If you are interested in keeping up to date with stocks making moves within the biotech, pharma and healthcare industries, and understanding the key trends and catalysts driving valuations ahead of the market, why not subscribe to my weekly newsletter via my Investing Group, Haggerston BioHealth ?Novo's tough 2025 continued with announcement this morning that it was cutting jobs and slashing profit guidance. While the news is somewhat shocking given the supreme potential of its best-selling drug molecule, s ...

核心观点 - 市场对Viking Therapeutics口服减肥药VK2735二期试验结果的负面反应可能过于草率 该股仍存在投资机会[1][3] - 尽管试验中因不良事件导致的停药率较高达20% 但药物疗效显著 体重减少率达12.2%[5][7] - 公司可能通过与大药企合作或优化剂量推进三期临床 或作为减肥后维持疗法 存在多种开发路径[8] 试验结果分析 - 二期Venture试验显示口服VK2735具有显著疗效 体重减少12.2% 但因不良事件停药率20%引发市场担忧[5][7] - 停药率高于礼来和诺和诺德三期试验数据：诺和诺德口服司美格鲁肽停药率6%（安慰剂4%）礼来口服Orforglipron停药率10.3%（安慰剂2.6%）[6][7] - 安全性问题与辉瑞此前终止同类口服减肥药开发的情况类似[5] 同业对比数据 - Viking口服VK2735二期体重减少率12.2% 与礼来Orforglipron三期减少12.4%及诺和诺德司美格鲁肽三期减少15%效果相当[7] - 因不良事件停药率：Viking试验组20%（安慰剂13%）显著高于诺和诺德试验组6%（安慰剂4%）和礼来试验组10.3%（安慰剂2.6%）[7] 未来发展前景 - 大药企可能通过收购或合作方式推进VK2735口服制剂三期临床 或通过剂量优化改善耐受性[8] - 药物潜在应用场景包括作为减肥后维持疗法 为开发提供更多可能性[8] - 皮下注射剂型三期结果预计2027年公布 当前市场关注度集中于口服制剂[2]

公司技术突破 - 公司宣布使用AmorphOX技术开发的粉末状鼻内索马鲁肽制剂在体内药代动力学研究中取得积极数据 涉及三种不同鼻内给药的粉末制剂 并与口服片剂Rybelsus和皮下注射剂Wegovy进行对比[1] - 其中两种AmorphOX粉末制剂的中位血浆值相比口服片剂提高7倍 虽然仍低于注射剂 但血浆浓度变异性更低[2] - AmorphOX技术能够将大分子配制成鼻内给药的粉末 提供无针给药方式 改善便利性 可能提高用药依从性 且无需冷藏 根据鼻内剂量强度和治疗水平 给药频率可能低于口服途径[3] 技术平台优势 - AmorphOX是公司专有药物递送平台 由药物、载体材料和可选其他成分组成的颗粒构成 呈现为无定形复合物 具有优异的化学和物理稳定性以及快速溶解特性[7] - 该技术适用于广泛活性成分 已在多项人体临床研究中得到验证 显示快速且广泛的药物暴露[8] - 临床前体内研究证明AmorphOX鼻内制剂的血浆浓度和生物利用度显著高于口服片剂 且能够开发通过粘膜膜良好吸收的大分子制剂[7] 战略发展方向 - 研发负责人表示AmorphOX技术成功配制和稳定大肽类分子 为索马鲁肽和其他GLP-1受体激动剂的有效鼻内递送铺平道路[4] - 研究结果支持公司更新AmorphOX战略 优先开发肽类、蛋白质和疫苗等大分子 并将通过建立战略合作伙伴关系扩展和加速这种新型递送方法的应用[4] - 公司是拥有30年经验的瑞典制药企业 专注于基于专有配方技术开发改进药物 2024年总净销售额达5.9亿瑞典克朗 员工110人[5] 行业背景 - 索马鲁肽属于GLP-1受体激动剂类别 目前有口服和皮下注射形式 主要用于治疗2型糖尿病和肥胖症[9] - 当前FDA批准的GLP-1和GLP-1/GIP受体激动剂均为需要每周注射和冷藏的注射药物 正在开发的口服制剂不需要冷藏 提供更好便利性和潜在更高依从性[10] - 索马鲁肽口服生物利用度在人类中变异性很高 口服制剂在胃肠道经历酶降解 影响生物利用度和有效性 且服用限制较多（需空腹用水服用 餐前至少30分钟）[11]

MetaVia (MTVA) FY 会议纪要关键要点分析 涉及的行业和公司 * 公司为专注于代谢性疾病和肥胖症治疗的生物技术公司MetaVia Inc [1] * 行业为生物制药行业 具体聚焦于心血管代谢疾病领域 包括肥胖症和非酒精性脂肪性肝炎(NASH) [3] 核心观点和论据 产品管线与科学原理 * 核心产品DA-1726为GLP-1/胰高血糖素双重激动剂 是一种每周注射一次的肽类药物 采用三比一(3:1)的平衡比例 旨在同时实现食欲抑制和能量消耗 [3][4][8] * DA-1726与竞争对手(pemvidutide的1:1比例 retatrutide的8:1比例)的关键差异在于其平衡比例能提供葡萄糖控制 这对于超过50%的肥胖患者同时患有2型糖尿病或糖尿病前期的患者群体至关重要 [3][4][7] * 另一核心产品DA-1241是一种每日一次的口服小分子GPR-119激动剂 通过促进肠道内天然GLP-1的产生并直接作用于肝脏受体来治疗NASH [4][25] * DA-1241在为期16周 超过100名患者的2A期研究中显示出令人信服的数据 [5] 临床数据与进展 * DA-1726在32毫克剂量组的1期研究中 仅4周治疗就实现了超过4%的体重减轻 且安全性良好 [10] * 公司正在继续进行48毫克剂量组的1期研究 计划延长至8周 目标是在8周内实现约7%或更高的体重减轻 [10][11][17] * 48毫克剂量组的研究将包括DEXA扫描(评估脂肪与瘦肉组织损失比例)和FibroScan(评估对肝脏大小的影响) 以全面评估药物效果 [19][21] * DA-1726显示出良好的耐受性 在32毫克剂量组中仅出现两例呕吐事件(首次给药后)和一例恶心事件 但均在后续给药后消退 与其他同类药物临床试验中约20%或更高的停药率形成对比 [10] 竞争格局与市场策略 * 公司认为由于NASH是一种非常复杂的肝脏疾病 单一药物无法治愈 因此组合疗法是未来的方向 [26][27][28] * DA-1241临床前数据显示其与semaglutide(司美格鲁肽)和FGF21类似物联用能产生更好的效果 [27] * 公司对DA-1726的合作持开放态度 特别是与尚未进入肥胖症领域的大型制药公司合作 以最大化药物潜力 [23] * 公司认为当前市场上已获批的NASH药物主要通过减肥间接起作用 而其带有胰高血糖素的双重激动剂药物能通过直接肝脏效应应对NASH [21] 未来战略与愿景 * 公司正与Synteca Bio合作 利用AI平台探索DA-1241的其他适应症 传统方法需要数年 AI驱动的研究可能仅需两到三个月 [31] * 公司与Immunoforge合作 积极寻找长效DA-1726的先导候选药物 目标是开发每月注射一次的剂型 [32] * 长期战略包括开发维持体重的药物(maintenance drug) 理想情况是患者使用DA-1726约6个月(无需滴定)减轻10%至15%体重后停药 依靠健康生活方式维持 而非终身服药 这符合美国保险 landscape 和患者需求(数据显示GLP-1药物一年停药率约70%) [33][34][35] * 公司对维持体重药物的定义是不应引起胃肠道问题 并能轻微助推患者维持更健康的生活方式 [35] 其他重要内容 * 48毫克剂量组研究因患者个人安排问题 可能无法让所有受试者都完成额外的4周延长研究 但数据仍足以观察早期信号 [11] * 公司寻求与DA-1241进行联合用药的合作伙伴 理想伙伴是处于接近批准阶段而非早期开发阶段的公司 [30] * 公司认为DA-1241因其出色的安全性 profile 有潜力扩展至其他适应症 [31]

