Apraglutide

New data highlight both stoma and colon-in-continuity (CIC) patients drove the positive primary endpoint with significant relative change from baseline in weekly parenteral support (PS) volume reduction at week 24 Additional secondary endpoints show significant increases in days off PS and clinical responder rates with apraglutide, including achieving enteral autonomy in both stoma and CIC patients Data from largest GLP-2 Phase III study to date adds to body of evidence on safety and efficacy of once-weekly apraglutide in adults with SBS-IF New details on safety and tolerability to be presented; showing apraglutide to be well tolerated with a safety pro with previously reported apraglutide studies in this patient population BOSTON--(BUSINESS WIRE)-- Ironwood Pharmaceuticals, Inc. (Nasdaq: IRWD), a GI-focused healthcare company, will present late-breaking data during the 2024 Digestive Disease Week® (DDW) meeting from its pivotal Phase III clinical trial, STARS, which evaluated the efficacy and safety of once-weekly subcutaneous apraglutide in adult patients with short bowel syndrome with intestinal failure (SBS-IF). These findings build on the positive topline data that Ironwood previously announced in February 2024. Based on these results, the company is working to submit a new drug application (NDA) to the U.S. Food and Drug Administration (FDA) and marketing applications to other regulatory agencies for apraglutide for the treatment of adult patients with SBS who are dependent on parenteral support (PS). SBS-IF, a rare chronic debilitating malabsorptive condition in which patients are dependent on PS, affects an estimated 18,000 adult patients in the U.S., Europe, and Japan. Apraglutide is the first and only investigational once-weekly GLP-2 analog that has successfully demonstrated positive results in a Phase III placebo-controlled study. The late-breaking data at DDW are from the largest global SBS-IF clinical trial conducted to date and are being shared during an oral presentation titled “Efficacy and Safety of Apraglutide Once-Weekly in Patients with Short Bowel Syndrome and Intestinal Failure (SBS-IF): Results from the STARS Study - A Global Phase 3 Double-Blind, Randomized, Placebo-Controlled Trial.” Ironwood previously reported that the STARS clinical trial met its primary endpoint of relative change from baseline in actual weekly PS volume at week 24 vs. placebo (-25.5% vs. -12.5%; p=0.001), driven by both stoma and colon-in-continuity subpopulations. Treatment effect with relative PS volume reduction was observed from week 8 onward (-8% vs -1.6% placebo, p=0.002). Findings from the late-breaking presentation include: Significantly more apraglutide-patients gained additional days off from PS per week at week 24 versus placebo (≥2 days: 24.5% vs 11.3%, p=0.021; ≥3 days: 11.8% vs 1.9%, p=0.006) Significantly more apraglutide-treated patients in the overall and the stoma populations were clinical responders and clinical high responders (defined as ≥20% and ≥40% PS volume reduction, respectively), at both weeks 20 and 24 versus placebo Overall population: Clinical responders 42.7% vs 20.8%, p=0.003; Clinical high responders 22.7% vs 9.4%, p=0.018 Stoma subpopulation: clinical responders 40.7% vs 15.4%, p=0.02; clinical high responders 20.4% vs 0%, p=0.009 Seven apraglutide-treated patients achieved enteral autonomy (three in the stoma subpopulation, four in the colon-in-continuity subpopulation) by week 24 (6.4% apraglutide vs 0% placebo, p=0.006). Three additional colon-in-continuity patients achieved enteral autonomy by week 48: 7/56 [12.5%] apraglutide vs 2/27 placebo [7.4%], p=0.387. “Given the burden that parenteral support places on people living with SBS-IF, the goal of treatment is to importantly gain additional days off PS, and ultimately achieve enteral autonomy in those who can achieve it,” said Kishore R Iyer, MBBS, FRCS (Eng), FACS, Director of Adult and Pediatric Intestine Rehabilitation & Transplantation at The Mount Sinai Hospital in New York, Coordinating Principal Investigator of the trial, paid scientific advisor to Ironwood and chair of the scientific steering committee for the STARS clinical trial. “The fact that some CIC and stoma patients on apraglutide achieved enteral autonomy at week 24 and sustained that autonomy through 48 weeks is an important outcome and demonstrates the potential of apraglutide for these patients.” Apraglutide also demonstrated statistical significance on two key secondary endpoints, with more patients in the combined population achieving at least one day/week off PS relative to baseline at week 24 versus placebo (43.0% vs. 27.5%; p=0.040) and more patients treated with apraglutide versus placebo demonstrating improvement in relative change from baseline in actual weekly PS volume at week 24 in the stoma subpopulation (-25.6% vs. -7.8%; p<0.001). Apraglutide was well-tolerated, with no new safety signals identified and the safety pro consistent with previous apraglutide studies. “Our data at DDW reflect Ironwood’s key priorities, which focus on advancing the treatment of GI diseases,” said Michael Shetzline, M.D., Ph.D., chief medical officer, senior vice president and head of research and drug development at Ironwood Pharmaceuticals. “The apraglutide findings showcase the breadth and depth of positive clinical trial outcomes with this compound to date, with the strength of the Phase III data enabling a strong submission and a path to potential FDA and other regulatory approvals. We’re excited for the opportunity to unlock a new and potentially differentiated treatment option for adult patients with SBS dependent on parenteral support.” In addition to the STARS Phase III oral presentation, Ironwood, and its collaborators presented data highlighting findings across the apraglutide development program. Impact of once weekly apraglutide on intestinal absorption Three posters were presented by Astrid