Development of BIO 300 as a MCM for lethal radiation pneumonitis/fibrosis

项目摘要 对于放射性肺炎的有效医学对策存在显著的需求， 肺纤维化与急性辐射照射的延迟效应有关。大 重要的是可以在没有医疗监督的情况下分发使用的对策， 口头有效的对策的高度兴趣和重要性。为了解决这一未满足的需求， Humanetics公司正在开发BIO 300口服混悬液（活性成分染料木黄酮）， 急性辐射暴露（DEARE）对肺的延迟效应。染料木黄酮，一种非特异性酪氨酸 激酶抑制剂，具有很强的安全性历史，并具有与其 具有较强的抗氧化能力、抗炎特性，并对细胞周期分裂有影响。在 本提案中总结的临床前研究BIO 300已显示出显著改善 全胸肺移植后存活率、减轻肺组织损伤、改善肺功能 辐照本提案的目的是确定BIO 300的最佳治疗剂量方案 为了减少肺损伤，并最大限度地提高急性辐射暴露后的生存可能性， 胸部区域放射性肺损伤的剂量反应和时程模型 将在拟议的研究中使用明确定义的损伤。还建议开展研究， 了解全身或部分照射对BIO 300药代动力学特性的影响。 拟议研究的总体目标是推进BIO 300作为医疗器械的发展。 FDA批准的对策。拟议的工作建立在研发经验， Humanetics公司致力于开发BIO 300作为急性 辐射暴露未来发展的主要重点将是推动BIO 300的发展 进行大型动物有效性试验，以确定在啮齿动物模型中观察到的阳性有效性数据 转化为更大的动物。BIO 300的持续发展无疑将扩大科学的 知识基础，并支持持续评估和开发预防和/或 治疗辐射的急性和慢性影响。此外，随着BIO 300的先进 作为医疗放射对策的发展，以及作为癌症放射疗法的辅助， 通过关键疗效试验提供了加速开发过程的机会， 执照

Project Summary A significant need exists for effective medical countermeasures for radiation-induced pneumonitis and pulmonary fibrosis associated with the delayed effects of acute radiation exposure. Of great importance are countermeasures that can be distributed for use without medical supervision, making orally effective countermeasures of high interest and importance. To address this unmet need, Humanetics Corporation is developing BIO 300 Oral Suspension (active ingredient genistein) to treat the delayed effects of acute radiation exposure (DEARE) in the lung. Genistein, a non-specific tyrosine kinase inhibitor, has a strong history of safety, and has substantial radioprotective effects linked to its strong antioxidant capacity, anti-inflammatory properties, and its effects on cell cycle division. In preclinical studies summarized in this proposal BIO 300 has been shown to significantly improve survival, mitigate lung tissue injury, and improve pulmonary function following whole thoracic lung irradiation. The aim of this proposal is to determine the optimum therapeutic dosing regimen of BIO 300 to reduce lung damage and maximize the likelihood for survival following acute radiation exposure to the thoracic region. Models in which the dose response and timecourse of radiation induced pulmonary damage are well defined will be used in the proposed studies. Studies are also proposed to further understand the effect that total or partial body irradiation has on BIO 300’s pharmacokinetic properties. The overall goal of the proposed studies is to advance the development of BIO 300 as a medical countermeasure towards FDA approval. The proposed work builds on the R&D experience of Humanetics Corporation toward the development of BIO 300 as a medical countermeasure for acute radiation exposure. The main emphasis of future development will be to move BIO 300 development into large animal efficacy testing to determine if the positive efficacy data observed in the rodent model translates to a larger animal. Continued development of BIO 300 will undoubtedly expand the scientific knowledge base and support the continued evaluation and development of agents to prevent and/or treat the acute and chronic effects of radiation exposure. Moreover, with BIO 300’s advanced development as a medical radiation countermeasure, and as an adjunct to cancer radiotherapy, it presents an opportunity for an accelerated development course through pivotal efficacy trials and to licensure.