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).

波士顿--（商业新闻短讯）--Ironwood Pharmaceuticals，Inc.（纳斯达克：IRWD），一家专注于胃肠道的医疗保健公司，将在其关键的III期临床试验STARS的2024年消化道疾病周（DDW）会议上提供最新数据，该试验评估了每周一次皮下注射阿帕鲁肽治疗成人短肠综合征伴肠衰竭（SBS-IF）患者的疗效和安全性。

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)..

这些发现基于Ironwood之前在2024年2月宣布的积极的底线数据。根据这些结果，该公司正在努力向美国食品和药物管理局（FDA）提交新药申请（NDA），并向其他监管机构提交阿帕鲁肽的营销申请，用于治疗依赖肠胃外支持（PS）的成年SBS患者。。

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..

SBS-IF是一种罕见的慢性衰弱性吸收不良疾病，患者依赖PS，在美国，欧洲和日本估计有18000名成年患者受到影响。阿帕鲁肽是第一个也是唯一一个每周一次的GLP-2类似物研究，在III期安慰剂对照研究中成功证明了阳性结果。。

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.

DDW的最新数据来自迄今为止进行的最大规模的全球SBS-IF临床试验，并在题为“短肠综合征和肠衰竭（SBS-IF）患者每周一次阿帕鲁肽的有效性和安全性”的口头报告中共享：STARS研究的结果-一项全球3期双盲，随机，安慰剂对照试验。“Ironwood先前报道，STARS临床试验在第24周达到了实际每周PS量相对于基线相对变化的主要终点。

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)..

安慰剂（-25.5%比-12.5%；p=0.001），由造口和结肠在连续亚群中驱动。从第8周开始观察到相对PS体积减少的治疗效果（-8%比-1.6%安慰剂，p=0.002）。。

Findings from the late-breaking presentation include:

从最新的演示中得出的发现包括：

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)

与安慰剂组相比，在第24周，阿帕鲁肽患者每周从PS获得额外的休息天数明显更多（≥2天：24.5%比11.3%，p=0.021；≥3天：11.8%比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

在第20周和第24周，与安慰剂相比，在总体和造口人群中，接受阿帕鲁肽治疗的患者中，临床反应者和临床高反应者（分别定义为PS体积减少≥20%和≥40%）明显更多

Overall population: Clinical responders 42.7% vs 20.8%, p=0.003; Clinical high responders 22.7% vs 9.4%, p=0.018

总体人群：临床反应者42.7%比20.8%，p=0.003；临床高反应者22.7%比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

造口亚群：临床反应者40.7%比15.4%，p=0.02；临床高反应者20.4%比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..

到第24周，7名接受阿帕鲁肽治疗的患者实现了肠内自主（造口亚群中有3名，连续亚群中有4名结肠）（6.4%阿帕鲁肽与0%安慰剂，p=0.006）。另外三名连续性结肠患者在第48周实现了肠内自主：7/56[12.5%]阿帕鲁肽与2/27安慰剂[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.

“考虑到肠胃外支持给SBS-IF患者带来的负担，治疗的目标是重要的是获得额外的PS休息日，并最终实现那些能够实现肠内自主的患者，”Kishore R Iyer，MBBS，FRCS（Eng），FACS，纽约西奈山医院成人和儿科肠道康复与移植主任，该试验的协调首席研究员，向Ironwood支付科学顾问和STARS临床试验科学指导委员会主席。

“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.”.

“一些服用阿帕鲁肽的CIC和造口患者在第24周实现了肠内自主，并在48周内保持了自主性，这是一个重要的结果，并证明了阿帕鲁肽对这些患者的潜力。”。

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.

阿帕鲁肽在两个关键的次要终点也显示出统计学意义，与安慰剂相比，联合人群中更多的患者在第24周相对于基线达到至少一天/周的PS（43.0%比27.5%；p=0.040），更多接受阿帕鲁肽治疗的患者与安慰剂相比，在造口亚群中，第24周实际每周PS体积相对于基线的相对变化有所改善（25.6%比25.6%）。

-7.8%; p<0.001). Apraglutide was well-tolerated, with no new safety signals identified and the safety profile was consistent with previous apraglutide studies..

