Ironwood Survey Findings at DDW 2026 Underscore Need for Therapies that Address Multiple Dimensions of Total Parenteral Nutrition (TPN) Burden in Short Bowel Syndrome (SBS)

– Surveyed HCPs identified reduction of days on TPN as a top priority –

– Improved quality of life, lower risk of infection and thrombosis viewed as key benefits of reduced TPN dependence –

– Additional presentations feature long-term apraglutide safety and tolerability data, new linaclotide data analyses across patient populations –

Ironwood Pharmaceuticals, Inc. (NASDAQ:IRWD), a biotechnology company developing and commercializing life-changing therapies for people living with gastrointestinal (GI) and rare diseases, presented new findings at Digestive Diseases Week® (DDW) 2026 from a survey assessing healthcare provider (HCP) perspectives on the use of total parenteral nutrition (TPN) in the treatment of short bowel syndrome (SBS). Surveyed HCPs emphasized the importance of reducing patient dependence on TPN to improve quality of life, reduce line infections and lower the risk of thrombosis. The majority (46.4%) identified reducing the number of days per week on TPN as a priority attribute of future therapies. An additional 30.1% prioritized reducing TPN hours per day, while fewer respondents (11.3%) prioritized reducing TPN volume.

SBS is a serious and chronic condition characterized by reduced absorptive capacity for fluids and/or nutrients, often requiring long-term dependence on parenteral support or PS (IV nutrition and/or IV hydration) to sustain life. Patients with SBS who are chronically dependent on PS, also referred to as SBS with intestinal failure (SBS-IF), frequently experience significant treatment burden, reduced quality of life and increased risk of severe complications such as infections. Despite current management approaches, substantial unmet need remains for therapies that reduce PS dependence and improve outcomes. An estimated 18,000 adult patients suffer from SBS-IF in the U.S., Europe and Japan, and have chronic dependence on PS.

"For many people living with short bowel syndrome, TPN is life-sustaining but can also profoundly affect quality of life. The LANDMARK survey shows that there remains a clear need for more therapies that further reduce TPN dependence," said Syed-Mohammed R. Jafri, M.D., a gastroenterologist and transplant hepatologist with Detroit-based Henry Ford Health and lead author of the study. "While reducing TPN volume is still important, reducing the number of days on TPN may have a more meaningful impact on patients' lives."

The survey findings also highlighted the significant burden associated with long-term TPN dependence among patients with SBS-IF. HCPs cited central line infections (59.8%), fatigue (47.9%), central line pain (43.2%), abdominal pain (40.5%), edema (37.5%) and thrombosis (29.5%) as the most common complications. Central line infections (49.7%) and central line pain (44.0%) were identified as the most distressing issues for patients. Nearly half of respondents (48.2%) cited central venous catheter related challenges – including infections, pain and thrombosis – as a primary limitation of TPN, followed by decreased quality of life (34.8%) and hepatotoxicity (32.4%).

"The survey findings underscore the real-world experience of patients suffering with SBS-IF while the endpoints in our STARS and STARS-2 clinical trials of apraglutide are designed to evaluate dimensions of parenteral support dependence, including reduction in TPN volume and increases in days off TPN," said Michael Shetzline, M.D., Ph.D., chief medical officer, senior vice president and head of research and drug development at Ironwood Pharmaceuticals. "By staying grounded in real-world insights from HCPs – and patients – we can better focus on improving patient outcomes."

In addition to the survey findings, Ironwood and its collaborators presented data from apraglutide and linaclotide studies. Key findings are summarized below.

Apraglutide Long-Term Safety Data

• Data pooled from the STARS clinical program – including the Phase 2 STARS Nutrition study, STARS Phase 3 randomized placebo-controlled parent study and the ongoing open-label extension STARS Extend – demonstrated that apraglutide showed a well-tolerated long-term safety profile consistent with previous studies, low discontinuation rates due to TEAEs and no new safety observations.

