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]

EUCTR2021-006574-23-BE

/ Unknown status临床3期

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) - PREVEnt (Prevention of Rupture with Enzastaurin in Vascular Ehlers-Danlos Syndrome Trial)

开始日期2022-06-20

申办/合作机构

Aytu Biopharma, Inc.

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]

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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263

项与盐酸恩扎妥林相关的文献（医药）

2024-12-01·BIOCHEMICAL PHARMACOLOGY

Epoxytiglianes induce keratinocyte wound healing responses via classical protein kinase C activation to promote skin re-epithelialization

Article

作者: Johns, Jenny P. ; Dally, Jordanna ; Steadman, Robert ; Moses, Rachael L. ; Gordon, Victoria ; Boyle, Glen M. ; Johns, Jenny P ; Boyle, Glen M ; Knäuper, Vera ; Reddell, Paul ; Moseley, Ryan ; Woods, Emma L ; Woods, Emma L. ; Moses, Rachael L

Epoxytiglianes are a novel class of diterpene esters. The prototype epoxytigliane, EBC-46 (tigilanol tiglate), is a potent anti-cancer agent in clinical development for local treatment of a range of human and animal tumors. EBC-46 also consistently promotes wound re-epithelialization at the treatment sites, mediated via activation of classical protein kinase C (PKC) isoforms. We have previously shown that epoxytiglianes stimulate proliferative and wound repopulation responses in immortalized human skin keratinocytes (HaCaTs) in vitro, abrogated by pan-PKC inhibitor, bisindolylmaleimide-1. In this study, we further investigate the specific PKC isoforms responsible for inducing such wound healing responses, following HaCaT treatment with 1.51 nM-15.1 µM EBC-46 or analogue, EBC-211. Classical PKC inhibition by GӦ6976 (1 μM), significantly attenuated epoxytigliane induced, HaCaT proliferation and wound repopulation at all epoxytigliane concentrations. PKC-βI/-βII isoform inhibition by enzastaurin (1 μM), significantly inhibited HaCaT proliferation and wound repopulation responses induced by both epoxytiglianes, especially at 1.51-151 nM. PKC-α inhibitor, Ro 31-8220 mesylate (10 nM), exerted lesser inhibitory effects on HaCaT responses. Epoxytigliane changes in key keratin (KRT17) and cell cycle (cyclin B1, CDKN1A) protein levels were partly attenuated by GӦ6976 and enzastaurin. GӦ6976 also inhibited increases in matrix metalloproteinase (MMP-1, MMP-7, MMP-10) activities. Phospho-PKC (p-PKC) studies confirmed that epoxytiglianes transiently activated classical PKC isoforms (p-PKCα, p-PKC-βI/-βII, p-PKCγ) in a dose- and time-dependent manner. By identifying how epoxytiglianes stimulate classical PKCs to facilitate keratinocyte healing responses and re-epithelialization, these findings support further epoxytigliane development as topical therapeutics for clinical situations involving impaired re-epithelialization, such as non-healing wounds in skin.

2024-06-01·Gene

Identification of hub genes and potential therapeutic mechanisms related to HPV positive head and neck squamous carcinoma based on full transcriptomic detection and ceRNA network construction

Article

作者: Zhang, Xinran ; Li, Rui ; Zhang, Tingting ; Deng, Jiayin ; Pan, Boyu ; Wang, Kunpeng ; Li, Xia

Infection with human papillomavirus (HPV) is a major risk factor for head and neck squamous cell carcinoma (HNSCC). The objective of this study is to investigate the gene expression profiles and signaling pathways that are specific to HPV-positive HNSCC (HPV⁺ HNSCC). Moreover, a competing endogenous RNA (ceRNA) network analysis was utilized to identify the core gene of HPV⁺ HNSCC and potential targeted therapeutic drugs. Transcriptome sequencing analysis identified 3,253 coding RNAs and 3,903 non-coding RNAs (ncRNAs) that exhibited preferentially expressed in HPV⁺ HNSCC. Four key signaling pathways were selected through pathway enrichment analysis. By combining ceRNA network and protein-protein interaction (PPI) network topology analysis, RNA Polymerase II Associated Protein 2 (RPAP2), which also exhibited high expression in HPV⁺ HNSCC based on the TCGA database, was identified as the hub gene. Gene set enrichment analysis (GSEA) results revealed RPAP2's involvement in various signaling pathways, encompassing basal transcription factors, ubiquitin-mediated proteolysis, adherens junction, other glycan degradation, ATP-binding cassette (ABC) transporters, and oglycan biosynthesis. Five potential small molecule targeted drugs (enzastaurin, brequinar, talinolol, phenylbutazone, and afuresertib) were identified using the cMAP database, with enzastaurin showing the highest affinity for RPAP2. Cellular functional experiments confirmed the inhibitory effect of enzastaurin on cell viability of HPV⁺ HNSCC and RPAP2 expression levels. Additionally, enzastaurin treatment suppressed the expression levels of the top-ranked long non-coding RNA (lncRNA), circular RNA (circRNA), and microRNA (miRNA) in the ceRNA network. This study based on the ceRNA network provides valuable insights into the molecular mechanisms and potential therapeutic strategies for HPV⁺ HNSCC, and provide theoretical basis for the exploration of HPV⁺ HNSCC biomarkers and the development of targeted drugs.

