Linaclotide

深度聚焦多肽、多肽偶联药物研发、质控、工艺开发，7月相约苏州，联系电话181160367981、多肽药物优势明显根据观研报告网发布的《中国多肽药物行业现状深度研究与发展前景分析报告（2024-2031年）》显示，多肽药物是指通过化学合成、基因重组或从动植物中提取的具有特定治疗作用的多肽，通常由10-50个氨基酸组成。多肽根据分泌部位可分为：内源性生物活性肽与外源性生物活性肽，即人体内存在的天然生物活性肽与人体外的肽类物质。相较于小分子化药和蛋白类药物均具有优势：相较于小分子化药，多肽具有更高的活性和更强的选择性，在治疗复杂疾病方面优势明显，且由于多肽本身是氨基酸组成的化合物，其代谢产物为氨基酸，对人体一般没有副作用或副作用很小；相对于蛋白质药物，多肽药物具有稳定性较好、纯度高、生产成本低、免疫原性较低或无免疫原性等优势。在药物研发阶段，还能通过化学修饰改进药物候选物的亲和力、溶解性、药代动力学性质（稳定性）、毒性等，支持多肽类药物候选物的快速筛选多肽药物与传统小分子化药和蛋白质药物的比较药物传统小分子化药多肽药物蛋白质药物相对分子量一般不高于500500-10000一般高于10000稳定性好较好差生物活性较低高高特异性弱强强免疫原性无无或低有纯度高高较低成本低高更高举例阿司匹林利拉鲁肽单克隆抗体原子个数：21相对分子量：180原子个数：531相对分子量：3751原子个数：＞25,000相对分子量：~150,000资料来源：观研天下数据中心整理2、多肽药物功能多样，市场规模稳健增长多肽药物功能多样：目前临床上主要的药用多肽有四种：（1）激素类多肽及其衍生药物由于多肽半衰期短且合成成本较高，早期的多肽药物研发主要以作用浓度低的人源激素肽为主，包括胰岛素、催产素、抗利尿激素、生长抑素、等短肽药物，目前仍在沿用。（2）源自动植物、微生物等的天然多肽产物典型的天然活性肽主要包含微生物的次级代谢产物，及分离自两栖动物、昆虫毒液的活性多肽，如ICK肽。（3）多肽疫苗由多肽制成的一种亚单位疫苗，相较于传统的灭活及减毒疫苗，多肽疫苗不仅可以作为感染或非感染性疾病的预防疫苗，还可以用于治疗阿尔兹海默症、恶性肿瘤等疾病。（4）以PDC为主的多肽药物递送系统。多肽药物市场规模稳健增长。据弗若斯特沙利文数据，全球多肽药物市场市场规模从2016年的568亿美元上升至2020年的628亿美元，年复合增速2.6%。预计2023年将达到795亿美元。中国多肽类药物行业市场规模呈现快速增长趋势，从2016年的435亿元上升至2020年的587亿元，年复合增速达到了8%，远远超过了全球增速，未来市场规模将进一步扩大，预计2023年达到904亿元。资料来源：弗若斯特沙利文，观研天下数据中心整理资料来源：弗若斯特沙利文，观研天下数据中心整理截至2023年1月，全球已上市多肽药物约180种。国际上的多肽药物主要分布在7大疾病治疗领域，包括罕见病、肿瘤、糖尿病、胃肠道、免疫、心血管疾病等，其中罕见病、肿瘤和糖尿病是拉动多肽药物市场的三驾马车。随着多肽结构修饰与化学改造方法迭代，包括肽链骨架的改造，以及引入脂肪酸、聚乙二醇、蛋白融合等进行修饰优化，叠加新靶点开发、新适应症拓展以及剂型优化，为多肽药物市场空间带来新增量，未来多肽药物市场空间有望持续扩大。