-7.8%；p＜0.001）。阿帕鲁肽耐受性良好，未发现新的安全信号，安全性与之前的阿帕鲁肽研究一致。。

“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.

Ironwood Pharmaceuticals首席医学官、高级副总裁兼研究和药物开发负责人、医学博士迈克尔·谢茨林（Michael Shetzline）表示：“我们在DDW的数据反映了Ironwood的关键优先事项，重点是推进胃肠道疾病的治疗。”。“阿格列肽的研究结果显示了迄今为止该化合物阳性临床试验结果的广度和深度，III期数据的强度使其能够强有力地提交，并有望获得FDA和其他监管部门的批准。

We’re excited for the opportunity to unlock a new and potentially differentiated treatment option for adult patients with SBS dependent on parenteral support.”.

我们很高兴有机会为依赖肠胃外支持的SBS成年患者开启一种新的，潜在的差异化治疗选择。”。

In addition to the STARS Phase III oral presentation, Ironwood, and its collaborators presented data highlighting findings across the apraglutide development program.

除了STARS第三阶段的口头报告外，Ironwood及其合作者还提供了数据，突出了阿帕鲁肽开发计划的发现。

Impact of once weekly apraglutide on intestinal absorption

每周服用一次阿帕鲁肽对肠道吸收的影响

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.

比利时法兰德斯鲁汶鲁汶大学胃肠疾病转化研究中心（TARGID）研究员阿斯特里德·韦比斯特（AstridVerbiest）发布了三张海报，总结了STARS营养学的新发现。STARS Nutrition是一项针对9名患者的多中心开放标签II期代谢平衡研究，旨在评估阿普鲁肽对连续患有SBS-IF和结肠的成年患者肠道吸收的安全性，药代动力学和有效性。

Positive final data from this study were announced in October 2023..

这项研究的最终积极数据于2023年10月公布。。

“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.

“通过MRI评估短肠综合征肠衰竭（SBS-IF）和连续性结肠患者的肠道形态和运动性的变化”（海报编号Su1946）表明，阿帕鲁肽治疗与小肠延长和十二指肠壁厚度增加有关，表明肠营养（刺激/调节肠组织的生长）效应可能有助于增加吸收表面积。

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..

作者注意到，肠道延长是否是由阿帕鲁肽的直接作用与被动延长引起的运动性变化引起的，还有待进一步研究。。

“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 profile and 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..

“用长效胰高血糖素样肽-2（GLP-2）类似物阿帕鲁肽治疗的连续性结肠短肠综合征肠衰竭（SBS-IF）患者的肠胃外支持断奶，临床益处和改善的患者报告结果”（海报编号Su1947）显示，阿帕鲁肽具有可接受的安全性，并且与连续性结肠的SBS-IF患者的PS需求显着降低相关，导致PS休息天数和基于患者报告结果的主观改善。。

'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.

“短肠综合征伴肠衰竭（SBS-IF）和连续性结肠的阿帕鲁肽治疗与48周时口服摄入量增加和能量和碳水化合物吸收改善有关”（海报编号Su1948）显示，在SBS-IF和连续性结肠患者中，阿帕鲁肽治疗导致粪便排出量早期减少，湿重吸收改善。

After 48 weeks, oral intake was increased despite stable fecal output, leading to increased energy and carbohydrate absorption..

48周后，尽管粪便输出稳定，但口服摄入量增加，导致能量和碳水化合物吸收增加。。

Impact of apraglutide on gastric emptying

阿帕鲁肽对胃排空的影响

'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..

“阿帕鲁肽对健康个体胃排空的影响：一项1期随机，安慰剂对照，双盲，单中心试验”（海报编号Su1949）由Ironwood Pharmaceuticals的Gerard Greig介绍。数据表明，通过对乙酰氨基酚药代动力学（PK）测量，阿帕鲁肽不影响健康个体的液体胃排空，因此可用于广泛的患者人群。。

Irritable Bowel Syndrome with Constipation (IBS-C) and Functional Constipation

肠易激综合征伴便秘（IBS-C）和功能性便秘

“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).

