# A Novel Immunologically Directed Probiotic for the Treatment of Type 1 Diabetes

> **NIH NIH R44** · RISE THERAPEUTICS, LLC · 2022 · $78,120

## Abstract

Project Summary
Our goal is to develop a novel, immunologically-directed L. lactis probiotic-based therapeutic for the treatment
of Type 1 Diabetes (T1D)1. T1D is a devastating disease and there is no curative treatment, with insulin the
only drug available. T1D affects not only glycemic control but also many important aspects of a patient's life,
including emotional well-being, quality of life, working ability, and social interactions25. In addition, T1D patients
present increased risk of developing blindness, kidney failure, stroke, and additional autoimmune disorders.
Therefore, there is an urgent need to develop new cutting-edge strategies for T1D.
The steep rise in the incidence and prevalence of T1D cannot be explained solely by genetic factors
implicating the environment, and specifically the gut microbiome, as culprit for the disease etiopathogenesis62.
The gut microbiome influences multiple host functions, including immunity, and T1D patients present changes
in gut microbiota associated with immunological deregulation and gut leakiness6. Moreover, while fecal
microbiome therapy (FMT) is fraught with difficulties as a general treatment including possible transfer of
pathogenic organisms, controlled clinical studies demonstrate that FMT halts the progress of new onset T1D63.
A promising and potentially safe approach to the treatment of T1D that leverages the body’s own natural
microbiome-associated immune regulatory mechanisms is to use oral, gut localized and targeted therapy to
control specific interactions between commensal microbes and host immune cells lining the gut epithelial layer
that express key immunoregulatory receptors.
R-2487 is an immunologically-directed probiotic consisting of the food-grade, Lactococcus (L.) lactis strain
expressing Colonization Factor Antigen I (CFA/I). R-2487 is a live biotherapeutic product that represents a
novel breakthrough approach for the treatment of T1D by combining the safety of a probiotic with the targeted
functionality of the CFA/I ligand. R-2487 has been showed to diminish T1D in animals9. R-2487 works via
targeted delivery of CFA/I to the intestinal tract where it engages mucosal dendritic cells to drive systemic
upregulation of regulatory T cells (Tregs). The induction of Tregs resets the balance with proinflammatory T
effector cells to reduce inflammatory processes that contribute to autoimmune disease, leading to bystander
tolerance. Since heterogeneous pathogenesis of autoimmune disease, including T1D, poses many challenges
for therapies that target specific antigens for tolerization or a single cell type or cytokine, R-2487-mediated
bystander tolerance induction offers a broader and more impactful mechanism of disease correction.
This application is designed to complete R-2487 IND enabling studies and file an IND with the FDA. The key
aims of this proposal are: 1) finalize in vivo characterization of R-2487; 2) GMP manufacturing of drug
substance and drug product; and 3) submit IND ap...

## Key facts

- **NIH application ID:** 10656851
- **Project number:** 3R44DK134274-01S1
- **Recipient organization:** RISE THERAPEUTICS, LLC
- **Principal Investigator:** Gary Fanger
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $78,120
- **Award type:** 3
- **Project period:** 2022-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10656851

## Citation

> US National Institutes of Health, RePORTER application 10656851, A Novel Immunologically Directed Probiotic for the Treatment of Type 1 Diabetes (3R44DK134274-01S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10656851. Licensed CC0.

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