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.

NCT03597581 / Recruiting临床1期

A Phase 1 Study of RGX-202-01 (Ompenaclid) , a Small Molecule Inhibitor of the Creatine Transporter SLC6a8, as a Single Agent and as Combination Therapy in Patients With Advanced Gastrointestinal Malignancies With Select Expansion Cohorts

This is a Phase 1 study currently evaluating PO administered ompenaclid in combination with FOLFIRI and bevacizumab in patients with advanced (i.e., locally advanced and unresectable, or metastatic) previously treated colorectal adenocarcinoma. The single agent ompenaclid dose escalation stage and the ompenaclid in combination with FOLFIRI and bevacizumab dose escalation stage of the study has been completed; the expansion stage of ompenaclid in combination with FOLFIRI and bevacizumab is ongoing. In April-24 a protocol amendment added a new dose escalation and expansion stage which will evaluate ompenaclid in combination with FOLFOX and bevacizumab in patients with metastatic CRC. It is anticipated that a total of 30 patients will be enrolled in this new dose escalation and expansion stage of the study.

开始日期2018-06-05

申办/合作机构

Inspirna, Inc.

100 项与 Ompenaclid 相关的临床结果

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100 项与 Ompenaclid 相关的转化医学

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100 项与 Ompenaclid 相关的专利（医药）

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项与 Ompenaclid 相关的文献（医药）

2024-01-01·Cell Metabolism

Myeloid cell-derived creatine in the hypoxic niche promotes glioblastoma growth

Article

作者: Billingham, Leah K ; Delay, Suzi ; Geng, Yuheng ; Katz, Joshua L ; Boland, Lauren ; Lee-Chang, Catalina ; Chandel, Navdeep S ; Park, Cheol H ; Lin, Hanchen ; Zolp, Andrew ; Sonabend, Adam ; Steffens, Alicia M ; Wang, Hanxiang ; Flowers, Mariah S ; Lesniak, Maciej S ; Zhang, Peng ; Castro, Brandyn ; Dmello, Crismita ; McCortney, Kathleen ; Silvers, Caylee ; Markwell, Steven M ; Brat, Daniel J ; Zilinger, Kaylee ; Lopez-Rosas, Aurora ; Rashidi, Aida ; Ahmed, Atique U ; Walshon, Jordain P ; Zhao, Junfei ; Heiland, Dieter H ; Jacob, Irene M ; Miska, Jason ; Arrieta, Victor A ; Chia, Tzu-Yi ; Hou, David

Glioblastoma (GBM) is a malignancy dominated by the infiltration of tumor-associated myeloid cells (TAMCs). Examination of TAMC metabolic phenotypes in mouse models and patients with GBM identified the de novo creatine metabolic pathway as a hallmark of TAMCs. Multi-omics analyses revealed that TAMCs surround the hypoxic peri-necrotic regions of GBM and express the creatine metabolic enzyme glycine amidinotransferase (GATM). Conversely, GBM cells located within these same regions are uniquely specific in expressing the creatine transporter (SLC6A8). We hypothesized that TAMCs provide creatine to tumors, promoting GBM progression. Isotopic tracing demonstrated that TAMC-secreted creatine is taken up by tumor cells. Creatine supplementation protected tumors from hypoxia-induced stress, which was abrogated with genetic ablation or pharmacologic inhibition of SLC6A8. Lastly, inhibition of creatine transport using the clinically relevant compound, RGX-202-01, blunted tumor growth and enhanced radiation therapy in vivo. This work highlights that myeloid-to-tumor transfer of creatine promotes tumor growth in the hypoxic niche.

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

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

项与 Ompenaclid 相关的新闻（医药）

2024-09-03

·PipelineReview

REGENXBIO Announces Positive Data from Pivotal Dose Level of RGX-121 Demonstrating Long-Term Systemic Effect

