A Phase 1 Study of TPI 287 Concurrent With Fractionated Stereotactic Radiotherapy (FSRT) in Treatment of Brain Metastases From Advanced Breast and Non-Small Cell Lung (NSCL) Cancer

The main purpose of this study is to see whether addition of TPI 287 to FSRT is safe and tolerable. Researchers also want to find out if adding TPI 287 to FSRT can help with better controlling the growth of brain lesions in people with brain metastases from their cancer.

开始日期2014-10-09

申办/合作机构

H. Lee Moffitt Cancer Center & Research Institute, Inc.

[+1]

NCT02133846

/ Completed临床1期IIT

A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Sequential Cohort, Dose-Ranging Study of the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of TPI 287 in Patients With Primary Four Repeat Tauopathies: Corticobasal Syndrome or Progressive Supranuclear Palsy

The purpose of this study is to determine the safety and tolerability [maximum tolerated dose (MTD) within planned dosing range] of intravenous (IV) infusions of TPI 287 administered once every 3 weeks for 9 weeks (for a total of 4 infusions) in patients with primary four repeat tauopathies (4RT), corticobasal syndrome (CBS; also called corticobasal degeneration, CBD) or progressive supranuclear palsy (PSP).

开始日期2014-05-01

申办/合作机构

The University of California, San Francisco

[+2]

NCT02047214

/ Terminated临床2期

Phase 2 Dose-Escalation Study of TPI 287 in Combination With Bevacizumab in Adults With Recurrent or Progressive Glioblastoma Following a Bevacizumab-Containing Regimen

The purpose of this study is to evaluate the safety, maximum tolerated dose (MTD), and efficacy of TPI 287 in combination with Avastin (bevacizumab) in subjects who have glioblastoma multiforme (GBM) that has progressed following prior radiation and temozolomide (TMZ) therapy and that has progressed following prior bevacizumab therapy.

开始日期2014-01-01

申办/合作机构

Cortice Biosciences, Inc.

100 项与 ARC-100 相关的临床结果

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100 项与 ARC-100 相关的转化医学

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100 项与 ARC-100 相关的专利（医药）

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项与 ARC-100 相关的文献（医药）

2024-01-01·Neuro-oncology advances

Phase 1 trial of TPI 287, a microtubule stabilizing agent, in combination with bevacizumab in adults with recurrent glioblastoma

Article

作者: Benkers, Tara ; Singer, Samuel ; Duic, Paul J ; Hsu, Sigmund ; Rao, Mayank ; Goldlust, Samuel A ; Nabors, Louis B ; Silberman, Sandra L ; Mohile, Nimish ; Cappello, Lori ; Farmer, George

Abstract:

Background:

Recurrent glioblastoma (rGBM) has limited treatment options. This phase 1 protocol was designed to study the safety and preliminary efficacy of TPI 287, a central nervous system penetrant microtubule stabilizer, in combination with bevacizumab (BEV) for the treatment of rGBM.

Methods:

GBM patients with up to 2 prior relapses without prior exposure to anti-angiogenic therapy were eligible. A standard 3 + 3 design was utilized to determine the maximum tolerated dose (MTD) of TPI 287. Cohorts received TPI 287 at 140–220 mg/m2 every 3 weeks and BEV 10 mg/kg every 2 weeks during 6-week cycles. An MRI was performed after each cycle, and treatment continued until progression as determined via response assessment in neuro-oncology criteria.

Results:

Twenty-four patients were enrolled at 6 centers. Treatment was generally well tolerated. Fatigue, myelosuppression, and peripheral neuropathy were the most common treatment emergent adverse events. Dose-limiting toxicity was not observed, thus the MTD was not determined. Twenty-three patients were evaluable for median and 6-month progression-free survival, which were 5.5 months (mo) and 40%, respectively. Median and 12-month overall survival were 13.4 mo and 64%, respectively. The optimal phase 2 dose was determined to be 200 mg/m2.

Conclusions:

TPI 287 can be safely combined with BEV for the treatment of rGBM and preliminary efficacy supports further investigation of this combination.

2023-02-01·Cancer chemotherapy and pharmacology

The CNS-penetrating taxane drug TPI 287 potentiates antiglioma activity of the AURKA inhibitor alisertib in vivo

Article

作者: Lehman, Norman L ; Teer, Landon ; Hey, Andrew J ; Williams, Brian J ; Kakar, Aastha ; Schier, Leslie M ; Sak, Müge ; Chen, Joseph ; Al-Kawaaz, Mustafa N G ; Wilson, Megan J ; Zumbar, Cory T

INTRODUCTION:

Glioblastoma (GBM) has a very poor prognosis despite current treatment. We previously found cytotoxic synergy between the AURKA inhibitor alisertib and the CNS-penetrating taxane TPI 287 against GBM tumor cells in vitro.

METHODS:

We used an orthotopic human GBM xenograft mouse model to test if TPI 287 potentiates alisertib in vivo. Western blotting, immunohistochemistry, siRNA knockdown, annexin V binding, and 3-dimensional Matrigel invasion assays were used to investigate potential mechanisms of alisertib and TPI 287 treatment interactions.

RESULTS:

Alisertib + TPI 287 combination therapy significantly prolonged animal survival compared to vehicle (p = 0.011), but only marginally compared to alisertib alone. Alisertib, TPI 287, and combined alisertib + TPI 287 reduced animal tumor volume compared to vehicle-treated controls. This was statistically significant for the combination therapy at 4 weeks (p < 0.0001). Alisertib + TPI 287 treatment decreased anti-apoptotic Bcl-2 protein levels in vivo and in vitro. Expression of the pro-apoptotic protein Bak was significantly increased by combination treatment (p < 0.0001). Pro-apoptotic Bim and Bak knockdown by siRNA decreased apoptosis by alisertib + TPI 287 in GB9, GB30, and U87 cells (p = 0.0005 to 0.0381). Although alisertib and TPI 287 significantly reduced GBM cell invasion (p < 0.0001), their combination was no more effective than TPI 287 alone.