Verbiest, researcher at the Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Leuven, Flanders, Belgium, summarizing new findings from STARS Nutrition. STARS Nutrition is a multicenter open-label Phase II metabolic balance study of nine patients that was designed to evaluate the safety, pharmacokinetics, and efficacy of apraglutide on intestinal absorption in adult patients who have SBS-IF and Colon-in-Continuity. Positive final data from this study were announced in October 2023. “Changes in Bowel Morphology and Motility Assessed by MRI in Patients with Short Bowel Syndrome Intestinal Failure (SBS-IF) and Colon-In-Continuity Treated with Apraglutide” (poster number Su1946) demonstrated that apraglutide treatment was associated with small bowel lengthening and increased duodenal wall thickness suggesting an intestinotrophic (stimulates/regulates growth of intestinal tissue) effect that may contribute to an increased surface area for absorption. The authors note that whether bowel lengthening results from a direct effect of apraglutide vs. changes in motility with passive elongation is subject of further investigation. “Parenteral Support Weaning, Clinical Benefit and Improved Patient Reported Outcomes in Short Bowel Syndrome Intestinal Failure (SBS-IF) Patients with Colon-In-Continuity Treated with The Long-Acting Glucagon-Like Peptide-2 (GLP-2) Analog Apraglutide” (poster number Su1947) showed that apraglutide has an acceptable safety pro is associated with significant reductions in PS needs in SBS-IF patients with colon-in continuity, resulting in days off PS and subjective improvement based on patient reported outcomes. "Apraglutide Treatment in Short Bowel Syndrome with Intestinal Failure (SBS-IF) and Colon-In-Continuity is Associated with Increased Oral Intake and Improved Energy and Carbohydrate Absorption at 48 Weeks" (poster number Su1948) showed that in patients with SBS-IF and colon-in-continuity, apraglutide treatment resulted in an early reduced fecal output and improved wet weight absorption. After 48 weeks, oral intake was increased despite stable fecal output, leading to increased energy and carbohydrate absorption. Impact of apraglutide on gastric emptying "The Effect of Apraglutide on Gastric Emptying in Healthy Individuals: A Phase 1 Randomized, Placebo-Controlled, Double-Blind, Single-Center Trial" (poster number Su1949) was presented by Gerard Greig, Ironwood Pharmaceuticals. The data suggest that apraglutide does not affect gastric emptying of liquids in healthy individuals, as measured by acetaminophen pharmacokinetics (PK), and can therefore be used in a broad patient population. Irritable Bowel Syndrome with Constipation (IBS-C) and Functional Constipation “Real World Prescribing Patterns for Pediatric Patients with Functional Constipation and Irritable Bowel Syndrome with Constipation” (presentation number Su2047) was presented by Julie Khlevner, M.D., New York Presbyterian Morgan Stanley Children’s Hospital, New York, NY, showing that, based on a retrospective, observational study, approximately one-third of children and adolescents diagnosed with FC or IBS-C were prescribed medication for constipation during a five year period (January 2018 – June 2023). Polyethylene glycol 3350 was the most frequently prescribed medication for pediatric FC and IBS-C, followed by lactulose. “Efficacy, Safety, and Time to Response of Linaclotide in Patients ≥ 65 with Irritable Bowel Syndrome with Constipation” (presentation number Tu1653) will be presented by Lin Chang, M.D., David Geffen School of Medicine at UCLA, Los Angeles, CA. The data were based on a post hoc analysis of >2,000 adults with IBS-C. Treatment-emergent adverse events were similar in both age groups and were consistent with the known safety pro linaclotide in patients with IBS-C. “Assessing US Healthcare Disparities in IBS Diagnosis: A National Survey Analysis” (presentation number Tu1027) will be presented by Christopher V Almario, M.D., MSHPM, Cedars Sinai Medical Center, Los Angeles, CA, summarizing survey data from nearly 90,000 adults in the US. The study analyzed healthcare-seeking behavior, including the likelihood of seeing a healthcare provider (HCP) and the type of HCP seen. Respondents who identified as Black or African American were less likely to be diagnosed with IBS than those who identified as White, even after controlling for potential confounding variables, such as socioeconomic status and symptom severity. About STARS The STARS (STudy of ApRaglutide in SBS) pivotal Phase III trial represents the largest Phase III 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 randomized 164 patients 2:1 and 163 were dosed to receive either once-weekly apraglutide or placebo. Patients were stratified approximately 50/50 by remnant bowel anatomy (stoma vs. colon-in continuity) and evaluated over 24 weeks (stoma and colon-in-continuity subpopulations) and 48 weeks (colon-in-continuity subpopulation only). 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 off PS at week 24 (overall population); relative change from baseline in actual weekly PS volume at week 24 (stoma subpopulation); patients who achieved a reduction from baseline of at least 1 day/week off PS at week 48 (colon-in-continuity subpopulation); and patients reaching enteral autonomy at week 48 (colon-in-continuity subpopulation). The study was conducted in 18 countries with enrollment from 68 study sites. About STARS Nutrition STARS Nutrition is the first-ever study to prospectively evaluate the clinical benefit of a GLP-2 analog specifically in patients with colon-in-continuity. This multicenter, open-label Phase II metabolic balance study was designed to evaluate the effect of once-weekly apraglutide 5-mg subcutaneous injection on intestinal absorption in SBS-IF patients with colon-in-continuity at 52 weeks. Safety and parameters indicative of clinical efficacy, including PS volume and energy content reduction, were