公司动态 - 诺和诺德将在2025年欧洲糖尿病研究协会(EASD)大会上展示35篇摘要 涵盖糖尿病和肥胖产品组合的临床及真实世界数据[1] - 公司将于9月17日举办研发投资者活动 通过官网直播介绍大会科学成果[2] - 首席科学官Martin Holst Lange强调司美格鲁肽具有最广泛的适应症批准范围 并正开发下一代疗法[3] 产品数据展示 - 口服司美格鲁肽心血管结局研究(SOUL试验)将于9月17日展示对2型糖尿病高危患者的心血管影响[5] - Wegovy®(司美格鲁肽2.4mg周制剂)和7.2mg新剂量版本将展示临床数据[6] - Ozempic®(司美格鲁肽1.0mg周制剂)将公布与度拉糖肽对比的心血管结局优势研究(REACH研究)[7] - Rybelsus®(口服司美格鲁肽14mg日制剂)将展示肝脏相关反应数据[9] 临床研究突破 - INFORM真实世界研究显示司美格鲁肽可降低"食物噪音" [7] - STEP UP临床试验证实司美格鲁肽7.2mg对饮食控制和身体成分的改善作用[8] - REDEFINE 1研究展示cagrilintide 2.4mg作为单药治疗的潜力[11] - CagriSema(司美格鲁肽2.4mg+cagrilintide 2.4mg)组合疗法将公布REDEFINE 2试验数据[16] - 新型分子amycretin将公布1b/2a期临床试验结果[17] 产品特性 - 司美格鲁肽是GLP-1受体激动剂 具有3300万患者年安全数据支持[13] - 产品线包含三种剂型: Wegovy®(周制剂2.4mg), Ozempic®(周制剂1.0mg), Rybelsus®(日制剂14mg)[14] - 作用机制模拟天然GLP-1激素 调节体重和血糖[13] 公司背景 - 诺和诺德成立于1923年 总部位于丹麦 在全球80个国家雇用78,400名员工[18] - 产品销往约170个国家 在纳斯达克哥本哈根交易所和纽约证券交易所上市[18]

核心观点 - 诺和诺德将在2025年欧洲糖尿病研究协会(EASD)大会上展示35项关于糖尿病和肥胖产品组合的研究摘要 包括司美格鲁肽的广泛健康益处和新一代肥胖疗法数据[1] - 司美格鲁肽拥有最广泛的批准适应症 在减肥和心血管保护方面具有显著效果 累计暴露患者年数超过3300万[3][14] - 公司将举办研发投资者活动 通过网络直播分享科学数据和摘要[2] 产品数据展示 - Wegovy(司美格鲁肽2.4mg每周一次)和7.2mg剂量版本将展示临床数据[6] - Ozempic(司美格鲁肽1.0mg每周一次)将展示与度拉糖肽心血管结局比较的真实世界研究[7] - Rybelsus(每日一次口服司美格鲁肽14mg)将展示SOUL试验心血管结局数据[10][16] - 司美格鲁肽对MASH(代谢相关脂肪性肝炎)患者肝脏反应的影响数据[10] 临床研究结果 - SOUL试验:口服司美格鲁肽对高心血管风险2型糖尿病患者心血管结局的影响[5][16] - INFORM真实世界研究:司美格鲁肽减少"食物噪音"的效果[8][9] - STEP UP临床试验:司美格鲁肽7.2mg对饮食控制和身体成分的影响[8][9] - REACH研究:Ozempic相比度拉糖肽在心血管事件(心梗和中风)方面的优越性[8] 新一代肥胖疗法 - CagriSema(司美格鲁肽2.4mg和cagrilintide 2.4mg组合):REDEFINE 2试验显示在不同体重减轻类别中改善血糖结局[17] - Cagrilintide:REDEFINE 1试验显示2.4mg剂量在超重/肥胖成人中的疗效和安全性[12][17] - Amycretin:新型单分子GLP-1和胰淀素受体激动剂 将展示1b/2a期临床试验结果[13][18] 公司背景 - 诺和诺德是全球领先的医疗保健公司 成立于1923年 总部位于丹麦[19] - 公司在80个国家雇用约78,400名员工 产品销往约170个国家[19] - B股在纳斯达克哥本哈根交易所上市 ADR在纽约证券交易所上市[19]

[角色] 你是一名拥有10年投资银行从业经验的资深研究分析师，专门负责上市公司、行业研究。你擅长解读公司财报、行业动态、宏观市场，发现潜在的投资机会和风险。 [任务] 你需要仔细研读一份上市公司或者行业研究的电话会议记录，请阅读全文，一步一步思考，总结全文列出关键要点，不要错过任何信息，包括： * 纪要涉及的行业或者公司 * 纪要提到的核心观点和论据 * 其他重要但是可能被忽略的内容 如果没有相关内容，请跳过这一部分，进行其他的部分。 总结时要全面、详细、尽可能覆盖全部的内容、不遗漏重点,并根据上述方面对内容进行分组。 要引用原文数字数据和百分比变化,注意单位换算(billion=十亿,million=百万,thousand=千)。 [注意事项] 1) 使用中文,不要出现句号 2) 采用markdown格式 3) 不使用第一人称,以"公司"、"行业"代替 4) 只输出关于公司和行业的内容 5) 在每一个关键点后用[序号]形式引用原文档id 6) 一个[序号]只应该包含一个数字，不能包含多个，如果多个就用[序号][序号]分开写，不要写成 [序号-序号] 7) 每个关键要点后边的 [序号] 不要超过 3 个 Content: --------- <doc id='1'>Company Participants Adam Steensberg - President & CEO Prakhar Agrawal - Managing Director Adam Steensberg People dropping off the GLP-1s. And we think we have with PetriniType an alternative product that can give patients the weight loss they're looking for, but in a more pleasant weight loss experience. And we really think that, you know, the dynamics we're looking at today will only be exaggerated further as we see alternatives coming out because then the conversations will change from can you tolerate a therapy to will you accept it? If there is an alternative, what will patients accept? And we at least speculate that even more patients will not accept being on a GLP-one with all the side effects you often see with these molecules.