CONCLUSIONS:

Results suggest that apoptosis is the dominant mechanism of potentiation of GBM growth inhibition by alisertib + TPI 287, in part through effects on Bcl-2 family proteins, providing a rationale for further laboratory testing of an AURKA inhibitor plus TPI 287 as a potential therapy against GBM.

2020-02-01·JAMA neurology1区 · 医学

Reactions to Multiple Ascending Doses of the Microtubule Stabilizer TPI-287 in Patients With Alzheimer Disease, Progressive Supranuclear Palsy, and Corticobasal Syndrome

1区 · 医学

Article

作者: Geldmacher, David S. ; Koestler, Mary ; Hare, Emma ; Powers, Ryan ; Shamloo, Merhdad ; Jung, Joo In ; Rosen, Howard J. ; Tsai, Richard M. ; Chuu, Emmeline L. ; Luong, Phi N. ; Mumford, Paige ; Rabinovici, Gil D. ; Wolf, Amy ; Miller, Zachary ; Boxer, Adam L. ; Ljubenkov, Peter A. ; Natelson-Love, Marissa ; Miller, Bruce L. ; Fagan, Anne M. ; Cobigo, Yann ; Wang, Ping ; Rojas, Julio C. ; McKinley, Emily C. ; Roberson, Erik D. ; Brown, Jesse A.

Importance:

Basket-design clinical trials that allow investigation of treatment effects on different clinical syndromes that share the same molecular pathophysiology have not previously been attempted in neurodegenerative disease.

Objective:

To assess the safety, tolerability, and pharmacodynamics of the microtubule stabilizer TPI-287 (abeotaxane) in Alzheimer disease (AD) or the 4-repeat tauopathies (4RT) progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS).

Design, Setting, and Participants:

Two parallel-design, double-blind, placebo-controlled phase 1 randomized clinical trials in AD and 4RT were conducted from December 20, 2013, through May 4, 2017, at the University of California, San Francisco, and University of Alabama at Birmingham. A total of 94 patients with clinically diagnosed AD (n = 39) and 4RT (n = 55) were screened; of these, 3 refused to participate, and 10 with AD and 11 with 4RT did not meet inclusion criteria. A total of 29 patients with AD, 14 with PSP, and 30 with β-amyloid-negative CBS (determined on positron emission tomography findings) were enrolled. Data were analyzed from December 20, 2013, through May 4, 2017, based on modified intention to treat.

Interventions:

Randomization was 8:3 drug to placebo in 3 sequential dose cohorts receiving 2.0, 6.3, or 20.0 mg/m2 of intravenous TPI-287 once every 3 weeks for 9 weeks, with an optional 6-week open-label extension.

Main Outcomes and Measures:

Primary end points were safety and tolerability (maximal tolerated dose) of TPI-287. Secondary and exploratory end points included TPI-287 levels in cerebrospinal fluid (CSF) and changes on biomarker, clinical, and neuropsychology measures.

Results:

A total of 68 participants (38 men [56%]; median age, 65 [range, 50-85] years) were included in the modified intention-to-treat analysis, of whom 26 had AD (14 women [54%]; median age, 63 [range, 50-76] years), and 42 had 4RT (16 women [38%]; median age, 69 [range, 54-83] years). Three severe anaphylactoid reactions occurred in TPI-287-treated patients with AD, whereas none were seen in patients with 4RT, leading to a maximal tolerated dose of 6.3 mg/m2 for AD and 20.0 mg/m2 for 4RT. More falls (3 in the placebo group vs 11 in the TPI-287 group) and a dose-related worsening of dementia symptoms (mean [SD] in the CDR plus NACC FTLD-SB [Clinical Dementia Rating scale sum of boxes with frontotemporal dementia measures], 0.5 [1.8] in the placebo group vs 0.7 [1.6] in the TPI-287 group; median difference, 1.5 [95% CI, 0-2.5]; P = .03) were seen in patients with 4RT. Despite undetectable TPI-287 levels in CSF, CSF biomarkers demonstrated decreased chitinase-3-like protein-1 (YKL-40) levels in the 4RT treatment arm (mean [SD], -8.4 [26.0] ng/mL) compared with placebo (mean [SD], 10.4 [42.3] ng/mL; median difference, -14.6 [95% CI, -30.0 to 0.2] ng/mL; P = .048, Mann-Whitney test).

Conclusions and Relevance:

In this randomized clinical trial, TPI-287 was less tolerated in patients with AD than in those with 4RT owing to the presence of anaphylactoid reactions. The ability to reveal different tau therapeutic effects in various tauopathy syndromes suggests that basket trials are a valuable approach to tau therapeutic early clinical development.

Trial Registration:

ClinicalTrials.gov identifiers: NCT019666666 and NCT02133846.

