Phase 2 Study of 9-ING-41, a Glycogen Synthase Kinase 3 Beta (GSK 3β) Inhibitor, Plus Carboplatin in Patients With Advanced, Metastatic Salivary Gland Carcinoma

9-ING-41 is a small molecule potent selective GSK-3β inhibitor with antitumor activity. This study investigates 9-ING-41 in combination with carboplatin chemotherapy in patients with incurable, recurrent or metastatic salivary gland carcinomas (SGC). Patients with advanced SGC (including all histologic subtypes and adenoid cystic carcinoma [ACC]) will receive 9-ING-41 intravenously (IV) along with carboplatin IV at standard dosing together on Day 1, and 9-ING-41 alone on Day 4 of a 21-day cycle. Participants will be enrolled to two histologic cohorts: Cohort 1 will be comprised of those with ACC, and Cohort 2 will include patients with non-ACC SGC (or all other salivary gland cancer histologies). Treatment will continue until progression of disease, death, or discontinuation of therapy for any reason.

开始日期2030-12-18

申办/合作机构

Actuate Therapeutics, Inc.初创企业

NCT05077800 / Recruiting临床2期

A Phase II Study of FOLFIRINOX Combined With the Glycogen Synthase Kinase-3 Beta (GSK-3 β) Inhibitor 9-ING-41 and the Transforming Growth Factor-β (TGF-β) Inhibitor Losartan in Patients With Untreated Metastatic Pancreatic Cancer

The purpose of this study is to find out if an experimental drug will prevent metastatic pancreatic adenocarcinoma from becoming resistant to standard treatment for the disease.
The names of the study drugs involved in this study are:
* 9-ING-41
* Losartan
* Ferumoxytol
* FOLFIRINOX (made up of 4 different drugs):
* 5-Fluorouracil (5-FU)
* Oxaliplatin
* Irinotecan
* Leucovorin

开始日期2022-03-21

申办/合作机构

Actuate Therapeutics, Inc.初创企业

[+1]

NCT05116800 / Withdrawn临床2期IIT

A Phase 2 Study of 9-ING-41, a Glycogen Synthase Kinase-3 Beta (GSK-3β) Inhibitor, Combined With Chemotherapy in Advanced Soft Tissue and Bone Sarcomas

This is an open label, two-stratum, phase 2 clinical trial evaluating the efficacy of 9-ING-41 in combination with gemcitabine/docetaxel in patients ≥10 years of age with advanced sarcoma. 9-ING-41 in combination with gemcitabine and docetaxel will lead to sustained disease control and/or increase the rates of objective response in patients with unresectable or metastatic soft tissue and bone sarcomas.

开始日期2022-03-01

申办/合作机构

Brown University

[+1]

100 项与 Elraglusib 相关的临床结果

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100 项与 Elraglusib 相关的转化医学

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100 项与 Elraglusib 相关的专利（医药）

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项与 Elraglusib 相关的文献（医药）

2024-06-01·JHEP Reports

Glycogen synthase kinase 3 activity enhances liver inflammation in MASH

Article

作者: Islam, Shahidul ; Kim, Iljung ; Pavelko, Kevin D ; Mazar, Andrew P ; Li, Hu ; Warasnhe, Khaled ; Bamidele, Adebowale O ; Ibrahim, Samar H ; Noh, Yung-Kyun ; Kim Lee, Hyun Se ; Holmes, Heather ; Valenzuela-Pérez, Lucía ; Furuta, Kunimaro ; Guo, Qianqian ; Romero, Michael F ; Correia, Cristina ; Khoury, Mireille ; Sussman, Caroline R ; Meroueh, Chady ; Hirsova, Petra

Background & Aims:

Metabolic dysfunction-associated steatohepatitis (MASH) is characterized by excessive circulating toxic lipids, hepatic steatosis, and liver inflammation. Monocyte adhesion to liver sinusoidal endothelial cells (LSECs) and transendothelial migration (TEM) are crucial in the inflammatory process. Under lipotoxic stress, LSECs develop a proinflammatory phenotype known as endotheliopathy. However, mediators of endotheliopathy remain unclear.

Methods:

Primary mouse LSECs isolated from C57BL/6J mice fed chow or MASH-inducing diets rich in fat, fructose, and cholesterol (FFC) were subjected to multi-omics profiling. Mice with established MASH resulting from a choline-deficient high-fat diet (CDHFD) or FFC diet were also treated with two structurally distinct GSK3 inhibitors (LY2090314 and elraglusib [9-ING-41]).

Results:

Integrated pathway analysis of the mouse LSEC proteome and transcriptome indicated that leukocyte TEM and focal adhesion were the major pathways altered in MASH. Kinome profiling of the LSEC phosphoproteome identified glycogen synthase kinase (GSK)-3β as the major kinase hub in MASH. GSK3β-activating phosphorylation was increased in primary human LSECs treated with the toxic lipid palmitate and in human MASH. Palmitate upregulated the expression of C-X-C motif chemokine ligand 2, intracellular adhesion molecule 1, and phosphorylated focal adhesion kinase, via a GSK3-dependent mechanism. Congruently, the adhesive and transendothelial migratory capacities of primary human neutrophils and THP-1 monocytes through the LSEC monolayer under lipotoxic stress were reduced by GSK3 inhibition. Treatment with the GSK3 inhibitors LY2090314 and elraglusib ameliorated liver inflammation, injury, and fibrosis in FFC- and CDHFD-fed mice, respectively. Immunophenotyping using cytometry by mass cytometry by time of flight of intrahepatic leukocytes from CDHFD-fed mice treated with elraglusib showed reduced infiltration of proinflammatory monocyte-derived macrophages and monocyte-derived dendritic cells.

