Treatment of Inflammatory Complications of Viral Pneumonia

病毒性肺炎炎症并发症的治疗

基本信息

批准号：
10383991
负责人：
Andy Agrawal
金额：
$ 30万
依托单位：
RESPANA THERAPEUTICS, INC.
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：
2022-06-20 至 2023-08-06
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10383991
关键词：
2019-nCoV Acceleration Acute Acute Lung Injury Acute Respiratory Distress Syndrome Acute respiratory failure Acute respiratory infection Address Adhesions Advanced Development Aftercare Alveolar Alveolar Macrophages Animals Antibodies Antiviral Agents Antiviral resistance Attenuated Bacterial Pneumonia Biochemical Biocompatible Materials Biological Availability Biological Models Blood Chemical Analysis Body Weight COVID-19 Cells Cellular Assay Cessation of life Critical Illness Data Development Disease Disease Outbreaks Drug Kinetics Effectiveness Etiology Fibrosis Genetic study Healthcare Systems Hematology Histopathology Hospitalization Host Defense Human Hypoxia Immune Immune response Immunity Immunocompromised Host Immunologic Receptors Impairment Individual Infection Inflammation Inflammatory Inflammatory Response Influenza Influenza A Virus, H1N1 Subtype Influenza A virus Injectable Intervention Lead Lung Lung infections Mediating Medical Methodology Methods Monoclonal Antibodies Morbidity - disease rate Mus Organ Pathogenicity Patient-Focused Outcomes Patients Peripheral Phagocytosis Pharmaceutical Preparations Pharmacology Phase Play Pre-Clinical Model Predisposition Prevention Property Protein Isoforms Proteins Public Health Pulmonary Inflammation Readiness Reagent Recovery Reporting Resolution Respiratory Tract Infections Risk Role SARS-CoV-2 infection Safety Shipping Source Surface Symptoms Testing Therapeutic Therapeutic Monoclonal Antibodies Time TimeLine Toxic effect Treatment Efficacy United States Vaccines Viral Viral Pneumonia Virus Virus Diseases Work airway obstruction base biophysical analysis co-infection combat commercialization cytokine experience extreme temperature fighting high risk high risk population humanized monoclonal antibodies humanized mouse improved outcome influenza infection innovation lung health lung injury macrophage monocyte mortality mouse model murine monoclonal antibody neonatal Fc receptor novel pandemic disease pandemic influenza pathogen pre-clinical prevent product development pulmonary function research clinical testing respiratory response restoration seasonal influenza superinfection surfactant surfactant protein A receptor targeted treatment trafficking young adult

项目摘要

ABSTRACT Respana Therapeutics, Inc., is developing and commercializing a proprietary humanized monoclonal antibody (mAb) targeting morbidities and mortality associated with inflammatory complications of viral pneumonia. The initial anticipated product is an injectable mAb that calibrates the immune response to respiratory infection, attenuates injurious inflammation and expedites restoration of lung health after influenza A virus (IAV) infection, both seasonal and pandemic. Influenza is α major source of acute lung injury in critically ill patients worldwide. Emerging evidence that influenza coinfection exacerbates susceptibility to SARS-CoV-2 infection with increased mortality anticipates an even larger burden of respiratory critical illness in the post-pandemic era in the years to come. Respiratory infections like influenza create a widespread immune system response causing acute inflammation in the lung. This inflammatory response, while necessary to fight the virus, can persist in the lung long after the virus is cleared. This can lead to further morbidities, including secondary bacterial pneumonia, hospitalization due to serious lung injury, and even death. To address that, Respana intends to develop a safe, affordable, scalable and widely available product that can be used to improve outcomes for patients, beginning with high-risk influenza sufferers. We anticipate that Respana’s product will reduce duration of symptoms, and reduce post-influenza bacterial respiratory infections and mortality, thereby strengthening the health care system’s ability to combat seasonal and pandemic influenza. Respana’s innovative work on the surfactant protein (SP-A) receptor SP-R210 has shown that it increases phagocytosis of SP-A-bound pathogens and modulates cytokine secretion by immune cells. SP-A plays an important role in pulmonary immunity by enhancing opsonization and clearance of pathogens and by modulating macrophage inflammatory responses. The data Respana has generated supports a biological model in which SP-R210 isoforms differentially regulate trafficking, expression, and activation of innate immune receptors on macrophages. Completed proof of concept studies convincingly show that IAV-infected mice, when treated with SP-R210 targeted murine mAb P2H10, recover more quickly, have better post-infection lung function, and show better lung histopathology than untreated mice. Our specific objective is to advance the development of humanized-P2H10 mAb to fulfill federal requirements for an IND application by validating its safety, bioactivity, pharmacokinetics, and therapeutic efficacy in humanized FcRn and SP-A pre-clinical models of viral infection.

抽象的 Respana Therapeutics, Inc. 正在开发一种专有的人源化药物并将其商业化针对与炎症相关的发病率和死亡率的单克隆抗体 (mAb) 最初预期的产品是一种可注射的单克隆抗体。校准对呼吸道感染的免疫反应，减轻有害炎症和加速甲型流感病毒 (IAV) 感染后肺部健康的恢复，无论是季节性还是流感大流行是全球危重患者急性肺损伤的主要来源。新证据表明流感合并感染会加剧 SARS-CoV-2 的易感性死亡率增加的感染预示着呼吸系统危重疾病的负担更大在未来几年的后疫情时代。流感等呼吸道感染会引起广泛的免疫系统反应，导致这种炎症反应虽然是对抗病毒所必需的，病毒被清除后仍可在肺部持续存在，这可能导致进一步的发病，包括继发细菌性肺炎、因严重肺损伤住院，甚至为了解决这个问题，Respana 打算开发一种安全、负担得起、可扩展且广泛使用的方法。从高风险开始，可用于改善患者治疗结果的可用产品我们预计 Respana 的产品将减少症状持续时间，以及减少流感后细菌性呼吸道感染和死亡率，从而加强卫生保健系统对抗季节性和大流行性流感的能力。 Respana 对表面活性剂蛋白（SP-A）受体 SP-R210 的创新工作表明，它增加 SP-A 结合病原体的吞噬作用并通过免疫调节细胞因子分泌 SP-A 通过增强调理作用和功能在肺部免疫中发挥重要作用。清除病原体并调节巨噬细胞炎症反应。 Respana 已生成支持生物模型，其中 SP-R210 异构体存在差异调节巨噬细胞上先天免疫受体的运输、表达和激活。已完成的概念验证研究令人信服地表明，感染 IAV 的小鼠在接受 SP-R210靶向鼠单克隆抗体P2H10，恢复更快，感染后肺功能更好功能，并且比未治疗的小鼠表现出更好的肺组织病理学。我们的具体目标是推进人源化 P2H10 mAb 的开发，以满足联邦政府的要求通过验证其安全性、生物活性、药代动力学和人源化 FcRn 和 SP-A 病毒感染临床前模型的治疗效果。