An Open-label, Multicenter, Phase 1a/1b Study of Aplitibart (IGM-8444) As a Single Agent and in Combination in Participants with Relapsed, Refractory, or Newly Diagnosed Cancers

This study is a first-in-human, Phase 1a/1b, multicenter, open-label study to determine the safety, tolerability, and pharmacokinetics of aplitabart as a single agent and in combination in participants with relapsed and/or refractory solid or hematologic cancers, as well as newly diagnosed cancers, and an open-label, randomized study of aplitabart+FOLFIRI+bevacizumab.

开始日期2020-09-23

申办/合作机构

IGM Biosciences, Inc.

NCT03803774

/ Terminated临床1期IIT

Birinapant and Intensity Modulated Re-Irradiation Therapy (IMRRT) for Locoregionally Recurrent Head and Neck Squamous Cell Carcinoma (HNSCC)

This phase I trial studies the side effects and best dose of birinapant when given together with intensity modulated re-irradiation therapy (IMRRT) in treating patients with head and neck squamous cell carcinoma that has come back at or near the same place as the original (primary) tumor (locally recurrent). Birinapant may stop the growth of tumor cells by blocking inhibitor of apoptosis (IAP), a protein needed for tumor cell survival. IMRRT uses thin beams of radiation of different intensities that are aimed at the tumor from many angles. This type of re-irradiation therapy reduces the damage to healthy tissue near the tumor. Giving birinapant with IMRRT may lower the chance of head and neck squamous cell carcinoma growing or spreading.

开始日期2019-09-25

申办/合作机构

National Cancer Institute

NCT02756130

/ Withdrawn临床1/2期IIT

A Phase I/II, Single Center, Proof-of-Concept Study of Birinapant in Combination With Platinum Based Chemotherapy Targeting Recurrent High Grade Serous Ovarian Carcinomas (HGSOC)

This phase I/II trial studies how well birinapant and carboplatin work in treating patients with ovarian, fallopian tube, or primary peritoneal cancer that has come back. Drugs used in chemotherapy, such as birinapant and carboplatin work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

开始日期2018-08-01

申办/合作机构

Jonsson Comprehensive Cancer Center

[+2]

100 项与 Birinapant 相关的临床结果

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100 项与 Birinapant 相关的转化医学

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100 项与 Birinapant 相关的专利（医药）

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194

项与 Birinapant 相关的文献（医药）

2025-03-04·IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY

Birinapant improves imiquimod-induced psoriasis in BALB/c mice

Article

作者: Parab, Siddhi ; Doshi, Gaurav

OBJECTIVES:

This study investigates the effects of birinapant, a novel compound, on psoriasis-like symptoms induced by imiquimod in Balb/c mice.

MATERIAL AND METHODS:

Male Balb/c mice were treated with imiquimod (IMQ) to induce psoriasis-like symptoms. The clinical characteristics of psoriasis were assessed using the Psoriasis Area and Severity Index, as well as back skin thickness, skin length and mass, and body weight alterations. The treatment groups included those receiving birinapant, with the assessment on the levels of interleukin-17 and tumor necrosis factor -α, two key cytokines involved in the inflammatory process of psoriasis. The study found that birinapant significantly reduced the levels of these cytokines, providing reassurance about its potential to combat psoriasis. Additionally, the study evaluated the effect of birinapant on oxidative stress levels to determine its role in maintaining skin homeostasis.

RESULT AND DISCUSSION:

The findings from this study revealed that mice subjected to IMQ-induced psoriasis exhibited positive responses to 21 days of treatment with birinapant (50 mg/kg). The levels of interleukin-17 and tumor necrosis factor-alpha, in the skin of IMQ-treated mice significantly decreased, indicating its effectiveness in reducing inflammation associated with psoriasis. Furthermore, Birinapant positively affected oxidative stress maintenance, suggesting its potential role in promoting skin health and homeostasis.

CONCLUSION:

By demonstrating birinapant's efficacy, this research paves the way for further studies that could lead to the development of more effective therapies for psoriasis.