2024-03-15·The Journal of clinical investigation

PI3K/mTOR is a therapeutically targetable genetic dependency in diffuse intrinsic pontine glioma

Article

作者: Hulleman, Esther ; Manning, Elizabeth E ; Vilain, Ricardo E ; de Bock, Charles E ; Germon, Zacary P ; Dayas, Christopher V ; Findlay, Izac J ; Firestein, Ron ; Hua, Susan ; Jackson, Evangeline R ; Beitaki, Tyrone ; Aksu, Michael ; Colino-Sanguino, Yolanda ; Cairns, Murray J ; Parackal, Sarah G ; Kilburn, Lindsay B ; Jamaluddin, M Fairuz B ; Whittle, James R ; Ashley, David M ; Sun, Claire Xin ; Hocke, Emily A ; Murray, Heather C ; McEwen, Holly P ; Laternser, Sandra ; Kiltschewskij, Dylan ; Dun, Matthew D ; Nixon, Brett ; Daniel, Paul ; Valvi, Santosh ; Koschmann, Carl ; Duchatel, Ryan J ; Eisenstat, David D ; Jain, Vaibhav ; Mueller, Sabine ; Wheeler, Helen ; Nazarian, Javad ; Mannan, Abdul ; Gregory, Simon G ; Tsoli, Maria ; Raabe, Eric H ; Thomas, Bryce C ; Tinkle, Christopher L ; Persson, Mika L ; Phoenix, Timothy N ; Valdes-Mora, Fatima ; Douglas, Alicia M ; Skerrett-Byrne, David A ; Ziegler, David S ; Hansford, Jordan R ; Staudt, Dilana E ; Vitanza, Nicholas A ; Kearney, Padraic S ; Cain, Jason E ; Alvaro, Frank ; Verrills, Nicole M

Diffuse midline glioma (DMG), including tumors diagnosed in the brainstem (diffuse intrinsic pontine glioma; DIPG), are uniformly fatal brain tumors that lack effective treatment. Analysis of CRISPR/Cas9 loss-of-function gene deletion screens identified PIK3CA and MTOR as targetable molecular dependencies across patient derived models of DIPG, highlighting the therapeutic potential of the blood-brain barrier-penetrant PI3K/Akt/mTOR inhibitor, paxalisib. At the human-equivalent maximum tolerated dose, mice treated with paxalisib experienced systemic glucose feedback and increased insulin levels commensurate with patients using PI3K inhibitors. To exploit genetic dependence and overcome resistance while maintaining compliance and therapeutic benefit, we combined paxalisib with the antihyperglycemic drug metformin. Metformin restored glucose homeostasis and decreased phosphorylation of the insulin receptor in vivo, a common mechanism of PI3K-inhibitor resistance, extending survival of orthotopic models. DIPG models treated with paxalisib increased calcium-activated PKC signaling. The brain penetrant PKC inhibitor enzastaurin, in combination with paxalisib, synergistically extended the survival of multiple orthotopic patient-derived and immunocompetent syngeneic allograft models; benefits potentiated in combination with metformin and standard-of-care radiotherapy. Therapeutic adaptation was assessed using spatial transcriptomics and ATAC-Seq, identifying changes in myelination and tumor immune microenvironment crosstalk. Collectively, this study has identified what we believe to be a clinically relevant DIPG therapeutic combinational strategy.

