A Phase 2, Double-Blind, Double-Dummy, Placebo-Controlled, Multicenter Study of the Efficacy, Safety, and Tolerability of Vurolenatide in Adult Patients With Short Bowel Syndrome

A Study of Vurolenatide in Adult Patients with Short Bowel Syndrome.

开始日期2021-06-14

申办/合作机构

9 Meters Biopharma, Inc.

NCT04379856 / Unknown status临床1/2期

A Phase I/II Proof of Concept, Open-Label, Repeat Dose, Dose Escalation Study of NM-002 in Adult Patients With Short Bowel Syndrome (SBS)

This is a Phase I/II. proof of concept, open label, two-dose, dose escalation study of NM-002 in adult patients with SBS who previously responded to exenatide. NM-002 is planned to be administered twice, at up to 3 different dose levels, in up to 3 cohorts, each consisting of 3-4 patients. Doses will be administered on Days 1 and 15 by subcutaneous injection. Patients will be monitored for their usage of parenteral supplementation, and will fill out a daily diary for their symptoms of SBS. Urine output will be measured on a daily basis. Patients will be followed for 6 weeks after the second dose.

开始日期2020-06-23

申办/合作机构

9 Meters Biopharma, Inc.

100 项与 NB-1001 相关的临床结果

登录后查看更多信息

100 项与 NB-1001 相关的转化医学

登录后查看更多信息

100 项与 NB-1001 相关的专利（医药）

登录后查看更多信息

项与 NB-1001 相关的文献（医药）

2010-05-01·Investigative ophthalmology & visual science2区 · 医学

Intracellular Thiol Redox Status Regulates Lymphangiogenesis and Dictates Corneal Limbal Graft Survival

2区 · 医学

ArticleOA

作者: Hamuro, Junji ; Maruyama, Kazuichi ; Kinoshita, Shigeru ; Fukumoto, Akiko ; Kajiya, Kentaro ; D'Amore, Patricia A. ; Walsh, Tony

PURPOSE:

Compounds regulating intracellular thiol redox status, such as N,N-diacetyl-L-cystine dimethylester (NM(2)), were shown to prolong corneal graft survival in a penetrating keratoplasty (PKP) model. However, the effect of NM(2) on hemangiogenesis and lymphangiogenesis has not been investigated. The effect of manipulating ambient thiol redox status on riskier (higher rejection rate) transplantation models, such as limbal graft survival and hemangiogenesis and lymphangiogenesis in a corneal suture model, were investigated.

METHODS:

C57BL/10 mice that received BALB/c corneas were treated by subconjunctival injection of NM(2), and limbal graft survival was assessed. Sutured C57BL/6 received daily intraperitoneal injections of NM(2), glutathione diethylester (GSH-OEt), or PBS. Lymphatic endothelial cell (LEC) and peritoneal mps were treated with NM(2) or GSHOEt, and then VEGFR3, neuropilin-2, podoplanin, and LYVE-1 expression were analyzed. Supernatants were collected for analysis of TNF-alpha and VEGF-A levels by ELISA.

RESULTS:

Significantly less cellular infiltration was detected in mice with corneal limbal transplant-treated NM(2)-treated mice. Hemangiogenesis and lymphangiogenesis were suppressed in the NM(2)-treated mice. NM(2) treatment of mps led to reduced levels of VEGFR3, neuropilin-2, podoplanin, and LYVE-1 expression compared with PBS- or GSHOEt- treated mps, lower levels of TNF-alpha, and increased secretion of VEGF. Moreover, NM(2)-treated LECs had reduced levels of LYVE-1 and Prox-1.

CONCLUSIONS:

Reduction of ambient redox status reduced inflammatory cell infiltrates. Consequently, reduced inflammatory response might have contributed to both the observed prolonged corneal limbal graft survival and the attenuated hemangiogenesis and lymphangiogenesis in cornea.

