A Phase 2, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics of CT-868 Administered for 16 Weeks to Overweight and Obese Adult Participants With Type 1 Diabetes Mellitus

This study will evaluate the changes in glycemic control in overweight and obese adults with Type 1 Diabetes Mellitus after receiving CT-868 for 16 weeks. The effectiveness and safety of CT-868 will be compared to placebo. All participants will continue with their standard diabetes care using either an insulin pump (CSII) or multiple daily injections (MDI). Alongside their designated treatment, participants will receive guidance on managing their diabetes, including monitoring blood glucose levels and diet and exercise recommendations. Treatment assignments, either CT-868 plus insulin or placebo plus insulin will be randomly determined.

开始日期2023-10-19

申办/合作机构

Carmot Therapeutics, Inc.

NCT05794581 / Recruiting临床1期

A Randomized, Double-Blind, Placebo and Comparator-Controlled Crossover Study to Assess the Effects of CT-868 Treatment on Glucose Homeostasis in Participants With Type 1 Diabetes

This study will be conducted primarily to evaluate the effects of CT-868 on glucose homeostasis in participants with Type 1 Diabetes Mellitus.

开始日期2023-03-21

申办/合作机构

Carmot Therapeutics, Inc.

NCT05110846 / Unknown status临床2期

A Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Multiple-Center Study to Evaluate the Efficacy, Safety, and Tolerability of CT-868 Administered for 26 Weeks to Overweight and Obese Participants With Type 2 Diabetes Mellitus

A Study to Assess the effect of CT-868 in hemoglobin A1c (HbA1c) in Overweight and Obese Participants with Type 2 Diabetes Mellitus.

开始日期2022-02-22

申办/合作机构

Carmot Therapeutics, Inc.

100 项与 CT-868 相关的临床结果

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100 项与 CT-868 相关的转化医学

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100 项与 CT-868 相关的专利（医药）

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项与 CT-868 相关的文献（医药）

2023-08-15·Proceedings of the National Academy of Sciences of the United States of America1区 · 综合性期刊

Structural analysis of the dual agonism at GLP-1R and GCGR.

1区 · 综合性期刊

Article

作者: Cong, Zhaotong ; Dai, Antao ; Zhou, Qingtong ; Wu, Beili ; Li, Yang ; Ying, Tianlei ; Zhao, Fenghui ; Chang, Rulue ; Yang, Dehua ; Wang, Ming-Wei

Glucagon-like peptide-1 receptor (GLP-1R) and glucagon receptor (GCGR), two members of class B1 G protein-coupled receptors, play important roles in glucose homeostasis and energy metabolism. They share a high degree of sequence homology but have different functionalities. Unimolecular dual agonists of both receptors developed recently displayed better clinical efficacies than that of monotherapy. To study the underlying molecular mechanisms, we determined high-resolution cryo-electron microscopy structures of GLP-1R or GCGR in complex with heterotrimeric G_s protein and three GLP-1R/GCGR dual agonists including peptide 15, MEDI0382 (cotadutide) and SAR425899 with variable activating profiles at GLP-1R versus GCGR. Compared with related structures reported previously and supported by our published pharmacological data, key residues responsible for ligand recognition and dual agonism were identified. Analyses of peptide conformational features revealed a difference in side chain orientations within the first three residues, indicating that distinct engagements in the deep binding pocket are required to achieve receptor selectivity. The middle region recognizes extracellular loop 1 (ECL1), ECL2, and the top of transmembrane helix 1 (TM1) resulting in specific conformational changes of both ligand and receptor, especially the dual agonists reshaped ECL1 conformation of GLP-1R relative to that of GCGR, suggesting an important role of ECL1 interaction in executing dual agonism. Structural investigation of lipid modification showed a better interaction between lipid moiety of MEDI0382 and TM1-TM2 cleft, in line with its increased potency at GCGR than SAR425899. Together, the results provide insightful information for the design and development of improved therapeutics targeting these two receptors simultaneously.

2023-04-01·Expert opinion on pharmacotherapy

GLP-1/GIP analogs: potential impact in the landscape of obesity pharmacotherapy.

