MK-3000, EYE103, F4L5.13, ANT-39, Restoret™ Clinical Multispecific, Trispecific, Biparatopic

June 2023: Clinical testing of AntlerA’s first-in class Norrin/Wnt-agonist antibody initiated through a strategic collaboration and licensing agreement with EyeBio Derived from ANT-Pharm platform, EYE103 is a Norrin/Wnt-agonist clinical antibody molecule developed by EyeBio in close collaboration with AntlerA for treatment of retinopathies F4L5.13 consists of a diabody formed by two identical paratopes recognizing FZD4 fused to the N-terminus of a heterodimeric Fc, and a diabody composed of two distinct paratopes, respectively, recognizing the first two propellers (E1E2; Wnt-1 binding site) and the membrane proximal two propellers (E3E4; Wnt-3 binding site) of LRP5 fused to the C-terminus of the Fc Here, we developed F4L5.13, a tetravalent antibody designed to induce FZD4 and LRP5 proximity in such a way as to trigger βcatenin signaling. Treatment of cultured endothelial cells with F4L5.13 rescued permeability induced by VEGF in part by promoting surface expression of junction proteins. Treatment of Tspan12−/− mice with F4L5.13 restored retinal angiogenesis and barrier function. F4L5.13 treatment also significantly normalized neovascularization in an oxygen-induced retinopathy model revealing a novel therapeutic strategy for diseases characterized by abnormal angiogenesis and/or barrier dysfunction. https://www.embopress.org/doi/full/10.15252/emmm.202113977 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261507/ "There is a significant unmet medical need in several rare pediatric retinopathies including FEVR/Norrie, Coats, and ROP, as there are no approved drugs for their treatment. Our Norrin/Wnt7-mimetic is an important drug candidate for these pediatric patients. Also, it will provide a new treatment modality for macular telangiectasia and diabetic retinopathy, which afflicts over 4 million people in the US alone. The mechanism of action of the drug is supported by strong human and mouse genetics and it acts by restoring signaling fundamental to junctional integrity of vascular blood vessels. We plan to bring this exciting drug to clinical trials rapidly," said Dr. Sekar Seshagiri, CEO of AntlerA Therapeutics.