ACX-375C

New analyses extend data on beneficial effects of ibezapolstat on the gut microbiome Confirmed ibezapolstat's favorable pharmacokinetics showing low systemic exposure and high colonic concentrations Selected ACX-375 analogues demonstrated in vitro activity against Anthrax (B. anthracis), a Bioterrorism Category A pathogen, including activity against ciprofloxacin resistant Anthrax. Planning is underway for an Anthrax bioterrorism development program Preparation continues to advance ibezapolstat into international Phase 3 clinical trials for treatment of C. difficile Infection (CDI) Preparing to submit requests for regulatory guidance to initiate clinical trials in the European Union, the United Kingdom, Japan and Canada Ibezapolstat has previously received FDA QIDP and Fast-Track Designation from FDA STATEN ISLAND, N.Y., Sept. 26, 2024 /PRNewswire/ -- Acurx Pharmaceuticals, Inc. (NASDAQ: ACXP) ("Acurx" or the "Company"), a late-stage biopharmaceutical company developing a new class of small molecule antibiotics for difficult-to-treat bacterial infections, today announced results from new analyses that extend data on the beneficial effects of ibezapolstat on the gut microbiome. The data show an increased proportion of Actinobacteriota and increased quantity of beneficial Bacillota (Firmicutes) leading to reversal of dysbiosis and contributing to the CDI anti-recurrence effect of ibezapolstat. Additionally, ibezapolstat's favorable pharmacokinetics properties were confirmed showing mean systemic exposure below 1mcg/mL and fecal concentrations well in excess of the minimal inhibitory concentration (MIC) for C. difficile. Microbiological testing of certain ACX-375 DNA pol IIIC analogues in independent qualified laboratories, including the University of Florida, demonstrated in vitro activity with MICs of 0.5-2mcg/mL against B. anthracis (Anthrax), a Bioterrorism Category A pathogen, including activity against ciprofloxacin resistant B. anthracis. The above results were presented at the premier International C. difficile Symposium (ICDS) held in Bled, Slovenia on September 17-19, 2024. Kevin Garey, PharmD, MS, FIDSA, Professor and Chair, University of Houston College of Pharmacy, Principal Investigator for microbiology and microbiome aspects of the ibezapolstat clinical trial program, and Acurx Scientific Advisory Board member delivered a presentation entitled: Ibezapolstat Preserves Key Clostridium leptum Species. Microbiome Results from the Phase 2, Randomized, Double-blind Study of ibezapolstat Compared with Vancomycin for the Treatment of Clostridioides Difficile Infection. According to Dr. Garey: "The microbiome data also show an unexpected finding of a unique microbiome signature in two vancomycin-treated patients in the Ph2b trial who experienced recurrence of CDI. Since these changes were evident and observed early during treatment and then consistently until the end of therapy, they may be predictive of pending CDI recurrence and suggest the need to modify therapy." Robert J. DeLuccia, Executive Chairman of Acurx, stated: "These new data add to and reinforce ibezapolstat's emerging overall distinctive product