Multi-specific long-acting antibodies for the treatment of retinal neovascular diseases

ABSTRACTRetinal neovascular diseases including neovascular age related macular degenerationdiabetic macular edema and retinal vein occlusion are the most vision threatening diseases among the working age population in the developed worldTherapies targeting vascular endothelial growth factorVEGFdelay the development of neovascularization in some but not all patientsimplicating additional factor sin retinal neovascular pathogenesisIn additionthese therapies require frequent intraocular injections representing a significant burden for both patients and physicians and entail a small risk of endophthalmitisuveitisvitreous hemorrhage and other complicationsThusthere is much needed a retinal neovascular disease treatment that can be delivered less frequently and yet provide the same or better vision protection than current anti VEGF therapiesAbzyme Therapeutics LLC recently has isolated several potent single domain modular antibodies against VEGF and CDthe latter being a potent angiogenic factor and an inducer of matrix metalloproteinase synthesis and also reported to be present at high levels in the vitreous humor of retinal neovascular patientsUsing these antibodies in combination with a single domain antibody that binds to hyaluronana major macromolecular component of the eyeandapos s vitreous compartmentwe propose to develop a novel long acting multi specific antibody capable of simultaneously inhibiting both VEGF and CDfor retinal neovascular disease treatmentIn Phase Ia panel of multi specific antibodies will be producedand their anti angiogenic inhibition activity will be validatedIn Phase IIthe anti neovascularization activity and in vivo half life of selected antibody drug candidates will be characterizedvalidated in animal models and humanized in preparation for IND submission NARRATIVEAs a result of this projecta novel multi specific antibody for treatment of retinal neovascular diseases will be producedMulti target long acting therapy will represent a major improvement in comparison with the current anti VEGF monospecific treatment as it covers a broader spectrum of retinal neovascular disease patients with less frequent dosing