# Developing a novel therapy for diabetic retinopathy

> **NIH NIH R44** · EVERGLADES BIOPHARMA, LLC · 2024 · $981,868

## Abstract

Project Summary
Diabetic retinopathy (DR) is a leading cause of vision loss in working adults, affecting more than 100 million
people worldwide. A breakthrough in DR therapy is the advent and approval of vascular endothelial growth factor
(VEGF) inhibitors as the first pharmacological treatment but with limited efficacy. Additionally, anti-VEGF therapy
indiscriminately inhibits both diseased and healthy vessels as well as neuronal function and may indirectly reduce
the efficacy to improve visual acuity. An unmet clinical need is to develop drug therapies against VEGF-
independent angiogenic factors for alternative or combination therapy to improve efficacy with optimal safety.
We recently discovered a novel disease-restricted pro-angiogenic factor that selectively binds to and stimulates
angiogenesis and vascular leakage of diabetic but not healthy vessels, whereas VEGF indiscriminately induces
angiogenesis and leakage. We further revealed that the new pro-angiogenic factor selectively binds to the DR-
stressed deep retinal vascular plexus with compromised endothelial junctions, but not the relatively healthy
superficial and intermediate retinal plexuses in diabetic mice with intact endothelial junctions. Therefore,
inhibition of this disease-restricted angiogenic factor may selectively target DR-stressed deep retinal plexus,
while sparing the relatively healthy superficial and intermediate vascular plexuses within the same diabetic retina.
To exploit this unique disease-targeted DR therapy, we generated neutralizing monoclonal antibodies and a
related humanized antibody (hAb) against the new angiogenic factor and demonstrated their high efficacy to
alleviate DR leakage in diabetic mice. We confirmed that the hAb stringently targets diseased but not healthy
vessels. More importantly, combination therapy simultaneously targeting VEGF and the new angiogenic factor
with distinct receptor signaling pathways synergistically improved the efficacy to ameliorate DR leakage. The
objective of this project is to complete all required preclinical studies for Investigational New Drug (IND)
application. In Aim 1, we will analyze IND-enabling pharmacokinetic studies and develop formulation and
bioanalytic assays. In Aim 2, we will submit a Pre-IND application to the FDA and seek the agency’s guidance
on relevant requirements for a formal IND application. In Aim 3, we will complete IND-enabling toxicology studies.
Successful implementation of the proposed studies will advance this first-in-class disease-targeted anti-
angiogenic therapy to IND application and clinical trials.

## Key facts

- **NIH application ID:** 10922002
- **Project number:** 2R44EY027665-02A1
- **Recipient organization:** EVERGLADES BIOPHARMA, LLC
- **Principal Investigator:** Wei Li
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $981,868
- **Award type:** 2
- **Project period:** 2017-09-30 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10922002

## Citation

> US National Institutes of Health, RePORTER application 10922002, Developing a novel therapy for diabetic retinopathy (2R44EY027665-02A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10922002. Licensed CC0.

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