– Data from pivotal dose level demonstrates long-term, sustained reductions in CSF levels of HS D2S6, a key biomarker of brain disease in MPS II – 80% of patients who received the pivotal dose discontinued intravenous enzyme replacement therapy or remained treatment-naïve – Submission of a rolling BLA using the accelerated approval pathway on track for Q3 2024 ROCKVILLE, MD, USA I September 3, 2024 I REGENXBIO Inc. (Nasdaq: RGNX ) today announced positive results from the Phase I/II/III CAMPSIITE ® trial of RGX-121 for the treatment of patients with Mucopolysaccharidosis Type II (MPS II), also known as Hunter syndrome. The results were presented at the Society for the Study of Inborn Errors of Metabolism (SSIEM) Annual Symposium 2024. The totality of evidence from the CAMPSIITE trial continues to support RGX-121 as the potential first gene therapy and one-time treatment for MPS II. In the United States, RGX-121 is also on track to be the first treatment that addresses the neurocognitive decline associated with MPS II, with the potential to be the first-line treatment for patients with neuronopathic disease. “As we quickly approach the BLA filing for RGX-121, we are very pleased with the data presented at SSIEM demonstrating encouraging evidence of systemic activity and long-term reductions of CSF D2S6,” said Steve Pakola, M.D., Chief Medical Officer of REGENXBIO. “The data continue to support that by restoring the gene missing in boys with Hunter syndrome, RGX-121 changes the course of disease and has the potential to significantly improve both vital brain function and the systemic manifestations of this devastating disease.” Data Summary In new, long-term data from the Phase I/II/III CAMPSIITE ® trial, patients receiving RGX-121 at the pivotal dose level demonstrated an 85% median reduction of cerebrospinal fluid (CSF) levels of heparan sulfate (HS) D2S6, a key biomarker of brain disease activity, approaching normal levels and sustained for up to two years. Topline results presented earlier this year from the CAMPSIITE trial demonstrated that the pivotal phase of the trial met its primary endpoint with statistical significance. Pivotal results were consistent with data from the dose-finding phase of CAMPSIITE, in which the majority of patients were shown to be exceeding expectations in neurodevelopmental function compared to natural history data up to four years. In the dose-finding part of the trial, investigators chose to discontinue standard-of-care intravenous enzyme replacement therapy (ERT) or to remain ERT-naïve for a majority of patients. At the pivotal dose level (dose level 3), 80% of patients were ERT-free at last time point, up to more than 18 months post-dosing. At dose level 2, 71% of patients were ERT-free at last time point, up to almost three years. As of January 5, 2024, RGX-121 continues to be well tolerated in 25 patients dosed across all phases of the CAMPSIITE trial. “A potential one-time treatment that can allow these boys to exceed the natural history of this disease in their neurocognitive development, as well as the ability to remain off enzyme replacement therapy for multiple years represents a meaningful option for patients and their families,” said Roberto Giugliani, M.D., Ph.D., Professor, Department of Genetics, UFRGS, Medical Genetics Service, HCPA, Porto Alegre, Brazil. “I continue to be very encouraged by the data supporting RGX-121 and look forward to the seeing this program advance towards potential approval for this community.” REGENXBIO is on track to initiate a rolling Biologics License Application (BLA) submission using the accelerated approval pathway in the third quarter of 2024 using CSF D2S6 as a surrogate endpoint reasonable likely to predict clinical benefit. Approval of the planned BLA could result in receipt of a Priority Review Voucher in 2025. Data presented is available on the “Publications” section of the REGENXBIO website at WWW.REGENXBIO.COM . About the CAMPSIITE ® Trial CAMPSIITE is a Phase I/II/III multicenter, open-label trial for boys aged four months up to five years with neuronopathic MPS II. The primary endpoint of the trial is measurement of CSF GAGs. Accurate and sensitive measurements of CSF GAGs, such as HS D2S6, have the potential to be considered a surrogate endpoint that is reasonably likely to predict clinical benefit in MPS II disease under the accelerated approval pathway, as buildup of GAGs in the CSF of MPS II patients correlates with clinical manifestations including neurodevelopmental deficits. The pivotal program is using commercial-scale cGMP material from REGENXBIO’s proprietary, high-yielding suspension-based manufacturing process, named NAVXpress™. In addition to measuring GAGs in the CSF, the trial will continue to collect neurodevelopmental data and caregiver-reported outcomes. About RGX-121 RGX-121 is a potential one-time AAV therapeutic for the treatment of boys with MPS II. RGX-121 expressed protein is structurally identical to normal I2S. RGX-21 Delivery of the IDS gene within cells in the CNS could provide a permanent source of secreted I2S beyond the blood-brain barrier, allowing for long-term cross correction of cells throughout the CNS. RGX-121 has received Orphan Drug Product, Rare Pediatric Disease, Fast Track and Regenerative Medicine Advanced Therapy designations from the U.S. Food and Drug Administration and advanced therapy medicinal products (ATMP) classification from the European Medicines Agency. About Mucopolysaccharidosis Type II (MPS II) MPS II, or Hunter Syndrome, is a rare, X-linked recessive disease caused by a deficiency in the lysosomal enzyme iduronate-2-sulfatase (I2S) leading to an accumulation of glycosaminoglycans (GAGs), including heparan sulfate (HS) in tissues which ultimately results in cell, tissue, and organ dysfunction, including in the central nervous system (CNS). MPS II is estimated to occur in 1 in 100,000 to 170,000 births. In severe forms of the disease, early developmental milestones may be met, but developmental delay is readily apparent by 18 to 24 months. Specific treatment to address the neurological manifestations of MPS II remains a significant unmet medical need. Key biomarkers of I2S enzymatic activity in MPS II patients include its substrate HS D2S6, which has been shown to correlate with neurocognitive manifestations of the disorder. ABOUT REGENXBIO Inc. REGENXBIO is a leading clinical-stage biotechnology company seeking to improve lives through the curative potential of gene therapy. Since its founding in 2009, REGENXBIO has pioneered the development of AAV Therapeutics, an innovative class of gene therapy medicines. REGENXBIO is advancing a pipeline of AAV Therapeutics for retinal and rare diseases, including ABBV-RGX-314 for the treatment of wet AMD and diabetic retinopathy, being developed in collaboration with AbbVie, RGX-202 for the treatment of Duchenne and RGX-121 for the treatment of MPS II. Thousands of patients have been treated with REGENXBIO’s AAV Therapeutic platform, including Novartis’ ZOLGENSMA for children with spinal muscular atrophy. Designed to be one-time treatments, AAV Therapeutics have the potential to change the way healthcare is delivered for millions of people. For more information, please visit www.regenxbio.com . SOURCE: REGENXBIO

