A Pilot Window of Opportunity Study Evaluating Durvalumab (MEDI4736) in Combination With Platinum Doublet Chemotherapy Followed by Evaluation of Durvalumab (MEDI4736) in Combination With Platinum Doublet Chemotherapy and Abequolixron (RGX-104) in Non-small Cell Lung Cancer

Non-Small Cell Lung Cancer (NSCLC) is one of the deadliest types of cancer. In lung cancer patients with a tumor that can be removed by surgery, adjuvant chemotherapy increases survival. Neoadjuvant therapy may have advantages such as, it may be more tolerable prior to surgery, earlier treatment may be more efficacious, and it can provide an indication of treatment response. Neoadjuvant treatment can provide pre- and post-treatment specimens for correlative analysis to better understand mechanisms of action and resistance.
This pilot study will investigate the effects of neoadjuvant durvalumab plus platinum doublet chemotherapy and neoadjuvant durvalumab plus platinum doublet chemotherapy in combination with abequolixron (RGX-104), an LXR/ApoE agonist, in subjects with NSCLC who are scheduled to undergo surgical resection as part of their standard of care.
The purpose of this study is to study how well using a combination of durvalumab, platinum doublet chemotherapy (carboplatin/abraxane or carboplatin/pemetrexed), and abequolixron treats non-small cell lung cancer before surgery. Durvalumab (a type of immunotherapy) and platinum doublet chemotherapy are drugs that are individually approved for use during the treatment of cancer. FDA (Food and Drug Administration) has not approved the combined use of these drugs in treating non-small cell lung cancer. Abequolixron is not FDA approved for the treatment of cancer.

开始日期2024-04-01

申办/合作机构

UNC Lineberger Comprehensive Cancer Center

[+2]

NCT05983367 / Recruiting临床2期

A Randomized Phase 2 Study of Ompenaclid Versus Placebo in Combination With FOLFIRI Plus Bevacizumab in Patients With Previously Treated RAS Mutant Advanced or Metastatic Colorectal Cancer

The purpose of this study is to measure tumor response to treatment with ompenaclid (RGX-202) in patients with previously treated RAS mutant advanced or metastatic CRC. All patients will receive treatment with FOLFIRI and bevacizumab. In addition, patients will be randomized to receive either ompenaclid 3000 mg BID or matching placebo (herein referred to as Study Drug). Each treatment cycle is 28 days in duration.

开始日期2023-10-10

申办/合作机构

Inspirna, Inc.

CTIS2023-503356-27-00 / Recruiting

A randomized Phase 2 Study of ompenaclid versus placebo in combination with FOLFIRI plus bevacizumab in patients with previously treated RAS mutant advanced or metastatic colorectal cancer - RGX-202-002

开始日期2023-10-02

申办/合作机构

Inspirna, Inc.

100 项与 Inspirna, Inc. 相关的临床结果

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0 项与 Inspirna, Inc. 相关的专利（医药）

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项与 Inspirna, Inc. 相关的文献（医药）

2021-10-08·Science advances1区 · 综合性期刊

Therapeutic targeting of SLC6A8 creatine transporter suppresses colon cancer progression and modulates human creatine levels

1区 · 综合性期刊

ArticleOA

作者: Rosen, Lee S. ; Takeda, Shugaku ; Gonsalves, Foster C. ; Tian, Helen S. ; McRee, Autumn J. ; Busby, Robert ; Hendifar, Andrew E. ; Barlas, Afsar ; Tavazoie, Sohail F. ; Manova-Todorova, Katia ; Kurth, Isabel ; Tavazoie, Masoud F. ; Cercek, Andrea ; Sridhar, Subhasree ; Loo, Jia Min ; Spector, Scott L. ; Andreu-Agullo, Celia ; Fakih, Marwan ; Yamaguchi, Norihiro ; Wasserman, Robert ; Szarek, Michael ; Strauss, James ; Raza, Syed ; Bendell, Johanna C.

RGX-202, a small-molecule creatine transporter SLC6A8 inhibitor, suppresses colorectal cancer and modulates human creatine levels.

