June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
The Half Maximal Effective Concentration (EC50) of a Novel VEGF-A and Ang-2 Bispecific Protein (RO-634) for Back of the Eye Disease
Author Affiliations & Notes
  • Alina Sinha
    University of Missouri Kansas City School of Medicine, Kansas City, Missouri, United States
  • Jeffrey L Olson
    University of Colorado Health, Aurora, Colorado, United States
  • Anthony Jones
    University of Colorado Health, Aurora, Colorado, United States
  • Josh Morgenstern
    University of Colorado Health, Aurora, Colorado, United States
  • Anne Strong
    University of Colorado Health, Aurora, Colorado, United States
  • Steven Droho
    University of Colorado Health, Aurora, Colorado, United States
  • Shaun Bevers
    University of Colorado Health, Aurora, Colorado, United States
  • Niklaus Mueller
    University of Colorado Health, Aurora, Colorado, United States
  • Michael Huvard
    University of Colorado Health, Aurora, Colorado, United States
  • Li Xu
    Independent Reseach Consultant, California, United States
  • Peter K Kaiser
    Cleveland Clinic Cole Eye Institute, Cleveland, Ohio, United States
  • Arshad M. Khanani
    Sierra Eye Associates, Nevada, United States
    University of Nevada Reno School of Medicine, Reno, Nevada, United States
  • Jeffrey S Heier
    OCB, Boston, Massachusetts, United States
  • John M Kunzeman
    Southern Illinois University School of Medicine, Springfield, Illinois, United States
  • Evan Sembell
    Southern Illinois University School of Medicine, Springfield, Illinois, United States
  • Ramanath Bhandari
    Springfield Clinic Eye Institute, Illinois, United States
  • Footnotes
    Commercial Relationships   Alina Sinha None; Jeffrey Olson None; Anthony Jones None; Josh Morgenstern None; Anne Strong None; Steven Droho None; Shaun Bevers None; Niklaus Mueller None; Michael Huvard None; Li Xu RevOpsis Therapeutics, Protagonist Therapeutics, Code C (Consultant/Contractor); Peter Kaiser AffaMed, Allergan, Bayer, Regeneron, Novartis, Kanghong, RevOpsis, Boerenger Ingelheim, Kodiak, Regeneron, RegenxBio; equity, RevOpsis, Code C (Consultant/Contractor); Arshad Khanani 4DMT, Adverum, Allergan, Genentech, Regeneron, Novartis, Kanghong, RevOpsis, Kodiak, Regeneron, RegenxBio; equity, RevOpsis, Code C (Consultant/Contractor); Jeffrey Heier 2020 Onsite, 4DMT, Abpro, Adverum, Allegro, Allergan, Annexon, Apellis, Asclepix, Aviceda, BVT, DTx, Gemini, Genentech/Roche, Graybug, Gyroscope, iRenix, Iveric, Johnson & Johnson, Kanghong, NGM, Notal Vision, Novartis, Ocular Therapeutix, Ocuphire, OcuTerra, Oriole, Oxurion, Regeneron, Regenxbio, Relay Therapeutics, RetinAI, Retrotope, Roche, Stealth Biotherapeutics, Surrozen, Thea, Unity Bio, Verseon, Clinical Research funding from: Aldeyra, Apellis, Asclepix, Bayer, Genentech, Gyroscope, Iveric, Janssen R&D, Kanghong, Kodiak, NGM, Notal Vision, Novartis, Regeneron, Regenxbio, Stealth, Equity in: Adverum, Aldeyra, Allegro, Aviceda, DTx Pharma, jCyte, Ocular Therapeutix, Vinci, Vitranu, Board of Directors member for: Ocular Therapeutix, Code C (Consultant/Contractor); John Kunzeman None; Evan Sembell None; Ramanath Bhandari Regeneron, Kodiak Biosciences, Owner: RevOpsis Therapeutics, Code C (Consultant/Contractor)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 1316 – F0150. doi:
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      Alina Sinha, Jeffrey L Olson, Anthony Jones, Josh Morgenstern, Anne Strong, Steven Droho, Shaun Bevers, Niklaus Mueller, Michael Huvard, Li Xu, Peter K Kaiser, Arshad M. Khanani, Jeffrey S Heier, John M Kunzeman, Evan Sembell, Ramanath Bhandari; The Half Maximal Effective Concentration (EC50) of a Novel VEGF-A and Ang-2 Bispecific Protein (RO-634) for Back of the Eye Disease. Invest. Ophthalmol. Vis. Sci. 2022;63(7):1316 – F0150.

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

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Abstract

Purpose : To investigate the half maximal effective concentration (EC50) of a novel bispecific protein, RO-634, to Vascular Endothelial Growth Factor-A (VEGF-A) and Angiopoietin-2 (Ang-2) individually versus in tandem. These findings may have important clinical implications for treatment of retinal disease including diabetic macular edema and exudative macular degeneration.

Methods : An Enzyme-linked Immunoassay (ELISA) was utilized to determine the EC50 of the bispecific RO-634 to recombinant human VEGF-A and human Ang-2 analytes independently and in combination. A polyclonal antibody was used to detect when RO-634 bound individually to VEGF-A or Ang-2, while Streptavidin Horseradish Peroxidase (SA-HRP) was used when RO-634 bound both analytes (Figure 1).

Results : The data demonstrate the bispecific RO-634 has an EC50 for solely VEGF-A of 10.04 pM and an EC50 for solely Ang-2 of 136 pM. The bispecific RO-634 demonstrated a lower EC50 to Ang-2 while bound jointly to VEGF-A of 101.9 pM (Figure 2).

Conclusions : Our data suggests EC50 for RO-634 to Ang-2 decreases when the bispecific is also bound to VEGF-A. This synergistic effect could be due to a conformational change that occurs when RO-634 is bound to VEGF-A. Further testing should be done to assess the pharmacokinetics behind the demonstrated synergistic effect.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

 

The binding configuration for the bispecific RO-634 to VEGF-A and Ang-2 test in the ELISA described.

The binding configuration for the bispecific RO-634 to VEGF-A and Ang-2 test in the ELISA described.

 

Comparison of RO-634 binding to the control vs VEGF and Ang-2 vs VEGF-A only vs Ang-2 only. EC50 in this graph is demonstrated using Log [RO-634] in nanomolars (nM).

Comparison of RO-634 binding to the control vs VEGF and Ang-2 vs VEGF-A only vs Ang-2 only. EC50 in this graph is demonstrated using Log [RO-634] in nanomolars (nM).

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