Development of CM-SV1, a monoclonal antibody treatment for Sudan Virus

PROJECT SUMMARY The filovirusesfamily Filoviridaecomprising five ebolavirusesa cuevavirusand two Marburg virusesare negative strand RNA viruses that cause severe hemorrhagic fever with up tohuman case fatality rateTheepidemic in Western Africacaused by the Zaire ebolavirusEBOVspecies demonstrated the potential for these viruses to cause dire health emergencies of global scopeand highlighted the need for development of therapeutics and vaccinesSudan virusSUDVBundibugyo virusBDBVand Marburg virusMARVhave all caused large human outbreaks with high case fatality ratesand thus have similar epidemic potentialIn particularwhile SUDVthe subject of this proposal caused thend largest filovirus outbreak to dateno therapy or vaccine is currently availableOur productCM SVis a humanized first in classsingle dosemonoclonal antibodymAbagainst SUDV for use as both a prophylactic and a therapeutic agentthus serving the needs of frontline medical staff and infected personsmAbs represent an attractive therapeutic modality for filoviruses because mAb cocktails or convalescent IgG has been demonstrated to provide post exposure protection of non human primatesFurthermoremAbs are generally well tolerated and have favorable pharmacokinetic and safety profilesGiven the sporadic and unpredictable nature of outbreaksit would be highly advantageous to have mAb therapies against each of the filoviruses ready for rapid deployment as emergency therapeuticsTo datewe have produced CM SVin both HEKand Nbethathasmiatobaccoand have demonstrated efficacy in lethal challenge models in murine and guinea pig models of SUDV infectionThe purpose of this proposal is to first determine developability of CM SVand then to develop CM SVto a technology readiness levelTRLin preparation for investigational new drugINDfilingIn Phase Iwe will engineer the Fc portion CM SVto have improved prophylactic capabilitiesproduce CM SVin an industry standard for manufacturingChinese Hamster ovary cellsdetermine developabilitydemonstrate non inferior efficacy compared to HEK produced CM SVin a murine challenge modeland determine success in engineering enhanced half lifeIn Phase IIwe will determine non inferior efficacy compared to HEK produced CM SVin a guinea pig challenge modeldetermine toxicityprepare and file a pre IND application and conduct a Type B meeting with FDAand finally demonstrate efficacy of CM SVin a non human primate SUDV lethal challenge modelAt the culmination of this program CM SVwill be optimized for cGMP manufacture and IND preparation PROJECT NARRATIVE Filovirusesincluding ebolaviruses and Marburg viruscause a rapidly progressing and fatal hemorrhagic fever and as demonstrated in theWest Africa epidemichave the potential to cause widespread diseaseCurrentlythere are no therapeutic strategies on market to mitigate Sudan virusSUDVone of the five types of ebolavirus that poses a highly lethal risk to communitiesaid workers and civilian populations in the event of a pandemicWe are developing CM SVa first in class single dose monoclonal antibody that can be used both as a therapeutic and a prophylactic treatment in the unfortunate event of a SUDV outbreak