</doc> <doc id='2'>Prakhar Agrawal Got it, and obviously we've seen a lot of activity in the amylin space recently, so there was cabrizema data at ADA, Lilly presented some data for their amylin drug which is with a cabrizema, it's a little bit early stage, Metsarah has an Amylin. So with all those competition coming in, which everyone probably predicted would happen, how do you sort of highlight some of petrolinitis differentiation in this increasing incompetent space? Space?</doc> <doc id='3'>Adam Steensberg Yeah. It is really good to start to see more clinical data readouts in this space of the amylin. And I would say with all the data that we have seen coming out this year, that confirms to us that we have what still looks to be the best in class opportunity. When you look at the totality of data, it is still important when you look at these molecules that you do not only focus on, let's say, efficacy and then disregard safety at the same. So you need to balance always what is what is the efficacy you're looking for and what is the safety profile that is our tolerability profile that comes along that efficacy.</doc> <doc id='4'>And when we look at the totality of of that experience, we still think that the Treinside by far looks to have the strongest profile among these clinical assets. If you take the quinolantide, which is of course the one that is furthest developed, where Novo's main focus so far has been Carcurisema, that's a combination product. That's not an alternative. And then but what we were excited about, considering that data set from their phase three program was actually the arm where they also tested monotherapy of cadrelioside, where they actually showed 12% weight loss with almost placebo like side effects. And we think we have a product that will give more weight loss due to the specific features of our molecules that really reconfirm our belief that Petrides has the potential to really lead in this new category and also that the category can actually become the largest category</doc> <doc id='5'>Prakhar Agrawal Okay. And maybe can you help us understand the specific differentiation versus gagrelentide? Is it the half life, potency or something else that you can do with petrolentide? Adam Steensberg Yeah. So a lot of these there's of course a lot lot of, you can say, scientific rigor behind choosing these molecules. And if you think about coagrelin type by Novo Nordisk and then petraintide by us, the way it interacts with the amylin receptors and the calitronin receptors, we believe are quite similar. And that's why it's really reassuring not only the efficacy signal from cadherin type, but also the safety signal from cadherin type. So we have a very balanced approach and we use also human amylin as the backbone.