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

基本信息

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
项目类别：
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

项目摘要

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.

拟议的I期SBIR将进行辅助研究以建立药代动力学（PK）和SARS-COV-2（COV-2）Sangivamycin（Sang）在黄金叙利亚人中的抗病毒功效仓鼠。 Sang是一种腺苷核苷类似物，我们发现它是一种有效的剂量 - 在尼亚德 - 迪特里克堡的综合研究设施（IRF）。 Sang具有明显优于与Remdesivir相比，COV-2的多种变体，但Sang也与Remdesivir相加当组合使用时。 COV-2是Covid-19的致病药物，首先是于2019年12月在中国记录，此后迅速遍及全球，领导世界卫生组织将于2020年3月11日宣布全球大流行。全世界受感染超过6亿个人，至少有640万人归因于死亡迄今为止。 Oyagen已与FDA（PIND 150794）举行了B型预告片会议。从历史上看在NCI癌症临床试验期间，在88名人类受试者中对Sang进行了安全测试，但被放弃了由于它对人类受试者的癌症缺乏疗效。在这个阶段，我寻求完成Sang的临床前开发，作为Covid-19的治疗候选者，以促进 IND申请进行适当的临床试验，导致监管批准和商业化。为了回应FDA的指导和对我们的预先提交文件的评论（150794）该提议的目标是在仓鼠动物模型（AIM 1）中进行Sang的PK以及确定在仓鼠covid-19模型中Sang的体内抗病毒功效（AIM 2）。这为感染患者开发SANG作为治疗性是医学对策免疫功能低下的人可能不会从免疫接种和停止差距中受益当前疫苗可能不太有效的新型COV菌株的治疗性。重要的是，我们的数据支持有可能增强其他治疗剂的功效联合疗法将来。