A Multicenter, Randomized, Double-blind, Placebo-controlled Study of Enzastaurin for the Prevention of Arterial Events in Patients With Vascular Ehlers-Danlos Syndrome (vEDS) Confirmed With COL3A1 Mutations, Followed by an Open Label Extension (OLE)

The purpose of this study is to investigate the efficacy of enzastaurin compared to placebo in preventing arterial events (rupture, dissection, pseudoaneurysm, carotid-cavernous sinus fistula, or aneurysm, fatal or not) leading to intervention or mortality attributable to an arterial event in patients with vEDS confirmed with pathogenic heterozygous COL3A1 gene mutations predicted to derive a mutant protein.

开始日期2025-01-01

申办/合作机构

Aytu Biopharma, Inc.

[+1]

CTR20210055

/ Completed临床3期

在新诊断为胶质母细胞瘤并且全新生物标记物DGM1 阳性患者中评估Enzastaurin联合替莫唑胺同步放化疗加辅助化疗方案的随机双盲安慰剂对照III期临床试验

主要目的：在新诊断为胶质母细胞瘤的Denovo基因标记物1（DGM1）阳性患者中，与安慰剂对照，评估enzastaurin联合替莫唑胺同步放化疗加辅助化疗方案在患者总生存期（OS）方面的优效性。次要目的： 1. 在DGM1生物标记物阳性患者中比较治疗组间的无进展生存期（PFS）。 2. 在DGM1生物标记物阳性患者中比较治疗组间的客观缓解率（ORR）。 3. 进一步评估enzastaurin加入替莫唑胺同步放化疗加辅助化疗方案后的安全性特征。探索性目的： 1. 在DGM1生物标记物阴性患者中评估总生存期（OS）。 2. 确定色素尿的存在（尿液呈橙色/红色）是否与服用enzastaurin的患者生存期改善存在关联。 3. 分析尿液中是否存在enzastaurin和enzastaurin代谢产物（尿液药代动力学[PK]）。 4. 评估其它胚系或肿瘤生物标记物的存在是否与服用enzastaurin的患者的疗效改善存在关联。 5. 确定enzastaurin和enzastaurin代谢产物的浓度，以便纳入后续的群体PK分析中。

开始日期2021-07-13

申办/合作机构

Denovo Biopharma LLC

[+2]

NCT03776071

/ Completed临床3期

A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study of Enzastaurin Added to Temozolomide During and Following Radiation Therapy in Newly Diagnosed Glioblastoma Patients Who Possess the Novel Genomic Biomarker DGM1

This study will be conducted as a randomized, double-blind, placebo-controlled, multi-center Phase 3 study. Approximately 300 subjects with newly diagnosed glioblastoma who meet all eligibility criteria will be enrolled.

开始日期2020-12-16

申办/合作机构

Denovo Biopharma LLC

100 项与盐酸恩扎妥林相关的临床结果

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100 项与盐酸恩扎妥林相关的转化医学

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100 项与盐酸恩扎妥林相关的专利（医药）

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项与盐酸恩扎妥林相关的文献（医药）

2025-08-01·MOLECULAR DIVERSITY

Integrating traditional QSAR and read-across-based regression models for predicting potential anti-leishmanial azole compounds

Article

作者: Priya, Ananya ; Sharma, Anupama ; Nandi, Rajat ; Kumar, Diwakar

Leishmaniasis, a neglected tropical disease caused by various Leishmania species, poses a significant global health challenge, especially in resource-limited regions. Visceral Leishmaniasis (VL) stands out among its severe manifestations, and current drug therapies have limitations, necessitating the exploration of new, cost-effective treatments. This study utilized a comprehensive computational workflow, integrating traditional 2D-QSAR, q-RASAR, and molecular docking to identify novel anti-leishmanial compounds, with a focus on Glycyl-tRNA Synthetase (LdGlyRS) as a promising drug target. A feature selection process combining Genetic Function Approximation (GFA)-Lasso with Multiple Linear Regression (MLR) was used to characterize 99 azole compounds across ten structural classes. The baseline MLR model (MOD1), containing seven simple and interpretable 2D features, exhibited robust predictive capabilities, achieving an R²_train value of 0.82 and an R²_test value of 0.87. To further enhance prediction accuracy, three qualified single models (two MLR and one q-RASAR) were used to construct three consensus models (CMs), with CM2 (MAE_test = 0.127) demonstrating significantly higher prediction accuracy for test compounds than the MOD1. Subsequently, Support Vector Regression (SVR) and Boosting yielded 0.88 (R²_train), 0.86 (R²_test), 0.92 (R²_train), and 0.82 (R²_test), respectively. Molecular docking highlighted interactions of potent azoles within the QSAR dataset with critical residues in the LdGlyRS active site (Arg226 and Glu350), emphasizing their inhibitory potential. Furthermore, the pIC50 values of an accurate external set of 2000 azole compounds from the ZINC20 database were simultaneously predicted by CM2 + SVR + Boosting models and docked against the LdGlyRS, which identified Bazedoxifene, Talmetacin, Pyrvinium, Enzastaurin as leading FDA candidates, whereas three novel compounds with the database code ZINC000001153734, ZINC000011934652, and ZINC000009942262 displayed stable docked interactions and favourable ADMET assessments. Subsequently, Molecular Dynamics (MD) simulations for 100 ns were conducted to validate the findings further, offering enhanced insights into the stability and dynamic behaviour of the ligand-protein complexes. The integrated approach of this study underscores the efficacy of 2D-QSAR modelling. It identifies LdGlyRS as a promising leishmaniasis target, offering a robust strategy for discovering and optimizing anti-leishmanial compounds to address the critical need for improved treatments.

