June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
Affinity and Potency of RTH258 (ESBA1008), a Novel Inhibitor of Vascular Endothelial Growth Factor A for the Treatment of Retinal Disorders
Author Affiliations & Notes
  • Julia Tietz
    ESBATech, a Novartis company; Novartis Institutes for BioMedical Research (NIBR), Zurich-Schlieren, Switzerland
  • Gunther Spohn
    ESBATech, a Novartis company; Novartis Institutes for BioMedical Research (NIBR), Zurich-Schlieren, Switzerland
  • Gerhard Schmid
    ESBATech, a Novartis company; Novartis Institutes for BioMedical Research (NIBR), Zurich-Schlieren, Switzerland
  • Juliane Konrad
    ESBATech, a Novartis company; Novartis Institutes for BioMedical Research (NIBR), Zurich-Schlieren, Switzerland
  • Sandra Jampen
    ESBATech, a Novartis company; Novartis Institutes for BioMedical Research (NIBR), Zurich-Schlieren, Switzerland
  • Patrik Maurer
    ESBATech, a Novartis company; Novartis Institutes for BioMedical Research (NIBR), Zurich-Schlieren, Switzerland
  • Anne Schmidt
    ESBATech, a Novartis company; Novartis Institutes for BioMedical Research (NIBR), Zurich-Schlieren, Switzerland
  • Dominik Escher
    ESBATech, a Novartis company; Novartis Institutes for BioMedical Research (NIBR), Zurich-Schlieren, Switzerland
  • Footnotes
    Commercial Relationships Julia Tietz, ESBATech, a Novartis company; Novartis Institutes for BioMedical Research (NIBR), Zurich-Schlieren, Switzerland (E), ESBATech, a Novartis company; Novartis Institutes for BioMedical Research (NIBR), Zurich-Schlieren, Switzerland (E), ESBATech, a Novartis company; Novartis Institutes for BioMedical Research (NIBR), Zurich-Schlieren, Switzerland (E), ESBATech, a Novartis company; Novartis Institutes for BioMedical Research (NIBR), Zurich-Schlieren, Switzerland (E); Gunther Spohn, ESBATech, a Novartis Company (E); Gerhard Schmid, ESBATech, a Novartis Company (E); Juliane Konrad, ESBATech, a Novartis Company (E); Sandra Jampen, ESBATech, a Novartis Company (E), ESBATech, a Novartis Company (E); Patrik Maurer, ESBATech, a Novartis Company (E), ESBATech, a Novartis Company (E); Anne Schmidt, ESBATech, a Novartis Company (E); Dominik Escher, ESBATech, a Novartis Company (E)
  • Footnotes
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Investigative Ophthalmology & Visual Science June 2015, Vol.56, 1501. doi:https://doi.org/
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      Julia Tietz, Gunther Spohn, Gerhard Schmid, Juliane Konrad, Sandra Jampen, Patrik Maurer, Anne Schmidt, Dominik Escher; Affinity and Potency of RTH258 (ESBA1008), a Novel Inhibitor of Vascular Endothelial Growth Factor A for the Treatment of Retinal Disorders. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):1501. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: RTH258 is a humanized monoclonal single-chain Fv (scFv) antibody fragment targeting VEGF-A. In this study, we characterized affinity and in vitro potency of RTH258 in comparison to the VEGF inhibitors bevacizumab, ranibizumab, and aflibercept under standardized conditions.

Methods: The properties of RTH258 and the other VEGF inhibitors were determined and compared under standardized conditions. Binding kinetics to human VEGF-A were evaluated using standardized surface plasmon resonance technology (SPR). Blockade of VEGF binding to its receptor VEGFR-2 was assessed in a highly sensitive competition ELISA. Potency was determined in primary human endothelial cells expressing VEGFR-2.

Results: When compared under standardized conditions, RTH258 exhibited similar high affinity to human VEGF as ranibizumab and superior affinity compared to bevacizumab. RTH258 inhibited binding of VEGF to its receptor and, similarly to other VEGF antagonists, RTH258 potently inhibited VEGF-induced proliferation of primary human endothelial cells.

Conclusions: RTH258 possesses valuable pharmacological properties, namely high affinity to VEGF and a high VEGF neutralizing capacity comparable to the anti-VEGF compounds that are in clinical use for the treatment of retinal disorders. Combined with excellent biophysical properties such as high solubility and stability, up to 6 mg can be administered, which represents a molar excess higher than 10- and 20-fold over aflibercept and ranibizumab clinical doses, respectively. Therefore, RTH258 may confer advantages over currently available therapies, potentially allowing for less frequent dosing resulting in a reduced treatment burden. Further clinical development of RTH258 is ongoing.

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