2000-03-01·Free radical biology & medicine2区 · 医学

Survival of hippocampal and cortical neurons in a mixture of MEM+ and B27-supplemented neurobasal medium

2区 · 医学

Article

作者: Chengsong Xie ; William R Markesbery ; Mark A Lovell

Serum-free B-27 supplemented neurobasal (NB) and a 10% fetal bovine serum-supplemented Eagle's minimum essential medium (MEM+) are used to culture rat embryonic hippocampal neurons for different purposes. Although NB medium leads to enhanced cell survival, it contains biological antioxidants and is not suitable for the study of free radical damage and oxidation in cultured neurons. MEM+ without additional antioxidants has been used widely in the study of free radical damage and oxidation, although it does not support optimum neuronal survival in culture. Serum in MEM+ leads to enhanced cell survival but also promotes glial cell proliferation. In this study, we used a new combination medium (NM-2) that consists of both NB and MEM+ for growing primary hippocampal and cortical neuronal cultures. NM-2 enhanced neuronal survival 78.9% for dissociated neurons at a density of 50 cells/mm(2) and 83.1% for 100 cells/mm(2), while decreasing glial cell proliferation to 2-3% and completely inhibiting oligodendrocytes. The NM-2 minimized the effectiveness of antioxidants in the medium to the neurotoxin 4-hydroxynonenal. It also decreased neuronal clumping and provided a more even distribution of neurons. Neurons survived for 4 weeks in NM-2 without changing the original medium. NM-2 provides a good environment for studies of free radical damage and oxidation of neurons. The combination incorporates the best of both NB and MEM+ that results in high neuron survival rate, low glial cell proliferation, reduced antioxidant level, and provides relatively pure cultures of hippocampal and cortical neurons.

1991-03-01·Human cell3区 · 生物学

[Resistance to anticancer drugs in NIH3T3 cells transfected with c-myc and/or c-H-ras genes].

3区 · 生物学

Article

作者: Niimi, S ; Terashima, Y ; Saijo, N ; Yokoyama, S

NIH3T3 cells transfected with c-H-ras and/or c-myc genes were examined for differences in drug sensitivity. The two transfectants used were NIH3T3-nm-1 (nm-1), pT22-3-nm-2. They were transfected with c-myc, c-myc plus activated c-H-ras, respectively. The relative resistances (IC50 values of transfectants/those of NIH3T3 cells) to cisplatin, adriamycin, 4-hydroperoxycyclophosphamide, melphalan, and CPT-11 were 2.1, 1.6, 4.7, 4.9, 1.6, respectively for nm-1 and 1.6, 2.2, 3.3, 9.1 and 2.2, respectively for nm-2. These results strongly suggest that the expression of the c-myc gene plays a role for the acquisition of drug resistance. The c-myc gene is believed to provide us an important clue for determining the mechanism of drug resistance.

