# Comparative Efficacy of Therapeutics for Clostridioides difficile Infection

> **NIH NIH R43** · BIOTHERAPEUTICS, INC. · 2024 · $300,000

## Abstract

Comparative Efficacy of Therapeutics for Clostridioides difficile Infection
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 precision
immunology therapeutics. Clostridioides difficile infection (CDI) is a gastrointestinal (GI) infection, established
upon disruption of gut microbiome commonly following antibiotic administration. Almost half a million people in
the United States are affected by CDI every year, causing an economic burden of over $6 billion..
Despite the status of CDI as an antibiotic-associated infection, the standard of care (SOC) for CDI is dominated
by antimicrobials, reporting high infection recurrence rates. Novel antimicrobial-free strategies have been
developed to address this dichotomy, including fecal microbiome transplantation and administration of
monoclonal antibodies against C. difficile toxin B (TcdB). However, safety concerns and high costs, create the
need for more effective, antimicrobial-free therapeutics with novel mechanisms of action.
BTI has developed a novel, oral, once-daily, first-in-class, immunoregulatory therapeutic being evaluated in
clinical development for inflammatory bowel disease (IBD) that provides therapeutic efficacy in acute and
recurrent CDI, in an antimicrobial-free, microbiome-preserving manner. This SBIR aims to accelerate the
development of this novel therapeutic through a head-to-head comparison of the efficacy of our product
candidate versus traditional and recently approved therapeutics for the treatment of CDI.
The specific aims of this project are to:
AIM 1. Evaluate the comparative efficacy of our new product candidate versus FDA-approved
therapeutics for CDI in two recurrent mouse models. We will assess weight loss, disease activity,
histopathological lesions, and colitis through flow cytometry immunophenotype and gene expression profile.
AIM 2. Compare the effects of our new product candidate versus current therapeutics in modulating gut
microbiome dynamics during CDI. In a recurrent model of CDI, we will assess gut microbiome composition
and diversity, plus abundance of C. difficile-resistant strains through 16S sequencing and metabolomic analysis.
Expected outcomes: i) ≥ 30% decrease of histopathological scores; ii) ≥ 40% decrease of Th17 infiltration; and
iii) ≥ 60% increase of alpha diversity compared to SOC.
The SBIR Phase II will validate the therapeutic efficacy in hamster and pig models of CDI. finalize IND-enabling
studies and file an IND for treating CDI.
Commercial application: The long-term goal of this project is to develop a new line of host-centered small
molecule therapeutics that are safer and more effective than standard of care (SOC) treatments for CDI, with
reduced disease severity and recurrence rates, and initial clinical testing expected by 2024.

## Key facts

- **NIH application ID:** 11007011
- **Project number:** 1R43AI184008-01A1
- **Recipient organization:** BIOTHERAPEUTICS, INC.
- **Principal Investigator:** Raquel Hontecillas
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $300,000
- **Award type:** 1
- **Project period:** 2024-07-01 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11007011

## Citation

> US National Institutes of Health, RePORTER application 11007011, Comparative Efficacy of Therapeutics for Clostridioides difficile Infection (1R43AI184008-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11007011. Licensed CC0.

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