Development of RespiraClear for targeted mucosal treatment of RSV infections

Project Summary Respiratory Syncytial VirusRSVis the leading cause of viral death in infants and young childrenand a major cause of respiratory illness in immune compromised adults and the elderlyUnfortunatelythere is currently no vaccine or effective therapy available for RSVSynagisa monthly intramuscular injection of the monoclonal antibodymAbpalivizumabis the only FDA approved intervention given to a very small subset of high risk infants as immunoprophylaxisHoweverit is not effective at treating RSVThusfor the tens of thousands of infants hospitalized for RSVonly supportive therapy is availableand morbidity and mortality are substantialInterestinglyRSV spreads in the lung via shedding of virus exclusively into the airwaythusRSV must traverse airway mucusAMbefore infecting neighboring cellsand RSV remains primarily restricted to the airways with little to no systemic viremiaWe believe an RSV specificsafeeffective and topicallydelivered antiviral would provide a powerful option addressing the current gap in pharmacological interventionsMucommune is developing RespiraClear to meet this goalbased on a proprietarymucotrappingmAb technology platform with core claims allowed by the USPTO and exclusively licensed from UNCRespiraClear is a topical mAb treatment based onire engineering RSV binding mAb with elevated expression of a fully human Fc glycosylation that enhances its ability to trap RSV in AM and purges the virus from the airways via natural mucociliary clearance mechanismsandiistably delivering it to the lung airways using a vibrating mesh nebulizerBy concentrating an optimized mAb at the site of infection rather than delivering it systemicallywe expect to enable efficacious and cost effective treatment of RSVwith little risk of adverse side effects due to limited systemic adsorption from pulmonary deliveryOur pilot studies demonstrate that RespiraClear can potently trap RSV in human AMfacilitate rapid elimination of viral particles from the mouse lung airwaysand remain stable when nebulized using a vibrating mesh nebulizerBuilding off these promising resultswe seek to verify in Phase I of this FastTrack proposal that RespiraClear is indeed superior to palivizumab injected intramuscularly in treating RSV infections in cotton ratsto date the most commonly used animal model for RSV infectionsIf successfulPhase II of the project will focus on accelerating the preclinical development of RespiraClearThis includes generating a stable CHO cell line for high yield production of RespiraClearAimpartnering with PARIa leading nebulizer manufacturerto develop a customized vibrating mesh nebulizer for RespiraClearAimAvalidating its delivery performance in a pediatric lung modelAimBand finallyevaluating RespiraClearandapos s efficacy in a neonatal lamb modelAimIf successfulthe proposed work will greatly accelerate the clinical evaluation of RespiraClearThe work will also help pave the way for improvedmolecularly targeted therapies against a broad spectrum of pathogens across all major mucosal surfaces Project Narrative Respiratory Syncytial VirusRSVremains one of the last common viral infections in young children where no vaccine or treatment is currently availableresulting in millions of infections and tens of thousands of hospitalizations each year in the U STo meet the urgent need for an RSV treatmentMucommune is developing RespiraCleara monoclonal antibody against RSV that can be directly delivered to the lung airways and rapidly eliminate RSV from the lung by trapping the virus in mucusIn a proof of concept studythis FastTrack SBIR will confirm whether RespiraClear more effectively treats RSV infection compared to intramuscular injection of palivizumabif successfulthe second phase will enable rapid pre clinical development of RespiraClear