2025-03-01·Nature Chemical Biology

A multiplex single-cell RNA-Seq pharmacotranscriptomics pipeline for drug discovery

Article

作者: Barker, Harlan ; Piki, Emilia ; Dini, Alice ; Sharma, Subodh ; Raivola, Juuli ; Ungureanu, Daniela ; Murumägi, Astrid

Abstract:

The gene-regulatory dynamics governing drug responses in cancer are yet to be fully understood. Here, we report a pipeline capable of producing high-throughput pharmacotranscriptomic profiling through live-cell barcoding using antibody–oligonucleotide conjugates. This pipeline combines drug screening with 96-plex single-cell RNA sequencing. We show the potential of this approach by exploring the heterogeneous transcriptional landscape of primary high-grade serous ovarian cancer (HGSOC) cells after treatment with 45 drugs, with 13 distinct classes of mechanisms of action. A subset of phosphatidylinositol 3-OH kinase (PI3K), protein kinase B (AKT) and mammalian target of rapamycin (mTOR) inhibitors induced the activation of receptor tyrosine kinases, such as the epithelial growth factor receptor (EGFR), and this was mediated by the upregulation of caveolin 1 (CAV1). This drug resistance feedback loop could be mitigated by the synergistic action of agents targeting PI3K–AKT–mTOR and EGFR for HGSOC with CAV1 and EGFR expression. Using this workflow could enable the personalized testing of patient-derived tumor samples at single-cell resolution.

2025-02-01·EXPERIMENTAL NEUROLOGY

PGAM5 promotes RIPK1-PANoptosome activity by phosphorylating and activating RIPK1 to mediate PANoptosis after subarachnoid hemorrhage in rats

Article

作者: Aihua, Liu ; Xiaoxin, Yan ; Jia, Zeng ; Wen, Yuan ; Zhen, Fang ; Fangen, Kong ; Fei, Liu ; Enyan, Jiang ; Jikai, Wang ; Jiajia, Duan ; Xiaojian, Zhang

Neuronal death plays a crucial role in early brain injury after subarachnoid hemorrhage (SAH). PANoptosis is a programmed form of cell death regulated by the PANoptosome, which possesses key characteristics of pyroptosis, apoptosis and necroptosis. Phosphoglycerate mutase family member 5 (PGAM5) has specific phosphatase activity that phosphorylates or dephosphorylates serine and threonine residues on bound proteins such as receptor-interacting protein kinase 1 (RIPK1), which are involved in programmed cell death. This study aimed to explore whether PANoptosis occurs after subarachnoid hemorrhage and to investigate the role of PGAM5 in early brain injury after SAH. A monofilament perforation SAH model in Sprague-Dawley rats was established, and PGAM5 siRNA (siPGAM5) was administered via intracerebroventricular injection 48 h before SAH modeling. The efficacy of siPGAM5 treatment was assessed via neurological scoring, and the impact of siPGAM5 on PANoptosis was evaluated via Western blotting, TUNEL staining and ELISA. To investigate its potential mechanism, the RIPK1 activator birinapant was administered intraperitoneally 0.5 h after SAH. The role of RIPK in PGAM5-mediated PANoptosis was evaluated by Western blotting and coimmunoprecipitation. Our findings indicate that PANoptosis occurs in neurons after SAH and that reducing PGAM5 in the cytosol after SAH can reduce PANoptosis and enhance the short-term and long-term neurological functions of SAH rats. Mechanistically, we discovered that PGAM5 can directly bind to and phosphorylate and activate RIPK1 (ser 166), triggering the assembly of the RIPK1-PANoptosome complex. In conclusion, our study revealed that the increased PGAM5 in the mitochondria-free cytosol after SAH can bind to and activate RIPK1 (ser 166), driving the assembly of the RIPK1-PANoptosome and mediating PANoptosis after SAH. PGAM5 and PANoptosis might be novel therapeutic targets for SAH.