</doc> <doc id='6'>Other companies have chosen different paths and I think we are starting to see now that maybe some of those decisions will then carry out carry some side effects and maybe even some quite significant safety signals, which so far it looks like we have avoided with the decisions we have made. Compared to caquilinide, we have a significant upside in the fact that we our molecule is stable and neutral pH, and what we believe that translate into is that we don't see the same degree of injection site reactions as has seen with ekaglutide, we have not seen</doc> <doc id='7'>the same degree of immunogenicity. And then we have a much higher bioavailability, so we get more drug to the receptor when we inject.</doc> <doc id='8'>Prakhar Agrawal Okay, got it. And you announced a deal with Roche earlier in the year. I thought it was great economics. But maybe strategically, why did you feel Roche was the right partner to maximize the value of Betterment Day? Adam Steensberg Yes.</doc> <doc id='9'>So we after we got our Phase 1b data last summer last year, we started a very kind of structured process to identify the right pharma partner for us to realize our vision of becoming a key player in obesity, which was extremely important for us, this was a very competitive process. I had been on quite a few last cap CEOs to ultimately choose us. What was extremely important for us was the strong commitment they have made to actually become a leader in this space. We didn't just wanna team up with somebody who just thought it would be hard to have an obesity asset. We actually, it's a big effort to go in and lead in this space and that was with with us.</doc> <doc id='10'>We found a company who convinced us that they wanna lead in this. We were impressed with how they presented their manufacturing plans because ultimately, you cannot just tap into existing manufacturing capacity. Yes, you can do that, but then you will not get the most efficient. And they convinced us that the plans they have by building new fit for purpose manufacturing capacity would be a huge edge for us as we launch these molecules together. And then of course, lastly, we actually managed to get 50% shared economics on also the combination products with their c c d three eighty eight, which is a GLP one GLP molecule.</doc> <doc id='11'>So of course, that added to the value opportunity. So so, yes, we are now sharing the the profit fifty fifty with us, but we actually also got a new value opportunity in, and at the same time, a lot of good economics. So those were probably the three main reasons.</doc> <doc id='12'>Prakhar Agrawal Yes. And on the manufacturing investments, we saw some announcements from Roche as well. I think 700,000,000 investment in the North Carolina plant. Like how much of that capacity is going to be focused on petrolinta, if you can speak about that? Adam Steensberg Yes, I cannot share the specifics, but just I can share that we feel very confident that HUS is making the right investments in this investments needed to support the launch without any, you can say, shortage. And it's perhaps also an aspect of this agreement which has been overlooked a little bit that while we will share all development cost and also the future profit, we, Zealand, do not have to finance any manufacturing investments. That would be us that is responsible for financing all these investments, which is of course also a lot of dollars short term at least for us that we save.