临床结果快速通道孤儿药突破性疗法临床研究

2024-08-04

·药明康德

使90%阿尔茨海默病患者认知功能稳定或改善的NK细胞疗法；旨在功能性治愈乙肝的创新疗法进入临床…… | 一周盘点

▎药明康德内容团队编辑本期看点 1. 治疗阿尔茨海默病（AD）的自然杀伤（NK）细胞疗法SNK01在一项1期临床试验中使90%患者的认知功能稳定或有改善。 2. FDA批准了能在体内制造嵌合抗原受体（CAR）-T细胞的创新疗法UB-VV111的IND申请，预计将于今年年底前启动1期临床试验。 3. 有望功能性治愈乙型肝炎病毒（HBV）感染的重组多克隆抗体疗法GIGA-2339获许可进入临床。药明康德内容团队整理 SNK01：公布1期临床试验的新数据 NKGen Biotech公布了其在研NK细胞疗法SNK01治疗阿尔茨海默病患者的临床试验数据。SNK01是一款自体、非基因工程改造的NK细胞产品，它具有增强的细胞毒性，活化受体表达率超过90%，可从任何供体中稳定生产。该候选疗法能够有效降低AD患者脑脊液（CSF）中的α-突触核蛋白（α-syn）水平，该蛋白的升高被认为与认知能力下降有关。目前，已批准的AD疗法均未将α-syn作为靶点。此前公布的1期试验结果显示，SNK01除了先前披露的对淀粉样蛋白β（Aβ）和神经炎症生物标志物的积极影响外，对晚期AD患者的认知功能也具有临床疗效。在10名可评估的AD患者中，90%患者的阿尔茨海默病综合评分（ADCOMS，一种反映患者认知功能的评分）较基线时有改善或保持稳定。此次公布的结果显示，尽管70%的受试者接受的是相对低剂量的SNK01治疗，仍有60%的受试者（6/10）的CSF α-syn水平较基线时有所下降。第11周时，6名患者中有5名受试者的α-syn下降与ADCOMS的稳定/下降相对应。安全性方面，没有观察到与治疗相关的不良事件。AD受试者对SNK01的耐受性良好，在所有测试剂量下均未观察到剂量限制性毒性。该公司表示，这些数据值得在更大剂量、更长疗程、更大规模的2期试验中进一步研究。 UB-VV111：IND申请获得FDA许可 Umoja Biopharma宣布，美国FDA已批准其在研CD19靶向原位生成（in-situ generated）CAR-T细胞疗法UB-VV111的IND申请，用以治疗血液恶性肿瘤。Umoja预计将在2024年底前启动1期试验并进行首位患者给药。根据新闻稿，UB-VV111可能是血液学人体试验中首个原位生成CD19靶向CAR-T细胞疗法。 UB-VV111是一款通过VivoVec平台开发的体内CAR-T细胞疗法。UB-VV111包含一个表面经过工程化的病毒包膜，以及编码CD19靶向CAR和雷帕霉素激活细胞因子受体（RACRTM）的转基因，旨在于患者体内扩增UB-VV111工程化CAR-T细胞。该疗法是VivoVec基因递送平台进入临床的首个管线。 GIGA-2339：IND申请获得FDA许可 GigaGen公司宣布，美国FDA已批准其IND申请，将于2024年第四季度启动一项1期试验，以评估该公司首款用于治疗HBV感染的重组多克隆抗体疗法GIGA-2339。GIGA-2339采用GigaGen的下一代平台开发，含有1000多种全人重组抗HBV抗体，旨在复制人体的自然免疫反应。GIGA-2339的效力是血浆衍生HBV药物的2000多倍，涵盖了广泛的循环HBV变异。在小鼠模型中，GIGA-2339中和并清除了HBV的病毒DNA及其抗原。通过这种独特的作用机制，GIGA-2339有可能清除病毒颗粒并激活免疫反应，从而提供HBV感染患者的功能性治愈。 Sabirnetug（ACU193）：公布1期临床试验的新数据 Acumen Pharmaceuticals公司公布了sabirnetug（ACU193）用于治疗AD的1期临床试验的新结果。Sabirnetug是一种选择性靶向毒性可溶性β淀粉样蛋白寡聚体（AβOs）的人源化单克隆抗体。Sabirnetug能够结合AβOs，由于其独特的结合特性，sabirnetug有可能在产生淀粉样蛋白相关成像异常（ARIA，一种抗体疗法产生的常见主要副作用）风险较低的情况下提供治疗益处，因为sabirnetug可以在不直接靶向淀粉样斑块的情况下阻断AβOs的毒性作用。此次公布的结果显示，接受sabirnetug给药3次可显著降低患者脑脊液中突触前和突触后蛋白水平，这与sabirnetug抑制AβOs突触结合的作用机制一致。VAMP2是一种与突触损伤相关的生物标志物，在所有多剂量递增组中均显著降低，似乎是该研究中发现的对sabirnetug最敏感的生物标志物。Acumen公司计划在正在进行的为期18个月的2期临床试验中评估生物标志物的长期变化及其与临床结果的关系，以进一步证实sabirnetug的作用机制。此外，Acumen公司还宣布了sabirnetug皮下制剂治疗早期AD的1期临床试验已完成首例受试者给药。 Pepinemab：公布1b/2a期临床试验数据 Vaccinex公司公布了pepinemab治疗AD的1b/2期试验数据的良好初步结果。Pepinemab是一种人源化IgG4单克隆抗体，旨在阻断SEMA4D与plexin-B1受体结合，从而避免引发细胞内肌动蛋白细胞骨架的崩溃，以及进一步导致的大脑中星形胶质细胞和其他胶质细胞以及免疫组织中树突状细胞的稳态功能丧失。此次公布的结果证实了以激活星形胶质细胞为目标的新型作用机制有望延缓AD从早期轻度认知障碍发展为老年痴呆症的进程。该研究结果与此前pepinemab治疗亨廷顿病的2期临床试验结果类似，因为AD与亨廷顿病在神经免疫病理学方面具有相似性。 