2017-03-01·Genes and immunity4区 · 医学

Identification of differentially expressed miRNAs in alopecia areata that target immune-regulatory pathways

4区 · 医学

Letter

作者: Patel, A V ; Harel, S ; Wang, E H C ; Cela, C ; Tavazoie, M ; Christiano, A M ; Drill, E ; DeStefano, G M

Alopecia areata (AA) is an autoimmune condition that results in patchy to total hair loss due to an aberrant T-cell attack on the hair follicle.Epigenetic gene regulation mechanisms, particularly those involving microRNA (miRNA), in AA pathogenesis have not been well described.In this study, we investigated the differential expression of miRNAs in the lesional skin of the C3H/HeJ mouse model of AA.We performed a miRNA array using skin from five C3H/HeJ mice that developed AA spontaneously and five matched, normal-haired littermates.We identified a panel of (approx.) 100 miRNAs that showed significantly different expression profiles between the AA and control mice.Subsequently, we determined the predicted targets of the miRNAs by integrating in silico prediction-based tools for target gene anal. (MicroCosm Targets (Hinxton, UK) and DIANA LAB (Vari, Greece)) and pathway anal. (Ingenuity Pathway Anal., Redwood, CA, USA).We uncovered miRNAs with dysregulated expression within key miRNA-mRNA networks with well-defined roles in autoimmunity, such as significant upregulation of mmu-miR-155 in lesional skin.Together with the collective body of literature on this miRNA, overexpression of mmu-miR-155 may represent a hallmark feature in AA disease pathogenesis and across multiple autoimmune conditions.

项与 Inspirna, Inc. 相关的新闻（医药）

2024-07-17

·Business Wire

Meliora Therapeutics Announces Appointment of Biopharma Luminaries to Board of Directors

SAN FRANCISCO--( BUSINESS WIRE )--Meliora Therapeutics (“Meliora”), a machine learning therapeutics company developing novel and transformative cancer drugs, today announced the appointment of Dieter Weinand, former Chairman and CEO of Bayer Pharmaceuticals, as Meliora’s Chairman of the Board, and the appointment of Jean-Jacques Bienaimé, former Chairman and CEO of BioMarin, to Meliora’s Board of Directors as Independent Director. “We are thrilled to have Dieter Weinand and Jean-Jacques Bienaimé join Meliora’s Board of Directors,” stated David Li, Meliora co-founder and Chief Executive Officer. “Their expertise and leadership in drug development will be incredible assets to our company. I look forward to working closely with both to further Meliora’s vision of being the world’s leading machine learning oncology therapeutics company.” Dieter Weinand is an experienced business leader with over 30 years of experience in the pharmaceutical industry and the former CEO and Chairman of the Board of Bayer Pharmaceuticals. During a career stretching back over 30 years, he has held various responsibilities in general management, commercial, operational and strategic leadership roles, leading business operations in the Asia-Pacific region, Europe, the Middle East, Africa, Latin America and the United States, for companies including Bayer, Pfizer, Bristol-Myers Squibb, and Sanofi. He has also led the development, launch, and commercialization of products in various therapeutic areas, including cardiovascular diseases, oncology, dermatology, immunology, and respiratory and inflammatory diseases. He is currently Chairman of the Board of Replimune (REPL), Umoja, and Inspirna, and Executive Chairman of the Board of Mnemo Therapeutics. He earned an M.S. in pharmacology and toxicology from Long Island University, New York, and a B.A. in biology from Concordia College, New York. “I am very pleased to become Chairman of the Board for Meliora, a company which has the potential to make a significant clinical difference in cancer patients’ lives using its novel machine learning powered approach. I look forward to working together with David and the Meliora team to advance the company through its next stages of growth and to achieve its strategic business and pipeline objectives,” Mr. Weinand commented. Mr. Jean-Jacques Bienaimé has over three decades of experience in the biotechnology and pharmaceutical industries, most recently serving as Chairman and Chief Executive Officer of BioMarin Pharmaceuticals. He joined BioMarin in May 2005, when the company had a single marketed product and approximately $26 million in annual revenues. Under Mr. Bienaimé's leadership, BioMarin grew significantly, from about 300 US-only employees to more than 3,400 people in almost 80 countries around the world and over $2.4 billion in sales in 2023. Biomarin received 8 drug approvals by the FDA during this time period. Before joining BioMarin, Mr. Bienaimé spent years in similar executive roles at other pharmaceutical and biotech companies and currently serves on the board of directors for Incyte, Immunome, Owkin, and Keros. Mr. Bienaimé studied economics at the École de Commerce de Paris and received an M.B.A from the University of Pennsylvania. “I am excited to join the Meliora Board of Directors as they endeavor to bring transformative oncology therapeutics to the patients most in need through their ML-powered approach,” commented Mr. Bienaimé. “In my career, focusing on patients while leveraging the latest technology has been critical to success, and Meliora is highly aligned in this approach. I look forward to enhancing Meliora’s ability to execute on its compelling vision.” About Meliora Therapeutics Meliora Therapeutics is discovering and developing small molecule oncology therapies for high value cancer targets with its proprietary machine learning powered platform, AnchorOmics. Pairing the first multimodal, mechanism-of-action machine learning algorithm and a world-class team of scientists and engineers, Meliora is pioneering a novel approach to create life-changing therapies for cancer patients. San Francisco and Cambridge-based Meliora Therapeutics has raised $11 million to date and is led by leaders from the fields of AI, biotechnology, and drug discovery. For more information, please visit: www.melioratx.com