项与 NB-1001 相关的新闻（医药）

2023-08-24

·赛柏蓝

不止降糖和减重，GLP-1R还可能有这些作用

GLP-1R是治疗2型糖尿病的重要靶点，而除此之外，降糖附带的减重效果，则更是意外之喜。除了2型糖尿病和肥胖症，GLP-1R药物在其他领域也有诸多意想不到的疗效，你知道哪些呢？01GLP-1R是什么‍？市场情况如何？GLP-1R靶点全称：Glucagon-like peptide 1 receptor(胰高血糖素样肽-1受体)，是一种B类、G蛋白连接的七个跨膜结构域蛋白，在胰腺、肺、心脏、肾脏、下丘脑和胃中都有广泛表达。结合GLP-1后能够刺激胰岛素的分泌，抑制胰高血糖素的分泌，从而促进葡萄糖的代谢，降低血糖；还能够延缓胃排空并抑制食欲。因此，GLP-1R已成为减重和治疗2型糖尿病的重要靶点。GLP-1R药物2021年市场情况数据来源：Pharma one智能药物大数据分析平台目前，全球获批的GLP-1R靶点药物共有11个，2021年销量前三的分别为度拉糖肽、司美格鲁肽和利拉鲁肽，GLP-1药物全球销售额高达169.8亿美元，市场前景巨大。02GLP-1R全球管线根据中国医药工业信息中心CPM新药研发监测数据库，GLP-1R靶点目前处于注册前和临床Ⅰ、Ⅱ、Ⅲ期的研究有137项，其中注册前的2项，Ⅲ期临床38项，Ⅱ期临床41项，Ⅰ期临床56项。GLP-1R在研药物数据来源：中国医药工业信息中心整理，下同。从适应症来看，目前在研的GLP-1R药物，2型糖尿病和肥胖症占据了约70%，而在其他适应症中，我们不难发现一些“意料之外”的治疗方向。GLP-1R在研适应症 03你不知道的神奇疗效● 非酒精性脂肪性肝炎非酒精性脂肪性肝病（Nonalcoholic Fatty Liver Disease，NAFLD）是一种以肝细胞显著脂肪变为病理特征的慢性代谢性疾病，已成为当前慢性肝病的首要病因，全球患病率高达25%，其中约20%的患者将发展为非酒精性脂肪性肝炎（Nonalcoholic steatohepatitis，NASH）。NASH患者数量庞大，但至今尚无针对该适应症的高效治疗药物。GLP-1R类药物目前虽然主要用于糖尿病的治疗，但是在控制血糖、改善代谢之外，它还对肝脏炎症，脂肪变性和纤维化有着显著改善作用。随机对照试验显示，利拉鲁肽(liraglutide)对治疗NASH有一定作用。与安慰剂组相比，利拉鲁肽组的患者肝脂肪变性和肝细胞气球样变得到了改善。目前治疗NASH的在研GLP-1R药物，有1项Ⅲ期临床和4项Ⅱ期临床正在进行，处于Ⅲ期临床的是Novo Nordisk A/S的semaglutide，其余产品包括Eli Lilly的tirzepatide、retatrutide和Hanmi Pharmaceutical的HM-15211。国内企业也有该领域的产品布局，如杭州先为达的ecnoglutide片剂，以及广东东阳光药业有限公司的HEC-88473注射剂。表1: GLP-1R 非酒精性脂肪性肝炎在研清单数据来源：CPM新药研发监测数据库中国医药工业信息中心。下同。● 短肠综合征短肠综合征是一种失去功能性小肠的罕见、衰弱型疾病。在成人当中，短肠综合征通常是因为创伤、血管性疾病、恶性肿瘤与慢性肠炎（IBD）所导致的肠切除引起。由于腹泻、脱水、营养不良等并发症，短肠综合征患者的生活品质与预期寿命严重受到影响。由于主要分泌此激素的回肠在短肠综合征患者内移除或较短，患者内的GLP-1含量下降，造成食物、液体快速通过肠胃道而缺乏吸收。Vurolenatide是一种长效的GLP-1受体激动剂，可以减缓进食后食物与液体经过胃与上肠道时的速度。Vurolenatide可以改善许多患者手术后胃蠕动的情形，并且具有良好的耐受性。它的长效性让患者每月最多只需接受两次治疗。目前在研的用于短肠综合征的靶向GLP-1R药物如下所示。表2: GLP-1R 短肠综合征在研清单● 阿尔茨海默氏病2型糖尿病是诱发阿尔茨海默病的高危因素，而高血糖素样肽-1(GLP-1)可诱导胰岛β细胞再生和增殖，改善胰岛素分泌，治疗糖尿病。GLP-1除了是调控血糖天然的肠促胰岛素激素，也是一种确认的神经递质，其受体在大脑的许多区域皆有表达，有研究发现GLP-1能降低脑内β淀粉样蛋白斑块沉积，减少氧化应激引起的神经细胞损伤，因此其在治疗神经退行性病变中也有重要的作用。临床前研究发现，给予GLP-1受体激动剂利拉鲁肽（liraglutide）可以改善记忆和学习能力，增加神经元数量，减少β淀粉样蛋白（Aβ），并防止tau蛋白累积。有回顾性研究发现曾使用GLP-1受体激动剂的糖尿病患的痴呆发生率明显低于对照组。在此背景下，Novo Nordisk A/S自2021年起便启动了两项司美格鲁肽用于治疗阿尔茨海默病患者的Ⅲ期临床试验，靶向GLP-1R的药物是否能成为治疗老年痴呆的新兴疗法，让我们拭目以待。表3: GLP-1R 阿尔茨海默氏病在研清单● 帕金森病帕金森病（PD）是仅次于阿兹海默病的一种最常见的神经退行性疾病，有研究表明，胰岛素信号通路的损伤可能与PD的发病相关，流行病学分析也发现糖尿病与神经退行性疾病之间存在联系。GLP-1受体在中枢神经系统中普遍存在，并具有神经保护作用，因此靶向GLP-1或许可以阻止帕金森病的疾病进展。对GLP-1活性的调节也能增加帕金森病小鼠模型体内的多巴胺（dopamine）水平。目前，针对帕金森病的GLP-1R在研药物主要是艾塞那肽和聚乙二醇艾塞那肽。表4: GLP-1R帕金森病在研清单数据来源：CPM新药研发监测数据库中国医药工业信息中心● 循环系统疾病GLP-1R药物对于循环系统疾病如高血压、动脉粥样硬化、心力衰竭等都有一定的治疗和改善作用。心衰是许多心血管疾病的终末阶段，严重威胁患者的生命健康，而肥胖是心衰的危险因素，尤其是射血分数保留心衰的危险因素。GLP-1R药物通常可以减重，有助于减少系统性炎症，改善代谢，稳定血糖和血压。Eli Lilly用于治疗心力衰竭的tirzepatide已经进入注册前状态，Novo Nordisk A/S的semaglutide也处于Ⅲ期临床。除了心衰，GLP-1R药物用于治疗高血压和动脉粥样硬化等疾病也都达到了Ⅲ期临床状态。表5: GLP-1R循环系统疾病在研清单数据来源：CPM新药研发监测数据库中国医药工业信息中心● 其他疾病其他疾病如骨关节炎、呼吸暂停、肺纤维化等，其在研管线也都有GLP-1R药物的身影，其中用于呼吸暂停的tirzepatide和用于骨关节炎的semaglutide目前都已处于Ⅲ期临床，相信在不久的将来，在这些领域也能看到GLP-1R药物闪闪发光。表6: GLP-1R其他疾病在研清单GLP-1R靶点百花盛开，绝不只是企业，更是在于适应症。糖尿病和减重之外，哪里会是GLP-1R的新归宿？END作者 | sean来源 | 医药地理扫描下方二维码，进入赛柏蓝药械交流群更多行业资讯，欢迎交流~↓点击下方阅读原文，获取更多详情

