Synergy Pharmaceuticals Highlights Mechanistic Features of Plecanatide, a Novel Investigational Drug for Chronic Idiopathic

Synergy Pharmaceuticals Highlights Mechanistic Features of Plecanatide, a
Novel Investigational Drug for Chronic Idiopathic Constipation

Scientific Poster Presentations This Week at ACG 2012 and UEG Week

NEW YORK, Oct. 22, 2012 (GLOBE NEWSWIRE) -- Synergy Pharmaceuticals Inc.
(Nasdaq:SGYP), a developer of new drugs to treat gastrointestinal disorders
and diseases, today announced the preclinical findings being presented by
Synergy scientists at two key gastroenterology congresses this week.

The scientific poster presentations describe the site of action and other
mechanistic features of plecanatide, Synergy's investigational drug for the
treatment of chronic idiopathic constipation (CIC) and irritable bowel
syndrome with constipation (IBS-C). Plecanatide is an agonist of the guanylate
cyclase-C receptor and an analog of the natriuretic peptide, uroguanylin, the
physiologic ligand of GC-C. As a uroguanylin analog, plecanatide is a member
of a new class of non-systemic oral drugs, known as guanylate cyclase-C (GC-C)
agonists, that act locally to promote intestinal fluid secretion.

"These preclinical studies helped to define plecanatide as a superior
candidate for clinical testing in patients with chronic constipation," said
Dr. Kunwar Shailubhai, Chief Scientific Officer of Synergy Pharmaceuticals,
who is presenting the data at the America College of Gastroenterology annual
meeting in Las Vegas, NV this week.

"In phase I and early phase II clinical testing, plecanatide exhibited an
excellent safety profile, and patients in the phase IIa trial experienced
relief from constipation without any remarkable diarrhea," said Stephen
Comiskey, Synergy's Vice President for Product Development, who is presenting
the preclinical data at the 20^th United European Gastroenterology Week in
Amsterdam, The Netherlands this week. "This summer Synergy achieved target
enrollment in an ongoing phase IIb/III clinical trial of plecanatide in
patients with chronic constipation, and we look forward to the results later
this year."

Key preclinical findings being presented that informed the clinical testing of
plecanatide as an optimal drug candidate include:

  *Orally administered plecanatide acts primarily in the proximal intestine
    to stimulate water secretion essential for normalizing bowel movement.
  *In vitro binding studies demonstrate that plecanatide binds to the same
    receptors in the proximal intestine as human uroguanylin.
  *Plecanatide is highly stable and potent, with even greater affinity for
    the human GC-C receptors than the natural uroguanylin hormone.

"There is a compelling need to find safe and effective treatments for patients
with CIC," said Douglas Drossman, Adjunct Professor of Medicine and Psychiatry
and Co-Director Emeritus, UNC Center for Functional GI and Motility Disorders,
UNC School of Medicine. "I am encouraged by the preclinical and early phase
clinical data that demonstrate proof of concept for plecanatide as a treatment
approach for chronic constipation, and look forward to seeing data from the
ongoing trials."

Earlier this fall, in a poster session at the Joint International
Neurogastroenterology and Motility Meeting, September 6-8, in Bologna, Italy,
Synergy scientists also shared data describing the identification and
selection of plecanatide (formerly SP-304) as a superior analog of uroguanylin
based on physiochemical properties.

Posters Cited


October 19-24, 2012, Las Vegas, NV

Orally Administered Plecanatide, A Guanylate Cyclase-C Agonist, Acts in the
Lumen of the Proximal Intestine to Facilitate Normal Bowel Movement in Mice
and Monkeys. (P451) Authored by Stephen Comiskey, John Foss, Gary Jacob, and
Kunwar Shailubhai.


October 20-24, 2012, Amsterdam, The Netherlands

Orally Administered Plecanatide, A Guanylate Cyclase-C Agonist, Acts in the
Proximal Intestine to Stimulate Fluid Secretion to Normalize Bowel Movement.

Authored by Stephen Comiskey, John Foss and Kunwar Shailubhai.


September 6-8, 2012, Bologna, Italy

Plecanatide, a Superior Analog of Uroguanylin, as an Oral Drug Candidate for
Treatment of Gastrointestinal Functional Disorders and Diseases. (P330)

Authored by Andrea Brancale, Gary Jacob and Kunwar Shailubhai.

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
(GI) 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 October, 2011, Synergy
initiated dosing 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 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 .

About Plecanatide

Plecanatide is a member of a new class of essentially non-systemic drugs,
referred to as guanylate cyclase C (GC-C) agonists, that are currently in
development to treat CIC and IBS-C. Plecanatide is a synthetic analog of
uroguanylin, a natriuretic hormone that regulates ion and fluid transport in
the GI tract. Orally-administered plecanatide binds to and activates GC-C
receptors expressed on epithelial cells lining the GI mucosa, resulting in
activation of the cystic fibrosis transmembrane conductance regulator (CFTR),
and leading to augmented flow of chloride and water into the lumen of the gut.
Activation of the GC-C receptor pathway is believed to facilitate bowel
movement as well as producing other beneficial physiological responses
including improvement in abdominal pain and inflammation. In animal models,
oral administration of plecanatide promotes intestinal secretion and also
ameliorates GI inflammation.

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
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