高管变更上市批准

2024-07-01

·CPHI制药在线

Xevinapant头颈鳞癌III期临床失败，默克肿瘤管线还有哪些储备？

关注并星标CPHI制药在线近日，德国默克集团宣布，其备受瞩目的IAP抑制剂Xevinapant与放化疗联合治疗局部晚期头颈癌的三期临床试验惨遭终止。该决定是基于独立数据监测委员会进行的期中分析而做出的，此分析认为该研究不太可能达到主要终点，即延长患者无事件生存期。这一突如其来的消息犹如一颗重磅炸弹，让市场对默克公司的前景产生了严重质疑，股价应声暴跌8%！除此以外，考虑到数据的完整性，默克还决定停止xevinapant联合放疗对比安慰剂联合放疗用于接受过手术切除的局部晚期头颈癌患者的III期X-Ray Vision研究。 Xevinapant是一款first-in-class高效口服小分子细胞凋亡蛋白抑制因子（IAP）的抑制剂。2021年3月，德国默克宣布与Debiopharm公司达成一项全球性许可协议，以约9亿欧元获得该药在全球范围内的开发和推广权益。彼时，Xevinapant被寄予厚望。在II期临床研究中，xevinapant加放化疗的患者五年生存率几乎是安慰剂的两倍（53% vs 28%）。2020年2月，它成为了首个获得FDA突破性疗法认定（Breakthrough Therapy Designation）的IAP抑制剂。结合目前的护理标准，用于先前未治疗的局部晚期头颈部鳞状细胞癌（LA SCCHN）。 Xevinapant及其II期临床研究结果简介图片来源：参考来源1 IAP蛋白高度表达且与多种癌症相联，包括肺癌、头颈癌、乳腺癌、胃肠癌，以及黑色素瘤和多发性骨髓瘤等，并且和预后密切相关。因此，IAPs是抗肿瘤药物研发的重要方向。不过，目前并没有IAP类药物获批上市，Xevinapant是目前全球研发进展最快的IAP抑制剂产品之一，其通过抑制IAP，不但促进癌细胞的死亡，还可以增强抗肿瘤的免疫反应。作为行业的领头羊，本次研究的终止对于默克来说，是一个很大的打击，直到2024年5月，默克的高管还在向分析师们保证，Xevinapant的三期试验“不太可能（unlikely）”失败。除了本次终止的两项III期研究外，目前默克产品管线中已经没有列出针对Xevinapant开展的其他试验。默克肿瘤产品管线图片来源：默克公司官网频繁出手扫货肿瘤创新药去年以来，默克相继与国内和誉医药和恒瑞医药达成独家许可协议，分别引进一款CSF-1R抑制剂（Pimicotinib）和一款高选择性PARP1抑制剂（HRS-1167/M9466）。 Pimicotinib 由和誉医药自主研发，是一款全新的口服、高选择性、高活性CSF-1R小分子抑制剂，当前已在中国、美国、加拿大和欧洲同步开展全球多中心三期临床试验，该研究是腱鞘巨细胞瘤疾病领域首个在中国、美国、加拿大和欧洲同步开展的全球III期研究。在去年11月的CTOS年会上，和誉医药还更新了Pimicotinib治疗TGCT患者的临床Ib期试验一年长期随访数据，ORR达到87.5%，展现出了药物的抗肿瘤活性和良好的安全性。此外，NMPA已批准Pimicotinib用于慢性移植物抗宿主病、晚期胰腺癌的临床试验，和誉医药也仍在探索该药物在多种实体瘤中的临床潜力。 HRS-1167（M9466）是恒瑞医药研发的一款选择性、高活性、可口服的 PARP1 小分子抑制剂，属于第二代 PARP 抑制剂。与第一代PARP抑制剂相比，HRS-1167对PARP1的选择性更高、亲和力更强，且可诱导DNA捕获。 M9466用于晚期实体肿瘤的Ⅰ期研究入选了ASCO 2024年会的壁报展示环节，研究显示：M9466在伴HRR突变的晚期实体肿瘤患者中显示出了突出的抗肿瘤疗效，对晚期卵巢癌患者的缓解效果更佳。再往前追溯，默克还曾于2022年9月斥资6500万美元首付款囊获Nerviano旗下PARP1抑制剂NMS-293的开发和商业化权益。两笔交易传达出的信号已十分明显，默克对于PARP1抑制剂是坚定看好而且势在必得。此外，今年年初默克还引进了Inspirna开发的一款first in class的结直肠癌药物ompenaclid的专利权。ompenaclid是肌酸转运通道SLC6A8的一流口服抑制剂，目前正在开发用于RAS突变（RASm）二线（2L）晚期或转移性结直肠癌（mCRC）和SLC6a8靶向后续化合物。去年10月在欧洲肿瘤内科学会（ESMO）大会上报告的Ib/II期数据表明，Ompenaclid与标准二线疗法（FOLFIRI化疗和贝伐珠单抗）结合有可能改善疗效，同时不会增加其毒性负担。