Linaclotide Data

• In pediatric patients aged 2-5 years with functional constipation, data from a Phase 3 open-label extension showed that linaclotide 72 mcg was well tolerated with no new safety signals. The majority of patients saw their FC symptoms resolve, with a low incidence of diarrhea.
• In adults with IBS-C, a post-hoc analysis showed that linaclotide was associated with improved IBS-C symptoms across race, ethnicity and age subgroups. Safety outcomes were consistent with the established safety profile.
• In adults with severe CIC, a post-hoc pooled analysis of Phase 3 studies showed that linaclotide 72 mcg or 145 mcg improved bowel movement frequency, stool consistency, straining and most abdominal symptoms, highlighting its ability to address both bowel function and symptom burden.
• A post-hoc analysis showed that linaclotide demonstrated efficacy across key clinical endpoints in adults with CIC and IBS-C irrespective of pH-modifying agent use, and in IBS-C irrespective of pH-modifying agent use, with safety outcomes consistent with the known safety profile.

About the LANDMARK Survey

The LANDMARK disease burden survey is a cross-sectional study of HCPs, patients and caregivers assessing the real-world burden of SBS and PS dependence. The HCP survey recruited 336 participants (U.S., n=123; Europe, n=213) with two or more years of experience treating patients with SBS-IF and actively managing one or more patients. Respondents included physicians (42.0%), pharmacists (23.0%), and dietitians (18.0%), practicing primarily in gastroenterology (45.2%), clinical nutrition/nutritional support (23.5%) and internal medicine (17.3%).

About STARS and STARS-2

The STARS (STudy of ApRaglutide in SBS) pivotal Phase 3 clinical trial represents the largest Phase 3 clinical trial in SBS-IF to date.

This global, multicenter, double-blind, randomized, placebo-controlled trial evaluated the efficacy and safety of weekly subcutaneous injections of apraglutide in adult patients with SBS-IF. STARS enrolled 164 patients and dosed 163 stratified approximately 50/50 (stoma vs. colon-in-continuity), then evaluated them over 24 weeks (stoma and colon-in-continuity populations) and 48 weeks (colon-in-continuity population only). Patients were randomized 2:1 to either once weekly apraglutide or placebo. The primary endpoint was relative change from baseline in actual weekly PS volume at week 24. Key secondary endpoints included patients who achieved a reduction from baseline of at least 1 day/week of PS at week 24 (all patients); relative change from baseline in actual weekly PS volume at week 24 (stoma population); patients who achieved a reduction from baseline of at least 1 day/week of PS at week 48 (colon-in-continuity population); and patients reaching enteral autonomy at week 48 (colon-in-continuity population). The study was conducted in 18 countries with 68 active sites.

STARS-2 is a planned confirmatory Phase 3 clinical trial of apraglutide for patients with SBS-IF. STARS-2 is planned to be a 24-week global, randomized, double-blind, placebo-controlled trial. The clinical trial will consist of a primary endpoint measuring relative change from baseline in actual weekly PS as well as additional key secondary endpoints.

About Apraglutide

Apraglutide is an investigational, next-generation, long-acting synthetic GLP-2 analog with the potential to treat a range of rare gastrointestinal diseases where GLP-2 can play a central role in addressing disease pathophysiology. Ironwood is advancing apraglutide for short bowel syndrome ("SBS") patients dependent on parenteral support ("PS"), a severe chronic malabsorptive condition. As the first and only GLP-2 to achieve a statistically significant reduction in weekly parenteral support volume with once-weekly administration, Ironwood believes apraglutide has the potential to improve the standard of care for adult patients with SBS who are dependent on PS.

About LINZESS (Linaclotide)

LINZESS® is the #1 prescribed brand in the U.S. for the treatment of 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 and constipation, associated with IBS-C in adults and pediatric patients 7 years of age and older. LINZESS has also been shown to relieve constipation, infrequent stools, hard stools, straining and incomplete evacuation associated with CIC in adult patients. LINZESS relieves constipation in children and adolescents aged 6 to 17 years with functional constipation.

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 for the treatment of irritable bowel syndrome with constipation (IBS-C) in adults and pediatric patients 7 years of age and older and for the treatment of chronic idiopathic constipation (CIC) in adults and for the treatment of functional constipation (FC) in children and adolescents 6 to 17 years of age.

