# A Novel Immunological-Directed Biotherapy for Treating Rheumatoid Arthritis

> **NIH NIH R44** · RISE THERAPEUTICS, LLC · 2024 · $987,225

## Abstract

Project Summary
Our goal is to develop a novel, immunological-directed L. lactis probiotic-based therapeutic for the treatment 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 immune cells, no therapy can induce long-term disease remission38. 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 immunotherapy 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 and 2) balance the effector cell relationships to prevent relapses of
chronic inflammation.
Originally conceived as a human diarrheal vaccine, we discovered that colonization factor antigen I (CFA/I) from
human enterotoxigenic E. coli is effective at inducing auto-Ag-specific Tregs when administered orally22, 56-58. To
avoid challenges associated with producing large quantities of CFA/I protein and improve the mucosal
pharmacokinetic (PK) and pharmacodynamic (PD) properties of CFA/I following oral administration, we
developed an L. lactis-CFA/I expressing product (referred to as R-2487) and validated its efficacy in multiple
autoimmune models. R-2487 was effective at reducing arthritis symptoms in animal model studies, along with
experimental models of Sjögren’s syndrome, diabetes, and multiple sclerosis17, 30, 59, 60. Prior SBIR and Seed
investment funding and an FDA pre-IND meeting has enabled us to position R-2487 ready for clinical testing.
This Fast Track application is focused on obtaining human validation for R-2487 by completing a first-in-human
Phase 1 RA proof-of-concept clinical trial. The Specific Aims are: 1) finalize R-2487 clinical supply packaging, 2)
prepare and file an IND with the FDA, 3) complete a Phase 1 proof-of-concept clinical trial, 4) analyze patient
samples before/after dosing to evaluate pharmacodynamic changes and biomarkers, 5) perform Phase 2 clinical
manufacturing scale up development to ready R-2487 for larger confirmatory trial.
Successful commercialization of R-2487 will provide a profound medical advancement for treating RA.

## Key facts

- **NIH application ID:** 11076391
- **Project number:** 4R44AG084484-02
- **Recipient organization:** RISE THERAPEUTICS, LLC
- **Principal Investigator:** Gary Fanger
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $987,225
- **Award type:** 4N
- **Project period:** 2023-09-04 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11076391

## Citation

> US National Institutes of Health, RePORTER application 11076391, A Novel Immunological-Directed Biotherapy for Treating Rheumatoid Arthritis (4R44AG084484-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11076391. Licensed CC0.

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