项与 Birinapant 相关的新闻（医药）

2024-07-05

·奇点网

癌王的化疗耐药又有了新解法。

*仅供医学专业人士阅读参考胰腺导管腺癌（PDAC）是癌症相关死亡的第四大原因，具有极高的恶性和侵袭性，其五年生存率不足12%。当前PDAC的治疗选择有限，以吉西他滨（GEM）作为一线化疗药物，但只有约23.8%的患者对其有临床反应，中位生存期仅为6.7到8.5个月。这种不理想的化疗治疗效果，主要是由于PDAC中存在癌症干细胞（CSCs）。与正常干细胞相似，癌症干细胞不仅具有自我更新和分化能力，还拥有能够帮助细胞排出有害物质的药物转运蛋白，并在身边形成保护性生态位、DNA损伤能力修复增强，抵御化疗药物的影响。因此，探索PDAC维持干性和化疗耐药性的机制，对于优化治疗策略至关重要。天津医科大学刘静、常安涛、黄崇标、郝继辉等人的最新研究于近日发表在《科学·进展》期刊上[1]。他们发现，蛋白质BICC1过度表达时，能够通过上调限速酶IDO1来促进色氨酸代谢，从而增强胰腺癌的干细胞特性和化疗耐药性。使用药理方法或饮食干预的方式抑制这条信号通路，可以增加BICC1高表达的胰腺癌细胞对吉西他滨的敏感性，延长小鼠生存期。论文首页 BICC1是一种RNA结合蛋白，能在细胞质中调控多个mRNA的翻译。天津医科大学团队在之前的工作中发现，BICC1通过促进PDAC中的血管生成来促进肿瘤生长，在PDAC中的高表达与不良的临床特征和预后有关[2]。此次，研究团队首先通过免疫组织化学（IHC）染色，分析了68例接受吉西他滨联合白蛋白紫杉醇（nab-paclitaxel）治疗的晚期PDAC患者的BICC1表达情况，结果显示BICC1低表达的患者对化疗反应更好。同样，在另一组包括65例接受根治性切除手术后吉西他滨辅助化疗的PDAC患者中，BICC1高表达的患者复发无病生存期更短。这些结果支持了BICC1在预测化疗反应和患者预后中的潜在价值。 BICC1表达与患者化疗反应相关通过构建几种BICC1过表达或BICC1沉默的PDAC细胞系，研究团队在体外实验和小鼠体内实验中验证表明，BICC1本身对PDAC细胞的存活和增殖影响甚微，但是会妨碍化疗药物的效果。BICC1过表达能够显著增强PDAC细胞对吉西他滨的耐药性，增加肿瘤体积和生长速度；而BICC1沉默则增强对吉西他滨的敏感性，导致诱导的凋亡细胞数量增加。此外研究发现，除了吉西他滨，BICC1还会增强PDAC细胞对5-氟尿嘧啶和白蛋白紫杉醇的耐药性，并在一定程度上增加其对TNF-α和Birinapant（一种细胞死亡诱导剂）组合治疗的抗性。这些表明BICC1在PDAC中广泛影响了多种化疗药物效果。接下来就是顺藤摸瓜，根据BICC1的作用机制找出相应的解决方案。考虑到化疗耐药性和癌细胞干细胞表型之间的关联已得到充分证实，研究团队将重点放在探索BICC1是否调节PDAC的干细胞特性。结果颇有收获。对100多例PDAC组织样本进行分析发现，BICC1能够帮助PDAC细胞维持癌症干细胞特征，上调与干性相关的基因，增强成球能力等干细胞特性。沉默BICC1会导致癌症干细胞的占比大幅降低。 BICC1促进PDAC干性，干细胞样PDAC细胞表达更多的BICC1 从机制上看，BICC1作为一种RNA结合蛋白，直接与色氨酸代谢限速酶的编码基因IDO1的mRNA结合，以增加其稳定性，从而增强IDO1的表达和促进色氨酸的代谢，提高色氨酸代谢产物水平。这些代谢物通过促进线粒体中进行的NAD+合成和氧化磷酸化（OXPHOS）过程，增强PDAC细胞的干性和化疗耐药性。机制既然已明确BICC1/IDO1/色氨酸通路的作用，研究团队尝试从已在临床应用或先前临床试验中验证过的药物里寻求新的治疗方案。氟他胺是一种用于前列腺癌治疗的非甾体雄激素受体拮抗剂，在这里，研究团队利用大规模毒理基因组学数据库和蛋白质印迹分析技术发现，氟他胺可作为PDAC中BICC1的强效抑制剂。异种移植瘤PDAC小鼠模型实验结果显示，氟他胺或Epacadostat（一种在III期临床试验中失败的IDO1抑制剂）治疗，或者低亮氨酸含量的饮食干预，与吉西他滨联合使用时对BICC1高表达的PDAC肿瘤具有明显的抑制作用，延长小鼠总生存期。不结合化疗、只针对BICC1/IDO1/色氨酸通路进行治疗时影响微乎其微，且联合治疗对BICC1低表达的肿瘤效果无提升。三种方法抑制BICC1/IDO1/色氨酸通路，可以增强PDAC对吉西他滨治疗的敏感性总之，这项研究表明BICC1可作为预测PDAC化疗结果的潜在生物标志物，并提出了靶向BICC1/IDO1/色氨酸代谢途径的治疗策略，包括副作用较小的饮食干预，有望提高PDAC患者对化疗的敏感性、改善治疗效果。未来的研究应进一步探索BICC1在肿瘤微环境中的作用，开发针对BICC1的特异性抑制剂，以评估其临床应用潜力。参考文献： [1]https://www.science.org/doi/10.1126/sciadv.adj8650 [2]C. Huang, H. Li, Y. Xu, C. Xu, H. Sun, Z. Li, Y. Ge, H. Wang, T. Zhao, S. Gao, X. Wang, S. Yang, P. Sun, Z. Liu, J. Liu, A. Chang, J. Hao, BICC1 drives pancreatic cancer progression by inducing VEGF-independent angiogenesis. Signal Transduct. Target. Ther. 8, 271 (2023). 本文作者丨张艾迪

