July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Activity of anti-Tissue Factor fusion protein ICON-1 in a swine model of choroidal neovascularization
Author Affiliations & Notes
  • William Greene
    Iconic Therapeutics, Inc., South San Francisco, California, United States
  • Grazia Spiga
    Powered Research, LLC, Research Triangle Park, North Carolina, United States
  • Brian C Gilger
    North Carolina State University, Raleigh, North Carolina, United States
  • David Culp
    Powered Research, LLC, Research Triangle Park, North Carolina, United States
  • Thi-Sau Migone
    Iconic Therapeutics, Inc., South San Francisco, California, United States
  • Footnotes
    Commercial Relationships   William Greene, Iconic Therapeutics, Inc. (E), Iconic Therapeutics, Inc. (P), Iconic Therapeutics, Inc. (R); Grazia Spiga, None; Brian Gilger, None; David Culp, None; Thi-Sau Migone, Iconic Therapeutics, Inc. (E), Iconic Therapeutics, Inc. (P)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 225. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      William Greene, Grazia Spiga, Brian C Gilger, David Culp, Thi-Sau Migone; Activity of anti-Tissue Factor fusion protein ICON-1 in a swine model of choroidal neovascularization. Invest. Ophthalmol. Vis. Sci. 2018;59(9):225.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : Immuno conjugate-1 (ICON-1) is a recombinant fusion protein targeting Tissue Factor (TF) was well tolerated and biologically active in a Phase II study in patients with wet age related macular degeneration. The objectives of the study were: a) to evaluate the swine laser-induced choroidal neovascularization (CNV) model for the presence of TF in the lesions and b) to evaluate the efficacy of ICON-1 in reducing lesion size and neovascularization.

Methods : 10-12 old week animals (Swine/Hampshire Cross) underwent bilateral laser to create approximately 6 single laser spots in each eye. The presence of TF mRNA in the lesions was determined in eyes enucleated from control animals 14 days post laser treatment by in situ hybridization (RNAScope, ACDBio). For efficacy assessments, ICON-1 at 300μg, 600μg and 900μg was administered intravitreally on Day 7 post-laser treatment. Fluorescein Angiography (FA) to determine lesion size was performed on day 7 (baseline), day 10 and day 14. Eyes were enucleated on Day 14 and retinal flat mounts analyzed for isolectin IB4 signal to quantify newly formed vessels.

Results : Higher levels of TFmRNA in the laser-induced lesions compared to non affected retina were observed. ICON-1 administration was well tolerated with no dose related ocular toxicities and no systemic effects. A dose-dependent reduction in lesion fluorescence, measured by FA, was observed in ICON-1 treated animals at Day 14, with the largest decrease in lesion fluorescence in the 900μg group compared to the vehicle-treated group. Reduced neovascularization, assessed by mean isolectin IB4 area on the flat mounts, correlated with lesion fluorescence data from the FA measurements.

Conclusions : The swine laser-induced choroidal neovascularization model is an appropriate model to evaluate the efficacy of a therapeutic agent that targets TF. ICON-1 administration resulted in a dose-dependent reduction in lesion fluorescence and neovascularization in a swine laser-induced model of CNV. Data from additional studies, comparing efficacy in animal models of ICON-1 to anti-VEGF agents and evaluating combination regimens will also be discussed.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×