# A novel oral immunotherapy for chronic visceral pain of irritable bowel syndrome

> **NIH NIH UG3** · FZATA, INC. · 2024 · $2,091,549

## Abstract

Abstract:
Chronic visceral pain is a defining feature of irritable bowel syndrome (IBS) that is currently considered as a
disorder of brain-gut interaction. Although pain is the most common driver of healthcare visits for IBS
patients, the current treatment options are often ineffective and associated with side effects. The use of
potent opioids for visceral pain has been reported to be associated with higher morbidity and mortality than
other pain conditions and contribute to the opioid epidemic. Although the etiology of IBS is not clearly
understood, the current studies indicate that neuroinflammation in gastrointestinal tract plays a critical role in
the pathogenesis of visceral pain. Gut inflammatory mediators modulate the intestinal nerve system, leading
to long-lasting functional alterations after resolution of the inflammatory insult. Among inflammatory
mediators, tumor necrosis factor-alpha (TNF-α) is a “master regulator” and found to be implicated in both
peripheral and central sensitization during pain induction in preclinical pain models and significantly elevated
in some IBS patients especially patients with post-infection/inflammation IBS. This preclinical and clinical
evidence supports the development of therapeutics targeting gut TNF-α for the treatment of IBS pain.
Fzata has developed a novel oral biotherapeutic, FZ006, an engineered probiotic yeast Saccharomyces
boulardii that secretes a neutralizing antibody against TNF-α. We demonstrated that oral FZ006 delivers anti-
TNF to gut and exhibited exceptional efficacy on relieving visceral pain in several animal models. To develop
FZ006 as a safe, non-addictive, first-in-class, oral therapeutic to treat chronic visceral pain, we propose the
UG3/UH3 plan with the final aim of an IND submission requesting clearance for phase I clinical trials.
Specifically, in the UG3 phase, we will determine the effective dose range of FZ006 and validate therapeutic
efficacy in humanized mice; perform small-scale manufacturing and generate a well-characterized research
cell bank; and prepare and submit pre-IND meeting request with the FDA. In the UH3 phase, we will
manufacture FZ006 under GMP to generate drug substance and drug product for clinical trials; perform
stability assessment and GLP toxicology studies; plan for first-in-human trial; and finally submit IND application
to the FDA for approval. Our ultimate goal is to develop FZ006 as an effective, safe, convenient, and non-
addictive oral therapeutic to treat chronic visceral pain in IBS patients.

## Key facts

- **NIH application ID:** 10976389
- **Project number:** 1UG3NS135350-01A1
- **Recipient organization:** FZATA, INC.
- **Principal Investigator:** Hanping Feng
- **Activity code:** UG3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $2,091,549
- **Award type:** 1
- **Project period:** 2024-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10976389

## Citation

> US National Institutes of Health, RePORTER application 10976389, A novel oral immunotherapy for chronic visceral pain of irritable bowel syndrome (1UG3NS135350-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10976389. Licensed CC0.

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