IMPORTANT SAFETY INFORMATION

WARNING: RISK OF SERIOUS DEHYDRATION IN PEDIATRIC PATIENTS LESS THAN 2 YEARS OF AGE

LINZESS is contraindicated in patients less than 2 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.

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 pediatric patients, diarrhea was also the most common adverse reaction of LINZESS-treated patients in IBS-C and FC clinical trials. In two double-blind trials, diarrhea was reported in 4% of pediatric patients 6 to 17 years of age with FC treated with LINZESS 72 mcg once daily, and 7% and 8% of pediatric patients 7 to 17 years of age with IBS-C treated with LINZESS 145 mcg and 290 mcg once daily, respectively. In clinical trials, severe diarrhea was reported in one pediatric patient with FC treated with LINZESS 72 mcg once daily and in one pediatric patient with IBS-C treated with LINZESS at a dosage higher than the recommended 145 mcg once daily dosage for IBS-C.

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

• In IBS-C or CIC adult patients: diarrhea, abdominal pain, flatulence and abdominal distension.
• Most common adverse reaction reported in pediatric patients with FC or IBS-C is diarrhea.

Please see full Prescribing Information including Boxed Warning: https://www.rxabbvie.com/pdf/linzess_pi.pdf

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) is a biotechnology company developing and commercializing life-changing therapies for people living with gastrointestinal (GI) and rare diseases. Ironwood is advancing apraglutide, a next-generation, long-acting synthetic GLP-2 analog being developed for short bowel syndrome patients who are dependent on parenteral support. In addition, Ironwood has been a pioneer in the development of LINZESS® (linaclotide), the U.S. branded prescription market leader for the treatment of irritable bowel syndrome with constipation (IBS-C) or chronic idiopathic constipation (CIC). Building upon our history of innovation, we keep patients at the heart of our R&D and commercialization efforts to reduce the burden of diseases and address significant unmet needs.

Founded in 1998, Ironwood Pharmaceuticals is headquartered in Boston, Massachusetts, with a site 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 X and on LinkedIn.

About DDW

Digestive Disease Week® (DDW) is the largest international gathering of physicians, researchers and academics in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery. Jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA), the American Society for Gastrointestinal Endoscopy (ASGE) and the Society for Surgery of the Alimentary Tract (SSAT), DDW is an in-person and online meeting.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Investors are cautioned not to place undue reliance on these forward-looking statements, including statements about the reduction of number of days on TPN may have a meaningful impact on patients' lives; the estimated adult population who suffer from SBS-IF in the U.S., Europe and Japan; the planned confirmatory Phase 3 clinical trial, STARS-2, for apraglutide; and insights from the LANDMARK survey. 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, apraglutide and our other product candidates; the risk of uncertainty relating to pricing and reimbursement policies in the U.S., which, if not favorable for our products, could hinder or prevent our products' commercial success; the risk that clinical programs and studies, including for linaclotide pediatric programs and apraglutide, 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 studies and clinical trials may not be replicated in later trials and earlier-stage clinical trials may not be predictive of the results we may obtain in later-stage clinical trials or of the likelihood of regulatory approval; the risk that apraglutide will not be approved by the FDA or other regulatory agencies; the risk of competition or that new products may emerge that provide different or better alternatives for treatment of the conditions that our products are approved to treat; the risk that healthcare reform and other governmental and private payor initiatives may have an adverse effect upon or prevent our products' or product candidates' commercial success; the efficacy, safety and tolerability of linaclotide and our product candidates; the risk that the commercial and therapeutic opportunities for LINZESS, apraglutide or our other 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; the risk that we are unable to manage our expenses or cash use, or are unable to commercialize our products as expected; the risk that the development of any of our linaclotide pediatric programs and/or apraglutide is not successful or that any of our product candidates does not receive regulatory approval or is not successfully commercialized; 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; the risk that our planned investments do not have the anticipated effect on our company revenues; 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 our indebtedness could adversely affect our financial condition or restrict our future operations; and the risks listed under the heading "Risk Factors" and elsewhere in our Annual Report on Form 10-K for the year ended December 31, 2025, and in our subsequent Securities and Exchange Commission filings.

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