Development of a Novel Oral Antibiotic for the Treatment of Drug Resistant Gonorrhea

开发一种治疗耐药性淋病的新型口服抗生素

• 批准号: 10546278
• 负责人: Laurene Wang
• 金额: $ 30.69万
• 依托单位: AIMMAX THERAPEUTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-08 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10546278
• 关键词: Address; Adherence; Advanced Development; Antibiotic Resistance; Antibiotic Therapy; Antibiotics; Azithromycin; Biological Assay; Biological Availability; Canis familiaris; Cardiovascular system; Ceftriaxone; Cell Line; Cells; Centers for Disease Control and Prevention (U.S.); Cephalosporins; Chlamydia; Chlamydia trachomatis; Classification; Clinic; Clinical; Clinical Research; Clinical Trials; Development; Disease; Disease Outbreaks; Dose; Doxycycline; Drug Interactions; Drug Kinetics; Drug-resistant Neisseria Gonorrhoeae; Evaluation; Excipients; Exposure to; Fertility; Fiber; Formulation; Frequencies; Goals; Gonorrhea; Guidelines; Hepatocyte; Human; In Vitro; Individual; Infection; Inferior; Injectable; Instruction; Intestines; Intramuscular Injections; Isoenzymes; Kinetics; Laboratory Diagnosis; Life; Liver Microsomes; Long-Term Effects; Macrolide-resistance; Measures; Microbiology; Modeling; Modernization; Multi-Drug Resistance; Mutation; Neisseria gonorrhoeae; No-Observed-Adverse-Effect Level; Oral; Organism; Patients; Pharmaceutical Preparations; Pharmacodynamics; Pharmacology Study; Phase; Physicians; Plasma; Plasma Enhancement; Program Development; Public Health; Rattus; Recommendation; Reporting; Reproductive Health; Resistance; Risk; Safety; Series; Sexually Transmitted Diseases; Signs and Symptoms; Site; Small Business Innovation Research Grant; Streptogramins; Technology; Therapeutic; Time; Toxic effect; Toxicology; absorption; antimicrobial; bactericide; base; clinical development; cytotoxicity; drug metabolism; drug-resistant gonorrhea; effective therapy; first-in-human; improved; inhibitor; manufacturing process; manufacturing scale-up; meetings; novel; novel antibiotic class; pathogen; programs; resistant strain; success; therapy development; transmission process; treatment guidelines

PROJECT SUMMARY / ABSTRACT The CDC has identified Neisseria gonorrhoeae as a pathogen of the highest threat level (“Urgent Threat”) to the US public health. Currently there is only a single recommended agent remaining on the CDC treatment guidelines, an intramuscular injection of the extended spectrum cephalosporin, ceftriaxone. However, in the past decade, reports of resistance to ceftriaxone have appeared across the globe. If one of these strains were to disseminate widely, we would be facing an era of untreatable gonorrhea. Untreated infections can cause serious and life-threatening sequelae. Thus, developing new antibiotics without cross-resistance to the current therapeutics is of critical importance to public health. Between 20 and 40% of individuals infected with N. gonorrhoeae are co-infected with Chlamydia trachomatis, a predominantly asymptomatic infection that can have devastating long-term effects on reproductive health and fertility if not treated. Ceftriaxone is not active against C. trachomatis and the clinical signs and symptoms of gonorrhea and chlamydia are indistinguishable from one another. Therefore, unless chlamydia can be excluded by a laboratory diagnosis, empiric treatment for gonorrhea typically involves administration of two different classes of antibiotics in order to cover both pathogens. A single oral antibiotic effective against both infections would change the current treatment paradigm, improving adherence to treatment as well as reducing the impact that dual antibiotic therapy can have on promoting resistance in co-infecting pathogens and commensal organisms. Furthermore, as an oral antibiotic, it would provide a much-needed treatment option to patients and physicians and allow for expedited partner therapy. AimMax Therapeutics has discovered a novel antibiotic with activity against N. gonorrhoeae that is comparable to ceftriaxone. It has demonstrated potent activity against multidrug- and pan-resistant N. gonorrhoeae isolates, including isolates resistant to ceftriaxone, with no evidence of cross-resistance to existing classes. The overall goal of this proposed FastTrack SBIR application is to develop a novel oral antibiotic for the treatment of gonorrhea as the top priority, and if suitable, for the treatment of chlamydia also, the two most common bacterial sexually transmitted infections in the US. The studies proposed herein will confirm the suitability of this new class of antibiotic for the treatment of gonorrhea and chlamydia, identify a formulation that delivers optimal oral bioavailability and plasma exposure to provide effective treatment, and advance development towards filing of an IND. Rising antibiotic resistance combined with ease of transmission, risks for outbreaks, and lack of second-line treatment options, all point to the critical need to identify new antibiotics for the treatment of gonorrhea and expeditiously advance their development to the clinic.

项目摘要/摘要 美国疾病控制与预防中心已将淋病奈瑟氏菌确定为对 美国公共卫生。目前，CDC治疗上只剩下一种推荐的药物 指南中，肌肉注射超广谱头孢菌素、头孢曲松。然而，在 在过去的十年里，有关头孢曲松耐药的报道出现在全球各地。如果这些菌株中的一个是 如果要广泛传播，我们将面临一个无法治愈的淋病时代。未经治疗的感染可能会导致 严重且危及生命的后遗症。因此，开发对当前病毒没有交叉耐药性的新抗生素 治疗学对公共卫生至关重要。20%至40%的人感染N。 淋球菌与沙眼衣原体合并感染，沙眼衣原体是一种主要无症状的感染，可 如果不治疗，会对生殖健康和生育产生毁灭性的长期影响。头孢曲松不起作用 对沙眼衣原体和淋病和衣原体的临床症状和体征难以区分 彼此之间的距离。因此，除非实验室诊断可以排除衣原体感染，否则经验性治疗。 淋病通常涉及两种不同类别的抗生素的管理，以涵盖这两种 病原体。一种对两种感染都有效的单一口服抗生素将改变目前的治疗方法。 范式，提高对治疗的依从性，并减少双重抗生素疗法可能产生的影响 在病原体和共生生物的共同感染中具有促进耐药性的作用。此外，作为一个口头的 抗生素，它将为患者和医生提供亟需的治疗选择，并允许加快 伴侣疗法。AimMax治疗公司发现了一种新的抗淋病奈瑟菌的抗生素 这与头孢曲松相当。它对多药耐药和泛耐药的N。 淋病分离株，包括对头孢曲松耐药的分离株，没有证据表明对 现有的类。这个提议的FastTrack SBIR应用程序的总体目标是开发一种新的口腔 用于治疗淋病的抗生素是最优先的，如果合适的话，也用于治疗衣原体， 美国最常见的两种细菌性性传播疾病。在此提出的研究将 确认这种新型抗生素适用于治疗淋病和衣原体，确定一种 提供最佳口服生物利用度和血浆暴露以提供有效治疗的配方，以及 推动IND备案工作的发展。抗生素耐药性的上升与易感性相结合 传播、暴发风险以及缺乏二线治疗选择，所有这些都表明迫切需要 发现治疗淋病的新抗生素，并尽快将其开发到 诊所。