更新于：2024-05-01

SRPK1

SRSF protein kinase 1

更新于：2024-05-01

基本信息

别名

Serine/arginine-rich protein-specific kinase 1、serine/arginine-rich splicing factor kinase 1、SFRS protein kinase 1

+ [5]

简介

Serine/arginine-rich protein-specific kinase which specifically phosphorylates its substrates at serine residues located in regions rich in arginine/serine dipeptides, known as RS domains and is involved in the phosphorylation of SR splicing factors and the regulation of splicing. Plays a central role in the regulatory network for splicing, controlling the intranuclear distribution of splicing factors in interphase cells and the reorganization of nuclear speckles during mitosis. Can influence additional steps of mRNA maturation, as well as other cellular activities, such as chromatin reorganization in somatic and sperm cells and cell cycle progression. Isoform 2 phosphorylates SFRS2, ZRSR2, LBR and PRM1. Isoform 2 phosphorylates SRSF1 using a directional (C-terminal to N-terminal) and a dual-track mechanism incorporating both processive phosphorylation (in which the kinase stays attached to the substrate after each round of phosphorylation) and distributive phosphorylation steps (in which the kinase and substrate dissociate after each phosphorylation event). The RS domain of SRSF1 binds first to a docking groove in the large lobe of the kinase domain of SRPK1. This induces certain structural changes in SRPK1 and/or RRM2 domain of SRSF1, allowing RRM2 to bind the kinase and initiate phosphorylation. The cycles continue for several phosphorylation steps in a processive manner (steps 1-8) until the last few phosphorylation steps (approximately steps 9-12). During that time, a mechanical stress induces the unfolding of the beta-4 motif in RRM2, which then docks at the docking groove of SRPK1. This also signals RRM2 to begin to dissociate, which facilitates SRSF1 dissociation after phosphorylation is completed. Isoform 2 can mediate hepatitis B virus (HBV) core protein phosphorylation. It plays a negative role in the regulation of HBV replication through a mechanism not involving the phosphorylation of the core protein but by reducing the packaging efficiency of the pregenomic RNA (pgRNA) without affecting the formation of the viral core particles. Isoform 1 and isoform 2 can induce splicing of exon 10 in MAPT/TAU. The ratio of isoform 1/isoform 2 plays a decisive role in determining cell fate in K-562 leukaemic cell line: isoform 2 favors proliferation where as isoform 1 favors differentiation.

关联

项与 SRPK1 相关的药物

EXN-407

靶点

SRPK1

作用机制

SRPK1拮抗剂

在研机构-

原研机构

Exonate Ltd.

在研适应症-

非在研适应症

糖尿病性黄斑水肿 [+1]

最高研发阶段无进展

首次获批国家/地区-

首次获批日期1800-01-20

项与 SRPK1 相关的临床试验

NCT04565756 / Completed临床1/2期

A Randomised, Double-Masked Vehicle-Controlled, Multiple Dose, Dose Escalation Study To Evaluate The Safety and Tolerability of EXN407 in Subjects With Centre Involved Diabetic Macular Oedema Secondary to Diabetes Mellitus

This first in human (FIH), Phase Ib/II study of EXN407 is a randomised, double-masked, vehicle-controlled, multiple dose, dose-escalating study to evaluate the safety and tolerability of EXN407 in subjects with centre involved Diabetic Macular Oedema (DMO), with Centre-subfield macular thickness (CMT) between 280-420 µm and Best corrected visual acuity (BCVA) better than or equal to 69 ETDRS score (approximate Snellen equivalent 20/40 (6/12 letters) in the study eye, which is considered secondary to diabetes mellitus.
This study will provide a basis for further clinical development of EXN407 ophthalmic solution.

开始日期2020-11-05

申办/合作机构

Exonate Ltd.

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100 项与 SRPK1 相关的临床结果

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100 项与 SRPK1 相关的转化医学

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0 项与 SRPK1 相关的专利（医药）

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295

项与 SRPK1 相关的文献（医药）

2024-02-07·PLoS pathogens

SRPK2 Mediates HBV Core Protein Phosphorylation and Capsid Assembly via Docking Interaction.