临床研究信使RNA临床结果

2024-02-15

·PRNewswire

MEDIVIR AB - YEAR-END REPORT JANUARY - DECEMBER 2023

STOCKHOLM, Feb. 15, 2024 /PRNewswire/ -- "The clinical efficacy of fostrox in combination with Lenvima continues to improve with median time to progression having increased to over 6 months" October – December Financial summary for the quarter Net turnover amounted to SEK 4.4 (2.3) million. The loss before interest, tax, depreciation and amortization (EBITDA) amounted to SEK -20.1 (-17.9) million. Basic and diluted earnings per share amounted to SEK -0.28 (-0.32) and SEK -0.28 (-0.32) respectively. Cash flow from operating activities amounted to SEK -4.6 (-24.7) million. Cash and cash equivalents at the end of the period amounted to SEK 169.5 (117.4) million. Significant events during the quarter In October, data from an investigator evaluation showed continued promising tumor control with fostrox + Lenvima in HCC. All patients in the phase 2a study had dosed at least two treatment cycles. In October, the Board of Directors announced that Anette Lindqvist is leaving her position as Board Member of Medivir AB due to personal reasons. In October the nomination committee was appointed ahead of the AGM in May 2024. The Nomination Committee consists of Karl Tobieson, appointed by Linc AB, Richard Torgerson, appointed by Nordea Investment Funds, Anders Hallberg, appointed by HealthInvest Partners and Uli Hacksell, Chairman of the Board, Medivir AB. The Q3 report and the subsequent webcast included in-depth interim data from the 18 patients in the phase 1b/2a study who had a minimum follow-up of 12 weeks. These data continued to demonstrate clear patient benefit for the fostrox + Lenvima combination. In November it was announced that the company's interactions with the FDA regarding fostrox's clinical development plan had intensified with a first Type D meeting with a positive response regarding critical elements of the design for the planned phase 2b study. Late November it was announced that the development of an updated formulation of fostrox, suitable for commercial manufacture, had been finalized. In December, Medivir's partner IGM Biosciences, communicated a strategic pipeline cost-saving prioritization that among other things affects IGM's DR-5-agonist, aplitabart, in combination with birinapant, which was licensed in from Medivir in 2021. In December it was announced that Medivir has signed an agreement with Lonza for the manufacture of fostrox drug substance for the planned phase 2b study. In December it was announced that the durable clinical benefit in the ongoing phase 1b/2a study continues to improve, as data become more mature. In December, a rights issue was carried out, through which the company received proceeds of approximately SEK 129 before deduction of costs attributable to the rights issue. January – December Financial summary for the period Net turnover amounted to SEK 7.6 (4.4) million. The loss before interest, tax, depreciation and amortization (EBITDA) amounted to SEK -88.7 (-84.8) million. Basic and diluted earnings per share amounted to SEK -1.48 (-1.59) and SEK -1.48 (-1.59) respectively. Cash flow from operating activities amounted to SEK -59.7 (-101.8) million. Cash and cash equivalents at the end of the period amounted to SEK 169.5 (117.4) million. Events after the end of the period In January, a directed issue to Hallberg Management AB was carried out amounting to approximately SEK 20 million before deduction of issuance costs. In January, positive data from the ongoing phase 1b/2a study in advanced liver cancer (HCC) showing further improved response and time to progression was presented at the ASCO GI Symposium in San Francisco. In January Tango Therapeutics announced that it has dosed the first patient with TNG348, a new USP1-inhibitor from the preclinical USP1 program inlicensed from Medivir in 2020 Conference call for investors, analysts and the media The Year-End Report January - December 2023 will be presented by Medivir's CEO, Jens Lindberg. Time: Thursday, February 15, 2024, at 14.00 (CET). To access the webcast and find information about the teleconference, please klick HERE! The conference call will also be streamed via a link on the website: . The presentation will be available on Medivir's website after completion of the conference. CEO's message Fostrox in combination with Lenvima continues to show improved efficacy for patients with advanced primary liver cancer (HCC). The data presented in January 2024 at the ASCO-GI congress in San Francisco showed a further increase in the proportion of patients who achieve a clinically relevant reduction of their liver tumor and that patients stay on treatment longer with interrupted tumor growth. These data attracted very strong interest, which makes