Jericho Sciences, LLC — Department of Health and Human Services SBIR Phase II: 105

Description

Abstract While highly active antiretroviral therapyHAARThas significantly improved the health of individuals infected with human immunodeficiency virusHIVavailable therapeutics largely target virus replication pathways such that treatment interruption results in the rapid resumption of viral replication and decline of immunologic functionEven despite successful therapeutic control of replicationchronic inflammationHIV associated neurocognitive disorderscardiovascular disease and other comorbidities further threaten the health of an estimatedmillion HIV infected people in the U SNew therapeutic strategies capable of longer term virus suppression and reductions in the sources of persistent virus would relieve consequences of daily drug compliance and comorbidities for overmillion HIV infected people globallyJericho Sciencesinvestigational small moleculeFXis proposed to target the highly conserved zinc finger domains of lentiviral nucleocapsidNCproteinsa well established therapeutic target for the treatment of HIVFXhas demonstrated preclinical safety and antiviral efficacy in multiple in vivoex vivo and in vitro models to support continuing translational testingZinc finger domainsZFDsof HIV nucleocapsidNCprotein are highly conserved therapeutic targets shared across all lentivirusesincluding felinesimian and human immunodeficiency virusesFIVSIV and HIVrespectivelyFollowing eight monotherapeutic doses of FXover four weeks in chronically FIV infected catsone of the research models for HIVblood plasma and cerebrospinal fluid viremia remainedbelow corresponding pretreatment levels up toweeks following cessation of treatmentin the absence of observed or measured adverse eventspltnone way ANOVAThese results are unprecedented in FIV infected catsConcurrentlyintegrated provirus in peripheral blood mononuclear cells continued to decrease byfrom the normalized starting virus loadpltnone way ANOVAWhile we have yet to fully elucidate mechanistic implications of the nucleocapsid target profilethe most differentiating feature is the potential long term control of virus production in an apparent systemic reduction of virus replication setpointWe propose here to conduct translational testing of FXin a simian immunodeficiency virus infected nonhuman primateSIV NHPmodel to establish the safety profiletherapeutic efficacyand clinical biomarkers that may implicate this strategic candidate molecule s potential utility toward a cotherapeutic functional eradication of HIV infection in humans