NAVIGEN, INC. — Department of Health and Human Services SBIR Phase II: NIAID

Description

PROJECT SUMMARYRespiratory syncytial virusRSVis the major cause of severe lower respiratory tract infections in children and infantsaffecting an estimatedmillion people and causing up todeaths worldwide per yearWHOIn the USyoung children andadults are hospitalized annually due to RSV infectionHigh risk adultsthe elderly and patients with chronic heart or lung diseaseexperience the highest RSV attributed mortality in the USdeaths yearcommensurate with the mortality rates of seasonal influenzaRSV costs the US healthcare system billions of dollars annuallyNo vaccines or safe and effective therapeutics for RSV are availablealthough several products are in clinical trialsCurrentlyRSV treatment is mostly limited to supportive carehoweverfor the most acute cases in childrenribavirina broad range antiviral with questionable RSV efficacy and significant safety issuescan be usedUse of Synagispalivizumaba monoclonal antibody that inhibits RSV infection in the lower respiratory tractis limited to the highest risk childrenFurthermoreSynagis is very expensive$$for a standard course of therapy for a premature infantand it only reduces RSV related hospitalizations byThere is an urgent need for new and more cost effective anti RSV prophylactics and therapies that can be applied to both children and adultsDuring Phase I of this awardNavigen employed an innovative strategy to identify a novelproteaseresistant D peptide drug leadCRTwhich targets the RSV entry machineryOur drug discovery platform employs an enantiomeric screening technologymirror image phage displaycoupled with protein designto identify D peptides that bind to a conserved and functionally critical site on the virusandapos s FfusionproteinCRT binds F with pM affinity and prevents it from completing a conformational change required for RSV to enter permissive cellsAs suchit is a potent inhibitor of RSV in vitroWe have successfully validated this platform technology by identifying promising inhibitors for several viruses that share a conserved entry mechanismOur analogous anti HIV D peptideCPTinhibits all major circulating HIVstrainspossesses an extremely high barrier to resistanceand has minimal immunogenicityCPThas demonstrated great potential in preclinical testingincluding initial safety and efficacy studies in rodents and non human primatesOur experience with CPTwill facilitate rapid advancement of CRTIn this three year Phase II applicationwe will determine the breadth of CRT against multiple primary RSV isolatesA and B strainsdetermine its potency in a gold standard animal model of RSV infection using both preventative and therapeutic dosing regimensand complete IND enabling studiesOur ultimate goal is to advance this promising drug candidate to the clinic where it will have a significant worldwide impact as a safe and effective preventative and therapeutic for RSV infection in children and adults PROJECT NARRATIVEHuman respiratory syncytial virusRSVis the most common cause of hospitalization for infants and young childrenreinfections can occur throughout lifeand it is a major cause of morbidity and mortality in the elderlycomparable to fluA partially effective antibody can reduce serious complications when administered prophylacticallyhoweverit is costly and only available to the highest risk infants and children andltmonths oldBecause no vaccine or safe and effective treatment is availableNavigen is advancing its potent anti RSV compound that has the potential to address the considerable unmet need to prevent and treat RSV infections in children and adults