2025-06-01·Frontiers of Medicine

Determining the biomarkers and pathogenesis of myocardial infarction combined with ankylosing spondylitis via a systems biology approach

Article

作者: Liu, Chunying ; Peng, Chengfei ; Zhang, Xiaolin ; Han, Yaling ; Jia, Xiaodong ; Song, Haixu ; Yan, Chenghui ; Liu, Dan

Ankylosing spondylitis (AS) is linked to an increased prevalence of myocardial infarction (MI). However, research dedicated to elucidating the pathogenesis of AS-MI is lacking. In this study, we explored the biomarkers for enhancing the diagnostic and therapeutic efficiency of AS-MI. Datasets were obtained from the Gene Expression Omnibus database. We employed weighted gene co-expression network analysis and machine learning models to screen hub genes. A receiver operating characteristic curve and a nomogram were designed to assess diagnostic accuracy. Gene set enrichment analysis was conducted to reveal the potential function of hub genes. Immune infiltration analysis indicated the correlation between hub genes and the immune landscape. Subsequently, we performed single-cell analysis to identify the expression and subcellular localization of hub genes. We further constructed a transcription factor (TF)-microRNA (miRNA) regulatory network. Finally, drug prediction and molecular docking were performed. S100A12 and MCEMP1 were identified as hub genes, which were correlated with immune-related biological processes. They exhibited high diagnostic value and were predominantly expressed in myeloid cells. Furthermore, 24 TFs and 9 miRNA were associated with these hub genes. Enzastaurin, meglitinide, and nifedipine were predicted as potential therapeutic agents. Our study indicates that S100A12 and MCEMP1 exhibit significant potential as biomarkers and therapeutic targets for AS-MI, offering novel insights into the underlying etiology of this condition.

2025-06-01·BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

Both carvedilol and cimetidine alleviate cisplatin-induced nephrotoxicity via downregulating OCT2

Article

作者: Jiao, Xiaoyan ; Wu, Huan ; Ning, Yichun ; Sun, Zhaoxing ; Ji, Ji ; Ding, Xiaoqiang ; Yu, Xiaofang ; Cheng, Xin ; Xu, Xiaoliang ; Lu, Min

BACKGROUND:

Cisplatin is a common chemotherapy agent for solid tumors but severe nephrotoxicity limits its application, with no effective pharmacological treatments. Organic cation transporter 2 (OCT2) is involved in cisplatin uptake in kidneys. This study aimed to find drugs with promising clinical applications that could prevent cisplatin-induced acute kidney injury (Cis-AKI) by inhibiting OCT2.

METHODS:

The mRNA level of OCT2 was examined in human induced pluripotent stem cells (iPSCs) from Cis-AKI patients and paired non-AKI patients. The association between OCT2 and Cis-AKI was investigated by HEK293FT cells and kidney organoids. We screened potential compounds exhibiting protective effects against Cis-AKI in US Food and Drug Administration-approved drugs through virtual screening and activity screening. Subsequently, we determined the effects of these compounds on OCT2 expression, cisplatin uptake, and apoptosis in cells, kidney organoids and mice. A549 and HeLa cells were adopted to observe the influence of drugs on the anti-tumor function of cisplatin.

RESULTS:

Compared to non-AKI patients, the OCT2 mRNA levels of iPSCs from Cis-AKI patients were elevated. OCT2 exhibits similar expression patterns in kidney organoids and human kidney tissues. Furthermore, the overexpression of OCT2 in kidney organoids and HEK293FT cells exacerbated the injury caused by cisplatin. Carvedilol and cimetidine were identified as potent OCT2 inhibitors by drug screening. Further analysis revealed that the pretreatment of carvedilol or cimetidine downregulated OCT2, reduced cisplatin uptake, and alleviated cisplatin-induced apoptosis, but the combination of the two drugs didn't further improve these outcomes. Additionally, carvedilol and cimetidine didn't compromise the cisplatin-induced cell death in A549 and HeLa cells.

CONCLUSION:

Our study confirmed that carvedilol and cimetidine exert protective effects against Cis-AKI by inhibiting OCT2, without altering the anti-tumor effects of cisplatin.