assessed. The study enrolled nine adult patients with a mean age of 46.8 years. About Short Bowel Syndrome SBS is a serious and chronic condition where there is diminished absorptive capacity for fluids and/or nutrients, sometimes requiring dependence on parenteral support to maintain health. Short bowel syndrome typically occurs because of extensive intestinal resection, and patients with SBS who are chronically dependent on parenteral support, also referred to as SBS with intestinal failure (SBS-IF), often experience significant quality of life impact and are at risk of severe complications such as infection. An estimated 18,000 adult patients suffer from SBS-IF in the U.S., Europe and Japan, and have chronic dependence on PS, which significantly impacts quality of life and carries the risk of severe complications such as infection. Those with the most severe SBS-IF require PS infusions for up to 10 to 15 hours per day. SBS-IF is associated with frequent complications, significant morbidity and mortality, high economic burden and an impaired quality of life. About Apraglutide Apraglutide is an investigational, next-generation, long-acting synthetic GLP-2 analog being developed for a range of rare gastrointestinal diseases where GLP-2 can play a central role in addressing disease pathophysiology, including short bowel syndrome with intestinal failure (SBS-IF) and Acute Graft-Versus-Host Disease (aGVHD). About LINZESS 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 for the treatment of both irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation (CIC) in adults 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 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 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: 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), which is the U.S. branded prescription market leader for adults with irritable bowel syndrome with constipation (IBS-C) or chronic idiopathic constipation (CIC) and is also indicated 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, 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. 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 assessment of the data from the Phase III STARS clinical trial of apraglutide; the efficacy, safety and tolerability of apraglutide; Ironwood’s plan to submit an NDA and marketing applications to other regulatory filings for apraglutide; the estimated adult population who suffer from SBS-IF in the U.S., Europe and Japan; that the findings and the strength of the Phase III data enable a strong submission and a path to potential FDA and other regulatory approvals; and the potential opportunity to unlock a new and differentiated treatment option for adult patients with SBS dependent on PS. 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 apraglutide; 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 completed nonclinical and clinical studies may not be replicated in later studies; the risk that the FDA may not approve our NDA submission; 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 our product candidates; the risk that the commercial and therapeutic opportunities for our product candidates are not as we expect; the risk that we are unable to successfully partner with other companies to develop and commercialize products or product candidates; decisions by regulatory and judicial authorities; the risk we may never get additional patent protection for our product candidates, that patents for our products may not provide adequate protection from competition, or that we are not able to successfully protect such patents; the risk that the development of 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; challenges from and rights of competitors or potential competitors; 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, 2023, and in our subsequent Securities and Exchange Commission filings. View source version on businesswire.com: Contacts Media: Beth Calitri, 978-417-2031 bcalitri@ironwoodpharma.com Investors: Greg Martini, 617-374-5230 gmartini@ironwoodpharma.com Matt Roache, 617-621-8395 mroache@ironwoodpharma.com Source: Ironwood Pharmaceuticals, Inc. View this news release online at:

Reported positive topline results from global Phase III STARS trial of once-weekly apraglutide in adults with short bowel syndrome with intestinal failure (SBS-IF) Reported positive results from Phase II exploratory STARGAZE trial of apraglutide in patients with steroid-refractory gastrointestinal acute Graft-versus-Host Disease (SR GI aGVHD) LINZESS® (linaclotide) EUTRx prescription demand growth of 10% year-over-year Revises FY 2024 financial guidance due to a LINZESS gross-to-net change in estimate BOSTON--(BUSINESS WIRE)-- Ironwood Pharmaceuticals, Inc. (Nasdaq: IRWD), a GI-focused healthcare company, today reported its first quarter 2024 results and recent business performance. “In the first quarter of 2024, we made significant advancements across our portfolio,” said Tom McCourt, chief executive officer of Ironwood. “LINZESS maintained its strong demand momentum, experiencing a rise in prescription volume by a robust 10% year-over-year, while continuing to generate meaningful cash flow. Particularly noteworthy during the quarter was the positive Phase III clinical data for apraglutide, which validates its potential as the first and only once-weekly GLP-2 analog for adult patients with short bowel syndrome who are dependent on parenteral support. The positive results from the STARS trial, coupled with our proven track record of effective commercial execution, uniquely position Ironwood in the market and reinforce our belief in the long-term value potential of apraglutide for patients and shareholders. We are working swiftly and plan to NDA as soon as possible for apraglutide for adult SBS patients dependent on parenteral support. In addition, we remain focused on executing across our strategic priorities by advancing our other GI pipeline assets, driving robust LINZESS demand growth, and delivering sustained profits and cash flow.” First Quarter 2024 Financial Highlights1 (in thousands, except for per share amounts) Q1 2024 Q1 2023 Total revenue2 $74,877 $104,061 Total operating expenses 63,857 43,964 GAAP net income (loss)2 (4,162) 45,714 GAAP net income (loss) – per share basic2 (0.03) 0.30 GAAP net income (loss) – per share diluted2 (0.03) 0.25 Adjusted EBITDA2 12,757 60,383 Non-GAAP net income (loss) 2 (2,933) 45,695 Non-GAAP net income (loss) per share – basic (0.02) 0.30 Non-GAAP net income (loss) per share – diluted (0.02) 0.25 1 Refer to the Reconciliation of GAAP Results to Non-GAAP Financial Measures table and to the Reconciliation of GAAP Net Income (Loss) to Adjusted EBITDA table at the end of this press release. Refer to Non-GAAP Financial Measures for additional information. 