RGX-202：公布1/2期临床试验的新数据 REGENXBIO公司宣布，其在研杜氏肌营养不良症（DMD）基因疗法RGX-202在治疗1至11岁DMD患者的1/2期临床试验中获得了积极的中期安全性和疗效数据。在接受关键性临床试验推荐剂量（剂量水平2）的RGX-202治疗的5.8岁和8.5岁患者中，接受治疗后三个月时微抗肌营养不良蛋白表达水平分别为健康对照组的77.2%和46.5%。该试验中按剂量和年龄分类的微抗肌营养不良蛋白表达结果如下表所示： ▲AFFINITY DUCHENNE试验中接受不同剂量RGX-202治疗患者的微抗肌营养不良蛋白表达水平（图片来源：参考资料[1]） RGX-202是一种一次性基于腺相关病毒载体（AAV）的基因疗法，它编码包含天然抗肌营养不良蛋白C端（CT）结构域的微抗肌营养不良蛋白，以更好地模拟天然蛋白的功能。临床前研究中，CT结构域已被证明可以保护肌肉免受收缩引起的应力，并提高其自我修复的能力。 XPro：公布1期临床试验数据 INmune Bio公司公布了其下一代肿瘤F坏死因子（TNF）抑制剂XPro用于治疗AD的1b期临床试验结果。XPro的作用与现有的TNF抑制剂不同，它能中和可溶性TNF（sTNF），而不影响跨膜TNF（tmTNF）或TNF受体。XPro可在不抑制免疫的情况下减轻神经炎症，从而对神经系统疾病患者产生潜在的实质性益处。此次公布的结果显示，接受XPro治疗12周后，患者的突触蛋白发生了显著变化，而突触蛋白对神经元之间的交流至关重要。 NTLA-3001：获批在英国启动1/2期临床试验 Intellia Therapeutics公司宣布其临床试验申请（CTA）获得英国药品与保健品管理局（MHRA）的授权，可启动一项1/2期研究以评估NTLA-3001治疗α1抗胰蛋白酶缺乏症（AATD）相关的肺部疾病的效果。AATD是一种罕见的遗传性疾病，最常见的表现是由于α1抗胰蛋白酶（AAT）蛋白水平不足导致的肺功能障碍。NTLA-3001是一种全身给药的体内一次性基因编辑疗法，它旨在通过CRISPR/Cas9技术精确插入编码AAT蛋白的SERPINA1基因的健康拷贝，单次给药就有可能使功能性AAT蛋白永久表达并恢复到治疗水平。这种方法旨在改善患者的治疗效果，包括消除每周静脉注射AAT的疗法或严重病例对肺移植的需求。 ▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放参考资料（可上下滑动查看） [1] REGENXBIO ANNOUNCES NEW POSITIVE DATA FROM AFFINITY DUCHENNE® TRIAL OF RGX-202. Retrieved August 1, 2024, from https://ir.regenxbio.com/news-releases/news-release-details/regenxbio-announces-new-positive-data-affinity-duchenner-trial [2] Acumen Pharmaceuticals Presents Patient Experience and Biomarker Data from Phase 1 INTERCEPT-AD Study at the Alzheimer’s Association International Conference (AAIC®) 2024. Retrieved August 2, 2024, from https://www.globenewswire.com/news-release/2024/07/28/2919969/0/en/Acumen-Pharmaceuticals-Presents-Patient-Experience-and-Biomarker-Data-from-Phase-1-INTERCEPT-AD-Study-at-the-Alzheimer-s-Association-International-Conference-AAIC-2024.html [3] Acumen Pharmaceuticals Announces First Subject Dosed in Phase 1 Study of Subcutaneous Sabirnetug (ACU193) for Early Alzheimer’s Disease. Retrieved August 2, 2024, from https://investors.acumenpharm.com/news-releases/news-release-details/acumen-pharmaceuticals-announces-first-subject-dosed-phase-1 [4] NKGen Biotech Presents New Positive SNK01 Biomarker Data at the 2024 Alzheimer’s Association International Conference. Retrieved August 2, 2024, from https://nkgenbiotech.com/nkgen-biotech-presents-new-positive-snk01-biomarker-data-at-the-2024-alzheimers-association-international-conference/ [5] Umoja Biopharma Announces FDA Clearance of IND Application for UB-VV111, a CD19 Directed in situ CAR T for