Ironwood Pharmaceuticals and Allergan Initiate Patient Dosing in Phase II Clinical Trial of MD-7246 in Patients with Abdominal Pain Associated with IBS-D

– Top-line data from Phase II trial expected in second half 2020 –

CAMBRIDGE, Mass.–(BUSINESS WIRE)–Ironwood
Pharmaceuticals, Inc. (NASDAQ:IRWD), a GI-focused healthcare
company, today announced the initiation of patient dosing in a Phase II
clinical trial evaluating MD-7246 in patients with abdominal pain
associated with irritable bowel syndrome with diarrhea (IBS-D). Data
from the Phase II trial are expected in the second half of 2020.

Ironwood and Allergan are evaluating MD-7246, an investigational new
product, as an oral, intestinal, non-opioid, pain-relieving agent for
patients suffering from abdominal pain associated with certain GI
diseases. MD-7246 is a delayed-release formulation of linaclotide
designed to provide targeted delivery of linaclotide to the colon, where
the majority of the abdominal pain associated with IBS-D is believed to
originate, and to limit fluid secretion in the small intestine resulting
in minimal impact on bowel function.

“Abdominal pain is a dominant symptom experienced by approximately 16
million people in the U.S. living with IBS-D, and there are a limited
number of treatment options for patients seeking effective pain relief,”
said Michael Shetzline, M.D., Ph.D., chief medical officer, senior vice
president and head of drug development at Ironwood. “Through its delayed
release and differentiated mechanism of action, we believe that MD-7246
has the potential to target abdominal pain in patients with IBS-D and
look forward to advancing it as a potential abdominal pain-relieving
agent for this population. If successful, we hope to explore the broader
potential of MD-7246 for the more than 50 million patients estimated to
suffer from recurring abdominal pain across a broader range of GI
disorders.”

The Phase II trial is a randomized, double-blind, placebo-controlled,
parallel-group, dose-range-finding, 12-week study. It is designed to
evaluate the safety, tolerability, treatment effect on abdominal pain,
and dose response of MD-7246 administered orally to patients with
abdominal pain associated with IBS-D. The study is expected to enroll
approximately 400 IBS-D patients who are randomized equally across three
dose levels of MD-7246 (300, 600 or 1,200 mcg), or matching placebo,
administered once daily.

Data from an earlier
Phase IIb trial in patients with IBS with constipation (IBS-C)
showed that MD-7246, as intended, numerically improved abdominal pain
relative to placebo, with no apparent effect on bowel movement function.

About IBS-D
Approximately 16 million patients suffer from
IBS-D in the United States. ^1,2 These patients report
frequent abdominal pain (approximately 86 days of the year), discomfort
and bloating, along with stools that are more loose or frequent than
usual. ³ More than 80% of surveyed patients report IBS-D
symptoms as somewhat to extremely severe.⁴

About MD-7246
MD-7246 is a delayed release formulation of
linaclotide being evaluated by Ironwood and its partner Allergan plc as
an oral, non-opioid, pain-relieving agent for patients in the U.S.
suffering from abdominal pain associated with IBS with diarrhea (IBS-D).
Linaclotide is thought to work in two different ways, based on
non-clinical studies: by increasing fluid secretion into the intestine
and by decreasing the activity of pain-sensing nerves. MD-7246 is
designed to provide targeted delivery of linaclotide to the colon, where
the majority of the abdominal pain associated with IBS-D is believed to
originate, and to limit fluid secretion in the small intestine resulting
in minimal impact on bowel function. Ironwood and Allergan have issued
patents and pending patent applications covering MD-7246 that are
expected to provide patent coverage into the mid-2030s.

About Ironwood Pharmaceuticals
Ironwood Pharmaceuticals
(Nasdaq:IRWD) is a GI-focused healthcare company dedicated to creating
medicines that make a difference for patients living with GI diseases.
We discovered, developed and are commercializing linaclotide, the U.S.
branded prescription market leader for adults with irritable bowel
syndrome with constipation (IBS-C) or chronic idiopathic constipation
(CIC). We are currently advancing a Phase IIIb trial evaluating the
efficacy and safety of linaclotide on multiple abdominal symptoms,
including bloating, pain, and discomfort, in adult patients with IBS-C.

