Treatment of Inflammatory Complications of Viral Pneumonia

病毒性肺炎炎症并发症的治疗

• 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
• 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

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.

摘要