Hematologic Malignancies. Retrieved July 31, 2024 from https://www.umoja-biopharma.com/news/umoja-biopharma-announces-fda-clearance-of-ind-application-for-ub-vv111-a-cd19-directed-in-situ-car-t-for-hematologic-malignancies/ [6] Intellia Therapeutics Receives Authorization to Initiate Phase 1/2 Clinical Trial of NTLA-3001 for the Treatment of Alpha-1 Antitrypsin Deficiency. Retrieved August 2, 2024, from https://www.globenewswire.com/news-release/2024/07/30/2920893/0/en/Intellia-Therapeutics-Receives-Authorization-to-Initiate-Phase-1-2-Clinical-Trial-of-NTLA-3001-for-the-Treatment-of-Alpha-1-Antitrypsin-Deficiency.html [7] Vaccinex Reports Positive Data for SIGNAL-AD Phase 1b/2 trial of Pepinemab in Alzheimer’s Disease. Retrieved August 2, 2024, from https://www.globenewswire.com/news-release/2024/07/31/2921918/34858/en/Vaccinex-Reports-Positive-Data-for-SIGNAL-AD-Phase-1b-2-trial-of-Pepinemab-in-Alzheimer-s-Disease.html [8] Citryll Completes Patient Dosing In The Repeat Dose Stage Of The Phase 1 Trial. Retrieved August 2, 2024, from https://citryll.com/newsitems/citryll-completes-patient-dosing-in-the-repeat-dose-stage/ [9] GigaGen Receives FDA Clearance of IND Application for Phase 1 Trial of Recombinant Polyclonal for HBV Treatment, GIGA-2339. Retrieved August 2, 2024, from https://www.globenewswire.com/news-release/2024/07/31/2921826/0/en/GigaGen-Receives-FDA-Clearance-of-IND-Application-for-Phase-1-Trial-of-Recombinant-Polyclonal-for-HBV-Treatment-GIGA-2339.html [10] Compugen Announces FDA Clearance of IND for COM503 for the Treatment of Solid Tumors. Retrieved August 2, 2024, from https://www.prnewswire.com/news-releases/compugen-announces-fda-clearance-of-ind-for-com503-for-the-treatment-of-solid-tumors-302208442.html [11] Georgiamune Announces First Patient Dosed in A First-In-Class Phase 1 Cancer Treatment Trial of GIM-531. Retrieved August 2, 2024, from https://www.globenewswire.com/news-release/2024/07/30/2921055/0/en/Georgiamune-Announces-First-Patient-Dosed-in-A-First-In-Class-Phase-1-Cancer-Treatment-Trial-of-GIM-531.html [12] INmune Bio Inc. Announces New Phase 1 Study Data Demonstrating Dose-Dependent Effect of XPro™ on Proteins that Regulation Synapses in Alzheimer’s Patients. Retrieved August 2, 2024, from https://www.inmunebio.com/index.php/newsroom/2024-news/muneioncnnouncesewhase1tudyataemonstrati20240729060507 免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

