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 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 CDI, antibiotic-associated diarrhea (AAD) and emergence of antibiotic-resistant organisms.

Synthetic Biologics, Inc

SYN-004 is designed as an oral enzyme tablet (blue) to be co-administered with IV beta-lactam antibiotics (yellow). For demonstration purposes, the SYN-004 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 Prevention of CDI and AAD
Preclinical Phase complete
Phase 1 Phase complete
Phase 2 Phase in progress
Phase 3 Phase not started
Market Phase not started

Differentiators/Key Benefits

SYN-004 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 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 Clostridium difficile as well as antibiotic-associated diarrhea. By protecting patients from CDI, SYN-004 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 Works

SYN-004 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 SYN-004 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 SYN-004, 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 SYN-004 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 SYN-004 in March 2015
    • Reported data from 10 participants; the data showed that SYN-004 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
    • Dosed the first participant in the second Phase 2a clinical trial of SYN-004, to evaluate the GI antibiotic-degrading effects and the safety of SYN-004, in the presence of the proton pump inhibitor (PPI), esomeprazole in June 2015
    • For more information about this trial, visit
  • Phase 2b Proof-of-Concept
    • Initiated a Phase 2b proof-of-concept clinical trial of SYN-004 in September 2015
    • This randomized, placebo-controlled clinical trial is expected to enroll approximately 370 patients at up to 75 global clinical sites
    • The clinical trial is intended to evaluate the effectiveness of SYN-004 to prevent CDI, C. difficile associated diarrhea (CDAD) and AAD in patients hospitalized for a lower respiratory tract infection and receiving IV ceftriaxone
    • For more information about this trial, visit

Phase 3 trial vision

  • Prevention of CDI and AAD among hospitalized patients receiving IV ceftriaxone and other beta-lactam antibiotics
  • Global study; multiple indications for IV beta-lactam therapy
  • Demonstrate no effect on blood levels of antibiotic or primary diagnosis cure rates

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