Treatment of Inflammatory Complications of Viral Pneumonia

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.Narrative: Respana Therapeutics is developing a novel and proprietary monoclonal antibody (mAb) targeting the short isoform of surfactant protein A receptor 210 (SP-R210S) for the treatment and/or prevention of inflammatory complications associated with complications of viral pneumonia caused by infections like Influenza A and SARS-CoV-2, the etiologic agent of COVID-19. Respana intends to advance its antibody by demonstrating efficacy of humanized P2H10 mAb in humanized mice and by determining the impact of humanized P2H10 mAb in cytokine responses in human monocytes, monocyte-derived macrophages, and alveolar macrophages. Through this work Respana intends to address an urgent public health need to develop interventions for the prevention and treatment of pulmonary complications due to acute respiratory infection.