Conclusion:

GSK3 inhibition attenuates lipotoxicity-induced LSEC endotheliopathy and could serve as a potential therapeutic strategy for treating human MASH.

Impact and Implications:

LSECs under lipotoxic stress in MASH develop a proinflammatory phenotype known as endotheliopathy, with obscure mediators and functional outcomes. The current study identified GSK3 as the major driver of LSEC endotheliopathy, examined its pathogenic role in myeloid cell-associated liver inflammation, and defined the therapeutic efficacy of pharmacological GSK3 inhibitors in murine MASH. This study provides preclinical data for the future investigation of GSK3 pharmacological inhibitors in human MASH. The results of this study are important to hepatologists, vascular biologists, and investigators studying the mechanisms of inflammatory liver disease and MASH, as well as those interested in drug development.

2024-02-01·Clinical cancer research : an official journal of the American Association for Cancer Research

Phase I Study of Elraglusib (9-ING-41), a Glycogen Synthase Kinase-3β Inhibitor, as Monotherapy or Combined with Chemotherapy in Patients with Advanced Malignancies

Article

作者: Cervantes, Andrés ; Cavalcante, Ludimila ; Munster, Pamela ; Borden, Brittany A. ; Harvey, R. Donald ; Powell, Steven ; Longstreth, James ; Coveler, Andrew L. ; Mikrut, William ; Mazar, Andrew P. ; Giles, Francis J. ; Kurzrock, Razelle ; Weisskittel, Taylor ; Li, Hu ; Koukol, Austin ; Smith, Sheri ; Bastos, Bruno ; Sahai, Vaibhav ; Steeghs, Neeltje ; Ma, Wen Wee ; Carneiro, Benedito A. ; Safran, Howard ; Davis, Elizabeth ; Mahalingam, Devalingam ; Sahebjam, Solmaz ; Saeed, Anwaar

Abstract:

Purpose::

The safety, pharmacokinetics, and efficacy of elraglusib, a glycogen synthase kinase-3β (GSK-3β) small-molecule inhibitor, as monotherapy or combined with chemotherapy, in patients with relapsed or refractory solid tumors or hematologic malignancies was studied.

Patients and Methods::

Elraglusib (intravenously twice weekly in 3-week cycles) monotherapy dose escalation was followed by dose escalation with eight chemotherapy regimens (gemcitabine, doxorubicin, lomustine, carboplatin, irinotecan, gemcitabine/nab-paclitaxel, paclitaxel/carboplatin, and pemetrexed/carboplatin) in patients previously exposed to the same chemotherapy.

Results::

Patients received monotherapy (n = 67) or combination therapy (n = 171) elraglusib doses 1 to 15 mg/kg twice weekly. The initial recommended phase II dose (RP2D) of elraglusib was 15 mg/kg twice weekly and was defined, without dose-limiting toxicity observation, due to fluid volumes necessary for drug administration. The RP2D was subsequently reduced to 9.3 mg/kg once weekly to reduce elraglusib-associated central/peripheral vascular access catheter blockages. Other common elraglusib-related adverse events (AE) included transient visual changes and fatigue. Grade ≥3 treatment-emergent AEs occurred in 55.2% and 71.3% of patients on monotherapy and combination therapy, respectively. Part 1 monotherapy (n = 62) and part 2 combination (n = 138) patients were evaluable for response. In part 1, a patient with melanoma had a complete response, and a patient with acute T-cell leukemia/lymphoma had a partial response (PR). In part 2, seven PRs were observed, and the median progression-free survival and overall survival were 2.1 [95% confidence interval (CI), 2–2.6] and 6.9 (95% CI, 5.7–8.4) months, respectively.

Conclusions::

Elraglusib had a favorable toxicity profile as monotherapy and combined with chemotherapy and was associated with clinical benefit supporting further clinical evaluation in combination with chemotherapy.

2023-06-14·Cell communication and signaling : CCS

Elraglusib (formerly 9-ING-41) possesses potent anti-lymphoma properties which cannot be attributed to GSK3 inhibition.

Article

作者: Coats, Josh T ; Tauro, Sudhir ; Sutherland, Calum

Elraglusib (formerly 9-ING-41) is an ATP-competitive inhibitor of glycogen synthase kinase-3β (GSK3β) undergoing clinical trials for the treatment of various cancers including non-Hodgkin lymphoma (NHL). The drug reduces proliferation of several NHL cell lines and has efficacy in xenograft models of the disease. To confirm the importance of its action on GSK3β, we treated 3 lymphoma cell lines with selective, structurally distinct GSK3 inhibitors: CT99021, SB216763, LY2090314, tideglusib, and elraglusib. Stabilization of β-catenin and reduced phosphorylation of CRMP2, two validated targets of GSK3, were used as functional read-outs for GSK3 inhibition. CT99021, SB216763, and LY2090314 failed to reduce proliferation or viability in any cell line at concentrations that stabilized β-catenin and reduced CRMP2 phosphorylation. There was partial reduction of CRMP2 phosphorylation but no significant effect on β-catenin at cytotoxic doses of elraglusib. There was no indication of GSK3 inhibition at doses of tideglusib that affected cell viability and apoptosis. Cell-free kinase screening confirmed several other targets of elraglusib, distinct from the GSK3 inhibitors with no anti-lymphoma actions, including PIM kinases and MST2. These data question GSK3 as the target of elraglusib in lymphoma, and hence the utility of GSK3 expression as a 'stand-alone', therapeutic biomarker in NHL. Video Abstract.

