Full Press Release Details
Synthetic Biologics Announces Positive Outcome of End-of-Phase 2 Meeting with FDA
on SYN-004 (ribaxamase) Development
Phase 3 Clinical Trial May be Sufficient for Approval
for Prevention of Antibiotic-Mediated
Clostridium difficile Infection (CDI) --
-- SYN-004 (ribaxamase) is in Development
as Potentially the First Intervention
Designed to Specifically Prevent Antibiotic
Damage to the Microbiome --
Rockville, MD, November 21, 2018 -
Synthetic Biologics, Inc. (NYSE American: SYN), a late-stage clinical company developing therapeutics designed to preserve
the microbiome to protect and restore the health of patients, today announced that it has successfully completed an End-of-Phase
2 meeting with the U.S. Food and Drug Administration (FDA) to discuss development of SYN-004 (ribaxamase) for the prevention of
antibiotic-mediated Clostridium difficile infection (CDI). Pursuant to the meeting, the FDA has proposed criteria for Phase
3 clinical efficacy and safety which, if achieved, may support submission for marketing approval of ribaxamase on the basis of
a single Phase 3 clinical trial. Final agreement on these criteria is contingent on FDA evaluation of a detailed Phase 3 clinical
"We are very pleased with the productive
advice we have received from the FDA during our recent End-of-Phase 2 meeting," said Steven A. Shallcross, Interim Chief
Executive Officer and Chief Financial Officer. "Having a clear path forward in the form of a Phase 3 clinical program for
ribaxamase is an exciting and important milestone for our company and should be highly beneficial in our ongoing strategic partnering
Synthetic Biologics, in consultation with
the FDA, has confirmed the key elements of the Phase 3 clinical program to support a marketing application for ribaxamase, the
Company's first-in-class oral enzyme designed to degrade certain intravenous (IV) beta-lactam antibiotics within the gastrointestinal
(GI) tract to prevent microbiome damage, Clostridium difficile infection (CDI), overgrowth of pathogenic organisms and the
emergence of antimicrobial resistance (AMR). The proposed ribaxamase Phase 3 clinical program will entail a single, global, event-driven
clinical trial with a fixed maximum number of patients for total enrollment and will evaluate the potential efficacy and safety
of ribaxamase in a broad patient population by enrolling patients with a variety of underlying infections treated with a range
of IV beta-lactam antibiotics.
The 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. The Company also confirmed that the FDA agreed to a primary safety endpoint of noninferiority in mortality
between the ribaxamase treatment group versus placebo at 3 months post-randomization. The designation of efficacy and safety as
separate and decoupled endpoints is critical for clinical studies of this nature, where the underlying population, regardless of
treatment group, is projected to have a comparatively high incidence of safety events that may significantly dilute the smaller
number of CDI events.
Synthetic Biologics anticipates initiating
the Phase 3 clinical program after securing additional potential financing via a strategic partnership. In parallel, the Company
is evaluating opportunities to advance ribaxamase through the pursuit of a more focused clinical indication in a specialty patient
population with multiple potential disease endpoints associated with IV beta-lactam-induced gut microbiome damage. Such a dual
approach is designed to advance ribaxamase in areas of clear unmet medical need while also expanding upon ribaxamase's current
data set and providing further validation for use in the broader indication for the prevention of CDI.
About Clostridium difficile infection
Clostridium difficile infection (CDI) is a leading hospital
acquired infection in the U.S., with more than 453,0001 patients diagnosed annually. CDI results in approximately 29,000
deaths1, $5.42 billion in additional healthcare costs, as well as significant and sometimes prolonged illness.
Approximately 1 in 5 CDI patients experience at least one CDI recurrence3.
About SYN-004 (ribaxamase) and the Phase
2b proof-of-concept clinical trial
SYN-004 (ribaxamase) is a first-in-class
oral enzyme 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 Clostridium difficile infection (CDI), overgrowth of pathogenic organisms
and the emergence of antimicrobial resistance (AMR). A previously completed randomized, double-blind, placebo-controlled Phase
2b proof-of-concept clinical trial of 412 patients met its primary endpoint of significantly reducing C. difficile infection
(CDI). Preliminary analysis of the data indicated seven confirmed cases of CDI in the placebo group compared to two cases in the
ribaxamase treatment group. Patients receiving ribaxamase achieved a 71.4% relative risk reduction (p-value=0.045) in CDI rates
compared to patients receiving placebo.