</doc> <doc id='13'>Prakhar Agrawal Got it. And when you were running the process and like what was attractive, what better than tied to Roche, what were the some of the two or three attributes that was really interesting? Was it a differentiated mechanism? Was it on the safety tolerability side? If you can just lay out the reasons that Roche will tolerate, we have to be involved in the ambulance space.</doc> <doc id='14'>Adam Steensberg Yes. I think they will, of course, have to speak for themselves either ultimately were so excited as I would say most of their peers in the industry was as well. So but I would but for me, it's a logical consequence of looking at the current market dynamics. With the GLP-1s, where we have two established brands, of course, it's going to be hugely difficult to come in with another GLP-one and start to lead if you already have very established brands. You're You're going to have high rebate walls, you're going to have a lot of prescribing experience with</doc> <doc id='15'>existing molecules, and you're also going to fight against ten, twenty years of data. So but coming in with a new modality, coming in with an alternative, then suddenly you have an opportunity to lead in a new category instead of trying to eat your way into something that is very established.</doc> <doc id='16'>That is a much more attractive value proposition. Also, you think about the launch years, it's it's a much more compelling opportunity to launch with a new category because you will be you can say the first alternative for people who do not know where else to go, if you launch and with a similar mode of action, then you will have to convince somebody why you should take that molecule rather than a new in a in a very existing and well known molecular entity. So this opportunity to lead in a new category, I think, is what was appealing to many of the companies we spoke to.</doc> <doc id='17'>Prakhar Agrawal Got it. Makes sense. Maybe onto the some of the clinical data, you have the ongoing Phase 2b that will read out the forty two weeks will read out next year. Just clear on what are you hoping to see maybe starting with efficacy? Adam Steensberg Yes. So what we hope to see is a molecule that can provide patients with a GLP-one like weight loss, and that is in the mid teens, so fifteen percent to twenty percent what we have seen. And then with a much more benign tolerability profile, we are already very confident in the tolerability profile because we have sixteen week data. We have also data from Novo Nordisk, which shows that it's almost placebo like experience that you have when you get a patrinetide as compared to when you get the GLP-1s. So and on the efficacy side, we achieved 8.6% weight loss over sixteen weeks.