profile, particularly the favorable microbiome-related unexpected findings." He added: "Furthermore, the initial in vitro activity shown against the Bioterrorism Category A pathogen B. anthracis (Anthrax) with some of our earlier-stage compounds included a ciprofloxacin-resistant strain. Selective microbiome effects will be tested with these new compounds as they proceed through development to treat infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and other critical gram-positive pathogens in parallel with planning for the Anthrax bioterrorism program. The presentation is available on the Acurx Pharmaceuticals website Acurx has previously announced that it had a successful FDA End-of-Phase 2 Meeting and Phase 3 Readiness for ibezapolstat for the Treatment of C. difficile Infection. Agreement with FDA was reached on key elements to move forward with its international Phase 3 clinical trial program. Agreement was also reached with FDA on the complete non-clinical and clinical development plan for filing of a New Drug Application (NDA) for marketing approval. Planning continues to advance ibezapolstat into international Phase 3 clinical trials for treatment of C. difficile Infection (CDI). Acurx is also preparing to submit requests for regulatory guidance to initiate clinical trials in the European Union, the United Kingdom, Japan and Canada. Key elements for the two Phase 3, non-inferiority, pivotal trials were confirmed and included agreement on the protocol design, patient population, primary and secondary endpoints, and size of the registration safety database. Based on FDA recommendations, and in anticipation of an EMA Scientific Advice Meeting, the primary efficacy analysis will be performed using a Modified Intent-To-Treat (mITT) population consistent with EMA requirements. This will result in an estimated 450 subjects in the mITT population, randomized in a 1:1 ratio to either ibezapolstat or standard-of-care vancomycin, enrolled into the initial Phase 3 trial. The trial design not only allows determination of ibezapolstat's ability to achieve Clinical Cure of CDI as measured 2 days after 10 days of oral treatment, but also includes assessment of ibezapolstat's potential effect on reduction of CDI recurrence in the target population. In the event non-inferiority of ibezapolstat to vancomycin is demonstrated, further analysis will be conducted to test for superiority. About the C. difficile Symposium (ICDS) The International C. difficile Symposium (ICDS) is now established as the premier venue for the review of Clostridium difficile research. The 1st meeting was held in Kranjska Gora in 2004, the 2nd in Maribor in 2007, while all earlier meetings were in Bled in 2010, 2012, 2015 and in 2018. ICDS in 2020 was held virtually. The 2024 meeting will provide the ideal opportunity to review progress in epidemiology, diagnostics, clinical trials, basic research and in understanding C. difficile pathogenesis and controlling the devastating disease it causes. About the Ibezapolstat Phase 2 Clinical Trial The completed multicenter, open-label single-arm segment (Phase 2a) study was followed by a