MITIGATION OF MULTI-ORGAN DELAYED EFFECTS OF ACUTE RADIATION EXPOSURE (DEARE) WITH ACE-INHIBITOR LISINOPRIL

急性辐射暴露的受害者可能会经历一系列晚期多器官毒性，这些毒性统称为急性辐射暴露的延迟效应（DEARE）。目前fda还没有批准用于DEARE的mcm。赖诺普利是缓解DEARE的主要候选MCM，因为它符合该BAA下MCM开发的所有技术要求，包括在动物研究中的先前有效性和在人体中的既定安全性。我们的主要目标是利用我们丰富的临床前经验，通过fda许可将赖诺普利作为DEARE的对策。为实现这一目标，我们制定了以下三个里程碑。里程碑1：赖诺普利剂量优化缓解放射性肺炎。里程碑2：赖诺普利对血液学急性放射综合征（H-ARS）幸存者的疗效。里程碑3：监管活动。

Victims of acute radiation exposure are likely to experience a range of late multi-organ toxicities, which are collectively referred to as delayed effects of acute radiation exposure (DEARE). Currently there are no FDA-approved MCMs for DEARE. Lisinopril is a lead candidate MCM for mitigation of DEARE as it meets all the technical requirements for MCM development under this BAA including prior efficacy in animal studies and an established safety profile in humans. Our main objective is to build on our extensive preclinical experience to forward lisinopril through FDA-licensure as a countermeasure for DEARE. To meet this objective, we have developed the following three milestones. Milestone 1: Lisinopril dose optimization for mitigation of radiation pneumonitis. Milestone 2: Lisinopril efficacy in survivors of hematologic acute radiation syndrome (H-ARS). Milestone 3: Regulatory Activities.