2 Figures presented in Q1 2024 include a $30.0 million reduction to collaborative arrangements revenue due to a LINZESS gross-to-net change in estimate related to the year ended December 31, 2023. First Quarter 2024 Corporate Highlights U.S. LINZESS Prescription Demand: Total LINZESS prescription demand in the first quarter of 2024 was 50 million LINZESS capsules, a 10% increase compared to the first quarter of 2023, per IQVIA. U.S. Brand Collaboration: LINZESS U.S. net sales are provided to Ironwood by its U.S. partner, AbbVie Inc. (“AbbVie”). LINZESS U.S. net sales were $256.6 million in the first quarter of 2024, a 3% increase compared to $250.2 million in the first quarter of 2023. Ironwood and AbbVie share equally in U.S. brand collaboration profits. Based on information subsequently provided by AbbVie, Ironwood recorded a $30 million reduction to collaborative arrangements revenue in its first quarter 2024 financial statements as a result of a LINZESS gross-to-net change in estimate related to the year ended December 31, 2023. See the LINZESS U.S. Commercial Collaboration table at the end of the press release. LINZESS commercial margin, excluding the gross-to-net change in estimate, was 71% in the first quarter of 2024, compared to 73% in the first quarter of 2023. See the U.S. LINZESS Full Brand Collaboration table at the end of this press release. Net profit for the LINZESS U.S. brand collaboration, net of commercial and research and development (“R&D”) expenses and excluding the gross-to-net change in estimate, was $175.6 million in the first quarter of 2024, compared to $175.2 million in the first quarter of 2023. See the U.S. LINZESS Full Brand Collaboration table at the end of this press release. Collaboration Revenue to Ironwood: Ironwood recorded $71.7 million in collaboration revenue in the first quarter of 2024 related to sales of LINZESS in the U.S., a decrease compared to $101.6 million for the first quarter of 2023, due to a $30.0 million reduction to collaborative arrangements revenue from a LINZESS gross-to-net change in estimate as noted above. See the U.S. LINZESS Commercial Collaboration table at the end of the press release. In January 2024, Ironwood announced a publication in The Lancet Gastroenterology & Hepatology of new linaclotide Phase III data in children and adolescents aged 6-17 years with functional constipation. The data highlighted additional efficacy endpoints from the company’s pivotal Phase III trial, which formed the basis of the June 2023 U.S. Food and Drug Administration (“FDA”) approval of linaclotide for the treatment of functional constipation in this population. Additional details can be found here. Pipeline Updates Apraglutide Ironwood is advancing apraglutide, a next-generation, synthetic glucagon-like peptide-2 (“GLP-2”) analog for short bowel syndrome patients dependent on parenteral support (“PS”), a severe chronic malabsorptive condition. Ironwood believes apraglutide has the potential to improve the standard of care for adult patients with SBS who are dependent on PS as the first and only GLP-2 with once-weekly administration, if approved. In February 2024, Ironwood announced positive topline results from its pivotal Phase III clinical trial, STARS, which evaluated the efficacy and safety of once-weekly subcutaneous apraglutide in reducing PS dependency in adult patients with short bowel syndrome with intestinal failure (“SBS-IF”). Based on the results from the STARS clinical trial, Ironwood plans to submit a new drug application and other regulatory filings for apraglutide for use in adult patients with SBS who are dependent on PS. Additional details on the topline results can be found here. Data from the Phase III STARS study was accepted as a late-breaker oral presentation and will be presented on May 21, 2024 at Digestive Disease Week® (DDW) 2024 in Washington D.C. In March 2024, Ironwood announced positive, primary results up to Day 91 for its Phase II exploratory trial, STARGAZE, to evaluate apraglutide in patients with steroid-refractory gastrointestinal acute Graft-versus-Host Disease (“SR GI aGvHD”), which evaluated the safety and tolerability of once-weekly apraglutide in SR GI aGvHD patients treated with standard of care, including systemic corticosteroids and ruxolitinib. The STARGAZE study will continue through its two-year endpoint, where apraglutide will be re-evaluated for safety and efficacy. Additional details can be found here. CNP-104 Ironwood has a collaboration and license option agreement with COUR Pharmaceuticals Development Company, Inc. (“COUR”). This agreement grants Ironwood an option to acquire an exclusive license to research, develop, manufacture and commercialize, in the U.S., products containing CNP-104 (“CNP-104”), a tolerizing immune modifying nanoparticle, for the treatment of primary biliary cholangitis (“PBC”), a rare autoimmune disease targeting the liver. If successful, CNP-104 has the potential to be the first approved disease modifying therapy for PBC. COUR is currently conducting a clinical study with CNP-104 evaluating the