A Phase 1/2 Study With Open-Label, Dose Escalation Phase Followed by Single-Arm Expansion at the Maximum Tolerated Dose to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy of NT219 Injection Alone and in Combination With ERBITUX® (Cetuximab) in Adults With Advanced Solid Tumors and Head and Neck Cancer

This is a phase 1/2, multi-center study with an open-label, dose escalation phase followed by a single-arm expansion phase to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of NT219 alone and in combination with ERBITUX® (cetuximab) in adults with recurrent and/or metastatic solid tumors.

开始日期2020-09-03

申办/合作机构

Tyrnovo Ltd.

100 项与 NT-219 相关的临床结果

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100 项与 NT-219 相关的转化医学

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100 项与 NT-219 相关的专利（医药）

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项与 NT-219 相关的文献（医药）

2023-10-01·Stem cells and development

Effect of Insulin on Bone Formation Ability of Rat Alveolar Bone Marrow Mesenchymal Stem Cells

Article

作者: Gao, Mingzhu ; Ma, Xiaocao ; E, Lingling ; Liu, Hongchen ; Zhang, Rong ; Lv, Yan ; Wang, Limei ; Zhang, Li ; Lu, Rongjian ; Zheng, Ying ; Zhang, Shaoli

The alveolar bone marrow mesenchymal stem cells (ABM-MSCs) play an important role in oral bone healing and regeneration. Insulin is considered to improve impaired oral bones due to local factors, systemic factors and pathological conditions. However, the effect of insulin on bone formation ability of ABM-MSCs still needs to be elucidated. The aim of this study was to determine the responsiveness of rat ABM-MSCs to insulin and to explore the underlying mechanism. We found that insulin promoted ABM-MSCs proliferation in a concentration-dependent manner, in which 10^-6 M insulin exerted the most significant effect. 10^-6 M insulin significantly promoted the type I collagen (COL-1) synthesis, alkaline phosphatase (ALP) activity, osteocalcin (OCN) expression, and mineralized matrix formation in ABM-MSCs, significantly enhanced the gene and protein expressions of intracellular COL-1, ALP, and OCN. Acute insulin stimulation significantly promoted insulin receptor (IR) phosphorylation, IR substrate-1 (IRS-1) protein expression, and mammalian target of rapamycin (mTOR) phosphorylation, but chronic insulin stimulation decreased these values, while inhibitor NT219 could attenuate these responses. When seeded on β-tricalcium phosphate (β-TCP), ABM-MSCs adhered and grew well, during the 28-day culture period, ABM-MSCs+β-TCP +10^-6 M insulin group showed significantly higher extracellular total COL-1 amino-terminus prolongation peptide content, ALP activity, OCN secretion, and Ca and P concentration. When implanted subcutaneously in severe combined immunodeficient mice for 1 month, the ABM-MSCs+β-TCP +10^-6 M insulin group obtained the most bone formation and blood vessels. These results showed that insulin promoted the proliferation and osteogenic differentiation of ABM-MSCs in vitro, and enhance osteogenesis and angiogenesis of ABM-MSCs in vivo. Inhibition studies demonstrated that the insulin-induced osteogenic differentiation of ABM-MSCs was dependent of insulin/mTOR signaling. It suggests that insulin has a direct anabolic effect on ABM-MSCs.

2016-04-01·FASEB journal : official publication of the Federation of American Societies for Experimental Biology2区 · 生物学

The inhibition of IGF‐1 signaling promotes proteostasis by enhancing protein aggregation and deposition

