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.

项目概要/摘要 疾病预防控制中心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 CDC 治疗中只剩下一种推荐药物 指南，肌内注射广谱头孢菌素头孢曲松。然而，在 过去十年，全球各地都出现了头孢曲松耐药性的报道。如果这些菌株之一是 如果要广泛传播，我们将面临一个淋病无法治愈的时代。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，开发新的抗生素而不与当前的抗生素产生交叉耐药性 治疗对于公共卫生至关重要。 20% 到 40% 的人感染了 N. 淋病菌与沙眼衣原体共同感染，这是一种主要无症状的感染，可以 如果不加以治疗，会对生殖健康和生育能力产生毁灭性的长期影响。头孢曲松没有活性 针对沙眼衣原体，淋病和衣原体的临床体征和症状无法区分 来自彼此。因此，除非实验室诊断可以排除衣原体，否则经验性治疗 对于淋病，通常需要使用两种不同类别的抗生素，以覆盖两者 病原体。对两种感染有效的单一口服抗生素将改变目前的治疗方法 范例，提高治疗依从性并减少双抗生素治疗的影响 具有促进共感染病原体和共生生物的抵抗力。此外，作为口头 抗生素，它将为患者和医生提供急需的治疗选择，并允许加快 伴侣治疗。 AimMax Therapeutics 发现了一种具有抗淋病奈瑟菌活性的新型抗生素 与头孢曲松相当。它已被证明对多重耐药和泛耐药的奈瑟氏菌具有有效的活性。 淋病分离株，包括对头孢曲松耐药的分离株，没有证据表明对头孢曲松具有交叉耐药性 现有课程。拟议的 FastTrack SBIR 应用的总体目标是开发一种新型口服药物 治疗淋病的抗生素是首要任务，如果合适的话，也可用于治疗衣原体， 美国两种最常见的细菌性传播感染。本文提出的研究将 确认此类新型抗生素是否适合治疗淋病和衣原体，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 推进 IND 申请的开发。不断上升的抗生素耐药性加上易于 传播、爆发风险以及缺乏二线治疗方案，所有这些都表明迫切需要 确定治疗淋病的新抗生素并迅速推进其开发 诊所。