safety, tolerability, pharmacodynamic effects and efficacy of CNP-104 in PBC patients. Enrollment is complete and topline data is expected in the third quarter of 2024. IW-3300 Ironwood is currently advancing IW-3300, a guanylate cyclase-C agonist being developed for the potential treatment of visceral pain conditions, such as interstitial cystitis / bladder pain syndrome (“IC/BPS”) and endometriosis. Ironwood is continuing the Phase II proof of concept study in IC/BPS. First Quarter 2024 Financial Results Total Revenue. Total revenue in the first quarter of 2024 was $74.9 million, compared to $104.1 million in the first quarter of 2023. As noted above, revenue was lower year-over-year primarily due to the $30.0 million LINZESS gross-to-net change in estimate recorded to collaborative arrangements revenue. Total revenue in the first quarter of 2024 consisted of $71.7 million associated with Ironwood’s share of the net profits from the sales of LINZESS in the U.S., including the $30.0 million reduction, and $3.2 million in royalties and other revenue. Total revenue in the first quarter of 2023 consisted of $101.6 million associated with Ironwood’s share of the net profits from the sales of LINZESS in the U.S. and $2.5 million in royalties and other revenue. Operating Expenses. Operating expenses in the first quarter of 2024 were $63.9 million, compared to $44.0 million in the first quarter of 2023. Operating expenses in the first quarter of 2024 consisted of $37.6 million in selling, general and administrative (“SG&A”) expenses, $25.8 million in R&D expenses and $0.4 million in restructuring expenses. Operating expenses in the first quarter of 2023 consisted of $31.1 million in SG&A expenses and $12.9 million in R&D expenses. Interest Expense. Interest expense was $7.2 million in the first quarter of 2024, primarily in connection with Ironwood’s convertible senior notes and revolving credit facility. Interest expense was $1.5 million in the first quarter of 2023, in connection with Ironwood’s convertible senior notes. Interest and Investment Income. Interest and investment income was $1.2 million in the first quarter of 2024. Interest and investment income was $7.3 million in the first quarter of 2023. Gain on Derivatives. Ironwood recorded a gain on derivatives of an insignificant amount in the first quarter of 2023, as a result of the change in fair value of its note hedge warrants. Ironwood’s note hedge warrants terminated unexercised upon expiration in April 2023. Income Tax Expense. Ironwood recorded $9.1 million of income tax expense in the first quarter of 2024, the majority of which was non-cash, as Ironwood continues to utilize net operating losses to offset taxable income for federal purposes and in many states. Ironwood recorded $20.1 million of income tax expense in the first quarter of 2023, the majority of which was non-cash, as Ironwood continued to utilize net operating losses to offset taxable income for federal purposes and in many states. GAAP Net Income (Loss). GAAP net loss was $4.2 million, or ($0.03) per share (basic and diluted), in the first quarter of 2024, which includes a $30.0 million reduction to collaborative arrangements revenue due to a LINZESS gross-to-net change in estimate, compared to GAAP net income of $45.7 million, or $0.30 per share (basic) and $0.25 per share (diluted), in the first quarter of 2023. Non-GAAP Net Income (Loss). Non-GAAP net loss was $2.9 million, or ($0.02) per share (basic and diluted), in the first quarter of 2024, which includes a $30.0 million reduction to collaborative arrangements revenue due to a LINZESS gross-to-net change in estimate, compared to non-GAAP net income of $45.7 million, or $0.30 per share (basic) and $0.25 per share (diluted), in the first quarter of 2023. Non-GAAP net income excludes the impact of mark-to-market adjustments on the derivatives related to Ironwood’s 2022 Convertible Notes, amortization of acquired intangible assets, restructuring expenses and acquisition-related costs, all net of tax effect. See Non-GAAP Financial Measures below. Adjusted EBITDA. Adjusted EBITDA was $12.8 million in the first quarter of 2024, which includes a $30.0 million reduction to collaborative arrangements revenue due to a LINZESS gross-to-net change in estimate, compared to $60.4 million in the first quarter of 2023. Adjusted EBITDA is calculated by subtracting mark-to-market adjustments on derivatives related to Ironwood’s 2022 Convertible Notes, restructuring expenses, net interest expense, income taxes, depreciation and amortization, and acquisition-related costs, from GAAP net income. See Non-GAAP Financial Measures below. Cash Flow Highlights. Ironwood ended the first quarter of 2024 with $121.5 million of cash and cash equivalents, compared to $92.2 million of cash and cash equivalents at the end of 2023. In the first quarter of 2024, Ironwood repaid $25.0 million of the outstanding principal balance on its revolving credit facility used to partially finance the VectivBio acquisition. The outstanding principal balance on the revolving credit facility was $275.0 million as of March 31, 2024. Ironwood generated $45.0 million in cash from operations in the first quarter of 2024, compared to $80.2 million in cash from operations in the first quarter of 2023. Ironwood 2024 Financial Guidance. Ironwood has revised its FY 2024 financial guidance due to a LINZESS gross-to-net change in estimate related to the year ended December 31, 2023. Ironwood now expects: Prior 2024 Guidance (February 15, 2024) Revised 2024 Guidance2 (May 9, 2024) U.S. LINZESS Net Sales3 Low-single digits % growth Mid-single digits % decline Total Revenue $435 to $455 million $405 to $425 million Adjusted EBITDA1 >$150 million Excludes potential CNP-104 option exercise >$120 million Excludes potential CNP-104 option exercise 1 Adjusted EBITDA is calculated by subtracting restructuring expenses, net interest expense, income taxes, depreciation