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其他预防性治疗方法。DecImmune的长期目标是开发治疗方法，以减少冠状动脉阻塞去除后严重的致命再灌注损伤。这一目标是基于我们对缺血组织再灌注过程中激活的新途径的鉴定，以及肽模位（N2）和单克隆抗体阻断炎症的发展。目前的申请是我们2012年IIB期申请的重新提交。我们在第一阶段的研究表明，我们在啮齿动物中发现的新途径在人类中也是保守的。在II期研究中，我们发现肽（N2）和我们的抗N2 （21G6）的小鼠单克隆抗体在急性心肌梗死期间具有保护作用，并且一种治疗性候选单克隆抗体已经人源化，生产工作已经开始。因此，为了将潜在的治疗方法推向临床试验，我们建议启动非GLP和GLP安全性研究，制造临床试验材料，完成正常志愿者人体1期安全性和耐受性研究，并启动心脏病发作患者的2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.