临床3期临床2期ASH会议申请上市

2023-08-23

·医药地理

GLP-1R，远不止降糖和减重

GLP-1R是治疗2型糖尿病的重要靶点，而除此之外，降糖附带的减重效果，则更是意外之喜。除了2型糖尿病和肥胖症，GLP-1R药物在其他领域也有诸多意想不到的疗效，你知道哪些呢？GLP-1R靶点全称：Glucagon-like peptide 1 receptor(胰高血糖素样肽-1受体)，是一种B类、G蛋白连接的七个跨膜结构域蛋白，在胰腺、肺、心脏、肾脏、下丘脑和胃中都有广泛表达。结合GLP-1后能够刺激胰岛素的分泌，抑制胰高血糖素的分泌，从而促进葡萄糖的代谢，降低血糖；还能够延缓胃排空并抑制食欲。因此，GLP-1R已成为减重和治疗2型糖尿病的重要靶点。GLP-1R市场情况‍图1: GLP-1R药物2021年市场情况数据来源：Pharma one智能药物大数据分析平台目前，全球获批的GLP-1R靶点药物共有11个，2021年销量前三的的分别为度拉糖肽、司美格鲁肽和利拉鲁肽，GLP-1药物全球销售额高达169.8亿美元，市场前景巨大。GLP-1R全球管线‍根据中国医药工业信息中心CPM新药研发监测数据库，GLP-1R靶点目前处于注册前和临床Ⅰ、Ⅱ、Ⅲ期的研究有137项，其中注册前的2项，Ⅲ期临床38项，Ⅱ期临床41项，Ⅰ期临床56项。图2: GLP-1R在研药物数据来源：中国医药工业信息中心整理从适应症来看，目前在研的GLP-1R药物，2型糖尿病和肥胖症占据了约70%，而在其他适应症中，我们不难发现一些“意料之外”的治疗方向。图3: GLP-1R在研适应症数据来源：中国医药工业信息中心整理GLP-1R你不知道的神奇疗效‍● 非酒精性脂肪性肝炎非酒精性脂肪性肝病（Nonalcoholic Fatty Liver Disease，NAFLD）是一种以肝细胞显著脂肪变为病理特征的慢性代谢性疾病，已成为当前慢性肝病的首要病因，全球患病率高达25%，其中约20%的患者将发展为非酒精性脂肪性肝炎（Nonalcoholic steatohepatitis，NASH）。NASH患者数量庞大，但至今尚无针对该适应症的高效治疗药物。GLP-1R类药物目前虽然主要用于糖尿病的治疗，但是在控制血糖、改善代谢之外，它还对肝脏炎症，脂肪变性和纤维化有着显著改善作用。随机对照试验显示，利拉鲁肽(liraglutide)对治疗NASH有一定作用。与安慰剂组相比，利拉鲁肽组的患者肝脂肪变性和肝细胞气球样变得到了改善。目前治疗NASH的在研GLP-1R药物，有1项Ⅲ期临床和4项Ⅱ期临床正在进行，处于Ⅲ期临床的是Novo Nordisk A/S的semaglutide，其余产品包括包括Eli Lilly的tirzepatide、retatrutide和Hanmi Pharmaceutical的HM-15211。国内企业也有该领域的产品布局，如杭州先为达的ecnoglutide片剂，以及广东东阳光药业有限公司的HEC-88473注射剂。表1: GLP-1R 非酒精性脂肪性肝炎在研清单数据来源：CPM新药研发监测数据库中国医药工业信息中心● 短肠综合征短肠综合征是一种失去功能性小肠的的罕见、衰弱型疾病。在成人当中，短肠综合征通常是因为创伤、血管性疾病、恶性肿瘤与慢性肠炎（IBD）所导致的肠切除引起。由于引起的腹泻、脱水、营养不良等并发症，短肠综合征患者的生活品质与预期寿命严重受到影响。由于主要分泌此激素的回肠在短肠综合征患者内移除或较短，患者内的GLP-1含量下降，造成食物、液体快速通过肠胃道而缺乏吸收。Vurolenatide是一种长效的GLP-1受体激动剂，可以减缓进食后食物与液体经过胃与上肠道时的速度。Vurolenatide可以改善许多患者手术后胃蠕动的情形，并且具有良好的耐受性。它的长效性让患者每月最多只需接受两次治疗。目前在研的用于短肠综合征的靶向GLP-1R药物如下所示。