项与盐酸恩扎妥林相关的新闻（医药）

2025-07-20

·药事纵横

5大创新药企人效PK：恒瑞、百济、石药、中生和翰森

声明：因水平有限，错误不可避免，或有些信息非最及时，欢迎留言指出。本文仅作医疗健康相关药物介绍，非治疗方案推荐（若涉及）;本文不构成任何投资建议。7月9日法国《回声报》报道，去年中国发现的新药物分子数量超过美国，成为全球新药研发的领头羊，欧洲则被甩开差距，退居世界第三，全球医药创新重心转向中国。中国创新药正式进入DEEPSEEK时刻！数据显示，中国在全球创新药BD交易中的项目数占比从2019年的3%跃升至2024年的13%，金额占比从1%提升至28%。2025上半年中国创新药Licenseout总金额更是已接近660亿美元，赶超2024全年BD交易总额，MNC对中国创新药资产关注度有望延续。作为中国创新药的标杆，恒瑞、百济、石药、中生和翰森，近年在NowCo与licenseout方面也是动作频频，快速走向全球。本文主要从人效数据（近5年人均创收、创利）、研发投入、管线布局等方面来看看这5家头部药企的发展现状。营收情况创新药行业的“效率竞赛”中，营收与净利润不仅是企业生存的根本。从营收规模看，石药集团以290.09亿元居首，但其-7.76%的同比增速暴露了传统药企转型的阵痛：尽管创新药收入占比已提升至48%，但仿制药集采续标降价的影响仍在消化，部分成熟产品线收入下滑拖累整体增长。紧随其后的恒瑞医药以279.85亿，同比增长22.63%的营收规模与中国生物制药288.66亿同比增长10.18%的数据，展现出更强的抗风险能力。恒瑞凭借PD-1卡瑞利珠单抗、ADC药物SHR-A1811等创新药快速放量。中生则依托肿瘤领域的安罗替尼、肝病领域的润众等基石产品等，实现了稳健增长。百济神州以272.14亿营收、同比56.19%的爆发式增速成为最大变量。BTK抑制剂泽布替尼全球销售额达18.6亿美元，PD-1替雷利珠单抗在国内医保放量。虽然目前净利润为负数，但净利润同比是呈现增长的趋势，表明其亏损在收窄。相比之下，翰森制药以122.61亿营收、同比21.35%的增速与43.72亿净利润，同比33%的增长，展现了专科药企的“小而美”优势。整体来看，2024年的营收与净利润数据打破了“规模越大越赚钱”的固有认知。管线布局情况恒瑞的管线延续了“全面布局+自主创新”的风格，覆盖肿瘤、自身免疫、代谢疾病、麻醉镇痛四大方向，且每个领域均有“阶梯化”储备。肿瘤线中，PD-1卡瑞利珠单抗已上市，ADC药物SHR-A1811目前为乳腺癌III期临床、CDK4/6抑制剂SHR6390处于乳腺癌II期临床阶段。自身免疫线，JAK1抑制剂SHR0302目前为银屑病III期、IL-17A抑制剂SHR1314处于强直III期，瞄准未满足需求。图：恒瑞医药研发管线图百济神州的管线几乎“全员出海”，核心逻辑是“用全球临床数据换全球市场”。肿瘤线中，BTK抑制剂泽布替尼已在全球超过65个国家获批，其针对CLL/SLL的III期头对头试验数据持续释放，有望进一步扩大适用人群；PD-1替雷利珠单抗则在欧盟提交鼻咽癌适应症上市申请，同时在东南亚、中东启动本地化生产。除肿瘤外，其BCL-2抑制剂BGB-11417目前为白血病II期临床、HPK1抑制剂BGB-15025实体瘤I期临床等管线均采用“中美双报”策略。图：百济神州研发管线图作为传统仿制药龙头，石药的管线正从“仿制药止血”向“创新药造血”快速切换。其创新药收入占比在不断提升，管线重点聚焦肿瘤、神经退行性疾病、心血管三大方向。肿瘤线中，PI3K抑制剂DP303c目前乳腺癌III期、Claudin 18.2 ADC处于胃癌II期是核心；神经领域，抗阿尔茨海默病新药DB102（Aβ单抗）已进入III期，瞄准全球超5000万患者的蓝海市场；心血管线则依托玄宁的品牌优势，拓展复方制剂及长效降压药管线。图：石药集团研发管线图中生的管线延续了“聚焦优势领域+适度扩展”的策略，核心围绕肿瘤、肝病、呼吸、外科/镇痛四大板块。肝病线是其“基本盘”：除了已上市的润众（恩替卡韦）、天晴甘美（异甘草酸镁），其长效干扰素派罗欣（聚乙二醇干扰素α-2a）在乙肝功能性治愈领域持续探索，联合疗法III期数据值得关注；在肿瘤线中，安罗替尼（多靶点TKI）已扩展至甲状腺癌、软组织肉瘤等8个适应症，2024年销售额超50亿，成为“单品王”；呼吸线则依托布地奈德吸入剂（天晴速乐）等成熟产品，向生物类似药（如抗IL-5单抗）延伸。图：中国生物制药部分管线进展图翰森的管线是典型的“集中火力打透细分市场”，80%的资源投入精神类、抗感染两大领域，其余20%布局代谢疾病。精神领域是其“护城河”：奥氮平改良型新药阿美宁已上市占据国内精神分裂症市场一定份额。抗抑郁新药HS-10353（5-HT1A受体激动剂）进入III期，瞄准“难治性抑郁”空白市场。抗感染线中，1类新药HS-10296（EGFR-TKI）虽因肺癌市场竞争激烈放缓，但其在耐药菌治疗领域的口服抗生素（如HS-10332）已进入II期。图：翰森制药部分管线，资料来源：华泰研究研发投入研发投入是企业技术储备的“晴雨表”。百济神州的研发费用以141.40亿绝对领先，占营收比例高达51.96%，但其10.35%的增速较前几年有所放缓——这并非“投入收缩”，而是进入“成果兑现期”的主动调整。恒瑞以65.83亿研发费用32.88%的增速紧随其后，增速为五家企业最高，反映出其“以投入补差距”的迫切性。作为传统仿制药转型代表，恒瑞近年面临集采常态化导致的存量业务收缩，因此通过加大研发投入加速创新管线落地。中生50.89亿15.58%的增速与石药研发投入51.91亿，7.47%同比的研发投入规模接近，但增速与战略重心差异显著。中生研发投入更多用于“优势领域的深化”，石药则因转型压力更大，其51.91亿的规模仍支撑了关键管线的推进。翰森研发费用投入27.02亿但其同比增速28.85%，增速仅次于恒瑞，体现出“小而精”的投入策略。人效：人均创收创利对比恒瑞的人均创收从2020年的105.10万增至2024年的138.28万，人均创利从21.90万增至31.31万，两项指标均保持“稳健增长”。百济的人均创收从2020年的41.16万飙升至2024年的245.72万，但人均创利始终为负，是五家企业中唯一“增收不增利”的代表。虽然目前为止人均创利为负，但其亏损在不断收窄，相信很快可以扭亏为盈。石药的人均创收呈现“先升后降”波动，但人均创利从2020年的23.97万下滑至2022年的24.53万，2024年回升至20.22万，其背后是传统药企转型的“阵痛与调整”。中生的人均创收从2020年的118.41万略降至2024年的98.09万，但人均创利从11.49万稳步提升至14.36万，呈现“创收降、创利升”的反向趋势。翰森的人均创收从2020年的136.40万大幅降至2024年的74.63万，但人均创利却从22.06万飙升至48.64万，是五家企业中“创利增速最快”的代表。在创新药行业从“规模扩张”转向“质量突围”的当下，人均创收与创利的“含金量”远胜绝对数值。毕竟，能更高效的利用人力创造更高盈利的企业，才是未来“活得更久、走得更远”的企业发展之路。参考资料：各企业官网