Review

作者: Flatt, Peter R. ; Lafferty, Ryan A. ; Irwin, Nigel

INTRODUCTION:

Obesity is recognized as a major healthcare challenge. Following years of slow progress in discovery of safe, effective therapies for weight management, recent approval of the glucagon-like peptide 1 receptor (GLP-1R) mimetics, liraglutide and semaglutide, for obesity has generated considerable excitement. It is anticipated these agents will pave the way for application of tirzepatide, a highly effective glucose-dependent insulinotropic polypeptide receptor (GIPR), GLP-1R co-agonist, recently approved for management of type 2 diabetes mellitus.

AREAS COVERED:

Following promising weight loss in obese individuals in Phase III clinical trials, liraglutide and semaglutide were approved for weight management without diabetes. Tirzepatide has attained Fast Track designation for obesity management by the US Food and Drug Association. This narrative review summarizes experimental, preclinical, and clinical data for these agents and related GLP-1R/GIPR co-agonists, prioritizing clinical research published within the last 10 years where possible.

EXPERT OPINION:

GLP-1R mimetics are often discontinued within 24 months meaning long-term application of these agents in obesity is questioned. Combined GIPR/GLP-1R agonism appears to induce fewer side effects, indicating GLP-1R/GIPR co-agonists may be more suitable for enduring obesity management. After years of debate, this GIPR-biased GLP-1R/GIPR co-agonist highlights the therapeutic promise of including GIPR modulation for diabetes and obesity therapy.

2023-03-13·Endocrinology

Enhanced Endosomal Signaling and Desensitization of GLP-1R vs GIPR in Pancreatic Beta Cells

Article

作者: Jones, Ben ; Chen, Shiqian ; Manchanda, Yusman ; Tomas, Alejandra ; Bernardino de la Serna, Jorge ; Bitsi, Stavroula ; Broichhagen, Johannes

Abstract:

The incretin receptors, glucagon-like peptide-1 receptor (GLP-1R) and glucose-dependent insulinotropic polypeptide receptor (GIPR), are prime therapeutic targets for the treatment of type 2 diabetes (T2D) and obesity. They are expressed in pancreatic beta cells where they potentiate insulin release in response to food intake. Despite GIP being the main incretin in healthy individuals, GLP-1R has been favored as a therapeutic target due to blunted GIPR responses in T2D patients and conflicting effects of GIPR agonists and antagonists in improving glucose tolerance and preventing weight gain. There is, however, a recently renewed interest in GIPR biology, following the realization that GIPR responses can be restored after an initial period of blood glucose normalization and the recent development of dual GLP-1R/GIPR agonists with superior capacity for controlling blood glucose levels and weight. The importance of GLP-1R trafficking and subcellular signaling in the control of receptor outputs is well established, but little is known about the pattern of spatiotemporal signaling from the GIPR in beta cells. Here, we have directly compared surface expression, trafficking, and signaling characteristics of both incretin receptors in pancreatic beta cells to identify potential differences that might underlie distinct pharmacological responses associated with each receptor. Our results indicate increased cell surface levels, internalization, degradation, and endosomal vs plasma membrane activity for the GLP-1R, while the GIPR is instead associated with increased plasma membrane recycling, reduced desensitization, and enhanced downstream signal amplification. These differences might have potential implications for the capacity of each incretin receptor to control beta cell function.