项与 Elraglusib 相关的新闻（医药）

2024-09-23

·GlobeNewswire-Health Care

Actuate Announces Scientific Reports Publication on Elraglusib’s Novel Immunomodulatory Mechanism of Action as a GSK-3β Inhibitor

New Mechanistic Insights Underscore Multiple Potential Roles for Elraglusib as an Immune Modulator in the treatment of NeuroblastomaStudy Illustrates Potential to Activate the Immune System Even in Cancers That Have Not Previously Responded to Checkpoint Inhibitors CHICAGO and FORT WORTH, Texas, Sept. 23, 2024 (GLOBE NEWSWIRE) -- Actuate Therapeutics, Inc. (NASDAQ: ACTU) (“Actuate” or the “Company”), a clinical-stage biopharmaceutical company, focused on developing therapies for the treatment of high-impact, difficult-to-treat cancers through the inhibition of glycogen synthase kinase-3 beta (GSK-3β), announced the Scientific Reports publication of novel mechanistic data for its development candidate, elraglusib. The article, entitled, “Targeted inhibition of glycogen synthase kinase‑3 using 9‑ING‑41 (elraglusib) enhances CD8 T‑cell‑reactivity against neuroblastoma cells” is available online. “The mechanistic data published in Scientific Reports provides crucial evidence of elraglusib’s ability to enhance activation of the immune system by tumor cells,” said Daniel Schmitt, President & Chief Executive Officer of Actuate. “By improving antigen presentation and enhancing the activation of CD8+ cytotoxic T cells, we are paving the way for more effective immunotherapeutic strategies including combinations of elraglusib with checkpoint inhibitors.” Using neuroblastoma, which is typically refractory to checkpoint inhibitors, as a model system, these findings illustrate the potential to activate the immune system even in cancers that have not previously responded to checkpoint inhibitors and underscore elraglusib’s potential as a highly innovative treatment for challenging cancers. The summary of key mechanistic findings: Elraglusib significantly enhances MHC-I molecule surface expression of neuroblastoma cells, improving their recognition by cytotoxic T lymphocytes (CTLs)Treatment with elraglusib leads to the disruption of NK-κB signaling, a key contributor to tumor cell survival, promoting cancer cell apoptosis and reducing treatment resistanceElraglusib boosts IFNγ signaling through the JAK/STAT pathway, particularly STAT1, which further supports improved antigen presentation and immune responseWhen combined with an anti-PD-1 treatment, elraglusib boosted CD8+ T cell proliferation and activation by neuroblastoma cells, showing potential for further development of these tumor immune response enhancing therapeutics. “Despite the clinical benefit observed with checkpoint inhibitors in many advanced cancer types, the majority of patients treated with checkpoint inhibitors fail to respond,” said Dr. Andrew Mazar, Actuate’s Scientific Co-founder and Chief Operating Officer. “The ability to enhance immunogenicity in a tumor such as neuroblastoma that is not unrecognized by the immune system, holds therapeutic promise for neuroblastoma patients and could potentially be translated for the treatment of other immunologically cold tumors as well.” Elraglusib is currently being evaluated in Phase 2 Trial in metastatic pancreatic cancer (NCT03678883) and Phase 1/2 Trial (NCT04239092) in Ewing Sarcoma (EWS) and EWS-related sarcomas. About Actuate Therapeutics, Inc. Actuate is a clinical-stage biopharmaceutical company focused on developing therapies for the treatment of high-impact, difficult-to-treat cancers. Actuate’s lead investigational drug product, elraglusib (a novel GSK-3β inhibitor), targets molecular pathways in cancer that are involved in promoting tumor growth and resistance to conventional cancer drugs such as chemotherapy including EMT, NF-kB-mediated resistance and several DDR pathways. Elraglusib also acts as a mediator of anti-tumor immunity through the inhibition of NF-kB in immune cells and regulates multiple immune checkpoints and immune cell function. For additional information, please visit the Company’s website at http://www.actuatetherapeutics.com. Forward-Looking Statements This press release contains forward-looking statements about us, including our clinical trials and development plans, and our industry. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “might,” “ongoing,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “will,” “would,” or the negative of these terms or other comparable terminology are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. All statements, other than statements related to present facts or current conditions or of historical facts, contained in this press release are forward-looking statements. Accordingly, these statements involve estimates, assumptions, substantial risks and uncertainties which could cause actual results to differ materially from those expressed in them, including but not limited to that clinical and preclinical drug development involves a lengthy and expensive process with uncertain timelines and outcomes, results of prior preclinical studies and early clinical trials are not necessarily predictive of future results, and elraglusib may not achieve favorable results in clinical trials or preclinical studies or receive regulatory approval on a timely basis, if at all; that we may not successfully enroll additional patients or establish or advance plans for further development; that elraglusib could be associated with side effects, adverse events or other properties or safety risks, which could delay or preclude regulatory approval, cause us to suspend or discontinue clinical trials or result in other negative consequences; our reliance on third parties to conduct our non-clinical studies and our clinical trials; our reliance on third-party licensors and ability to preserve and protect our intellectual property rights; that we face significant competition from other biotechnology and pharmaceutical companies; and our ability to fund development activities. In addition, any forward-looking statements are qualified in their entirety by reference to the factors discussed under the heading “Risk Factors” in our final prospectus filed with the SEC on August 13, 2024 pursuant to Rule 424(b)(4) under the Securities Act with respect to our Registration Statement on Form S-1 (File No. 333-279734) and other filings with the SEC. Because the risk factors referred to above could cause actual results or outcomes to differ materially from those expressed in any forward-looking statements made by us or on our behalf, you should not place undue reliance on any forward-looking statements. Further, any forward-looking statement speaks only as of the date on which it is made. New factors emerge from time to time, and it is not possible for us to predict which factors will arise. In addition, we cannot assess the impact of each factor on our business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in any forward-looking statements. Unless legally required, we do not undertake any obligation to release publicly any revisions to such forward-looking statements to reflect events or circumstances after the date of this press release or to reflect the occurrence of unanticipated events. Investor Contact Mike Moyer Managing Director LifeSci Advisors, LLC mmoyer@lifesciadvisors.com

