SYN-004 (ribaxamase)


C. difficile is the leading type of hospital acquired infection and is frequently associated with intravenous (IV) beta-lactam antibiotic treatment. Beta-lactam antibiotics are often the treatment of choice for hospitalized patients with infections; they include commonly used penicillin and cephalosporin antibiotics, such as ceftriaxone. However, antibiotics have the potential to cause harmful effects within the gastrointestinal (GI) tract including disruption of the natural balance of the gut microbiome, leading to 453,000 C. difficile infections (CDI) and > 29,000 C. difficile-related deaths in the United States each year.

SYN-004 (ribaxamase) is an oral prophylactic therapy designed to degrade certain IV beta-lactam antibiotics within the GI tract and maintain the natural balance of the gut microbiome for the prevention of Clostridioides difficile infection (CDI), overgrowth of pathogenic organisms, the emergence of antimicrobial resistance (AMR) and acute graft-versus-host-disease (aGVHD) in allogeneic hematopoietic cell transplant (HCT) recipients.

Synthetic Biologics, Inc

SYN-004 (ribaxamase) is designed as an oral enzyme tablet (blue) to be co-administered with IV beta-lactam antibiotics (yellow). For demonstration purposes, the ribaxamase tablet is portrayed in blue and the IV antibiotic is portrayed in yellow.

Candidate Pipeline

Candidate & Indication Development Stage
Preclinical Phase 1 Phase 2 Phase 3 Market
SYN-004 (ribaxamase) Prevention of CDI, pathogenic overgrowth and AMR
SYN-004 (ribaxamase) Prevention of CDI, pathogenic overgrowth and AMR
Preclinical Phase complete
Phase 1 Phase complete
Phase 2 Phase complete
Phase 3 Phase not started
Market Phase not started

Differentiators/Key Benefits

SYN-004 (ribaxamase) is a first-in-class oral enzyme designed to protect the gut microbiome from disruption caused by commonly used IV beta-lactam antibiotics. SYN-004 (ribaxamase) is not systemically absorbed, does not interfere with the efficacy of IV beta-lactam antibiotics and, by protecting the patient’s native gut microbiome, may prevent the overgrowth and associated infection with Clostridioides difficile as well as antibiotic-associated diarrhea. By protecting patients from CDI, ribaxamase has the potential to shorten hospital stays, diminish morbidity and mortality and reduce antibiotic resistance and the costs associated with the inadvertent consequences of IV beta-lactam antibiotic use.

Synthetic Biologics, Inc

How SYN-004 (ribaxamase) Works

SYN-004 (ribaxamase) is an oral prophylactic therapy designed to degrade certain IV beta-lactam antibiotics within the GI tract.

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Clinical Overview

Phase 1a and 1b

  • Initiated Phase 1a and 1b clinical trials of ribaxamase in December 2014
  • Reported positive topline safety and tolerability results from the Phase 1a clinical trial in December 2014
  • Reported positive topline results from the Phase 1b clinical trial of escalating doses of oral ribaxamase, with no safety or tolerability issues reported at dose levels and dose regimens both meeting and exceeding those expected to be studied in upcoming clinical trials in February 2015
  • Reported positive pharmacokinetic data from both Phase 1 clinical trials, with supportive evidence that ribaxamase should have no effect on the IV antibiotic in the bloodstream, allowing the antibiotic to fight the primary infection in March 2015

Phase 2

  • First Phase 2a
    • Initiated first Phase 2a clinical trial to evaluate the gastrointestinal (GI) antibiotic-degrading effects and the safety of ribaxamase in March 2015
    • Reported data from 10 participants; the data showed that ribaxamase degraded IV ceftriaxone in the chyme of the healthy participants with functioning ileostomies without affecting the ceftriaxone in the bloodstream in December 2015
    • For more information about this trial, visit
  • Second Phase 2a
    • Reported data in May 2016 from 14 participants that demonstrated ribaxamase degraded IV ceftriaxone alone, and in the presence of the proton pump inhibitor (PPI), esomeprazole, to levels that were near or below detectable in the intestinal chyme of healthy participants with functioning ileostomies without affecting the ceftriaxone in the bloodstream.
  • Phase 2b Proof-of-Concept
    • Initiated global Phase 2b randomized, placebo-controlled, proof-of-concept clinical trial of ribaxamase in September 2015
    • Announced the successful completion of enrollment of 413 patients in September 2016
    • Topline results demonstrate SYN-004 (ribaxamase) met its primary endpoint of significantly reducing C. difficile infection (CDI)
    • Patients receiving ribaxamase achieved a 71.4% relative risk reduction (p-value=0.045) in CDI rates compared to patients receiving placebo
    • Analysis of the topline results also demonstrated a significant reduction in new colonization by vancomycin-resistant enterococci (VRE) (p-value=0.0002) and a positive trend towards a reduction in antibiotic-associated diarrhea (p-value=0.13) for patients receiving ribaxamase compared to placebo.
    • Reported supportive data from several exploratory endpoints demonstrating ribaxamase protected the gut microbiome from antibiotic-mediated dysbiosis, compared to placebo.
    • Patients receiving ribaxamase demonstrated significantly better maintenance and recovery of the composition of the gut microbiome as well as lower incidences of new colonization by opportunistic and potentially pathogenic microorganisms, compared to placebo.
    • These data are consistent with ribaxamase's mechanism of action designed to protect and preserve the natural balance of the gut microbiome from the unintended effects of IV antibiotic use.
    • For more information about this trial, visit

Phase 3 Clinical Program

  • Announced positive outcome from End-of-Phase 2 meeting with FDA in Q4 2018
  • Single Phase 3 clinical trial maybe sufficient for approval for the prevention of antibiotic-mediated Clostridioides difficile infection (CDI)
  • Phase 3 clinical program will entail a single, global, event-driven clinical trial with a fixed maximum number of patients for total enrollment
  • Primary efficacy endpoint of the Phase 3 clinical trial will be the reduction in the incidence of CDI at one month after the last drug dose in the ribaxamase treatment group versus placebo
  • A co-primary safety endpoint of noninferiority will evaluate mortality between the ribaxamase treatment group versus placebo at 3 months post-randomization
  • Phase 3 population is patients at high risk for CDI receiving IV β-lactam antibiotics
    • Evaluate multiple β-lactam antibiotics
    • Evaluate different index infections
    • Enroll based on patient risk factors for CDI

Market Need

14 Million


Patients who are administered IV beta-lactam antibiotics in the U.S., annually



Patients infected with C. difficile, annually



C. difficile-related deaths, annually