Humanized Monoclonal Antibody to Treat Acinetobacter Infections

DESCRIPTIONprovided by applicantNational surveillance data confirm thatof Abaumannii isolates from US intensive care units are extreme drug resistanceXDRfar higher than other pathogensAt leastandcases of XDR Abaumannii infections occur annually in the US and globallyin developed countriesrespectivelyThese infections result inanddeaths and excess healthcare costs of $million and $million in the US and globallyannuallyFurthermorein contrast to other resistant bacteriavirtually no antibiotics are in the pipeline to deal with XDR AbaumanniiNew prevention and treatment strategies are critically neededWe will develop a therapeutic monoclonal antibody to treat Abaumannii infectionsas an adjunct to antibioticsIn a series of pathogenesis studieswe found that Abaumannii virulence was driven by an initial evasion of innate immune mediated clearanceresulting in sustained LPS TLRactivation that drove sepsis syndromeThus enhancement of innate immune mediated clearance was a promising immune therapeutic strategy to improve outcomes from infectionFurthermorepassive immunization with polyclonal immune serum targeting Abaumannii improved survival of infected recipient micevalidating the approachWe have a MAbBioAIMthat binds to the surface of multiple strains of Abaumannii as well as polyclonal immune serumand is nearly completely protective in otherwise fatal models of XDR Abaumannii bacteremic sepsis and aspiration pneumoniathe most common clinical syndromes of Abaumannii infectionDuring phase I of the funded STTR grantwe humanized the MAbIn phase IIwe seek to advance it towards IND filingAimEstablish GMP manufacturing for our candidate MAbsGMP scale up will be established by STC BiologicsThe GMP process will include establishment of a master cell bankcompletion of scale up including an initial GMP like manufacturing run followed by repeat runs and a finalL reactor runas well as stability studiesWe will confirm the in vitro and in vivo activity of the material producedOur highly experienced teamwhich has taken prior companies to IPO and taken drugs through NDA BLAwill manage the vendorAimComplete pre clinical toxicity studies to support an IND applicationToxicity studies have been designed based on FDA guidanceand their execution will be contracted to a qualified vendorWe will hold a pre IND meeting with the FDA to confirm our plans for toxicity studies and the future phase I clinical triaCompletion of pre clinical toxicity studies using GMP like material and will be targeted for yearUpon completion of funding we will be positioned to file an IND that will allow subsequent initiation of a phase I clinical trialThe impact of the MAb once developed will be to markedly improve survival and morbidity from highly lethalXDR and pan drug resistantPDRAbaumannii infectionsThe impact will be particularly great given the absence of new antibiotics in development to treat Abaumannii