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

基于 VasaPlex 的生物制剂用于治疗心肌梗死后的再灌注损伤

基本信息

批准号：
10382838
负责人：
JEFFREY L SPEES
金额：
$ 49.83万
依托单位：
SAMBA BIOLOGICS INCORPORATED
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-03-11 至 2024-03-09
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10382838
关键词：
Acute Acute myocardial infarction Angioplasty Animal Model Animals Arteries Binding Biological Biological Products Biotechnology Blood Circulation Blood Vessels Blood capillaries Blood coagulation Blood flow Cardiac Cardiac Death Cardiac Myocytes Catheters Cessation of life Clinical Complex Coronary artery Coronary heart disease Data Development Dissociation Distal Drug Design Edema Exhibits FDA approved FGF2 gene Family suidae Fc domain Formulation Foundations Functional disorder Goals Heart Heart Injuries Heart failure Histology Immunoglobulin G Infarction Infusion procedures Intervention Ischemic Stroke Kinetics Link Measures Mechanics Medicine Modeling Myocardial Myocardial Infarction Myocardial perfusion Myocardial tissue Necrosis Nutrient Osmolar Concentration Outcome Oxygen Patient-Focused Outcomes Patients Peripheral arterial disease Pharmaceutical Preparations Phase Probability Procedures Prognosis Quality of life Reperfusion Injury Reperfusion Therapy Risk Rupture Safety Sepsis Site Small Business Innovation Research Grant Small Business Technology Transfer Research Standardization Stents Structure Swelling Temperature Time Tissue Survival Tissues Transplantation United States United States National Institutes of Health Universities Vasospasm Vermont angiogenesis base capillary bed cardioprotection circulating biomarkers commercialization coronary angioplasty design glycosylation heart function heart preservation improved improved outcome innovation mortality negative affect organ injury percutaneous coronary intervention phase III trial porcine model pre-clinical preservation product development programs standard of care survival outcome thrombolysis tissue injury vascular injury

项目摘要

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.

项目概要导致急性心肌梗塞（MI；心脏病发作）的冠心病是死亡的主要原因在世界范围内，心肌梗死的基石治疗旨在恢复受阻的血流（即“再灌注”）。尽管减少了介入时间并成功放置了支架，但仍有 30-50% 的原发性冠状动脉经皮冠状动脉介入治疗 (PCI) 患者表现出低复流或“无复流”，这种现象与血液循环不良有关当宏观血管出现低/无复流时，会增加心力衰竭和死亡的可能性。通过支架置入或溶栓打开，但远端心肌灌注仍然受到损害。 “VasaPlex”（HGF:IgG 复合物）和“VasaPlex-F2”（FGF2:HGF:IgG 复合物）具有血管和心脏保护作用我们设计的生物药物可以增强血管完整性并保护受到以下疾病危害的心脏组织再灌注损伤和低/无复流的大型动物（猪）再灌注急性心肌梗死模型。输注 VasaPlex 可保留 48 ± 12% 的危险心肌组织。我们提出以下具体目标： 1. 确定 VasaPlex 或 VasaPlex-F2 冠状动脉内治疗对心脏结构的影响 MI 和 PCI 后 1 个月的功能和功能里程碑：获取心脏循环生物标志物的数据。损伤、组织组织学和心脏功能的超声心动图测量表明 VasaPlex 和/或 VasaPlex-F2 治疗在临床前、再灌注心肌梗死大动物模型。 2. 制定标准化条件来形成和维护基于 VasaPlex 的产品。里程碑：获得我们药物成分的解离/缔合动力学的基本数据以及 IgG 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。可交付成果：根据 NIH STTR 计划的目标，Samba BioLogics, Inc. 将提供新的、创新且有效的产品，可改善心肌梗死后患者的生存、结果和生活质量。