June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
OCU200 (transferrin-tumstatin fusion protein): A potential therapeutic for DME, DR, and wet-AMD
Author Affiliations & Notes
  • Arun K Upadhyay
    R&D, Ocugen, Inc., Malvern, Pennsylvania, United States
  • Rasappa Arumugham
    R&D, Ocugen, Inc., Malvern, Pennsylvania, United States
  • Pratap Naha
    R&D, Ocugen, Inc., Malvern, Pennsylvania, United States
  • Dinesh Singh
    R&D, Ocugen, Inc., Malvern, Pennsylvania, United States
  • Footnotes
    Commercial Relationships   Arun Upadhyay, Ocugen, Inc. (E); Rasappa Arumugham, Ocugen, Inc. (C); Pratap Naha, Ocugen, Inc. (E); Dinesh Singh, Ocugen, Inc. (E)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 992. doi:
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      Arun K Upadhyay, Rasappa Arumugham, Pratap Naha, Dinesh Singh; OCU200 (transferrin-tumstatin fusion protein): A potential therapeutic for DME, DR, and wet-AMD. Invest. Ophthalmol. Vis. Sci. 2021;62(8):992.

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

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Abstract

Purpose : Purpose of this study was to evaluate efficacy of OCU200 in in-vitro and in-vivo models for ocular neovascular diseases. Angiogenesis and neovascularization are hallmarks for diabetic macular edema (DME), diabetic retinopathy (DR), and wet age-related macular degeneration (wet-AMD). Most approved therapeutics target vascular endothelial growth factor (VEGF), a pro-angiogenic factor with neurotrophic and neuroprotective effects. However, these therapies are effective only in about 50% of patients. OCU200 is a fusion protein designed to have improved efficacy in DME, DR, and wet-AMD patients.

Methods : Effect of OCU200 on in-vitro cell proliferation, invasion and tube formation were assessed by MTT assay, scratch assay and endothelial cell culture on basement membrane matrix, respectively. In -vivo efficacy was evaluated in an oxygen-induced retinopathy (OIR) mouse model (age-P12), dosed intravitreally with various doses of OCU200 (2.5, 5.0, and 10 µg/eye) and compared to an approved anti-VEGF positive control (aflibercept, 20 µg/eye). Retinal tissues were collected at P18 age to assess avascular areas (AVAs) and neovascular tufts (NVs) areas of Isolectin GS IB4 immunostained retinal flat mounts. AVA and NVs regression in retina indicate therapeutic benefit of test compound. Quantitative data was analyzed by paired Student’s t test or One-Way ANOVA followed by Dunnett’s or Tukey’s multiple comparisons test.

Results : OCU200 inhibited cell proliferation, cell invasion and tube formation by endothelial cells. In OIR mice, OCU200 significantly reduced avascular areas at low dose (68% reduction, P < 0.05) and high dose (68% reduction, P < 0.05), and significantly reduced neovascular tufts (NVs) at low dose (59% reduction, P < 0.05) and high dose (58% reduction, P < 0.05) compared to vehicle-treated eyes. Aflibercept reduced NVs by 77% (P < 0.01). OCU200 showed comparable activity to aflibercept at 2 to 8-fold lower doses.

Conclusions : OCU200 acts on endothelial cells specifically to decrease cell proliferation, cell invasion, and tube formation. In addition, the in vivo results suggest that OCU200 is efficient in reducing neovascularization and damage to retina in mouse OIR model and has comparable/slightly improved activity to aflibercept. These findings demonstrate OCU200 as a potential therapeutic for the treatment of DME, DR, and wet-AMD.

This is a 2021 ARVO Annual Meeting abstract.

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