2022年全球销售额top25多肽药物药物商品名公司适应症首次批准2022年销售额（亿美元）司美格鲁肽Rybelsus/Ozempic/Wegovy诺和诺德糖尿病、肥胖2018109.14度拉糖肽Trulicity礼来糖尿病201474.40甘精胰岛素Basaglar/Lantus/Toujeo礼来、赛诺菲糖尿病200043.10门冬胰岛素Novomix/Fiasp/ NovoRapid诺和诺德糖尿病200035.52利拉鲁肽Victoza/Saxenda诺和诺德糖尿病、肥胖201032.50人胰岛素Humulin/Human Insulin礼来、诺和诺德糖尿病198221.76赖脯胰岛素Humalog礼来糖尿病199620.61德谷胰岛素Tresiba诺和诺德糖尿病201313.22罗米司亭Nplate安进原发免疫性血小板减少症200813.07兰瑞肽Somatuline益普生肢端肥大症200712.81卡非佐米Kyprolis安进多发性骨髓瘤201212. 47奥曲肽Sandostatin诺华肿瘤198812.38利那洛肽Linzess/Constella安斯泰来、艾伯维便秘型肠易激综合征201210.88环孢菌素Restasis/Neoral/Sandimmun艾伯维、诺华免疫疾病、器官移植19839.76戈舍瑞林Zoladex阿斯利康癌症19899.27亮丙瑞林Leuplin/ Enantone武田制药中枢性青春早熟症19898.32替度鲁肽Gattex/Revestive武田制药短肠综合症20127.40格拉替雷Copaxone梯瓦制药复发性多发性硬化症19966.91地特胰岛素Levemir诺和诺德糖尿病20056.47特立帕肽Forteo礼来骨质疏松症20026.13曲普瑞林Decapeptyl益普生激素依赖性前列腺癌、子宫内膜异位症19865.57促皮质素.Acthar GelMallinckrodt (万灵科)活动性风湿病、类风湿性关节炎、红斑性狼疮等19505.16替尔泊肽Mounjaro礼来糖尿病、减肥20224.83镥氧阳奥曲肽Lutathera诺华胃肠胰腺神经内分泌肿瘤20174.71广冬/德谷胰岛素Ryzodeg诺和诺德糖尿病20134.08资料来源：公开资料3、肥胖问题日益严峻，全球减重药物管线已破百，研发热度高涨WHO定义成人超重BMI为25.0~29.9kg/m²，肥胖BMI≥30.0kg/㎡。全球超重/肥胖问题日益严峻。2020年全球已有超过26亿人受到超重/肥胖影响，据《World Obesity Atlas 2023 Report》预测，到2035年可能有超过40亿人受到影响。肥胖患者的患病率将从14%上升到24%，到2035年将影响近20亿成人、儿童和青少年。在2020年至2035年期间预计儿童和青少年肥胖率的上升速度最快，全球男孩的肥胖率将从10%上升到20%，女孩的肥胖率将从8%上升到18%。中国成人超重/肥胖率已过半。世界肥胖地图预测中国在2035年有18%的成年人BMI≥30kg/㎡，达到肥胖。2020-2035年成人肥胖的年增长率高达5.4%，儿童肥胖年增长率高达6.6%，2035年超重对国家GDP的影响为3.1%。近年来，中国慢性非传染性疾病致死率高达90%，而超重/肥胖是慢性病的主要危险因素，亟需引起关注。2035年全球近40亿人受到肥胖影响，肥胖患者患病率将达到24%，全球GLP1管线（减重药物管线）已破百，国内已有20多家公司启动了GLP1生物类似药的在研项目，其中九源基因以及齐鲁制药等公司已将产品推至II期临床。国内部分公司已推进GLP1方向创新药的研发，其中乐普生物、恒瑞医药、双鹭药业等公司进展最快已推进至III期临床，预计2024年将实现GLP1方向首批III期临床数据揭盲。资料来源：观研天下数据中心整理资料来源：观研天下数据中心整理资料来源：观研天下数据中心整理资料来源：观研天下数据中心整理资料来源：观研天下数据中心整理资料来源：观研天下数据中心整理（qmm）END深度聚焦多肽、多肽偶联药物研发、质控、工艺开发，7月相约苏州，联系电话18116036798戳“阅读原文”立即报名多肽药物论坛吧!

