VAP-1

近日，减肥药巨头诺和诺德股价大跌约18%，市值蒸发625亿美元，约合4600亿元人民币。其市值急剧下跌的主要原因是该公司公布的减肥药物CagriSema临床数据未能达到市场预期，引发了投资者的广泛担忧。 01 市值蒸发625亿美元 CagriSema是诺和诺德开发的一种用于治疗肥胖症或超重成人的药物，它是一种固定剂量的复方制剂，包含长效胰淀素类似物cagrilintide 2.4 mg和GLP-1受体激动剂semaglutide 2.4 mg。这种药物设计为每周一次的皮下注射，通过减少饥饿感、增加饱腹感来帮助患者减少食量和降低卡路里摄入，从而实现体重减轻。 此前，诺和诺德已经公布了CagriSema在治疗2型糖尿病的II期临床试验中的积极结果，显示其不仅能有效降低糖化血红蛋白（HbA1c）水平，还具有显著的减肥效果。 而在近期诺和诺德最新公布的临床3期试验REDEFINE 1的主要结果中，CagriSema的患者在68周后平均减轻了22.7%的体重，低于此前公司25%的预期水平，导致了股价的下跌。 图片来源：诺和诺德官网 这一低于预期数据，对诺和诺德来说打击不小。此前，诺和诺德凭借Wegovy打开了肥胖症的市场，本想以差异化产品组合，打出王牌CagriSema以夺取先机，以期超越礼来的减肥药Zepbound，迭代减肥药市场霸主地位，然而事与愿违，随着不及预期临床数据结果的披露，导致了公司市值的强烈反应。 尽管如此，诺和诺德表示将会继续探索CagriSema作为减重疗法的潜力，并期待第二项关键性3期试验REDEFINE 2的结果，“在REDEFINE1试验中，CagriSema的减肥效果显示出其单一疗法优于semaglutide和cagrilintide，这让我们感到鼓舞。尽管只有57%的患者达到了最高的CagriSema剂量，但还是实现了这一目标。”诺和诺德负责开发的执行副总裁Martin Holst Lange说道。“凭借REDEFINE1试验获得的见解，我们计划进一步探索CagriSema的额外减肥潜力。” 第二项关键3期试验REDEFINE2的结果预计将于2025年上半年公布，该试验针对患有肥胖或超重的2型糖尿病成人患者。 资料显示，除了CagriSema外，诺和诺德的GLP-1受体和胰淀素受体的长效共激动剂Amycretin正在开发皮下注射（每周一次）和口服（每天一次）两种剂型，目前拟开发的适应症为肥胖。 在诺和诺德公布的小型1期临床研究中，患者接受Amycretin治疗12周后体重下降幅度达到13.1%，而安慰剂组仅为1.1%。这一结果表明Amycretin具有快速减重的效果以及较好的临床应用潜力，有望成为减重领域新星。 02 诺和诺德的下一步 作为糖尿病和肥胖症治疗领域的领导者，诺和诺德凭借其相关创新产品占据市场主导地位。但随着全球制药巨头礼来通过其相关王牌药物奋力追赶，“两王”格局已基本形成。 CagriSema的试验结果不及预期，不仅影响了诺和诺德的股价，也可能改变其在激烈竞争的减肥药市场中的定位。但诺和诺德早已未雨绸缪，不断拓宽研发边界，强化慢性病治疗、心血管领域的布局。 慢性病治疗领域 诺和诺德的业务定位相对集中，其产品主要涉及糖尿病、肥胖、罕见病以及其他慢性疾病四大治疗领域。截至2023年底，司美格鲁肽全球超百余项临床试验，除了糖尿病和肥胖症适应症以外，在NASH、疼痛、慢性肾病、卒中等方面均有布局。 其中，司美格鲁肽治疗NASH的Ⅱ期临床试验已取得积极疗效数据，目前正在进行全球III期临床试验。另外，司美格鲁肽在治疗射血分数保留型心力衰竭肥胖成人患者的III期临床试验中同样取得了积极的疗效结果。 其正在拓宽慢性病治疗边界，管线中有超过50%的项目基于全新的疾病机理，并希望在2025年实现50%的研发管线项目来源于外部合作。这种内生+外延并举的策略，积极向新兴治疗领域扩张，覆盖MR、ANGPTL3、VAP-1、NLRP3等靶点，主要治疗心血管疾病、MASH、帕金森病等适应症。 心血管疾病领域 在心血管疾病领域，诺和诺德专注于两大重点：动脉粥样硬化性心血管疾病（ASCVD）和心力衰竭。 ASCVD包括血脂异常、系统性炎症、未控制高血压和难治性高血压；心力衰竭包括射血分数保留的心力衰竭（HFpEF）和转甲状腺素蛋白淀粉样变性心肌病（ATTR-CM）。 今年3月，诺和诺德通过收购德国生物技术公司Cardior，强化了其在心血管疾病领域的研发管线。Cardior专注于开发靶向RNA，以预防、修复及逆转心脏疾病，其首要化合物CDR132L处于针对心力衰竭的2期临床研发阶段。CDR132L显示出良好的安全性和耐受性，同时相较于安慰剂可改善心力衰竭患者的心脏功能。诺和诺德新闻稿称“此项收购是诺和诺德进军心血管疾病领域相关战略向前迈出的重要一步”。 综上，诺和诺德在慢性病治疗和心血管领域的布局显示了其在强化降糖减重全球地位的同时，通过内生+外延策略，不断布局新兴治疗领域，以期在未来实现更大的增长和创新。 03 结语 药物研发过程中，临床数据不及预期的情况虽然可能引起市场和投资者的短期忧虑，但从长远来看，这也可以视为研发过程中的一个自然现象，这些挑战同时也带来了改进、学习和创新的机会。长期趋势来看，医药行业的研发活动仍在稳步推进，技术的进步和以患者为中心的设计理念将继续推动新药研发向前发展。 参考来源： 1.https://www.yicai.com/news/102062642.html 2.https://www.novonordisk.com/content/nncorp/global/en/news-and-media/news-and-ir-materials/news-details.html?id=915082 3.https://xueqiu.com/4376152234/261753538 4.https://mp.weixin.qq.com/s/4v-ufb_d9n8ds4XPOCkyYQ 5.https://mp.weixin.qq.com/s/rIfLVzlWHgLiUYLX04_CgQ 友情推荐：医药行业深度技术内容，点击“博药”查看详情~ 声明：本内容仅用作医药行业信息传播，为作者独立观点，不代表药智网立场。如需转载，请务必注明文章作者和来源。对本文有异议或投诉，请联系maxuelian@yaozh.com。 责任编辑 | 史蒂文 合作、投稿、转载开白 | 马老师 18323856316（同微信）  阅读原文，是受欢迎的文章哦

Both ECC4703 and ECC0509 demonstrated best-in-class potential, with favorable safety and tolerability profiles, clear target engagement and encouraging efficacy signalsBOSTON and SHANGHAI, Nov. 15, 2024 (GLOBE NEWSWIRE) -- Eccogene, a clinical-stage biopharmaceutical company developing next-generation oral small molecule therapeutics for chronic cardiometabolic and inflammatory conditions, today announced that two late-breaking abstracts on new Phase 1 data covering its novel oral THR-β full agonist (ECC4703) and oral SSAO inhibitor (ECC0509) will be reviewed in poster presentations at the American Association for the Study of Liver Diseases (AASLD) The Liver Meeting®. The congress is taking place November 15-19 in San Diego, California. “We are pleased that our Phase 1 results for ECC4703 