</doc> <doc id='18'>And those models would suggest that we can easily achieve the weight loss we're looking for. What I think is super important as we continue to mature our view on the future BT market is to maybe that go a little bit of that, what is the number? This is about a profile of a drug. Most patients, if you ask them, are looking for a 10% to 20% weight loss. And we and and thus, we we have to get away from this weight loss Olympics.</doc> <doc id='19'>We need to get into talking about what is the profile of the drug, which drugs can give patients that weight loss they're looking for, but in a more pleasant experience. And then importantly, which is the big big big miss of the current therapies is how do we manage to get patients to stay in therapy. The reason that we have so low volumes of patients on treatment is because they stopped taking the GLP-1s far, far too early today. And we think we can change that with enamelin.</doc> <doc id='20'>Prakhar Agrawal Yes. And I think that's an important point because I think people under appreciate the duration of therapy for Alnylam drug. So like what are you based on your research, what's the sort of the state time for GLP-1s and how much further can you improve with an amylin therapy even as monotherapy option? Adam Steensberg Yes, but I think it has actually not changed a lot this daytime on a GLP-1s. And we know, I mean, from the launch years, I mean that within the one already in one once we have thirty percent who drops off and probably within a year is less than than fifty percent who are still on on therapy. By those who leaves, the majority are actually people who say it's because I cannot tolerate the drug. Of course, there are other reasons as well, but the major极是 because they cannot tolerate it. And there's actually a big dilemma here because if you only achieve a weight loss and you don't manage to maintain it, we actually you could actually be worse off.</doc> <doc id='21'>So it is so important we start to think about how do we get people to stay on therapy. And we all know that an obese person is very motivated to lose weight. Once you have achieved the weight loss, you become less motivated, and that also means that you will accept less side effects. And that's where we think amylin will come in and be something you can actually have that you can also enjoy being on when you have achieved your 极是 loss because it has this feature of making people feel full faster rather than losing their appetite. So it's actually also beyond the classical tolerability issues</doc> <doc id='22'>Prakhar Agrawal</doc> <极是 id='23'>And on the safety tolerability side, obviously, we have been comparing it with semaglutide, but don't you think the market is moving now more closer to tirzepatide, which has really good safety tolerability as well, so how would you compare ambulance versus let's say dual agonist, like Adam Steensberg a GLP, GLP agonist which has good safety? Yeah, but I politely probably have to disagree with your statement there. In my book, think the safety and tolerability profiles between Vigovi and and and Zepbound are quite similar. You may data at least suggest that you could get a higher weight loss on on Zepbound, but again, as we discussed before, if you balance things net net, you still have all the side effects with the GLP one TIP class that we have also seen with the GLP one class. I think another kind of fact underscoring this is that while the clinical data we always discuss for these molecules are data generated with the highest doses,极是 what was the weight loss you achieved with, let's say, fifteen milligrams of of of of Z bound, then the real world evidence suggests that very, few patients ever get to these doses.