Synergy Pharmaceuticals Announces Positive Results of Plecanatide Phase 2b Study in Patients with Irritable Bowel Syndrome with

  Synergy Pharmaceuticals Announces Positive Results of Plecanatide Phase 2b
  Study in Patients with Irritable Bowel Syndrome with Constipation

Business Wire

NEW YORK -- April 30, 2014

Synergy Pharmaceuticals Inc. (NASDAQ:SGYP) today announced positive top-line
results from a phase 2b dose-ranging study assessing plecanatide’s safety and
efficacy in 424 patients with irritable bowel syndrome with constipation
(IBS-C). The primary objective of this trial was to determine an effective,
safe and well tolerated dose for plecanatide phase 3 trials with IBS-C
patients. Synergy is pleased to report this trial has achieved that objective.
Preliminary analysis of the data indicates that plecanatide demonstrated
statistically significant improvement in complete spontaneous bowel movement
(CSBM) frequency – the study’s primary endpoint – and was safe and well
tolerated. Notably, patients taking the plecanatide 3.0mg dose experienced
statistically significant improvement in change from baseline versus placebo
in worst abdominal pain and met the FDA overall responder endpoint for IBS-C
over the 12-week treatment. An overall responder for the FDA endpoint fulfills
both ≥30% reduction in worst abdominal pain and an increase of ≥1 complete
spontaneous bowel movements (CSBMs) from baseline in the same week for at
least 50% of the weeks (i.e. 6/12 weeks).

“We are very pleased to see a consistent response at the 3.0mg plecanatide
dose for statistical improvement in CSBM frequency with a less than 10%
diarrhea rate for treating both CIC and IBS-C indications,” said Dr. Gary S.
Jacob, CEO and Chairman of Synergy Pharmaceuticals. “In addition, the 3.0mg
dose has now demonstrated a statistically significant improvement for worst
abdominal pain as well as the overall responder FDA endpoint for IBS-C. We
believe this is the ideal dose for normalizing bowel movements and treating
the symptoms of both CIC and IBS-C patients with a more favorable tolerability
profile that’s suitable for chronic use. We plan to immediately move forward
with plecanatide in IBS-C patients at the 3.0mg dose and expect to initiate
our phase 3 trials in the second half of this year.”

“IBS-C is a complex disorder associated with both chronic constipation and
abdominal pain symptoms that are unique to each patient,” said Dr. Philip B.
Miner, President and Medical Director of the Oklahoma Foundation for Digestive
Research. “There is a significant medical need among patients and physicians
for more treatment options that are effective, safe and well tolerated for
chronic, everyday use. I am encouraged by the data observed in this trial as
plecanatide has demonstrated efficacy and a favorable tolerability profile for
treating IBS-C patients."

The plecanatide 3.0mg dose was selected for phase 3 based on achieving
statistically significant improvement in the study’s primary endpoint and key
secondary endpoints assessed in the topline analyses, which included change
from baseline versus placebo over 12 weeks in: CSBM frequency (1.29 placebo
vs. 2.74, p=<0.001), worst abdominal pain intensity (-1.4 [-24.5%] placebo
vs.-2.0 [-33.9%], p=<0.05) and stool consistency (BSFS) (1.01 placebo vs.
2.49, p=<0.001). Importantly, plecanatide 3.0mg dose also showed a
statistically significant difference from placebo in the overall FDA responder
endpoint (21% placebo vs. 41.9%, p=<0.05). The treatment effects of
plecanatide occurred within the first week.

Plecanatide was safe and well tolerated with no treatment-related serious
adverse events. The most common event was diarrhea, which occurred in 9.3
percent of the 3.0mg plecanatide-treated patients.

At this time the company has reviewed only top-line results and further
analyses will be conducted in the coming weeks. Once full analysis of the data
is complete, Synergy plans to present the results of the trial at an
appropriate scientific conference.

The company intends to initiate pivotal phase 3 trials in IBS-C patients in
the second half of 2014.

