# A Novel Immunological Probiotic for Treating Inflammatory Bowel Disease

> **NIH NIH R44** · RISE THERAPEUTICS, LLC · 2021 · $895,539

## Abstract

Project Summary
The goal of this project is to develop a novel immunologically designed probiotic therapy 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)6. IBD is typically diagnosed in the second or third
decades of life; it is life-long, and there is no cure. Current IBD treatments are systemic and can have serious
side-effects. Novel therapies that are safe and effective, particularly restoring the natural interaction between
the immune system and gut microbiome, are needed and would be life-changing for patients.
Intestinal immune regulatory signals tightly govern healthy gut homeostasis, and their breakdown may result in
IBD38. 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 function39. Lactobacillus (L.) acidophilus, a common bacterial species sold as a probiotic that
‘promotes immune health’, contains unique surface layer proteins (Slps), including SlpA, SlpB, SlpX, and
lipoteichoic acid (LTA)40-43. These Slps interact with pattern recognition receptors (PRR; e.g., C-type lectin
receptors) expressed on innate intestinal cells to fine-tune immunity in steady state and disease conditions42.
Recently, our research team demonstrated that SlpA binding 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 models3. Oral delivery of SlpA reduced inflammatory
cytokines, strengthened the mucosal membrane barrier, and supported a healthier microbiota make-up in
animal models of gut inflammation. In contrast, the effects and protection were not observed in Signr3-/- mice,
suggesting that SlpA interaction with SIGNR3 plays a key protective role in regulating the disease condition3.
Our goal is to develop R-3750, a SlpA-expressing, thymidine-dependent L. lactis strain, as a novel, orally
administered probiotic that functions in IBD to reduce gut inflammation, improve gastrointestinal mucosal
barrier function, and restore the natural microbiome make-up. L. lactis provides two key advantages as a
delivery vehicle for conveying SlpA to the gut; namely, it has already been safely used in human clinical trials
in a genetically manipulated form1, 4 and it does not express any native Slps but can be engineered to
selectively overexpress SlpA. This Phase II SBIR application is intended to build upon success of the Phase I
and advance R-3750 towards clinical testing. The specific Aims are: 1) optimize R-3750 upstream process
development to support manufacturing, 2) create GMP master cell bank...

## Key facts

- **NIH application ID:** 10167703
- **Project number:** 5R44DK117726-03
- **Recipient organization:** RISE THERAPEUTICS, LLC
- **Principal Investigator:** Gary Fanger
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $895,539
- **Award type:** 5
- **Project period:** 2018-07-01 → 2022-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10167703

## Citation

> US National Institutes of Health, RePORTER application 10167703, A Novel Immunological Probiotic for Treating Inflammatory Bowel Disease (5R44DK117726-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10167703. Licensed CC0.

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