“功能性便秘和肠易激综合征伴便秘的儿科患者的现实世界处方模式”（介绍编号Su2047）由纽约州纽约市纽约长老会摩根士丹利儿童医院医学博士朱莉·克莱夫纳（Julie Khlevner）介绍，表明根据一项回顾性观察性研究，大约三分之一被诊断患有FC或IBS-C的儿童和青少年在五年期间（2018年1月至2023年6月）接受了便秘处方药治疗。

Polyethylene glycol 3350 was the most frequently prescribed medication for pediatric FC and IBS-C, followed by lactulose..

聚乙二醇3350是儿科FC和IBS-C最常用的处方药，其次是乳果糖。。

“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.

“利那洛肽对≥65岁的肠易激综合征伴便秘患者的疗效、安全性和反应时间”（报告编号Tu1653）将由加利福尼亚州洛杉矶加州大学洛杉矶分校DavidGeffen医学院的Lin Chang医学博士介绍。数据基于对2000多名IBS-C成年人的事后分析。

Treatment-emergent adverse events were similar in both age groups and were consistent with the known safety profile of linaclotide in patients with IBS-C..

两个年龄组的治疗紧急不良事件相似，与利那洛肽在IBS-C患者中的已知安全性一致。。

“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.

“评估美国IBS诊断中的医疗保健差异：全国调查分析”（报告编号Tu1027）将由加利福尼亚州洛杉矶Cedars-Sinai医疗中心MSHPM医学博士Christopher V Almario介绍，总结美国近90000名成年人的调查数据。该研究分析了寻求医疗保健的行为，包括看到医疗保健提供者（HCP）的可能性和看到的HCP类型。

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..

即使在控制了潜在的混杂变量（如社会经济地位和症状严重程度）之后，被确定为黑人或非裔美国人的受访者被诊断为IBS的可能性也低于被确定为白人的受访者。。

About STARS

关于星星

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

STARS（SBS中阿帕鲁肽的研究）关键的III期临床试验代表了迄今为止SBS-IF中最大的III期临床试验。

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.

这项全球性，多中心，双盲，随机，安慰剂对照试验评估了成年SBS-IF患者每周皮下注射阿帕鲁肽的有效性和安全性。STARS随机分配164名2:1和163名患者，每周服用一次阿帕鲁肽或安慰剂。通过残余肠道解剖将患者分层约50/50（造口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)..

连续结肠），并在24周（连续亚群中的造口和结肠）和48周（仅连续亚群中的结肠）进行评估。主要终点是第24周实际每周PS量与基线的相对变化。关键的次要终点包括在第24周（总体人群）PS从基线至少减少1天/周的患者；第24周实际每周PS量与基线的相对变化（造口亚群）；在第48周（连续性结肠亚群）PS从基线至少减少1天/周的患者；患者在第48周达到肠内自主（连续性亚群中的结肠）。。

The study was conducted in 18 countries with enrollment from 68 study sites.

这项研究在18个国家进行，来自68个研究地点。

About STARS Nutrition

关于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.

STARS营养学是首次前瞻性评估GLP-2类似物在连续性结肠患者中的临床益处的研究。这项多中心，开放标签的II期代谢平衡研究旨在评估每周一次的阿普鲁肽5 mg皮下注射对52周连续结肠SBS-IF患者肠道吸收的影响。

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..

评估了指示临床疗效的安全性和参数，包括PS体积和能量含量降低。该研究招募了9名平均年龄为46.8岁的成年患者。。

About Short Bowel Syndrome

关于短肠综合征

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.

SBS是一种严重的慢性疾病，对液体和/或营养物质的吸收能力降低，有时需要依赖肠胃外支持来维持健康。短肠综合征通常是由于广泛的肠切除而发生的，长期依赖肠外支持的SBS患者，也称为肠衰竭SBS（SBS-IF），通常会对生活质量产生重大影响，并有感染等严重并发症的风险。

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.

在美国，欧洲和日本，估计有18000名成年患者患有SBS-IF，并且长期依赖PS，这会严重影响生活质量，并有感染等严重并发症的风险。那些SBS-IF最严重的患者每天需要输注PS长达10至15小时。

SBS-IF is associated with frequent complications, significant morbidity and mortality, high economic burden and an impaired quality of life..