该药物总缓解率可达37%（41名接受治疗的患者中有11名病情得到了缓解），中位无进展生存期（PFS）为10.2个月，中位总生存期（OS)为19.1个月。深耕“合成致死”领域 ATR，即共济失调毛细血管扩张突变（ATM）基因和Rad3相关激酶，激活后可通过多种信号调控细胞生物过程, 包括细胞周期阻滞、抑制复制起点、促进脱氧核苷酸合成、启动复制叉以及修复DNA双链断裂。研究发现，ATM和ATR 激酶在癌细胞中被激活或上调，同时ATR是ATM突变的合成致死靶点，ATM缺失的肿瘤细胞对于ATR抑制剂更加敏感。二者间的选择性抑制为肿瘤治疗提供了新的思路，也为肿瘤研究提供了新的工具。除了PARP1抑制剂，默克在“合成致死”领域还分别布局了一款ATR抑制剂(M1774)和ATM抑制剂(M4076)，其中M1774进展较快已经进入II期临床，M4076尚处于I期临床。 Tuvusertib(M1774)是默克开发的一款潜在的best-in-class ATR抑制剂。2024年美国临床肿瘤学会(ASCO)年会上发布的DDRiver 301 Part B数据表明，预测有效剂量的tuvusertib与PARP抑制剂尼拉帕利联合治疗具有能力，并且在PARP预处理过的卵巢癌中具有令人鼓舞的活性。这些发现补充了4月份在美国癌症研究协会(AACR)年会上首次提出的tuvusertib和lartesertib联合疗法的数据。默克正在三个II期研究中探索tuvusertib： 1.正在进行的Ib/II期DDRiver NSCLC 322研究(NCT05882734)联合cemiplimab治疗具有生物标志物分层的耐药晚期非小细胞肺癌(NSCLC)； 2.最近开展的2期DDRiver EOC 302研究(NCT06433219)将tuvusertib联合lartesertib或尼拉帕利用于生物标志物选择的parp耐药卵巢癌; 3.近期开展的JAVELIN DDRiver膀胱II期研究(NCT06424717)联合BAVENCIO®(avelumab)治疗ci耐药晚期尿路上皮癌。 ADC：新兴靶点打头阵默克的ADC管线以靶向CEACAM5 M9140为首，CEACAM5作为一种细胞表面蛋白，在健康的成年人组织中表达较少，但在多种腺癌中却高度表达，特别是在结直肠癌中，高达90%的病例都有CEACAM5的表达。该药物的治疗窗宽，并且在血液循环中也稳定，该药与DDR抑制剂合用可产生协同作用。M9140中的细胞毒性有效负载是拓扑异构酶1 (TOP1) 抑制剂，可防止DNA修复。目前，M9140处于结直肠癌的Ⅰ期临床研究阶段。在今年的ASCO大会上，M9140的Ⅰ期临床试验结果备受瞩目。该试验纳入了来自美国、欧盟和日本的40名晚期结直肠癌患者，他们在接受标准治疗后病情仍有所进展。在接受7个不同剂量的M9140治疗后，10%的患者出现了明确的治疗反应，而42.5%的患者病情保持稳定，其中6名患者的病情稳定期超过了100天。此外，15%的患者病情出现进展。初步数据显示，中位无进展生存期为6.7个月。截至数据统计时，仍有15名患者（占比37.5%）正在接受M9140的治疗。参考来源: 1.Bourhis, J., Burtness, B., Licitra, L. F., Nutting, C., Schoenfeld, J. D., Omar, M., … Cohen, E. E. (2022). Xevinapant or placebo plus chemoradiotherapy in locally advanced squamous cell carcinoma of the head and neck: TrilynX phase III study design. Future Oncology, 18(14), 1669– 2.James Waldron. Merck KGaA drops xevinapant with phase 3 head and neck cancer trial on course for failure. FierceBiotech. Jun 25, 2024. 3.Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021 May;71(3):209-249. doi: 10.3322/caac.21660. Epub 2021 Feb 4. 4.默克公司官网来源：CPHI制药在线声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。投稿邮箱：Kelly.Xiao@imsinoexpo.com ▼更多制药资讯，请关注CPHI制药在线▼ 点击阅读原文，进入智药研习社~

