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While intravitreal anti\u2010VEGF therapies remain the standard of care, they necessitate frequent injections, posing risks such as endophthalmitis and elevated intraocular pressure, alongside economic and adherence challenges. Here, we present Pene\/LQ015, a novel eye drop formulation comprising the anti\u2010VEGFA nanobody (LQ015) and a proprietary penetratin analog for noninvasive delivery. LQ015 demonstrates superior VEGF\u2010blocking activity, broad binding specificity across species, and robust stability and scalability using a yeast expression system. Topical administration of Pene\/LQ015 achieved effective retinal\u2010choroid complex drug levels and suppressed neovascularization in preclinical models. Notably, in the cynomolgus monkey laser\u2010induced choroidal neovascularization model, 30 days of continuous topical application significantly reduced neovascularization and vascular leakage, with excellent safety and tolerability. These findings highlight Pene\/LQ015's potential as a game\u2010changer in treating neovascular eye diseases. It offers a groundbreaking, noninvasive alternative to intravitreal injections, addressing key limitations of current therapies by enabling continuous dosing, improving patient adherence, and reducing treatment burden. These findings underscore its potential to transform the management of neovascular retinal and choroidal diseases, with promising implications for clinical application.<\/jats:p>","DOI":"10.1002\/advs.202504660","type":"journal-article","created":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T17:23:36Z","timestamp":1761067416000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Continuous Suppression of Pathological Retinal and Choroidal Neovascularization in Cynomolgus Monkeys via Noninvasive Ophthalmic Delivery of a Novel Anti\u2010VEGFA Nanobody and Proprietary Penetratin Analog Formulation"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8625-5367","authenticated-orcid":false,"given":"Chong","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Shanghai General Hospital, School of Medicine, National Clinical Research Center for Eye Diseases, Shanghai Key Laboratory of Ocular Fundus Diseases Shanghai Jiao Tong University  Shanghai 200080 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Zhu","sequence":"additional","affiliation":[{"name":"Shanghai Novamab Biopharmaceuticals Co., Ltd.  Shanghai 201315 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingyan","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics School of Pharmacy Key Laboratory of Smart Drug Delivery (Fudan University) Ministry of Education National Key Laboratory of Advanced Drug Formulations for Overcoming Delivery Barriers Fudan University  Shanghai 201203 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kangjia","family":"Lv","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Shanghai General Hospital, School of Medicine, National Clinical Research Center for Eye Diseases, Shanghai Key Laboratory of Ocular Fundus Diseases Shanghai Jiao Tong University  Shanghai 200080 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuan","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics School of Pharmacy Key Laboratory of Smart Drug Delivery (Fudan University) Ministry of Education National Key Laboratory of Advanced Drug Formulations for Overcoming Delivery Barriers Fudan University  Shanghai 201203 China"},{"name":"Eye Institute and Department of Ophthalmology, Eye and ENT Hospital Fudan University  Shanghai 200031 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuchen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Shanghai General Hospital, School of Medicine, National Clinical Research Center for Eye Diseases, Shanghai Key Laboratory of Ocular Fundus Diseases Shanghai Jiao Tong University  Shanghai 200080 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoliang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Shanghai General Hospital, School of Medicine, National Clinical Research Center for Eye Diseases, Shanghai Key Laboratory of Ocular Fundus Diseases Shanghai Jiao Tong University  Shanghai 200080 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinming","family":"Qi","sequence":"additional","affiliation":[{"name":"Center for Drug Safety Evaluation and Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica Chinese Academy of Sciences  Shanghai 201203 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin TK","family":"Lee","sequence":"additional","affiliation":[{"name":"Alephoson Biopharmaceuticals Limited  Hong Kong SAR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yakun","family":"Wan","sequence":"additional","affiliation":[{"name":"Shanghai Novamab Biopharmaceuticals Co., Ltd.  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