JAN BIOTECH, INC. — Department of Health and Human Services SBIR Phase II: R

Description

PROJECT SUMMARY ABSTRACT Public Health Problem In the U Speople agedyears and older are living with HIV infectionwith approximatelyothers infected but undiagnosedFor most HIV positive individualsavailable treatments can only control HIV infection and delay progression to AIDSHAART has substantial side effects and fails to prevent at leastof patients from developing HIVassociated neurocognitive disordersPre exposure prophylaxisPrEPhas been an exciting development for reduction of HIV acquisition risk and transmissionbut it remains unclear when it is safe to discontinue PrEP treatmentThe ultimate value of the SBIR Phase II project will demonstrate the ability of our technology to predict time to viral load rebound after treatment interruptionwhich remains a critical unmet need in the HIV cure fieldIssues with Current Solutions andampHow Product Meets Unmet Needs Current methods of quantifying the latent reserve include the quantitative viral outgrowth assayQ VOAPCR and RT PCRQ VOA is a time and resource intensive procedure while RT PCR can be used to detect viral RNA tovirus particles per mL and thus reduces the time to result of QVOA and is generally applicable for measuring viral loadbut does not directly detect replication competent latent HIV infected cellsJan Biotech s HIV qLDR offers clear advantages includingdetection of latent reservoir cells in the blood without activationdirect detection of RNA to improve quantitative ability that is lost in other assaysnonenzymatic amplificationwhich relieves the need for RNA purification and its attendant loss of RNAdetection of short segments of RNAproviding effective detection even in the presence of RNase degradative enzymesJan Biotech s qLDR PNA probes enable the use of short sequences complementary to highly conserved regions of the HIVgenomewhich allows for breadth of detection across the highly genetically diverse HIVsubtypesSummary of Approach The Phase I qLDR probe sets differentiated between latent and activated HIV infected cells in peripheral bloodwhich has great promise for accurate measurement of the level of the replication competent latent reservoirThe Phase II Specific Aims will demonstrate the ability of the assay to predict time to viral load rebound after treatment interruption using ex vivo and in vivo samplesTesting will evaluate the utility of the assay as a clinical endpoint to guide treatment interruption decisions and facilitate HIV remission and cure discoveryCollaborators and Unique Resources Jan BiotechIncwith expertise in molecular diagnostic developmentwill consult with Jonathan LiMDMMSc Assistant Professor of MedicineHarvard Medical Schoolin a AIDS Clinical Trials GroupACTGstudyJudith CurrierMDMScVice Chair of the ACTG Network will oversee sample collection from the treatment interruption studyAQ VOA cross validation testing will be performed by Southern Research InstitutePhase II Specific AimsSpecific AimHIV qLDR prediction of replication competent latent reservoirTaskOptimization of qLDR probe setsTaskEx vivo rebound after treatment interruptionTISpecific AimHIV qLDR prediction of HIV rebound during Analytical Treatment InterruptionTaskHIV qLDR prediction of Viral Rebound after Analytical Treatment InterruptionATITaskComparison of HIV qLDR to other assays used in ATI studySpecific AimPreclinical Validation of HIV qLDRTaskValidation of qLDR performance characteristicsTaskQVOA validation Market after Phase II Completion Both Gilead and Bionor are commercially interested in the technology and look forward to results generated from the Phase II and the ACTG studyRegulatory approval will be sought for commercialization Relevance to Public Health The CDC estimates thatmillion people agedyears and older are living with HIV infection in the U Swith approximatelyundiagnosedHighly active anti retroviral therapyHAARTcombination anti retroviral therapycARTwhile keeping HIV infection in remissionfails to eradicate reservoirs of latent HIV infected cells in patientsStrategies targeting this latent reservoir are now being tested in clinical trialsand well validated high throughput assays that quantify this reservoir are urgently needed to facilitate the complete eradication of HIV AIDSThe proposed latent HIV diagnostic has the potential to predict whether an individual can safely end treatment and remain virus free