# Targeting the Immunometabolic Hub Nlrx1 as a Novel Therapeutic for Asthma

> **NIH NIH R43** · BIOTHERAPEUTICS, INC. · 2021 · $361,510

## Abstract

Targeting the Immunometabolic Hub Nlrx1 as a Novel Therapeutic for Allergic Asthma
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 allergy and asthma.
Our Product: BTI has developed first-in-class, small-molecule therapeutics that bind and activate the novel regulatory
molecule, NLRX1. The goal of this project is to validate NLRX1 as a target for allergic asthma and develop NX-73 as an
oral therapeutic to treat mild to moderate to severe asthma.
Significance: Asthma is a chronic disease afflicting over 330 million individuals globally and 40 million in the U. S. Asthma
is a chronic, widespread allergic disease with total expenses exceeding $80 billion annually in the U.S. In particular,
neutrophilic, non-type 2 asthma has a lower responsiveness to current treatments. Though recent years have witnessed an
increase in the number of biologics for asthma, these biologics are specific to certain endotypes, are very costly, and require
up to 26 visits per year for treatment via injections. Inhaled corticosteroids, another common form of treatment have
moderate to serious adverse side-effects and are thought to reduce in effectiveness overtime. Thus, there is an unmet medical
need for safer and more efficacious oral therapeutics for asthma. This SBIR Phase I application will develop NX-73 as a
novel NLRX1-binding product candidate and validate its safety, efficacy, and specificity for the NLRX1 target. Success
in this project will launch a new drug development program centered on NLRX1-activating orally active therapeutics with
a long-term goal of entering clinical trials for asthma by 2022. The Specific Aims are to:
Aim 1. Determine the in vivo proof-of-concept therapeutic efficacy of NX-73 in mouse models of allergic asthma.
Aim 2. Evaluate whether NX-73 reduces Th2 and/or Th17 responses by dendritic cells and airway epithelial cells.
Aim 3. Conduct preliminary pharmacokinetic (PK) and toxicity studies with NX-73 to determine the oral
bioavailability and pulmonary distribution and 7-day repeat-dose toxicity in rats.
Expected Successful Outcomes: i) Validation of the therapeutic efficacy of NX-73 as a lead molecule for suppressing
asthma by targeting Nlrx1; ii) Reduction of asthma symptoms with oral doses of NX-73 ≤ 10 mg/kg; iii) Loss of NX-73
function in Nlrx1-/- mice and cells; and iv) Benign safety profile with NOAEL ≥ 1,000 mg/kg oral in rats.
SBIR Phase II: Will validate the translation of NX-73 effects in human CD141hi dendritic cells and airway epithelial cells
from individuals with mild-to-moderate and moderate-to-severe asthma, assess the therapeutic efficacy of NX-73...

## Key facts

- **NIH application ID:** 10323994
- **Project number:** 1R43HL160260-01
- **Recipient organization:** BIOTHERAPEUTICS, INC.
- **Principal Investigator:** Josep Bassaganya-Riera
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $361,510
- **Award type:** 1
- **Project period:** 2021-08-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10323994

## Citation

> US National Institutes of Health, RePORTER application 10323994, Targeting the Immunometabolic Hub Nlrx1 as a Novel Therapeutic for Asthma (1R43HL160260-01). Retrieved via AI Analytics 2026-06-08 from https://api.ai-analytics.org/grant/nih/10323994. Licensed CC0.

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