项与 CT-868 相关的新闻（医药）

2024-05-16

·BioSpace

Roche Sees Early ROI on $2.7B Carmot Buy with Phase I Data for Obesity Candidate

Pictured: Roche tower in Basel, Switzerland/iStock, olli0815 Roche subsidiary Genentech on Thursday unveiled Phase Ib data for its investigational weight-loss treatment CT-388, demonstrating that a once-weekly subcutaneous shot could significantly lower body weight in healthy adults with obesity. At 24 weeks of follow-up, CT-388 lowered body weight by 18.8% versus placebo. The effect was statistically significant, with a p-value less than 0.001, according to Genentech’s announcement. In addition, 100% of treated patients showed more than 5% weight loss at 24 weeks, while 45% of participants lost more than 20% of their body weight. A subgroup analysis also showed that all pre-diabetic participants at the start of the study achieved normal blood glucose levels after 24 weeks of treatment, while those in the placebo group saw no meaningful change in glycemic status. In terms of safety, CT-388 was well-tolerated in the Phase Ib study with most of its side effects classified as mild to moderate in severity. There were also no unexpected safety signals and CT-388’s adverse event pro consistent with other medications in the incretin drug class. Levi Garraway, CMO and head of global product development at Roche, in a statement called Thursday’s data “highly encouraging” for CT-388 and further “underscore its potential to become a best-in-class therapy with durable weight loss and glucose control.” The company will continue to develop the candidate as a treatment for obesity and type 2 diabetes. Initially developed by Carmot Therapeutics, CT-388 is a dual agonist of the GLP-1 and GIP receptors that shows none or minimal recruitment of β-arrestin proteins, which would otherwise interfere with the receptors’ downstream signaling cascades and dampen the overall therapeutic effects of the obesity treatment, according to Carmot’s website. CT-388’s biased mechanism of action allows it to prevent or lower desensitization to treatment, prolonging its pharmacological activity. CT-388 is designed to be delivered via a once-weekly subcutaneous injection. Roche acquired Carmot for $2.7 billion in December 2023 and is now running a multi-part, multi-cohort Phase I trial of CT-388 in overweight or obese patients with or without obesity. In addition to CT-388, the Carmot deal gave Roche other promising obesity candidates including the Phase II CT-868, which is also a dual agonist of the GLP-1 and GIP receptors but is designed as a daily subcutaneous injection. Roche also owns the early-stage CT-996, which is an oral small molecule GLP-1 agonist. Thursday’s readout makes Roche a potential contender in the lucrative obesity market, which is currently dominated by Novo Nordisk’s Wegovy (semaglutide) and Eli Lilly’s Zepbound (tirzepatide). Despite efforts from the frontrunners to boost their manufacturing capacities, they are both still unable to keep up with the market’s voracious appetite for weight-loss treatments, causing protracted drug shortages. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