表2: GLP-1R 短肠综合征在研清单数据来源：CPM新药研发监测数据库中国医药工业信息中心● 阿尔茨海默氏病2型糖尿病是诱发阿尔茨海默病的高危因素，而高血糖素样肽-1(GLP-1)可诱导胰岛β细胞再生和增殖，改善胰岛素分泌，治疗糖尿病。GLP-1除了是调控血糖天然的肠促胰岛素激素，也是一种确认的神经递质，其受体在大脑的许多区域皆有表达，有研究发现GLP-1能降低脑内β淀粉样蛋白斑块沉积,减少氧化应激引起的神经细胞损伤，因此其在在治疗神经退行性病变中也有重要的作用。临床前研究发现，给予GLP-1受体激动剂利拉鲁肽（liraglutide）可以改善记忆和学习能力，增加神经元数量，减少β淀粉样蛋白（Aβ），并防止tau蛋白累积。有回顾性研究发现曾使用GLP-1受体激动剂的糖尿病患的痴呆发生率明显低于对照组。在此背景下，Novo Nordisk A/S自2021年起便启动了两项检司美格鲁肽用于治疗阿尔茨海默病患者的Ⅲ期临床试验，靶向GLP-1R的药物是否能成为治疗老年痴呆的新星疗法，让我们拭目以待。表3: GLP-1R 阿尔茨海默氏病在研清单数据来源：CPM新药研发监测数据库中国医药工业信息中心● 帕金森病帕金森病（PD）是仅次于阿兹海默病的一种最常见的神经退行性疾病，有研究表明，胰岛素信号通路的损伤可能与PD的发病相关，流行病学分析也发现糖尿病与神经退行性疾病之间存在联系。GLP-1受体在中枢神经系统中普遍存在，并具有神经保护作用，因此靶向GLP-1或许可以阻止帕金森病的疾病进展。对GLP-1活性的调节也能增加帕金森病小鼠模型体内的多巴胺（dopamine）水平。目前，针对帕金森病的GLP-1R在研药物主要是艾塞那肽和聚乙二醇艾塞那肽。表4: GLP-1R帕金森病在研清单数据来源：CPM新药研发监测数据库中国医药工业信息中心● 循环系统疾病GLP-1R药物对于循环系统疾病如高血压、动脉粥样硬化、心力衰竭等都有一定的治疗和改善作用。心衰是许多心血管疾病的终末阶段，严重威胁患者的生命健康，而肥胖是心衰的危险因素，尤其是射血分数保留心衰的危险因素。GLP-1R药物通常可以减重，有助于减少系统性炎症，改善代谢，稳定血糖和血压。Eli Lilly用于治疗心力衰竭的tirzepatide已经进入注册前状态，Novo Nordisk A/S的semaglutide也处于了Ⅲ期临床。除了心衰，GLP-1R药物用于治疗高血压和动脉粥样硬化等疾病也都达到了Ⅲ期临床状态。表5: GLP-1R循环系统疾病在研清单数据来源：CPM新药研发监测数据库中国医药工业信息中心● 其他疾病其他疾病如骨关节炎、呼吸暂停、肺纤维化等，其在研管线也都有GLP-1R药物的身影，其中用于呼吸暂停的tirzepatide和用于骨关节炎的semaglutide目前都已处于Ⅲ期临床，相信在不久的将来，在这些领域也能看到GLP-1R药物闪闪发光。表6: GLP-1R其他疾病在研清单数据来源：CPM新药研发监测数据库中国医药工业信息中心结语GLP-1R靶点百花盛开，绝不只是企业，更是在于适应症。糖尿病和减重之外，哪里会是GLP-1R的新归宿？年度发布2023年《全球药研新动态》《中国医院市场用药格局》（2023版）2023年《数图药讯》权威发布2021年度中国医药工业百强榜单解读中国仿制药发展报告（2022版）《2023年专利到期药品概述》医药行业专项报告中国医药中间体和原料药行业调研报告中国非甾体抗炎类原料药市场调研报告中国祛痰类原料药市场调研报告中国钙拮抗剂类原料药市场调研报告中国血管紧张素Ⅱ受体拮抗剂类原料药市场调研报告中国口服血糖调节类原料药市场调研报告中国中枢兴奋类原料药市场调研报告中国抗痛风类原料药市场调研报告中国脑血管病类原料药市场调研报告END如需获取更多数据洞察信息或公众号内容合作，请联系医药地理小助手微信号：pharmadl001

