• Data reinforce the impact of linaclotide on symptoms of IBS-C and CIC 
• Additional studies highlight the burden of these disorders on patients 

BOSTON / Oct 23, 2023 / Business Wire / Ironwood Pharmaceuticals, Inc. (Nasdaq: IRWD), a global GI-focused healthcare company, presented new data from four scientific abstracts during the American College of Gastroenterology (ACG) 2023 Annual Scientific Meeting and Postgraduate Course. These data provide further insight into the impact of linaclotide on symptoms of irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation (CIC), as well as the burden of these disorders on patients.

“IBS-C and CIC are complex disorders that involve more than just constipation, and continued research into their persistent burden promotes better understanding of the multiple needs among these patients,” said Michael Shetzline, M.D., Ph.D., chief medical officer, senior vice president and head of research and drug development at Ironwood Pharmaceuticals. “The data presented at ACG peel back the many layers of these disorders’ impact. While pain is usually associated with IBS-C, it also can be experienced by those with CIC and both patient groups can be affected by anal/rectal-related adverse consequences. Ironwood is committed to understanding the impact of linaclotide on the full spectrum of symptoms in these disorders.”

Impact of Linaclotide in Patients with IBS-C and CIC

• A poster titled Effect of Menopausal Status Defined by Age on Treatment Efficacy in Women with Irritable Bowel Syndrome with Constipation: A Post Hoc Analysis of Pooled Phase 2b/3 Trials was presented by Lin Chang, M.D., David Geffen School of Medicine at UCLA, Los Angeles, CA. In this post-hoc analysis of efficacy data from Phase 2b/3 trials, a numerically higher percentage of responders were observed for abdominal pain and constipation, 30% improvement in abdominal pain, and degree of relief of IBS symptoms in patients aged >45 vs ≤45 years; adequate relief was also significantly higher in patients aged >45. Comparing treatment response within similar age groups, significant improvements were observed in patients receiving linaclotide versus placebo for every efficacy and responder endpoint assessed (all P<0.0001).
• A poster titled Linaclotide Improves Abdominal Symptoms over Placebo in Patients with Chronic Idiopathic Constipation: A Pooled Analysis was presented by Philip S. Schoenfeld, M.D., Gastroenterology Section, John D. Dingell Veterans Affairs Medical Center, Detroit, MI. The post-hoc analysis showed that at 12 weeks the patients with CIC receiving linaclotide had statistically significant decreases in change from baseline (CFB) and % CFB for abdominal pain, discomfort, and bloating compared to patients receiving placebo (all P<0.0001). Significant improvements in all three abdominal symptoms with linaclotide versus placebo were seen starting at week 1 and sustained through week 12. A significantly greater proportion of patients receiving linaclotide were responders for improvements in abdominal pain, discomfort and bloating versus those patients receiving placebo (all P≤0.001).
• A poster titled Treatment Satisfaction and Quality of Life in Patients with Irritable Bowel Syndrome with Constipation and Chronic Idiopathic Constipation was presented by Brian Lacy, Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL. The analysis of data from a large, nationwide survey of adults in the U.S. from August 2020 to December 2021 showed that participants taking prescription medications for IBS-C and CIC were more likely to be satisfied with control of bowel or abdominal symptoms than participants taking only over-the-counter medication.

Burden of IBS-C and CIC

• A poster titled Burden of Anal/Rectal-Related Adverse Consequences Associated with Chronic Straining Among Patients with Irritable Bowel Syndrome and/or Constipation was presented by Kathy Kosch, AbbVie Inc., North Chicago, IL. This retrospective cohort study derived from health insurance claims found that non-D IBS and CIC cases had a higher proportion of anal/rectal-related adverse events versus controls, with the most common event being hemorrhoids. Non-D-IBS and CIC cases had higher costs versus controls on both a per-patient and a per-utilization basis.

About Linaclotide

LINZESS^® is the #1 prescribed brand in the U.S. for the treatment of adult patients with irritable bowel syndrome with constipation (“IBS-C”) or chronic idiopathic constipation (“CIC”), based on IQVIA data.

LINZESS is a once-daily capsule that helps relieve the abdominal pain, constipation, and overall abdominal symptoms of bloating, discomfort and pain associated with IBS-C, as well as the constipation, infrequent stools, hard stools, straining, and incomplete evacuation associated with CIC. LINZESS relieves constipation in children and adolescents aged 6 to 17 years with functional constipation. 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. In children with functional constipation aged 6 to 17 years, the recommended dose is 72 mcg.

