C2E2-An Orally Administered Radionuclide Decorporation Agent

 描述（由申请方提供）：Capture Pharmaceuticals，Inc.正在开发一种名为C2 E2的药物，用于治疗因意外或核恐怖事件而受到放射性超铀元素污染的个人。C2 E2是一种放射性核素解毒剂，其工作原理是将这些元素结合在血流中，并在它们被捕获到肝脏和骨骼等靶器官内之前增强它们的消除。由于C2 E2可以口服，因此它在大规模伤亡情况下的使用比目前可用的必须通过静脉注射给药的产品具有显着优势，并且上级其他竞争技术。该项目的最终目标是通过FDA产品注册推进C2 E2，并将其生产销售给需要为钚和镅等放射性元素大规模污染人口的可能性做好准备的地方、国家和国际各方。这包括负责维持关键药物库存的州和联邦政府机构（例如，美国战略国家储备），以及核恐怖主义威胁持续和迫在眉睫的外国实体。Capture与FDA举行了IND前会议，当时确立了C2 E2的监管途径。已经完成了一些IND使能任务，包括药物分子的详细处方前表征，广泛的安全性毒理学评估和动物模型中的疗效研究。这些研究证明了C2 E2作为口服放射性核素去甲剂的可行性，并证明了提交本直接进入II期SBIR提案的合理性。该SBIR提案将由Capture及其学术合作伙伴（BARDA）执行，其目标是完成定义明确的IND使能活动，使C2 E2产品达到足够的技术就绪水平，以便生物医学高级研究与开发管理局（巴尔达）的后续资金可以用于制造/扩大规模活动、人体安全性评估，根据“动物规则”在动物中进行疗效测量，并提交新药申请。这将通过完成C2 E2的代谢和生物利用度研究，开发IND的化学，生产和控制部分，完成安全性-药理学研究和准备IND申请来实现。国际刑警组织2014年的一份报告强调，仍然需要一种放射性核素去污剂，以防止意外或故意造成超铀元素污染，该报告警告说，核恐怖主义的威胁日益增加，并呼吁紧急做好准备。为了扩大C2 E2的商业用途，研究其在施用后充当Gd解毒剂的能力 还将评估MRI造影剂。该SBIR应用程序的目标符合巴尔达2011-2016年战略计划，该计划强调开发私营企业尚未开发的医疗对策，以解决因核恐怖主义等故意威胁公共卫生而导致的未满足需求，以及公共卫生紧急医疗对策企业的目标。

 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.