ROCKVILLE, Md., May 23, 2016 /PRNewswire/ -- Synthetic
Biologics, Inc. (NYSE MKT: SYN), a clinical stage company focused
on developing therapeutics to protect the gut microbiome, reported
detailed data supporting positive clinical outcomes from two
previously reported Phase 2 clinical trials of its proprietary
SYN-010 product candidate for the treatment of irritable bowel
syndrome with constipation (IBS-C). Data from both trials were
presented by Mark Pimentel, MD,
FRCP(C), Director of the GI Motility Program and Laboratory at
Cedars-Sinai, during a poster session yesterday at Digestive
Disease Week® (DDW® 2016) in San Diego, CA. Synthetic Biologics
will host a conference call today at 8:30 a.m. (EDT) to recap
clinical results from both Phase 2 clinical trials of SYN-010, the
Company's proprietary, modified-release formulation of lovastatin
lactone designed to reduce methane production in the gut to treat
an underlying cause of IBS-C.
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"Results from the first and second Phase 2 clinical trials of
SYN-010 presented during DDW® 2016 continue to suggest the
potential ability of both the 21 mg and 42 mg dose strengths of
SYN-010 to lower breath methane in IBS-C patients and treat an
underlying cause of the abdominal pain and bloating associated with
this disease," said Dr. Pimentel. "Unlike current treatments which
are focused on relieving symptoms, outcomes from these latest
SYN-010 studies strongly suggest a potential role for SYN-010 in
treating an underlying cause of IBS-C by reducing the production of
methane in the gut and improving the quality of life for IBS-C
patients."
The two SYN-010 Phase 2 clinical trials are comprised of a
randomized, double-blind, placebo-controlled, 4-week study
comparing SYN-010 21 mg and 42 mg dose strengths to placebo (Study
1), followed by an open-label study in which eligible patients who
completed Study 1 received SYN-010 42 mg for an additional 8 weeks
(Study 2). The two Phase 2 SYN-010 clinical trials evaluated the
change from baseline (Day 1 of Study 1) in breath methane, stool
frequency and abdominal pain and bloating at the end of weeks 1, 4,
8 and 12 (Study 2 – Day 84) in patients diagnosed with IBS-C and
with breath methane levels greater than 10 parts per million (ppm)
at screening. Clinical data from patients who completed Study 1
(n=63) and Study 2 (n=54) showed clinically meaningful improvements
in measurable endpoints, including:
- An increase from Study 1 baseline (Day 1) to the end of Study 2
(Day 84) in the percentage of patients identified as Monthly
Responders, an FDA-defined composite measure incorporating
improvements in CSBMs and abdominal pain1:
- Placebo / SYN-010 42 mg: 46%
- SYN-010 21 mg / SYN-010 42 mg: 47%
- SYN-010 42 mg / SYN-010 42 mg: 33%
- A clinically meaningful reduction from Study 1 baseline (Day 1)
to the end of Study 2 (Day 84) in the IBS-Symptom Severity Score
(IBS-SSS), which includes abdominal pain, bloating, stool frequency
and quality of life scores:
- Placebo / SYN-010 42 mg: p<0.004
- SYN-010 21 mg / SYN-010 42 mg: p<0.001
- SYN-010 42 mg / SYN-010 42 mg: p<0.001
Data analyzed from all patients who completed Study 1 and Study
2, and who were administered the 42 mg dose of SYN-010 for at least
8 weeks, demonstrated an inverse correlation (p-value=0.026)
between breath methane area under the curve (AUC) and complete
spontaneous bowel movements (CSBM). A similar inverse correlation
(p-value=0.003) was observed between breath methane AUC and
spontaneous bowel movements (SBM). Clinical data from Study 1
demonstrates that patients in both the 21 mg and 42 mg SYN-010
treatment groups used 60% less rescue medication (bisacodyl; 5 mg)
when compared to placebo. SYN-010 was well tolerated in both Study
1 and Study 2 patients, and the few reported adverse events (AE)
were balanced between groups. One mild incidence of diarrhea was
reported during both studies and identified by the investigator as
unrelated to SYN-010. No severe adverse events (SAEs) were
reported.