LINZESS is not a laxative; it is the first medicine approved by the FDA in a class called 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 AbbVie co-develop and co-commercialize LINZESS for the treatment of adults with IBS-C or CIC. In Europe, AbbVie 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 AbbVie for development and commercialization of linaclotide in all other territories worldwide.

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) and functional constipation (FC) in children and adolescents 6 to 17 years of age. It is not known if LINZESS is safe and effective in children with FC less than 6 years of age or in children with IBS-C less than 18 years of age.

IMPORTANT SAFETY INFORMATION

Contraindications

• LINZESS is contraindicated in patients less than 2 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

• LINZESS is contraindicated in patients less than 2 years of age. In neonatal mice, linaclotide increased fluid secretion as a consequence of age-dependent elevated guanylate cyclase (GC-C) agonism, which was associated with increased mortality within the first 24 hours due to dehydration. There was no age dependent trend in GC-C intestinal expression in a clinical study of children 2 to less than 18 years of age; however, there are insufficient data available on GC-C intestinal expression in children less than 2 years of age to assess the risk of developing diarrhea and its potentially serious consequences in these patients.

Diarrhea

• In adults, 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.
• In children and adolescents 6 to 17 years of age, diarrhea was the most common adverse reaction in 72 mcg LINZESS-treated patients in the FC double-blind placebo-controlled trial. Severe diarrhea was reported in <1% of 72 mcg LINZESS treated 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 or CIC adult patients: diarrhea, abdominal pain, flatulence, and abdominal distension.
• In FC pediatric patients: diarrhea.

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

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.

About Ironwood Pharmaceuticals

Ironwood Pharmaceuticals (Nasdaq: IRWD), an S&P SmallCap 600^® company, is a leading global gastrointestinal (GI) healthcare company on a mission to advance the treatment of GI diseases and redefine the standard of care for GI patients. We are pioneers in the development of LINZESS^® (linaclotide), the U.S. branded prescription market leader for adults with irritable bowel syndrome with constipation (IBS-C) or chronic idiopathic constipation (CIC). LINZESS is also approved for the treatment of functional constipation in pediatric patients ages 6-17 years-old. Ironwood is also advancing apraglutide, a next-generation, long-acting synthetic GLP-2 analog being developed for rare gastrointestinal diseases, including short bowel syndrome with intestinal failure (SBS-IF) as well as several earlier stage assets. Building upon our history of GI innovation, we keep patients at the heart of our R&D and commercialization efforts to reduce the burden of GI diseases and address significant unmet needs.

Founded in 1998, Ironwood Pharmaceuticals is headquartered in Boston, Massachusetts, and has additional operations in Basel, Switzerland.

We routinely post information that may be important to investors on our website at www.ironwoodpharma.com. In addition, follow us on Twitter and on LinkedIn.

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 the impact of linaclotide on symptoms of IBS-C and CIC, as well as the burden of these disorders on patients. These forward-looking statements speak only as of the date of this press release, and Ironwood undertakes no obligation to update these forward-looking statements. 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 effectiveness of development and commercialization efforts by us and our partners; preclinical and clinical development, manufacturing and formulation development of linaclotide and our product candidates; the risk that clinical programs and studies may not progress or develop as anticipated, including that studies are delayed or discontinued for any reason, such as safety, tolerability, enrollment, manufacturing, economic or other reasons; the risk that findings from our completed nonclinical and clinical studies may not be replicated in later studies; the risk that we or our partners are unable to obtain, maintain or manufacture sufficient LINZESS, apraglutide or our product candidates, or otherwise experience difficulties with respect to supply or manufacturing; the efficacy, safety and tolerability of linaclotide, apraglutide and our product candidates; the risk that the therapeutic opportunities for LINZESS, apraglutide or our product candidates are not as we expect; decisions by regulatory and judicial authorities; the risk we may never get additional patent protection for linaclotide, apraglutide and other product candidates, that patents for linaclotide, apraglutide or other products may not provide adequate protection from competition, or that we are not able to successfully protect such patents; outcomes in legal proceedings to protect or enforce the patents relating to our products and product candidates, including abbreviated new drug application litigation; the risk that financial and operating results may differ from our projections; developments in the intellectual property landscape; challenges from and rights of competitors or potential competitors; developments in accounting guidance or practice; Ironwood’s or AbbVie’s accounting practices, including reporting and settlement practices as between Ironwood and AbbVie; the risk that we are unable to manage our expenses or cash use, or are unable to commercialize our products as expected; and the risks listed under the heading “Risk Factors” and elsewhere in our Annual Report on Form 10-K for the fiscal year ended December 31, 2022, and in our subsequent SEC filings.