临床结果临床1期临床2期并购

2024-04-21

·药融圈

融资21亿元，开发下一代肥胖和代谢性疾病药物

▲5月30-31日第八届广州生物医药创新者峰会扫码立即报名注：本文不构成任何投资意见和建议，以官方/公司公告为准；本文仅作医疗健康相关药物介绍，非治疗方案推荐（若涉及），不代表平台立场。任何文章转载需得到授权。4月18日，减肥初创公司Metsera Therapeutics宣布推出新一代治疗肥胖和代谢性疾病的药物。Metsera由Population Health Partners和ARCH Venture Partners创立，由The Medicines Company前高管领导，正在迅速推进口服和注射肠促胰岛素、非肠促胰岛素和组合疗法的广泛组合，这些疗法以一流的方式设计，以解决多个靶点，并满足快速发展的减肥治疗领域的未来需求。Metsera已完成2.9亿美元（21亿人民币）的融资，由ARCH Venture Partners领投，其他领先的医疗保健投资者也参与其中，包括F-Prime Capital、GV、Mubadala Capital、Newpath Partners、软银愿景基金2和其他未披露的投资者。该公司已从一家韩国生物技术公司获得了6种肥胖候选药物的授权，并收购了一家伦敦生物技术公司Zihipp，且计划在未来12至24个月内申请多达7项IND。Metsera已获得许可的候选肥胖药物来自韩国生物技术公司D&D Pharmatech。去年4月，两家公司宣布了一项关于三种产品的初始授权协议:一种口服GLP-1激动剂DD02S，一种口服GLP-1/GCG/GIP，称为“triple G”激动剂的DD03和MET06。今年3月18日，两家公司宣布了一项扩大协议，获得DD07和DD14的许可。DD07是一种口服胰肽受体激动剂，DD14是一种口服GLP-1/GIP受体双重激动剂。根据D&D制药公司在韩国的新闻稿，Metsera和D&D同时宣布了第二笔交易，授权一种名为DD15的注射用triple G候选药物，计划在2025年上半年进入临床试验，该新闻稿还提到了DD15治疗肝病MASH的潜力。两笔交易加在一起，对D&D的里程碑式支付价值可能超过1万亿韩元(7.39亿美元)。由此，Metsera借助D&D Pharmatech和Zihipp，组成了非常丰富的治疗肥胖症的产品管线组合，其中，DD03、DD07、DD14、DD15均处于临床前阶段，DD02S正在IND申请阶段。而且，这些管线均进行了不同程度的创新，在靶点方面，它们都不再只着眼于GLP-1，而是进行多靶点的组合创新，如DD03是GLP-1/GCG/GIP三重激动剂，DD15则是GLP-1R/GIPR/GCGR 三重激动剂。此外，这些药物均以口服为主要给药方式，用于克服现阶段GLP-1注射给药的局限性。总结就目前GLP-1赛道的火热程度来看，不少早期临床成功的小型初创公司已成为生物技术领域最热门的公司之一：罗氏斥资27 亿美元收购了糖尿病和肥胖疗法明星企业Carmot Therapeutics；GLP-1药物有力市场竞争者之一Viking Therapeutics凭借令人鼓舞的数据，市值飙升至80亿美元以上；私营初创公司 Aardvark Therapeutics计划筹集高达2亿美元的资金来进行IPO。3月5日，派格生物递交招股书，准备在港交所主板上市，这是今年第一个减肥药IPO，派格生物旗下共有6款在研药物，其中有4条管线与GLP-1类药物相关，适应症几乎都是针对肥胖、超重、糖尿病等领域。2月底，印度的太阳制药、Cipla、Dr Reddys 和Lupin都表示，他们已经开始研发自己的“Wegovy”，太阳制药正在开发自己的新型专利治疗肥胖症和2型糖尿病的药物，但还需要通过临床试验。参考资料：公司官网版权声明：本文转自生物药大时代，如不希望被转载的媒体或个人可与我们联系，我们将立即删除活动推荐 5月 • 第八届大湾区生物医药创新者峰会关键词：小分子，XDC，多肽及GLP-1热点话题，80+行业专家（点击下方图片查看详情）▼【关于药融圈】药融圈PRHub旨在帮助生物医药科技型企业进行品牌推广及商务拓展服务，针对客户的真实需求制定系统化解决方案，通过“翻译-降维-场景化”将客户的品牌信息以直白易懂的方式被公众知悉，同时在流量渠道覆盖100万+垂直用户基础上实现合作目的，帮助合作伙伴完成从品牌开始到商务为终的闭环营销服务。我们已经完成了数十场线下1000人规模的生物医药研发类会议，涵盖小分子新药，大分子新药，改良型新药，BD跨境交易等多个领域，服务了百余家上市/独角兽/生物技术/制药企业。

