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:
- 金额:$ 30万
- 依托单位:
- 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:
- 关键词:2019-nCoVAccelerationAcuteAcute Lung InjuryAcute Respiratory Distress SyndromeAcute respiratory failureAcute respiratory infectionAddressAdhesionsAdvanced DevelopmentAftercareAlveolarAlveolar MacrophagesAnimalsAntibodiesAntiviral AgentsAntiviral resistanceAttenuatedBacterial PneumoniaBiochemicalBiocompatible MaterialsBiological AvailabilityBiological ModelsBlood Chemical AnalysisBody WeightCOVID-19CellsCellular AssayCessation of lifeCritical IllnessDataDevelopmentDiseaseDisease OutbreaksDrug KineticsEffectivenessEtiologyFibrosisGenetic studyHealthcare SystemsHematologyHistopathologyHospitalizationHost DefenseHumanHypoxiaImmuneImmune responseImmunityImmunocompromised HostImmunologic ReceptorsImpairmentIndividualInfectionInflammationInflammatoryInflammatory ResponseInfluenzaInfluenza A Virus, H1N1 SubtypeInfluenza A virusInjectableInterventionLeadLungLung infectionsMediatingMedicalMethodologyMethodsMonoclonal AntibodiesMorbidity - disease rateMusOrganPathogenicityPatient-Focused OutcomesPatientsPeripheralPhagocytosisPharmaceutical PreparationsPharmacologyPhasePlayPre-Clinical ModelPredispositionPreventionPropertyProtein IsoformsProteinsPublic HealthPulmonary InflammationReadinessReagentRecoveryReportingResolutionRespiratory Tract InfectionsRiskRoleSARS-CoV-2 infectionSafetyShippingSourceSurfaceSymptomsTestingTherapeuticTherapeutic Monoclonal AntibodiesTimeTimeLineToxic effectTreatment EfficacyUnited StatesVaccinesViralViral PneumoniaVirusVirus DiseasesWorkairway obstructionbasebiophysical analysisco-infectioncombatcommercializationcytokineexperienceextreme temperaturefightinghigh riskhigh risk populationhumanized monoclonal antibodieshumanized mouseimproved outcomeinfluenza infectioninnovationlung healthlung injurymacrophagemonocytemortalitymouse modelmurine monoclonal antibodyneonatal Fc receptornovelpandemic diseasepandemic influenzapathogenpre-clinicalpreventproduct developmentpulmonary functionresearch clinical testingrespiratoryresponserestorationseasonal influenzasuperinfectionsurfactantsurfactant protein A receptortargeted treatmenttraffickingyoung 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.
摘要
项目成果
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