# A Novel Immunological-Directed Live Biotherapy Product for Treating Ulcerative Colitis

> **NIH NIH R44** · RISE THERAPEUTICS, LLC · 2024 · $914,660

## Abstract

Project Summary
The goal of this project is to develop a novel immunological-directed Live Biotherapeutic Product (LBP) that
leverages natural microbiome pathways to inhibit gut inflammatory processes for the treatment of inflammatory
bowel disease (IBD). Over 3 million adults in the U.S. suffer from IBD, an umbrella term encompassing two
chronic inflammatory diseases of the gastrointestinal tract: Crohn’s disease (CD) and ulcerative colitis (UC)1.
IBD is typically diagnosed in the second or third decades of life, is life-long, and there is no cure. Current IBD
treatments can have serious side-effects, and patients become refractory. Novel therapies that are safe and
effective, particularly restoring the intestinal membrane barrier, are needed and would be life changing.
Intestinal immune regulatory signals tightly govern healthy gut homeostasis, and their breakdown may result in
IBD39. The human microbiome, harboring trillions of bacteria, is a critical regulator of these mechanisms.
Commensal bacteria function to maintain intestinal epithelial barrier integrity and regulate innate and adaptive
immune cell function40. Surface layer proteins (Slps), including SlpA, SlpB, SlpX, and lipoteichoic acid (LTA)
interact with pattern recognition receptors (PRR) expressed on innate immune intestinal cells to fine immunity
in steady state and diseased conditions41-44. Recently, our research team demonstrated that SlpA is the
predominant anti-inflammatory Slp signal. SlpA binds to the C-type lectin Specific Intracellular adhesion
molecule-3 Grabbing Non-integrin homolog-Related 3 (SIGNR3) receptor expressed on dendritic cells lining
the gut prevents experimentally induced colitis in multiple models15. Oral delivery of SlpA via L. lactis (also
known as R-3750 or R110) reduced inflammatory cytokines, strengthened the mucosal membrane barrier, and
supported a healthier microbiota make-up in animal models of gut inflammation64. Notably, the effects and
protection mediated by SlpA were not observed in Signr3-/- mice, suggesting that SlpA interaction with SIGNR3
plays a key protective role in regulating the disease condition15.
Our goal is to develop R-3750, a SlpA-expressing Lactococcus (L.) lactis strain, as a novel, orally administered
drug that functions as immune therapy to reduce gut inflammation, improve gastrointestinal mucosal barrier
function, and restore the natural microbiome make-up in IBD patients. L. lactis provides two key advantages as
a delivery vehicle for conveying SlpA to the gut: 1) it has already been safely used in human clinical trials in
wild type and genetically manipulated forms16, 45 19 and 2) it does not express any native Slps but can be
engineered to selectively overexpress SlpA. This Fast-Track SBIR application is focused on obtaining human
validation for R-3750 by completing a first-in-human Phase 1 proof-of-concept clinical trial. The Specific Aims
are: 1) prepare and file an IND with the FDA, 2) complete capsule manufacturing t...

## Key facts

- **NIH application ID:** 10894064
- **Project number:** 5R44DK133061-03
- **Recipient organization:** RISE THERAPEUTICS, LLC
- **Principal Investigator:** Gary Fanger
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $914,660
- **Award type:** 5
- **Project period:** 2022-07-05 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10894064

## Citation

> US National Institutes of Health, RePORTER application 10894064, A Novel Immunological-Directed Live Biotherapy Product for Treating Ulcerative Colitis (5R44DK133061-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10894064. Licensed CC0.

---

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