**涉及的公司和行业** * 公司：Skye Bioscience (NasdaqGM:SKYE) [1] * 行业：生物制药/肥胖症治疗 [4] 核心观点和论据 **1 二期临床试验（CBION）主要终点结果** * 200毫克单药治疗组未达到主要终点，与安慰剂相比的最小二乘均值变化为-1.5% vs -0.3% [8] * 公司承认该结果，但认为原因在于药物暴露量低于预期 [8] **2 药物暴露量不足的解释与未来方向** * 药代动力学（PK）和暴露反应分析显示，200毫克每周剂量的药物暴露量低于基于一期模型的预测，大多数参与者未达到稳态水平 [8][9] * 临床前数据表明，200毫克剂量可能处于暴露反应曲线的低端，仅产生相对最小的体重减轻 [12] * 观察到方向性的暴露反应模式，药物暴露量较高的参与者体重变化更有利 [11] * 未来的逻辑下一步是测试更高剂量（如600毫克至1000毫克每周），以验证假设并达到曲线的有效部分 [11][12][49][50][71][72] **3 联合治疗结果的积极信号** * 在联合治疗组（Nimasumab + semaglutide）中，在符合方案分析集中观察到临床意义的额外体重减轻：26周时体重减轻-14.3%，而semaglutide单药为-10.8% [13] * 联合治疗的安慰剂调整后体重减轻为12.94%，优于semaglutide单药的9.99% [35] * 26周时未观察到体重减轻平台期，表明有持续减轻的潜力 [13] * 在符合方案分析集中，100%的联合治疗参与者实现了至少5%的体重减轻，三分之二实现了至少10%的体重减轻 [14] **4 安全性和耐受性概况** * Nimasumab在测试的暴露量下显示出良好的安全性和耐受性概况 [16] * 作为单药治疗，其不良事件概况与安慰剂相似；在联合治疗中，未增加相对于semaglutide单药的胃肠道副作用 [16] * 未报告与Nimasumab相关的神经精神系统不良事件 [16][56] * 即使在研究中达到较高暴露量的参与者中，也未观察到神经精神系统不良事件 [19] * 总体而言，81%的参与者报告了治疗中出现的不良事件，各研究组之间基本平衡，95%为轻度或中度 [52] **5 身体成分（DEXA扫描）数据** * 联合治疗组总体重减轻中有76%是脂肪减少，而semaglutide单药为72% [38] * 联合治疗组的瘦体重减少为24%，而semaglutide单药为28% [38] * 联合治疗组的瘦体重与脂肪比率改善（增加0.26），优于semaglutide单药（增加0.13）[39] **6 作用机制与差异化潜力** * Nimasumab（外周CB1抑制剂）和semaglutide（GLP-1受体激动剂）的作用机制被认为是互补的：semaglutide通过中枢和胃部机制起作用，而Nimasumab调节外周代谢和脂质过程 [15][60] * 即使在暴露量欠佳的情况下，外周CB1抑制似乎也足以增强semaglutide的效果 [15] * 公司认为Nimasumab的清洁安全性概况、外周作用机制以及与GLP-1的互补生物学，使其在当今以GLP-1为主导的肥胖治疗领域具有潜在竞争力和互补性的产品特征 [21][60] 其他重要内容 **7 下一步计划和里程碑** * 正在进行的扩展研究正在评估300毫克剂量，预计将提供额外的PK和疗效数据点 [24][62] * 52周的联合治疗组数据预计将在2026年第一季度获得，这将有助于描述效果的持久性并为潜在的二期设计提供信息 [62][64] * 基于26周主要终点的更深入数据切割结果将在ObesityWeek上作为最新突破性口头报告呈现 [65] * 现金储备预计可持续至2027年第一季度，足以支持进一步分析并为下一项临床研究做准备 [65] * 公司正在评估最有效的路径来了解剂量和暴露反应，包括探索一项侧重于联合治疗的剂量范围试验 [62] **8 关于暴露量可变性和依从性的讨论** * 在16周时间点观察到的谷浓度值范围相对较宽，许多参与者的浓度处于或低于预测的最低水平 [42][43] * 初步抗药物抗体分析表明ADA不是驱动Nimasumab清除的主要原因 [45] * 最终的PK分析将结合临床日记评估，以更好地了解可能是这些次优暴露关键驱动因素的潜在依从性问题 [46][99][100] * 外部专家指出，在当前的GLP-1和体重管理研究中，暴露量与实际给药剂量不一致是一个普遍现象，并非CBION试验独有 [105][106] **9 配方与给药考虑** * CBION研究中使用的药物配方为100毫克/毫升的预充式注射器，200毫克剂量需要注射两针 [128] * 对于未来的更高剂量，公司正在研究解决方案，包括从配方角度或设备递送角度，以可耐受的方式递送更大体积的剂量 [129] * 最终的上限剂量将受PK建模、CMC可行性和商业设计参数的指导 [63]

All drugs are investigational and subject to regulatory approval. Phase 2a Topline Clinical Data October 2025 Nasdaq: SKYE © 2025 Skye Bioscience, Inc. 1 Disclaimer and Important Information for Investors This presentation ("Presentation") has been prepared solely for general information purposes by or on behalf of Skye Bioscience, Inc. (together with its subsidiaries and affiliates, "Skye"). Any discussion of the potential use or expected success of our product candidates is subject to our product candidat ...