"We are excited about the results of these clinical trials and
are very enthusiastic about the potential for SYN-010 to be a
best-in-class IBS-C therapeutic. We appreciate the contributions of
the patients, investigators and committed staff who participated in
these trials, and we look forward to continuing our clinical
progress with the goal of making SYN-010 commercially available to
the millions of patients suffering from this disease," said
Jeffrey Riley, President and Chief
Executive Officer. "During an advisory board meeting held this
weekend at DDW®, we received valuable feedback from IBS-C and GI
key opinion leaders which we intend to incorporate into the end of
Phase 2 meeting with the FDA expected this summer. We also remain
on track to initiate our Phase 3 clinical program for SYN-010 for
the treatment of IBS-C later this year."
SYN-010 Pharmacokinetic Study in Healthy Human
Volunteers
A separate, recently completed randomized, open-label clinical
study of healthy volunteers evaluated the pharmacokinetic (PK)
profile of the active ingredient of SYN-010, lovastatin lactone and
its beta-hydroxyacid metabolite which is responsible for lowering
cholesterol. Single 21 mg, 42 mg or 84 mg doses of SYN-010 were
administered to three groups of eight fasted volunteers, once a day
for each of four days. Plasma concentrations of lovastatin lactone
and its beta-hydroxyacid metabolite were measured on Day 1 and Day
4. Plasma concentration vs. time profiles for lovastatin lactone
and its beta-hydroxyacid metabolite, following administration of
the first dose of all three dose strengths of SYN-010, showed a
significant lag before first measurable concentrations were
observed, followed by gradually increasing plasma levels of each
component over the 24-hour analysis period. PK parameters were dose
proportional and concentrations of SYN-010 reached a steady state
by Day 4 of administration. Plasma levels of the beta-hydroxyacid
metabolite were approximately half of those reported in the
literature for similar doses of currently approved lovastatin
products. The PK data in healthy volunteers support the
modified-release profile of SYN-010 which is designed to avoid drug
release in the stomach and deliver the antimethanogenic drug form,
lovastatin lactone, into the lower small intestine and colon while
reducing systemic exposure to the cholesterol-lowering lovastatin
beta-hydroxyacid metabolite.
Conference Call
Synthetic Biologics' management will host a conference call
today, Monday, May 23, 2016 at 8:30 a.m. (EDT), along with featured
guest speaker, Dr. Mark Pimentel.
Dr. Pimentel intends to recap the SYN-010 Phase 2 clinical trial
data following the poster presentation at DDW® 2016 on Sunday, May
22, 2016 in San Diego. The dial-in
information for the call is as follows:
U.S. toll free: 1-888-347-5280
International: +1 412-902-4280
Participants are asked to dial in 15 minutes before the start of
the call to register. The call and associated slide presentation
will be webcast over the Internet at
https://www.webcaster4.com/Webcast/Page/1096/14387. An archive of
the call will be available for approximately six months at the same
URL https://www.webcaster4.com/Webcast/Page/1096/14387 beginning
approximately one hour after the call's conclusion. Slides
associated with this conference call were filed with the SEC
earlier today and are available on the investors section of our
website www.syntheticbiologics.com.
About Synthetic Biologics' Two Phase 2 Clinical Trials of
SYN-010
In the first four-week Phase 2 clinical trial of SYN-010, 63
patients with IBS-C and a breath methane value > 10 parts per
million at screening were randomly assigned to receive placebo, a
21 mg SYN-010 dose or a 42 mg SYN-010 dose orally once daily for 28
days at multiple centers. The primary endpoint was the change from
baseline in the AUC of breath methane production at Day 7, based on
a 180-minute lactulose breath test (LBT). Secondary efficacy
assessments included change in methane AUC at day 28, stool
frequency and consistency, abdominal pain, and safety data.