Article

作者: Ryan Pak Hong Yip ; Doris Ching Ying Kwok ; Louis Tung Faat Lai ; Siu-Ming Ho ; Ivan Chun Kit Wong ; Chi-Ping Chan ; Wilson Chun Yu Lau ; Jacky Chi Ki Ngo

Members of the serine-arginine protein kinase (SRPK) family, SRPK1 and SRPK2, phosphorylate the hepatitis B core protein (Cp) and are crucial for pregenomic RNA encapsidation during viral nucleocapsid assembly. Among them, SRPK2 exhibits higher kinase activity toward Cp. In this study, we identified Cp sites that are phosphorylated by SRPK2 and demonstrated that the kinase utilizes an SRPK-specific docking groove to interact with and regulate the phosphorylation of the C-terminal arginine rich domain of Cp. We determined that direct interaction between the docking groove of SRPK2 and unphosphorylated Cp inhibited premature viral capsid assembly in vitro, whereas the phosphorylation of the viral protein reactivated the process. Pull-down assays together with the new cryo-electron microscopy structure of the HBV capsid in complex with SRPK2 revealed that the kinases decorate the surface of the viral capsid by interacting with the C-terminal domain of Cp, underscoring the importance of the docking interaction in regulating capsid assembly and pregenome packaging. Moreover, SRPK2-knockout in HepG2 cells suppressed Cp phosphorylation, indicating that SRPK2 is an important cellular kinase for HBV life cycle.

2024-02-06·Biomedicines

SRPK1 Promotes Glioma Proliferation, Migration, and Invasion through Activation of Wnt/β-Catenin and JAK-2/STAT-3 Signaling Pathways.

Article

作者: Mengna Shi ; Dan Sun ; Lu Deng ; Jing Liu ; Min-Jie Zhang

Currently, the treatment of gliomas still relies primarily on surgery and radiochemotherapy. Although there are various drugs available, including temozolomide, the overall therapeutic effect is unsatisfactory, and the prognosis remains poor. Therefore, the in-depth study of the mechanism of glioma development and a search for new therapeutic targets are the keys to improving the therapeutic treatment of gliomas and improving the prognosis of patients. Immunohistochemistry is used to detect the expression of relevant molecules in tissues, qPCR and Western blot are used to detect the mRNA and protein expression of relevant molecules, CCK-8 (Cell Counting Kit-8) is used to assess cell viability and proliferation capacity, Transwell is used to evaluate cell migration and invasion ability, and RNA transcriptome sequencing is used to identify the most influential pathways. SRPK1 (SRSF protein kinase 1) is highly expressed in gliomas but is not expressed in normal tissues. Its expression is positively correlated with the grades of gliomas and negatively correlated with prognosis. SRPK1 significantly promotes the occurrence and development of gliomas. Knocking down SRPK1 leads to a significant decrease in the proliferation, migration, and invasion abilities of gliomas. Loss of SRPK1 expression induces G2/M phase arrest and mitotic catastrophe, leading to apoptosis in cells. Overexpression of SRPK1 activates the Wnt/β-catenin (wingless-int1/β-catenin) and JAK-2/STAT-3 (Janus kinase 2/signal transducer and activator of transcription 3) signaling pathways, promoting the proliferation, migration, and invasion of gliomas. Overexpression of SRPK1 rescues the reduced cell proliferation, migration, and invasion abilities caused by the silencing of β-catenin or JAK-2. A stable shRNA-LN229 cell line was constructed, and using a nude mouse model, it was found that stable knockout of SRPK1 significantly reduced the tumorigenic ability of glioma cells, as evidenced by a significant decrease in the subcutaneous tumor volume and weight in nude mice. We have demonstrated that SRPK1 is highly expressed in gliomas. Overexpression of SRPK1 activates the Wnt/β-catenin and JAK-2/STAT-3 signaling pathways, promoting the proliferation, migration, and invasion of gliomas. Silencing SRPK1-related signaling pathways may provide potential therapeutic options for glioma patients.

2024-01-03·Indian journal of cancer

Role of Serine arginine protein kinase 1 and Minichromosome maintenance protein 2 in predicting epithelial ovarian cancer response to treatment and prognosis.

Article

作者: Enas Elkholy ; Asmaa Gaber Abdou ; Alshimaa Mahmoud Alhanafy ; Tarek Hashem ; Reham Hassan ; Mohamed Shehata

BACKGROUND:

Serine-Arginine (SR) proteins are a conserved family of proteins involved in RNA splicing and are reported to be over-expressed in multiple cancers. The aim of the study is evaluation of the expression of Serine arginine protein kinase 1 (SRPK1) and Minichromosome maintenance protein 2 (MCM2) in epithelial ovarian cancer (EOC) and their correlation with clinicopathological features, response to therapy, progression-free survival (PFS), and cancer-specific survival (CSS).

METHODS:

This study was carried out on surgical specimens of 65 patients diagnosed with EOC which were submitted to immunohistochemical staining by SRPK1 and MCM2 antibodies.

RESULTS:

About 89.2% of cases showed SRPK1 expression and its high expression was significantly associated with type II tumors and advanced stage. All cases showed nuclear immunoreaction for MCM2 with high expression in 49.2% of cases. There was a significant relationship between high values of SRPK1 H-score and percentage of MCM2. Postmenopause, type II pathology, advanced stage, absence of complete response to the treatment, resistance to platinum-based chemotherapy, and surgery done by a general surgeon were the factors affecting PFS. Response to treatment and platinum sensitivity were the most independent factors affecting patients' PFS. The factors associated with shorter CSS were suboptimal debulking, advanced stage, absence of complete response to the treatment, platinum resistance, and high SRPK1. High SRPK1 expression and platinum sensitivity were the independent factors affecting patients' CSS.

CONCLUSIONS:

SRPK1 is an unfavorable biomarker in EOC patients because of its association with aggressive histologic type, advanced International Federation of Gynecology and Obstetrics (FIGO) stage, and worse survival. SRPK1 could promote the proliferation of EOC by up-regulation of MCM2.

项与 SRPK1 相关的新闻（医药）

2024-03-15

·Firstwordpharma

Study failure of diabetic retinopathy eye drop leaves OcuTerra in tears

OcuTerra Therapeutics on Thursday announced that its topical diabetic retinopathy candidate nesvategrast – the only asset in its pipeline – failed to meet the primary and key secondary efficacy endpoints of a Phase II study. “We are disappointed that the top-line data…did not demonstrate a statistically significant impact on severity or progression of diabetic retinopathy,” remarked OcuTerra CEO Kerrie Brady. She added that the company would review the trial’s complete dataset to decide on the next steps for the small-molecule RGD integrin inhibitor, also known as OTT166, and explore strategic alternatives.The DR:EAM study investigated daily nesvategrast across two dose levels against placebo in 225 patients with diabetic retinopathy. While the top-line data demonstrated favourable safety and tolerability for nesvategrast, it failed to show a significant improvement on the Diabetic Retinopathy Severity Scale (DRSS) versus placebo, which was the primary efficacy endpoint. The drug also fell short on the secondary goal of disease progression, but managed to meet the other secondary endpoint of preventing vision threatening events by week 24 in patients with baseline DRSS levels between 47 and 53.Another topical small molecule vying for a spot in the diabetic retinal diseases space is Exonate’s SRPK1 inhibitor EXN-407, which recently showed favourable safety, tolerability and biological activity in a Phase Ib/IIa trial, making its way to the Phase IIb CLEAR-DM study.