免疫疗法临床2期临床结果

2024-09-23

·药渡Daily

【药渡药闻报告-创新药篇】-2024年第36期/总第157期

全球药物批准/研发动态 01 全球新药批准情况根据药渡数据统计分析，本次统计周期（2024.09.07-09.13）全球（不含中国）共有3个新药获批上市。其中，BLA批准1个，新适应症批准1个，新剂型批准1个。与上个统计周期相比，本次增加2个批准新药。 9月11日，Johnson & Johnson宣布FDA已批准TREMFYA（Guselkumab）用于治疗患有中度至重度活动性溃疡性结肠炎的成人患者。TREMFYA可阻断IL-23，同时还能结合CD64，CD64是产生IL-23的细胞上的受体。研究数据显示，50%接受TREMFYA 200 mg皮下（SC）维持治疗每4周的患者和45%接受TREMFYA 100 mg SC每8周的患者在第44周达到临床缓解的主要终点；34%（200 mg）和35%（100 mg）的患者在接受TREMFYA SC维持治疗后一年内达到内窥镜缓解。 9月13日，Lilly宣布，FDA已批准靶向IL-13抑制剂EBGLYSS™（Lebrikizumab-lbkz）用于治疗体重至少88磅（40公斤）的中度至重度特应性皮炎成人和12岁及以上儿童。研究显示，38%的服用EBGLYSS的人在16周时获得了清晰或几乎清晰的皮肤，这些患者中77%的人在每月给药一次的情况下将此结果保持了一年。43%的服用EBGLYSS的人在16周时感到瘙痒缓解，这些患者中85%的人在每月维持给药治疗一年后仍保持缓解。全球（不含中国）新药批准情况（部分） 02 全球新药申报进展根据药渡数据统计分析，本次统计周期（2024.09.07-09.13）全球（不含中国）共有2个新药申报上市。其中，NDA申报1个，BLA申报1个。与上次统计周期相比，本次减少1个NDA/BLA申报。 9月9日，ARS Pharmaceuticals宣布向FDA提交sNDA，为体重15至30公斤的I型过敏反应儿科患者提供Neffy® 1mg剂量。数据表明该药物没有与针头相关的不良事件的风险，简单的插入和按压机制几乎可以立即输送肾上腺素且年仅10岁未经训练的儿童可以轻松使用。Neffy允许高达50°C的温度暴露。 NDA/BLA申报根据药渡数据统计分析，本次统计周期（2024.09.07-09.13）全球（不含中国）共有4个药物获监管机构特殊资格认定。其中，化学药3个，生物药1个。与上次统计周期相比，本次增加2个获监管机构特殊资格认定的药物。 9月11日，Ascendis Pharma宣布获得YORVIPATH®（Palopegteriparatide）治疗成人甲状旁腺功能减退症的孤儿药在美国七年独家经营权。YORVIPATH是一种甲状旁腺激素（PTH[1-34]）的前药，每天给药一次，旨在在24小时给药期间持续暴露于释放的PTH。甲状旁腺功能减退症是一种罕见的内分泌疾病，由甲状旁腺激素水平不足引起，影响多个器官。同日，Actuate宣布FDA已授予Elraglusib孤儿药资格认定，用于治疗软组织肉瘤。临床前研究表明，Elraglusib是一种领先的GSK-3β抑制剂，诱导显着的STS细胞凋亡，并与化疗产生协同作用，为转移性STS的临床评估提供了依据，已在包括黑色素瘤、尤文肉瘤、结直肠癌和胰腺癌在内的多种实体瘤中显示出良好的安全性和抗肿瘤活性。特殊资格认定情况（部分） 03 全球新药研发进展根据药渡数据统计分析，本次统计周期（2024.09.07-09.13）全球（不含中国）新药临床研发状态更新共计74条，涉及肿瘤、血液和淋巴疾病、遗传代谢病、神经疾病以及免疫系统疾病等共计13个领域。其中，肿瘤领域临床进展更新居各领域之首，为37条：涉及化学药18条，生物药15条，细胞疗法1条，疫苗3条。 9月10日，艾力斯在2024WCLC主席研讨会发布了伏美替尼单药一线治疗EGFR PACC突变非小细胞肺癌的研究数据。在240mg QD剂量组，BICR评估的ORR为81.8%，BICR确认的ORR（cORR）为63.6%；在伴随中枢神经系统转移灶的患者中，cORR为46.2%。在一线转移性患者的治疗中，伏美替尼表现出剂量相关的活性，包括与其高脑渗透性一致的CNS抗肿瘤活性。 9月13日，宜联生物YL201项目在2024年欧洲肿瘤内科学会上公布其临床数据。有效性方面，截至2024年8月9日，在276例存在至少一次基线后肿瘤评估的患者中，客观缓解率(ORR)为44.6%，疾病控制率(DCR)为83.7%。安全性方面，312例总体人群中≥G3 TRAE发生率为51%，SAE发生率为28%。全球新药研发进展详情（部分） 04 全球医药交易事件本次统计周期（2024.09.07-09.13）全球（含中国）医药交易时间共计34起，涉及药物权益转让、公司并购等多起交易事件。全球医药交易时间汇总表（部分）国内药物批准/研发动态 01 国内新药批准情况根据药渡数据统计分析，本次统计周期（2024.09.07-09.13）国内共有2个新药获NMPA批准上市。其中，BLA批准1个，新适应症批准1个。与上次统计周期相比，本次减少2个NMPA批准新药。 9月12日，康诺亚宣布康悦达®（司普奇拜单抗注射液）正式获得NMPA批准上市，用于治疗成人中重度特应性皮炎。研究结果显示，康悦达®首剂单药治疗1天，即可快速缓解瘙痒症状；治疗2周，对全身各部位皮损均有强效改善作用。单药治疗52周，超过九成患者实现湿疹面积和严重指数程度改善75%以上，近八成患者实现湿疹面积和严重指数程度改善90%以上，并能够持续环节瘙痒，安全性和耐受性良好。 9月14日，默沙东宣布其PD-1抑制剂帕博利珠单抗（可瑞达®）已获得NMPA批准，将产品说明书中黑色素瘤适应证由“帕博利珠单抗适用于经一线治疗失败的不可切除或转移性黑色素瘤的治疗”变更为“帕博利珠单抗适用于不可切除或转移性黑色素瘤的一线治疗”。