Bispecific VEGF-A and Angiopoietin-2 Antagonist RO-101 Preclinical Efficacy in Model of Neovascular Eye Disease.

Autor:	Xu L; Independent Research Consultant, Contrator for RevOpsis Therapeutics, Inc., San Carlos, California., Prentice JR; Springfield Clinic Eye Institute, Springfield, Illinois., Velez-Montoya R; Retina Department. Asociacion para Evitar la Ceguera en Mexico IAP, Mexico City, Mexico., Sinha A; University of Missouri-Kansas City School of Medicine, Kansas City, Missouri., Barakat MR; Retinal Consultants of Arizona, and University of Arizona College of Medicine, Phoenix, Arizona., Gupta A; Vanderbilt School of Medicine, Nashville, Tennessee., Lowenthal R; Springfield Clinic Eye Institute, Springfield, Illinois., Khanani AM; Sierra Eye Associates, and University of Nevada, Reno School of Medicine, Reno, Nevada., Kaiser PK; Cole Eye Institute, Cleveland, Ohio., Heier JS; Ophthalmic Consultants of Boston, Boston, Massachusetts., Jones A; Sue Anschutz Rodgers Eye Center, University of Colorado, Aurora, Colorado., Morgenstern JL; Sue Anschutz Rodgers Eye Center, University of Colorado, Aurora, Colorado., Strong Caldwell A; Sue Anschutz Rodgers Eye Center, University of Colorado, Aurora, Colorado., Mueller N; Sue Anschutz Rodgers Eye Center, University of Colorado, Aurora, Colorado., Quiroz-Mercado H; Retina Department. Asociacion para Evitar la Ceguera en Mexico IAP, Mexico City, Mexico., Huvard M; University of Michigan Kellogg Eye Center, Ann Arbor, Michigan., Olson JL; Sue Anschutz Rodgers Eye Center, University of Colorado, Aurora, Colorado., Bhatt R; Independent Research Consultant, Contrator for RevOpsis Therapeutics, Inc., San Carlos, California., Bhandari R; Springfield Clinic Eye Institute, Springfield, Illinois.
Jazyk:	angličtina
Zdroj:	Ophthalmology science [Ophthalmol Sci] 2024 Jan 18; Vol. 4 (4), pp. 100467. Date of Electronic Publication: 2024 Jan 18 (Print Publication: 2024).
DOI:	10.1016/j.xops.2024.100467
Abstrakt:	Objective: To investigate preclinical data regarding the efficacy and biocompatibility of a bispecific protein, RO-101, with effects on VEGF-A and angiopoietin-2 (Ang-2) for use in retinal diseases. Design: Experimental study. Subjects: Brown Norway rats and New Zealand White Cross rabbits. Methods: Preclinical study data of RO-101 in terms of target-specific enzyme-linked immunosorbent assay binding affinity to VEGF-A and Ang-2, vitreous half-life, inhibition of target-receptor interaction, laser choroidal neovascular membrane animal model, human umbilical vein endothelial cell migration, and biocompatibility was obtained. Where applicable, study data were compared with other anti-VEGF agents. Main Outcome Measures: Binding affinity, half-life, biocompatibility, and efficacy of RO-101. Neovascularization prevention by RO-101. Results: RO-101 demonstrated a strong binding affinity for VEGF-A and Ang-2 and in vitro was able to inhibit binding to the receptor with higher affinity than faricimab. The half-life of RO-101 is comparable to or longer than current VEGF inhibitors used in retinal disease. RO-101 was found to be biocompatible with retinal tissue in Brown Norway rats. RO-101 was as effective or more effective than current anti-VEGF therapeutics in causing regression of neovascular growth in vivo. Conclusions: RO-101 is a promising candidate for use in retinal diseases. In preclinical models, RO-101 demonstrated similar or higher regression of neovascular growth to current anti-VEGF therapeutics with comparable or longer half-life. It also demonstrates a strong binding affinity for VEGF-A and Ang-2. It also was shown to be biocompatible with retinal tissue in animal studies, indicating potential compatibility for use in humans. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article. (© 2024 by the American Academy of Ophthalmology.)
Databáze:	MEDLINE
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