and amortization, and acquisition-related costs from GAAP net income. For purposes of the 2024 guidance, Ironwood has assumed it will not incur material expenses related to business development activities in 2024 and excludes any costs associated with potential CNP-104 option exercise. Ironwood does not provide guidance on GAAP net income or a reconciliation of expected adjusted EBITDA to expected GAAP net income because, without unreasonable efforts, it is unable to predict with reasonable certainty the non-GAAP adjustments used to calculate adjusted EBITDA. These adjustments are uncertain, depend on various factors and could have a material impact on GAAP net income for the guidance period. Management believes this non-GAAP information is useful for investors, taken in conjunction with Ironwood’s GAAP financial statements, because it provides greater transparency and period-over-period comparability with respect to Ironwood’s operating performance. These measures are also used by management to assess the performance of the business. Investors should consider these non-GAAP measures only as a supplement to, not as a substitute for or as superior to, measures of financial performance prepared in accordance with GAAP. In addition, these non-GAAP financial measures are unlikely to be comparable with non-GAAP information provided by other companies. 2 Based on information provided by AbbVie, Ironwood estimates a $60.0 million LINZESS gross-to-net change related to the year ended December 31, 2023, and has recorded a $30.0 million reduction to collaborative arrangements revenue in its first quarter 2024 financial statements to reflect this change in estimate. 3 2024 U.S. LINZESS Net Sales guidance presented as year-over-year change relative to 2023 U.S. LINZESS Net Sales as reported by AbbVie of $1,073.2 million. Non-GAAP Financial Measures Ironwood presents non-GAAP net income and non-GAAP net income per share to exclude the impact, net of tax effects, of net gains and losses on derivatives related to Ironwood’s 2022 Convertible Notes that are required to be marked-to-market, amortization of acquired intangible assets, restructuring expenses, and acquisition-related costs. Non-GAAP adjustments are further detailed below: The gains and losses on the derivatives related to Ironwood’s 2022 Convertible Notes were highly variable, difficult to predict and of a size that could have a substantial impact on the company’s reported results of operations in any given period. Amortization of acquired intangible assets are non-cash expenses arising in connection with the acquisition of VectivBio and are considered to be non-recurring. Restructuring expenses are considered to be a non-recurring event as they are associated with distinct operational decisions. Included in restructuring expenses are costs associated with exit and disposal activities. Acquisition-related costs in connection with the acquisition of VectivBio are considered to be non-recurring and include direct and incremental costs associated with the acquisition and integration of VectivBio to the extent such costs were not classified as capitalizable transaction costs attributed to the cost of net assets acquired through acquisition accounting. Ironwood also presents adjusted EBITDA, a non-GAAP measure, as well as guidance on adjusted EBITDA. Adjusted EBITDA is calculated by subtracting mark-to-market adjustments on derivatives related to Ironwood’s 2022 Convertible Notes, restructuring expenses, net interest expense, income taxes, depreciation and amortization, and acquisition-related costs from GAAP net income. The adjustments are made on a similar basis as described above related to non-GAAP net income, as applicable. Management believes this non-GAAP information is useful for investors, taken in conjunction with Ironwood’s GAAP financial statements, because it provides greater transparency and period-over-period comparability with respect to Ironwood’s operating performance. These measures are also used by management to assess the performance of the business. Investors should consider these non-GAAP measures only as a supplement to, not as a substitute for or as superior to, measures of financial performance prepared in accordance with GAAP. In addition, these non-GAAP financial measures are unlikely to be comparable with non-GAAP information provided by other companies. For a reconciliation of non-GAAP net income and non-GAAP net income per share to GAAP net income and GAAP net income per share, respectively, and for a reconciliation of adjusted EBITDA to GAAP net income, please refer to the tables at the end of this press release. Ironwood does not provide guidance on GAAP net income or a reconciliation of expected adjusted EBITDA to expected GAAP net income because, without unreasonable efforts, it is unable to predict with reasonable certainty the non-GAAP adjustments used to calculate adjusted EBITDA. These adjustments are uncertain, depend on various factors and could have a material impact on GAAP net income for the guidance period. Conference Call Information Ironwood will host a conference call and webcast at 8:30 a.m. Eastern Time on Thursday, May 9, 2024 to discuss its first quarter 2024 results and recent business activities. Individuals interested in participating in the call should dial (888) 596-4144 (U.S. and Canada) or (646) 968-2525 (international) using conference ID number and event passcode 3416473. To access the webcast, please visit the Investors section of Ironwood’s website at at least 15 minutes prior to the start of the call to ensure adequate time for any software downloads that may be required. The call will be available for replay via telephone starting at approximately 11:30 a.m. Eastern Time on May 9, 2024, running through 11:59 p.m. Eastern Time on May 23, 2024. To listen to the replay, dial (800) 770-2030 (U.S. and Canada) or (609) 800-9909 (international) using conference ID