# Preclinical Evaluation of CRS3123 for the Treatment of Helicobacter pylori Infections

> **NIH NIH R43** · CRESTONE, INC. · 2020 · $143,960

## Abstract

The goal of this program is to evaluate the small-molecule therapeutic agent CRS3123 for
efficacy in a mouse model of H. pylori infection (HPI). Resistance to commonly used first- and
second-line antibiotics to treat HPI is on the rise, resulting in a steady decrease of clinical
efficacy. We are developing a novel mode-of-action agent with exquisite potency against HP.
CRS3123 demonstrated good in vitro activity against all HP strains tested (MIC range of 0.06 - 1
µg/mL and MIC90 = 0.5 µg/mL), including a multidrug-resistant strain and the most pathogenic
strains of the vacA s1-m1 and cagA-positive genotype. CRS3123 has already been
demonstrated to be safe in humans in single dose and multiple ascending dose Phase I clinical
studies toward its development as a novel agent to treat C. difficile infection. Limited systemic
absorption and high accumulation of CRS3123 in the gut (>1,000 µg/g in stool) has been
observed, thus, we are confident that CRS3123 has the potential to accumulate to high levels at
the site of HPI in the stomach. Furthermore, CRS3123 has a very narrow spectrum of activity
with regard to gastrointestinal bacteria (H. pylori, Clostridia), thus sparing most beneficial
constituents of normal gut microbiota. CRS3123 targets the bacterial MetRS enzyme and
therefore inhibits protein synthesis. The immediate and effective blocking of de novo toxin
production has already been demonstrated for C. difficile. CRS3123 is expected to inhibit
production of HP toxins CagA and VacA in vitro as well, which may aide in the resolution of
symptoms of HP-associated peptic ulcer disease. In addition, CRS3123 is expected to block the
production of urease, which is essential for acid acclimation and survival of HP. Our approach
will begin with an in-depth microbiological evaluation of CRS3123 against H. pylori, including the
determination of spontaneous resistance rate and mutant prevention concentration. Drug
combination studies will be performed to monitor in vitro synergy with common first- and
second-line antibiotics typically used to treat HP infections. Pharmacokinetics and efficacy of
CRS3123 will be assessed in the standard mouse model of HPI. Levels of CRS3123 will be
determined in the stomach; we expect to see high accumulation of CRS3123 in the stomach
and limited systemic exposure, concomitant with a reduction of the H. pylori burden. We believe
that CRS3123, as a single agent or in combination with a proton pump inhibitor (PPI),
represents an excellent potential alternative to currently approved regimens involving two or
three antibiotics and a PPI, such as standard triple or quadruple therapy of HPI.

## Key facts

- **NIH application ID:** 10009197
- **Project number:** 1R43AI149820-01A1
- **Recipient organization:** CRESTONE, INC.
- **Principal Investigator:** Urs Arnold Ochsner
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $143,960
- **Award type:** 1
- **Project period:** 2020-04-15 → 2021-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10009197

## Citation

> US National Institutes of Health, RePORTER application 10009197, Preclinical Evaluation of CRS3123 for the Treatment of Helicobacter pylori Infections (1R43AI149820-01A1). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10009197. Licensed CC0.

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