可瑞达是截至目前首个且唯一一个在中国境内获批晚期黑色素瘤一线治疗的PD-1抑制剂。国内新药批准情况（部分） 02 国内新药临床默示许可进展根据药渡数据统计分析，本次统计周期（2024.09.09-09.13）国内共有37个新药获临床默示许可，涉及61个受理号。其中，化学药22个，治疗用生物制品14个，预防用生物制品1个。与上次统计周期相比，本次增加37个临床默示许可获批受理号。本周国内新药临床默示许可进展（部分） 03 国内新药申报进展根据药渡数据统计分析，本次统计周期（2024.09.07-09.13）国内共有5个新药申报上市，涉及7个受理号。其中，化药3个，治疗用生物制品2个。与上个统计周期相比，本次减少4个新药申报上市受理号。国内新药申报上市情况根据药渡数据统计分析，本次统计周期（2024.09.07-09.13）国内共有48个新药申报临床，涉及76个受理号。其中，化学药24个，治疗用生物制品23个，预防用生物制品1个。与上次统计周期相比，本次增加23个临床申报受理号。国内新药临床申报情况（部分）根据药渡数据统计分析，本次统计周期（2024.09.07-09.13）国内共有4个药物获NMPA特殊资格认定。其中，化学药3个，生物药1个。与上次统计周期相比，本次减少1个获监管机构特殊资格认定的药物。 9月9日，CDE官网公示，海思科HSK31858片拟定适应症为非囊性纤维化支气管扩张。HSK31858片是一款小分子二肽基肽酶1（DPP1）抑制剂，其作用机制是通过抑制DPP1，进而抑制下游的与支气管扩张炎症相关的中性粒细胞丝氨酸蛋白酶（NSPs）而发挥药理作用。该产品临床拟用于治疗支气管扩张症及急性肺损伤/急性呼吸窘迫综合征引起的下呼吸道疾病。 9月12日，CDE官网显示，晖致制药（大连）有限公司申报的普瑞巴林胶囊拟纳入优先审评品种，主要用于治疗带状疱疹后神经痛、糖尿病性外周神经痛、纤维肌痛、癫痫部分性发作等疾病。其作用机制包括阻断CACNA2D1和CACNA2D2钙通道，从而有效地治疗这些疾病。2021年普瑞巴林胶囊被纳入第四批国家集采，以普瑞巴林胶囊（150mg）为例，集采后每粒价格从14.5元下降到0.5441元，降幅96%，每月可节约费用约837元。国内监管机构特殊资格认定药物（部分） 04 国内新药研发进展根据药渡数据统计分析，本次统计周期（2024.09.07-09.13）国内新药临床研发状态更新共计7条，涉及肿瘤、遗传和代谢疾病、呼吸系统疾病和皮肤病共计4个领域。其中，化学药7条。与上次统计周期相比，本次增加2条国内新药临床研发状态更新。近日，复星医药自主研发的治疗ALK阳性非小细胞肺癌（NSCLC）的创新药复瑞替尼（Foritinib，SAF-189s）III期研究期中分析结果于2024 WCLC发布。研究结果显示复瑞替尼治疗组的ORR达到92.8%，相较于克唑替尼治疗组提高12%；且对于基线脑转移的患者，复瑞替尼治疗组的颅内ORR可达到100%。安全性方面，复瑞替尼治疗组患者3/4级治疗相关不良事件（TRAEs）的发生率为37.7%。 9月9日，华东医药在国内启动一项III期临床，评估HDM3010治疗白癜风患者的效果和安全性。HDM3010是一款JAK1/JAK2抑制剂。这是首个在国内启动白癜风III期临床的国产JAK抑制剂，研究的目的是评估 HDM3010 治疗中国白癜风患者的有效性和安全性。有效性的主要终点指标为：治疗第24周面部白癜风面积评分指数（F-VASI）较基线至少改善 75% 的受试者比例。国内新药研发进展 05 国内新药研发领域政策法规动态关于公开征求《生物类似药药学相似性研究的问题与解答（征求意见稿）》意见的通知为进一步指导和规范生物类似药的药学相似性研究，我中心组织起草了《生物类似药药学相似性研究的问题与解答（征求意见稿）》。我们诚挚地欢迎社会各界对征求意见稿提出宝贵意见和建议，并及时反馈给我们，以便后续完善。征求意见时限为自发布之日起一个月。 06 国内新药研发领域热点新闻恒瑞医药放大招：创新药收入直指503亿 9月8日，“医药一哥”恒瑞医药发布了《2024年员工持股计划》。公告显示，参加该持股计划的员工总人数预计不超过1203人（其中，董监高不超过18人，大部分为公司核心管理人员、骨干员工），本员工持股计划拟受让公司回购股份的数量不超过1220万股（含预留份额），受让价格为21.20元/股。而截至9月9日收盘，恒瑞医药股价为44.55元，按此计算折扣率达52.41%，意味着员工能以半价购入股票，优惠颇大。更多资讯，请阅读原文强生IL-23双重抑制剂获FDA批准用于溃疡性结肠炎 2024年9月11日，强生宣布FDA已批准Tremfya（Guselkumab）用于治疗中度至重度活动性溃疡性结肠炎成人患者。据悉，Tremfya是首个也是唯一一个获批用于治疗活动性溃疡性结肠炎的针对白细胞介素23（IL-23）的双重作用抑制剂。在关键的QUASAR研究中，该药物在一年内表现出具有高度统计学意义的内镜缓解率。更多资讯，请阅读原文康方再发力，全球首个CD47实体瘤III期研究启动 9月11日，根据药渡数据，康方生物在药物临床试验登记与信息公示平台上登记了一项III期研究：PD-1/VEGF双抗药物AK112（依沃西单抗）+CD47单抗AK117（莱法利单抗/Ligufalimab）vs PD-1抑制剂帕博利珠单抗一线治疗PD-L1表达阳性复发/转移性头颈部鳞状细胞癌，预计目标入组510人。据悉，这是全球首个启动的CD47实体瘤III期研究，也是PD-1/VEGF双抗药物AK112的第5项头对头III期临床研究。更多资讯，请阅读原文咨询、合作请联系作者小D有话说为方便读者阅读及保存，我们将周报原文整理成了PDF版本，如需获取全文，可点击最上方蓝字，在药渡Daily公众号后台回复“0923创新药周报”，即可下载。

