# A selective angiogenesis blocker to treat retinopathy of prematurity

> **NIH NIH R24** · BAYLOR COLLEGE OF MEDICINE · 2021 · $2,092,566

## Abstract

Project Summary
Retinopathy of prematurity (ROP) is a leading cause of vision loss in children and is currently treated by laser
therapy or cryotherapy. However, both treatments destroy the peripheral vision to save the central vision with
limited efficacy and do not address the underlying cause of pathological retinal neovascularization. There is no
approved drug therapy for ROP. Vascular endothelial growth factor (VEGF) is critical to vascular and retinal
development in embryos, and anti-VEGF therapy interferes with vasculogenesis and retinogenesis in premature
infants, leading to adverse effects. As a result, VEGF inhibitors are not approved for ROP therapy. To address
this urgent unmet clinical need, we recently discovered secretogranin III (Scg3) as a highly disease-restricted
pro-angiogenic factor that preferentially binds to and stimulates angiogenesis of diseased but not normal vessels.
This is in contrast to VEGF which indiscriminately binds to and induces angiogenesis of both diseased and
normal vessels. Among thousands of quantified endothelial ligands, Scg3 had the highest binding activity ratio
to diseased vs. control vasculature and lowest binding to normal retina. Therefore, Scg3 represents the first
highly disease-selective angiogenic factor. We developed Scg3-neutralizing monoclonal antibodies (mAb) and
demonstrated high efficacy and safety to alleviate ROP in animal models. The safety of anti-Scg3 therapy is also
supported by the normal development of Scg3 knockout mice, whereas VEGF knockout mice are embryonic
lethal with severely defective vasculogenesis. We hypothesize that Scg3-neutralizing antibody represent a new
class of selective angiogenesis blockers to alleviate ROP with high efficacy and minimal side effects on the
developing retina. In Aim 1, we will characterize the pharmacodynamic characteristics of humanized anti-Scg3
antibody (hAb). In Aim 2, we will delineate the unique mechanisms of action of the Scg3 hAb as a selective
angiogenesis blocker. In Aim 3, we will investigate preclinical safety and pharmacokinetics of anti-Scg3 hAb. To
our knowledge, anti-Scg3 antibody is the first selective angiogenesis blocker described to date. Therefore, this
project is to develop not just another novel anti-angiogenic drug, but a founding member of a new class of
selective angiogenesis blockers for targeted therapy. The outcomes of this project will facilitate the discovery
and development of other selective angiogenic factors and their inhibitors. Successful implementation of this
project will lead to a first-in-human clinical trial for this new class of selective blockers. Anti-Scg3
antibody has the potential to become the first approved drug for ROP therapy to save the vision of
thousands of ROP infants each year.

## Key facts

- **NIH application ID:** 10238704
- **Project number:** 7R24EY028764-03
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Wei Li
- **Activity code:** R24 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $2,092,566
- **Award type:** 7
- **Project period:** 2019-02-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10238704

## Citation

> US National Institutes of Health, RePORTER application 10238704, A selective angiogenesis blocker to treat retinopathy of prematurity (7R24EY028764-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10238704. Licensed CC0.

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