# Novel Long-Acting Inhibitors of Vascular Endothelial Growth Factor (VEGF) for Treatment of Intraocular Vascular Disorders

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2021 · $481,890

## Abstract

ABSTRACT
Neovascularization is a key feature of ischemic retinal diseases and the wet form of age-related
macular degeneration (AMD), all leading causes of severe vision loss. Vascular endothelial
growth factor (VEGF) inhibitors have transformed the treatment of these disorders. Currently,
three anti-VEGF drugs are widely used in the USA for ophthalmological indications, bevacizumab,
ranibizumab and aflibercept. Millions of patients have been treated with these drugs worldwide.
After five-year treatment with these drugs, about half of neovascular AMD patients had good
vision, i.e. visual acuity 20/40 or better, an outcome that would have been out of reach before
anti-VEGF agents were available. However, in real-life clinical settings, many patients do not
experience the same degree of benefit observed in clinical trials, in part because they receive
fewer anti-VEGF injection. So, there is an urgent need to discover and identify novel long-acting
VEGF inhibitors. We hypothesized that the ability to bind heparan sulfate proteoglycans in the
vitreous may be a strategy to promote intraocular retention, ultimately leading to a reduced burden
of intravitreal injections. We designed a series of VEGF receptor 1 variants and identified some
with strong heparin-binding characteristics and ability to bind to the vitreous. Preliminary data
indicate that some of our variants have longer duration and greater efficacy in animal models of
intraocular neovascularization than current standard of care. Our proposal represents the first
systematic attempt to exploit the functional diversity associated with heparin-affinity of a VEGF
receptor. We anticipate that it will result in the discovery and development of more effective and
durable VEGF inhibitors for intravitreal administration.

## Key facts

- **NIH application ID:** 10134358
- **Project number:** 5R01EY031345-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Napoleone Ferrara
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $481,890
- **Award type:** 5
- **Project period:** 2020-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10134358

## Citation

> US National Institutes of Health, RePORTER application 10134358, Novel Long-Acting Inhibitors of Vascular Endothelial Growth Factor (VEGF) for Treatment of Intraocular Vascular Disorders (5R01EY031345-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10134358. Licensed CC0.

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