About Synthetic Biologics, Inc.
Synthetic Biologics, Inc. (NYSE American:
SYN) is a late-stage clinical company developing therapeutics that preserve the microbiome to protect and restore the health of
patients. The Company's lead candidates are: (1) SYN-004 (ribaxamase) which is designed to protect the gut microbiome from the
effects of certain commonly used intravenous (IV) beta-lactam antibiotics to prevent microbiome damage, C. difficile infection
(CDI), overgrowth of pathogenic organisms and the emergence of antimicrobial resistance (AMR), and (2) SYN-010 which is intended
to reduce the impact of methane producing organisms in the gut microbiome to treat an underlying cause of irritable bowel syndrome
with constipation (IBS-C). The Company's preclinical pursuits include an oral formulation of the enzyme intestinal alkaline
phosphatase (IAP) to treat both local GI and systemic diseases as well as monoclonal antibody therapies for the prevention and
treatment of pertussis, and novel discovery stage biotherapeutics for the treatment of phenylketonuria (PKU). For more information,
please visit Synthetic Biologics' website at www.syntheticbiologics.com.
This release contains forward-looking
statements within the meaning of the Private Securities Litigation Reform Act of 1995. In some cases forward-looking statements
can be identified by terminology such as "may," "should," "potential," "continue," "expects,"
"anticipates," "intends," "plans," "believes," "estimates," and similar expressions,
and includes statements regarding a single Phase 3 clinical trial being sufficient for approval for prevention of antibiotic-mediated
clostridium difficile infection, the achievement of the FDA proposed criteria for Phase 3 clinical efficacy and safety supporting
submission for marketing approval of SYN-004 (ribaxamase) on the basis of a single Phase 3 clinical trial, having a clear path
forward in the form of a Phase 3 clinical program for SYN-004 being highly beneficial in our ongoing strategic partnering discussions,
the anticipated initiation of the Phase 3 clinical program after securing additional potential financing via a strategic partnership,
development of SYN-004 (ribaxamase) as potentially the first intervention designed to specifically to prevent antibiotic damage
to the microbiome, opportunities that would enable the advancement of SYN-004 through the pursuit of a more focused clinical indication
in a specialty patient population with multiple potential disease endpoints associated with IV beta-lactam-induced gut microbiome
damage and the potential benefits of SYN-004 and SYN-010. These forward-looking statements are based on management's expectations
and assumptions as of the date of this press release and are subject to a number of risks and uncertainties, many of which are
difficult to predict that could cause actual results to differ materially from current expectations and assumptions from those
set forth or implied by any forward-looking statements. Important factors that could cause actual results to differ materially
from current expectations include, among others, Synthetic Biologics' ability to design a Phase 3 trial with the co-primary endpoints
and receive FDA approval for such design, Synthetic Biologics' ability to initiate the Phase 3 clinical program after securing
additional financing via a strategic partnership, Synthetic Biologics' ability to establish a path forward to develop ribaxamase
and conduct a robust, controlled and well-designed clinical trial that may provide sufficient efficacy and safety data to support
a pathway towards marketing approval for ribaxamase, Synthetic Biologics' ability to regain compliance with the continued listing
standards of the NYSE American by September 2, 2019, Synthetic Biologics' ability to comply with other continued listing requirements
of the NYSE American, the ability of its product candidates to demonstrate safety and effectiveness, as well as results that are
consistent with prior results, Synthetic Biologics' clinical trials continuing enrollment as expected, a failure to receive the
necessary regulatory approvals for commercialization of Synthetic Biologics' therapeutics, including approval of proposed trial
designs, a failure of Synthetic Biologics' clinical trials, and those conducted by investigators, for SYN-004 and SYN-010 to be
commenced or completed on time or to achieve desired results and benefits, a failure of Synthetic Biologics' clinical trials to
continue enrollment as expected or receive anticipated funding, a failure of Synthetic Biologics to successfully develop, market
or sell its products, Synthetic Biologics' inability to maintain its material licensing agreements, or a failure by Synthetic Biologics
or its strategic partners to successfully commercialize products, Synthetic Biologics' ability to achieve acceptance of its
product candidates in the marketplace and the successful development, marketing or sale of Synthetic Biologics' products by competitors
that render Synthetic Biologics' products obsolete or non-competitive, the continued maintenance and growth of Synthetic Biologics' patent
estate, Synthetic Biologics becoming and remaining profitable, Synthetic Biologics' ability to obtain or maintain the capital