VasaPlex-based biologics for treatment of reperfusion injury after myocardial infarction

项目总结 导致急性心肌梗死(MI；心脏病发作)的冠心病是死亡的主要原因 全世界。心肌梗死的基石治疗旨在恢复阻塞的血流(即再灌流) 冠状动脉。尽管介入时间减少，支架置入成功，但30%-50%的初诊患者 接受经皮冠状动脉介入治疗的患者表现为低复流或无复流，这一现象与不良有关 结果，心力衰竭和死亡的概率增加。宏观血管发生低/无回流 可以通过支架或溶栓打开，但远端心肌灌注仍然受到影响。 “VasaPlex”(HGF：Ig G复合体)和“VasaPlex-F2”(FGF2：HGF：Ig G复合体)具有血管和心脏保护作用 我们设计的生物药物旨在提高血管完整性并保存受 再灌注损伤和低/无复流。大动物(猪)冠状动脉内急性心肌梗死再灌注模型 VasaPlex输注保存了48±12%的危险心肌组织。我们提出了以下具体目标： 1.确定冠脉内应用VasaPlex或VasaPlex-F2对心脏结构的影响 心梗后1个月及术后1个月恢复功能。里程碑：获得心脏循环生物标志物的数据 显示心脏功能的损伤、组织学和超声心动图测量 VasaPlex和/或VasaPlex-F2治疗在临床前、 心肌梗死再灌流的大动物模型。 2.开发标准化条件，以形成和维护基于VasaPlex的产品。 里程碑：获得我们药物成分的解离/缔合动力学的基础基础数据 以及Ig G Fc结构域糖基化的影响；这些数据将帮助我们生产更多产品 高效，提高产品安全性，支持IND备案和产品商业化。 交付成果：根据NIH STTR计划的目标，Samba Biologics，Inc.将提供新的、 创新和有效的产品，改善患者的生存，结果和心肌梗死后的生活质量。

PROJECT SUMMARY Coronary heart disease leading to acute myocardial infarction (MI; heart attack) is a principal cause of mortality worldwide. Cornerstone treatments for MI are designed to restore blood flow (i.e. to “reperfuse”) blocked coronary arteries. Despite reduced times to intervention, and successful stent placement, 30-50% of primary Percutaneous Coronary Intervention (PCI) patients exhibit low- or “no-reflow”, a phenomenon linked to poor outcomes, increased probability of heart failure, and death. Low/no-reflow occurs when macroscopic vessels are opened by stenting or thrombolysis, but distal myocardial perfusion remains compromised. “VasaPlex” (HGF:IgG complex) and “VasaPlex-F2” (FGF2:HGF:IgG complex) are vaso- and cardioprotective biologic drugs we designed to increase vascular integrity and preserve cardiac tissue jeopardized by reperfusion injury and low/no-re-flow. In a large animal (pig) model of acute MI with reperfusion, intracoronary infusion of VasaPlex preserved 48 ± 12% of myocardial tissue at risk. We propose the following Specific Aims: 1. Determine effects of intracoronary treatment with VasaPlex or VasaPlex-F2 on cardiac structure and function 1 month after MI and PCI. Milestone: Obtain data for circulating biomarkers of cardiac injury, tissue histology, and echocardiographic measures of cardiac function that demonstrate significant long-term benefit conferred by VasaPlex and/or VasaPlex-F2-treatment in a pre-clinical, large animal model of MI with reperfusion. 2. Develop standardized conditions to form and maintain VasaPlex-based products. Milestone: Obtain basic, foundational data for dissociation/association kinetics of our drug components and the effects of IgG Fc domain glycosylation; these data will help us to generate our products more efficiently, improve product safety, and support IND filing and product commercialization. Deliverables: In alignment with the goals of the NIH STTR program, Samba BioLogics, Inc., will provide new, innovative and effective products that improve patient survival, outcomes and quality of life after MI.