# Multi-specific long-acting antibodies for the treatment of retinal neovascular diseases

> **NIH NIH R44** · ABZYME THERAPEUTICS, LLC · 2024 · $831,927

## Abstract

ABSTRACT. Retinal neovascular diseases including neovascular age-related macular degeneration, diabetic
macular edema and retinal vein occlusion are the most vision-threatening diseases in the working-age population
in the developed world. Therapies targeting vascular endothelial growth factor (VEGF) delay the development
of neovascularization in some, but not all, patients, implicating additional factor(s) in retinal neovascular
pathogenesis. In addition, the frequent intraocular injection is a significant burden for both patients and
physicians entailing a small risk of endophthalmitis, uveitis, vitreous hemorrhage and other complications. Thus,
there is much needed retinal neovascular disease treatment that can be delivered less frequently and yet provide
the same or better vision than current anti-VEGF therapies.
Phase I has been completed. We have successfully obtained a panel of potent, single domain modular antibodies
(nanobodies) against VEGF and CD147, the latter is a potent angiogenic factor and an inducer of matrix
metalloproteinase synthesis and also reported to have high levels in the vitreous of retinal neovascular disease
patients. The functional activities of VEGF and CD147 antibodies have been characterized in vitro including the
assessment of their anti-angiogenic activities in tube formation assays. Using a 12-mer phage display peptide
library we have isolated three unique peptides that binds to hyaluronan, a major macromolecular component of
the eye’ vitreous. Recombinant VHH antibodies (single variable domain on a heavy chain [VHH] antibodies, also
referred to as nanobodies) fused with hyaluronan-binding peptides shown extended retainment in a 3-D
hyaluronic gel. In addition to anti-VEGF and anti-CD147 nanobodies, we also successfully generated potent
antibodies against three targets related to eye diseases. Phase II will be performed in collaboration with Dr.
Rohrer’s group at Medical University of South Carolina: the anti-neovascularization activity and in-vivo half-life
of selected antibody drug candidates targeting VEGF and CD147 will be characterized, validated in animal
models and humanized pursuing the IND application.

## Key facts

- **NIH application ID:** 10819656
- **Project number:** 2R44EY030821-02
- **Recipient organization:** ABZYME THERAPEUTICS, LLC
- **Principal Investigator:** Hiep T Tran
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $831,927
- **Award type:** 2
- **Project period:** 2019-09-01 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10819656

## Citation

> US National Institutes of Health, RePORTER application 10819656, Multi-specific long-acting antibodies for the treatment of retinal neovascular diseases (2R44EY030821-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10819656. Licensed CC0.

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