number 3416473. The archived webcast will be available on Ironwood’s website for 1 year beginning approximately one hour after the call has completed. About Ironwood Pharmaceuticals Ironwood Pharmaceuticals (Nasdaq: IRWD), an S&P SmallCap 600® company, is a leading 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, 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 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 for the treatment of both irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation (CIC) in adults 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 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 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: 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; our financial performance and results, and guidance and expectations related thereto; LINZESS prescription demand growth, LINZESS U.S. net sales growth, total revenue and adjusted EBITDA in 2024; our plan to NDA for apraglutide as soon as possible and apraglutide's potential, if approved, to be the first and only once-weekly GLP-2 analog for adult SBS patients who are dependent on PS; our belief that the positive results from the STARS Phase III trial, coupled with our proven track record of effective commercial execution, position Ironwood uniquely in the market and reinforce our belief in the long-term value potential of apraglutide for patients and shareholders; our plan to NDA for apraglutide for adult SBS patients dependent on PS as soon as possible; and the timing of topline data for CNP-104 and that, if successful, CNP-104 has the potential to be the first approved disease modifying therapy for PBC. 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, CNP-104, IW-3300, 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, apraglutide, CNP-104 and IW-3300, 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 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 we are unable to execute on our strategy to in-license externally developed products or product candidates; the risk that we are unable to successfully partner with other companies to develop and commercialize products or product candidates; 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, apraglutide, CNP-104 and/or IW-3300 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, 2023, and in our subsequent Securities and Exchange Commission filings. Condensed Consolidated Balance Sheets (In thousands) (unaudited) March 31, 2024 December 31, 2023 Assets Cash and cash equivalents $ 121,540 $ 92,154 Accounts receivable, net 72,015 129,122 Prepaid expenses and other current assets 14,619 12,012 Total current assets 208,174 233,288 Property and equipment, net 5,288 5,585 Operating lease right-of-use assets 12,208 12,586 Intangible assets, net 3,478 3,682 Deferred tax assets 206,273 212,324 Other assets 3,398 3,608 Total assets $ 438,819 $ 471,073 Liabilities and stockholders’ equity Accounts payable $ 6,222 $ 7,830 Accrued research and development costs 11,880 21,331 Accrued expenses and other current liabilities 31,398 44,254 Current portion of operating lease liabilities 3,142 3,126 Current portion on convertible senior notes 199,800 199,560 Total current liabilities 252,442 276,101 Operating lease liabilities, net of current portion 14,004 14,543 Convertible senior notes, net of current portion 198,477 198,309 Revolving credit facility 275,000 300,000 Other liabilities 29,414 28,415 Total stockholders’ deficit (330,518) (346,295) Total liabilities and stockholders’ deficit $ 438,819 $ 471,073 Condensed Consolidated Statements of Income (Loss) (In thousands, except per share amounts) (unaudited) Three Months Ended March 31, 2024 2023 Total revenue1 74,877 104,061 Collaborative arrangements revenue1 71,700 101,600 Operating expenses: Research and development 25,815 12,847 Selling, general and administrative 37,605 31,117 Restructuring expenses 437 - Total operating expenses 63,857 43,964 Income from operations 11,020 60,097 Other income (expense): Interest expense and other financing costs (7,231) (1,527) Interest and investment income 1,169 7,272 Gain on derivatives - 19 Other income (expense), net (6,062) 5,764 Income before income taxes 4,958 65,861 Income tax expense (9,120) (20,147) GAAP net income (loss)1 $ (4,162) $ 45,714 GAAP net income (loss) per share—basic1 ($0.03) $0.30 GAAP net income (loss) per share—diluted1 ($0.03) $0.25 ______________________________ 1 Figures presented in Q1 2024 reflect a $30.0 million reduction to collaborative arrangements revenue due to a LINZESS gross-to-net change in estimate related to the year ended December 31, 2023. Reconciliation of GAAP Results to Non-GAAP Financial Measures (In thousands, except per share amounts) (unaudited) A reconciliation between net income (loss) on a GAAP basis and on a non-GAAP basis is as follows: Three Months Ended March 31, 2024 2023 GAAP net income (loss)1,2 $ (4,162) $ 45,714 Adjustments: Mark-to-market adjustments on the derivatives related to convertible notes, net - (19) Amortization of acquired intangible assets 204 - Restructuring expenses 437 - Acquisition-related costs 787 - Tax effect of adjustments (199) - Non-GAAP net income (loss)1,2 $ (2,933) $ 45,695 ______________________________ 1 Q1 2024 GAAP and non-GAAP net loss reflect costs associated with the acquisition of VectivBio in the second quarter of 2023. 