孤儿药上市批准

2024-09-16

·GlobeNewswire-Health Care

Actuate Announces Upcoming Presentation on Initial Data on Elraglusib in Combination with FOLFIRINOX at the AACR Special Conference on Advances in Pancreatic Cancer Research

Preclinical Study Highlight the Potential of Elraglusib in Overcoming FOLFIRINOX-induced Chemoresistance Through Downregulation of Epithelial to Mesenchymal Transition (EMT)Initial Data Demonstrates Early Evidence of Increased Clinical Activity of Combining FOLFIRINOX with Elraglusib and Losartan in Patients with Untreated Metastatic Pancreatic Ductal Adenocarcinoma (PDAC)Deep, Durable Responses Observed in 3/6 patients with Extensive Liver Metastases CHICAGO and FORT WORTH, Texas, Sept. 16, 2024 (GLOBE NEWSWIRE) -- Actuate Therapeutics, Inc. (NASDAQ: ACTU) (“Actuate” or the “Company”), a clinical-stage biopharmaceutical company, focused on developing therapies for the treatment of high-impact, difficult-to-treat cancers through the inhibition of glycogen synthase kinase-3 beta (GSK-3β), announced data from the safety cohort of an ongoing Phase 2 trial of FOLFIRINOX in combination with elraglusib and losartan for untreated metastatic pancreatic adenocarcinoma at the American Association for Cancer Research (AACR) Special Conference on Advances in Pancreatic Cancer Research taking place on September 15-18, 2024, in Boston, Massachusetts. “We are encouraged by the data presentation at this year’s AACR’s Special Conference underscoring elraglusib’s potential in addressing critical challenges in pancreatic cancer treatment,” said Daniel Schmitt, President & Chief Executive Officer of Actuate. “These initial findings provide early clinical evidence that elraglusib may overcome a key chemoresistance mechanism associated with FOLFIRINOX thus enhancing the effectiveness of the combination therapy.” The Phase 2 trial (NCT05077800) is an open-label, multi-arm, non-comparator study of FOLFIRINOX in combination with elraglusib and losartan for the treatment of adult patients with untreated metastatic pancreatic adenocarcinoma. The primary objectives of the trial are to determine the safety, tolerability, and progression-free survival of the combination therapy. The trial will enroll up to 70 treatment-naïve metastatic pancreatic adenocarcinoma patients. Actuate Therapeutics supports this trial by supplying the study drug, elraglusib. The Lustgarten Foundation is providing funding support for this study through a research grant. “We are excited by the promising safety profile and initial evidence of clinical activity demonstrated by the combination of FOLFIRINOX, elraglusib and losartan in this study,” said Colin Weekes, MD, Ph.D., Director of Medical Oncology Research for Pancreatic Cancer, Massachusetts General Hospital, and the study’s Principal Investigator. “The synergy observed with these drugs suggests that this combination could offer a novel and effective therapeutic strategy for patients with metastatic pancreatic cancer.” Poster presentation details Abstract: C073 Title: “FOLFIRINOX with Glycogen Synthase Kinase-3 Beta (GSK-3β) Inhibitor Elraglusib and Transforming Growth Factor- β (TGFβ) Inhibitor Losartan in Untreated Metastatic Pancreatic Ductal Adenocarcinoma (PDAC): Interim analysis of safety cohort.”Presenting Author: Priyadarshini Pathak, MD, Medical Oncologist, Massachusetts General Hospital Session date: Tuesday, September 17, 6:45-9 p.m. ETLocation: Westin Copley Place The abstract is available online and the poster will be available on Actuate’s website after the AACR Meeting. About Actuate Therapeutics, Inc. Actuate is a clinical-stage biopharmaceutical company focused on developing therapies for the treatment of high-impact, difficult-to-treat cancers. Actuate’s lead investigational drug product, elraglusib (a novel GSK-3β inhibitor), targets molecular pathways in cancer that are involved in promoting tumor growth and resistance to conventional cancer drugs such as chemotherapy including several DDR pathways. Elraglusib is designed to act as a mediator of anti-tumor immunity through the inhibition of NF-kB and regulates multiple immune checkpoints and immune cell function. For additional information, please visit the Company’s website at http://www.actuatetherapeutics.com. About Massachusetts General HospitalMassachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The Mass General Research Institute conducts the largest hospital-based research program in the nation, with annual research operations of more than $1 billion and comprises more than 9,500 researchers working across more than 30 institutes, centers and departments. MGH is a founding member of the Mass General Brigham healthcare system. Forward-Looking Statements This press release contains forward-looking statements about us, including our clinical trials and development plans, and our industry. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “might,” “ongoing,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “will,” “would,” or the negative of these terms or other comparable terminology are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. All statements, other than statements related to present facts or current conditions or of historical facts, contained in this press release are forward-looking statements. Accordingly, these statements involve estimates, assumptions, substantial risks and uncertainties which could cause actual results to differ materially from those expressed in them, including but not limited to that clinical and preclinical drug development involves a lengthy and expensive process with uncertain timelines and outcomes, results of prior preclinical studies and early clinical trials are not necessarily predictive of future results, and elraglusib may not achieve favorable results in clinical trials or preclinical studies or receive regulatory approval on a timely basis, if at all; that we may not successfully enroll additional patients or establish or advance plans for further development; that elraglusib could be associated with side effects, adverse events or other properties or safety risks, which could delay or preclude regulatory approval, cause us to suspend or discontinue clinical trials or result in other negative consequences; our reliance on third parties to conduct our non-clinical studies and our clinical trials; our reliance on third-party licensors and ability to preserve and protect our intellectual property rights; that we face significant competition from other biotechnology and pharmaceutical companies; and our ability to fund development activities. . In addition, any forward-looking statements are qualified in their entirety by reference to the factors discussed under the heading “Risk Factors” in our final prospectus filed with the SEC on August 13, 2024 pursuant to Rule 424(b)(4) under the Securities Act with respect to our Registration Statement on Form S-1 (File No. 333-279734) and other filings with the SEC. Because the risk factors referred to above could cause actual results or outcomes to differ materially from those expressed in any forward-looking statements made by us or on our behalf, you should not place undue reliance on any forward-looking statements. Further, any forward-looking statement speaks only as of the date on which it is made. New factors emerge from time to time, and it is not possible for us to predict which factors will arise. In addition, we cannot assess the impact of each factor on our business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in any forward-looking statements. Unless legally required, we do not undertake any obligation to release publicly any revisions to such forward-looking statements to reflect events or circumstances after the date of this press release or to reflect the occurrence of unanticipated events. Investor Contact Mike Moyer Managing Director LifeSci Advisors, LLC mmoyer@lifesciadvisors.com

临床2期AACR会议

100 项与 Elraglusib 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB16047

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
转移性黑色素瘤	临床2期	美国	Actuate Therapeutics, Inc.初创企业	2023-05-31
转移性黑色素瘤	临床2期	美国	Lantern Pharma, Inc.	2023-05-31
转移性胰腺腺癌	临床2期	美国	Actuate Therapeutics, Inc.初创企业	2022-03-21
胰腺继发性恶性肿瘤	临床2期	美国	Actuate Therapeutics, Inc.初创企业	2022-03-21
尤文肉瘤	临床2期	美国	Actuate Therapeutics, Inc.初创企业	2022-03-01
晚期胰腺腺癌	临床2期	美国	Actuate Therapeutics, Inc.初创企业	2022-01-26
晚期胰腺腺癌	临床2期	美国	Incyte Corp.	2022-01-26
转移性涎腺癌	临床2期	美国	Actuate Therapeutics, Inc.初创企业	2021-09-14
肿瘤转移	临床2期	美国	Actuate Therapeutics, Inc.初创企业	2021-09-14
唾液腺癌复发	临床2期	美国	Actuate Therapeutics, Inc.初创企业	2021-09-14