Skye Bioscience said on Monday its experimental obesity drug did not meet the main goal of a mid-stage study. ...

Nimacimab monotherapy did not meet its primary endpoint for weight loss; preliminary pharmacokinetic analysis showed lower than expected drug exposure, potentially indicating the need for higher dosing as a monotherapy.Clinically meaningful additional weight loss observed with combination of nimacimab, a peripheral CB1 inhibitor, and semaglutide compared to semaglutide alone.Nimacimab alone and in combination demonstrated a clean safety profile, with no added gastrointestinal adverse events and no nimacimab ...

Skye Bioscience, Inc. (NASDAQ: SKYE ) stock is having a good month with double-digit gains and even firmer (+145%) over the past 6 months. The current gains could be cemented by the most recent positiveGamu Dave Innocent Pasi is a seasoned financial professional and writer, bringing a wealth of experience from his prior roles as a financial analyst and in investment research. With a strong background in analyzing financial statements, capital markets, and the macro-economy, Gamu has a proven track record of ...

Skye Bioscience, Inc. (NASDAQ: SKYE ) stock is having a good month with double-digit gains and even firmer (+145%) over the past 6 months. The current gains could be cemented by the most recent positiveGamu Dave Innocent Pasi is a seasoned financial professional and writer, bringing a wealth of experience from his prior roles as a financial analyst and in investment research. With a strong background in analyzing financial statements, capital markets, and the macro-economy, Gamu has a proven track record of ...

On Friday, Skye Bioscience, Inc. SKYE announced the presentation of results from the Phase 1b study of nimacimab in subjects with metabolic-associated steatotic liver disease (MASLD) at the European Association for the Study of Diabetes (EASD) Annual Meeting.The study demonstrated that nimacimab was safe, well-tolerated, and exhibited predictable pharmacokinetics and low immunogenicity across multiple ascending dose cohorts.There were no serious adverse events, no discontinuations due to adverse events, and ...

临床研究结果 - 公司宣布nimacimab在代谢相关脂肪性肝病受试者中的1b期研究结果在欧洲糖尿病研究协会年会上展示 [1] - 研究证明nimacimab安全且耐受性良好 在所有多剂量递增队列中表现出可预测的药代动力学和低免疫原性 [2] - 无严重不良事件报告 无因不良事件导致的研究中止 无神经精神安全性信号证据 胃肠道副作用罕见且轻微 [2] 产品特性与竞争优势 - 该外周CB1抑制抗体展现出差异化的耐受性特征 [2] - 首席医疗官表示这些结果显示了标杆式的安全性和耐受性特征 使nimacimab在抗肥胖药物领域脱颖而出 [3] - 肥胖是多因素疾病 涉及肝脏、脂肪组织和肌肉等多个关键器官的重叠通路 [3] 研发进展与战略规划 - 公司近期重点是将发布的CBeyond™ 2a期肥胖研究顶线结果 [3] - 当前在肥胖糖尿病MASLD人群中的良好发现有助于确立nimacimab在代谢疾病治疗中的潜在作用 [3] - 该1b期研究最初由Bird Rock Bio进行 公司于2023年完成收购 [3] 研究展示详情 - 研究结果在"新药展望"口头报告环节展示 标题为"评估nimacimab安全性和耐受性的多剂量研究" [4] - 演示文稿可在公司网站Spotlight页面获取 [4] 公司背景与研发管线 - 公司专注于通过开发调节G蛋白偶联受体的新一代分子来解锁代谢健康新治疗途径 [5] - 研发策略利用具有大量人体机制验证的生物靶点 开发具有临床和商业差异化的首创疗法 [5] - 正在开展nimacimab的2a期临床试验 评估其单药及与GLP-1R激动剂Wegovy®联合使用的效果 [5]

PresentationFrank TangManaging Director Good morning, everyone. My name is Frank Tang, and I'm with the Investment Banking division at Morgan Stanley. Before we get started, I'd like to read a quick disclaimer. For important disclosures, please see the Morgan Stanley research disclosure website at www.morganstanley.com/researchdisclosures. If you have any questions, please reach out to your Morgan Stanley sales representative. With that, thank you all for joining us today for the fireside chat with Skye Bio ...

PresentationFrank TangManaging Director Good morning, everyone. My name is Frank Tang, and I'm with the Investment Banking division at Morgan Stanley. Before we get started, I'd like to read a quick disclaimer. For important disclosures, please see the Morgan Stanley research disclosure website at www.morganstanley.com/researchdisclosures. If you have any questions, please reach out to your Morgan Stanley sales representative. With that, thank you all for joining us today for the fireside chat with Skye Bio ...