项与 ARC-100 相关的新闻（医药）

2025-10-30

·CNSight

阿尔茨海默病新药研发的多靶点探索

阿尔茨海默病（AD）新药研发关键靶点阿尔茨海默病（AD）作为痴呆主要诱因，正成为21世纪健康难题。全球现约2500万-3000万患者，2040年预计增至三倍，且现有治疗多为对症，无法根治。近期《Acta Pharmaceutica Sinica B》综述梳理AD新药研发关键靶点，为攻克疾病提供方向。 AD病理特征与现有治疗局限 AD于1907年由神经学家Alois Alzheimer发现，以进行性认知衰退为主，早期轻度记忆障碍，后期丧失交流能力，还伴语言问题、冲动行为。核心病理是细胞外β-淀粉样蛋白（Aβ）老年斑沉积与细胞内tau蛋白构成的神经原纤维缠结，二者致突触和神经元丢失、大脑萎缩。 AD按遗传分家族性（FAD）和散发性（SAD），按发病时间分早发型（EOAD）和晚发型（LOAD）。发病风险因素多，包括自噬缺陷、衰老、APOE4基因、Trem2基因、生活方式、微生物群改变、心血管疾病、脑外伤及教育水平、高血压、肥胖等。目前FDA已批准的AD治疗药包括：3种乙酰胆碱酯酶（AChE）抑制剂（多奈哌齐、卡巴拉汀、加兰他敏）和1种NMDA受体拮抗剂（美金刚）。它们仅短期改善认知，无法阻病情进展。AChE抑制剂通过抑制乙酰胆碱降解提脑内浓度，NMDA受体拮抗剂减少谷氨酸过度激活致的钙内流、减轻神经损伤，但均不针对AD根本病理。除此之外，FDA还批准了3种Aβ单抗类药物：阿杜卡单抗、仑卡奈单抗、多奈单抗。图2.示意性地描述了AD的乙酰胆碱释放周期和胆碱能假说图3.FDA批准用于治疗AD的药物的二维结构图4.全新NMDA受体拮抗剂的结构图5.谷氨酸在健康大脑中的传播经典靶点：β-淀粉样蛋白（Aβ）相关策略 Aβ异常代谢是AD核心病理，围绕其研发药物有抑制聚集、金属螯合剂、抗Aβ免疫疗法、调控分泌酶等方向。抑制Aβ聚集 Aβ易聚集形成寡聚体、纤维和斑块，可溶性寡聚体神经毒性最强。现有两种聚集抑制剂进入临床：司来吉兰（ELND005）：低剂量（250mg）安全但疗效欠佳，高剂量引发感染甚至死亡，需进一步评估。曲美普拉明：III期试验对认知评分无显著影响，重新分析发现其前药ALZ-801对ApoE4纯合子患者有益。此外，表没食子儿茶素-3-没食子酸酯（EGCG）因多生物活性，正考虑开展AD患者III期试验。图6.淀粉样蛋白聚集抑制剂的结构已扩展临床试验金属螯合剂 AD患者脑内铝、锌、铁、铜等金属离子升高，促Aβ聚集和神经毒性，金属螯合剂可结合这些离子抑Aβ积累。去铁胺（DFO）：两年研究显示，用药患者大脑新皮质铝浓度低，行为能力改善，还可能螯合锌、铜。氯喹诺尔：APP转基因小鼠用药9周，脑内可溶性Aβ升52%，提示可抑制Aβ聚集，且可溶性Aβ水平与认知障碍相关，早于斑块沉积，阻其积累关键。图7.金属螯合剂的结构抗Aβ免疫疗法通过主动或被动免疫促Aβ清除，机制有小胶质细胞吞噬、外周清除、解聚，但临床进展不顺：早期药AN1792引发脑膜脑炎等；甘特珠单抗减缓淀粉样蛋白沉积但疗效未证实；索拉珠单抗耐受好，却对1000名轻至中度患者无效；贝叶斯分析显示该疗法对AD无显著疗效。图8.主动免疫和被动免疫的分子基础调控分泌酶 Aβ由APP经β、γ分泌酶切割生成，α分泌酶切割可避Aβ产生，调控这三种酶是减少Aβ关键。 γ-分泌酶抑制剂（GSIs）与调节剂（GSMs）：GSIs理论减Aβ，但因影响Notch受体等，非选择性GSIs副作用大，如塞米司他试验终止；GSMs可选择性减Aβ₄₂，如NSAIDs证实可行性，他仑氟比尔II期安全但III期无效，且GSMs面临脑穿透性差等挑战。 β-分泌酶（BACE1）抑制剂：BACE1是APP切割限速酶，基因敲除小鼠无Aβ且无副作用，是理想靶点，但多种抑制剂如PF-05297909、AZD3293等因疗效欠佳或副作用终止试验，研发需克服选择性等难题。 