# R-5280, A Novel Modified Superior Resistant Starch Therapy for Type 1 Diabetes

> **NIH NIH R44** · RISE THERAPEUTICS, LLC · 2024 · $995,869

## Abstract

Project Summary
Type 1 diabetes (T1D) is a devastating disease and there is no current curative treatment, with insulin being
the only product 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 interactions29. In addition, persons
with T1D present increased risk of developing other serious complications. Therefore, there is an urgent need
to develop new cutting-edge strategies for T1D management.
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 a culprit for the disease
etiopathogenesis45. The gut microbiome influences multiple host functions, including immunity, and persons
with T1D present changes in gut microbiota associated with immunological deregulation and gut leakiness6.
Clinical studies demonstrate that fecal microbiome therapy (FMT) and probiotics can halt the progression of
new onset T1D13, corroborating the importance of the gut microbiome.
A promising and safe approach for the treatment of T1D that leverages the body’s own natural microbiome-
associated immune regulatory mechanisms is the use of resistant starches. High amylose starch (HAMS) is a
well-tolerated source of dietary fiber that modulate the gut microbiome and the host immune response. HAMS
consumption shifts the gut microbiome profile towards dietary fiber fermenters, producing the beneficial short
chain fatty acids SCFAs. However, HAMS only partially ameliorates T1D in humans. A potentially better
strategy is to use HAMS that has been esterified, releasing larger amounts of SCFAs in the intestinal tract and
eventually the circulation. Rise Therapeutics is developing R-5280, a modified version of HAMS that has been
butyrylated and acetylated. In our prior Phase 1 clinical trial enrolling adolescents with recent onset of T1D,
oral administration of R-5280 increased SCFA production leading to improved overall glycemic control. In
addition, R-5280 consumption resulted in significant increases in specific beneficial metabolites, and reduction
of inflammatory T cells. Given the limited success of prior therapeutic strategies and potential long-term risks of
immunomodulatory therapies in patients with T1D, the use of a microbiome modulating therapy like R-5280
offers a simple, safe, and inexpensive alternative approach to mitigating this devastating disease.
The goal of this proposal is to perform a confirmatory double blinded placebo-controlled Phase 2 clinical trial of
adolescents with early onset of T1D. The key aims of this proposal are: 1) compounding of R-5280 and
placebo to prepare for patient distribution; 2) execute the Phase 2 clinical trial; and 3) expand biomarker
discovery and characterization. Successful commercialization of R-5280 will provide a profound medical
advancement for treating T1D.

## Key facts

- **NIH application ID:** 10906121
- **Project number:** 5R44DK137649-02
- **Recipient organization:** RISE THERAPEUTICS, LLC
- **Principal Investigator:** Gary Fanger
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $995,869
- **Award type:** 5
- **Project period:** 2023-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10906121

## Citation

> US National Institutes of Health, RePORTER application 10906121, R-5280, A Novel Modified Superior Resistant Starch Therapy for Type 1 Diabetes (5R44DK137649-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10906121. Licensed CC0.

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