2 Q1 2024 GAAP and non-GAAP net loss reflect a $30.0 million reduction to collaborative arrangements revenue due to a LINZESS gross-to-net change in estimate related to the year ended December 31, 2023. A reconciliation between basic net income (loss) per share on a GAAP basis and on a non-GAAP basis is as follows: Three Months Ended March 31, 2024 2023 GAAP net income (loss) – basic $ (0.03) $ 0.30 Adjustments to GAAP net income (loss) per share (as detailed above) 0.01 (0.00) Non-GAAP net income (loss) per share – basic $ (0.02) $ 0.30 Weighted average number of common shares used to calculate net income (loss) per share — basic 157,700 154,452 A reconciliation between diluted net income (loss) per share on a GAAP basis and on a non-GAAP basis is as follows: Three Months Ended March 31, 2024 2023 GAAP net income (loss) per share – diluted $ (0.03) $ 0.25 Adjustments to GAAP net income (loss) per share (as detailed above) 0.01 (0.00) Non-GAAP net income (loss) per share – diluted $ (0.02) $ 0.25 Weighted average number of common shares used to calculate net income (loss) per share — diluted 157,700 186,680 Reconciliation of GAAP Net Income (Loss) to Adjusted EBITDA (In thousands) (unaudited) A reconciliation of GAAP net income (loss) to adjusted EBITDA: Three Months Ended March 31, 2024 2023 GAAP net income (loss)1,2 $ (4,162) $ 45,714 Adjustments: Mark-to-market adjustments on the derivatives related to convertible notes, net - (19) Restructuring expenses 437 - Interest expense 7,231 1,527 Interest and investment income (1,169) (7,272) Income tax expense 9,120 20,147 Depreciation and amortization 513 286 Acquisition-related costs 787 - Adjusted EBITDA1,2 $ 12,757 $ 60,383 ______________________________ 1 Q1 2024 GAAP net loss and adjusted EBITDA reflect costs associated with the acquisition of VectivBio in the second quarter of 2023. 2 Q1 2024 GAAP net loss and adjusted EBITDA reflect a $30.0 million reduction to collaborative arrangements revenue due to a LINZESS gross-to-net change in estimate related to the year ended December 31, 2023. U.S. LINZESS Commercial Collaboration1 Revenue/Expense Calculation (In thousands) (unaudited) Three Months Ended March 31, 2024 2023 LINZESS U.S. net sales as reported by AbbVie2 $ 256,600 $ 250,214 AbbVie & Ironwood commercial costs, expenses and other discounts3 73,362 66,408 Commercial profit on sales of LINZESS $ 183,238 $ 183,806 Commercial Margin4 71% 73% Ironwood’s share of net profit 91,619 91,903 Reimbursement for Ironwood’s commercial expenses 10,096 9,728 Ironwood’s portion of gross-to-net change in estimate5 (30,000) - Ironwood’s collaborative arrangements revenue $ 71,715 $ 101,631 ______________________________ 1 Ironwood collaborates with AbbVie on the development and commercialization of linaclotide in North America. Under the terms of the collaboration agreement, Ironwood receives 50% of the net profits and bears 50% of the net losses from the commercial sale of LINZESS in the U.S. The purpose of this table is to present calculations of Ironwood’s share of net profit (loss) generated from the sales of LINZESS in the U.S. and Ironwood’s collaboration revenue/expense; however, the table does not present the research and development expenses related to LINZESS in the U.S. that are shared equally between the parties under the collaboration agreement. Please refer to the table at the end of this press release for net profit for the U.S. LINZESS brand collaboration with AbbVie. 2 LINZESS net sales are recognized using AbbVie’s revenue recognition accounting policies and reporting conventions. As a result, certain rebates and discounts are classified as LINZESS U.S. commercial costs, expenses and other discounts within Ironwood’s calculation of collaborative arrangements revenue. 3 Includes certain discounts recognized and cost of goods sold incurred by AbbVie; also includes commercial costs incurred by AbbVie and Ironwood that are attributable to the cost-sharing arrangement between the parties. 4 Commercial margin is defined as commercial profit on sales of LINZESS as a percent of total LINZESS U.S. net sales. 5 Based on information provided by AbbVie, Ironwood estimates a $60.0 million LINZESS gross-to-net change related to the year ended December 31, 2023, and has recorded a $30.0 million reduction to collaborative arrangements revenue in its first quarter 2024 financial statements to reflect this change in estimate. US LINZESS Full Brand Collaboration1 Revenue/Expense Calculation (In thousands) (unaudited) Three Months Ended March 31, 2024 2023 LINZESS U.S. net sales as reported by AbbVie2 $ 256,600 $ 250,214 AbbVie & Ironwood commercial costs, expenses and other discounts3 73,362 66,408 AbbVie & Ironwood R&D Expenses4 7,636 8,650 Total net profit on sales of LINZESS5 $ 175,602 $ 175,156 ______________________________ 1 Ironwood collaborates with AbbVie on the development and commercialization of linaclotide in North America. Under the terms of the collaboration agreement, Ironwood receives 50% of the net profits and bears 50% of the net losses from the commercial sale of LINZESS in the U.S. The purpose of this table is to present calculations of the total net profit (loss) generated from the sales of LINZESS in the U.S., including the commercial costs and expenses and the research and development expenses related to LINZESS in the U.S. that are shared equally between the parties under the collaboration agreement. 2 LINZESS net sales are recognized using AbbVie’s revenue recognition accounting policies and reporting conventions. As a result, certain rebates and discounts are classified as LINZESS U.S. commercial costs, expenses and other discounts within Ironwood’s calculation of collaborative arrangements revenue. 3 Includes certain discounts recognized and cost of goods sold incurred by AbbVie; also includes commercial costs incurred by AbbVie and Ironwood that are attributable to the cost-sharing arrangement between the parties. 4 R&D expenses related to LINZESS in the U.S. are shared equally between Ironwood and AbbVie under the collaboration agreement. 5 Total net profit on sales of LINZESS does not reflect the estimated gross-to-net change related to the year ended December 31, 2023. View source version on businesswire.com: Contacts Investors: Greg Martini, 617-374-5230 gmartini@ironwoodpharma.com Matt Roache, 617-621-8395 mroache@ironwoodpharma.com Media: Beth Calitri, 978-417-2031 bcalitri@ironwoodpharma.com Source: Ironwood Pharmaceuticals, Inc. View this news release online at: