VIROGENOMICS BIODEVELOPMENT, INC. — Department of Health and Human Services STTR Phase II: NIAID

Description

PROJECT SUMMARY ABSTRACT Our recently completed Phaseanimal studies demonstrated the ability of our novel second generation partialp MHC constructDRhMOGto treat acute and chronic EAE with potency comparable to the parent RTLmoleculepDRMOGin matched DRTg mice and in DRnegative mismatched miceHaving met our Phasemilestonesour Phase II application will produce a fully humanized DRhMOGmolecule and assemble preclinical data necessary to support a pre IND meeting with FDAat which critical input will be obtained in order to enable the filing of a Phasesafety and tolerability study in humansThese data will include characterization of the pharmacokineticsPKtoxicokineticsTKand downstream effects of potential anti drug antibodyADAproductionAdditionallythis study will assess as an in vivo biomarker the intrinsic activity of DRhMOGto inhibit peripheral blood mononuclear cellPBMCexpression of CDthe major cellular receptor for macrophage migration inhibitory factorMIFthat has been implicated in MS disease progression both in the literature and in samples from MS subjectsOur proposed studies are patterned after the preclinical development plan that enabled RTLhuman clinical trials and are designed to stage DRhMOGfor cGMP manufacture and formal preclinical studies necessary for a Phaseclinical trial in human subjectsThe clinical protocol to be supported by these preclinical studies will generally follow that used for RTLDouble BlindPlacebo ControlledPhaseDose Escalation Study of the Safety of a Single Dose of RTLin Subjects with Relapsing Remitting or Secondary Progressive Multiple Sclerosiswhich demonstrated that RTLwas safe and well tolerated at doses ltmgg kgDoses of DRhMOGto be infused in the human Phasetrial will be guided by pre IND discussions with FDA and will depend on the minimal effective doseMEDas well as the maximum tolerated doseMTDto be determined for both sexes in this proposalData from our PhaseSTTR has established that a higher dose of DRhMOGis required for inhibiting T cell activation in vitro and for treatment of chronic EAE in females vsmalesthus necessitating establishment of separate MEDs and overlapping efficacy curves to yield a common dose rangeIt is anticipated that these studies will facilitate filing of a successful IND for initiating therapeutic trials with DRhMOGin subjects with MS