细胞疗法临床申请临床1期免疫疗法临床2期

2024-08-03

·药明康德

FDA批准首款TCR-T细胞疗法；体内制造CAR-T疗法获许可进入临床…… | CGT周报

▎药明康德内容团队编辑近期，全球细胞和基因疗法（CGT）领域迎来系列进展。FDA批准首款T细胞受体（TCR）T细胞疗法Tecelra，该疗法也是十多年来治疗滑膜肉瘤的首个有效疗法。治疗阿尔茨海默病（AD）的自然杀伤（NK）细胞疗法SNK01在一项1期临床试验中使90%患者的认知功能稳定或有改善。体内制造嵌合抗原受体（CAR）-T细胞的创新疗法UB-VV111的IND申请获得FDA许可，预计将于今年年底前启动1期临床试验。本文将节选其中部分重要进展做简单介绍，仅供读者参阅。图片来源：123RF ———✦研发进展✦——— ◇ Adaptimune Therapeutics公司宣布，美国FDA批准其在研工程化T细胞疗法Tecelra（afami-cel）用以治疗既往接受过化疗的某些HLA类型的晚期MAGE-A4+滑膜肉瘤成人患者。Afami-cel是一种针对MAGE-A4癌症靶点的工程化TCR-T细胞疗法，被设计作为一种用于晚期滑膜肉瘤的一次性疗法。根据新闻稿，afami-cel为首款用于治疗实体瘤的工程化T细胞疗法，也是十多年来治疗滑膜肉瘤的首个有效疗法。此次批准主要是基于一项关键性研究SPEARHEAD-1中队列1的积极数据。该研究达到了主要疗效终点，44例患者的总缓解率（ORR）为43%，完全缓解率为4.5%，中位缓解持续时间为6个月（95% CI：4.6，未达到）。在获得缓解的患者中，39%患者的缓解持续时间≥12个月。安全性方面，毒性反应包括细胞因子释放综合征和可逆的血液学毒性，这与之前的研究结果一致，表明afami-cel的安全性是可以接受的。 ◇ NKGen Biotech公布了其在研NK细胞疗法SNK01治疗阿尔茨海默病患者的临床试验数据。SNK01是一款自体、非基因工程改造的NK细胞产品，它具有增强的细胞毒性，活化受体表达率超过90%，可从任何供体中稳定生产。该候选疗法能够有效降低AD患者脑脊液（CSF）中的α-突触核蛋白（α-syn）水平，该蛋白的升高被认为与认知能力下降有关。目前，已批准的AD疗法均未将α-syn作为靶点。此前公布的1期试验结果显示，SNK01除了先前披露的对淀粉样蛋白β（Aβ）和神经炎症生物标志物的积极影响外，对晚期AD患者的认知功能也具有临床疗效。在10名可评估的AD患者中，90%患者的阿尔茨海默病综合评分（ADCOMS，一种反映患者认知功能的评分）较基线时有改善或保持稳定。此次公布的结果显示，尽管70%的受试者接受的是相对低剂量的SNK01治疗，仍有60%的受试者（6/10）的CSF α-syn水平较基线时有所下降。第11周时，6名患者中有5名受试者的α-syn下降与ADCOMS的稳定/下降相对应。安全性方面，没有观察到与治疗相关的不良事件。AD受试者对SNK01的耐受性良好，在所有测试剂量下均未观察到剂量限制性毒性。该公司表示，这些数据值得在更大剂量、更长疗程、更大规模的2期试验中进一步研究。 ◇ REGENXBIO公司宣布，其在研杜氏肌营养不良症（DMD）基因疗法RGX-202在治疗1至11岁DMD患者的1/2期临床试验中获得了积极的中期安全性和疗效数据。在接受关键性临床试验推荐剂量（剂量水平2）的RGX-202治疗的5.8岁和8.5岁患者中，接受治疗后三个月时微抗肌营养不良蛋白表达水平分别为健康对照组的77.2%和46.5%。该试验中按剂量和年龄分类的微抗肌营养不良蛋白表达结果如下表所示： ▲AFFINITY DUCHENNE试验中接受不同剂量RGX-202治疗患者的微抗肌营养不良蛋白表达水平（图片来源：参考资料[7]） RGX-202是一种一次性基于腺相关病毒载体（AAV）的基因疗法，它编码包含天然抗肌营养不良蛋白C端（CT）结构域的微抗肌营养不良蛋白，以更好地模拟天然蛋白的功能。临床前研究中，CT结构域已被证明可以保护肌肉免受收缩引起的应力，并提高其自我修复的能力。 ◇ Umoja Biopharma宣布，美国FDA已批准其在研CD19靶向原位生成（in-situ generated）CAR-T细胞疗法UB-VV111的IND申请，用以治疗血液恶性肿瘤。Umoja预计将在2024年底前启动1期试验并进行首位患者给药。根据新闻稿，UB-VV111可能是血液学人体试验中首个原位生成CD19靶向CAR-T细胞疗法。 UB-VV111是一款通过VivoVec平台开发的体内CAR-T细胞疗法。UB-VV111包含一个表面经过工程化的病毒包膜，以及编码CD19靶向CAR和雷帕霉素激活细胞因子受体（RACRTM）的转基因，旨在于患者体内扩增UB-VV111工程化CAR-T细胞。该疗法是VivoVec基因递送平台进入临床的首个管线。 ◇ Intellia Therapeutics公司宣布其临床试验申请（CTA）获得英国药品与保健品管理局（MHRA）的授权，可启动一项1/2期研究以评估NTLA-3001治疗α1抗胰蛋白酶缺乏症（AATD）相关的肺部疾病的效果。AATD是一种罕见的遗传性疾病，最常见的表现是由于α1抗胰蛋白酶（AAT）蛋白水平不足导致的肺功能障碍。NTLA-3001是一种全身给药的体内一次性基因编辑疗法，它旨在通过CRISPR/Cas9技术精确插入编码AAT蛋白的SERPINA1基因的健康拷贝，单次给药就有可能使功能性AAT蛋白永久表达并恢复到治疗水平。这种方法旨在改善患者的治疗效果，包括消除每周静脉注射AAT疗法或严重病例对肺移植的需求。 ◇ 中国国家药监局药品审评中心（CDE）官网公示，贝斯昂科生物申报的1类新药NK510细胞注射液的IND申请获得受理。公开资料显示，NK510是一款基于碱基编辑技术的NK细胞产品，拟开发用于晚期实体肿瘤的治疗。据悉，通过精心设计和工艺流程优化，贝斯生物已经成功地利用“零脱靶”碱基编辑器AccuBase在外周血单核细胞（PBMC）来源的NK细胞中实现了超过90%的编辑效率。贝斯生物的方案能够实现NK510细胞百万倍级别的扩增，突破了异体NK细胞体外扩增倍数少、转染效率低的难题。尤其值得注意的是，碱基编辑赋予了NK510细胞靶向肿瘤的能力，在多项体外、体内实验中展现出强大的抗肿瘤能力。 ———✦融资、合作、M&A✦——— 图片来源：123RF ◇ Outpace Bio公司宣布完成超额认购的B轮融资，筹集1.44亿美元，获得的资金将用于推进多种T细胞候选疗法，以期在实体肿瘤治疗中获得早期临床概念验证。该公司的主打项目OPB-101是一种针对间皮素的CAR-T细胞，利用Outpace的专有技术OUTSMART、OUTLAST、OUTSPACER和OUTSAFE进行增强，计划于2025年获得IND许可并首次在晚期铂耐药性上皮性卵巢癌、输卵管癌或原发性腹膜癌患者进行给药。此外，这些资金还将支持Outpace利用其模块化技术平台扩展未来的产品线。 ◇ taiba Healthcare集团宣布向Immuneel Therapeutics公司投资1200万美元，旨在推进CAR-T细胞研究，尤其侧重于使CAR-T细胞疗法以可承受的价格投入商业应用，并进行针对B细胞恶性肿瘤（包括白血病和淋巴瘤）的CD19靶向CAR-T细胞疗法IMN-003A的首个2期试验。 ◇ Calidi Biotherapeutics公司宣布，Ronald Rigor博士向其新子公司Nova Cell战略投资200万美元，用于推进Calidi的成人脂肪同种异体（AAA）干细胞创新项目。Rigor博士还向Calidi公司追加投资100万美元，以推进其肿瘤学管线。五年前，Calidi公司开始从健康的成人捐献者身上采集AAA干细胞，用于其癌症平台CLD-201（SuperNova）。