并购临床申请临床研究

2024-02-29

·生物制品圈

超10款GLP/GIP药物临床数据将揭晓

GLP-1药物是目前医药领域最热门的开发项目，除诺和诺德的Wegovy, Ozempic和礼来的Zepbound, Mounjaro之外；还有一系列GLP-1受体激动剂或者GLP-1受体共激动剂喷薄欲出，包括辉瑞的Danuglipron（小分子），阿斯利康的ECC5004（小分子），礼来的retatrutide（多肽），西兰制药和勃林格殷格翰的survodutide（多肽），以及Amgen的MariTide（maridebart cafraglutide，抗体多肽偶联物）等在内。值得注意的是，GLP-1受体激动剂作为减肥领域的“龙头”产品，市场增速飞涨。据相关分析师预测2030年减肥药市场将达800亿至1000亿美元。然而，GLP-1受体激动剂类减肥药物在不良反应、停药后体重反弹等方面仍存在诸多待改进之处。为了应对这些问题，新一代减肥药物亟需引入新的药物作用机制（MOA，Mechanism of Action），以弥补GLP-1药物在减重适应症方面的不足。在日益繁荣的减肥药物市场中，新产品需凭借显著优势脱颖而出，以实现有效竞争。制药企业已意识到，在GLP-1受体激动剂药物研发中过度依赖“me too”策略可能导致发展困境。因此，对于有志于布局减肥药市场的制药公司而言，研发具有新型靶点和作用机制的药物至关重要，而在Wegovy和Zepbound等卓越产品的背景下，“me better”策略或为更为明智的选择。10余款新型GLP-1激动剂2024将公布最新临床研究数据在2024年的减肥药研发领域，除上述介绍的几款GLP-1受体激动剂外，一些具有创新作用机制的非GLP-1受体激动剂（包括多受体共激动剂）亦备受瞩目。这些药物的临床数据预计将于2024年揭晓，表1总结了这些非单纯GLP-1药物的作用机制及临床数据。表1. 2024年有临床数据的减肥药数据来源：药智数据、企业公告等公开资料APH-012 （远端空肠释放葡萄糖珠，口服递送）正在进行一项 2 期概念验证研究，对 174 名肥胖症患者进行评估，并针对肥胖症和糖尿病前期进行研究，预计将于今年3月公布临床结果。APHD-012 的作用机制是模仿旁路手术（bypass surgery）的代谢益处，同时避免负面副作用，并包含远端空肠释放葡萄糖珠。Shionogi 的口服单酰基甘油酰基转移酶 2 (MGAT2) 抑制剂S-309309是另一项新型非 GLP-1受体激动剂肥胖症候选药。MGAT2 在小肠中高表达，促进单酰基甘油和酰基辅酶 A 转化为二酰基甘油，显著影响器官内的脂质代谢（图2）。据公开资料显示，S-309309对 365 名肥胖参与者进行的 II 期试验预计将于 6 月得出结果。图2. S-309309减肥作用机制。图片来源：ShionogiBimagrumab是一种全人源单克隆抗体，能够结合激活素Ⅱ型受体（ActRII），通过这种机制阻止ActRII的自然配体对骨骼肌生长所产生的下调作用。ActRII拮抗剂还促进了骨骼肌以外的作用，包括对褐色脂肪组织（BAT）分化和活动的影响。不仅显著减少了总体脂肪量，还增加了瘦体重，并改善了胰岛素敏感性。Bimagrumab可能代表治疗肥胖及相关代谢紊乱患者的新方法。在一项 Ⅱa 期研究中，根据 2023 年 1 月 12 日发布的 48 周数据，bimagrumab 使肥胖和 2 型糖尿病患者的瘦体重增加了 4.5%，同时脂肪量减少了 21.9%。Versanis Bio 的 bimagrumab的 Ⅱb 期试验 (NCT05616013) 预计将于今年6月份公布。而值得提及的是，Versanis 在2023年8月被礼来以19.25亿美元收购。Bimagrumab 的给药频率可能低至每年仅五次，可以显著减轻患者的治疗负担。诺和诺德的CagriSema是胰淀素类似物cagrilintide 和semaglutide的联合疗法。诺和诺德正在 III 期 REDEFINE 1 试验 (NCT05567796) 中研究其减肥效果，预计 12 月得出结果。CagriSema肩负着诺和诺德减肥药推陈出新的重大使命。双/三受体激动剂新型减肥药趋势双受体共激动剂也是减肥药发展的趋势之一，通过同时靶向两个甚至三个受体，来实现减肥和其他代谢调控的精准平衡。礼来的tirzepatide就是GLP-1/GIP双受体共激动剂，在有效性和安全性上都有非常好的表现。CT-388 和 CT-868是罗氏于 2023 年 12 月以 27 亿美元收购 Carmot Therapeutics 所得的正在在开发的两种 GIP/GLP-1受体共激动剂。两种双受体共激动剂疗法都是皮下注射，但CT-388是每天注射一次，而CT-868是每周注射一次，目前CT-868正在针对1型糖尿病肥胖患者进行评估。双激动剂可以通过作用于两个靶标来提高治疗肥胖症的功效，从而促进胰岛素分泌和脂质代谢；此外，其可减少胃排空，从而减少食物摄入并导致体重减轻。有分析师预计，到 2026 年GIP受体激动剂的销售额将超越GLP-1受体激动剂。其他正在开发中靶向受体的药物候选物包括安进公司的 AMG-133（maridebart cafraglutide，MariTide），该药物正处于肥胖症的Ⅱ 期研究中。其第一阶段结果显示，最高剂量 12 周后体重减轻达 14.5%。AMG-133的独特性体现在其结构，即两个GLP-1受体激动剂多肽分子连接至一个抗GIP抗体。这与大多数其他药物，例如礼来的双重激动剂Mounjaro不同，AMG-133既是GLP-1受体激动剂也是GIP受体拮抗剂，其作用机制别具一格。人们担忧，抑制GIP受体可能对糖尿病患者血糖水平产生影响，这也是即将进行的2期临床试验研究之一。值得注意的是，AMG-133表现出停药后反弹不明显的特点，因此受到了业内广泛重视。此外，其抗体多肽偶联物模式颇具创新性，有望成为“规则改变者”。分析师表明，未来的减肥药发展将更多地寻求双受体激动剂和三受体激动剂，“这将成为公司在肥胖领域开发疗法的必由之路”。dapiglutide是Zealand Pharma 正在开发的一种双重激动剂，其靶向 GLP-1和 GLP-2受体，其 Ⅱ 期试验预计将于今年 6 月下旬公布。而礼来的retaglutide同时靶向三个受体，即GLP-1受体、GIP受体和Glucagon受体，因此被称作“3G减肥药”。它已经表现出了非常强劲的减肥数据。Ⅱ期数据最高剂量48 周平均体重高达 24.2%，可以说retaglutide寄托了更大的期望，预计将在2027年上市。小结在抑制食欲的基础上，人们还在持续研究各类减肥策略。未来，肥胖治疗的核心将转向提升能量消耗。实现此目标的一种途径是尝试增加“棕色脂肪”的含量，这种脂肪可有助于消耗多余的能量。此开发思路的挑战在于，如何仅通过激活相关的β3－肾上腺素能受体，而非引发血压升高的其他β受体来刺激棕色脂肪的生成。参考资料：1.Lilly Completes Acquisition of Versanis Bio. Eli Lilly Press Release. 14. 08. 2023.2.Heymsfield, S. B. et al. Effect of Bimagrumab vs Placebo on Body Fat Mass Among Adults With Type 2 Diabetes and Obesity. JAMA Netw Open. 2021 Jan; 4(1): e2033457.3.AMGEN PRESENTS NEW AMG 133 PHASE 1 CLINICAL DATA AT WCIRDC 2022. Amgen Press Release. 12. 01. 2022.4.Maragkou, I. Biotechs ride obesity drug wave with novel approaches that go beyond GLP-1RAs. Pharmaceutical Technology. 15. 02. 2024.识别微信二维码，添加生物制品圈小编，符合条件者即可加入生物制品微信群！请注明：姓名+研究方向！版权声明本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观点，不代表本站立场。

