IND-Enabling Development of a Small Molecule COVID Therapeutic

IND 促进小分子新冠肺炎治疗药物的开发

• 批准号: 10697173
• 负责人: Ryan P Bennett
• 金额: $ 30万
• 依托单位: OYAGEN, INC.
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10697173
• 关键词: 2019-nCoV; Acute; Adenosine; Agreement; Animal Model; Animals; Antiviral Agents; Body Weight decreased; COVID-19; COVID-19 pandemic; COVID-19 therapeutics; COVID-19 treatment; Canis familiaris; Caymans; Cells; Chemicals; Chickens; China; Clinic; Clinical; Clinical Trials; Combined Modality Therapy; Control Animal; Coronavirus; Data; Development; Dose; Drops; Drug Kinetics; Drug resistance; Ducks; Enzymes; Evaluation; FDA approved; Family suidae; Felis catus; Ferrets; Formulation; Funding; Future; Goals; Guide RNA; Half-Life; Hamsters; Hour; Human; Immunization; Immunocompromised Host; In Vitro; Individual; Infection; Inflammatory Response; Intravenous; Label; Legal patent; Licensing; Lower respiratory tract structure; Lung; Macaca; Malignant Neoplasms; Maximum Tolerated Dose; Mesocricetus auratus; Modeling; Mus; Nasal cavity; National Institute of Allergy and Infectious Disease; Outcome; Ownership; Patients; Persons; Pharmacologic Substance; Phase; Phase I Clinical Trials; Phosphorylation; Published Comment; Pulmonary Inflammation; RNA; Recommendation; Recovery; Regimen; Research; SARS-CoV-2 antiviral; SARS-CoV-2 infection; SARS-CoV-2 inhibitor; SARS-CoV-2 variant; Safety; Serum; Small Business Innovation Research Grant; Technology; Testing; Texas; Therapeutic; Tissues; Tritium; Upper respiratory tract; Vaccines; Variant; Viral; Viral Load result; Viremia; Virus; World Health Organization; animal safety; anti-cancer therapeutic; anti-viral efficacy; attributable mortality; cancer clinical trial; chemical synthesis; combat; commercialization; comparison control; coronavirus therapeutics; design; effective therapy; fighting; healthy volunteer; human subject; in vivo; intravenous injection; medical countermeasure; meetings; nucleoside analog; pandemic disease; preclinical development; preclinical study; programs; remdesivir; research facility; resistant strain; response; sangivamycin; small molecule; therapeutic candidate; timeline; viral RNA

The proposed Phase I SBIR will conduct IND-enabling studies to establish the pharmacokinetics (PK) and SARS-CoV-2 (CoV-2) antiviral efficacy of sangivamycin (Sang) in Golden Syrian hamsters. Sang is an adenosine nucleoside analog that we discovered to be a potent, dose- dependent inhibitor of CoV-2 during in vitro viral infectivity studies conducted at the NIAID- Integrated Research Facility (IRF) at Fort Detrick. Sang had significantly superior efficacy against multiple variants of CoV-2 compared with Remdesivir but Sang also was additive with Remdesivir when used in combination. CoV-2 is the causative agent of COVID-19, which was first documented in China in December 2019 and has since rapidly spread across the globe, leading the World Health Organization to declare a global pandemic on March 11, 2020. CoV-2 has infected greater than 600 million individuals worldwide with at least 6.4 million attributable deaths to date. OyaGen has held type B preIND meetings with the FDA (PIND 150794). Historically, Sang was safely tested in 88 human subjects during NCI cancer clinical trials but was abandoned due to its lack of efficacy against cancers in human subjects. In this Phase I SBIR OyaGen seeks to complete preclinical development of Sang as a therapeutic candidate for COVID-19 to facilitate an IND application to conduct appropriate clinical trials leading to regulatory approval and commercialization. In response to FDA guidance and comments to our preIND filing (150794) the goal of this proposal is to conduct PK of Sang in a hamster animal model (Aim 1) as well as to determine in vivo antiviral efficacy of Sang in the hamster COVID-19 model (Aim 2). The development of Sang as a therapeutic for infected patients is a medical countermeasure for immunocompromised people who may not benefit from immunization as well as a stop gap therapeutic for new strains of CoV for which current vaccines may be less effective. Importantly, our data support that Sang has the potential to enhance the efficacy of other therapeutics as a combination therapy option in the future.

拟定的I期SBIR将进行IND使能研究，以确定药代动力学 (PK)和SARS-CoV-2（CoV-2）的抗病毒疗效的桑霉素（桑）在黄金叙利亚 仓鼠桑是一种腺苷核苷类似物，我们发现它是一种有效的，剂量- 在NIAID进行的体外病毒感染性研究期间， 位于德特里克堡的综合研究设施。Sang具有显著的上级功效， 与Remdesivir相比，CoV-2的多种变体，但Sang也与Remdesivir相加 当结合使用时。CoV-2是COVID-19的病原体， 2019年12月在中国记录在案，此后迅速蔓延到地球仪， 世界卫生组织于2020年3月11日宣布全球大流行。CoV-2 全球感染人数超过6亿，至少640万人死亡 迄今OyaGen已与FDA举行了B类preIND会议（PIND 150794）。从历史上看， 在NCI癌症临床试验期间，Sang在88名人类受试者中进行了安全测试，但被放弃 这是由于其对人类受试者的癌症缺乏功效。在第一阶段SBIR中，OyaGen寻求 完成Sang作为COVID-19候选治疗药物的临床前开发， IND申请，以进行适当的临床试验，从而获得监管批准， 商业化为了回应FDA指南和对我们的preIND申请（150794）的评论， 本提案的目的是在仓鼠动物模型中进行Sang的PK（目的1），以及 确定Sang在仓鼠COVID-19模型中的体内抗病毒功效（目的2）。的 开发桑作为感染患者的治疗药物是一种医疗对策， 免疫功能低下的人可能无法从免疫接种中受益， 治疗新的CoV菌株，目前的疫苗可能不太有效。重要的是， 我们的数据支持Sang有潜力提高其他疗法的疗效， 联合治疗的选择。