临床3期临床2期免疫疗法优先审批突破性疗法

2024-03-29

·精准药物

默克BTK抑制剂 evobrutinib终止开发，MUCI/EGFR双抗ADC消失

默克公司在周四的 2023 年第四季度业绩中指出，该公司已取消用于治疗多发性硬化症的 BTK 抑制剂evobrutinib。首席执行官贝伦·加里霍（Belén Garijo）在投资者电话会议上表示，该计划已正式终止。2023年12月，该公司宣布其两项研究 evobrutinib 安全性和有效性的 III 期试验并未达到降低多发性硬化症 (MS) 患者年复发率的主要终点。然而，终止合同似乎并没有阻止加里霍参加电话会议。她指出，尽管 evobrutinib 遇到了挫折，但该公司“对我们在医疗保健领域的定位相当稳固和良好”。加里霍提到，解约成本为 9500 万欧元（1.038 亿美元）。然而，这是一次性付款。她还表示，evobrutinib 不会像去年那样产生上市前费用。Merck KGaA 在其 BTK 抑制剂方面曾遇到过障碍。2023 年 4 月，在两名多发性硬化症患者出现肝损伤迹象后，FDA 暂停了 III 期试验。当时，不允许该公司招募新患者参加试验，并且已停止接受该药物治疗不到70天的参与者的给药。BTK 抑制剂作为一类药物也遇到了障碍。就在默克公司 III 期试验失败之前，罗氏用于治疗多发性硬化症的 BTK 抑制剂因一些潜在的肝损伤病例而被 FDA 暂停临床。具体来说，参与罗氏 III 期研究的两名患者在接受剂量后出现肝转氨酶水平异常升高。FDA 已对其他 BTK 抑制剂进行了部分临床搁置。与此同时，默克公司一直在研究其他领域。2023 年 1 月，该公司通过预付 4500 万美元从 Inspirna 获得两项资产许可，扩大了其结直肠癌产品组合。周一，这家德国公司还向 C4 Therapeutics 预付了 1600 万美元，后者可能获得超过 7.4 亿美元的潜在里程碑付款，以建立研究合作，发现两种针对“关键致癌蛋白”的靶向蛋白质降解剂.现在，evobrutinib也已经消失了在管线中而且多日不追踪，那个曾经的MUCI/EGFR双抗ADC药物M1231同样也已经在两家管线中消失不见。2023年9月份，这个产品还是在的2021年，就写过这个品种，大家不妨看看当时就提出了EGFR/双抗，包括Met声明：发表/转载本文仅仅是出于传播信息的需要，并不意味着代表本公众号观点或证实其内容的真实性。据此内容作出的任何判断，后果自负。若有侵权，告知必删！长按关注本公众号粉丝群/投稿/授权/广告等请联系公众号助手觉得本文好看，请点这里↓

引进/卖出临床3期抗体药物偶联物医药出海

100 项与 Inspirna, Inc. 相关的药物交易

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2024年11月20日管线快照

管线布局中药物为当前组织机构及其子机构作为药物机构进行统计，早期临床1期并入临床1期，临床1/2期并入临床2期，临床2/3期并入临床3期

临床前

临床2期

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药物(靶点)	适应症	全球最高研发状态

Ompenaclid ( SLC6A8 )	RAS 突变结直肠癌更多	临床2期
Abequolixron ( APOE x LXR x NR1H2 )	晚期恶性实体瘤更多	临床1期
RGX-019-MMAE(Inspirna) ( MerTK x TUB )	肿瘤更多	临床前
RGX-019 ( MerTK )	三阴性乳腺癌更多	临床前
RGX-014 ( IGFBP2 )	乳腺癌更多	无进展