</doc> <doc id='24'>They end at much lower doses. I actually believe that the average dose being used real world for Zepbound is around seven and a half milligram, which is a very low dose. So they don't actually experience the weight loss that the clinical data suggest they can do. And then you might ask yourself, why is that? Why do they not get to those numbers? And we think a lot of that has to do with the tolerability profile. We used to talk a lot about just vomiting and nausea, but I think we need to discuss diarrhea in particular because these are side effects that tend to stick and not be able to titrate yourself out, especially when we start to think about the new classes of all GLP-1极是 where in my book, at least looks to be even worse.</doc> <doc id='25'>Prakhar Agrawal Got it. And you disclosed some pooled baselines during the last earnings call. But maybe just a broader question on obesity trials. We are seeing a lot of discontinuations in the obesity trials, especially in the placebo arm as well. We saw this with Lilly's orfagriplone data. Viking had a little readout that had极是 lot of disc conditions as well. What are you doing to mitigate this risk? Because this is a forty two week trial as well.</doc> <doc id='26'>Adam Steensberg Yes. But I mean, we, of course, don't have the data yet, but but I also hear other companies who have not seen the same issue. So I I don't know. Before we see the actual data, it's it's actually difficult to say what the real reasons are behind those discontinuations. Of course, there is this observation that if people don't achieve a weight loss in a placebo group, they could be less motivated to stay in the study.</极是> <doc id='27'>That could also, again, coming back to ofroglipin, why you had more discontinuations than average on on even on active drug because people did not achieve the weight loss they were looking for. So I think we need to see the individual data before we can start to draw conclusions.</doc> <doc id='28'>Prakhar Agrawal Anything you can comment on the pool discrimination rates in the ongoing trial? Adam Steensberg No. I mean, again, we try to keep a high level of data integrity on our clinical studies and not be too, you can say, to introduce any risks. So we like to keep things blinded until we have the data.</doc> <doc id='29'>Prakhar Agrawal Okay. And once you have the forty two weeks, I know there will be an interim readout this year to progress for to start the regulatory discussions around the Phase III plan. But what could a Phase III development plan look like? And a follow-up to that, like does Roche plan to run a CV outcomes trial for Amlens? Adam Steens