2区 · 生物学

Article

作者: Cohen, Ehud ; Ben‐Gedalya, Tziona ; Reuveni, Hadas ; Moll, Lorna

The discovery that the alteration of aging by reducing the activity of the insulin/IGF-1 signaling (IIS) cascade protects nematodes and mice from neurodegeneration-linked, toxic protein aggregation (proteotoxicity) raises the prospect that IIS inhibitors bear therapeutic potential to counter neurodegenerative diseases. Recently, we reported that NT219, a highly efficient IGF-1 signaling inhibitor, protects model worms from the aggregation of amyloid β peptide and polyglutamine peptides that are linked to the manifestation of Alzheimer's and Huntington's diseases, respectively. Here, we employed cultured cell systems to investigate whether NT219 promotes protein homeostasis (proteostasis) in mammalian cells and to explore its underlying mechanisms. We found that NT219 enhances the aggregation of misfolded prion protein and promotes its deposition in quality control compartments known as "aggresomes." NT219 also elevates the levels of certain molecular chaperones but, surprisingly, reduces proteasome activity and impairs autophagy. Our findings show that IGF-1 signaling inhibitors in general and NT219 in particular can promote proteostasis in mammalian cells by hyperaggregating hazardous proteins, thereby bearing the potential to postpone the onset and slow the progression of neurodegenerative illnesses in the elderly.-Moll, L., Ben-Gedalya, T., Reuveni, H., Cohen, E. The inhibition of IGF-1 signaling promotes proteostasis by enhancing protein aggregation and deposition.

Nature cancer

IRS1 phosphorylation underlies the non-stochastic probability of cancer cells to persist during EGFR inhibition therapy

Article

作者: Bar, Jair ; Straussman, Ravid ; Blum, Galia ; Tanay, Amos ; Friedlander, Gilgi ; Gilad, Shlomit ; Reizel, Yitzhak ; Jacob Berger, Adi ; Pilpel, Yitzhak ; Harush, Uzi ; Haviv, Izhak ; Gavert, Nancy ; Zwang, Yaara ; Stemmer, Salomon M ; Mardamshina, Mariya ; Reuveni, Hadas ; Prior, Amir ; Merquiol, Emmanuelle ; Barzel, Baruch ; Levin, Yishai ; Kamer, Iris ; Kupershmidt, Lana ; Meir, Zohar ; Geiger, Tamar ; Kaminski Strauss, Sivan ; Gigi, Elinor

Stochastic transition of cancer cells between drug-sensitive and drug-tolerant persister phenotypes has been proposed to play a key role in non-genetic resistance to therapy. Yet, we show here that cancer cells actually possess a highly stable inherited chance to persist (CTP) during therapy. This CTP is non-stochastic, determined pre-treatment and has a unimodal distribution ranging from 0 to almost 100%. Notably, CTP is drug specific. We found that differential serine/threonine phosphorylation of the insulin receptor substrate 1 (IRS1) protein determines the CTP of lung and of head and neck cancer cells under epidermal growth factor receptor inhibition, both in vitro and in vivo. Indeed, the first-in-class IRS1 inhibitor NT219 was highly synergistic with anti-epidermal growth factor receptor therapy across multiple in vitro and in vivo models. Elucidation of drug-specific mechanisms that determine the degree and stability of cellular CTP may establish a framework for the elimination of cancer persisters, using new rationally designed drug combinations.