财报引进/卖出临床1期临床3期抗体药物偶联物

2024-04-28

·研发客

用7年，验证一个抑郁症biomarker | DJS

// 索元生物历经7年，用其全基因组平台找到其在研产品DB104的生物标志物DGM4，且已证明了药物疗效。DB104的治疗群体是难治性抑郁症，其生物标志物DGM4在20%的难治性抑郁症患者中呈阳性。近期索元已经开启对外授权合作的步伐。在5月的2024年DJS创新合作峰会上，索元生物将现场路演。撰文 | 殷丹妮索元生物董事长罗文博士告诉研发客，公司正在和多家国际大药厂接洽合作事宜。这主要得益于DB104治疗难治性抑郁症（TRD）的关键性临床试验积极结果的公布。从2012年成立至今12年，索元终于在首个产品上证明了其精准医疗“基因组学+新药”的研发理念。综观索元的模式，乃是引入临床“失败”新药，利用大数据组学打造的全基因组平台发现生物标志物（biomarker），通过新发现的biomarker筛选患者并重新开展临床试验，验证药物疗效。DB104在2b期临床中证明了对TRD的疗效，也证明了索元模式“biomarker+新药”的可行性。索元生物董事长罗文罗文认为，如果DB104能成功上市，将是CNS领域第一个精准医疗的突破，类似于当年易瑞沙找到EGFR突变对于肺癌的意义。同时他表示，随着DB104的成功，将有计划重启IPO之路。2017年，索元生物从BMS收购DB104时，研发客就采访过罗文（拓展阅读索元获AMRI/BMS抗抑郁药全球授权，新模式见真章）。7年过后，索元不仅找到DB104的生物标志物DGM4，且已证明了药物疗效。索元生物首席财务官陈纪正女士将在2024DJS代表公司路演。欢迎参与投票“谁是您最喜爱的路演公司”，投票时间从即日起至5月15日16:00，活动详情见本期次条。或将申请有条件上市研发客：请您介绍一下DB104治疗难治性抑郁症的具体研究情况、疗效如何？罗文：这项关键性国际多中心临床研究ENLIGHTEN，共纳入197例患者，治疗6周后，在基因生物标志物DGM4阳性TRD患者中达到主要临床终点和所有次要终点。其中在主要终点蒙哥马利-阿斯伯格抑郁量表（MADRS）总分相对于基线的变化方面，DB104用药组量表打分相比安慰剂组要低4.4分（p值0.0056）, 将近40%的改善。单从MADRS评分看，DB104疗效与已获批治疗TRD的Spravato疗效相当。Spravato在56mg或84mg剂量的MADRS总分未超过4分。并且DB104在安全性和使用便利性层面也具备优势。Spravato为鼻喷制剂，DB104是每天口服一次的片剂。DB104在2017年被收购前，BMS已开展了11项1期、3项2b期大型临床试验，在上千例患者中验证了产品的安全性和耐受性。而Spravato改良于麻醉剂氯胺酮，上市后因安全性问题和滥用风险被FDA加以黑框警告，只能在医生监督下使用，给药两小时内须由专业人员陪护，一定程度上限制了其临床应用。研发客：DB104将来上市将有多大的市场空间？销售峰值将达多少？罗文：DB104的治疗群体是难治性抑郁症。根据人民日报发布《2022年国民抑郁症蓝皮书》，中国患抑郁症人数超过9500万，其中难治性抑郁症患者占这近1亿例中的约三分之一。且DB104的生物标志物DGM4在20%的TRD患者中呈阳性。20%的比例在生物标志物中已属于较高比例，一些肿瘤突变基因NTRK1、ROS1、RET等只有1%~2%比例，但不妨碍各大药厂投入重金研发。从竞争对手看，Spravato于2019年在美国上市后销量持续上涨，2024年第一季度销售额达2.25亿美金，同比增长72%，成为年销售额超过十亿美金的“重磅炸弹”应该没有悬念。DB104从药物依从性、安全性各方面相较Spravato都有优势。我们预测DB104上市后全球的峰值销售可能会接近20亿美金。研发客：索元生物对DB104进一步的规划是什么？罗文：产品的注册申请程序正在按部就班的进行中。DB104在2b期临床试验获得积极数据，我认为有可能尝试将其作为关键性临床（pivotal trial）结果向药监部门申请有条件上市的批准。此外，我们也正在和一些国际大厂沟通合作事宜。近年国内药企授权出海浪潮正热，一些创新药甚至在临床前就被授权。而且大药厂有强势回归CNS趋势，仅2023年底就有两笔大额收购交易，即BMS以140亿美金收购Karuna、艾伯维87亿美金收购Cerevel。类似于DB104的first-in-class新药，也高度符合MNC的需求，尤其是DB104已获得2b期积极结果。从索元公司本身看，自2012成立至今一直坚持精准医疗，需要有一个突破口证明我们的研发策略是正确的。如今DB104获得重大突破，索元短期将集中所有资源用于这款产品开发。