Humanized Antibody Therapeutic to Improve Cardiac Function Following Myocardial I

描述（由申请人提供）：项目摘要/摘要急性心肌梗死（AMI）每年影响超过100万美国人，目前除了直接经皮冠状动脉介入治疗外，没有预防性治疗。DecImmune的长期目标是开发治疗方法，以减少冠状动脉阻塞清除后严重的致命性再灌注损伤。这一目标是基于我们鉴定出一种在缺血组织再灌注过程中激活的新途径，以及开发出一种阻断炎症的肽模拟物（N2）和单克隆抗体。目前的申请是我们2012年IIB期申请的重新提交。我们的I期研究表明，我们在啮齿动物中发现的新途径在人类中是保守的。在第二阶段，我们发现肽（N2）和我们的鼠抗N2单克隆抗体（21 G6）在急性心肌梗死期间具有保护作用，并且治疗性候选单克隆抗体已被人源化并开始生产。因此，为了将潜在的治疗方法转移到临床试验中，我们建议开始非GLP和GLP安全性研究，生产临床试验材料，完成正常志愿者人体I期安全性和耐受性研究，并在心脏病发作患者中启动II期临床试验。

DESCRIPTION (provided by applicant): Project Summary/Abstract Acute myocardial infarction (AMI) affects over 1 million US individuals a year and at the present there are no preventive therapeutics other than direct percutaneous coronary intervention. DecImmune's long-term goal is to develop therapeutics to reduce the severe lethal reperfusion injury that follows removal of coronary artery blockage. This goal is based on our identification of a novel pathway that is activated during reperfusion of ischemic tissues and development of a peptide mimetope (N2) and monoclonal antibodies that block inflammation. The current application is a re-submission of our Phase IIB application of 2012. Our studies from Phase I demonstrated that the novel pathway we identified in rodents is conserved in humans. In Phase II, we showed that both the peptide (N2) and our murine monoclonal antibody against N2 (21G6) were protective during acute myocardial infarction and that a therapeutic candidate monoclonal antibody has been humanized and manufacturing efforts have begun. Therefore, in order to move the potential therapeutics to clinical trials, we propose to start non-GLP and GLP safety studies, manufacture clinical trial material, complete a normal volunteer human Phase 1 safety and tolerability study and initiate Phase 2 clinical trials in heart attack patients.