# Anti-angiogenic gene therapy of ocular vascular diseases

> **NIH NIH R43** · EVERGLADES BIOPHARMA, LLC · 2020 · $225,000

## Abstract

Project Summary
Neovascular age-related macular degeneration (nAMD) with choroidal neovascularization (CNV) is a leading
cause of blindness in the elderly in developed countries. All currently approved anti-angiogenic drugs for nAMD,
such as ranibizumab and aflibercept, target vascular endothelial growth factor (VEGF) but have limited
therapeutic efficacy. Patients with poor response to one anti-VEGF drug are often switched to another VEGF
inhibitors due to the lack of approved drugs against other angiogenic pathways. Furthermore, repeated
intravitreal injections in anti-VEGF-resistant patients may increase the risk of injection-related ocular
complications. A new strategy is to improve the efficacy is to develop novel therapies against VEGF-independent
angiogenic factors for alternative or combination therapy. Another strategy to circumvent repetitive intravitreal
injections is to develop anti-angiogenesis gene therapy that requires only a single injection for long-lasting
efficacy. However, current approach of anti-VEGF gene therapy yielded marginal treatment benefit to
complement ranibizumab, possibly because of their similar mechanisms of action. To circumvent these problems,
we recently discovered a novel angiogenic factor with high disease selectivity and VEGF-independent
mechanisms. We developed a monoclonal antibody (mAb) against this target and demonstrated its high efficacy
for anti-angiogenic therapy of CNV. This project is to develop anti-angiogenesis gene therapy against this novel
target using an adeno-associated viral (AAV) vector.
 In Aim 1, we will generate AAV vectors to express an antibody Fab fragments against the novel target
and VEGF under the direction of constitutive or hypoxia-inducible promoters and characterize expression,
binding and neutralizing activity of Fab fragments in vitro. In Aim 2, we will determine the therapeutic efficacy
and safety of these AAV vectors to alleviate CNV in animal models. Additionally, we will investigate combination
gene therapy by simultaneously targeting both factors in the same mouse models to define possible synergy and
efficacy improvement. Successful implementation of this project will lead to a novel anti-angiogenesis gene
therapy that will improve treatment efficacy of CNV and reduce the requirement for monthly intravitreal injection
of anti-VEGF protein drugs.

## Key facts

- **NIH application ID:** 9909566
- **Project number:** 1R43EY031238-01
- **Recipient organization:** EVERGLADES BIOPHARMA, LLC
- **Principal Investigator:** Wei Li
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $225,000
- **Award type:** 1
- **Project period:** 2020-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9909566

## Citation

> US National Institutes of Health, RePORTER application 9909566, Anti-angiogenic gene therapy of ocular vascular diseases (1R43EY031238-01). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/9909566. Licensed CC0.

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