2024-03-10

·药明康德

12周体重下降超13%的下一代减重疗法；使半数患者获益的实体瘤CAR-T疗法… | 一周盘点

▎药明康德内容团队编辑本期看点1. 诺和诺德（Novo Nordisk）的下一代减重疗法amycretin的1期临床试验结果亮眼，患者在接受治疗12周后体重下降幅度达13.1%。2. 用于治疗复发性和难治性恶性胶质瘤的CAR-T细胞疗法MB-101在1期临床试验中使50%的患者有获益，两名患者获得了完全缓解（CR），其中一名已维持超过66个月。3. 用于治疗1型强直性肌营养不良（DM1）的抗体偶联RNAi疗法del-desiran在早期临床试验中获得了积极的长期数据，与自然疾病历史数据相比，在多个临床终点逆转了患者的疾病进展。4. 拜耳（Bayer）用于治疗帕金森病的干细胞疗法BRT-DA01在1期临床研究中继续保持了良好的耐受性，且患者获益随时间继续增长。5. 治疗杜氏肌营养不良（DMD）的基因疗法RGX-202的早期临床试验的额外中期安全性和有效性数据积极，将于今年启动关键试验。药明康德内容团队整理Amycretin：公布1期临床试验数据诺和诺德公布了其口服GLP-1和胰淀素的长效共激动剂amycretin的最新临床试验结果。在这项包含16位患者的小型1期试验当中，患者在接受治疗12周后其体重下降幅度达13.1%，相较之下，安慰剂组患者的体重下降幅度仅为1.1%。此外，amycretin展现良好的药代动力学特性，以及与诺和诺德所开发的GLP-1类疗法类似的良好安全性、耐受性以及不良反应。行业媒体Fierce Biotech指出，过去STEP-1临床试验结果显示，司美格鲁肽组患者在68周试验期间的体重降幅为14.9%。虽然不同临床试验之间的结果难以一同比较，然而amycretin在1期试验早期结果中所展现快速减重的效果，展现了该药物的巨大潜力。▲口服amycretin在1期试验当中展现显著减重效果（图片来源：诺和诺德公司官网）该公司预计在2024年下半年启动2期试验，在2型糖尿病患者中探索口服与皮下注射amycretin的疗效与安全性。MB-101：公布1期临床试验数据Mustang Bio公司宣布，其CAR-T细胞疗法MB-101在治疗复发性和难治性恶性胶质瘤（包括胶质母细胞瘤）患者方面具有良好的安全性和临床活性。MB-101是一种靶向IL13Rα2的CAR-T细胞疗法，IL13Rα2是一种局限在GBM中表达的受体，在大多数多形性胶质母细胞瘤（GBM）中大量表达。MB-101包括铰链优化的第二代CAR，其IgG4接头中的突变可以减少脱靶Fc相互作用、4-1BB（CD137）共刺激信号结构域可以提高CAR-T细胞的持久性。它同时表达CD19的细胞外结构域作为筛选/安全标记。此次公布的结果显示，MB-101的耐受性良好，50%（29/58）的患者达到了疾病稳定（SD）或更好的状况，两位患者达到了部分缓解（PR），两位患者达到了CR。两位达到CR的患者分别维持了7.5个月和超过66个月。复发性GBM患者的的预期生存期为6个月，该研究中所有患者的中位总生存期（OS）为8个月，而接受肿瘤内（ICT）/脑室内（ICV）双重给药和优化制造工艺的MB-101治疗的复发性GBM患者的中位OS为10.2个月，较此类患者的预期生存期延长了70%，。Del-desiran（AOC 1001）：公布1/2期临床试验的长期数据Avidity Biosciences公司公布了其抗体偶联RNAi疗法del-desiran（曾用名AOC 1001）治疗1型强直性肌营养不良患者的开放标签扩展试验MARINA-OLE的最新积极长期数据。Del-desiran由Avidity专有的靶向1型转铁蛋白受体（TfR1）单克隆抗体与靶向DMPK基因mRNA的siRNA偶联所构成。临床前研究显示，它能够成功递送siRNA至肌肉组织，在骨骼肌、心肌与平滑肌等组织中引起持续性、剂量依赖性DMPK的mRNA水平下降。美国FDA与欧洲药品管理局（EMA）皆授予其孤儿药资格，FDA还授予此疗法快速通道资格。DM1是一种未被充分认识、逐渐恶化且常常致命的神经肌肉疾病，目前没有获批的治疗方法。此次公布的数据显示，与匹配的自然病史研究人群相比，接受del-desiran治疗的DM1患者一年内在多个终点上逆转了疾病的进展，包括肌张力、肌肉力量和患者报告的日常生活活动。该公司计划在今年第二季度启动3期临床试验HARBOR，▲Del-desiran显著改善vHOT临床终点（图片来源：Avidity Biosciences公司官网）▲Del-desiran显著改善手握力和定量肌肉测试指标（图片来源：Avidity Biosciences公司官网）Bemdaneprocel（BRT-DA01）：公布1期临床试验的新数据拜耳及其旗下BlueRock Therapeutics公司公布了其在研干细胞衍生疗法bemdaneprocel（BRT-DA01）治疗帕金森病的1期临床试验的新数据。Bemdaneprocel是一种在研细胞疗法，由多能干细胞衍生、可产生多巴胺的神经元组成，可通过手术植入帕金森病患者的大脑。