Oncoimmune Inc — Department of Health and Human Services SBIR Phase I: NHLBI

Description

Project Summary Abstract Infection with Human Immunodeficiency VirusHIVaffects an estimatedmillion worldwideIn the United Statesan estimatedmillion people are infectedAs the access to antiretroviral treatmentARThas increasedthe population of people infected with HIV live longerPatients with viral suppression have increased life expectancyHowevercompare to age matched individual without HIV infectionthey have shortened lifespan with higher rates of comorbiditiesincluding cardiovascular diseasesCVDPersistent inflammation and chronic immune activation caused by HIV and likely ART results in a pro inflammatory state that increases the risk for cardiovascular diseaseThough statins have been used to decrease the effects of hyperlipidemia and inflammation on progression of cardiovascular diseaseuse of statins is underutilized in patients with HIV and falls short of realistic goals for LDL reduction in these high risk patientsHuman CDFcdeveloped by OncoImmuneIncis a recombinant fusion protein composed of the extracellular domain of human CDand the Fc fragment of human IgGCDis expressed in wide range of cell types as an important genetic modifier for several autoimmune diseases and inflammation in response to dangerassociated molecular patternDAMPsOur published data demonstrated that CDFc prevented SIV infected macaques from developing AIDS through induction of inhibitors of inflammation while suppressing promotors for inflammation and autoimmune diseaseOur unpublished data showed that in human CDhematopoietic stem cell reconstituted mouse HIV modelCDFc treatment suppressed production of inflammatory cytokines and reduced activation and loss of CDT cellsIn a Phase I clinical trial in healthy peopleascending doses of CDFcup tomgsignificantly decreased fasting LDL level and induced leptin level in serumThe reduction of fasting LDL by CDFc is confirmed in a Phase IIa clinical trial in patients undergo hematopoietic stem cell transplantation for leukemiaThe results are consistent with the recently discovered connection between inflammation and metabolic disordersBased on these preliminary resultswe propose that treatment with CDFc can fortify negative regulation of innate immune responsesdecrease LDLand thus reduce the risk of cardiovascular disease in HIV patientsTo test this hypothesiswe will evaluatein HIV infected individualsthe safety and efficacy of CDFc in normalizing lipid metabolismreducing T cell activation and viral reservoirSixty four patients aged overwith HIV infection who are virally suppressed on antiretroviral therapy for overyears will be randomized in aratio to receive eithermg of CDFc or placebo forweekswith aweek follow up periodWe will evaluate the safety and tolerability of the drug as well as the changes in LDL and other cellular and soluble inflammatory parameters with CDFc treatment and perform nuclear imaging studies to evaluate changes in myocardial perfusion and function with CDFc treatmentThis clinical trial will enroll an HIV cohort withof African AmericanThe study will uncover critical knowledge in our understanding of the pathogenesis of adverse cardiovascular outcomes in HIVinfected patients and test a novel approach for treating refractory hyperlipidemia Project Narrative Individuals with human immunodeficiency virusHIVinfection undergo antiretroviral treatmentARThave abnormal cholesterol level and increased morbidity due to cardiovascular diseasesOncoImmune is developing a novel biologicCDFcwhich has a novel mechanism of action to reduce serum LDL and chronic inflammationThe proposed Phase I II randomizedplacebo controlledsingle blinded clinical trial clinical trial enrolling HIV cohorts withof African Americanwill assess safety and efficacy of CDFc in reduction of LDL and in controlling cardiovascular disease risks of HIV infected patients