α-分泌酶激活剂：α-分泌酶（主要ADAM10）切割APP可避Aβ产生，sAPPα有神经保护作用，AD患者脑脊液sAPPα低，激活策略有激活PKC、M1受体激动剂，激活ADAM10更优。图9.APP在非淀粉样变和淀粉样变通路中被α或β分泌酶裂解图10.人γ分泌酶复合物三维结构（PDBID：6IYC) 图11.已扩展临床试验的γ分泌酶抑制剂的结构图12.γ分泌酶调节剂的结构，这已经扩展了临床试验图13.人类BACE1的三维结构（PDBID：1FKN）图14.β分泌酶抑制剂的结构新兴靶点：tau蛋白与神经炎症通路 tau蛋白异常和神经炎症也是AD关键病理，相关靶点研究提供新方向。 tau靶向治疗 AD中tau过度磷酸化，解离聚集形成缠结致神经元损伤，治疗包括：激酶抑制剂：tau过度磷酸化与激酶（GSK-3β、CDK5）和磷酸酶失衡有关。GSK-3β抑制剂NP-031112临床前减tau磷酸化等，锂盐动物有效但患者无效，SB216763等因毒性或疗效差失败；CDK5抑制剂临床前能穿透血脑屏障降Aβ，但试验因疗效差或副作用终止。 tau聚集抑制剂：TRx0237 II期显高生物利用度，III期进行中；微管稳定剂如紫杉醇毒性大，TPI287对认知等有积极影响，烟酰胺小鼠实验有效，II期试验进行中。图15.tau聚集抑制剂（TRx0237）和tau稳定剂（紫杉醇和依泊替隆D）的结构图16.分别是抗甲状腺药物和不可逆葛兰素史克抑制剂的结构图17.GSK3抑制剂的结构，已延长临床试验 TREM2 TREM2是免疫球蛋白超家族跨膜受体，主要在髓系细胞表达，调控细胞功能。其基因变异与AD风险相关，p.Arg47His变异在欧美增风险2-3倍，东亚等人群无关联。TREM2缺陷减小胶质细胞聚集和吞噬，激活则促其极化等，发挥神经保护，但靶向治疗面临生物标志物缺乏等挑战。图18.TREM2信号通路 BIN1 BIN1是晚发型AD第二大遗传易感基因，通过tau通路影响AD风险，参与膜运输等，影响缠结形成。AD患者脑内BIN1表达异常，敲低可减tau介导神经毒性，还与自噬、钙通道运输相关，调控BIN1或能护神经。其他潜力靶点：神经递质、感染与Notum酶神经递质相关靶点 AD患者多神经递质紊乱，除已批准药物，还有：丁酰胆碱酯酶（BuChE）：AD患者脑内部分区域BuChE升高，抑制它或有神经保护作用，相关抑制剂在研。5-羟色胺受体（5-HT₆、5-HT₄）：5-HT₆拮抗剂英特匹定、5-HT₄拮抗剂普瑞昔单抗均进入II期试验。烟碱型乙酰胆碱受体（nAChR）：激动剂EVP-6124、POZANICLINE等在研，EVP-6124I/II期安全，III期评估认知改善。图19.胆碱酯酶抑制剂的结构，已扩展临床试验图20.胆碱酯酶抑制剂的结构感染相关靶点感染或参与AD发病，如牙龈卟啉单胞菌等感染增AD风险。COR388可抑牙龈卟啉单胞菌的牙龈蛋白酶，减神经炎症，小鼠实验挽救神经元、降Aβ₁₋₄₂，提供抗感染方向。 Notum酶 Notum负向调控Wnt信号通路，AD患者脑内Wnt信号下调，抑制Notum可护神经。Notum有明确晶体结构，是理想靶点，现有ABC99、褪黑素、咖啡因等抑制剂，ABC99增神经祖细胞，褪黑素减Aβ沉积和tau磷酸化，为研发更好抑制剂奠基。图21.（A）涉及Notum的羧酸酯酶活性在Wnt上释放棕榈油酸基团的化学反应。（B）结合相互作用的二维表示图22.卡通中所示的Notum结构图23.与激素褪黑激素相关的Notum抑制剂图24.咖啡因和茶碱是Notum抑制剂图25.恶二唑2和三唑3是由片段产生的两个互补先导 AD治疗需多靶点、多策略联合 AD病理复杂，单一靶点药难控病情，从经典到新兴靶点，研究者持续探索。虽部分研发遇挑战，但随病理理解加深及多靶点药物、联合治疗推进，未来有望研发出延缓甚至阻止AD进展的新药，为患者带来希望。关注 “CNSight” 公众号，后台回复“ AD靶点”即可获取原文资料 CNSight 一个专注于CNS前沿领域的资讯分享平台

