可能影响肠道炎症易感性。进一步的病毒组移植实验表明，来自E2型人群的病毒组可在小鼠中诱导更严重的肠道炎症，表现为更明显的体重下降、结肠缩短及更高的炎症评分。机制研究发现，E2型中富集的噬菌体øBTZT001P可溶原感染溶纤维拟杆菌(Bacteroides thetaiotaomicron)，显著提升鞘氨醇(sphingosine)产生，并进一步抑制共生菌Blautia obeum，最终加重肠道炎症。该研究揭示了一条“噬菌体—细菌—代谢物—宿主”的跨界调控轴(phage-bacteria-sphingosine-intestine axis)，表明肠道噬菌体不仅塑造菌群结构，还可通过调控细菌代谢驱动炎症反应，为基于噬菌体的肠道微生态干预提供了新的理论基础。 doi: 10.1016/j.chom.2026.01.016 No.5  Nat Microbiol Alvaro San Millan 团队 携带转座元件的质粒驱动染色体基因失活加速耐药进化 近日，来自西班牙国家生物技术中心(CSIC)的Alvaro San Millan团队揭示了质粒促进抗生素耐药进化的全新机制。传统观点认为质粒主要通过传播耐药基因促进抗菌耐药。该研究发现，携带转座元件的质粒还能通过破坏细菌染色体基因，加速新的耐药突变产生。研究人员以临床常见耐药质粒pOXA-48为模型，在肺炎克雷伯菌中开展实验。结果显示，携带pOXA-48的菌株获得黏菌素(colistin)耐药的突变率显著升高，其中37.2%的耐药突变由质粒编码的IS1转座元件(insertion sequence)插入基因导致，而无质粒菌株仅为4.4%。这些IS1插入事件主要破坏调控基因mgrB，从而改变脂多糖结构并产生耐药表型。进一步实验表明，pOXA-48还能显著促进环丙沙星、氯霉素和卡那霉素等多种抗生素耐药的产生。对超过42000个细菌基因组的分析显示，质粒携带的IS元件是染色体基因失活的重要来源，并与耐药表型显著相关。此外，在模拟肠道细菌群落的实验中，pOXA-48可通过接合(conjugation)在不同细菌之间传播，并进一步促进IS介导的耐药突变产生。该研究表明，质粒不仅是耐药基因传播载体，还可通过转座元件驱动耐药突变的产生，为理解细菌耐药进化提供了新的重要机制。 doi: 10.1038/s41564-026-02290-x 免责声明： 创噬纪和噬纪家园不对发布到推送中的新闻稿的准确性负责。 噬纪家园 是本公众号开设的新专栏，该栏目每周推送最新的科研进展、行业新闻和会议动态，也欢迎各位观众联系投稿。 文字及新闻整理 |  C 编辑 | C 请谨慎点击左下角阅读原文，那可能是一条广告 往期回顾 【噬纪家园】重磅！柳叶刀子刊：CRISPR噬菌体首次人体试验完成，安全性获证实；两会上的噬菌体声音；鲍曼不动杆菌促胃癌转移机制 【噬纪家园】Nature：新型膜结合防御系统切断注入DNA；第四类噬菌体尾结构被发现；不同噬菌体趋同靶向细胞壁核心蛋白 【噬纪家园】Nature:核苷酸信号实现抗噬菌体免疫的精准“开关”；可编程的噬菌体感染谱扩展策略；噬菌体-抗生素联用使用顺序决定进化路径 【噬纪家园】Nature: 几何结构识别触发RAZR抗噬菌体免疫；前噬菌体编码单蛋白构成最精简抗噬菌体防线；生态分区驱动噬菌体抗生素互补清除 ✦ PHAGE & News 更多精彩资讯 请关注我们

F2G plans to resubmit its antifungal to the FDA after collecting Phase 3 data this coming June, CEO Francesco Maria Lavino told Endpoints News . The biotech’s oral candidate, called olorofim, was spurned by the FDA in 2023 for use in invasive fungal infections. At the time of a $100 million Series H in September 2024, Lavino said the biotech aimed to resubmit after collecting more Phase 2b data on the drug. Now, F2G will wait about six to eight months longer than initially planned to resubmit for approval, so it can include the Phase 3 data, the executive said. “The FDA encouraged us to look for a better historical control,” Lavino told Endpoints on Friday. “We tried, but the reality is that in the meantime, the Phase 3 started enrolling well, so we decided to really focus on a Phase 3 approach, especially because this is far more de-risked and because of the 12 years of regulatory exclusivity.” The Phase 2b open-label data were published in The Lancet Infectious Diseases in June 2025. The company last year completed enrollment in the Phase 3 , which is comparing olorofim to AmBisome in patients with invasive fungal disease caused by invasive aspergillosis. “We didn’t want to run the risk to submit another NDA and then get the FDA saying, ‘Well, now you have completed your Phase 3, why don’t you send me the Phase 3?'” Lavino said. F2G aims to resubmit by December and get approval in the US around June 2027, versus an initial target of October or November 2026 had it resubmitted based on the Phase 2b trial, Lavino said. The biotech will then plan to launch the drug itself in July 2027. If F2G is successful, it would mark a major milestone. The foundation for the Manchester, UK-based biotech was laid in 1998. The biotech currently has about 50 employees across Manchester, Vienna and Princeton, NJ, Lavino said. Shionogi has the European and Asia-Pacific rights, and F2G will help support its Japanese pharma partner in submitting to the European Medicines Agency by the end of this year, Lavino said. F2G will also look to secure partners in Latin America, Canada, Africa, the Middle East and elsewhere. Lavino said F2G has the capital to get olorofim onto the market in the US and expand into coccidioidomycosis, commonly referred to as valley fever. In the second half of this year, the biotech will start a Phase 2 trial in valley fever. That trial will validate the endpoint, Lavino said, and a Phase 3 would likely then be conducted to get approval. In September, the FDA issued draft guidance on developing drugs for the condition. The company will likely look to raise more money toward the end of this year to further bolster the commercial launch and broaden F2G’s portfolio with additional assets