SBS-IF与频繁的并发症，显着的发病率和死亡率，高经济负担和生活质量受损有关。。

About Apraglutide

关于阿普拉鲁肽

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)..

Apraglutide是一种研究性的下一代长效合成GLP-2类似物，正在为一系列罕见的胃肠道疾病开发，其中GLP-2可以在解决疾病病理生理学方面发挥核心作用，包括短肠综合征伴肠衰竭（SBS-IF）和急性移植物抗宿主病（aGVHD）。。

About LINZESS

关于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.

根据IQVIA数据，LINZESS®是美国第一大处方品牌，用于治疗患有便秘的肠易激综合征（“IBS-C”）或慢性特发性便秘（“CIC”）的成年患者。LINZESS是一种每日一次的胶囊，有助于缓解腹痛，便秘和与IBS-C相关的腹胀，不适和疼痛的整体腹部症状，以及与CIC相关的便秘，罕见大便，硬便，紧张和不完全撤离。

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缓解6至17岁患有功能性便秘的儿童和青少年的便秘。IBS-C患者的推荐剂量为290 mcg，CIC患者的推荐剂量为145 mcg，根据患者的个体表现或耐受性，批准用于CIC的剂量为72 mcg。对于6至17岁的功能性便秘儿童，推荐剂量为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.

LINZESS不是泻药；这是FDA批准的第一种GC-C激动剂类药物。LINZESS含有一种称为利那洛肽的肽，可激活肠道中的GC-C受体。GC-C的激活被认为会导致肠液分泌增加，运输加速，肠道中疼痛感应神经的活性降低。

The clinical relevance of the effect on pain fibers, which is based on nonclinical studies, has not been established..

基于非临床研究的疼痛纤维效应的临床相关性尚未确定。。

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.

在美国，Ironwood和AbbVie共同开发并共同商业化了LINZESS，用于治疗患有IBS-C或CIC的成年人。在欧洲，AbbVie以CONSTELLA®品牌销售用于治疗中度至重度IBS-C成人的利那洛肽。在日本，Ironwood的合作伙伴Astellas以LINZESS品牌销售用于治疗IBS-C或CIC成人的利那洛肽。

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..

Ironwood还与阿斯利康（AstraZeneca）合作，在中国开发和商业化LINZESS，并与艾伯维（AbbVie）合作，在全球所有其他地区开发和商业化利那洛肽。。

LINZESS Important Safety Information

LINZESS重要安全信息

INDICATIONS AND USAGE

适应症和用法

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..

LINZESS®（利那洛肽）适用于治疗成人便秘型肠易激综合征（IBS-C）和慢性特发性便秘（CIC）以及6至17岁儿童和青少年的功能性便秘（FC）。目前尚不清楚LINZESS对FC小于6岁的儿童或IBS-C小于18岁的儿童是否安全有效。。

IMPORTANT SAFETY INFORMATION

重要安全信息

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

警告：2岁以下儿科患者有严重脱水的风险

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.

LINZESS在2岁以下的患者中是禁忌的。在新生小鼠的非临床研究中，单次临床相关成人口服剂量的利那洛肽会导致脱水死亡。

Contraindications

禁忌症

LINZESS is contraindicated in patients less than 2 years of age due to the risk of serious dehydration.

由于严重脱水的风险，LINZESS在2岁以下的患者中是禁忌的。

LINZESS is contraindicated in patients with known or suspected mechanical gastrointestinal obstruction.

LINZESS是已知或疑似机械性胃肠道梗阻患者的禁忌症。

Warnings and Precautions

警告和注意事项

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..

LINZESS在2岁以下的患者中是禁忌的。在新生小鼠中，利那洛肽由于年龄依赖性鸟苷酸环化酶（GC-C）激动作用升高而增加了液体分泌，这与脱水导致的前24小时内死亡率增加有关。在2至18岁以下儿童的临床研究中，GC-C肠道表达没有年龄依赖性趋势；然而，关于2岁以下儿童GC-C肠道表达的数据不足，无法评估这些患者发生腹泻的风险及其潜在的严重后果。。

Diarrhea

腹泻

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..

