# Validation of Immunometabolic NLRX1 Therapeutics for IBD

> **NIH NIH R44** · BIOTHERAPEUTICS, INC. · 2021 · $643,417

## Abstract

Validation of Immunometabolic NLRX1 Therapeutics for IBD
Biotherapeutics Inc (BTI) is an emerging biotech company that synergistically combines the power of advanced
computational modeling with translational experimentation to accelerate the development of novel products for
precision medicine and health. This SBIR application stems from data showing a vital role for nucleotide-binding
oligomerization domain, leucine rich repeat containing X1 (NLRX1) as a new therapeutic target for IBD.
Our Product: BTI has identified the first family of small-molecule compounds that bind and activate the novel
regulatory molecule, NLRX1. In a Phase I SBIR, we successfully established NX-13 as a NLRX1-specific agonist
that reduces inflammatory lesions by 90% in CD4+ T cell-specific immunometabolic mechanisms.
Background: IBD is a chronic widespread and debilitating illness that afflicts over 5 million people worldwide
with total expenses exceeding $15 billion annually in the U.S alone. Current treatments are only modestly
successful with significant adverse side effects. Thus, there is an unmet clinical need for safer, more efficacious
IBD therapeutics. NLRX1 can suppress intestinal inflammation during infections and autoimmune disorders. BTI
has validated that loss of NLRX1 causes reduced mucosal healing, increased fibrosis, >5-fold up-regulation in
inflammatory cytokine biomarkers, and complete restructuring of gut microbiome ecology during IBD. This SBIR
Phase II application will characterize microbial and anti-fibrotic mechanisms of NX-13, demonstrate
translational efficacy in human UC primary cells and conduct IND-enabling safety studies.
The Specific Aims are to:
AIM 1. Determine the effect of NX-13 on the intestinal microbiome during colitis through 16S gut
microbiome sequencing and signatures of gut-microbiome interactions.
AIM 2. Characterize the anti-fibrotic mechanisms of NX-13 in chronic colitis models and in vitro effects on
fibroblast gene expression and extracellular matrix deposition.
AIM 3. Validate the translational efficacy of NX-13 in PBMCs and LPMCs from UC patients through
evaluation of overall cellular response and CD4-specific immunometabolic mechanisms.
AIM 4. Conduct an IND-enabling GLP toxicity study in a non-rodent species with a 28-day repeat dose
toxicity study at three dose levels (250, 500, 1000 mg/kg) compared to vehicle.
Expected Outcomes: Validation of NX-13 as a lead agonistic molecule for targeting NLRX1 through: i)
identification of gut microbial and anti-fibrotic mechanisms of NX-13; ii) 50% reduction in TNFα and IFNγ
production in human PBMCs and LPMCs; and iii) a benign safety profile with oral NOAEL ≥ 1,000 mg/kg.
Commercial Application: Success in this project will launch a new drug development pipeline centered on
NLRX1-activating therapeutics with anti-inflammatory and anti-fibrotic effects. BTI’s new NLRX1-targeting oral
therapeutics could disrupt a market of over $10B annually growing at 25% annual rates.

## Key facts

- **NIH application ID:** 10163181
- **Project number:** 5R44DK121561-03
- **Recipient organization:** BIOTHERAPEUTICS, INC.
- **Principal Investigator:** Andrew Leber
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $643,417
- **Award type:** 5
- **Project period:** 2019-04-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10163181

## Citation

> US National Institutes of Health, RePORTER application 10163181, Validation of Immunometabolic NLRX1 Therapeutics for IBD (5R44DK121561-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10163181. Licensed CC0.

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