it could in-license, Lavino said. The biotech added $8 million to its Series H last year with the support of SymBiosis. Its other backers include AMR Action Fund, ICG, Novo Holdings, Advent Life Sciences, Sofinnova Partners, Forbion and others. The company drew investor interest at last week’s JP Morgan Healthcare Conference, Lavino said, with “a number of very interesting meetings.” F2G will one day be a public company, he said, adding that the biotech was ready to IPO as far back as 2022, with a banking syndicate in place and F-1 paperwork submitted to the SEC. Going forward, “the best time for taking F2G public is probably after launch, after a few quarters of sales,” Lavino said. “But if the market opens, and there is an opportunity, we will be ready to take advantage of that.” F2G is positioning olorofim as a rare disease play rather than a broad or more general anti-infective. “We are really focusing on infection that had limited or, in many cases, no option,” Lavino told Endpoints in 2024. “That’s a very different value proposition than a more general anti-infective or antibiotic, where you are dealing with a lot of generics.”

A new collaboration between Shionogi and BioVersys focuses on ansamycin candidates, a class of antibiotics that are produced by a group of bacteria called Actinomycetes and disrupt RNA manufacturing within targeted bacterial cells.\n Storied Japanese pharma Shionogi is upping its arsenal in the fight against antibiotic resistance. The company is paying 5 million Swiss francs ($6.3 million) upfront for a preclinical antibiotic program from BioVersys, which the two companies will work together to turn into clinical candidates.BioVersys can earn as much as 479 million Swiss francs (about $604 million) in regulatory and sales milestones, as well as tiered royalties, should Shionogi decide to exercise its option on clinic-ready antibiotics, according to a July 2 release.The program that caught Shionogi’s eye is BV500, BioVersys’ effort to develop new treatments for nontuberculous mycobacterial (NTM) infections. Mycobacteria are found all over the world and can cause lung infections, mainly in patients who already have a lung condition like chronic obstructive pulmonary disease.The new collaboration focuses on ansamycin candidates, a class of antibiotics that are produced by a group of bacteria called Actinomycetes and disrupt RNA manufacturing within targeted bacterial cells.“This collaboration reduces research and development risk for BioVersys while preserving financial discipline,” BioVersys co-founder and CEO Marc Gitzinger, Ph.D., said in the release. “It also expands the reach of our pipeline and ensures the expedited development of our drug candidates.”BioVersys’ research teams in France and Switzerland have developed multiple ansamycin compounds that kill NTMs, the company said in the release. These assets don’t lead to cross-resistance with other kinds of antibiotics, BioVersys noted, which is when a microbe evolves a work-around for one kind of antibiotic that also works against other antibiotics. The most common NTM lung infections are caused by Mycobacterium avium complex and Mycobacterium abscessus subspecies, which BioVersys said affect about 250,000 people every year. Treating NTM infections can take years and multiple different antibiotics, according to the American Lung Association.“This collaboration reflects our commitment to advancing innovative treatments for infectious diseases with significant unmet medical needs,” John Keller, Ph.D., senior vice president of Shionogi’s R&D supervisory unit, said in the release. “Shionogi will be bringing our scientific knowledge and operational capabilities fully to bear to maximize the potential of BioVersys’ BV500 program.”The $6.3 million Shionogi is pledging upfront for the BV500 program pales in comparison to the $100 million bet the Japanese giant placed on F2G’s novel antifungal olorofim in 2022, a gamble that has yet to pay off. While Shionogi took charge of European and Asian development of the asset, U.K.-based F2G has had little luck in North America, with the FDA rejecting olorofim in 2023.