double-blind, randomized, active-controlled, non-inferiority, segment (Phase 2b) at 28 US clinical trial sites which together comprise the Phase 2 clinical trial. (see ). This Phase 2 clinical trial was designed to evaluate the clinical efficacy of ibezapolstat in the treatment of CDI including pharmacokinetics and microbiome changes from baseline. from study centers in the United States. In this cohort, 10 patients with diarrhea caused by C. difficile were treated with ibezapolstat 450 mg orally, twice daily for 10 days. All patients were followed for recurrence for 28± 2 days. Per protocol, after 10 patients of the projected 20 Phase 2a patients completed treatment (100% cured infection at End of Treatment). In the now completed Phase 2b trial segment, which was discontinued due to success, 32 patients with CDI were enrolled and randomized in a 1:1 ratio to either ibezapolstat 450 mg every 12 hours or vancomycin 125 mg orally every 6 hours, in each case, for 10 days and followed for 28 ± 2 days following the end of treatment for recurrence of CDI. The two treatments were identical in appearance, dosing times, and number of capsules administered to maintain the blind. The Company previously reported that the overall observed Clinical Cure rate in the combined Phase 2 trials in patients with CDI was 96% (25 out of 26 patients), based on 10 out of 10 patients (100%) in Phase 2a in the Modified Intent to Treat Population, plus 15 out of 16 (94%) patients in Phase 2b in the Per Protocol Population, who experienced Clinical Cure during treatment with ibezapolstat. Ibezapolstat was well-tolerated, with three patients each experiencing one mild adverse event assessed by the blinded investigator to be drug-related. All three events were gastrointestinal in nature and resolved without treatment. There were no drug-related treatment withdrawals or no drug-related serious adverse events, or other safety findings of concern. In the Phase 2b vancomycin control arm, 14 out of 14 patients experienced Clinical Cure. The Company is confident that based on the pooled Phase 2 ibezapolstat Clinical Cure rate of 96% and the historical vancomycin cure rate of approximately 81% (Vancocin® Prescribing Information, January 2021), we will demonstrate non-inferiority of ibezapolstat to vancomycin in Phase 3 trials in accordance with the applicable FDA Guidance for Industry (October 2022). In the Phase 2 clinical trial, the Company also evaluated pharmacokinetics (PK) and microbiome changes and test for anti-recurrence microbiome properties, including the change from baseline in alpha diversity and bacterial abundance, especially overgrowth of healthy gut microbiota Actinobacteria and Firmicute phylum species during and after therapy. Phase 2a data demonstrated complete eradication of colonic C. difficile by day three of treatment with ibezapolstat as well as the observed overgrowth of healthy gut microbiota, Actinobacteria and Firmicute phyla species, during and after therapy. Very importantly, emerging data show an increased concentration of secondary bile acids during and following ibezapolstat therapy which is known to correlate with colonization resistance against