临床3期免疫疗法临床结果

2025-01-05

·同写意

别了，一年股价暴跌99%的Biotech们

众所周知，二级市场是资本创新要素流动的重要部分，而IPO则一度成为未获盈利Biotech的康庄大道。公司上市以后，更容易筹集资金投入新药开发，通过产品商业化创造收益，反哺股市投资者——这个正向循环构，构成过去生物制药行业发展的主线之一，尤其在资本市场活跃时期，似乎只要获得入场券，一家Biotech日后便大概率平步青云。以美股为代表的IPO窗口，在2024年率先重新洞开，20多家Biotech由此进入二级市场。但是，它们很快发现，另一边的形势也不容乐观。许多新上市的公司，很快跌破发行价。尽管美股Biotech股价与临床阶段缺乏强关联，可大体上，一家公司股价暴跌，背后一定是出现不小的问题，无论临床开发的失败，抑或战略布局的踏空。下文，将结合GEN收录数据，对从2024年股价跌幅排名前五的Biotech进行梳理，尝试为行业勾勒出“2025年避坑指南”。正如在上一篇文章里提到的，反向股票分割常作为公司股价低迷时期的自救之举，Exicure似乎凭借这种操作，在2024年底将股价拉升了近500%。不过，我们也要看到更大的背景。五家跌幅超99%的Biotech案例中，反向股票分割都被提上日程，结果于事无补，甚至有的下跌反而是在实施该措施之后发生。大健康领域一度被视为蓝海，事实却证明，要讲好一个由生物技术驱动、横跨消费与严肃医疗的故事并不容易。生物技术的高回报建立在高风险上，如果不能找到技术落地与市场需求的平衡，被时代甩下便并非杞人忧天。股价涨幅有情绪的影响，问题是，如果负面情绪不能得到很好地管理，连锁反应很可能会伤及根本，比如2024年，TFF Pharmaceuticals就宣布破产清算。 1 Aditxt 2024年跌幅：99.90% 2023年12月，Aditxt曾宣布以1亿美元收购Evofem Biosciences，当日收获高达83.95%的股价涨幅。2024年，这家Biotech陷入低迷之际，再次祭出并购的法宝。但很可惜，“故技重施”并非万金油。自从2024年4月签署跟Appili Therapeutics的最终协议以来，Aditxt股价不升反降，一度被纳斯达克警告退市。这大概离不开交易进展缓慢的影响。事实上，就连Evofem的并购案进度，也超出Aditxt本来的预期，继续延至2025年1月。为阻止股价下滑，并重新符合纳斯达克的最低出价规则，Aditxt从去年10月2日起实施“1比40”反向股票分割。如今，Aditxt还在悬崖边上。 2017年设立的Aditxt开发了一种免疫重编程技术，旨在重新训练免疫系统以诱导耐受性，解决移植器官排斥、自身免疫性疾病和过敏问题。作为关联资产，Aditxt还发明出一套提供检测免疫系统概况的工具。目前，上述想法仍未变成现实。根据最新计划，自免候选药物ADI-100会在近期向FDA递交IND申请，用于治疗1型糖尿病、牛皮癣、僵人综合征等。如果一切顺利，首次人体试验最早也要在2025年下半年才能完成。钱是绕不开的话题，尤其考虑到两笔尚未完成的收购。基于低迷的股价表现，Aditxt已暂停股权融资，将其融资策略转向债务融资，为其收购计划提供资金。 Aditxt一些手牌看起来不错。例如，FDA对Appili旗下的ATI-1801开发战略给予了积极反馈，这款外用抗寄生虫产品符合NDA提交的要求。不确定在于，尚缺乏有关NDA提交的具体要求或时间表的重要细节。尽管这看起来像是“拆东墙补西墙”，Aditxt将新一年的现金流，希望寄托在两家要被收购的公司上。 2024年上半年，Evofem的收入为780万美元。而现阶段，Appili已从美国国防部获得约600万美元资助。这项资助的总额在1400万美元，旨在开发一种传染病疫苗ATI-1701。 2 CNS Pharmaceuticals 2024年跌幅：99.81% CNS Pharmaceuticals的惨痛，是从2024开年就开始的。去年年初，该Biotech股价迅速从约每股60美元的高位，一路“跌跌不休”。这背后，似乎有财务上的阴霾影响。2023年第三季度报告显示，CNS Pharmaceuticals净亏损进一步扩大，同比下降37.93%，对投资者的信心不得不说是个打击。随后进入2024年，生物技术板块整体下行的情况，无疑更加放大了对某些个股的担忧。 2017年成立以来，CNS Pharmaceuticals专注于开发治疗大脑和中枢神经系统肿瘤的药物。贝柔比星（Berubicin）是其主要候选管线，具备穿过血脑屏障潜力，但最快的一项研究仍在II期临床。至于另一项资产微管抑制剂TPI 287，则来自Cortice Biosciences授权。2024年7月，Cortice跟CNS Pharmaceuticals签署协议，允许后者在四个国家/地区对TPI 287进行开发。吊诡的是，这次合作并不被二级市场看好，相反，声明引发该股的又一次下跌。关键问题是，CNS Pharmaceuticals如何支付对价？答案是用股票。为该笔交易，它增发60多万股股票，大大稀释了现有股东的股权。早前，“1比50”的反向股票分割曾帮助CNS Pharmaceuticals拉升了股价，但效果并不持久。2024年9月，纳斯达克再度发出退市警告。 CNS Pharmaceuticals的苦苦挣扎，凸显了制药行业一些Biotech面临的持续资金挑战。而众所周知，神经系统疾病方面，长期充斥着临床失败的消息，包括辉瑞、渤健等巨头都先后受挫。想要开启变革，Biotech显然需要更大的勇气和实打实的准备。根据资产负债表，CNS Pharmaceuticals持有的现金暂且多于债务。但该公司还在迅速消耗现金储备，如果趋势持续下去，可能会加剧与纳斯达克的合规问题。此外，该股的相对强弱指数（RSI）表明其处于超卖区域，这或许会引起反向投资者或那些寻求潜在扭转局面的投资者的兴趣，包括MNC的并购。 I期临床数据显示，44%的患者在贝柔比星治疗后获得了临床反应。CNS Pharmaceuticals预计，2025年上半年，II期临床结果的主要分析数据会对外公布，公司“准备在短期内为所有利益相关者释放价值”。 3 Allarity Therapeutics 2024年跌幅：99.66% 区别于其他Biotech，Allarity虽然同样没有盈利，却至少保证现金流眼下无虞。根据2024年第三季度报告，它的流动资产总额为2036.6万美元，相对应的总负债只有741.4万美元。然而，投资者明显对这家2012年成立的药企有更高的期待。否则我们无法解释，为何Allarity会出现在跌幅最大的Biotech名单上。纵观管线布局，Allarity可以说是围绕MNC的资产展开。早前，Allarity从卫材引进PARP/tankyrase双重抑制剂Stenoparib。在2018年，Allarity又通过交易，从诺华获得小分子泛酪氨酸激酶抑制剂Dovitinib的许可。