Synergy Pharmaceuticals Initiates Dosing of Healthy Volunteers in Phase I Trial of SP-333, a Second-Generation GC-C Agonist to

Synergy Pharmaceuticals Initiates Dosing of Healthy Volunteers in Phase I
Trial of SP-333, a Second-Generation GC-C Agonist to Treat Ulcerative Colitis

NEW YORK, Oct. 22, 2012 (GLOBE NEWSWIRE) -- Synergy Pharmaceuticals Inc.
(Nasdaq:SGYP), a developer of new drugs to treat gastrointestinal disorders
announced today that on October 19, 2012 the company initiated oral dosing of
healthy adult volunteers in a Phase I clinical trial of SP-333, a guanylate
cyclase C (GC-C) agonist designed to treat ulcerative colitis (UC). SP-333
has exhibited potent anti-inflammatory activity in animal studies of colitis,
displaying a novel mechanism-of-action that the company believes can provide a
new way to treat UC patients with mild to moderate disease.

The present trial is designed as a placebo-controlled, dose-escalating,
single-dose study in healthy adult volunteers that is primarily focused on
exploring the safety profile of SP-333.A multi-dose, dose-escalation trial is
planned for early 2013.

"Disruption of intestinal barrier function resulting in mucosal inflammation
and immune activation is one of the primary causes of the pathogenesis of
inflammatory bowel diseases such as ulcerative colitis," said Dr. Kunwar
Shailubhai, Chief Scientific Officer of Synergy Pharmaceuticals. "Oral
treatment with SP-333 to augment intestinal GC-C activation represents a novel
approach for restoring mucosal barrier function and suppressing
inflammation.In experimental models of colitis in mice, we have found that
treatment with SP-333 ameliorates GI inflammation, likely through inhibition
of NF-kappa B signaling to suppress production of pro-inflammatory cytokines."

About SP-333

SP-333 is a synthetic analog of uroguanylin, a natriuretic peptide hormone
which is normally produced in the lumen of the intestinal tract. Deficiency of
uroguanylin is likely to be one of the primary reasons associated with
formation of polyps as well as debilitating and difficult-to-treat GI
inflammatory disorders such as ulcerative colitis and Crohn's disease.
Orally-administered SP-333 binds to and activates the GC-C receptor expressed
on epithelial cells lining the GI mucosa, resulting in stimulation of cyclic
GMP in target tissues. SP-333 has been found to be highly stable against
proteolysis in simulated intestinal fluid for up to 24 hours. Its enhanced
stability makes this peptide an extremely potent GC-C agonist in animal
studies in mice and monkeys, promoting bowel movement in monkeys, and
ameliorating GI inflammation in mice, respectively.

About Ulcerative Colitis

More than 500,000 Americans are afflicted with ulcerative colitis (UC), a type
of Inflammatory Bowel Disease (IBD) that causes chronic inflammation of the
colon.Along with Crohn's disease, the other major form of IBD, ulcerative
colitis is painful and debilitating. Patients with UC are at increased risk
for colon cancer and may ultimately require surgical removal of the colon.
There is currently no medical cure for ulcerative colitis. Long-term
remission with current treatments is limited. Therefore, there is a need for
new treatment approaches to treat patients with ulcerative colitis.

About Synergy Pharmaceuticals Inc.

Synergy is a biopharmaceutical company focused on the development of new drugs
to treat gastrointestinal disorders and diseases. Synergy's lead proprietary
drug candidate plecanatide is a synthetic analog of the human gastrointestinal
hormone uroguanylin, and functions by activating the guanylate cyclase C
receptor on epithelial cells of the GI tract. Synergy completed a Phase I
study of plecanatide in healthy volunteers and a Phase IIa clinical trial in
CIC patients. In October, 2011, Synergy initiated dosing of patients in a
major Phase II/III clinical trial of plecanatide to treat chronic idiopathic
constipation. Plecanatide is also being developed to treat
constipation-predominant irritable bowel syndrome, with the first trial in
IBS-C patients planned for the second half of 2012. Synergy's second GC-C
agonist SP-333 is in clinical development to treat inflammatory bowel
diseases, and is presently in a Phase I trial in healthy volunteers. More
information is available at

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, 2011 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 Contact
         Janet Skidmore
         Office: 215-658-4915
         Mobile: 215-429-2917
         Investor Contact
         Danielle Spangler
         The Trout Group
         (646) 378-2924
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