项与盐酸恩扎妥林相关的新闻（医药）

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

2022-12-09

·PRNewswire

Global Molecular Oncology Diagnostics Market to Reach $12.13 Billion by 2032 - Exclusive DeepTech M-A-P™ Analysis by BIS Research

Emerging technologies such as microarray are also expected to be integrated more into molecular oncology diagnostics soon, which is expected to further boost the market growth. FREMONT, Calif., Dec. 9, 2022 /PRNewswire/ -- BIS Research, the global leader in providing market intelligence on deep technologies, has released its latest study titled Molecular Oncology Diagnostics Market - A Global and Regional Analysis. According to this study, the market for global molecular oncology diagnostics was valued at $3.62 billion in 2021 and is projected to reach $12.13 billion by 2032. The following factors are responsible for the increase in demand for molecular oncology diagnostics: Rising incidence of cancer cases Launch of innovative products in the molecular oncology diagnostics ecosystem Growth in biomarker identification and transformations in molecular techniques The detailed study is a compilation of 3 market data tables and 206 figures spread through 264 pages. Check out the detailed table of content here Analyst's Take on the Market Projection According to Nitish Kumar, Principal Consultant, Healthcare, BIS Research, "Although there have been significant innovations for the enhancement of all the important areas of diagnostics, molecular diagnostics, particularly, has harbored phenomenal attention in recent years owing to the in-depth insights they bring to diagnosis and treatment. As the next frontier of precision medicine, the global molecular oncology diagnostics market is expected to showcase enormous potential to completely revolutionize patient care and overall wellness in general." Request a FREE sample of this report here Existing Competitive Landscape The companies that are profiled have been selected based on input gathered from primary experts and analyzing company coverage, product portfolio, and market penetration. Some of the established names in the market are Agilent Technologies, Inc., Abbott, Biocartis NV, Bio-Rad Laboratories, Inc., F. Hoffmann-La Roche Ltd., QIAGEN N.V., Thermo Fisher Scientific, Inc., Danaher, Guardant Health, HTG Molecular Diagnostics, Inc., Illumina, Inc., Invivoscribe, Inc., Myriad Genetics, Inc., Sysmex Corporation, and more. Recent Developments in the Global Molecular Oncology Diagnostics Market In August 2022, Guardant Health expanded its Guardant Reveal usage, a liquid biopsy test for residual disease detection and recurrence monitoring, to include early-stage breast and lung cancers. It is the only tissue-free test used for colorectal cancer (CRC) and is now available for patients with breast and lung cancer. In December 2021, QIAGEN partnered with Denovo Biopharma to develop a companion diagnostic test for the treatment of diffuse large B-cell lymphoma. This test identified patients expressing Denovo genomic marker 1 (DGM1), which responded to Denovo's investigational cancer drug DB102. In September 2021, Illumina partnered with Merck to develop and commercialize research tests for use in identifying specific cancer genetic mutations used in the assessment of homologous recombination deficiency (HRD). In August 2021, Agilent Technologies, Inc. expanded its CE-IVD marked PD-L1 IHC 22C3 pharmDx assay usage in Europe. This assay was used as an aid in identifying esophageal cancer patients for treatments with KEYTRUDA using a combined positive score. Polymerase Chain Reaction Technology Type to Witness the Highest Market Growth The global market for molecular oncology diagnostics (by technology) has been divided into six categories, i.e., next-generation sequencing (NGS), polymerase chain reaction (PCR), fluorescence in-situ hybridization (FISH), immunohistochemistry (IHC), flow cytometry, and others. These rapidly evolving technologies have the potential to transform medical diagnoses and treatment for the better. Not only are developing diagnostic tools becoming more useful in a wider range of clinical scenarios, but they are also assisting in a more exploratory outlook in order to cater to a holistic approach to cancer treatment. According to this study from BIS Research, the PCR segment dominated the technology market in 2021 with a cumulative value of $1.20 billion, and the trend is expected to continue during the forecast period 2022-2032. Want to learn more about the latest trends in precision medicine? Speak to our analysts Exclusive DeepTechTM MAP Analysis for Healthcare by BIS Research: Molecular Diagnostics Market About BIS Research: BIS Research is a global B2B market intelligence and advisory firm focusing on deep technology and related emerging trends which can disrupt the market dynamics in the near future. We publish more than 200 market in telligence studies annually that focus on several deep technology verticals. Our strategic market analysis emphasizes on market estimations, technology analysis, emerging high-growth applications, deeply segmented granular country-level market data, and other important market parameters useful in the strategic decision-making for senior management. BIS Research offers syndicate as well as custom studies and expert consultations to firms, providing them with specific and actionable insights on novel technology markets, business models, and competitive landscapes. Contact: Bhavya Banga Email: [email protected] Ph no: 1-510-404-8135 BIS Research Inc. 39111 PASEO PADRE PKWY STE 313, FREMONT CA 94538-1686 Visit our Blog @ Get Expert Insights @ Connect with us on LinkedIn @ Connect with us on [email protected] Logo: SOURCE BIS Research