C. difficile. A decrease in primary bile acids and the favorable increase in the ratio of secondary-to-primary bile acids suggest that ibezapolstat may reduce the likelihood of CDI recurrence when compared to vancomycin. The company also recently reported positive extended clinical cure (ECC) data for ibezapolstat (IBZ), its lead antibiotic candidate, from the Company's recently completed Phase 2b clinical trial in patients with CDI. This exploratory endpoint showed that 12 patients who agreed to be followed up to three months following Clinical Cure of their infection, 5 of 5 IBZ patients experienced no recurrence of infection. In the vancomycin control arm of the trial, 7 of 7 patients experienced no recurrence of infection. ECC success is defined as a clinical cure at the TOC visit (i.e., at least 48 hours post EOT) and no recurrence of CDI within the 56 ± 2 days post EOT (ECC56) and 84 ± 2 days post EOT (ECC84) in patients who consented to extended observation. In the Phase 2b trial, 100% (5 of 5) of ibezapolstat-treated patients who agreed to observation for up to three months following Clinical Cure of CDI experienced no recurrence of infection. About Ibezapolstat Ibezapolstat is the Company's lead antibiotic candidate planning to advance to international Phase 3 clinical trials to treat patients with C. difficile Infection (CDI). Ibezapolstat is a novel, orally administered antibiotic, being developed as a Gram-Positive Selective Spectrum (GPSS®) antibacterial. It is the first of a new class of DNA polymerase IIIC inhibitors under development by Acurx to treat bacterial infections. Ibezapolstat's unique spectrum of activity, which includes C. difficile but spares other Firmicutes and the important Actinobacteria phyla, appears to contribute to the maintenance of a healthy gut microbiome. In June 2018, ibezapolstat was designated by the U.S. Food and Drug Administration (FDA) as a Qualified Infectious Disease Product (QIDP) for the treatment of patients with CDI and will be eligible to benefit from the incentives for the development of new antibiotics established under the Generating New Antibiotic Incentives Now (GAIN) Act. In January 2019, FDA granted "Fast Track" designation to ibezapolstat for the treatment of patients with CDI. The CDC has designated C. difficile as an urgent threat highlighting the need for new antibiotics to treat CDI. About Clostridioides difficile Infection (CDI) According to the 2017 Update (published February 2018) of the Clinical Practice Guidelines for C. difficile Infection by the Infectious Diseases Society of America (IDSA) and Society or Healthcare Epidemiology of America (SHEA), CDI remains a significant medical problem in hospitals, in long-term care facilities and in the community. C. difficile is one of the most common causes of health care- associated infections in U.S. hospitals (Lessa, et al, 2015, New England Journal of Medicine). Recent estimates suggest C. difficile approaches 500,000 infections annually in the U.S. and is associated with approximately 20,000 deaths annually. (Guh, 2020, New England Journal of Medicine). Based on internal estimates, the recurrence rate for