Apraglutide

– Ironwood Chief Medical Officer and Head of Research and Drug Development Dr. Michael Shetzline to Retire After 30-Year Career Advancing GI Science and Patient Care – – Dr. Silber, a Drug Development Veteran, Will Lead Ironwood’s Next Phase of R&D Strategy and Execution – BOSTON--(BUSINESS WIRE)-- Ironwood Pharmaceuticals, Inc. (Nasdaq: IRWD), a biotechnology company developing and commercializing life‑changing therapies for people living with gastrointestinal (GI) and rare diseases, today announced the retirement of Chief Medical Officer and Head of Research and Drug Development Dr. Michael Shetzline and the appointment of Dr. Jeffrey Silber as his successor. Dr. Silber will oversee Research and Drug Development, Regulatory Affairs and Medical Affairs reporting to Chief Executive Officer Tom McCourt. Dr. Silber joins Ironwood on July 20, 2026 and Dr. Shetzline will remain an advisor to the company to ensure a seamless transition. The company also announced today that the confirmatory Phase 3 STARS-2 trial of apraglutide in patients with short bowel syndrome with intestinal failure (SBS-IF) was initiated in June and is now actively recruiting patients. “I would like to congratulate Mike on a distinguished 30-year career and thank him for his leadership and many contributions, including building strong R&D, Regulatory Affairs and Medical Affairs organizations at Ironwood – most recently leading the team through the initiation of STARS-2,” said Ironwood Pharmaceuticals Chief Executive Officer Tom McCourt. “It’s a pleasure to welcome Jeff to our leadership team. His broad medical and scientific leadership expertise will help us build on the strong foundation we already have in place, supporting the continued growth of LINZESS and helping Ironwood bring apraglutide to patients as quickly as possible.” “I am excited to join Ironwood at such an important time for the company and to help advance apraglutide. Based on the positive Phase 3 STARS data, I believe apraglutide has the potential to be a best-in-class therapy for patients with SBS-IF who continue to face significant unmet needs,” said Dr. Jeffrey Silber, newly appointed Chief Medical Officer and Head of Research and Drug Development at Ironwood Pharmaceuticals. “I look forward to working with the team to continue executing the STARS-2 trial as we work to bring apraglutide to patients living with SBS-IF swiftly.” Dr. Silber joins Ironwood from Vedanta Biosciences where he was Chief Medical Officer since 2020, leading the research and clinical development of microbiome-based oral therapies for inflammatory and infectious gastrointestinal diseases. Prior to Vedanta, Dr. Silber was Senior Vice President in Clinical Development and Head of Development Sciences at EMD Serono/Merck KGaA where he oversaw global program leadership, global patient safety, fertility/endocrine clinical research, biostatistics and epidemiology, and translational medicine. Before joining EMD Serono, Dr. Silber was Vice President and Head of Strategic Portfolio Development at AbbVie. During a 16-year tenure at Merck & Co., Dr. Silber held roles of increasing responsibility in vaccines, anti-infectives, and neuroscience, ultimately assuming the position of Vice President and Therapeutic Area Head, Vaccine Clinical Research. In academia, Dr. Silber was an Assistant Professor of Medicine at UMDNJ/Robert Wood Johnson School of Medicine in Camden, NJ. He received a B.A. in biology from Harvard University and an M.D. from the Albert Einstein College of Medicine. Dr. Silber completed training in Internal Medicine at NYU Medical Center/Bellevue Hospital and in Infectious Diseases at the Hospital of the University of Pennsylvania. 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 . In addition, follow us on X and on LinkedIn . 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 2 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 IBS-C in adults and pediatric patients 7 years of age and older, CIC in adults and functional constipation (FC) in pediatric patients 2 years of age and older. 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 Grand Life Sciences 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, chronic idiopathic constipation (CIC) in adults, and functional constipation (FC) in pediatric patients 2 years of age and older. 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 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 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 adult patients with IBS-C or CIC treated with LINZESS 145 mcg or 290 mcg once daily, and in <1% of adult patients with CIC treated with LINZESS 72 mcg once daily. In pediatric patients, diarrhea was also the most common adverse reaction in clinical trials of patients 7 to 17 years of age with IBS-C and 6 to 17 years of age with FC treated with LINZESS. 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 dose higher than the recommended 145 mcg once daily dosage for IBS-C. If severe diarrhea occurs, dosing should be suspended and the patient rehydrated. Common Adverse Reactions (incidence ≥2% and greater than placebo) In adult patients with IBS-C or CIC: diarrhea, abdominal pain, flatulence and abdominal distension. In pediatric patients 7 to 17 years of age with IBS-C and 6 to 17 years of age with FC: diarrhea. Please see full Prescribing Information including Boxed Warning: 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 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 Ironwood’s ability to execute on its mission; Ironwood’s strategy, business, financial position and operations; Ironwood’s ability to drive growth and profitability; the commercial potential of LINZESS; Ironwood’s financial performance and results, and guidance and expectations related thereto; LINZESS prescription demand growth, LINZESS U.S. net sales, total revenue and adjusted EBITDA in 2026; the planned confirmatory STARS‑2 Phase 3 clinical trial design, endpoints and timing to initiate such trial; and our belief that highly potent, selective, and long-acting pharmacologic properties of apraglutide have the potential to drive best-in-class efficacy and tolerability with once-weekly dosing and redefine the standard of care in SBS-IF. 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 statements. 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. Contacts Company contact: Chris Stamm Vice President, Investor Relations and Communications cstamm@ironwoodpharma.com Investors: Precision AQ Stephanie Ascher Stephanie.Ascher@precisionaq.com

BOSTON--(BUSINESS WIRE)-- Ironwood Pharmaceuticals, Inc. (Nasdaq: IRWD), today announced that management will participate in a fireside chat at the Jefferies Global Healthcare Conference on Thursday, June 4 th at 11:05 a.m. ET. A live webcast of Ironwood’s fireside chat will be accessible through the Investors & Media section of the company’s website at . A replay of the webcast will be available on Ironwood’s website following the conference. 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 adults with 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 In addition, follow us on X and on LinkedIn . Contacts Company contact: Jeff Ruberti jruberti@ironwoodpharma.com Investors: Precision AQ (formerly Stern Investor Relations) Stephanie Ascher stephanie.ascher@precisionaq.com