We are also advancing two late-stage, first-in-category GI product
candidates: IW-3718 is a gastric retentive formulation of a bile acid
sequestrant being developed for the potential treatment of persistent
gastroesophageal reflux disease, and MD-7246 is a delayed-release
formulation of linaclotide that is being evaluated as an oral,
intestinal, non-opioid, pain-relieving agent for patients suffering from
abdominal pain associated with IBS with diarrhea.

Ironwood was founded in 1998 and is headquartered in Cambridge, Mass.
For more information, please visit our website at www.ironwoodpharma.com
or www.twitter.com/ironwoodpharma;
information that may be important to investors will be routinely posted
in both these locations.

Forward-Looking Statements
This press release contains
forward-looking statements. Investors are cautioned not to place undue
reliance on these forward-looking statements, including, but not limited
to, the design of the Phase II clinical trial of MD-7246 in patients
with abdominal pain associated with IBS-D, including the target
indication and expected enrollment and dosing; the anticipated timing of
data from the Phase II trial; the mechanism of action of MD-7246 and
linaclotide; the prevalence of abdominal pain associated with certain GI
diseases and the unmet need for effective treatment; the potential for
MD-7246 to offer IBS-D patients and other patients suffering from a
broader range of GI disorders relief from abdominal pain; and the
development and regulatory plans for MD-7246. Each
forward-looking statement is subject to risks and uncertainties that
could cause actual results to differ materially from those expressed or
implied in such statement. Applicable risks and uncertainties include
those related to preclinical and clinical development, manufacturing and
formulation development; the risk that future clinical studies need to
be discontinued for any reason, including safety, tolerability,
enrollment, manufacturing or economic reasons; the risk that findings
from our completed nonclinical and clinical studies may not be
replicated in later studies; efficacy, safety and tolerability of our
products and product candidates; the risk that the therapeutic
opportunities for MD-7246 are not as we expect; decisions by regulatory
and judicial authorities; the risk that we are unable to successfully
commercialize MD-7246; the risk that we may never get sufficient patent
protection for our products and our product candidates or that we are
not able to successfully protect such patents; the outcomes in legal
proceedings to protect or enforce the patents relating to our products
and product candidates, including ANDA litigation; developments in the
intellectual property landscape; challenges from and rights of
competitors or potential competitors; the risk that our planned
investments do not have the anticipated effect on our company revenues,
products or product candidates; the risk that we are unable to manage
our operating expenses or cash use for operations, or are unable to
commercialize our products, within the guided ranges or otherwise as
expected; and the risks listed under the heading “Risk Factors” and
elsewhere in Ironwood’s Quarterly Report on Form 10-Q for the quarter
ended March 31, 2019, and in our subsequent SEC filings. These
forward-looking statements (except as otherwise noted) speak only as of
the date of this press release, and Ironwood undertakes no obligation to
update these forward-looking statements.

¹ Grundmann O, Yoon SL. Irritable bowel syndrome:
Epidemiology, diagnosis and treatment: An update for health-care
practitioners. J Gastroenterol Hepatol. 2010;25:691-699.
²
Quick Facts-United States. United States Census Bureau website. https://www.census.gov/quickfacts/table/PST045215/00.
Accessed October 28, 2016.
³ American Society for
Gastrointestinal Endoscopy. Understanding Irritable Bowel Syndrome with
Diarrhea (also known as IBS-D). Available at: https://www.asge.org/home/for-patients/patient-information/understanding-irritable-bowel-syndrome-with-diarrhea-also-known-as-ibs-d.
Accessed May 10, 2019
⁴ Drossman DA, Morris CB, Schneck
S, et al. International survey of patients with IBS: symptom features
and their severity, health status, treatments, and risk taking to
achieve clinical benefit. J Clin Gastroenterol.
2009;43(6):541–550. doi:10.1097/MCG.0b013e318189a7f9

Contacts

Media and Investors:
Meredith Kaya, 617-374-5082
Vice
President, Investor Relations and Corporate Communications
[email protected]