临床2期临床结果

100 项与 CT-868 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
1型糖尿病	临床2期	美国	Carmot Therapeutics, Inc.	2023-10-19
2型糖尿病	临床2期	美国	Carmot Therapeutics, Inc.	2022-02-22
2型糖尿病	临床2期	墨西哥	Carmot Therapeutics, Inc.	2022-02-22
肥胖	临床2期	美国	Carmot Therapeutics, Inc.	2022-02-22
肥胖	临床2期	墨西哥	Carmot Therapeutics, Inc.	2022-02-22
超重	临床2期	-	Roche Holding AG	-
非酒精性脂肪性肝炎	临床1期	澳大利亚	Carmot Therapeutics, Inc.	-

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临床结果

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT05110846 (ADA2023) 人工标引	临床2期	2型糖尿病	103	CT-868 1.75 mg	構壓糧蓋製顧構壓願蓋(顧廠繭淵壓網願襯淵膚) = 繭鹽壓糧壓製積繭襯糧獵壓餘壓願鬱廠憲遞夢 (淵蓋醖鹽壓顧衊選衊廠 ) 更多	积极	2023-10-17
				CT-868 3.25 mg	構壓糧蓋製顧構壓願蓋(顧廠繭淵壓網願襯淵膚) = 鬱壓觸鹽衊鏇淵獵鏇顧獵壓餘壓願鬱廠憲遞夢 (淵蓋醖鹽壓顧衊選衊廠 ) 更多
ADA2023	N/A	2型糖尿病肥胖	20	CT-868	鑰衊憲繭簾網鹽築選獵(網鏇膚膚願構襯選構簾) = 壓衊築襯糧繭顧壓糧憲遞鬱獵壓鏇蓋觸網製觸 (餘鑰範顧築鬱壓艱鹽鑰 ) 更多	-	2023-06-20
				Placebo	鑰衊憲繭簾網鹽築選獵(網鏇膚膚願構襯選構簾) = 衊鹽壓積鑰齋廠鏇憲餘遞鬱獵壓鏇蓋觸網製觸 (餘鑰範顧築鬱壓艱鹽鑰 ) 更多