Synergy Pharmaceuticals Presents Poster on Novel Mechanism of Action of SP-333, an Agonist of Guanylate Cyclase-C for Treatment

Synergy Pharmaceuticals Presents Poster on Novel Mechanism of Action of
SP-333, an Agonist of Guanylate Cyclase-C for Treatment of Ulcerative Colitis

Scientific Poster Presentation at 2012 Advances in IBD Conference

NEW YORK, Dec. 14, 2012 (GLOBE NEWSWIRE) -- Synergy Pharmaceuticals Inc.
(Nasdaq:SGYP), a developer of new drugs to treat gastrointestinal disorders
and diseases, today announced that a poster presentation on SP-333, Synergy's
next-generation guanylate cyclase-C (GC-C) agonist to treat ulcerative
colitis, will be made at the 2012 Advances in Inflammatory Bowel Diseases,
Crohn's & Colitis Foundation's Clinical & Research Conference. The conference
takes place December 13-15 at the Westin Diplomat in Hollywood, FL.

The poster describes animal studies showing that oral treatment with SP-333,
an analog of uroguanylin, ameliorated gastrointestinal (GI) inflammation in
dextran sodium sulfate (DSS) induced colitis in mice, and that down-regulation
of NF-kB and pro-inflammatory cytokines was associated with SP-333
administration. The data also demonstrate that systemic absorption of orally
administered SP-333 is minimal, and is unaffected by the severity of the
experimental colitis. Synergy recently completed a single-dose,
dose-escalating Phase I trial of SP-333 in healthy adult volunteers, and is
planning to initiate a multi-dose, dose-escalation study in healthy volunteers
in early 2013.

Recent studies suggest that expression of uroguanylin, the native GC-C agonist
expressed in the human GI tract, is down-regulated in inflamed tissue from
patients with Crohn's disease and in patients with ulcerative colitis,
implying that uroguanylin deficiency may be associated with disruption of
intestinal barrier function, one of the primary hypothesized causes of the
pathogenesis of inflammatory bowel disease.

"Oral treatment with SP-333 to augment intestinal GC-C activation may
represent a novel approach for restoring mucosal barrier function and
suppressing inflammation," said Dr. Kunwar Shailubhai, Chief Scientific
Officer of Synergy Pharmaceuticals, Inc. "In experimental models of colitis in
mice, treatment with SP-333 ameliorates GI inflammation possibly through
inhibition of NF-kappa B signaling to suppress production of pro-inflammatory

The poster: SP-333, a Guanylate Cyclase-C Agonist, Ameliorates DSS-colitis in
Mice via a Novel Cyclic GMP-Mediated Mechanism (P-198), authored by Kunwar
Shailubhai, John Foss, Graham Zhang, Krishna P Arjunan, Rong Feng, Stephen
Comiskey, Gary S. Jacob, and Scott E. Plevy, will be presented by Dr.
Shailubhai on Friday December 14 between 6 PM and 7PM at the Westin Diplomat
in Hollywood, FL.

About SP-333

SP-333 is a synthetic analog of uroguanylin, a natriuretic hormone which is
normally produced in the body's 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 guanylate cyclase C (GC-C) expressed on epithelial cells lining
the GI mucosa, resulting in stimulation of cyclic GMP in target tissues.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 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
chronic idiopathic constipation (CIC) patients. In August of 2012, Synergy
completed enrollment of patients in a major Phase II/III clinical trial of
plecanatide to treat CIC. Plecanatide is also being developed to treat
irritable bowel syndrome with constipation (IBS-C), with the first trial in
IBS-C patients initiated in 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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