and ECC0509 were selected as late-breaking abstracts at this premier medical congress – the first time human data for these programs will be publicly presented,” said Jingye Zhou, Chief Executive Officer of Eccogene. “Our Phase 1 results – which demonstrate favorable safety and tolerability profiles, PK and PD profiles supporting a once daily dose, and clear target engagement – highlight the potential for both candidates to be best-in-class molecules and provide the confidence needed to continue advancing these compounds into Phase 2 development.” Late-Breaking Poster Presentation Details: ECC4703 Title: Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ECC4703, a Highly Selective Liver Targeting Thyroid Hormone Receptor-beta (THR-β) Full Agonist for MASH (#5019)Session: Poster Session IV Date / Time: November 18, 2024 from 8:00 am - 5:00 pm PT Presenter: Dr. Sam Pak, PPD/AES, a part of Thermo Fisher Scientific Abstract Data Summary: ECC4703 exhibited a favorable safety and tolerability profileThe observed pharmacodynamic biomarker changes indicated clear target engagement, effectively lowering a panel of atherogenic lipids, with significant LDL reduction observed over 14 days of treatment ECC0509 Title: Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ECC0509, a SSAO Inhibitor for MASH (#5020)Session: Poster Session IV Date / Time: November 18, 2024 from 8:00 am - 5:00 pm PTPresenter: Dr. Angela Rowland, CMAX Clinical Research Pty Ltd Abstract Data Summary: ECC0509 demonstrated a favorable safety and tolerability profilePlasma SSAO activity was almost entirely inhibited by low doses of ECC0509, whereas plasma methylamine increased dose-dependently The abstracts for Eccogene’s poster presentations are now available on the AASLD website. The Company will make the posters available on its corporate website following the presentation session. About EccogeneEccogene is a clinical-stage biopharmaceutical company developing next-generation oral small molecule therapeutics for chronic cardiometabolic and inflammatory conditions. Since its founding, Eccogene has been dedicated to discovering safer and more effective oral therapies that can be used alone or synergistically with a GLP-1 receptor agonist to treat conditions beyond obesity. The Company’s diverse pipeline of small molecule candidates leverages its world-class expertise in translational research, small molecule discovery, and a deep understanding of diabetes, weight loss and cardiometabolic disease pathways. Eccogene’s oral small molecule GLP-1 receptor agonist, ECC5004, is a potentially best-in-class asset. ECC5004 was licensed to AstraZeneca and Eccogene retains the rights to co-develop and co-commercialize in China. The Company also has clinical programs underway that target THR-β and SSAO, as well as preclinical programs targeting proven pathways, such as GIP. For more information, please visit www.eccogene.com or follow the Company on LinkedIn. Media Contact Amy Bonanno Lyra Strategic Advisory abonanno@lyraadvisory.com