很可惜，这种“反向策略”，并没有将新药开发的概率提高多少。随之而来的，是接二连三的麻烦。 2021年12月，Allarity提交了Dovitinib的NDA申请，希望将转移性肾细胞癌（mRCC）三线治疗作为商业化的突破口。可在2022年2月，FDA发出CRL，表示申请“不够完整，无法进行实质性审查”。同年晚些时候，FDA对Dovitinib的申报提出新的研究要求。单药不行，那就联用——Allarity的对策是，调转方向，把Dovitinib和Stenoparib等其他潜在疗法组合在一起。结果，因为没有如约支付费用，2024年1月，诺华终止Stenoparib的授权。失去Dovitinib之后，Allarity只好重新回到仅有的Stenoparib上面，但负面影响却并未终止。 2024年7月，SEC发出“韦尔斯通知”（Wells Notice），建议对Allarity涉嫌违反《美国联邦证券法》的行为采取执法行动。报道显示，“韦尔斯通知”与Allarity开发Dovitinib期间在FDA会议上的某些“披露”有关。 Allarity认为自己的行为适当。事实上，此事后续也暂无后文，但投资者却进一步投出不信任票。在运营和财务方面，Allarity去年实施战略变革，不仅扩大与Ascendiant Capital Markets的场外交易协议，还任命新的CFO Alexander Epshinsky。Allarity也做了“1比30”的反向股票分割。资金的灵活性给Allarity一定的腾挪空间。2024年9月，Allarity表示，在Stenoparib治疗晚期卵巢癌的II期试验中，两名患者已接受治疗超过一年。这一结果凸显了持久的临床益处和成药潜力。然而，2025年会如何，Allarity还需要拿出更多的结果来说服投资者。 4 Elevai Labs 2024年跌幅：99.37% 2023年11月，Elevai顶着“外泌体抗衰第一股”的光环在纳斯达克上市。但这次风光登场，已经是仅有的高光时刻，随后该公司股价一路跳水。大健康领域通常被视为“奶与蜜之地”，因为消费医疗的属性，让其有更多溢价空间。事实上，Elevai确实推出一系列主打促进胶原蛋白再生的护肤产品，销售至美国、加拿大和其他国际市场的皮肤科、整形外科和专业医疗中心。除了功能护肤，Elevai也布局了生物制药，开发针对肥胖症和增肌的候选药物EL-22和EL-32。众所周知，市场上已获批用于减肥的GLP-1药物，如诺和诺德的Ozempic、Wegovy，礼来的 Zepbound、Mounjaro，已经改变了肥胖治疗领域。然而，高达40%的体重减轻是由于肌肉损失造成的。 Elevai认为，当前肥胖领域未满足的关键需求之一，是避免在减肥治疗期间出现肌肉流失。EL-22正是一种含有肌肉生长抑制素抗原的工程益生菌，通过引发免疫反应，帮助人们在保持肌肉质量的同时实现大幅减脂。实际上，这条道路并不宽敞。肌肉生长抑制素与肌细胞膜上的ActRIIB结合导致肌肉退化，已并非什么冷门洞见，包括礼来在内，都在围绕阻断该过程进行下一代药物开发。在其他药企高举高打的同时，Elevai却只有一项在韩国开展的小规模I期临床，来表明EL-22良好安全性和耐受性，投资者的担忧也就不难理解。据透露，Elevai正与KCRN Research合作，为预计在2025年第一季度与FDA进行pre-IND会议做准备，希望打通EL-22这种工程益生菌的临床开发制定监管途径。换言之，EL-22能否进入美国市场仍面临巨大的未知。 Elevai的案例，凸显了一家志在多元化发展的Biotech的艰难。反观近几年，辉瑞、GSK、强生等巨头，都已开启消费健康部门等拆分计划，暗示着战略聚焦的重要性。 2024年前三季度，Elevai的净亏损进一步扩大至431万美元。同年11月，Elevai试图通过“1拆200”的反向股票分割来阻止投资者抛售股票。 Elevai还2024年底更名为PMGC Holdings，并将注册地从特拉华州迁至内华达州。至于市场是否有耐心等待它的重组变革，或许就另说了。 5 TFF Pharmaceuticals 2024年跌幅：99.07% 对于TFF Pharmaceuticals来说，2024年是历史性的一年——12月12日，这家Biotech结束了最后一个交易日，收盘价为每股6.5美分。第二天，纳斯达克暂停了该股票交易。去年11月，TFF宣布解散。而在该消息发布的两个月前，TFF Pharmaceuticals还宣布，与埃默里大学和生物医学高级研究与发展局建立新的伙伴关系。此次合作志向远大，双方希望测试将mRNA药物转化为干粉吸入制剂的可行性，而无需冷链储存。TFF Pharmaceuticals将为此提供技术支持，实验室数据表明，该工艺生产的吸入型干粉制剂的空气动力学特性，可以将多达75%的剂量输送到肺部深处。从原理上说，TFF Pharmaceuticals平台不会引入高温、剪切应力等可能损坏治疗成分完整性的因素，而是将这些材料重新配制成易于储存且常温稳定储存的干粉剂型，使治疗药物和疫苗更容易覆盖全球。与口服药物相比，这种新剂型能够将治疗药物直接输送到目标器官（如肺）中，以较低的剂量给药，从而减少不必要的毒性和副作用。 2024年11月，一项采用甲型流感病毒血凝素（HA）mRNA疫苗作为样本进行的研究证明，TFF Pharmaceuticals专有的薄膜冷冻干燥技术（TFFD）可用于制备HA mRNA-LNP干粉制剂，但需要足够量的赋形剂，来最大限度减少HA mRNA-LNP疫苗受到冷冻干燥过程中复杂应力引起的物理性质、结构和免疫原性的变化。这或许是挑战之处。尽管存在突破可能，TFF Pharmaceuticals仍需讲好一个商业化闭环的故事，而市场认为，它的财务状况已不允许。 TFF Pharmaceuticals自2018年成立，迅速受到多方关注。2019年，该公司在纳斯达克IPO。而IPO后的6轮融资中，它筹集到超过6000万美元资金，投资者包括美国国家过敏和传染病研究所、Leidos和Liquid Venture Partners。人员方面，2023年诺贝尔生理学或医学奖得主Drew Weissman，一度是TFF Pharmaceuticals的科学顾问。而在药物市场端，根据早前研究，约40%的上市药物和约90%的在研药物由难溶性分子组成。这意味着，诸如TFF Pharmaceuticals开发的粉末制剂，有望利用自身更强的稳定性、适用性和便携性脱颖而出。可一副好牌最终还是打烂了。宣布解散前，TFF Pharmaceuticals董事会批准了一项清算计划，并任命会计师事务所Verdolino & Lowey负责人Craig Jalbert身兼数职，负责监督公司的清算工作。参考资料： 1.StockWatch: Wall Street’s Leaders and Laggards of 2024 同写意媒体矩阵，欢迎关注↓↓↓