如今，该公司正通过其新成立的子公司Nova Cell，将AAA干细胞的潜在用途从肿瘤学扩展到其他需要再生医学应用的领域，如化妆品、整形外科、自身免疫性疾病和其他各种疗法。 ◇ 神济昌华生物科技有限公司宣布完成了近亿元Pre-A轮融资，所融资金将主要用于神济昌华首个管线SNUG01的IND申报及其他管线产品的推进等。据新闻稿，本轮融资由中关村资本领投，中博聚力、传化资本和三美投资跟投。神济昌华是一家专注于神经系统疾病基因治疗的生物医药公司，致力于攻克肌萎缩侧索硬化（ALS）、脑卒中、帕金森病等神经系统疾病。SNUG01是神济昌华首个进入临床试验阶段的基因治疗药物，适应症为ALS，其以AAV为载体，采用一个潜在“first-in-class”治疗靶点，在临床前动物实验中展现出显著的神经元保护作用。SNUG01正在北京大学第三医院开展研究者发起的临床研究（IIT），并已完成四例受试者入组。 ▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放参考资料（可上下滑动查看） [1] NKGen Biotech Presents New Positive SNK01 Biomarker Data at the 2024 Alzheimer’s Association International Conference. Retrieved August 2, 2024, from https://nkgenbiotech.com/nkgen-biotech-presents-new-positive-snk01-biomarker-data-at-the-2024-alzheimers-association-international-conference/ [2] Umoja Biopharma Announces FDA Clearance of IND Application for UB-VV111, a CD19 Directed in situ CAR T for Hematologic Malignancies. Retrieved July 31, 2024 from https://www.umoja-biopharma.com/news/umoja-biopharma-announces-fda-clearance-of-ind-application-for-ub-vv111-a-cd19-directed-in-situ-car-t-for-hematologic-malignancies/ [3] Intellia Therapeutics Receives Authorization to Initiate Phase 1/2 Clinical Trial of NTLA-3001 for the Treatment of Alpha-1 Antitrypsin Deficiency. Retrieved August 2, 2024, from https://www.globenewswire.com/news-release/2024/07/30/2920893/0/en/Intellia-Therapeutics-Receives-Authorization-to-Initiate-Phase-1-2-Clinical-Trial-of-NTLA-3001-for-the-Treatment-of-Alpha-1-Antitrypsin-Deficiency.html [4] 神济昌华完成近亿元Pre-A轮融资，致力于神经系统疾病的创新药物研发. Retrieved Aug 1，2024,from https://mp.weixin.qq.com/s/6NzRPo_jAhTs8CJtO0ZJ4w [5] 中国国家药监局药品审评中心（CDE）官网.Retrieved Jul 29，2024,from https://www.cde.org.cn/main/xxgk/listpage/da6efd086c099b7fc949121166f0130c [6] Adaptimmune Receives U.S. FDA Accelerated Approval of TECELRA® (afamitresgene autoleucel), the First Approved Engineered Cell Therapy for a Solid Tumor. Retrieved August 1, 2024, from https://www.adaptimmune.com/investors-and-media/news-center/press-releases/detail/271/adaptimmune-receives-u-s-fda-accelerated-approval-of [7] REGENXBIO ANNOUNCES NEW POSITIVE DATA FROM AFFINITY DUCHENNE® TRIAL OF RGX-202. Retrieved August 1, 2024, from https://ir.regenxbio.com/news-releases/news-release-details/regenxbio-announces-new-positive-data-affinity-duchenner-trial [8] taiba Make Strategic Investment in Immuneel Therapeutics to advance CAR T-cell Research and Make Therapies More Affordable. Retrieved August 2, 2024, from https://www.businesswire.com/news/home/20240730522797/en [9] Outpace Bio Announces $144M Oversubscribed Series B Financing to Advance AI-powered Cell Therapies into Clinical Development. Retrieved August 1, 2024, from https://www.outpacebio.com/news/outpace-bio-announces-144m-oversubscribed-series-b-financing-to-advance-ai-powered-cell-therapies-into-clinical-development [10] Calidi Biotherapeutics Announces Launch of Nova Cell Subsidiary and $3 Million Aggregate Investment from Dr. Ronald Rigor. Retrieved August 1, 2024, from https://www.globenewswire.com/news-release/2024/07/29/2920310/0/en/Calidi-Biotherapeutics-Announces-Launch-of-Nova-Cell-Subsidiary-and-3-Million-Aggregate-Investment-from-Dr-Ronald-Rigor.html 免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

