# A Novel Immunologically Enhanced Probiotic for Treating Rheumatoid Arthritis

> **NIH NIH R44** · RISE THERAPEUTICS, LLC · 2022 · $1,000,000

## Abstract

Project Summary
Our goal is to commercialize R-2487 as a novel, orally administered therapy for long-term disease remission of
rheumatoid arthritis (RA). RA is a chronic, systemic inflammatory disorder affecting up to 1% of the US
population1, 2. While many organs are affected in RA, the synovial joints are primarily afflicted with debilitating
inflammation. Approximately half of all RA patients become disabled as the disease progresses.
Treatment of RA remains a significant unmet medical need. Despite highly effective therapies targeting
cytokines and T-B interactions, no therapy can induce long-term disease remission34. TNF-α antagonists can
effectively diminish inflammation and attenuate destruction of cartilage and bone7-10. However, some patients
either fail to respond to, or relapse with, anti-TNF therapy. Prolonged treatment can make patients susceptible
to cancer and opportunistic infections11-14. Moreover, many current treatments for RA, no matter how effective,
consign patients to a lifetime of costly biologic therapies with attendant risks for iatrogenic complications. For
these reasons, we are developing an oral immunotherapeutic that regulates auto-Ag-specific regulatory T cells
(Tregs) to provide bystander tolerance. The two main goals of this approach are: 1) to “switch off” the immune
response against the host’s own tissues in an enduring manner and 2) maximally balance the relationships
between effector cells of different lineages to prevent relapses of chronic inflammation. Such an approach will
provide patients long-term remission and increased safety without systemic immunosuppression.
Originally conceived as a human diarrheal vaccine, we found that colonization factor antigen I (CFA/I) from
human enterotoxigenic E. coli (ETEC) is effective at inducing auto-Ag-specific T regulatory cells18, 22, 54, 55, 56.
CFA/I administered orally as purified protein or delivered via an L. lactis or Salmonella bacterial vector was
effective at preventing and treating multiple experimental models for arthritis16, 18, 33, 57, as well as models for
Sjogren’s syndrome, diabetes, and multiple sclerosis17, 58, 59. To avoid challenges associated with producing
sufficient quantities of recombinant CFA/I and to improve the mucosal PK/PD properties of CFA/I following oral
administration, we successfully developed a new L. lactis strain (referred to as R-2487) that expresses
functional CFA/I from a genome-integrated expression operon. We also validated that R-2487 possesses the
important key design features for a viable biotherapeutic candidate including functionality on human cells.
Now that we have met with the FDA in the context of a pre-IND meeting to finalize our product development
strategy, this Phase II SBIR application is intended to build upon our success and advance R-2487 towards the
IND filing stage. The objectives are: 1) produce sufficient quantities of R-2487 to support in vivo development,
2) develop PK assays to measure R-2487 and CFA/...

## Key facts

- **NIH application ID:** 10357904
- **Project number:** 5R44AI157031-02
- **Recipient organization:** RISE THERAPEUTICS, LLC
- **Principal Investigator:** Gary Fanger
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,000,000
- **Award type:** 5
- **Project period:** 2021-02-23 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10357904

## Citation

> US National Institutes of Health, RePORTER application 10357904, A Novel Immunologically Enhanced Probiotic for Treating Rheumatoid Arthritis (5R44AI157031-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10357904. Licensed CC0.

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