当这些细胞被移植后，它们有可能重建帕金森病患者脑内受破坏的神经网络，借此恢复患者的运动和非运动功能。该研究使用Hauser Diary对患者进行分类，患者在“开通”（on）状态表示症状得到良好控制；在“关闭”（off）状态则表示症状恶化。此前公布的结果显示，和基线相比，参与bemdaneprocel临床试验的高剂量组受试者在一年后处于“开通”状态的时间多2.16小时，且没有出现运动障碍；处于“关闭”状态的时间相应减少了1.91小时。低剂量组受试者处于“开通”状态的时间比基线多0.72小时，且没有出现运动障碍，处于“关闭”状态的时间相应减少了0.75小时。在高剂量组中，通过帕金森病评定量表MDS-UPDRS第三部分为“停药”状态下bemdaneprocel一年期疗效进行评分，得到相较于基线降低13.0分的结果。低剂量组结果为较基线降低7.6分。此次更新的数据显示，第18个月时，bemdaneprocel继续保持了良好的耐受性，没有发生重大安全性问题。移植到大脑中的细胞存活并定植了下来，在第12个月停止免疫抑制治疗后，F-DOPA信号依然在增加。此外，与基线相比，两个剂量队列的探索性临床终点都有所改善，高剂量队列的受试者表现出更大的改善。和基线相比，高剂量组受试者处于“开通”状态的时间多2.7小时；处于“关闭”状态的时间相应减少了2.7小时。低剂量组受试者处于“开通”状态的时间比基线多0.2小时，处于“关闭”状态的时间相应减少了0.8小时。此外，高剂量组18个月时的疗效评分与基线相比降低了23分，低剂量组较基线降低了8.6分。RGX-202：公布1/2期临床试验的新数据REGENXBIO公司公布了其在研基因疗法RGX-202在4至11岁杜氏肌营养不良患者中进行的1/2期AFFINITY DUCHENNE试验的额外中期安全性和有效性数据。RGX-202是一款基于AAV8载体的基因疗法，旨在递送表达微肌营养不良蛋白的转基因进入骨骼肌和心肌组织。接受两种剂量水平的所有4例患者皆完成了在第三个月时的试验评估，分析显示，其体内RGX-202微肌营养不良蛋白的表达皆有所增加，并且血清肌酐激酶（CK）水平较基线有所下降，显示该疗法具潜在临床疗效。首位接受剂量水平2治疗的12.1岁患者的数据显示，在三个月时其RGX-202微肌营养不良蛋白表达为标准对照的75.7%，且在十周时观察到患者的血清CK水平较基线降低了77%。CK水平的升高与肌肉损伤有关，DMD患者的CK水平普遍升高。试验详细数据如下所示：▲RGX-202试验疗效结果摘要（图片来源：参考资料[14]）EXN407：公布1b/2a期临床试验数据Exonate公司公布了其主打候选药物EXN407在1b/2a期临床试验中获得积极结果。EXN407是一种每日两次的眼科配方，主要成分为SRPK1小分子抑制剂。这种眼药水配方利用SRPK1在血管内皮生长因子（VEGF）的选择性剪接中的作用，VEGF是一种在血管生长调节中起重要作用的蛋白质。通过抑制SRPK1，EXN407可以选择性地靶向导致视网膜血管疾病进展的VEGF亚型，抑制眼内渗漏血管的异常生长。此次公布的结果显示，EXN407具有良好的安全性和耐受性，以及明显的生物活性信号。与安慰剂组相比，EXN407组黄斑厚度持续减少，与先前报道的抗VEGF注射效果相仿。该试验结果进一步显示，EXN407组60%的患者血管渗漏显著减少，安慰剂组这一数值为20%。新闻稿指出，这些数据支持进一步开发EXN407成为治疗糖尿病视网膜病和糖尿病性黄斑水肿等视网膜血管疾病的首个外用治疗方法。Exonate计划将EXN407推进到2b期临床试验。UB-312：公布1期临床试验数据Vaxxinity公司公布了其用于治疗帕金森病的疫苗UB-312取得的积极临床数据。UB-312旨在靶向导致帕金森病和其他突触核蛋白病的毒性物质——聚集形式的α突触核蛋白（α-synuclein，aSyn）。通过点印迹法测定，UB-312诱导的抗体优先与聚集的aSyn结合，而几乎不与正常的aSyn单体结合。经种子扩增试验（SAA）测定，单次治疗后，300/100/100 µg剂量组患者脑脊液（CSF）中聚集的aSyn与基线相比下降了20%，而安慰剂组则增加了3%（p<0.05）。此外，根据UPDRS II临床量表的结果，CSF中可检测到UB-312诱导抗体的患者的日常生活能力有所改善（p<0.01）。这些数据还表明，大脑中聚集的aSyn减少与MDS-UPDRS II的变化之间存在相关性（R=0.52，p=0.001）。Vaxxinity公司的新闻稿指出，UB-312是首个可减少帕金森病患者CSF中病理性aSyn的候选免疫疗法。NT-0796：公布1b/2a期临床试验数据NodThera公司公布了其NLRP3炎症小体抑制剂NT-0796在帕金森病患者中开展的早期临床试验的积极数据。结果显示，NLRP3炎症小体抑制剂NT-0796的安全性和耐受性良好，可在28天内将帕金森病患者的主要神经炎症和炎症生物标志物（例如IL-1β、IL-6、CCL2、CXCL1和CXCL8）降至健康老年对照组的水平。此外，研究人员还观察到神经退行性标志物的减少，包括神经丝轻链（NfL）和sTREM2。