**89Bio (ETNB) Citi Biopharma 活动电话会议纪要 2025年9月3日** 涉及的行业与公司 * 行业为生物制药 专注于非酒精性脂肪性肝炎（NASH）及严重高甘油三酯血症（SHTG）领域 [1][3] * 公司为89Bio 核心产品为Pegosofirmin（一种FGF21类似物） [1][7] 核心观点与论据：NASH市场与竞争格局 * NASH市场前景广阔 目前已有两款药物（Resmetirom和Semaglutide）获批 将驱动更多患者诊断和治疗 市场将随之扩大 [4][5] * 现有获批药物被视为第一代代谢类药物 其抗纤维化效果有限（Semaglutide的纤维化安慰剂调整后获益仅为14%） 而下一代强效抗纤维化药物（如Pegosofirmin）有望将治疗水平提升到新高度 [7][10] * 尽管GLP-1药物（如Semaglutide）被广泛使用 但其通过改善胰岛素敏感性和肥胖间接作用于肝脏 并非直接靶向肝脏 许多患者病情仍会进展 这为肝脏靶向的强效抗纤维化药物留下了巨大的市场空间 [10][11][12] * 在肝硬化（F4）患者群体中 GLP-1药物被证明无效 而FGF21类药物（如Pegosofirmin）可能是未来唯一能获批用于F4患者的药物类别 [20] 核心观点与论据：Pegosofirmin (ENLIGHTEN) 临床项目进展 * 两项全球性三期研究（ENLIGHTEN-F2F3纤维化研究和ENLIGHTEN-F4肝硬化研究）正在推进 已激活超过250个研究中心 覆盖20多个国家 患者筛查数量众多 显示出巨大的未满足需求 [15][16][17] * 研究设计允许患者使用稳定剂量的GLP-1药物入组 并按GLP-1使用情况进行分层 基于内部假设 公司认为即使在GLP-1使用者亚组中也拥有足够的统计效力来显示差异 [12][25][26] * 暂无计划进行中期分析 目前仅计划进行一次组织学终点分析和一次临床结局终点分析 除非有新数据表明当前的样本量估算过于保守 [58][59][61] 核心观点与论据：Pegosofirmin的差异化优势 * **疗效**：在绝对纤维化改善方面与其他FGF21药物相当 但在相对风险降低方面表现最佳 [41] * **安全性与耐受性**：胃肠道事件（如恶心、呕吐）发生率显著低于同类竞品（Efruxifermin和BMS的FGF21） 并且未观察到具有统计学或临床意义的骨矿物质密度或骨生物标志物变化 这对已有肌肉减少症风险的F4患者至关重要 [42] * **给药方案与便利性**：研究每周一次和每两周一次给药方案（竞品Efruxifermin仅为每周一次） 且为液体预充式注射剂（竞品为需 reconstitution 的冻干粉剂） 这为未来与GLP-1药物（多为液体）的复方制剂提供了潜在可能 [43][44][45] 核心观点与论据：与GLP-1药物的协同潜力及商业考量 * 一项涉及37名患者的回顾性分析显示 在GLP-1基础上加用Pegosofirmin 在肝脏纤维化标志物、炎症、脂肪变性以及HbA1c和血脂等代谢指标上显示出额外获益 [21][22] * 机制上 FGF21直接作用于肝脏（减少肝脏脂肪新生、直接抗纤维化和抗炎） GLP-1则间接减少脂肪向肝脏的流入 两者作用机制互补 [23][24] * GLP-1药物的停药率很高（一年后停药率低至30%-40%或40%-50%） 体重反弹会再次影响肝脏 而体重循环可能对NASH不利 因为影响纤维化需要长期维持体重下降 [27][29] * 关于复方制剂的支付方反应 组合疗法通常不会按A+B定价 而是接近单药定价或略高 最终定价将取决于组合数据的强度 [49][50] 核心观点与论据：SHTG项目及其他潜在适应症 * SHTG研究已完全入组 数据读出预计在明年第一季度（2026Q1） 若结果符合目标产品特征 将启动第二项研究 策略是先主导NASH适应症 随后将SHTG作为补充BLA申报 [63][64] * Pegosofirmin的定位在于同时患有高甘油三酯和其他代谢合并症（如肝脏脂肪、肝酶升高、血糖控制问题）的患者 近期APOC3抑制剂在HTG中显示出血糖控制恶化 这可能为Pegosofirmin创造独特空间 [65][66] * 潜在的新适应症探索包括其他病因（如乙肝、丙肝、酒精）引起的肝硬化 以及其他纤维化领域（如肾脏纤维化、心脏纤维化） 公司将在推进NASH三期研究的同时开始考虑这些生命周期管理机会 [71][72] 其他重要内容 * **试验设计与区域差异**：国际（OUS）与美国（US）站点各占50%-60% OUS地区GLP-1使用率较低且多用于糖尿病而非肥胖 剂量有所不同 公司正努力标准化饮食和生活方式咨询 并调整了亚洲患者的BMI截止值等入排标准 但不担心会产生国家间的偏倚 [32][33][37] * **商业化与合作伙伴关系**：公司对在欧美市场自行商业化持开放态度 但也认为与能带来价值的战略伙伴合作是优化产品价值的好方法 区域合作是为其他适应症筹集资金的一种方式 但在同一领域划分权利更为复杂 [75][76] * **医生视角与患者坚持**：在无症状的慢性疾病中 安全性和耐受性对患者的长期坚持至关重要 市场调研显示 更好的耐受性会显著影响医生的处方份额分配 [52][53]

法律调查事件 - Berger Montague律师事务所正在对Hims & Hers Health Inc（NYSE: HIMS）展开证券欺诈调查，涉及潜在违反联邦证券法的行为 [1][4] 调查时间范围 - 调查针对2025年4月29日至2025年6月22日期间购买或获得Hims & Hers证券的投资者，申请成为首席原告代表的截止日期为2025年8月25日 [2] 事件触发原因 - 2025年6月23日诺和诺德（Novo Nordisk）宣布终止与Hims & Hers的合作关系，指控公司进行欺骗性营销并销售未经批准的复合版本司美格鲁肽（semaglutide） [3] - 公告发布后Hims & Hers股价在盘中交易时段下跌超过34%，反映投资者对监管合规性和声誉风险的担忧 [3] 指控具体内容 - 诉讼指控公司在整个调查期间就GLP-1产品的性质、监管状态、相关风险及与诺和诺德的合作关系作出重大虚假或误导性陈述，或隐瞒重要信息 [4] - 调查重点包括公司及部分高管是否通过向投资者提供虚假或误导性陈述违反联邦证券法 [4]

核心观点 - 诺和诺德旗下重磅药物Wegovy获FDA批准新增适应症 展示其药物在多疾病领域的治疗潜力及公司研发实力 [1][2][5] - 司美格鲁肽（semaglutide）成分的药物平台具备持续扩展适应症的能力 为未来增长提供明确路径 [5][6] 产品进展 - Wegovy于8月中旬获FDA批准用于治疗非肝硬化性代谢功能障碍相关脂肪性肝炎（MASH）合并中度至晚期肝纤维化成人患者 [3] - 该药物需与增加体育锻炼及减少热量摄入联合使用 [3] - 此次批准证明Wegovy及其姊妹药物Ozempic有望治疗多种其他疾病 [5] 研发能力 - 公司成功将药物拓展至肝脏疾病治疗领域 证明其擅长开发分子用于多种适应症 [5] - 诺和诺德拥有广泛且令人印象深刻的研发管线 司美格鲁肽仅是其中一部分 [6] - 司美格鲁肽用于治疗阿尔茨海默病的研究已进入后期阶段 [6] - 公司拥有大量其他分子项目 覆盖多个治疗方向 [6] 市场潜力 - 美国肥胖问题影响人群远超过MASH患者群体 但MASH适应症获批验证了药物平台扩展性 [5] - 高活跃度的研发活动为司美格鲁肽及其他研究药物带来光明前景 [6]