Synergy Pharmaceuticals Initiates Multiple Ascending Dose Phase Ib Trial in Healthy Volunteers of SP-333, a Second Generation

Synergy Pharmaceuticals Initiates Multiple Ascending Dose Phase Ib Trial in
Healthy Volunteers of SP-333, a Second Generation Guanylate Cyclase C Agonist
for the Treatment of Ulcerative Colitis

SP-333 Advances to Multiple-Dosing Safety Study

NEW YORK, Jan. 28, 2013 (GLOBE NEWSWIRE) -- Synergy Pharmaceuticals, Inc.
(Nasdaq:SGYP), a developer of new drugs to treat gastrointestinal (GI)
disorders, announced today that oral dosing of healthy volunteers has begun in
a Phase I clinical trial of SP-333, a guanylate cyclase C (GC-C) agonist for
the treatment of inflammatory bowel disease (IBD) including 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
could provide a new way to treat UC patients with mild-to-moderate disease.

"We're pleased with the results of our SP-333 single-dose-ascending trial in
healthy volunteers, which was completed in late 2012, and are eager to move
forward with further development of SP-333," said Dr. Gary S. Jacob, President
and CEO of Synergy Pharmaceuticals. "This second trial is an important step in
ultimately evaluating SP-333's potential to treat GI inflammatory diseases
such as UC."

The present trial, designed as a placebo-controlled, dose-escalating,
multiple-dose study in 64 healthy adult volunteers, is focused on exploring
the safety profile of SP-333.The study will take place in one site in the
United States.

"SP-333 is our first clinical candidate for evaluating the anti-inflammatory
potential of GC-C receptors to treat GI anti-inflammatory conditions such as
UC," said Dr. Kunwar Shailubhai, Synergy's Chief Scientific Officer."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
normally produced in the lumen of the intestinal tract. Deficiency of
uroguanylin is likely to be one of the primary causes for the formation of
polyps, as well as debilitating and difficult-to-treat GI inflammatory
disorders such as UC and Crohn's disease. Orally-administered SP-333 binds to
and activates the GC-C receptor expressed on epithelial cells lining the GI
mucosa, thereby stimulating cyclic GMP in target tissues. SP-333 was shown to
be highly stable against proteolysis in simulated intestinal fluid for up to
24 hours. Its stability profile has made this peptide an extremely potent GC-C
agonist in studies of mice and monkeys. SP-333 promoted bowel movement in
studies of monkeys and ameliorated GI inflammation in studies of mice.

About Ulcerative Colitis

More than a half million Americans live with UC, a type of IBD that causes
chronic inflammation of the colon.Along with Crohn's disease, the other major
form of IBD, UC is painful and debilitating. Patients with UC are at increased
risk for colon cancer and may ultimately require surgical removal of the
colon. There are no medical cures for UC, and long-term remission with current
treatments is limited. New treatments for UC patients are urgently needed.

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 positive Phase I study of plecanatide in healthy volunteers, and
positive Phase IIa and Phase IIb/III clinical trials in patients with chronic
idiopathic constipation (CIC). Detailed positive findings from a recently
completed Phase IIb/III clinical trial will be presented at a major scientific
meeting this year.Synergy is also developing plecanatide for the treatment of
irritable bowel syndrome with constipation (IBS-C), having initiated the first
trial in IBS-C patients in late 2012. Synergy's second GC-C agonist, SP-333,
is in clinical development to treat inflammatory bowel diseases, and has just
completed its first Phase I trial in healthy volunteers. More information is
available at http://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, 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
         skidmorecomm@earthlink.net
        
         Investor Contact:
         Danielle Spangler
         The Trout Group
         synergy@troutgroup.com
         (646) 378-2924
 
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