并购IPO

2024-12-05

·access wire

CNS Pharmaceuticals to Host Virtual Analyst & Investor Day on December 11, 2024

Live webcast discussion featuring internationally renowned Glioblastoma Multiforme (GBM) Key Opinion LeadersCompany committed to addressing the most aggressive type of brain cancer with an average survival of only 14 to 16 months after diagnosis and no cureRegister for the event here HOUSTON, TX / ACCESSWIRE / December 5, 2024 / CNS Pharmaceuticals, Inc. (NASDAQ:CNSP) ("CNS" or the "Company"), a biopharmaceutical company specializing in the development of novel treatments for primary and metastatic cancers in the brain and central nervous system, today announced it will host a Virtual Analyst & Investor Day on Wednesday, December 11th from 11:30 AM - 1:00 PM ET.For the event, John Climaco, Chief Executive Officer, Sandra Silberman, MD, PhD, Chief Medical Officer and Zena Muzyczenko, Vice President of Clinical Operations at CNS Pharmaceuticals will be joined by Key Opinion Leaders: Michael Weller, Prof. Dr. med. Director of Department, Department of Neurology, Universitatsspital, Zurich, Switzerland; Samuel Goldlust, MD, Board-certified and fellowship-trained neuro oncologist with Saint Luke's Cancer Specialists; and Erin Dunbar, MD founding physician of the Brain Tumor Center and Director of Neuro-Oncology at Piedmont Atlanta Hospital.As part of the event, the members of the CNS Pharmaceuticals management team and participating KOLs will discuss GBM and provide an overview of Berubicin and next steps for the clinical development program. Additionally, participants will discuss the Company's second asset, TPI 287, and its development and regulatory strategy moving forward.A live video webcast of the event will be available on the Events page of the Investors section of the Company's website (cnspharma.com). A webcast replay will be available two hours following the live presentation and will be accessible for 90 days.About CNS Pharmaceuticals, Inc.CNS Pharmaceuticals is a clinical-stage pharmaceutical company developing a pipeline of anti-cancer drug candidates for the treatment of primary and metastatic cancers of the brain and central nervous system. The Company's lead drug candidate, Berubicin, is a novel anthracycline and the first anthracycline to appear to cross the blood-brain barrier. Berubicin is currently in development for the treatment of a number of serious brain and CNS oncology indications including glioblastoma multiforme (GBM), an aggressive and incurable form of brain cancer.For more information, please visit www.CNSPharma.com, and connect with the Company on X, Facebook, and LinkedIn.Forward-Looking StatementsSome of the statements in this press release are forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, Section 21E of the Securities Exchange Act of 1934 and the Private Securities Litigation Reform Act of 1995, which involve risks and uncertainties. These statements relate to future events, future expectations, plans and prospects. Although CNS believes the expectations reflected in such forward-looking statements are reasonable as of the date made, expectations may prove to have been materially different from the results expressed or implied by such forward-looking statements. CNS has attempted to identify forward-looking statements by terminology including ''believes,'' ''estimates,'' ''anticipates,'' ''expects,'' ''plans,'' ''projects,'' ''intends,'' ''potential,'' ''may,'' ''could,'' ''might,'' ''will,'' ''should,'' ''approximately'' or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. These statements are only predictions and involve known and unknown risks, uncertainties and other factors, including market and other conditions and those discussed under Item 1A. "Risk Factors" in CNS's most recently filed Form 10-K filed with the Securities and Exchange Commission ("SEC") and updated from time to time in its Form 10-Q filings and in its other public filings with the SEC. Any forward-looking statements contained in this press release speak only as of its date. CNS undertakes no obligation to update any forward-looking statements contained in this press release to reflect events or circumstances occurring after its date or to reflect the occurrence of unanticipated events, except as required by law.CONTACTS:Investor Relations ContactJTC Team, LLCJenene Thomas908.824.0775[email protected]SOURCE: CNS Pharmaceuticals, Inc.

100 项与 ARC-100 相关的药物交易

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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	Cortice Biosciences, Inc.	2013-09-01
复发性神经母细胞瘤	临床2期	美国	Cortice Biosciences, Inc.	2011-12-01
髓母细胞瘤	临床2期	美国	Cortice Biosciences, Inc.	2011-12-01
乳腺癌	临床2期	美国	Cortice Biosciences, Inc.	2011-08-16
乳腺癌脑转移	临床2期	美国	Cortice Biosciences, Inc.	2011-08-16
多形性胶质母细胞瘤	临床2期	美国	Cortice Biosciences, Inc.	2010-04-01
复发性胶质母细胞瘤	临床2期	美国	Cortice Biosciences, Inc.	2010-04-01
不能切除性胰腺癌	临床2期	美国	Cortice Biosciences, Inc.	2007-10-01
不能切除性胰腺癌	临床2期	西班牙	Cortice Biosciences, Inc.	2007-10-01
转移性前列腺癌	临床2期	美国	Cortice Biosciences, Inc.	2007-01-01

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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


