C2E2-An Orally Administered Radionuclide Decorporation Agent

C2E2-口服放射性核素脱除剂

• 批准号: 9096012
• 负责人: Alan Parr
• 金额: $ 74.16万
• 依托单位: CAPTURE PHARMACEUTICALS, INC
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-01 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9096012
• 关键词: Accidents; Address; Animal Model; Animals; Binding; Binding Proteins; Biological Assay; Biological Availability; Blood Circulation; Boxing; Canis familiaris; Cardiovascular system; Chemistry; Clinical; Clinical Protocols; Clinical Trials; Contrast Media; Data; Development; Drug Design; Drug Kinetics; Elements; Enzyme Inhibition; Event; Federal Government; Feedback; Fibrosis; Formulation; Funding; Gadolinium; Goals; Government; Government Agencies; Health; Human; Indium; Individual; Industry; International; Investigational Drugs; Investigational New Drug Application; Label; Liver; Magnetic Resonance Imaging; Manufacturer Name; Marketing; Measurement; Measures; Medical; Medicine; Metabolic; Metabolism; Metals; Nuclear; Oral; Organ; Pharmaceutical Preparations; Pharmacologic Substance; Pharmacology; Phase; Plutonium; Population; Production; Public Health; Radioactive; Radioactive Elements; Radioisotopes; Rattus; Readiness; Regulatory Pathway; Reporting; Risk; Safety; Sales; Scheme; Secure; Skeleton; Small Business Innovation Research Grant; State Government; Strategic Planning; Technology; Terrorism; Time; Toxicology; United States Food and Drug Administration; Update; Work; Writing; analytical method; animal rule; authority; base; bone; gadolinium oxide; improved; interest; intravenous injection; manufacturing scale-up; mass casualty; meetings; novel therapeutics; public health emergency; research and development; respiratory; safety study

 DESCRIPTION (provided by applicant): Capture Pharmaceuticals, Inc. is developing a drug called C2E2 for treatment of individuals who have been contaminated by radioactive transuranic elements, either by accident or following a nuclear terrorism event. C2E2 is a radionuclide decorporation agent that works by binding these elements in the bloodstream and enhancing their elimination before they can be trapped inside target organs such as the liver and skeleton. Because it can be taken orally, C2E2 has significant advantages for use in a mass casualty scenario over currently available products which must be administered by intravenous injection, and is superior to other competing technologies. The ultimate goal of this project is to advance C2E2 through FDA product registration and manufacture it for sale to local, national and international parties that need to prepare for the potential of mass contamination of the population with radioactive elements like plutonium and americium. This includes state and federal government agencies responsible for maintaining stockpiles of critical medicines (e.g., the U.S. Strategic National Stockpile), as well as foreign entities where the threat of nuclear terrorism is constant and imminent. Capture had a pre-IND meeting with the FDA at which time the regulatory pathway for C2E2 was established. A number of IND-enabling tasks have been completed, including detailed pre-formulation characterization of the drug molecule, extensive safety-toxicology assessments and efficacy studies in animal models. These studies demonstrated the feasibility of C2E2 as an oral radionuclide decorporation agent and justify submission of this Direct-to-Phase II SBIR proposal. The goal of this SBIR proposal, which will be conducted by Capture and its academic partner (UNC), is to complete well-defined IND-enabling activities that will bring the C2E2 product to a sufficient Technology Readiness Level so that subsequent funding from the Biomedical Advanced Research and Development Authority (BARDA) can be secured for manufacturing/scale- up activities, safety assessment in humans, efficacy measurements in animals as per the 'Animal Rule', and submission of a New Drug Application. This will be achieved by completing metabolic and bioavailability studies with C2E2, developing the Chemistry, Manufacturing & Controls section of the IND, completing safety- pharmacology studies and preparing an IND application. The continuing need for a radionuclide decorporation agent for accidental or deliberate contamination with transuranic elements has been highlighted by a 2014 INTERPOL report which warned of the increasing threat of nuclear terrorism and called for urgent preparedness. In order to expand the commercial utility of C2E2, its ability to serve as a Gd detoxifying agent following administration of MRI contrast agents will also be assessed. The goals of this SBIR application fit the BARDA Strategic Plan for 2011-2016, which emphasizes development of medical countermeasures not being developed by private industry to address unmet needs resulting from intentional threats to public health like nuclear terrorism, as well as the goals of the Public Health Emergency Medical Countermeasures Enterprise.

 描述（由申请人提供）：Capture Pharmaceuticals, Inc. 正在开发一种名为 C2E2 的药物，用于治疗因意外或核恐怖主义事件而受到放射性超铀元素污染的个体。C2E2 是一种放射性核素脱除剂，其作用原理是。将这些元素结合在血液中，并在它们被困在肝脏和骨骼等目标器官内之前增强它们的消除，因为 C2E2 可以口服，因此在大量使用时具有显着的优势。该项目的最终目标是通过 FDA 产品注册来推进 C2E2 的发展，并将其生产销售给有需要的当地、国家和国际各方。为人口可能遭受钚和镅等放射性元素的大规模污染做好准备，这包括负责维持关键药物库存的州和联邦政府机构（例如美国战略国家库存），以及核恐怖主义威胁持续且迫在眉睫的外国实体，Capture 与 FDA 举行了 IND 前会议，当时建立了 C2E2 的监管途径，其中包括详细的 IND 授权任务。药物分子的制剂前表征、广泛的安全毒理学评估和动物模型中的功效研究证明了 C2E2 作为口服放射性核素脱色剂的可行性，并证明了提交此直接二期 SBIR 的合理性。该 SBIR 提案将由 Capture 及其学术合作伙伴 (UNC) 进行，其目标是完成明确定义的 IND 支持活动，使 C2E2 产品达到足够的技术准备水平，以便后续提供资金。可以确保生物医学高级研究和开发局 (BARDA) 进行制造/扩大规模活动、人体安全评估、根据“动物规则”进行动物功效测量以及提交新药申请。通过完成代谢和2014 年的一份报告强调了对放射性核素脱除剂的持续需求，以应对意外或故意的超铀元素污染。国际刑警组织的报告警告说，核恐怖主义的威胁日益严重，并呼吁立即做好准备，以扩大 C2E2 的商业用途，及其作为 Gd 的能力。给药后解毒剂 还将评估该 SBIR 应用的目标符合 BARDA 2011-2016 年战略计划，该计划强调发展非私营企业开发的医疗对策，以解决因核等对公共健康的故意威胁而导致的未满足的需求。恐怖主义以及公共卫生紧急医疗对策企业的目标。