ECC5004/AZD5004 is an investigational oral small molecule GLP-1 receptor agonist licensed to AstraZeneca in November 2023 BOSTON, MA, USA and SHANGHAI, China I October 23, 2024 I Eccogene, a clinical-stage biopharmaceutical company developing next-generation oral small molecule therapeutics for chronic cardiometabolic and inflammatory conditions, announced that it will receive a $60 million payment from AstraZeneca, which is being triggered by successfully achieving milestones related to the development of ECC5004/AZD5004 including the first patient dosed in the Phase 2b program. VISTA ( NCT06579092 ) and SOLSTICE ( NCT06579105 ) are two global Phase 2b multicenter trials assessing the efficacy and safety of ECC5004/AZD5004, administered orally, once daily, to participants who are obese or overweight with at least one weight-related comorbidity and type 2 diabetes, respectively. AstraZeneca licensed the global rights to ECC5004/AZD5004 from Eccogene in November 2023, for which the Company received an upfront payment of $185 million and can receive up to $1.825 billion in future milestones, as well as royalty payments. Eccogene retains co-development and co-commercialization rights to ECC5004/AZD5004 in China. “Obesity and its associated comorbidities affect over one billion people worldwide and continue to grow in prevalence. We are pleased to see ECC5004/AZD5004 – our internally discovered oral small molecule GLP-1 receptor agonist – advancing into Phase 2b clinical trials for obesity and type 2 diabetes. This is an important milestone for Eccogene, as it provides strong validation for our translational research platform and underscores the efficiency and effectiveness of our close collaboration with AstraZeneca,” said Jingye Zhou, Chief Executive Officer of Eccogene. Sharon Barr, Executive Vice President, BioPharmaceuticals R&D at AstraZeneca, commented: “Rapidly progressing AZD5004 is a priority, as novel solutions are needed for patients to address interrelated cardiometabolic disease and the serious risks associated with type 2 diabetes, obesity or overweight with comorbidities. The start of our two Phase 2b trials marks a significant milestone in our efforts to provide an alternative to current injectable therapies that can be offered as a monotherapy as well as in combination for addressing interrelated diseases.” Leveraging its translational research platform and deep understanding of metabolic disease pathways – in addition to ECC5004/AZD5004 – Eccogene discovered and is advancing a pipeline of next-generation oral therapeutics that can be used alone or in combination with GLP-1 receptor agonists. This includes the Company’s clinical-stage THR-β agonist and SSAO inhibitor – both of which are differentiated compounds, and when used in combination, can potentially help augment the efficacy of GLP-1 to address comorbidities of obesity. Eccogene is also advancing several innovative preclinical programs, such as a small molecule GIP receptor modulator. About Eccogene Eccogene is a clinical-stage biopharmaceutical company developing next-generation oral small molecule therapeutics for chronic cardiometabolic and inflammatory conditions. Since its founding, Eccogene has been dedicated to discovering safer and more effective oral therapies that can be used alone or synergistically with a GLP-1 receptor agonist to treat conditions beyond obesity. The Company’s diverse pipeline of small molecule candidates leverages its world-class expertise in translational research, small molecule discovery, and a deep understanding of diabetes, weight loss, and cardiometabolic disease pathways. Eccogene’s oral small molecule GLP-1 receptor agonist, ECC5004/AZD5004, is a potentially best-in-class asset, which was licensed to AstraZeneca. Eccogene also has clinical programs underway that target THR-β and SSAO, as well as preclinical programs targeting proven pathways, such as GIP. For more information, please visit www.eccogene.com or follow the Company on LinkedIn . SOURCE: Eccogene