the antibiotics currently used to treat CDI is between 20% and 40% among approximately 150,000 patients treated. We believe the annual incidence of CDI in the U.S. approaches 600,000 infections and a mortality rate of approximately 9.3%. About the Microbiome in C. difficile Infection (CDI) and Bile Acid Metabolism C. difficile can be a normal component of the healthy gut microbiome, but when the microbiome is thrown out of balance, the C. difficile can thrive and cause an infection. After colonization with C. difficile, the organism produces and releases the main virulence factors, the two large clostridial toxins A (TcdA) and B (TcdB). (Kachrimanidou, Microorganisms 2020, 8, 200; doi:10.3390/microorganisms8020200.) TcdA and TcdB are exotoxins that bind to human intestinal epithelial cells and are responsible for inflammation, fluid and mucous secretion, as well as damage to the intestinal mucosa. Bile acids perform many functional roles in the GI tract, with one of the most important being maintenance of a healthy microbiome by inhibiting C. difficile growth. Primary bile acids, which are secreted by the liver into the intestines, promote germination of C. difficile spores and thereby increase the risk of recurrent CDI after successful treatment of an initial episode. On the other hand, secondary bile acids, which are produced by normal gut microbiota through metabolism of primary bile acids, do not induce C. difficile sporulation and therefore protect against recurrent disease. Since ibezapolstat treatment leads to minimal disruption of the gut microbiome, bacterial production of secondary bile acids continues which may contribute to an anti-recurrence effect. Beneficial effects of bile acids include a decrease in primary bile acids and an increase in secondary bile acids in patients with CDI, which was observed in the Company's Ph2a trial results and previously reported (CID, 2022). About Acurx Pharmaceuticals, Inc. Acurx Pharmaceuticals is a late-stage biopharmaceutical company focused on developing a new class of small molecule antibiotics for difficult-to-treat bacterial infections. The Company's approach is to develop antibiotic candidates with a Gram-positive selective spectrum (GPSS®) that blocks the active site of the Gram-positive specific bacterial enzyme DNA polymerase IIIC (pol IIIC), inhibiting DNA replication and leading to Gram-positive bacterial cell death. Its R&D pipeline includes antibiotic product candidates that target Gram-positive bacteria, including Clostridioides difficile, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin resistant Enterococcus (VRE) and drug-resistant Streptococcus pneumoniae (DRSP). To learn more about Acurx Pharmaceuticals and its product pipeline, please visit Forward-Looking Statements Any statements in this press release about our future expectations, plans and prospects, including statements regarding our strategy, future operations, prospects, plans and objectives, and other statements containing the words "believes," "anticipates," "plans," "expects," and similar expressions, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: whether ibezapolstat will benefit from