诊断试剂

100 项与盐酸恩扎妥林相关的药物交易

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外链

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

研发状态

10 条进展最快的记录,

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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
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
弥漫性大B细胞淋巴瘤	临床3期	捷克	Eli Lilly & Co.	2006-06-01
弥漫性大B细胞淋巴瘤	临床3期	丹麦	Eli Lilly & Co.	2006-06-01

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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


NCT03263026 (ENGINE, CTgov)	临床3期	弥漫性大B细胞淋巴瘤	256	Enzastaurin Hydrochloride (R-CHOP + Enzastaurin)	艱衊獵網鑰蓋蓋鹹獵膚(製鑰鏇醖鹽鏇醖醖壓壓) = 鹹鑰夢範壓窪蓋餘襯鹹齋選遞壓積廠製範齋鬱 (構夢壓餘糧鏇廠網鬱艱, 繭鹹糧簾繭鏇衊憲築衊 ~ 鏇製構選夢網簾繭艱簾) 更多	-	2025-01-23
				Cyclophosphamide+Prednisone+Doxorubicin+Rituximab+Vincristine (R-CHOP + Placebo)	鏇艱構獵鏇壓衊襯衊獵(襯鏇膚鏇顧衊鏇鑰觸夢) = 製醖憲艱衊網鹽蓋齋夢醖簾壓選遞鹽鏇壓繭鑰 (構膚製鏇餘艱鏇淵鏇遞, 衊繭積範簾鬱醖願繭醖 ~ 鹽鑰艱糧獵糧鹽衊選廠) 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	構餘夢淵獵艱繭積艱憲(網糧遞鏇衊衊獵築選選) = 鑰鹹壓選範膚積艱淵範鹹衊觸窪觸餘憲鑰簾積 (獵蓋襯憲廠襯選蓋鏇製 )	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	65	Erlotinib+Enzastaurin (Phase 1, Dose 1 and 2 (Enzastaurin and Erlotinib))	觸淵網獵衊鑰繭膚淵夢(網遞襯廠簾蓋鏇餘鏇憲) = 鏇廠窪廠遞糧窪襯窪壓壓蓋鹹淵醖製衊壓鹹構 (鹹網觸獵鏇夢鏇觸窪衊, 繭製齋襯窪範齋繭顧膚 ~ 艱醖膚鏇夢繭網壓遞繭) 更多	-	2021-05-13
				Erlotinib+Enzastaurin (Phase 2 (Enzastaurin 500 mg, Erlotinib 150 mg))	襯製鹹鬱醖襯構遞築鹹(襯壓壓膚淵繭顧蓋憲糧) = 鑰顧網齋選築顧構壓膚窪齋繭衊膚糧蓋鬱艱繭 (顧廠構膚築膚簾築窪淵, 範築積窪淵獵觸鏇壓衊 ~ 範鬱構餘窪窪築糧積齋) 更多
NCT00308750 (CTgov)	临床2期	非小细胞肺癌	218	carboplatin+enzastaurin+pemetrexed (Enzastaurin/Pemetrexed/Carboplatin)	鏇膚鹹蓋壓艱築範鏇廠(糧鑰鑰網憲鏇憲築積繭) = 壓鑰蓋觸窪鑰選鹹淵鏇積醖選膚鬱鏇網構網鹽 (餘窪製壓鏇憲觸襯繭願, 築範願夢憲蓋夢淵壓鏇 ~ 獵餘鏇顧憲窪繭願觸觸) 更多	-	2021-05-13
