# A Novel Humanized Tetra-specific Antibody against Clostridium difficile Infection

> **NIH NIH R01** · FZATA, INC. · 2020 · $2,154,339

## Abstract

Abstract
Antibacterial resistance is a global public health crisis. Antibiotic-resistant Clostridium difficile is responsible for
more than 29,000 deaths in the US each year and the infection represents an urgent threat to public health
worldwide. Of most concern is that the incidence of C. difficile infection (CDI) and disease severity is rapidly
increasing in recent years due to the emergence of hypervirulent and antibiotic-resistant strains. CDI is caused
by two major toxins TcdA and TcdB, absent which the bacterium is avirulent. Current standard treatment with
antibiotics is sub-optimal and accompanied by a high recurrence rate due to the disruption of gut microbiota.
Approaches using antibodies to target the major virulence factors represent a new treatment option against
CDI. However, the most advanced therapeutic antibody bezlotoxumab, an anti-TcdB monoclonal antibody from
Merck, only showed a comparable effect as antibiotic fidaxomicin on reducing CDI recurrence in recent Phase
III trials. This less-than-desirable efficacy is likely due to targeting a single epitope of the toxin and low potency
of the antibody. We have developed a novel tetra-specific, humanized antibody FZ001 based on 4 VHHs
targeting distinct epitopes, two on each of the toxins. FZ001 potently and broadly neutralizes both toxins from
different clinical isolates and demonstrates a potent therapeutic efficacy against both primary and recurrent
CDI in mice. cGMP-grade CHO lines have been constructed with a high expression level of FZ001. In
response to RFA-AI-16-034, we propose to develop cell culture parameters and analytic assays and
subsequent manufacturing process in order to generate FZ001 for GLP toxicology. This project will allow the
generation of the critical data of chemical, manufacturing, and control (CMC) for future IND filing and Phase I
clinical trials.

## Key facts

- **NIH application ID:** 9941044
- **Project number:** 5R01AI132207-04
- **Recipient organization:** FZATA, INC.
- **Principal Investigator:** Hanping Feng
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $2,154,339
- **Award type:** 5
- **Project period:** 2017-06-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9941044

## Citation

> US National Institutes of Health, RePORTER application 9941044, A Novel Humanized Tetra-specific Antibody against Clostridium difficile Infection (5R01AI132207-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9941044. Licensed CC0.

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