us even more convinced of fostrox's future role in the treatment of HCC and creates the opportunity for a faster route to market. The unmet medical need in the treatment of advanced HCC is significant. Primary liver cancer is the third leading cause of cancer-related deaths. In today's treatment guidelines, an immunotherapy combination (Tecentriq®/Avastin®) is recommended as first-line treatment. However, when this combination has stopped working, there are no approved alternatives for second-line treatment. There is thus a large need for additional treatment options in second-line that attacks the tumor in different ways compared to what Tecentriq and Avastin does. Fostrox is an organ specific, so-called smart chemotherapy, that selectively kills cancer cells in the liver. Together with Lenvima, these two form a unique combination of complementary drugs that have shown promising interim results in an ongoing phase 1b/2a study, including a complete tumor response in one patient. All patients in the study have now had at least 18 weeks of follow-up. The more mature and in-depth data we see from the study, the more convincing the clinical benefit for patients has become. Data from this study was presented at the ASCO GI Congress on January 19, 2024. These results, evaluated by investigators and local radiologists, showed further improvement as the Overall Response Rate (ORR) had increased to 25% (RECIST 1.1), a notably higher percentage than the 5-10% shown in second-line HCC in previous studies. The update also showed continued good tolerability without any new unexpected side effects. At the time of this quarterly report over 40% of patients remain on treatment in the study, and the clinical efficacy keeps improving. The median time to progression has increased further to 6.3 months, compared to 5.1 months at ASCO GI, significantly better than previous studies in second-line HCC. The patient who has benefited the longest remains on treatment after 18 months with partial response and continued shrinking tumor. Our data was met with great interest at ASCO GI, where we had the opportunity to discuss with leading global experts what the fostrox + Lenvima combination could mean for these patients. The discussions confirmed the great need that exists in the second-line treatment of HCC, where patients are today without any approved treatment alternative. With these promising data, fostrox has the opportunity to become the first approved medicinal treatment in a market worth ~2.5 billion USD annually, through a so-called accelerated approval by the regulatory authorities. We have therefore put in a higher gear in 2023 to ensure maximum momentum in fostrox's development program based on this possibility of accelerated approval. In Q4 2023 the development of an updated, commercially adapted formulation of fostrox was completed. In parallel, we have initiated the process with the FDA for a so-called Type C meeting to discuss the final study design of the planned registrational phase 2b study. In conjunction with these measures, we can now also deepen our discussions with potential partners, in accordance with previously communicated plans. We can also note that several of the projects that Medivir has licensed out to collaboration partners is entering clinical stage. In January 2024, Tango Therapeutics initiated a phase 1/2 study and dosed the first patient with TNG348, a USP-1 inhibitor developed from the preclinical USP1 program that was in-licensed from Medivir in 2020. INFEX Therapeutics also intends to initiate phase 1 study in 2024 - with the preclinical program MBLI, previously in-licensed from Medivir. IGM Biosciences has completed the fifth dose escalation cohort in the company's phase 1 study in solid tumors with Medivir's clinical project birinapant in combination with its own DR5 agonist antibody IGM-8444, now called aplitabart. For Medivir, the clinical development of fostrox is clearly in focus. With the promising data showing further improved clinical efficacy compared to expected treatment results in second-line HCC, we are even more confident that fostrox can become an effective liver cancer drug that makes a real difference to patients. I would like to thank old and new shareholders for the trust in our rights issue and for the capital injection that benefited us in the directed share issue. I look forward to keeping you informed of Medivir's continued development. Jens Lindberg Chief Executive Officer For further information, please contact Magnus Christensen, CFO Phone: +46 (0)8 5468 3100 E-mail: [email protected] This report has not been subject to auditors' review. The information was submitted for publication at 08.30 CET on February 15, 2024 The following files are available for download: SOURCE Medivir