在成人中，在合并的IBS-C和CIC双盲安慰剂对照试验中，腹泻是LINZESS治疗患者最常见的不良反应。IBS-C和CIC人群的腹泻发生率相似。145 mcg和290 mcg LINZESS治疗的患者中有2%报告有严重腹泻，72 mcg LINZESS治疗的CIC患者中有1%报告有严重腹泻。。

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..

在FC双盲安慰剂对照试验中，在6至17岁的儿童和青少年中，腹泻是72 mcg LINZESS治疗患者中最常见的不良反应。据报道，在72 mcg LINZESS治疗的患者中，有1%的患者出现严重腹泻。如果发生严重腹泻，应停止给药并使患者重新水化。。

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

常见不良反应（发生率≥2%，大于安慰剂）

In IBS-C or CIC adult patients: diarrhea, abdominal pain, flatulence, and abdominal distension.

在IBS-C或CIC成年患者中：腹泻，腹痛，肠胃气胀和腹胀。

In FC pediatric patients: diarrhea.

FC儿科患者：腹泻。

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

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.

LINZESS®和CONSTELLA®是Ironwood Pharmaceuticals，Inc.的注册商标。本新闻稿中提及的任何其他商标均为其各自所有者的财产。保留所有权利。

About Ironwood Pharmaceuticals

关于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.

Ironwood Pharmaceuticals（Nasdaq:IRWD）是一家标准普尔SmallCap 600®公司，是全球领先的胃肠道（GI）保健公司，其使命是推进胃肠道疾病的治疗并重新定义胃肠道患者的护理标准。我们是美国LINZESS®（利那洛肽）开发的先驱。

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.

针对患有便秘的肠易激综合征（IBS-C）或慢性特发性便秘（CIC）的成年人的品牌处方市场领导者，也适用于治疗6-17岁儿科患者的功能性便秘。Ironwood还正在开发阿帕鲁肽，这是一种下一代长效合成GLP-2类似物，正在开发用于罕见的胃肠道疾病，包括伴有肠衰竭的短肠综合征（SBS-IF）以及一些早期资产。

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..

在我们胃肠道创新历史的基础上，我们将患者置于研发和商业化努力的核心，以减轻胃肠道疾病的负担并解决重大未满足的需求。Ironwood Pharmaceuticals成立于1998年，总部位于马萨诸塞州波士顿，总部位于瑞士巴塞尔。。

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.

我们经常在我们的网站www.ironwoodpharma.com上发布对投资者可能很重要的信息。此外，请在X和LinkedIn上关注我们。

Forward-Looking Statements

前瞻性声明

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.

本新闻稿包含1995年《私人证券诉讼改革法案》所指的前瞻性声明。提醒投资者不要过度依赖这些前瞻性声明，包括关于评估阿帕鲁肽III期STARS临床试验数据的声明；阿帕鲁肽的有效性，安全性和耐受性；Ironwood计划向其他监管机构提交阿帕鲁肽的NDA和营销申请；美国，欧洲和日本患有SBS-IF的估计成年人口；第三阶段数据的发现和强度能够有力地提交并获得潜在的FDA和其他监管批准；以及为依赖PS的SBS成年患者开启新的差异化治疗选择的潜在机会。

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.

这些前瞻性声明仅在本新闻稿发布之日有效，Ironwood没有义务更新这些前瞻性声明。每个前瞻性声明都存在风险和不确定性，这些风险和不确定性可能导致实际结果与该声明中明示或暗示的结果存在重大差异。

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.

适用的风险和不确定性包括与我们和我们的合作伙伴的开发和商业化工作的有效性有关的风险和不确定性；阿格列肽的临床前和临床开发，制造和制剂开发；临床计划和研究可能无法按预期进展或发展的风险，包括由于任何原因（例如安全性，耐受性，入学，制造，经济或其他原因）延迟或中断研究；完成的非临床和临床研究的结果可能无法在以后的研究中复制；FDA可能面临的风险。