项与 NT-219 相关的新闻（医药）

2024-03-03

·药明康德

使100%目标肺部病灶缩小的创新疗法；降低渐冻症患者疾病进展速率58%的小分子疗法... | 一周盘点

▎药明康德内容团队编辑本期看点1. 在一项1期研究中，T细胞受体（TCR）-T细胞疗法TSC-100和TSC-101与同种异体造血干细胞移植联用，让所有8名接受治疗的血液癌症患者没有出现复发。2. 肿瘤活化T细胞接合器JANX008的早期临床数据积极，一位接受JANX008治疗的非小细胞肺癌（NSCLC）患者100%的目标肺部病灶缩小。3. 治疗运动神经元病（MND）/肌萎缩侧索硬化（ALS）患者的小分子疗法monepantel的早期临床结果积极，高剂量组患者的疾病进展速率降低了58%。药明康德内容团队整理TSC-100、TSC-101：公布1期临床试验数据TScan Therapeutics公布了其开发的两种TCR-T细胞疗法TSC-100和TSC-101在1期临床试验中的更新数据。TSC-100和TSC-101是TScan Therapeutics公司开发的TCR-T细胞疗法，分别靶向次要组织相容性抗原HA-1和HA-2。它们旨在与同种异体的造血干细胞移植（HCT）联用，消灭残余血液癌细胞，预防疾病复发。此次公布的结果显示，所有8名接受TSC-100或TSC-101治疗的患者没有出现复发。其中，一名携带TP53基因突变的高风险骨髓增生异常综合征（MDS）患者在接受TSC-101治疗后已经无复发超过1年。JANX007、JANX008：公布1a期临床试验数据Janux Therapeutics公司公布了两项肿瘤活化T细胞接合器JANX007与JANX008的积极临床数据。JANX007是一款在研、潜在“best-in-class”的PSMA靶向肿瘤激活T细胞接合器，在临床上用于治疗转移性去势抵抗性前列腺癌（mCRPC），为Janux的主打项目。JANX008则是一种EGFR靶向肿瘤活化T细胞接合器，旨在克服患者产生细胞因子释放综合征（CRS）与已知的针对EGFR靶点的正常组织毒性问题。此次公布的分析结果显示，有83%接受JANX007治疗的晚期mCRPC患者达成前列腺特异性抗原（PSA）水平≥50%下降。一位接受JANX008治疗的NSCLC患者100%的目标肺部病灶缩小。根据此积极结果，Janux将持续进行这些疗法的剂量优化试验。Monepantel：公布1期临床试验数据PharmAust公司宣布，monepantel用于治疗运动神经元病/肌萎缩侧索硬化（俗称“渐冻症”）患者的1期临床试验达到了安全性和耐受性的主要终点，并显示出了具有潜在疗效的积极信号。此次公布的结果表明，monepantel的安全性和耐受性优于目前已获FDA批准的ALS/MND疗法。初步疗效数据显示，根据FDA主要疗效终点ALS功能评分量表修订版（ALSFRS-R），monepantel高剂量组患者的疾病进展速率降低了58%。该研究还证实了在患者的脑脊液中均可检测到monepantel及其活性代谢物。▲该1期临床试验的结果（图片来源：参考资料[14]）CYP-006TK：公布1期临床试验的初步数据Cynata Therapeutics公司公布了CYP-006TK治疗糖尿病足溃疡（DFU）的1期临床试验的首批16名患者伤口表面积的初步分析结果。CYP-006TK是Cynata公司的Cymerus诱导多能干细胞（iPSC）衍生间充质干细胞外用伤口敷料候选产品，它将间充质干细胞植入到一种新型硅敷料上。在这项试验中，CYP-006TK作为一种促进DFU患者伤口愈合的潜在治疗方法，受试者被随机分配接受以下两种治疗：（1）CYP-006TK治疗四周，然后在剩余的研究期间接受标准护理治疗；（2）在整个研究期间接受标准护理治疗。治疗10周后，CYP-006TK组（n=8）患者伤口表面积减少的百分比中位数为87.6%，而对照组（n=8）患者的这一比例为51.1%。这些结果与2023年4月公布的本试验首批6名患者（每组3人）截至第28天的结果所观察到的趋势一致。GDA-201：公布1期临床试验的初步数据Gamida Cell公司公布了其自然杀伤（NK）细胞疗法候选药物GDA-201的1期研究的首批12名CD20阳性非霍奇金淋巴瘤患者的初步数据。GDA-201可以通过增加细胞毒性以及在骨髓和淋巴器官中的扩增数量和留存时间来解决NK细胞疗法的局限性。此外，GDA-201还改善了NK细胞的抗体依赖性细胞毒性和肿瘤靶向性。入组患者之前接受过中位线数为六线的治疗，包括CAR-T细胞疗法和造血干细胞移植。患者接受了GDA-201联用利妥昔单抗的治疗，没有出现输液反应、剂量限制性毒性或相关严重不良事件。初步结果显示，7名患者的肿瘤负荷有所减轻。疗效评估显示，3名患者达到完全缓解（CR），2名患者达到部分缓解（PR），2名患者保持病情稳定（SD）。2名患者出现CRS（分别为1级和2级），没有出现免疫效应细胞相关神经毒性综合征（ICANS）或移植物抗宿主病（GvHD）的病例报告。该试验的全部结果预计将于2024年第一季度公布。AL01211：公布1期临床试验的初步数据AceLink Therapeutics公司公布了其用于治疗法布里病的新型GCS抑制剂在健康受试者中的1期临床试验数据。AL01211具有优秀的效力（个位数纳摩尔半抑制浓度IC50）、高选择性和其他良好的、可支持每日一次口服的药物特性，为目前需频繁静脉注射酶替代疗法的法布里病患者提供了口服小分子疗法的潜在选择。此次公布的结果显示，AL01211的安全性和耐受性良好。AL01211显示出剂量依赖性的药代动力学特征，能够有效降低健康受试者体内的疾病生物标志物的含量，如葡萄糖神经酰胺（glucosylceramide）和三己糖酰基鞘脂醇（globotriaosylceramide）。NT219：公布1/2期临床试验数据Purple Biotech公司公布了其潜在“first-in-class”的IRS1/2和STAT3双重抑制剂NT219的一项1/2期临床试验的新数据。这项1/2期研究旨在评估NT219联用西妥昔单抗治疗复发/转移性头颈部鳞状细胞癌（SCCHN）的安全性、药代动力学、药效学和疗效。该研究中，17名复发/转移性SCCHN患者既往接受治疗的中位线数为2线，94%的患者既往接受过免疫疗法。截至2024年1月25日的数据，患者对该联合疗法的耐受性和安全性良好。最常见的不良事件是输液相关反应和恶心，没有观察到与治疗相关的4/5级不良事件。药代动力学分析表明，NT219血浆浓度的增加与剂量有关。15名患者接受了疗效评估，其中7名患者观察到了抗肿瘤活性。在这7名患者中，2人确诊PR，3人达到SD（所有PR和SD的患者均为HPV阴性），客观缓解率（ORR）为29%，疾病控制率（DCR）为71%。所有剂量组患者的中位随访时间为9.4个月，15名患者中有8名仍在随访中。MaaT033：公布1期临床试验数据MaaT Pharma公司宣布，独立数据安全与监控委员会（DSMB）审查了IASO临床试验中使用MaaT033治疗的首批8位肌萎缩侧索硬化患者的安全性数据。MaaT033是一种源自供体、高浓度、高多样性的口腔微生物群生态系统疗法（Microbiome Ecosystem Therapy），目前正作为一种辅助疗法进行开发，以提高接受HCT和其他细胞疗法的患者的总生存率。此前，MaaT033已被欧洲药品管理局（EMA）授予孤儿药资格。此次DSMB的结论是，MaaT033的安全性良好，没有观察到严重不良事件，也没有发现可能与MaaT033有关的感染性事件，建议继续进行试验，不做任何修改。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] Frontier Medicines Announces Oversubscribed $80 Million Series C Financing to Support Progress of Clinical-Stage Pipeline. Retrieved February 23, 2024 from https://www.frontiermeds.com/newsroom/press-releases/frontier-medicines-announces-oversubscribed-80-million-series-c-financing[2] Gamida Cell Data Presented at the 2024 Tandem Meetings of ASTCT® and CIBMTR. Retrieved February 26, 2024 from https://investors.gamida-cell.com/news-releases/news-release-details/gamida-cell-data-presented-2024-tandem-meetings-astctr-and/[3] Expert Systems Celebrates Completion of Single Dose Studies and Start of Multiple Human Dosing for Lomonitinib, a Selective Pan-FLT3/IRAK4 Inhibitor, Achieved in Just 3 Years. Retrieved February 26, 2024 from https://www.prnewswire.com/news-releases/expert-systems-celebrates-completion-of-single-dose-studies-and-start-of-multiple-human-dosing-for-lomonitinib-a-selective-pan-flt3irak4-inhibitor-achieved-in-just-3-years-302069988.html[4] TScan Therapeutics Presents Promising Updated Phase 1 Clinical Results on TSC-100 and TSC-101 at the 2024 Tandem Meetings of ASTCT and CIBMTR. Retrieved February 26, 2024 from https://www.globenewswire.com/news-release/2024/02/26/2835007/0/en/TScan-Therapeutics-Presents-Promising-Updated-Phase-1-Clinical-Results-on-TSC-100-and-TSC-101-at-the-2024-Tandem-Meetings-of-ASTCT-and-CIBMTR.html[5] AceLink Therapeutics Announces Publication of Phase 1 Clinical Trial Data Evaluating AL01211 in Healthy Volunteers. Retrieved February 26, 2024 from https://www.businesswire.com/news/home/20240226569957/en[6] Kura Oncology Doses First Patient in KOMET-008 Trial of Ziftomenib in Combination with Standards of Care, Including