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: 10815305
• 负责人: Laurene Wang
• 金额: $ 100万
• 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 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10815305
• 关键词: Development; Novel; Oral; Antibiotic; Treatment

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 疾病预防控制中心已将淋病奈瑟氏菌视为最高威胁水平的病原体（“紧急威胁”） 美国公共卫生。目前，CDC处理中只有一个建议的代理 指南，肌内注射延伸光谱头孢菌素，头孢曲松。但是，在 过去的十年，全球范围内出现了对头孢曲松的抵抗的报道。如果这些菌株之一是 为了广泛传播，我们将面临一个无法治疗的淋病时代。未经治疗的感染可能导致 严重和威胁生命的后遗症。这是开发新的抗生素，而没有抗逆流 治疗对公共卫生至关重要。感染N。20％至40％的人。 淋病与沙眼衣原体共同感染，这是一种主要不对称感染，可以 如果不治疗，对生殖健康和生育能力产生毁灭性影响。头孢曲松不活跃 反对沙眼梭状芽胞庭以及淋病和衣原体的临床体征和症状是无法区分的 彼此。因此，除非可以通过实验室诊断，经验治疗将衣原体排除在外 对于淋病，通常涉及两种不同类别的抗生素，以覆盖 病原体。对两种感染有效的单一口服抗生素将改变当前治疗 范式，改善对治疗的依从性以及减少双重抗生素治疗的影响 在共同感染病原体和共生生物中具有促进性。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发现了一种新型抗生素，具有针对淋病链球菌的活性 这与头孢曲松相当。它显示了对多种耐药和泛耐药的潜在活性。 淋病分离株，包括对头孢曲氨酸抗性的分离株，没有交叉抗性的证据 现有类。该提议的FastTrack Sbir应用程序的总体目标是开发新颖的口头 用于治疗淋病的抗生素作为首要任务，如果适合治疗衣原体 在美国，两种最常见的细菌性传播感染。本文提出的研究将 确认这种新类抗生素对淋病和衣原体的治疗的适用性，确定 提供最佳口服生物利用度和血浆暴露以提供有效治疗的形成，以及 提前开发申请IND。抗生素耐药性上升易于 传播，暴发风险以及缺乏二线治疗方案，所有这些都表明至关重要 确定新的抗生素治疗淋病，并迅速将其发展推向 诊所。