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

• 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
• 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

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.

项目摘要 冠心病导致急性心肌梗死（MI;心脏病发作）是死亡的主要原因 国际吧MI的基础治疗旨在恢复阻塞的血流（即“再灌注”） 冠状动脉尽管介入时间缩短，支架置入成功，但30-50%的原发性 经皮冠状动脉介入治疗（PCI）患者表现出低或“无复流”，这是一种与不良 结果，心力衰竭和死亡的可能性增加。当肉眼可见血管出现低/无复流时 通过支架植入术或血栓溶解术打开，但远端心肌灌注仍然受损。 “VasaPlex-F2”（HGF：IgG复合物）和“VasaPlex-F2”（FGF 2：HGF：IgG复合物）是血管和心脏保护性的。 我们设计的生物药物是为了增加血管的完整性，保护心脏组织， 再灌注损伤和低/无再流。在急性MI伴再灌注的大型动物（猪）模型中， 输注Vasavir可保护48 ± 12%的危险心肌组织。我们提出以下具体目标： 1.确定VasaplaxTM或VasaPlex-F2冠状动脉内治疗对心脏结构的影响 术后1个月功能恢复良好。里程碑：获得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， 在临床前， MI再灌注大动物模型。 2.制定标准化条件，以形成和维护基于VasaPlex的产品。 里程碑：获得我们药物组分解离/缔合动力学的基础数据 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申报和产品商业化。 可接受：与NIH STTR计划的目标一致，桑巴舞生物逻辑公司，将提供新的， 创新和有效的产品，改善MI后患者的生存率、结局和生活质量。