# Therapeutic inhibition of Fas-mediated retinal cell death and inflammation in dry AMD

> **NIH NIH R42** · ONL THERAPEUTICS, INC. · 2022 · $120,000

## Abstract

PROJECT SUMMARY / ABSTRACT
Age-related macular degeneration (AMD) is the leading, and due to the aging baby boomers, a growing cause
of irreversible vision loss in the United States, and is strongly associated with exposure to cigarette smoke
(CS) and high fat diets (HFD). While effective treatment is available for neovascular AMD, the AREDS II
antioxidant vitamins are the only proven treatment for intermediate dry AMD. Unfortunately, AREDSII is not
effective for early or late dry disease, and in intermediate AMD, it merely slows the progression to advanced
disease. Treatments that target dry AMD will have a huge impact on the afflicted individual and save billions of
health care dollars per year. Impairment of the oxidative stress response, autophagy, mitochondrial function,
and the unfolded protein response, as well as dysregulated innate immunity have been implicated in AMD, and
thus, have been investigated as treatment targets. Ultimately, these abnormalities cause death of retinal
pigment epithelial (RPE) cells and photoreceptors (PR), leading to permanent vision loss. Fas-mediated cell
death is the major mechanism of outer retinal cell loss in many retinal diseases including AMD. With no
therapy to prevent Fas-mediated outer retinal cell death in AMD, a logical treatment strategy is to prevent Fas-
mediated signaling, irrespective of the upstream impairment. ONL Therapeutics, an ophthalmic biotechnology
company developing innovative therapies that prevent retinal cell death to improve visual outcomes for
patients, has demonstrated the effectiveness of Fas inhibition in preventing retinal cell death in an acute model
of AMD. Additionally, a gene therapy that inhibits Fas signaling has been developed and tested in acute and
chronic models of glaucoma, wherein the vector provided significant inner retinal neuroprotection. Due to the
role of Fas in AMD and the effect of Fas inhibition in protecting the retina following ocular stress, this proposal
will examine the effect of the Fas inhibitors in acute and chronic models of atrophic AMD. The project proposed
in this Administrative Supplement will generate key data that will help the company understand recent findings
in a repeat dose rabbit safety study and inform the design of upcoming 6-month GLP repeat dose toxicology
studies to enable the use of ONL1204 in chronic indications, including dry AMD. Successful execution of the
project will support the continued pre-clinical development of the Fas inhibitors for dry AMD and help attract
additional investor interest in the company.

## Key facts

- **NIH application ID:** 10523617
- **Project number:** 3R42EY029625-03S2
- **Recipient organization:** ONL THERAPEUTICS, INC.
- **Principal Investigator:** James T Handa
- **Activity code:** R42 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $120,000
- **Award type:** 3
- **Project period:** 2020-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10523617

## Citation

> US National Institutes of Health, RePORTER application 10523617, Therapeutic inhibition of Fas-mediated retinal cell death and inflammation in dry AMD (3R42EY029625-03S2). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10523617. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*