容易检测到的biomarker研发客：可否请您以DB104为例，解释一下索元筛选biomarker的过程？罗文：我们收集了BMS针对DB104开展的两项2b期临床试验，在试验受试者的全血样本中提取DNA，对其中上百例样本进行了全基因组扫描，从上百万个位点中通过大数据分析、人工智能等多种计算工具，历经两年时间，最终发现了一个全新的生物标志物并将其命名为Denovo Genomic Marker4（DGM4）。同时，为验证DGM4是预测疗效的药物基因组生物标志物，而非疾病预后生物标志物。我们在对照组受试者中开展相同的生物标志物分析，结果表明，DGM4是可以预测疗效的生物标志物。索元的生物标志物发现平台研发客：索元生物标志物发现平台的特点和难点是什么？罗文：biomarker的寻找已历经3代，第一代的典型是易瑞沙，药物靶点就是biomarker；第二代的代表是结肠癌治疗药物Erbitux，靶点是EGFR，biomarker则是KRAS。KRAS在EGFR信号传导通路的下游，寻找起来相对复杂。一代和二代生物标志物都是从已有的科学文献推测，属于知识导向。索元模式是第三代，不再局限于已知的生物信息传导通路，而是以数据导向的反向式检索，在全人类基因组中扫描。这也应对了索元生物的英文名称Denovo，完全从头发现，是从0到1的过程。这是索元模式的核心也是难点。人类基因组共有30亿个碱基对，从30亿位点中找出一两个跟药效相关的biomarker，无异于大海捞针。所以，尽管前期我们收购药物时进行了精挑细选，也不能保证每个项目都能找到biomarker。例如DB103，自收购至今6年多时间仍未找到其生物标志物，但我们仍未放弃。索元管线的8款产品（见下图）中，有DB102、DB104和DB107发现了biomarker，分别是DGM1、DGM4和DGM7。而一旦找到了biomarker，其应用就非常容易，普及率很高。以肿瘤生物标志物来做对比。通常抗肿瘤药的伴随诊断所针对的肿瘤突变基因，必须从肿瘤组织提取进行活检。而索元的biomarker是由SNP（单核苷酸多态性）组成的生物标志物，胚系SNP来自父母遗传，存在于全身各个细胞中，因此通过血液、甚至唾液就能检测，不需要获取病灶组织的样本。这种核酸检测简易快捷，方便临床患者，可以做到无创检测。总结起来，找biomarker特别困难，但检测非常容易，这也是索元模式的一大特色。我们在DB104临床入组预筛时就使用过该方法，效率非常高。上市之路可能重启研发客：索元生物的研发理念需要哪些核心技术的融合？罗文：索元生物的研发模式，是一项跨学科的系统工程，将大数据基因组学应用于创新药研发，汇集了大数据、基因组学、分子生物学、临床各类学科人才。而我本身的职业生涯也跨越了多个领域。本科是临床医学，研究生是分子生物学。工作后在蛋白激酶研发前沿公司Sugen（后被辉瑞收购），及Ligand Pharmaceutical从事新药研发。在人类基因组完成的2000年，加入当时最大的基因组学公司Incyte Genomics，对于基因组大数据的价值有切身感受。跨学科的职业经历，也让我认定要将基因组学应用于创新药的研发。研发客：索元生物在关注哪些前沿技术，开展哪些技术合作？罗文：索元生物本身就是商业模式及技术平台超前的研发驱动公司，自然对各类创新技术充满兴趣，也正在和全球最前沿的公司和科研院所合作，不断提升自身研发水平。如，与Nurosene合作，利用AI技术NetraPlacebo帮助解决CNS临床试验中的安慰剂效应，提升试验成功率。索元生物还与哈佛大学、清华大学的脑电波专家合作过。目前CNS临床终点大多是量表打分，例如抑郁症的汉密尔顿抑郁量表、蒙哥马利抑郁量表，而量表打分具有主观性，脑电波是客观的定量指标。不过这些都属于探索性实践合作，真正用于临床还需要获得监管部门的认可，在此之前的临床终点还是必须依据现有国际金标准。研发客：2021年撤回科创板IPO申请后，索元还考虑上市吗？罗文：2021年中国药品市场热点是biosimilar和me-too药物，科创板、港股上市的大部分是这类药企。索元模式至今在全球范围内都没有同类企业，当时更是没有。公司独特的商业模式没有得到验证，这都是挑战。而如今DB104临床成功，核心技术DGM生物标志物发现平台得到验证，我认为公司的上市之路已被打开。同时，DB104对外授权合作也在同步展开，产生的超额收益使公司能够提前进入投资丰收期。而且药监部门一直在支持精准医疗开发。2021年底CDE发布了《生物标志物在抗肿瘤药物临床研发中应用的技术指导原则》，而后在ADC、PD-1/L1、基因治疗等各类指南中都提及生物标志物的重要性。编辑 | 姚嘉yao.jia@PharmaDJ.com 总第2097期访问研发客网站可浏览更多文章www.PharmaDJ.com