细胞疗法临床1期临床申请临床结果基因疗法

100 项与 Ompenaclid 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
结肠转移性腺癌	临床2期	西班牙	Inspirna, Inc.	2023-10-10
结肠转移性腺癌	临床2期	法国	Inspirna, Inc.	2023-10-10
结肠转移性腺癌	临床2期	比利时	Inspirna, Inc.	2023-10-10
RAS 突变结直肠癌	临床2期	美国	Inspirna, Inc.	2023-06-01
KRAS突变肿瘤	临床1期	美国	Inspirna, Inc.	2018-06-05
转移性结直肠癌	临床1期	美国	Inspirna, Inc.	2018-06-05
胃癌	临床1期	美国	Inspirna, Inc.	2018-06-05

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分期

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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


Corporate Publications 人工标引	临床2期	RAS 突变结直肠癌二线 RAS-mutated	41	Ompenaclid+FOLFIRI +bevacizumab	(衊廠顧衊蓋選餘構顧願) = 齋積夢願積顧衊淵艱壓獵選遞窪鏇遞蓋願窪遞 (遞夢簾壓衊壓繭顧獵艱 ) 更多	积极	2024-01-04
NCT03597581 (RGX-202-01, ESMO2023) 人工标引	临床1/2期	RAS 突变结直肠癌二线 RAS mutation	33	Ompenaclid + FOLFIRI+bevacizumab	(鏇觸鑰鬱範廠鑰窪夢繭) = nausea (50%), diarrhea (44%) 衊衊壓夢遞遞夢鬱醖範 (艱網築餘遞遞顧鑰蓋鹹 ) 更多	积极	2023-10-22
				Ompenaclid + FOLFIRI+bevacizumab (RASm)
NCT03597581 (P-125, ESMO_GI2022)	临床1期	晚期结直肠腺癌二线	17	RGX-202-01 2400mg BID	(遞齋範顧繭鬱鹹膚衊鏇) = 觸餘襯構願艱網鹽艱遞遞選範鏇顧衊鑰鏇餘醖 (糧製壓鏇鬱製鬱糧觸願 ) 更多	积极	2022-07-02
				RGX-202-01 3000mg BID	(遞齋範顧繭鬱鹹膚衊鏇) = 艱觸壓鹽憲簾憲獵淵膚遞選範鏇顧衊鑰鏇餘醖 (糧製壓鏇鬱製鬱糧觸願 ) 更多
NCT03597581 (ASCO2022) 人工标引	临床1期	晚期结直肠腺癌二线 KRAS Mutation	16	FOLFIRI+RGX-202-01+bevacizumab (dose escalation)	(壓襯壓網鏇廠衊壓願鹹) = 餘顧鑰觸餘襯齋範簾膚鹽糧鑰餘範夢壓鏇鬱獵 (範製網範遞艱鬱膚範壓 ) 更多	积极	2022-06-02
				FOLFIRI+RGX-202-01+bevacizumab (dose expansion)	-
NCT03597581 (ESMO2022 \| ASCO2022) 人工标引	临床1期	晚期结直肠腺癌二线	-	bevacizumab+FOLFIRI+RGX-202	(窪齋顧壓糧獵獵餘醖餘) = 2 events (neutropenia, pulmonary embolus) 鹹鑰餘襯廠憲鏇襯夢顧 (淵觸醖築製膚鬱築齋觸 ) 更多	积极	2022-06-02
NCT03597581 (ASCO2020) 人工标引	临床1期	胃肠道肿瘤	17	FOLFIRI+RGX-202	(製壓網廠衊夢衊衊廠夢) = Not reached 顧壓膚夢構顧觸膚鹽艱 (壓選網願鏇廠獵鏇鏇膚 ) 更多	积极	2020-05-29