Market Overview

Ironwood Pharmaceuticals Completes Separation of Cyclerion Therapeutics and Becomes a Gastrointestinal (GI)-focused Healthcare Company

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– Ironwood capitalizing on GI leadership and expertise in an effort
to bring innovative therapies to patients –

– Strategy centered on accelerating LINZESS®
(linaclotide) growth and advancing late-stage programs IW-3718 and
MD-7246 –

– Business poised to drive revenue growth and begin generating
profits –

Ironwood
Pharmaceuticals, Inc.
(NASDAQ:IRWD), a GI-focused healthcare
company, today announced that it has completed the tax-free spin-off of
its soluble guanylate cyclase (sGC) business, Cyclerion Therapeutics,
Inc. (Cyclerion).

Ironwood is executing on its strategy to drive growth as a GI-focused
company, building upon its commercial success with LINZESS and advancing
its late-stage, first-in-category development candidates including
IW-3718 for the potential treatment of persistent gastroesophageal
reflux disease (GERD) and MD-7246 for the potential treatment of
abdominal pain associated with irritable bowel syndrome with diarrhea
(IBS-D). In 2018, Ironwood grew revenue 16% year-over-year to $347
million, driven primarily by U.S. LINZESS collaboration revenue of $264
million and linaclotide API sales of $70 million. In 2019, Ironwood
expects revenue to be in the range of $370 to $390 million. The company
also expects to provide guidance on 2019 non-GAAP profitability from
continuing operations on its first quarter 2019 investor update.

Mark Mallon, chief executive officer of Ironwood, stated, "Today marks
the beginning of a new chapter for Ironwood, one that combines a strong
drug development and commercial foundation with a sharpened focus on our
core objective – creating medicines that make a difference for people
living with GI diseases. We are well positioned to deliver on our
strategic initiatives, which include accelerating growth of LINZESS,
advancing our GI development portfolio, and generating profits from
continuing operations on a non-GAAP basis. I am honored and excited to
lead a spectacular team in this next phase of Ironwood's growth and
development, and to drive further innovation within the GI market in
order to deliver differentiated therapies to patients."

Cyclerion common stock will begin regular way trading on the Nasdaq
Global Select Market under the symbol "CYCN" on April 2, 2019. Ironwood
will continue to trade on Nasdaq under the ticker symbol "IRWD."

As previously announced, the separation was completed through today's
distribution to Ironwood shareholders of one share of Cyclerion common
stock for every 10 shares of Ironwood common stock held as of the close
of business on March 19, 2019, the record date for the distribution.
Ironwood shareholders of record will also receive cash in lieu of any
fractional shares of Cyclerion common stock that those holders would
have received after application of the above ratio.

About Ironwood Pharmaceuticals

Ironwood Pharmaceuticals (NASDAQ:IRWD) is a GI-focused healthcare
company focused on 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 newly launched 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.

About LINZESS (linaclotide)

LINZESS® is the #1 prescribed brand for the treatment of adult patients
with irritable bowel syndrome with constipation (IBS-C) and chronic
idiopathic constipation (CIC), based on IQVIA data. Since its FDA
approval in August of 2012 and subsequent launch in December 2012,
greater than 2.5 million unique patients have filled approximately 12.2
million prescriptions for LINZESS, according to IQVIA.

LINZESS is a once-daily capsule that helps relieve the abdominal pain
and constipation associated with IBS-C, as well as the constipation,
infrequent stools, hard stools, straining, and incomplete evacuation
associated with CIC. The recommended dose is 290 mcg for IBS-C patients
and 145 mcg for CIC patients, with a 72-mcg dose approved for use in CIC
depending on individual patient presentation or tolerability. LINZESS
should be taken at least 30 minutes before the first meal of the day.

LINZESS is contraindicated in pediatric patients less than 6 years of
age. The safety and effectiveness of LINZESS in pediatric patients less
than 18 years of age have not been established. In neonatal mice,
linaclotide increased fluid secretion as a consequence of GC-C agonism
resulting in mortality within the first 24 hours due to dehydration. Due
to increased intestinal expression of GC-C, patients less than 6 years
of age may be more likely than patients 6 years of age and older to
develop severe diarrhea and its potentially serious consequences. In
adults with IBS-C or CIC treated with LINZESS, the most commonly
reported adverse event was diarrhea.

LINZESS is not a laxative; it is the first medicine approved by the FDA
in a class called guanylate cyclase-C (GC-C) agonists. LINZESS contains
a peptide called linaclotide that activates the GC-C receptor in the
intestine. Activation of GC-C is thought to result in increased
intestinal fluid secretion and accelerated transit and a decrease in the
activity of pain-sensing nerves in the intestine. The clinical relevance
of the effect on pain fibers, which is based on nonclinical studies, has
not been established.

In the United States, Ironwood and Allergan plc co-develop and
co-commercialize LINZESS for the treatment of adults with IBS-C or CIC.
In Europe, Allergan markets linaclotide under the brand name CONSTELLA®
for the treatment of adults with moderate to severe IBS-C. In Japan,
Ironwood's partner Astellas markets linaclotide under the brand name
LINZESS for the treatment of adults with IBS-C or CIC. Ironwood also has
partnered with AstraZeneca for development and commercialization of
LINZESS in China, and with Allergan for development and
commercialization of linaclotide in all other territories worldwide.