并购IPO临床2期申请上市临床1期

2023-11-21

·PRNewswire

KAZIA PROVIDES OVERVIEW OF PAXALISIB RELATED PRESENTATIONS FROM THE SOCIETY OF NEURO-ONCOLOGY 2023 ANNUAL MEETING

SYDNEY, Nov. 21, 2023 /PRNewswire/ -- Kazia Therapeutics Limited (NASDAQ: KZIA), an oncology-focused drug development company, is pleased to provide key highlights of the clinical and preclinical paxalisib related presentations given by key thought leaders at the Society of Neuro-Oncology 2023 Annual Meeting. "The 2023 SNO Annual Meeting was another successful event with the latest advances in clinical trials, diagnosis and treatment of pediatric and adult patients with CNS malignancies," stated Dr. John Friend, CEO Kazia. "We are highly encouraged with the preliminary overall survival data from the PNOC022 clinical study that we believe will provide an alternative to the current therapies considered as standard of care." Key paxalisib highlights from the meeting: Friday, November 17th Combining ONC201 and paxalisib for the treatment of diffuse midline glioma (DMG); the preclinical results underpinning the international Phase II clinical trial (NCT05009992). Presenter: Evangeline R. Jackson; University of Newcastle, NSW, Australia The mechanism of action of both paxalisib and ONC201 were reviewed as well as the synergistic effects of their combination in DMG preclinical models Specifically, the authors observed how ONC201 over activates the PI3K-AKT pathway, which is the target pathway for paxalisib Consistent and statistically significant improvements were observed with the combination of paxalisb and ONC201 in DMG preclinical mouse models Two patient case studies were discussed; each receiving the combination of paxalisib and ONC201 through compassionate access 16-year old female with advanced and relapsed diffuse intrinsic pontine glioma (DIPG) who demonstrated significant neurological improvements as well as rapid tumour regression after receiving the combination Six-year old female with DIPG who received the combination of paxalisib and ONC201 after upfront radiation therapy. Tumor regression has been maintained for more than two years on paxalisib and ONC201 Exploiting the genetic dependency on PI3K/mTOR signaling for the treatment of H3-altered Diffuse Midline Glioma Presenter: Ryan Duchatel, PhD; University of Newcastle, NSW, Australia PI3K pathway activation is observed in >80% of all DMGs and was shown to be required for DMG cell growth The authors stated that the success of a monotherapy in DMG is highly unlikely; therefore they explored several combinations [of other therapies] with paxalisib with the aim of optimizing tolerability and efficacy of such combinations in preclinical mouse studies Adding metformin to paxalisib was observed to improve hyperglycemia (elevated blood glucose) as well as extend the overall survival rate The combination of paxalisib and enzastaurin (PKC inhibitor) was observed to further extend the overall survival when combined to radiation treatment Authors concluded the triple combination of paxalisib, enzastaurin and metformin warranted further investigation in clinical trials Phase I study of paxalisib and radiotherapy for CNS disease harboring PI3K pathway mutations: pilot analysis of circulating tumor DNA for patient eligibility confirmation and post-treatment response Presenter: Brandon Imber, MD, Memorial Sloan Kettering Cancer Center, NYC, USA This is a multi-institutional, Phase I trial of concurrent paxalisib and radiation therapy in patients with brain metastases with documented PI3K pathway mutations Study has expanded after data from the initial stage identified the maximal tolerated dose (45mg once daily) along with observed signals of clinical activity (100% response rate) The authors observed that plasma circulating tumor DNA (ctDNA) was able to accurately confirm the tumor's genetic mutations at baseline and can potentially be used as a biomarker to assess patient treatment response The authors presented a representative case from the ongoing Phase I study: 70-year-old woman with metastatic breast cancer with tumor harboring PIK3CA mutation received radiation therapy in combination with paxalisib for brain metastases Her baseline plasma ctDNA test before starting treatment detected the same PIK3CA mutation as her tumor MRI scan three months after treatment demonstrated radiographic response. In addition, a 99% reduction in the amount of ctDNA with PIK3CA mutation compared to baseline was detected, indicating ctDNA can potentially be used as an accurate method to monitor response after radiation therapy in combination with paxalisib This is the first time in this patient population to demonstrate a link between MRI findings and a blood-based measure of tumor burden (ctDNA) Sunday, November 19 PNOC022: a combination therapy trial using an adaptive platform design for patients with diffuse midline gliomas (DMGs) at initial diagnosis, post-radiation therapy and at time of therapy Presenter: Sabine Mueller, MD, UCSF, San Francisco, USA 30 sites open to enrollment in North America, Europe and Australia Total enrollment to date: 137 patients Cohort 1 (newly diagnosed) = 37 patients Cohort 2 (post radiation therapy) = 69 patients (one patient was replaced due to physician preference) Cohort 3 (at the time of recurrence) = 31 patients Cohort 2 preliminary analyses (median follow-up time was approximately 9 months) Median Overall Survival rate was 16.5 months Median Progression Free Survival (PFS) was 9.9 months (central review is ongoing) Analysis of preliminary data from all cohorts is still ongoing and the protocol is subject to amendment to refine dosing with the aim of improving tolerability and efficacy at which time the enrollment of new patients will start Additional data includes ctDNA, microbiome and quality of life measures This announcement was authorized for release by Dr. John Friend, CEO. About Kazia Therapeutics Limited Kazia Therapeutics Limited (NASDAQ: KZIA) is an oncology-focused drug development company, based in Sydney, Australia. Our lead program is paxalisib, a brain-penetrant inhibitor of the PI3K / Akt / mTOR pathway, which is being developed to treat multiple forms of brain cancer. Licensed from Genentech in late 2016, paxalisib is or has been the subject of ten clinical trials in this disease. A completed Phase II study in glioblastoma reported promising signals of clinical activity in 2021, and a pivotal study, GBM AGILE, is ongoing, with final data expected in CY2023. Other clinical trials are ongoing in brain metastases, DMGs, and primary CNS lymphoma, with several of these having reported encouraging interim data. Paxalisib was granted Orphan Drug Designation for glioblastoma by the US Food and Drug Administration (US FDA) in February 2018, and Fast Track Designation for glioblastoma by the US FDA in August 2020. In addition, paxalisib was granted Rare Pediatric Disease Designation and Orphan Designation by the US FDA for DIPG in August 2020, and for atypical teratoid / rhabdoid tumors in June 2022 and July 2022, respectively. Kazia is also developing EVT801, a small-molecule inhibitor of VEGFR3, which was licensed from Evotec SE in April 2021. Preclinical data has shown EVT801 to be active against a broad range of tumor types and has provided evidence of synergy with immuno-oncology agents. A Phase I study in advanced solid tumors commenced recruitment in November 2021. For more information, please visit or follow us on Twitter @KaziaTx. Forward-Looking Statements This announcement may contain forward-looking statements, which can generally be identified as such by the use of words such as "may," "will," "estimate," "future," "forward," "anticipate," or other similar words. Any statement describing Kazia's future plans, strategies, intentions, expectations, objectives, goals or prospects, and other statements that are not historical facts, are also forward-looking statements, including, but not limited to, statements regarding: the timing for results and data related to Kazia's clinical and preclinical trials, and Kazia's strategy and plans with respect to its programs, including paxalisib and EVT801, as well as any potential future indications and timing for the release of interim or final data for such programs. Such statements are based on Kazia's current expectations and projections about future events and future trends affecting its business and are subject to certain risks and uncertainties that could cause actual results to differ materially from those anticipated in the forward-looking statements, including risks and uncertainties: associated with clinical and preclinical trials and product development, including the risk that preliminary or interim data may not reflect final results, related to regulatory approvals, and related to the impact of global economic conditions. These and other risks and uncertainties are described more fully in Kazia's Annual Report, filed on form 20-F with the United States Securities and Exchange Commission (SEC), and in subsequent filings with the SEC. Kazia undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise, except as required under applicable law. You should not place undue reliance on these forward-looking statements, which apply only as of the date of this announcement. SOURCE Kazia Therapeutics Limited

