June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Preclinical Animal Model for Functional Biocompatibility of a Novel VEGF and Ang-2 Bispecific Protein (RO-634) Using ERG Analysis
Author Affiliations & Notes
  • Nikhil Gupta
    Glenwood High School, Chatham, Illinois, United States
  • Jeffrey L Olson
    Sue Anschutz Rodgers Eye Center, University of Colorado, Aurora, Colorado, United States
  • Anthony Jones
    Sue Anschutz Rodgers Eye Center, University of Colorado, Aurora, Colorado, United States
  • Josh Morgenstern
    Sue Anschutz Rodgers Eye Center, University of Colorado, Aurora, Colorado, United States
  • Anne Strong
    Sue Anschutz Rodgers Eye Center, University of Colorado, Aurora, Colorado, United States
  • Steven Droho
    Sue Anschutz Rodgers Eye Center, University of Colorado, Aurora, Colorado, United States
  • Shaun Bevers
    Structural Biology and Biochemistry, University of Colorado, Aurora, Colorado, United States
  • Niklaus Mueller
    Sue Anschutz Rodgers Eye Center, University of Colorado, Aurora, Colorado, United States
  • Michael Huvard
    Sue Anschutz Rodgers Eye Center, University of Colorado, Aurora, Colorado, United States
  • Li Xu
    Independent Research Consultant, California, United States
  • Peter K Kaiser
    Cleveland Clinic Cole Eye Institute, Cleveland, Ohio, United States
  • Arshad M. Khanani
    Sierra Eye Associates, Reno, Nevada, United States
    University of Nevada, Reno School of Medicine, Reno, Nevada, United States
  • Jeffrey S Heier
    OCB, Boston, Massachusetts, United States
  • Alina Sinha
    University of Missouri Kansas City School of Medicine, Kansas City, Missouri, United States
  • Evan Sembell
    Southern Illinois University School of Medicine, Springfield, Illinois, United States
  • Ramanath Bhandari
    Springfield Clinic Eye Institute, Springfield, Illinois, United States
  • Footnotes
    Commercial Relationships   Nikhil Gupta None; Jeffrey Olson RevOpsis Therapeutics, 2C Tech, Code O (Owner); 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 Consultant, AffaMed, Allergan, Bayer, Novartis, Kanghong, RevOpsis, Boerenger Ingelheim, Kodiak, Regeneron, RegenxBio, Code C (Consultant/Contractor), RevOpsis, Code F (Financial Support); Arshad Khanani 4DMT, Adverum, Allergan, Genentech, Regeneron, Novartis, Kanghong, RevOpsis, Kodiak, RegenxBio, Code C (Consultant/Contractor), RevOpsis, Code F (Financial Support); 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, Code C (Consultant/Contractor), Aldeyra, Apellis, Asclepix, Bayer, Genentech, Gyroscope, Iveric, Janssen R&D, Kanghong, Kodiak, NGM, Notal Vision, Novartis, Regeneron, Regenxbio, Stealth, Code F (Financial Support), Adverum, Aldeyra, Allegro, Aviceda, DTx Pharma, jCyte, Ocular Therapeutix, Vinci, Vitranu, Code I (Personal Financial Interest), Board of Directors member for Ocular Therapeutix, Code S (non-remunerative); Alina Sinha None; Evan Sembell None; Ramanath Bhandari Regeneron, Kodiak Biosciences, Code C (Consultant/Contractor), RevOpsis Therapeutics, Code O (Owner)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 286 – F0089. doi:
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    • Get Citation

      Nikhil Gupta, 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, Alina Sinha, Evan Sembell, Ramanath Bhandari; Preclinical Animal Model for Functional Biocompatibility of a Novel VEGF and Ang-2 Bispecific Protein (RO-634) Using ERG Analysis. Invest. Ophthalmol. Vis. Sci. 2022;63(7):286 – F0089.

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

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Abstract

Purpose : To evaluate the in vivo ocular biocompatibility of a novel intravitreal bispecific protein, RO-634, designed to target Vascular Endothelial Growth Factor-A (VEGF-A) and Angiopoietin-2 (Ang-2) using electroretinogram (ERG).

Methods : All experiments were performed in accordance with the ARVO statement for Use of Animals in Ophthalmic and Vision Research. Five Brown Norway rats received intravitreal injections of RO-634 in the right eye and balanced saline solution (BSS) in the left eye to evaluate for possible retinal toxicity. One month after intravitreal injection, ERGs were performed to assess potential damage to the retina. Animals were dark-adapted overnight prior to the ERG. ERGs were performed on the Celeris device (Diagnosys LLC, Lowell, MA). The test consisted of flash stimuli at 0.01, 0.1, 1.0, and 3.0 cd-s/m2. Student Paired T-test was used for statistical comparison of the amplitude and peak times between the control and experimental eye at each level of stimuli.

Results : RO-634 was well tolerated in brown Norway rats, demonstrating biocompatibility. ERG analysis of scotopic and photopic light response showed cone and rod functional activity with no statistically significant difference in the A and B wave amplitudes and peak times between the control and the experimental eye. Figure 1 is an illustration of similar ERG response in the experiment and control arm at flash stimuli of 3.0 cd-s/m2.

Conclusions : In this preclinical animal study, the novel bispecific, RO-634, showed physiologic ocular compatibility as measured by ERG. Future studies are needed to evaluate the clinical potential of this novel and promising agent for treatment of back of the eye disease.

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

 

Graph showing ERG with similar A and B wave amplitudes and response times between the experimental and control eyes at 3.0 cd-s/m2.

Graph showing ERG with similar A and B wave amplitudes and response times between the experimental and control eyes at 3.0 cd-s/m2.

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