About IW-3718

IW-3718 is a novel, gastric retentive formulation of colesevelam, a bile
acid sequestrant, developed by Ironwood using the proprietary Acuform®
drug delivery formulation technology licensed from Assertio
Therapeutics, Inc. IW-3718 is designed to deliver the bile acid
sequestrant to the stomach over an extended period of time where it is
positioned to intercept bile before it reaches the esophagus. Data from
non-clinical and clinical studies collectively support the extended
release and gastric-retentive profile of IW-3718. Ironwood has issued
patents and pending patent applications for IW-3718 that are expected to
provide patent coverage into the mid-2030s.

About MD-7246

MD-7246 is a delayed release formulation of linaclotide being evaluated
by Ironwood and its partner Allergan 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 ways, based on non-clinical studies: by decreasing the
activity of pain-sensing nerves and by increasing fluid secretion into
the intestine. MD-7246 is designed to provide targeted delivery of
linaclotide to the colon, where the majority of the abdominal pain
associated with IBS is believed to originate, with minimal effect on
fluid secretion thereby reducing its impact on bowel function. Ironwood
and Allergan have issued patents and pending patent applications for
MD-7246 that are expected to provide patent coverage into the mid-2030s.

LINZESS Important Safety Information

INDICATIONS AND USAGE

LINZESS (linaclotide) is indicated in adults for the treatment of both
irritable bowel syndrome with constipation (IBS-C) and chronic
idiopathic constipation (CIC).

IMPORTANT SAFETY INFORMATION

 

WARNING: RISK OF SERIOUS DEHYDRATION IN PEDIATRIC PATIENTS

LINZESS is contraindicated in patients less than 6 years of
age. In nonclinical studies in neonatal mice, administration of a
single, clinically relevant adult oral dose of linaclotide caused
deaths due to dehydration. Use of LINZESS should be avoided in
patients 6 years to less than 18 years of age. The safety and
effectiveness of LINZESS have not been established in patients
less than 18 years of age.

 

Contraindications

  • LINZESS is contraindicated in patients less than 6 years of age due to
    the risk of serious dehydration.
  • LINZESS is contraindicated in patients with known or suspected
    mechanical gastrointestinal obstruction.

Warnings and Precautions

Pediatric Risk

  • LINZESS is contraindicated in patients less than 6 years of age. The
    safety and effectiveness of LINZESS in patients less than 18 years of
    age have not been established. In neonatal mice, linaclotide increased
    fluid secretion as a consequence of GC-C agonism resulting in
    mortality within the first 24 hours due to dehydration. Due to
    increased intestinal expression of GC-C, patients less than 6 years of
    age may be more likely than patients 6 years of age and older to
    develop severe diarrhea and its potentially serious consequences.
  • Use of LINZESS should be avoided in pediatric patients 6 years to less
    than 18 years of age. Although there were no deaths in older juvenile
    mice, given the deaths in young juvenile mice and the lack of clinical
    safety and efficacy data in pediatric patients, use of LINZESS should
    be avoided in pediatric patients 6 years to less than 18 years of age.

Diarrhea

  • Diarrhea was the most common adverse reaction in LINZESS-treated
    patients in the pooled IBS-C and CIC double-blind placebo-controlled
    trials. The incidence of diarrhea was similar in the IBS-C and CIC
    populations. Severe diarrhea was reported in 2% of 145 mcg and 290 mcg
    LINZESS-treated patients, and in <1% of 72 mcg LINZESS-treated CIC
    patients. If severe diarrhea occurs, dosing should be suspended and
    the patient rehydrated.

Common Adverse Reactions (incidence ≥2% and greater than placebo)

  • In IBS-C clinical trials: diarrhea (20% vs 3% placebo), abdominal pain
    (7% vs 5%), flatulence (4% vs 2%), headache (4% vs 3%), viral
    gastroenteritis (3% vs 1%) and abdominal distension (2% vs 1%).
  • In CIC trials of a 145 mcg dose: diarrhea (16% vs 5% placebo),
    abdominal pain (7% vs 6%), flatulence (6% vs 5%), upper respiratory
    tract infection (5% vs 4%), sinusitis (3% vs 2%) and abdominal
    distension (3% vs 2%). In a CIC trial of a 72 mcg dose: diarrhea (19%
    vs 7% placebo) and abdominal distension (2% vs <1%).

Please see full Prescribing Information including Boxed Warning: http://www.allergan.com/assets/pdf/linzess_pi

IRONWOOD®, the three-leaf logo, LINZESS® and CONSTELLA® are registered
trademarks of Ironwood Pharmaceuticals, Inc. Any other trademarks
referred to in this press release are the property of their respective
owners. All rights reserved.

Forward-Looking Statements

This press release contains forward-looking statements. Investors are
cautioned not to place undue reliance on these forward-looking
statements, including statements about Ironwood's ability to achieve
profitability and its competitiveness and strategic positioning; the
development, launch, commercial availability and commercial potential of
our products, product candidates and the other products that we promote
and the drivers, timing, impact and results thereof; the potential
indications for, and benefits of, our products and product candidates;
patent coverage for IW-3718 and MD-7246; and our financial performance
and results, and guidance and expectations related thereto (including
the drivers and timing thereof), including expectations related to
revenue. 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 the possibility that we may not
achieve the expected benefits of the separation and that the separation
could harm our business, results of operations and financial condition;
the risk that the costs of the separation outweigh the benefits of the
separation; the effectiveness of development and commercialization
efforts by us and our partners; preclinical and clinical development,
manufacturing and formulation development; 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; decisions by regulatory and judicial authorities;
the risk that we may never get sufficient patent protection for our
products and 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, our 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; the risk that
Ironwood may not achieve profitability; the risk that a separation may
adversely impact our ability to attract or retain key personnel; and the
risks listed under the heading "Risk Factors" and elsewhere in
Ironwood's Annual Report on Form 10-K for the year ended December 31,
2018, 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.

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