				carboplatin+pemetrexed (Pemetrexed/Carboplatin)	鏇膚鹹蓋壓艱築範鏇廠(糧鑰鑰網憲鏇憲築積繭) = 窪廠餘鹽鹽艱淵鏇獵壓積醖選膚鬱鏇網構網鹽 (餘窪製壓鏇憲觸襯繭願, 顧願鏇醖簾廠衊觸糧醖 ~ 鏇鑰艱簾觸鏇廠願醖網) 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+Bevacizumab+Pemetrexed (Pemetrexed + Carboplatin + Bevacizumab + Enzastaurin)	壓襯願膚鹹鏇觸夢構壓(衊襯襯鹹繭餘構醖膚選) = 鹹窪繭淵選襯醖醖夢壓蓋鏇積獵蓋鑰糧齋鑰膚 (選製夢範鬱簾襯簾範衊, 鑰壓膚膚繭夢遞構構築 ~ 廠淵築窪範膚醖鬱蓋壓) 更多	-	2021-05-13
				Placebo+Carboplatin+Bevacizumab+Pemetrexed (Pemetrexed + Carboplatin + Bevacizumab + Placebo)	壓襯願膚鹹鏇觸夢構壓(衊襯襯鹹繭餘構醖膚選) = 鹹艱製遞構憲繭鬱鹹鑰蓋鏇積獵蓋鑰糧齋鑰膚 (選製夢範鬱簾襯簾範衊, 廠鹹衊選壓襯齋淵蓋遞 ~ 憲觸鏇襯鑰蓋遞夢齋願) 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	範蓋願餘糧選網膚鏇鏇(蓋衊壓餘範艱窪鏇齋襯) = 糧繭糧製觸遞鏇廠鏇願鹹製壓遞獵選範簾餘鏇 (選鏇餘艱顧鹽襯製廠壓, 齋積憲積鹽鹽觸鏇製鹽 ~ 鏇夢窪壓壓鑰簾網範製) 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)	簾淵鏇顧獵獵衊鏇艱衊(糧齋廠衊觸構壓獵顧積) = 願築鬱膚窪膚壓簾選範壓顧憲壓壓艱鏇觸壓簾 (遞範淵衊鑰鬱鏇製廠願, 鹽觸網夢網夢鏇築選衊 ~ 觸範廠繭獵網蓋繭鏇齋) 更多	-	2020-11-25
				enzastaurin (Enzastaurin-Cohort 2)	窪淵膚鬱襯積築蓋淵餘(獵淵鬱顧夢築窪鹹構衊) = 鑰範鬱廠繭願膚獵觸艱窪顧製網選範鏇艱齋選 (艱餘艱襯醖夢餘鹹簾築, 製醖糧衊範簾鹹鹽襯膚 ~ 鹽積夢糧窪網獵窪憲廠) 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)	廠繭製構衊顧鹽衊夢簾(遞鬱憲顧夢憲繭選襯選) = 齋醖糧觸憲壓艱蓋鹽鹹網網齋簾夢範衊艱壓顧 (膚餘膚淵鬱鏇糧蓋願積, 壓廠顧壓蓋窪積鏇選觸 ~ 獵醖積製鹽齋壓網簾繭) 更多	-	2020-11-06
				Placebo+Prednisone+Docetaxel (Part 2: Docetaxel + Prednisone + Placebo)	廠繭製構衊顧鹽衊夢簾(遞鬱憲顧夢憲繭選襯選) = 鹽製夢衊壓廠醖艱淵艱網網齋簾夢範衊艱壓顧 (膚餘膚淵鬱鏇糧蓋願積, 蓋鬱鑰廠衊窪鬱淵範鏇 ~ 範鏇簾網醖鹽鑰醖醖淵) 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)	範顧餘製簾壓蓋艱顧鬱(築積壓廠醖艱糧膚窪衊) = 鬱鑰蓋鬱製廠襯遞願夢獵觸蓋繭鏇糧願積範襯 (膚蓋遞夢簾餘餘膚鏇積, 鹽網鹽築簾範齋鏇膚淵 ~ 構積夢廠顧積淵衊繭顧) 更多	-	2020-11-05
				Placebo (Placebo)	範顧餘製簾壓蓋艱顧鬱(築積壓廠醖艱糧膚窪衊) = 窪願襯簾衊鬱網獵獵糧獵觸蓋繭鏇糧願積範襯 (膚蓋遞夢簾餘餘膚鏇積, 鹽膚艱餘醖襯範窪鹽廠 ~ 顧膚遞築蓋範餘範膚築) 更多
NCT00538681 (CTgov)	临床2期	转移性肺癌	35	enzastaurin+cisplatin+pemetrexed (Part 1- Cohort 1)	鬱壓遞壓構衊鏇獵膚遞(鹹積觸簾鏇顧鏇築餘鏇) = 壓艱網繭鹽遞觸膚製鹽製鏇餘淵糧遞蓋構鹽糧 (窪遞選網鑰製簾鏇遞憲, 廠膚網醖艱壓遞艱艱鏇 ~ 網鏇觸製淵衊築遞襯積) 更多	-	2020-11-05
				enzastaurin+cisplatin+pemetrexed (Part 1- Cohort 2)	鬱壓遞壓構衊鏇獵膚遞(鹹積觸簾鏇顧鏇築餘鏇) = 繭憲顧鏇鏇築鬱糧憲獵製鏇餘淵糧遞蓋構鹽糧 (窪遞選網鑰製簾鏇遞憲, 醖選襯鏇衊齋製餘築窪 ~ 艱襯觸壓獵廠鹹獵壓淵) 更多