药代动力学结果表明，NT-0796在大脑中的浓度可在24小时内保持不变，支持每日一次的给药方案。该研究表明，NT-0796有可能改变帕金森病的治疗模式，并通过改变疾病进程阻止疾病进展。大家都在看药明康德为全球生物医药行业提供一体化、端到端的新药研发和生产服务，服务范围涵盖化学药研发和生产、生物学研究、临床前测试和临床试验研发、细胞及基因疗法研发、测试和生产等领域。如您有相关业务需求，欢迎点击下方图片填写具体信息。▲如您有任何业务需求，请长按扫描上方二维码，或点击文末“阅读原文/Read more”，即可访问业务对接平台，填写业务需求信息▲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] Cullinan Oncology Announces U.S. FDA Clearance of Investigational New Drug Application for Novel MICA/B Antibody, CLN-619, for Relapsed/Refractory Multiple Myeloma. 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Retrieved March 7, 2024 from https://www.prnewswire.com/news-releases/dragonfly-has-received-milestone-payment-following-dosing-of-first-patient-in-abbvie-phase-1-clinical-trial-evaluating-df4101abbv-303-302078923.html[19] Vaxxinity Announces Positive Target Engagement Data from Phase 1 Clinical Trial for Parkinson’s Disease at AD/PD™ 2024. Retrieved March 7, 2024 from https://www.globenewswire.com/news-release/2024/03/07/2842413/0/en/Vaxxinity-Announces-Positive-Target-Engagement-Data-from-Phase-1-Clinical-Trial-for-Parkinson-s-Disease-at-AD-PD-2024.html[20] Mustang Bio Announces Publication in Nature Medicine of Data from Phase 1 Trial Evaluating MB-101 IL13Rα2-targeted CAR T-Cells in High-Grade Glioma. Retrieved March 7, 2024 from https://ir.mustangbio.com/news-events/press-releases/detail/175/mustang-bio-announces-publication-in-nature-medicine-of[21] Alligator Bioscience and Aptevo Therapeutics Announce Positive Interim Data of Dose Escalation Phase of ALG.APV-527 Phase 1 Study in Solid Tumor Cancers Expressing Tumor Antigen 5T4. Retrieved March 7, 2024 from https://alligatorbioscience.se/en/mfn_news/alligator-bioscience-and-aptevo-therapeutics-announce-positive-interim-data-of-dose-escalation-phase-of-alg-apv-527-phase-1-study-in-solid-tumor-cancers-expressing-tumor-antigen-5t4/[22] NodThera’s NLRP3 Inhibitor NT-0796 Reverses Neuroinflammation in Parkinson’s Disease Phase Ib/IIa Trial. Retrieved March 7, 2024 from https://www.nodthera.com/news/nodtheras-nlrp3-inhibitor-nt-0796-reverses-neuroinflammation-in-parkinsons-disease-phase-ib-iia-trial/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期临床结果基因疗法免疫疗法