IBS-C Phase 2b Study

This was a randomized, 12-week, double-blind, placebo-controlled, dose-ranging
study to assess the safety and efficacy of plecanatide in patients with IBS-C.
The study evaluated the effects of 0.3, 1.0, 3.0 or 9.0 mg plecanatide or
placebo administered orally once daily to adults meeting Rome III criteria for
IBS-C. In addition, patients were required to meet the criteria for the IBS-C
subtype, which is further characterized by stool pattern, such that ≥ 25% of
defecations are hard or lump stools and ≤ 25% of defecations are loose or
watery stools. During pre-treatment at baseline, patients are required to have
at least 3 days in each week with pain scores ≥ 3 on a 0 to 10 scale.

Participants underwent two-week-baseline, 12-week-treatment, and two-week-post
treatment evaluations with daily assessments of bowel habits and symptom
severity using an interactive voice response system. The primary efficacy
endpoint was the change from baseline in the mean number of CSBMs over the
12-week treatment period. Key secondary endpoints were: (1) abdominal pain and
(2) stool consistency. Abdominal pain intensity was measured on an 11-point
severity scale (0 to 10) and stool consistency using the Bristol Stool Form
Scale (BSFS). An overall responder for the FDA endpoint fulfills both ≥30%
reduction in worst abdominal pain and an increase of ≥1 complete spontaneous
bowel movements (CSBMs) from baseline in the same week for at least 50% of the
weeks (i.e. 6/12 weeks).

About Plecanatide

Plecanatide is Synergy’s lead guanylate cyclase-C (GC-C) agonist in
development to treat patients with chronic idiopathic constipation (CIC) and
irritable bowel syndrome with constipation (IBS-C). Plecanatide is a
16-amino-acid analog of the human gastrointestinal (GI) hormone, uroguanylin,
a natural agonist for the intestinal GC-C receptor. Orally administered
plecanatide mimics uroguanylin’s functions by binding to and activating the
GC-C receptor to stimulate fluid secretion and transit required for normal
digestion. Synergy has successfully completed a phase 2b trial of plecanatide
with CIC patients and is currently enrolling patients into its pivotal phase 3
CIC program. For more information please visit www.synergypharma.com.

Forward-Looking Statements

Certain statements in this press release are forward-looking within the
meaning of the Private Securities Litigation Reform Act of 1995. These
statements may be identified by the use of forward- looking words such as
"anticipate," "planned," "believe," "forecast," "estimated," "expected," and
"intend," among others. These forward-looking statements are based on
Synergy's current expectations and actual results could differ materially.
There are a number of factors that could cause actual events to differ
materially from those indicated by such forward-looking statements. These
factors include, but are not limited to, substantial competition; our ability
to continue as a going concern; our need for additional financing;
uncertainties of patent protection and litigation; uncertainties of government
or third party payer reimbursement; limited sales and marketing efforts and
dependence upon third parties; and risks related to failure to obtain FDA
clearances or approvals and noncompliance with FDA regulations. As with any
pharmaceutical under development, there are significant risks in the
development, regulatory approval and commercialization of new products. There
are no guarantees that future clinical trials discussed in this press release
will be completed or successful or that any product will receive regulatory
approval for any indication or prove to be commercially successful. Investors
should read the risk factors set forth in Synergy's Form 10-K for the year
ended December 31, 2012 and other periodic reports filed with the Securities
and Exchange Commission. While the list of factors presented here is
considered representative, no such list should be considered to be a complete
statement of all potential risks and uncertainties. Unlisted factors may
present significant additional obstacles to the realization of forward-looking
statements. Forward-looking statements included herein are made as of the date
hereof, and Synergy does not undertake any obligation to update publicly such
statements to reflect subsequent events or circumstances.

Contact:

Media:
Synergy Pharmaceuticals
Gem Gokmen
Office: 212-584-7610
Mobile: 646-637-3208
ggokmen@synergypharma.com
or
Investor:
Bernard Denoyer
Office: 212-297-0020
Mobile: 203-300-8147
bdenoyer@synergypharma.com
 
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