# Immunosuppressive Gene Therapy for Ocular Graft vs Host Disease

> **NIH NIH R41** · BEDROCK THERAPEUTICS, INC. · 2021 · $328,150

## Abstract

Abstract
Bedrock Therapeutics, Inc., is developing a method of controlling the immunologic response to allogenic
hematopoietic stem cell transplants (HSCT) with the aim of preventing ocular manifestations of graft vs host
disease (OGvHD), which significantly lower the quality of life of afflicted patients. Over 20,000 patients receive
allogenic HSCTs per year in the US to treat hematological disorders. Of these, an estimated 35-54%, or
approximately 7,000-11,000 patients annually, develop OGvHD. OGvHD is a manifestation of chronic graft vs
host disease. The most common clinical development of OGvHD is dry eye, or keratoconjunctivitis sicca, which
leads to symptoms such as ocular irritation, pain, conjunctival redness, photophobia, and reduced visual acuity.
The dry eye of OGvHD significantly reduces quality of life of HSCT patients and limits their daily activities.
Therapies for OGvHD are largely ineffective (response rate of only 23% at 6 months) and are directed at reducing
symptoms, control of chronic disease, and prevention of tissue damage. Treatments include the use of multiple
daily applications of topical lubricants, calcineurin inhibitors, corticosteroids, autologous serum, in addition to the
use of bandage contact lenses, limbal or amnion membrane transplantation, and/or systemic
immunosuppressants. Despite these treatments the therapeutic response is poor resulting in significantly
reduced visual function and thus a large unmet need for effective treatment of OGvHD. Given the considerable
number of HSCT performed annually in the US and the high incidence of OGvHD there is a critical need
for an effective and practical means of treatment of OGvHD. Bedrock Therapeutics’ strategy for treatment
of OGvHD is based on the immunomodulatory activities of Human Leukocyte Antigen G (HLA-G) proteins, which
are natural proteins that act to prevent maternal rejection of the developing fetus. Our innovative optimized gene
therapy methodology relies on use of adeno-associated virus (AAV) to deliver a novel engineered, HLA-G
based, single chain immunomodulatory (scIM) protein to modulate the immunologic response following
HSCT. To develop a single drug to ease regulatory development, Bedrock has engineered a functional scIM
protein (BDRK#004) whose conformation mimics a beta2-microglubulin (B2M) bound HLA-G dimer complex
whose cDNA can be packaged and delivered using a single AAV8 vector packaged with a self-complementary
genome, which are enhanced >10-fold in transduction efficiency compared to single-strand AAV genomes. This
innovative therapeutic will fulfill the unmet need for a safe and effective single dose drug for OGvHD and
possibly other immune-mediated ocular diseases, such as keratitis, diabetic retinopathy, and age-related macular
degeneration. Bedrock Therapeutics proposes in this phase I application to evaluate its single dose scIM drug
formulation for tolerability and function on primary human T cells (Aim 1) and its efficacy, safety, a...

## Key facts

- **NIH application ID:** 10326039
- **Project number:** 1R41EY033262-01
- **Recipient organization:** BEDROCK THERAPEUTICS, INC.
- **Principal Investigator:** BRIAN C GILGER
- **Activity code:** R41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $328,150
- **Award type:** 1
- **Project period:** 2021-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10326039

## Citation

> US National Institutes of Health, RePORTER application 10326039, Immunosuppressive Gene Therapy for Ocular Graft vs Host Disease (1R41EY033262-01). Retrieved via AI Analytics 2026-08-12 from https://api.ai-analytics.org/grant/nih/10326039. Licensed CC0.

---

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