the QIDP designation; whether ibezapolstat will advance through the clinical trial process on a timely basis; whether the results of the clinical trials of ibezapolstat will warrant the submission of applications for marketing approval, and if so, whether ibezapolstat will receive approval from the FDA or equivalent foreign regulatory agencies where approval is sought; whether, if ibezapolstat obtains approval, it will be successfully distributed and marketed; and other risks and uncertainties described in the Company's annual report filed with the Securities and Exchange Commission on Form 10-K for the year ended December 31, 2023, and in the Company's subsequent filings with the Securities and Exchange Commission. Such forward- looking statements speak only as of the date of this press release, and Acurx disclaims any intent or obligation to update these forward-looking statements to reflect events or circumstances after the date of such statements, except as may be required by law. Investor Contact: Acurx Pharmaceuticals, Inc. David P. Luci, President & CEO Tel: 917-533-1469 Email: [email protected] SOURCE Acurx Pharmaceuticals, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

作者｜YY头孢，阿莫西林，阿奇霉素，红霉素，左氧氟沙星……这些名字你一定不陌生，甚至家家必备，他们都有一个共同的名称 -- “抗生素”。正是抗生素的普及与非处方，导致目前抗生素耐药现象愈发严重，然而，大部分人却依旧没有意识到事态的严重性。世卫组织早在2019年就将抗生素耐药性列为全球十大公共卫生威胁之一。每年全世界至少有70万人死于对抗生素产生耐药性的细菌感染。如果我们不能减缓耐药性蔓延或找到新药物，到2050年，这个数字很可能会激增到1000万人。人们对抗生素若不敏感的话，常规的手术和轻伤都可能危及人类生命。为什么会产生抗生素耐药？细菌和真菌等微生物产生耐药性的机制（图1）从大的方面可分为以下几类： 图1. 病菌（细菌与真菌）发展耐药性的机制示意图（CDC）抗生素耐药机制如下：★ 限制抗生素的进入★ 摆脱抗生素或抗真菌：利用细胞壁中的外泌胞泵排除掉那些已经进入细胞的抗生素药物 ★ 改变或破坏抗生素：细菌可以利用酶和其它蛋白来改变或破坏抗生素药物分子。★ 改变抗生素靶标：许多抗生素药物精确瞄准细菌的特定部分（靶标）。但细菌可以改变抗生素的靶点，使药物不再发挥作用。★ 绕过抗生素的作用：细菌会开发出新的细胞生物过程，避免产生抗生素针对的靶点，以此方式躲避抗生素的摧毁作用。值得注意的是，细菌针对抗生素的耐药性甚至可以在不同的细菌之间“传染”（图2），这种“狼狈为奸”的机制直接增加了耐药性问题的严峻性。 图2. 抗生素耐药性基因在不同细菌之间传播的机制。（图片来源：CDC）针对致病微生物的疯狂反扑，人们也一直没有停下对抗耐药性的脚步，有多家生物科技公司专注于解决抗生素耐药性问题，开发出了多种具有不同“抗耐药性”机制的新型抗生素药物。  01  Acurx PharmaceuticalsAcurx的方法是开发候选抗生素，阻断新靶标DNA 聚合酶 IIIC (Pol IIIC)，抑制 DNA 复制，导致革兰氏阳性细菌细胞死亡。Acurx的管道资产包括一项II期临床阶段项目（Ibezapolstat）、一项针对革兰氏阳性细菌的临床前候选药物（ACX-375C），以及一项处于药物发现期的革兰氏阳性菌项目（CCP）。Acurx的这些候选药物针对革兰氏阳性菌，用于口服和肠胃外治疗艰难梭菌、肠球菌（包括万古霉素耐药菌株）、葡萄球菌（包括耐甲氧西林金黄色葡萄球菌的耐药菌株）和链球菌（包括抗生素耐药菌株）。这些候选抗生素产品在早期研究中均已证明能够有效阻断 DNA 聚合酶 IIIC。Acurx管线内最先进的候选药物是 ibezapolstat，治疗艰难梭菌感染患者。它是 Acurx 首款DNA 聚合酶 IIIC 抑制剂。Acurx 已成功完成 ibezapolstat 的 2a 期和 2b 期试验，并于 2023 年 11 月宣布其积极的顶线疗效结果。在2a期和2b期总共26名接受ibezapolstat治疗的患者中，临床治愈率为96%。此外，该药物耐受性良好，没有报告与药物相关的严重不良事件。图3. Ibezapolstat化学结构Ibezapolstat是一款口服小分子药物，是一种双取代鸟嘌呤衍生物（图3），靶向细菌 DNA 聚合酶 IIIC。DNA聚合酶IIIC是临床开发的新靶点，是低鸟嘌呤和胞嘧啶含量的细菌中必需的酶，包括芽孢杆菌、梭状芽胞杆菌、肠球菌、支原体、乳杆菌、李斯特菌、肺炎球菌、葡萄球菌和链球菌。据 Acurx 称，他们目前正在与FDA 计划 推进ibezapolstat的III期临床试验，今年四月会产生最新进展。  02  Antabio Antabio关注危及生命的呼吸道感染， 包括耐碳青霉烯类的医院获得性肺炎和慢性肺部疾病。Antabio的主要管线MEM-ANT3310用于治疗医院获得性感染，例如由耐碳青霉烯类鲍曼不动杆菌和耐碳青霉烯类肠杆菌引起的医院获得性肺炎。碳青霉烯类抗生素是一种重要的抗生素药物，通常用于治疗肺炎、败血症、腹膜炎等感染。耐碳青霉烯类抗生素细菌就是对碳青霉烯类抗生素产生了耐药性的细菌。MEM-ANT3310是一种联合疗法，结合了meropenem（一种著名的碳青霉烯类抗生素）与Antabio开发的丝氨酸-β-内酰胺酶（SBL）抑制剂ANT3310（图4）。Antabio这种联合疗法适用于很多革兰氏阴性病原体，包括 OXA 碳青霉烯耐药鲍曼不动杆菌、KPC 和 OXA 碳青霉烯耐药肠杆菌以及铜绿假单胞菌 (PA)。 去年 5 月，第一批患者在 MEM-ANT3310 的 1 期试验中接受了给药。图4. MEM-ANT3310活性成分化学结构Antabio 最近还在 B 轮融资中筹集了 2500 万欧元（2720 万美元）。