临床2期临床1期财报加速审批临床结果

2023-12-07

·佰傲谷BioValley

裁员22%，砍掉所有血液瘤管线

裁员、砍管线是资金困难的生物药企活下去最经常采用的办法。近日，总部位于美国加州的IGM Biosciences决定裁员22%，并且停止所有血液瘤项目以及其靶向细胞因子候选产品的临床开发。IGM预计通过裁员和管线消减可以将公司现金流从原来坚持到2025年下半年延长到2026年第二季度。根据美国证券交易委员会（SEC）的文件，截至2023年9月30日，IGM拥有290名全职员工。IGM首席执行官表示，虽然公司停止的项目临床和临床前的数据表现都很亮眼，但是鉴于公司在资本市场融资困难，日子越来越难过，只能决定集中资源在最可能在近期产生效益的项目上。押注实体瘤和自免IGM表示将和赛诺菲继续合作，一起开发肿瘤学、免疫学和炎症候选药物。集中资源开发其治疗结直肠癌的IgM死亡受体5（DR5）激动剂抗体，以及用于自身免疫性疾病的IgMT细胞接合抗体。死亡受体5（DR5）激动剂Aplitabart联合FOLFIRI和贝伐珠单抗治疗二线转移性结直肠癌的随机临床试验正在招募患者，目标是到2024年第一季度末招募约110名患者。除了美国的临床试验地点外，该试验还包括亚洲和欧洲的多个临床试验地点。Aplitabart在晚期结直肠癌患者中应用的单臂联合临床试验也正在进行中。预计在2024年上半年完成10mg/kg Aplitabart和FOLFIRI治疗后期结直肠癌的患者入组。Aplitabart联合FOLFIRI治疗的一组患者报告的1期数据显示，其安全性与单独化疗的预期安全性大致相当。剂量为3mg/kg的Aplitabart和不含贝伐珠单抗的FOLFIRI的组合在24例患者组中的中位无进展生存期（PFS）为5.6个月，高于标准护理三线结直肠癌治疗（不含贝伐珠单抗）约2个月的历史中位无进展生存期。该组观察到的最长无进展生存期已超过16个月，且多位患者使用Aplitabart和FOLFIRI的治疗持续时间比之前的FOLFIRI方案更长。与此同时，IGM将优先推进imvotamab的临床开发，这是一种基于IgM的CD20xCD3双特异性T细胞结合抗体，用于自身免疫性疾病。关于imvotamab目前正在进行两项1b期临床试验，一项用于严重系统性红斑狼疮（SLE），另一项用于严重类风湿性关节炎（RA）。这些临床试验正在扩大到包括多个美国和国际临床试验地点。最近IGM还获得了FDA的批准，批准了其使用imvotamab治疗特发性炎症性肌病（肌炎）的IND申请，并且正在准备推进该临床试验。在临床前体内研究中，imvotamab已证明组织内的深部B细胞耗竭，其中致病性免疫细胞的耗竭可能对自身免疫性疾病的长期临床益处至关重要。Imvotamab还在临床前体外研究中证明，与利妥昔单抗相比，它可以更有效地消耗CD20表达水平低的B细胞。此外，IGM还划提交IND，以开始IGM-2644的临床开发，IGM-2644是一种CD38xCD3T细胞接合抗体，正在研究用于治疗自身免疫性疾病。亏损扩大，裁员缩管线2023年11月14日，IGM发布Q3财报，2023财年前三财季累计收入147.90万美元，去年同期累计收入为69.70万美元，同比增长112.20%。2023财年前三财季累计净亏损1.86亿美元，去年同期累计净亏损为1.69亿美元，同比扩大10.20%。作为公司战略重整的一部分，IGM将停止所有血液肿瘤学临床开发以及其靶向细胞因子候选产品的临床开发。包括Aplitabart联合birinapant用于治疗急性髓系白血病；IGM-2644（CD38xCD3）治疗多发性骨髓瘤；以及IGM-2537（CD123xCD3）和IGM-7354（IL-15xPD-L1）。去年11月，IGM在2022年美国血液学会（ASH）年会上，以海报的形式展示了几款候选药物在血液瘤中的临床前数据。数据显示与传统IgG抗CD38抗体相比，IgM-2644具有更强的补体依赖性细胞毒性(CDC)活性，此外，IGM-2644以最小的细胞因子释放实现了对达雷妥尤单抗耐药细胞系的强效T细胞依赖性细胞毒性（TDCC）杀伤，以及对骨髓瘤患者样本的强效TDCC杀伤。在人源化异种移植模型中，IGM-2644 也被证明可以抑制CD38+肿瘤生长，且与IgG双特异性T 细胞接合剂相比，它避免了杀死免疫效应细胞。IgM-2537在细胞因子释放最少的情况下显示有效的体外和体内活性。IGM-2537 被证明与人 CD123 结合具有高亲和力和特异性。IGM-2537 与CD123和CD3抗原共同参与，导致T细胞重定向杀伤急性髓系白血病（AML）细胞系，同时伴随 T 细胞活化，并在离体测定中以生理相关的效应/靶标比率消除AML原始细胞。与 IgGT细胞接合分子相比，IGM-2537还显示出显着减少的细胞因子释放，例如IFN-γ、TNF-α和IL-6。虽然数据鼓舞人心，但是资金的缺乏加上创新药物的开发需要的超额预算让IGM不得不放弃血液瘤管线。值得注意的是，IGM去年和赛诺菲刚刚达成巨额交易。2022年3月29日，赛诺菲和IGM达成超过60亿美元的合作协议。根据协议，双方将利用IGM公司独有的IgM抗体技术平台，开发针对3个肿瘤学靶点和3个免疫学/炎症靶点的激动剂。IGM公司将获得1.5亿美元的前期付款，在开发、监管和商业里程碑方面的总金额可能超过60亿美元。针对每个肿瘤学靶点，IGM公司可能获得高达9.4亿美元的里程碑付款；在免疫学/炎症领域，针对每个靶点，IGM公司有资格获得高达10.65亿美元的里程碑付款。在血液瘤方面管线的缩减，可能会影响到赛诺菲给予的里程碑付款。参考来源：1.https://endpts.com/igm-biosciences-cuts-22-of-workforce-axes-hematologic-oncology-program/2.https://www.globenewswire.com/news-release/2023/12/05/2791338/0/en/IGM-Biosciences-Announces-Strategic-Pipeline-Prioritization-and-Cash-Runway-Extension.html3.https://investor.igmbio.com/news-releases/news-release-details/igm-biosciences-presents-data-t-cell-engager-portfolio本周好文推荐如需转载请联系佰傲谷并在醒目位置注明出处﹀ ···