临床3期临床2期ASH会议临床成功申请上市

2023-07-19

·FierceBiotech

9 Meters calls it quits after measuring options, reports just $150K in cash

9 Meters was planning on running a second phase 2 trial for its lead asset before deciding to file for bankruptcy. You can’t get far with $150,000 in drug development, a painful realization that 9 Meters Biopharma knows all too well, as the North Carolina-based biotech filed for bankruptcy. The company disclosed its decision late Tuesday, a day after telling a federal bankruptcy court that it couldn’t continue. The company reported roughly $152,000 in cash on hand in addition to $4 million in intangibles and intellectual property, according to a court filing. The biotech previously reported having $6.9 million in cash and cash equivalents as of the end of March. The irony is that the company currently has a mid-stage GLP-1 inhibitor, a potentially hot-ticket item given the class's budding use in weight loss management. But 9 Meters was aiming vurolenatide at short bowel syndrome. The drug had also begun to stall in the clinic, after the company announced in late May that, following a conversation with U.S. regulators, it was likely best for vurolenatide to be tested in another phase 2 trial rather than advance to phase 3. The company also announced at the time that CEO John Temperato was resigning. But there was no explicit indication in 9 Meters’ most recent earnings report that the biotech was on the precipice of dissolving. In fact, the company said at the time that it had positive interactions with the FDA regarding the potential launch of NM-136—an anti-GIP antibody to treat obesity—into the clinic and was planning on doing so. 9 Meters also raised a $5 million direct offering in mid-March that was slated to fund both further development of vurolenatide and NM-136. But the company was also contending with a lender that held millions in a convertible note. 9 Meters and the holder of the note reached an agreement in late April whereby the biotech didn’t have to pay up in full, at least at the time—an agreement that was subsequently amended twice. Those extensions have been terminated as a result of the bankruptcy filing. Though 9 Meters seemed to be making progress, albeit at a trickle, the biotech was still stalked by prior failures, most recently in 2022 when larazotide flopped in a phase 3 trial for patients with celiac disease. The company has since pivoted, aiming that drug at a couple of COVID-related conditions, including multi-system inflammatory syndrome in children and long COVID.