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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


NCT04239092 (GlobeNewswire) 人工标引	临床1/2期	尤文肉瘤 \| 促纤维增生性小圆细胞瘤	8	elraglusib	範糧衊積淵觸蓋獵網壓(選獵願艱積遞憲網積衊) = 簾醖膚鬱醖繭憲鏇膚顧糧鏇鹹襯壓襯範壓選網 (襯鑰餘遞淵獵淵窪壓糧 ) 更多	积极	2024-09-09
NCT03678883 (ASCO2023) 人工标引	临床2期	晚期胰腺导管腺癌	42	gemcitabine+Albumin-Bound Paclitaxel+Elraglusib	齋鑰糧鏇遞繭廠網選艱(觸鏇觸蓋膚構觸夢廠範) = 鹽鏇構鹽鹹齋鑰鹽繭壓簾積蓋鬱鏇艱簾廠鏇積 (鬱鹹繭襯獵製願鹹壓範, 32.5 ~ 70.6) 更多	积极	2023-05-26
NCT03678883 (AACR2023) 人工标引	临床1/2期	晚期癌症三线	-	elraglusib (melanoma)	鬱製憲鏇選觸網鑰製網(醖簾鏇壓糧顧鹹鹽夢醖) = 膚繭襯顧艱糧淵鏇願鑰醖憲壓選鹽鬱壓範遞築 (遞餘膚夢壓範積願製衊 )	积极	2023-04-14
NCT03678883 (AACR2023) 人工标引	临床1/2期	晚期癌症三线	-	elraglusib (colorectal cancer)	衊窪壓鬱蓋鬱製網願範(獵觸窪膚蓋廠築觸鑰製) = 範積鑰憲憲醖糧糧淵蓋簾襯鬱糧廠糧積積壓顧 (簾製製艱製觸築齋簾鏇 ) 更多	积极	2023-04-14
NCT04239092 (ASCO2022)	临床1/2期	癌症	23	Elraglusib + temozolomide/irinotecantemozolomide/irinotecan	鹹觸廠構衊衊築窪積範(蓋鬱衊願醖壓糧鏇廠衊) = a single adverse event (Grade 4 hypotension/infusion reaction) was reported 構觸顧製襯醖遞網構衊 (鏇願範鹽觸齋餘選遞遞 ) 更多	-	2022-06-02
NCT03678883 (Pubmed) 人工标引	临床1/2期	癌症 \| 脑恶性胶质瘤	18	Lomustine+Elraglusib	簾醖艱範選製獵積網範(繭觸齋憲餘願壓獵築壓) = mild vision changes 50%, infusion reactions 22% 衊鏇襯夢憲鹽網築構築 (範獵積廠簾鬱顧餘衊艱 ) 更多	积极	2022-02-07
AACR2021	N/A	结直肠癌	-	9-ING-41	夢築網壓顧糧簾獵遞觸(範淵憲淵壓膚鹹獵膚衊) = 壓夢憲願糧窪壓構鹽襯齋積觸遞淵鬱夢餘齋襯 (獵遞網製築窪鑰繭獵簾 ) 更多	-	2021-07-01
NCT03678883 (ASCO2021) 人工标引	临床1/2期	实体瘤 \| 脑恶性胶质瘤 \| 难治性血液恶性肿瘤	227	lomustine+9-ing-41	鬱鹽憲鏇夢窪築構齋鹽(簾淵構簾齋遞鬱鏇淵積) = 願醖觸觸蓋鹹鏇製製餘繭選鹹遞鬱夢選壓艱願 (選鬱齋網網糧夢觸襯願 ) 更多	积极	2021-05-28
NCT03678883 (ASCO2020)	临床1期	癌症	101	9-ING-41 combined with chemotherapy	網構繭膚膚鏇鏇遞夢願(襯衊窪鏇網顧襯構壓鹽) = n = 14 糧簾蓋願願廠繭觸構顧 (壓繭鏇衊製齋獵艱衊簾 ) 更多	积极	2020-05-25
NCT04218071 \| NCT03678883 \| NCT04239092 (Pubmed \| Anticancer Drugs)	N/A	神经母细胞瘤	17	9-ING-41	製衊衊獵蓋壓觸獵窪選(遞憲夢糧觸膚鬱選餘築) = 壓膚遞鹹選壓簾選壓廠製選窪構積鹽糧壓顧蓋 (壓糧衊衊齋糧廠積簾鑰 )	-	2018-09-01
ICML2017	N/A	B细胞淋巴瘤 GSK-3ß	-	9-ING-41	憲築築選遞製願鹽範鬱(餘廠構廠鬱窪窪構壓觸) = 顧選鹽襯襯鑰窪鑰醖衊簾構鑰齋餘遞壓選範壓 (糧蓋糧壓範淵夢構構鹹 )	积极	2017-06-07