Fifty-four patients, who completed the first Phase 2 clinical
trial of SYN-010, rolled over into the second Phase 2 open-label
clinical trial of SYN-010 which was conducted for an additional
eight weeks at multiple centers. The primary endpoint of this
extension study was to evaluate the sustainability of the effect of
one daily dose strength (42 mg) of SYN-010 on breath methane
production in breath methane-positive patients with IBS-C.
Secondary endpoints included evaluation of the reduction in
abdominal pain and bloating, the improvement in stool frequency and
overall quality of life.
About SYN-010
SYN-010 is a proprietary, modified-release formulation of
lovastatin lactone that is intended to reduce methane production by
certain microorganisms (Methanobrevibacter smithii) in the
gut while minimizing disruption to the microbiome to treat an
underlying cause of IBS-C. SYN-010
is intended to act primarily in the intestinal lumen while avoiding
systemic absorption, thereby targeting a major cause of IBS-C, not
just the symptoms. To access the SYN-010 mechanism of action video
on Synthetic Biologics' website, please click here.
About Synthetic Biologics, Inc.
Synthetic Biologics, Inc. (NYSE MKT: SYN) is a clinical stage
company developing therapeutics to protect the gut microbiome while
targeting pathogen-specific diseases. The Company's lead candidates
in Phase 2 development are: (1) 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), and (2) SYN-004 which is designed to protect
the gut microbiome from the effects of certain commonly used
intravenous (IV) beta-lactam antibiotics for the prevention of
C. difficile infection and antibiotic-associated diarrhea
(AAD). In collaboration with Intrexon Corporation, the Company is
also developing preclinical stage 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 include statements
regarding the potential ability of both the 21 mg and 42 mg dose
strengths to lower breath methane in IBS-C patients, the potential
role for SYN-010 in treating a major underlying cause of IBS-C by
reducing the production of methane in the gut and improving the
quality of life for IBS-C patients, the potential for SYN-010 to be
a best-in-class IBS-C therapeutic, the continued clinical progress
with the goal of making SYN-010 commercially available to treat
IBS-C, timing of the interim analysis, the potential benefits of
SYN-004 and SYN-010, timing of planned end of Phase 2 meeting with
the FDA and initiation of Phase 3 development of SYN-010 and the
market size. 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' product candidates
demonstrating safety and effectiveness, as well as results that are
consistent with prior results, Synthetic Biologics' ability to
initiate clinical trials and if initiated, to complete them on time
and achieve desired results and benefits, Synthetic Biologics'
clinical trials continuing enrollment as expected, Synthetic
Biologics' ability to obtain regulatory approvals for
commercialization of product candidates or to comply with ongoing
regulatory requirements, regulatory limitations relating to
Synthetic Biologics' ability to promote or commercialize its
product candidates for specific indications, acceptance of its
product candidates in the marketplace and the successful
development, marketing or sale of Synthetic Biologics' products,
Synthetic Biologics' ability to maintain its license agreements,
the continued maintenance and growth of Synthetic Biologics' patent
estate, Synthetic Biologics becoming and remaining profitable,
Synthetic Biologics' ability to establish and maintain
collaborations, Synthetic Biologics' ability to obtain or maintain
the capital or grants necessary to fund its research and
development activities, a loss of any of Synthetic Biologics' key
scientists or management personnel, and other factors described in
Synthetic Biologics' Annual Report on Form 10-K for the year ended
December 31, 2015 and its other
filings with the SEC, including subsequent periodic reports on
Forms 10-Q and 8-K. The information in this release is provided
only as of the date of this release, and Synthetic Biologics
undertakes no obligation to update any forward-looking statements
contained in this release on account of new information, future
events, or otherwise, except as required by law.
1 A Monthly Responder is defined as a patient who has
a Weekly Response in at least 50% of the weeks of treatment during
the month. A Weekly Responder is defined as a patient who
experiences a decrease in weekly average score for worst abdominal
pain in the past 24 hours of at least 30% compared with Study 1
Baseline and a stool frequency increase of 1 or more CSBM per week
compared with Study 1 Baseline.
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