– First prospective trial of a glucagon-like peptide (GLP-2) analog in SR GI aGVHD – – Results up to Day 91 show that apraglutide in SR GI aGVHD was well-tolerated with an acceptable safety profile, the study’s primary objective – – Exploratory secondary efficacy data showed lower GI tract responses maintained through Day 91 in SR GI aGVHD patients treated with apraglutide and standard of care – BOSTON--(BUSINESS WIRE)-- Ironwood Pharmaceuticals, Inc. (Nasdaq: IRWD), a GI-focused healthcare company, today announced positive, primary results up to Day 91 for its Phase II exploratory STARGAZE trial evaluating apraglutide in patients with steroid-refractory gastrointestinal acute Graft-versus-Host Disease (SR GI aGVHD). The primary objective of the trial was to evaluate the safety and tolerability of once-weekly apraglutide, a next-generation, long-acting glucagon-like peptide-2 (GLP-2) analog, in SR GI aGVHD patients treated with standard of care, including systemic corticosteroids and ruxolitinib. This was a first-of-its-kind study combining a GLP-2 analog with immunosuppressive therapy in patients with SR GI aGVHD. The safety and tolerability observed in this trial was consistent with the standard of care and known safety of GLP-2 analogs, as well as observed events in the GVHD population. The emerging safety pro apraglutide in the SR GI aGVHD population was monitored by an independent safety review committee that endorsed the continuation of the study without modification. In addition to evaluating safety, secondary endpoints evaluated efficacy using lower GI and all-organ responses, indicative of organ-level improvement from baseline per the Mount Sinai Acute GVHD International Consortium (MAGIC) grading system. The majority of patients responded to treatment by Day 28 and Day 56. All lower GI responders at Day 28 maintained their response through Days 56 and 91, considering available organ staging assessments. “The findings presented here are an important step forward for patients with SR GI aGVHD given limited duration of response with currently approved agents,” said Robert Zeiser, M.D., Professor of Hematology and Oncology at the University of Freiburg and Principal Investigator for the STARGAZE study. “Given its potential GI effect on tissue regeneration and function, apraglutide may have a role in the advanced management of acute GI GVHD through a non-immunosuppressive approach, and we look forward to longer-term findings in this patient population.” aGVHD is a rare, life-threatening condition that occurs when immune cells of the donor (the graft) attack a recipient’s (host) healthy cells after an allogeneic hematopoietic stem cell transplant (HSCT). The condition typically affects the skin, GI tract, and liver. GI aGVHD, is a leading cause of morbidity and mortality following HSCT with approximately 70% of aGVHD cases having GI involvement. While treatment options exist for aGVHD, a significant number of patients do not respond to 1st line therapy, such as corticosteroids. Despite receiving 2nd line therapy, many patients also do not maintain response over time, with significant non-relapse mortality (NRM) after six months. “These results from the first-of-its-kind STARGAZE trial in a population of patients with SR GI aGVHD add to the body of evidence about the safety and tolerability pro apraglutide,” said Michael Shetzline, M.D., Ph.D., Senior Vice President, Chief Medical Officer and Head of Research and Development at Ironwood Pharmaceuticals. “Other studies have shown that GLP-2 promotes intestinal healing and regeneration, and we look forward to further understanding the data from this trial given the high unmet medical need of these patients who suffer from high morbidity and mortality.” Additional data from the STARGAZE trial are expected to be presented at an upcoming medical congress. The STARGAZE study will continue through its two-year endpoint, where apraglutide will be re-evaluated for safety and efficacy. About STARGAZE STARGAZE (Study of Apraglutide in Graft-versus-Host Disease) is a randomized, single-blind, Phase II exploratory trial designed to evaluate weekly dosing of apraglutide in combination with standard of care, including systemic corticosteroids and ruxolitinib in patients with steroid-refractory GI aGVHD for up to 90 days with a follow-up period lasting up to two years after the first dose. STARGAZE is the first prospective trial of a glucagon-like peptide (GLP-2) analog focusing on patients with steroid-refractory GI aGVHD. The trial enrolled 31 patients and at this primary analysis, evaluated them for safety and tolerability, pharmacokinetics, and efficacy, including response rate, duration of response, and survival-related outcomes. This study’s population consisted of more than 87% Grade III and IV patients, the most severe cohort as measured by the Mount Sinai Acute Graft Versus Host Disease International Consortium (MAGIC) scale. About Acute Graft-Versus-Host Disease (aGVHD) Acute Graft-Versus-Host Disease (aGVHD) is a severe condition which occurs when immune cells from the donor attack a recipient’s healthy cells after an allogeneic hematopoietic stem cell transplant (HSCT), the standard last-line treatment for many forms of blood cancer. aGVHD typically emerges within the first 100 days post-transplant and predominantly affects the skin, gastrointestinal (GI) tract and liver. GI GvHD is one of the leading causes of morbidity and mortality following HSCT. The predominant manifestations of GI GVHD are abdominal pain and diarrhea. The diarrhea is secretory, occurs independently of oral intake and can be profound and incessant, with up to several liters of output and more than 10 episodes per day, often requiring parenteral support to feed and hydrate patients. More than 26,000 allogeneic HSCTs take place in the U.S., Europe and Japan annually and aGVHD occurs in an estimated 30-50% of patients. While treatment options exist for aGVHD, a significant number of patients do not respond to 1st line therapy, such as corticosteroids. Despite receiving 2nd line therapy, many patients also do not maintain response over time, with significant non-relapse mortality (NRM) after six months. 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 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. Investors are cautioned not to place undue reliance on these forward-looking statements, including statements about the assessment of the data from the Phase II exploratory STARGAZE trial of apraglutide in patients with steroid-refractory GI aGVHD and the continuation of the study through its two-year endpoint; the safety, tolerability and efficacy of apraglutide in this trial; the potential effect of apraglutide on intestinal healing, function and regeneration; and the therapeutic potential of apraglutide for the treatment of aGVHD. 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 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.