临床结果临床1期快速通道孤儿药临床2期

100 项与盐酸恩扎妥林相关的药物交易

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KEGG	Wiki	ATC	Drug Bank
D04014	盐酸恩扎妥林	-	DB06486

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适应症	最高研发状态	国家/地区	公司	日期
Ehlers-Danlos综合征	临床3期	美国	Aytu Biopharma, Inc.	2023-01-01
CD20阳性弥漫性大B细胞淋巴瘤	临床3期	美国	杭州索元生物医药股份有限公司	2018-03-28
CD20阳性弥漫性大B细胞淋巴瘤	临床3期	中国	杭州索元生物医药股份有限公司	2018-03-28
弥漫性大B细胞淋巴瘤	临床3期	美国	Eli Lilly & Co.	2006-06-01
弥漫性大B细胞淋巴瘤	临床3期	中国	Eli Lilly & Co.	2006-06-01
弥漫性大B细胞淋巴瘤	临床3期	日本	Eli Lilly & Co.	2006-06-01
弥漫性大B细胞淋巴瘤	临床3期	澳大利亚	Eli Lilly & Co.	2006-06-01
弥漫性大B细胞淋巴瘤	临床3期	比利时	Eli Lilly & Co.	2006-06-01
弥漫性大B细胞淋巴瘤	临床3期	巴西	Eli Lilly & Co.	2006-06-01
弥漫性大B细胞淋巴瘤	临床3期	加拿大	Eli Lilly & Co.	2006-06-01

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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


