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.

项目总结/摘要 CDC已将淋病奈瑟菌确定为最高威胁级别（“紧急威胁”）的病原体， 美国公共卫生。目前只有一个单一的推荐代理剩余的疾病预防控制中心的治疗 肌肉注射超广谱头孢菌素，头孢曲松。但在 在过去的十年中，头孢曲松耐药的报道遍及地球仪。如果其中一种菌株 如果要广泛传播，我们将面临一个无法治愈的淋病时代。未经治疗的感染会导致 严重且危及生命的后遗症。因此，开发新的抗生素而不交叉耐药性， 治疗学对公众健康至关重要。20%~ 40%的人感染了N. 淋病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， 如果得不到治疗，对生殖健康和生育力具有毁灭性的长期影响。头孢曲松钠没有活性 针对C.沙眼与淋病和衣原体的临床体征和症状难以区分 彼此隔绝。因此，除非衣原体可以通过实验室诊断排除，否则经验性治疗 淋病的治疗通常涉及两种不同类型的抗生素的施用， 病原体一种对两种感染都有效的口服抗生素将改变目前的治疗方法 范例，提高治疗依从性，以及减少双重抗生素治疗的影响， 对促进共同感染的病原体和寄生生物体的抗性具有作用。此外，作为口头 抗生素，它将提供一个急需的治疗选择，病人和医生，并允许加快 伴侣治疗AimMax Therapeutics发现了一种新的抗生素，对N。淋病 与头孢曲松相当。它已被证明对多药耐药和泛耐药N。 淋病分离株，包括对头孢曲松耐药的分离株，无交叉耐药证据， 现有的类。该建议的FastTrack SBIR应用程序的总体目标是开发一种新的口服 抗生素治疗淋病的首要任务，如果合适的话，衣原体的治疗也， 这是美国最常见的两种细菌性性传播感染。本报告提出的研究将 确认这种新型抗生素对治疗淋病和衣原体的适用性， 提供最佳口服生物利用度和血浆暴露以提供有效治疗的制剂，以及 推进IND申报的发展。抗生素耐药性上升， 传播、爆发风险以及缺乏二线治疗方案，都表明迫切需要 确定治疗淋病的新抗生素，并迅速将其开发推向 诊所