2024-03-07

·药明康德

有望成为首款！潜在“first-in-class”眼药水临床结果积极

Exonate今天宣布其主打候选药物EXN407在1b/2a期临床试验中获得积极结果。数据显示了EXN407的安全性和耐受性，以及明显的生物活性信号。新闻稿指出，这些数据支持进一步开发EXN407成为治疗糖尿病视网膜病和糖尿病性黄斑水肿等视网膜血管疾病的首个外用治疗方法。Exonate计划将EXN407推进到2b期临床试验。 EXN407是一种每日两次的眼科配方，主要成分为SRPK1小分子抑制剂。这种眼药水配方利用SRPK1在血管内皮生长因子（VEGF）的选择性剪接中的作用，VEGF是一种在血管生长调节中起重要作用的蛋白质。通过抑制SRPK1，EXN407可以选择性地针对导致视网膜血管疾病进展的VEGF亚型，抑制眼内渗漏血管的异常生长。这项1b/2a期临床研究评估了EXN407单药治疗的安全性、耐受性以及生物活性信号，在未接受过治疗的轻度/中度非增生性糖尿病视网膜病和轻度糖尿病性黄斑水肿患者中进行。独立的剂量递增委员会认为EXN407安全且耐受性良好，100%的患者完成了研究，无需抗VEGF挽救治疗，且未报告与EXN407相关的重大或严重不良事件。此外，EXN407的耐受性良好，滴眼舒适度评分与安慰剂和人工泪液相似。除了达到主要安全性和耐受性终点外，研究还观察到了可喜的生物活性信号，与安慰剂组相比，EXN407组黄斑厚度持续减少，与先前报道的抗VEGF注射效果相仿。该试验结果进一步显示，EXN407组60%的患者血管渗漏显著减少，安慰剂组这一数值为20%。参考资料：[1] Exonate first-in-class eye drop Phase Ib/IIa trial data demonstrate safety and biological activity in treatment of diabetic retinopathy and diabetic macular oedema. Retrievd March 5, 2024, from https://www.businesswire.com/news/home/20240304540449/en 内容来源于网络，如有侵权，请联系删除。