Therapeutic Antibody for CMV

Abstract Human cytomegalovirusHCMVis the major viral cause of medical complications associated with bone marrow and organ transplantationViral transmission from mother to fetus is implicated inof stillbirths andbirth defects annually in the USPassive immunization using human immune globulinHIGhas shown promising activity for both indicationsHIG is a complexvariable product that may cause side effects from off target antibody bindingA monoclonal antibodymAboffers qualitative advantages over HIG including potencysafetyproduction efficiency and quality controlTrellis Bioscience has discovered a high affinity native human mAbTRLagainst the most conserved site on the HCMV viriongB ADSite IThis mAb neutralizedout ofclinical isolates of diverse serotypesIt protected all of the specialized cell types relevant to human pathologyIt was also fully protective in a model of the human placenta grown as tissue explants ex vivoThis published work was completed under a Phase I II SBIR grantA Master Cell Bank has been developed that expresses TRLin CHO cells at a commercially useful levelg Lat theL fermentor scaleNearly all IND enabling analytical work has been completedincluding GLP toxicology in rats and tissue reactivity profilingWe now seek CRP funding for developing manufacturing under GMP and for manufacturing material for Phaseandhuman clinical trialsWe anticipate initiation of a Phasetrial withinmonths after fundingand of a Phasetrial withinmonthsNon grant funding will be used for the actual clinical trial expenses and for manufacturing costs beyond the grant funding levelTo support possible extension from the initial transplant indication to the maternal fetal transmission indicationwe propose a nonclinical experimental and regulatory strategy program in yearof the grant Project NarrativeThis SBIR CRP project will advance the development of TRLa native human therapeutic monoclonal antibody against a highly conserved site on Human CytomegalovirusHCMVgB proteinThe antibody provides broad spectrum protection against clinical HCMV strains which are a leading cause of disease in transplant patients and a key contributor to birth defects when transmitted from mother to developing fetusThe project will supplement other funding to accelerate initiation of clinical trials by supporting the acquisition of services in manufacturing and regulatory consulting