所得款项将用于支持 MEM-ANT3310 的临床开发，推动期 2 期临床研究。  03  BiomX BiomX 关注开发天然和工程噬菌体混合物，针对慢性疾病中的有害细菌，例如囊性纤维化、炎症性肠病、特应性皮炎和结直肠癌。噬菌体（Phage），也称为细菌噬菌体（bacteriophage），是一种寄生于细菌体内的病毒。噬菌体是由蛋白质外壳包裹着的一小段DNA或RNA构成，它能够通过尾部的附着蛋白结构与细菌细胞表面的受体结合，然后将其遗传物质注入细菌内部。在细菌内部，噬菌体的遗传物质会利用细菌的生物机制开始复制，生产新的噬菌体颗粒。这些新的噬菌体颗粒最终会导致细菌细胞壁破裂，从而导致细菌的溶解和死亡的溶解释放，这一过程称为lysis。噬菌体在自然界中广泛存在，是细菌的天然天敌。它们在调控细菌种群数量、影响细菌的生态系统以及在生物学和医学研究中具有重要作用。在医学领域，噬菌体是一种治疗细菌性感染的方法，被称为噬菌疗法。今年 3 月 6 日，BiomX 宣布已与抗生素抗性生物技术公司 Adaptive Phage Therapeutics (APT) 达成最终合并协议，创建一家专注于将两种工程噬菌体疗法推向临床的公司。全股票交易完成后，BiomX 现有股东将拥有约 55% 的新公司股份，而 APT 股东将拥有其余 45% 的股份。BiomX的主要候选产品包括 BX004，用于治疗囊性纤维化患者中铜绿假单胞菌引起的慢性肺部感染（预计将于 2025 年第三季度公布），以及 APT 的临床II期资产BX211，用于治疗糖尿病足骨髓炎患者的金黄色葡萄球菌感染，预计将于 2025 年第一季度上市。慢性铜绿假单胞菌感染导致上皮表面损伤和气道堵塞，逐渐损害肺功能。与未感染铜绿假单胞菌的患者相比，长期感染铜绿假单胞菌的患者显示出更严重的肺功能下降、更多的肺部症状加重、更多的住院治疗和更高的死亡率。铜绿假单胞菌感染通常始于儿童期，经过长期和重复的广谱抗生素疗程后，抗生素耐药性增强，并导致多重耐药 (MDR) 菌株的出现。在临床前体外研究中，BX004 对铜绿假单胞菌抗生素耐药菌株具有活性，并具有穿透生物膜的能力，而细菌细胞膜阻碍抗生素药物进入是产生耐药性的关键因素之一（图1）。  04  Clarametyx Clarametyx Biosciences的主要技术平台针对病原体生物膜来对抗持续感染，实现更有效的免疫反应和抗生素干预。他们目前正在开发一系列免疫疗法和疫苗，针对与生物膜相关的细菌感染，近期重点关注具有挑战性的呼吸道感染。Clarametyx 的主要候选药物CMTX-101 是一种免疫增强抗体疗法，与针对革兰氏阴性和革兰氏阳性细菌的多种标准护理抗生素同时施用，目的是精确快速地破坏细菌生物膜。由于生物膜普遍存在于细菌，细菌天生更喜欢生物膜环境。类似粘液的生物膜可以保护细菌群落，免受免疫或抗生素攻击。这些生物膜大多由细胞外聚合物 (EPS) 和“支架基质”构成，后者包括细胞外 DNA (eDNA) 和“linchpin”结合蛋白。生物膜保护细菌并增强其抵抗力，导致抗生素失效、抗生素耐药性、炎症反应和不良的临床结果。生物膜包裹的细菌对抗生素的抵抗力比未受生物膜保护的细菌高出 1000 倍。针对细菌的生物膜，Clarametyx 的管线资产CMTX-101抗体可以结合并去除细菌生物膜上的关键“linchpin”结合蛋白，导致生物膜快速崩解。它可以增强免疫，实现更有效的免疫效应干预，消除致病细菌；实现抗生素增敏，增强抗生素活性的有效性；抑制炎症，减少生物膜相关炎症并减少炎症反应，而不损害免疫反应。2024年1月份，Clarametyx宣布已在 A 轮融资中筹集了 3300 万美元，使其能够加快整个管道的开发，包括评估 CMTX-101抗体对抗囊性纤维化患者感染的潜力。在筹款的同时，Clarametyx 还启动了一项 1b/2a 期临床试验，评估 CMTX-101 对囊性纤维化患者的疗效。  05  MinervaX 丹麦的MinervaX 的成立是基于瑞典隆德大学的研究开发一种针对 B 族链球菌 (GBS) 的预防性疫苗。MinervaX 以此为出发点，开发一种用于孕产妇免疫的 GBS 疫苗（因为 GBS 可能对新生儿造成潜在的破坏性感染）。试验数据表明，与正在开发的其他 GBS 候选疫苗相比，其功效更佳。MinervaX 的疫苗是一种纯蛋白疫苗，来自 GBS 表面蛋白的高免疫原性和保护性蛋白结构域的融合。这款GBS 疫苗正处于临床II期，MinervaX 目前正在丹麦、英国、乌干达和南非的 470 名孕妇中进行两项II期临床试验，目前给出了积极的数据，表明疫苗具有良好的安全性，高度免疫原性，并产生功能活性抗体。除了孕妇之外，该疫苗还在第一阶段试验中探索用于老年人，因为 GBS 会导致严重疾病，如败血症、肺炎、蜂窝织炎和软组织感染。2023 年 10 月，MinervaX 筹集了 5400 万欧元的大规模融资，使这家抗生素耐药性公司能够在 2024 年将GBS 疫苗推向III期临床试验。  06  VenatorxVenatorx 专注于多重耐药细菌感染，以及难以治疗的病毒感染。他们的主要资产cefepime-taniborbactam（图5）是一种临床抗生素，已完成针对患有复杂尿路感染 (cUTI)（包括肾盂肾炎）的成人的III期研究。Cefepime是一种广泛使用的 β-内酰胺抗生素，可对抗敏感的革兰氏阴性和革兰氏阳性细菌。Taniborbactam是一种β-内酰胺酶抑制剂，与Cefepime联合使用，可以起到保驾护航的作用，成为针对抗生素耐药革兰氏阴性菌引起的严重细菌感染的潜在联合疗法。由两种活性物质组成，一种针为抗生素，另一种为酶抑制剂的联合疗法开发也是针对抗生素耐药性常见的策略。图5. Cefepime和taniborbactam化学结构Venatorx 还在开发一种口服抗菌药物ceftibuten-ledaborbactam etzadroxil（图6），这个联合疗法针对治疗选择有限，由某些细菌引起的 cUTI。该候选药物目前正在完成第一阶段的开发，并将直接进入全球第三阶段的 cUTI 试验。图6. Ceftibuten和ledaborbacam etzadroxil化学结构  写在最后  抗生素耐药性是当今世界面临的重大挑战之一，对人类健康和医疗实践造成了严重影响。随着时间的推移，抗生素的过度使用和滥用导致了微生物对这些药物的耐受性逐渐增强，形成了耐药性。这一问题的严重性在于，耐药性细菌的出现使得一些常见感染疾病变得难以治疗，增加了治疗失败和并发症的风险，甚至可能导致死亡。解决抗生素耐药性问题需要全球性的合作和综合性的策略。这包括但不限于改变抗生素的使用方式，促进更加负责任的处方和使用实践，加强监测和控制措施，推动新型抗生素的研发和创新，以及提高公众对抗生素耐药性问题的认识和意识。虽然面临着严峻的挑战，但我们仍然可以通过持续的努力和跨学科的合作来缓解和解决抗生素耐药性问题。这需要政府、医疗机构、学术界、行业以及公众共同努力，共同致力于保护人类健康，确保抗生素继续发挥其治疗作用，为全球健康安全作出贡献。参考资料：[1] Shah-Neville, W. 6 biotech companies tackling antibiotic resistance. Labiotech. 07. 03. 2024.[2] Clarametyx Biosciences. BiomX.Antabio.Acurx Pharmaceuticals.共建Biomedical创新生态圈！如何加入BiG会员？