临床申请

100 项与 Birinapant 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D10417	-	-	DB11782

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
高级别输卵管浆液性腺癌	临床2期	美国	TetraLogic Pharmaceuticals Corp.	2018-08-01
卵巢高级别浆液性腺癌	临床2期	美国	TetraLogic Pharmaceuticals Corp.	2018-08-01
原发性腹膜高级别浆液性腺癌	临床2期	美国	TetraLogic Pharmaceuticals Corp.	2018-08-01
复发性原发性腹膜癌	临床2期	美国	TetraLogic Pharmaceuticals Corp.	2018-08-01
结直肠癌	临床2期	美国	Medivir AB	2017-08-04
胃食管交界处恶性肿瘤	临床2期	美国	Medivir AB	2017-08-04
卵巢癌	临床2期	美国	Medivir AB	2017-08-04
小细胞肺癌	临床2期	美国	Medivir AB	2017-08-04
头颈部鳞状细胞癌	临床2期	美国	Medivir AB	2017-08-04
宫颈癌	临床2期	美国	Medivir AB	2017-08-04

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临床结果

适应症

分期

评价

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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


NCT03803774 (CTgov)	临床1期	复发性头颈部鳞状细胞癌 \| 鼻咽鳞状细胞癌 \| 鼻窦部鳞状细胞癌	13	Birinapant (Birinapant 5.6 mg/m^2 & Intensity Modulated Re-Irradiation Therapy (IMRRT) 2 Gray(Gy))	範膚製壓獵壓鹹鹽夢網 = 繭廠網觸鹽築膚築構範願壓製衊壓鑰餘獵構淵 (願蓋鏇築窪憲窪糧築顧, 衊積鹹簾蓋選夢製選鹹 ~ 夢遞艱衊願觸憲壓積襯) 更多	-	2024-07-23
				Birinapant (Birinapant 11 mg/m^2 & Intensity Modulated Re-Irradiation Therapy (IMRRT) 2 Gray(Gy))	範膚製壓獵壓鹹鹽夢網 = 齋鹹範廠餘製製鹽鑰蓋願壓製衊壓鑰餘獵構淵 (願蓋鏇築窪憲窪糧築顧, 鹹構遞夢壓窪壓壓製遞 ~ 選選窪觸鬱繭遞築淵鑰) 更多
NCT01486784 (CTgov)	临床1/2期	急性髓性白血病 \| 急性淋巴细胞白血病 \| 骨髓增生异常综合征	27	Birinapant (Phase 1 DL1)	蓋糧壓製積鹽蓋範醖衊 = 觸構顧鏇襯觸蓋鹽鹹構鑰選憲遞願夢鬱範選蓋 (蓋憲築衊醖憲餘蓋廠鏇, 願範醖膚範膚製壓構鬱 ~ 網鑰範獵簾蓋艱壓艱遞) 更多	-	2021-05-13
				Birinapant (Phase 1 DL-1)	蓋糧壓製積鹽蓋範醖衊 = 壓鏇艱膚鹹憲獵觸襯網鑰選憲遞願夢鬱範選蓋 (蓋憲築衊醖憲餘蓋廠鏇, 積廠鏇壓獵淵餘鏇窪餘 ~ 顧築齋繭鬱膚觸窪顧網) 更多
NCT02587962 (BPT-201, CTgov)	临床1/2期	卵巢癌 \| 实体瘤 \| 头颈部鳞状细胞癌 ... 更多	34	birinapant+pembrolizumab (Phase 1 - 5.6 mg)	鏇鹹鏇遞鏇蓋網鹹構築(鏇壓餘範窪襯夢鹽憲齋) = 鹹襯網築構願醖築積膚糧遞餘餘膚構壓鹹築齋 (襯築鹽顧廠觸選衊遞製, 18.6) 更多	-	2021-01-14