NCT02133846 \| NCT01966666 (Pubmed \| JAMA Neurol) 人工标引	临床1期	阿尔茨海默症 \| 皮质基底节变性 \| 进行性核上性麻痹	68	TPI-287	積簾窪窪構選顧繭獵鑰(構遞築衊夢糧壓餘壓膚) = 衊鹽蓋齋構願遞製鹽簾鏇築廠範築範窪製鏇襯 (艱鬱範壓願衊衊觸積範 ) 更多	积极	2020-02-01
NCT02133846 \| NCT01966666 (Pubmed \| JAMA Neurol) 人工标引	临床1期	阿尔茨海默症 \| 皮质基底节变性 \| 进行性核上性麻痹	68	Placebo	積簾窪窪構選顧繭獵鑰(構遞築衊夢糧壓餘壓膚) = 簾觸鬱遞積艱鹽夢壓獵鏇築廠範築範窪製鏇襯 (艱鬱範壓願衊衊觸積範 ) 更多	积极	2020-02-01
NCT01582152 (CTgov)	临床1/2期	复发性胶质母细胞瘤	12	Bevacizumab+TPI (TPI 287 160 mg/m2 + Bevacizumab)	夢艱淵糧鹹憲繭蓋顧膚(積網製選繭膚廠觸製鏇) = 淵餘壓膚窪構廠蓋淵齋簾襯醖選鏇鏇獵膚鏇願 (窪膚繭範鬱窪醖夢網觸, 餘築憲遞鏇糧襯顧廠憲 ~ 獵膚衊憲鬱鹽製觸窪獵) 更多	-	2019-06-05
NCT01582152 (CTgov)	临床1/2期	复发性胶质母细胞瘤	12	Bevacizumab+TPI (TPI 287 140 mg/m2 + Bevacizumab)	夢艱淵糧鹹憲繭蓋顧膚(積網製選繭膚廠觸製鏇) = 艱憲顧鹹醖鹽顧廠襯範簾襯醖選鏇鏇獵膚鏇願 (窪膚繭範鬱窪醖夢網觸, 鑰壓製鹽醖夢醖繭構憲 ~ 壓餘憲範積網淵淵積餘) 更多	-	2019-06-05
NCT01332630 (CTgov)	临床2期	乳腺癌脑转移 \| 乳腺癌	24	Dexamethasone+TPI 287+Ranitidine+Benadryl	鏇鬱顧糧窪範獵觸鏇遞 = 衊範簾艱積憲夢積積鑰壓觸鏇蓋構膚憲齋窪餘 (餘願糧簾窪遞製構夢齋, 積鬱鏇夢廠淵淵鬱繭艱 ~ 範廠糧憲襯窪簾憲憲願) 更多	-	2018-07-10
CB-017 (SNO2017)	临床1/2期	复发性胶质母细胞瘤 unmethylated MGMT promoter	-	TPI 287	壓網鹽醖餘築鹹壓遞構(蓋選鹽範顧衊淵夢膚糧) = 醖構網築憲簾顧鏇構蓋鑰顧製餘鬱餘襯襯簾艱 (窪餘艱廠鑰餘遞糧顧衊 ) 更多	积极	2017-11-06
NCT01933815 (ASCO 12017 \| ASCO 22017) 人工标引	临床1/2期	复发性胶质母细胞瘤	24	bevacizumab+TPI 287	構夢選淵選糧獵構積鹽(艱願範網蓋網鏇選醖餘) = 範淵夢餘醖鬱蓋鑰鹹蓋鏇餘觸鏇簾選襯觸壓鹹 (鹹顧鬱積鹹淵蓋構夢積 ) 更多	积极	2017-06-05
NCT01067066 (Pubmed \| Melanoma Res) 人工标引	临床1期	转移性黑色素瘤	21	temozolomide+TPI 287	鏇鬱願簾鏇積艱鏇糧鹽(鑰糧憲遞齋鏇糧餘觸壓) = neuropathy and six patients experienced grade III neuropathy 鹹網積夢艱夢襯製願網 (窪築顧齋膚獵築窪膚膚 ) 更多	积极	2016-12-01
SNO2016	临床1/2期	复发性胶质母细胞瘤	-	TPI 287	積範選艱範構製選醖淵(簾構觸遞鑰觸衊觸蓋廠) = myelosuppression (n=3) was the only drug-related grade 3/4 adverse event 鹹鏇顧壓遞獵簾鹽膚壓 (鏇淵蓋廠積選醖觸廠廠 )	积极	2016-11-07
NCT01113463 (CTgov)	临床2期	多形性胶质母细胞瘤 \| 复发性胶质母细胞瘤	17	TPI 287	鹽廠餘膚鏇膚鹽範鏇鑰 = 鹽淵膚鏇製糧鹽鏇獵淵積獵遞糧獵獵製衊製簾 (獵膚鏇餘鏇餘構鑰構觸, 鹽簾鑰構鹹鬱繭艱齋壓 ~ 構窪製遞願鹹淵鹽範鑰) 更多	-	2016-10-31
NCT00867568 (CTgov)	临床1期	复发性髓母细胞瘤 \| 神经母细胞瘤 \| 髓母细胞瘤	18	TPI 287	願獵選蓋範選鹽淵壓齋 = 夢繭淵壓壓鑰壓繭憲構網鏇壓齋鏇積鬱獵顧廠 (範淵範襯衊淵鹹鹹願鏇, 襯齋憲淵鬱醖鏇夢構憲 ~ 遞願醖淵鏇構艱蓋選鏇) 更多	-	2016-10-28
NCT01505608 (CTgov)	临床1/2期	复发性神经母细胞瘤 \| 神经母细胞瘤	14	Temozolomide+Irinotecan (Arm A- Temozolomide and Irinotecan)	齋夢鑰齋壓鏇網顧積衊 = 鹹夢鹽鏇繭襯襯艱鏇範鏇願餘顧構製築鹹鏇獵 (鹽觸遞獵蓋鏇鹹窪膚夢, 簾淵襯憲鬱願鑰遞糧鏇 ~ 廠膚憲壓繭壓糧願衊壓) 更多	-	2016-10-28
NCT01505608 (CTgov)	临床1/2期	复发性神经母细胞瘤 \| 神经母细胞瘤	14	Temozolomide+TPI 287+Irinotecan (Arm B- Temozolomide/Irinotecan + TPI 287)	鬱鏇鬱鹽衊顧衊構壓鏇 = 膚積選構積鑰齋觸壓衊選衊窪窪夢製積構範衊 (鏇糧簾窪鏇鏇鏇遞選艱, 憲壓憲糧壓鏇簾鏇齋憲 ~ 鑰簾憲願齋鏇願積繭構)	-	2016-10-28