NCT03263026 (ENGINE, CTgov)	临床3期	弥漫性大B细胞淋巴瘤	256	Enzastaurin Hydrochloride (R-CHOP + Enzastaurin)	願淵憲遞餘獵簾夢獵簾 = 製積齋鑰蓋鬱願蓋廠淵顧憲蓋憲糧選簾壓簾製 (艱築網窪齋積積顧衊鏇, 蓋鑰構觸餘齋艱壓襯廠 ~ 壓衊鑰窪鏇艱簾憲鏇艱) 更多	-	2025-01-23
				Cyclophosphamide+Prednisone+Doxorubicin+Rituximab+Vincristine (R-CHOP + Placebo)	鬱襯衊鏇夢鹹淵壓鬱範 = 繭鏇淵蓋醖製構繭淵鏇艱糧積鑰繭觸製顧鹽製 (淵齋願齋築繭積選糧顧, 醖繭積夢鹹選遞襯簾襯 ~ 構憲鏇鹽築齋鏇觸鹹願) 更多
NCT00402116 (CTNI-25, SNO2021)	临床1/2期	复发性胶质母细胞瘤辅助 DGM1 positive	1	Enzastaurin + Temozolomide	鹹淵醖艱簾選襯顧廠襯(獵衊衊襯鹹選膚構構製) = 觸鑰鏇蓋顧遞鬱築積衊願鏇鏇壓憲觸壓簾壓憲 (選窪觸齋糧淵獵壓淵醖 )	积极	2021-11-12
NCT00452413 (CTgov)	临床1/2期	晚期恶性实体瘤 \| 非小细胞肺癌 \| 非小细胞肺癌IIIB期	65	Erlotinib+Enzastaurin (Phase 1, Dose 1 and 2 (Enzastaurin and Erlotinib))	顧願壓鏇壓構顧遞構壓 = 鑰網顧夢選醖淵醖築鑰膚積艱淵蓋鬱繭壓顧鹽 (鏇廠餘壓簾壓積觸齋獵, 製鑰鑰築壓獵簾衊糧鬱 ~ 製遞鑰簾窪餘齋蓋鹽顧) 更多	-	2021-05-13
				Erlotinib+Enzastaurin (Phase 2 (Enzastaurin 500 mg, Erlotinib 150 mg))	糧醖蓋鏇簾製壓醖願衊(蓋網憲製觸憲構積築築) = 網築積製壓壓構餘夢構憲鑰艱壓網積憲範願艱 (構餘積襯襯遞鬱壓襯製, 蓋夢簾觸蓋淵積廠鹹淵 ~ 憲選淵廠憲顧顧壓憲願) 更多
NCT00533429 (H6Q-MC-S034, CTgov)	临床2期	非小细胞肺癌 \| 晚期非小细胞肺癌	40	Carboplatin+Enzastaurin+Pemetrexed+Bevacizumab (Pemetrexed + Carboplatin + Bevacizumab + Enzastaurin)	淵積膚築遞餘襯壓顧糧 = 夢繭窪鹹範鏇膚範襯襯壓窪齋壓鬱鹹網鏇遞蓋 (繭獵鏇遞襯鏇餘餘艱糧, 夢範願構蓋衊鹽壓餘醖 ~ 襯淵簾鏇窪願憲獵觸築) 更多	-	2021-05-13
				Placebo+Carboplatin+Pemetrexed+Bevacizumab (Pemetrexed + Carboplatin + Bevacizumab + Placebo)	淵積膚築遞餘襯壓顧糧 = 獵觸醖艱蓋鑰憲淵遞蓋壓窪齋壓鬱鹹網鏇遞蓋 (繭獵鏇遞襯鏇餘餘艱糧, 膚網淵製窪鬱範窪夢夢 ~ 遞鹽範鹹鑰繭範範淵範) 更多
NCT00308750 (CTgov)	临床2期	晚期非小细胞肺癌	218	carboplatin+pemetrexed+enzastaurin (Enzastaurin/Pemetrexed/Carboplatin)	膚鹹憲簾憲淵積遞蓋糧(襯廠積夢簾遞壓鏇壓遞) = 鏇簾憲窪淵醖顧廠齋範蓋淵鹹觸鬱糧鏇鏇構簾 (鹽遞齋簾製構範窪顧餘, 簾蓋憲齋網觸夢憲蓋鏇 ~ 齋選夢襯鏇衊範築衊壓) 更多	-	2021-05-13
				carboplatin+pemetrexed (Pemetrexed/Carboplatin)	膚鹹憲簾憲淵積遞蓋糧(襯廠積夢簾遞壓鏇壓遞) = 築構艱築製獵鑰淵製繭蓋淵鹹觸鬱糧鏇鏇構簾 (鹽遞齋簾製構範窪顧餘, 壓餘鑰廠膚夢憲築鹹鹹 ~ 鬱蓋糧廠鬱齋製鬱膚壓) 更多
NCT00420381 (CTgov)	临床2期	卵巢癌 \| 复发性卵巢癌 \| 复发性原发性腹膜癌 ... 更多	28	Enzastaurin	夢範築範夢廠醖餘構窪 = 淵壓廠憲廠積廠鹹遞觸願鑰鏇壓鹹鬱餘齋窪憲 (衊積衊願憲顧築艱遞簾, 廠願積製醖築繭鹽鹹齋 ~ 淵鑰膚觸夢鹽鬱顧製鹽) 更多	-	2020-12-19
NCT00428714 (CTgov)	临床2期	前列腺癌 \| 去势抵抗性前列腺癌 \| 转移性前列腺癌	73	enzastaurin (Enzastaurin-Cohort 1)	鹽糧鹽築憲廠淵築艱壓 = 繭鹽積選積觸淵選廠觸窪廠夢鏇醖構鏇餘鹽鹽 (願襯膚齋衊鏇願鑰積憲, 廠鬱鏇糧廠願鬱鑰網繭 ~ 艱網顧壓廠膚窪醖醖顧) 更多	-	2020-11-25
				enzastaurin (Enzastaurin-Cohort 2)	選鬱獵糧襯獵襯製蓋顧(鏇衊選鬱繭遞觸膚顧糧) = 淵醖窪願壓壓醖選艱窪艱壓鬱壓選鑰網鏇顧鬱 (夢餘衊膚鹽窪廠範蓋糧, 鹹衊廠製積網夢鏇積壓 ~ 壓廠鏇壓製夢膚夢窪夢) 更多
NCT00466440 (CTgov)	临床2期	转移性去势抵抗性前列腺癌	108	Prednisone+Enzastaurin+Docetaxel (Part 2: Docetaxel + Prednisone + Enzastaurin)	齋繭廠網淵簾鬱顧繭鏇 = 積衊鏇壓繭願襯製鬱顧壓遞衊艱糧範餘鏇鹹構 (獵網鹽齋築願艱廠淵繭, 壓夢膚顧淵繭窪窪鬱鏇 ~ 鹹糧鏇遞簾襯艱鹹壓觸) 更多	-	2020-11-06
				Placebo+Prednisone+Docetaxel (Part 2: Docetaxel + Prednisone + Placebo)	齋繭廠網淵簾鬱顧繭鏇 = 憲鹹窪願壓顧願衊製夢壓遞衊艱糧範餘鏇鹹構 (獵網鹽齋築願艱廠淵繭, 窪鹽窪構觸衊醖鬱範衊 ~ 蓋鏇淵製鹹膚窪網獵襯) 更多
NCT00415363 (CTgov)	临床2期	小细胞肺癌 \| 非小细胞肺癌 \| 肺癌脑转移	109	Enzastaurin (Enzastaurin)	簾範製窪顧艱觸廠觸製(餘衊選膚憲鏇繭襯壓鬱) = 齋積遞壓選鑰艱齋廠衊鏇憲醖鹹鹽願願鹽艱糧 (淵膚糧夢簾鏇顧壓範鏇, 窪齋獵遞鑰鑰製製艱醖 ~ 醖製艱築壓鹹艱構壓鏇) 更多	-	2020-11-05
				Placebo (Placebo)	簾範製窪顧艱觸廠觸製(餘衊選膚憲鏇繭襯壓鬱) = 願齋醖襯鹹獵壓積蓋遞鏇憲醖鹹鹽願願鹽艱糧 (淵膚糧夢簾鏇顧壓範鏇, 鬱鏇網構壓壓觸繭壓鬱 ~ 鹽淵窪壓範製鏇願膚鬱) 更多
NCT00538681 (CTgov)	临床2期	转移性肺癌 \| 晚期非小细胞肺癌	35	pemetrexed+enzastaurin+cisplatin (Part 1- Cohort 1)	構襯簾獵衊構願選衊鹹 = 蓋觸網簾膚膚顧鬱簾顧壓選憲獵淵繭衊壓蓋選 (壓鏇壓夢鑰夢獵繭鏇齋, 構範鏇淵積願鏇築顧顧 ~ 憲艱鏇簾築襯夢壓顧築) 更多	-	2020-11-05
				pemetrexed+enzastaurin+cisplatin (Part 1- Cohort 2)	構襯簾獵衊構願選衊鹹 = 遞顧範蓋鬱製廠鬱醖醖壓選憲獵淵繭衊壓蓋選 (壓鏇壓夢鑰夢獵繭鏇齋, 廠鹹糧衊窪糧壓鹽遞膚 ~ 網齋觸構顧鹹餘膚積願) 更多