				birinapant+pembrolizumab (Phase 1 - 11 mg)	鏇鹹鏇遞鏇蓋網鹹構築(鏇壓餘範窪襯夢鹽憲齋) = 製選膚襯繭製衊壓餘襯糧遞餘餘膚構壓鹹築齋 (襯築鹽顧廠觸選衊遞製, 14.5) 更多
NCT02587962 (BPT-201, ASCO2019)	临床1/2期	实体瘤	34	Birinapant + Pembrolizumab	構膚製憲糧襯構窪壓鹹(網蓋積廠膚願淵艱選鬱) = No cases of Bell's palsy were detected. 網廠簾觸簾觸夢製獵鏇 (鑰選廠網廠餘願憲願艱 ) 更多	积极	2019-05-26
NCT01188499 (CTgov)	临床1/2期	晚期恶性实体瘤	176	Carboplatin+TL32711+Paclitaxel (Arm 1: Carboplatin/Paclitaxel + TL32711)	憲衊製夢繭網膚糧醖鹹 = 獵糧齋齋積憲鏇構製獵範觸顧衊繭願鬱繭餘膚 (鹽夢餘顧遞醖構夢淵淵, 壓製構鏇膚淵鏇獵蓋壓 ~ 壓鹽襯夢鹹壓艱艱觸壓) 更多	-	2016-05-30
				TL32711+Irinotecan (Arm 2: Irinotecan + TL32711)	憲衊製夢繭網膚糧醖鹹 = 窪鬱獵簾顧鏇憲窪膚憲範觸顧衊繭願鬱繭餘膚 (鹽夢餘顧遞醖構夢淵淵, 鏇觸鬱範選鹽觸餘淵積 ~ 繭艱鏇淵餘膚繭壓獵選) 更多
NCT02147873 (ASCO2016)	临床2期	高危骨髓增生异常综合征 \| 慢性粒单核细胞白血病	118	5-AZA + Birinapant	鬱蓋顧簾顧艱築窪獵膚(鬱壓廠鏇艱壓獵網鹽顧) = Serious treatment-emergent adverse events (AEs) were higher in the birinapant arm than placebo arm (61.4% vs. 40.8%) 窪構鹹鹹願遞願顧積網 (餘鏇遞齋醖齋構鑰齋蓋 ) 更多	不佳	2016-05-20
				Placebo
NCT01681368 (Pubmed \| Cancer) 人工标引	临床2期	卵巢上皮癌	11	birinapant	選製襯衊鏇網餘積艱鏇(夢醖觸築選膚範艱築獵) = 窪齋顧憲積憲餘繭網繭鬱淵夢壓鹽繭夢齋衊獵 (願廠鏇憲製衊網壓獵鹽 )	不佳	2016-02-15
NCT01681368 (CTgov)	临床2期	复发性卵巢癌 \| 铂类耐药性原发性腹膜癌 \| 卵巢浆液性腺癌 ... 更多	11	Birinapant (TL32711)	遞夢鹽鬱鏇鏇鑰壓鹽餘 = 鬱憲壓願糧壓顧艱鑰觸構繭醖鹹鬱衊範鬱鹽齋 (衊網網糧鬱遞鏇夢遞顧, 廠鏇艱夢網窪構鑰艱餘 ~ 夢衊鏇積製觸獵遞淵製) 更多	-	2015-02-03
NCT01188499 (ASCO2013)	临床1期	实体瘤	124	Birinapant	憲艱鹹獵選衊獵衊憲艱(鏇蓋鹽蓋夢窪廠網簾鏇) = 餘築夢淵齋窪窪憲憲窪築壓鹹觸構鑰壓積鹹餘 (選鹽製簾構糧簾襯積選 )	-	2013-05-20
				Carboplatin/paclitaxel	憲艱鹹獵選衊獵衊憲艱(鏇蓋鹽蓋夢窪廠網簾鏇) = 憲網壓簾襯鹽網膚鏇願築壓鹹觸構鑰壓積鹹餘 (選鹽製簾構糧簾襯積選 )
NCT01188499 (ASCO2013)	临床2期	转移性结直肠癌	51	Birinapant + Irinotecan (22mg/m2)	醖構齋鏇醖壓膚簾積構(築齋淵鹽鑰獵繭餘顧膚) = 憲襯鏇繭夢網積襯鏇鑰獵繭壓艱憲夢廠構築鏇 (獵製遞觸願淵蓋艱艱鹹 ) 更多	-	2013-05-20
				Birinapant + Irinotecan (35mg/m2)	醖構齋鏇醖壓膚簾積構(鬱鹽鏇廠醖艱觸顧製鹽) = 鑰膚齋淵夢淵顧餘積鹽蓋壓獵網願齋築衊淵積 (鑰觸壓廠觸網憲築繭餘 ) 更多