FLT3 Inhibitor, in Acute Myeloid Leukemia. Retrieved February 26, 2024 from https://ir.kuraoncology.com/news-releases/news-release-details/kura-oncology-doses-first-patient-komet-008-trial-ziftomenib[7] Encouraging Initial Data from CYP-006TK Diabetic Foot Ulcer Clinical Trial. Retrieved February 26, 2024 from https://www.prnewswire.com/news-releases/encouraging-initial-data-from-cyp-006tk-diabetic-foot-ulcer-clinical-trial-302070709.html[8] Purple Biotech Presents Data of its Phase 1 Head & Neck Cancer of NT219 in combination with Cetuximab at ESMO TAT Congress 2024. Retrieved February 28, 2024 from https://www.globenewswire.com/news-release/2024/02/27/2835842/0/en/Purple-Biotech-Presents-Data-of-its-Phase-1-Head-Neck-Cancer-of-NT219-in-combination-with-Cetuximab-at-ESMO-TAT-Congress-2024.html[9] Janux Announces Encouraging Safety and Efficacy Data in Ongoing Dose Escalation Trials for PSMAxCD3-TRACTr JANX007 in mCRPC and EGFRxCD3-TRACTr JANX008 in Solid Tumors. Retrieved February 27, 2024 from https://investors.januxrx.com/investor-media/news/news-details/2024/Janux-Announces-Encouraging-Safety-and-Efficacy-Data-in-Ongoing-Dose-Escalation-Trials-for-PSMAxCD3-TRACTr-JANX007-in-mCRPC-and-EGFRxCD3-TRACTr-JANX008-in-Solid-Tumors/default.aspx[10] Curadev Announces First Treatment Cycle Completion for the First Patient Dosed in a Phase 1a/b Clinical Trial of its Allosteric STING Agonist CRD3874-SI in Patients with Advanced Cancer at Memorial Sloan Kettering Cancer Center in New York. Retrieved February 27, 2024 from https://www.prnewswire.com/news-releases/curadev-announces-first-treatment-cycle-completion-for-the-first-patient-dosed-in-a-phase-1ab-clinical-trial-of-its-allosteric-sting-agonist-crd3874-si-in-patients-with-advanced-cancer-at-memorial-sloan-kettering-cancer-center-in-302071911.html[11] Gain Therapeutics Announces the Initiation of the Multiple Ascending Dose (MAD) Part of the Phase 1 Clinical Trial of GT-02287, a Novel GCase-targeting Small Molecule Therapy for GBA1 Parkinson’s Disease. Retrieved February 27, 2024 from https://www.globenewswire.com/news-release/2024/02/27/2836361/0/en/Gain-Therapeutics-Announces-the-Initiation-of-the-Multiple-Ascending-Dose-MAD-Part-of-the-Phase-1-Clinical-Trial-of-GT-02287-a-Novel-GCase-targeting-Small-Molecule-Therapy-for-GBA1.html[12] ARTHEx Biotech Receives IND Clearance from FDA to Initiate the Phase I-IIa ArthemiR™ Trial of ATX-01 for Myotonic Dystrophy Type 1 (DM1). Retrieved February 29, 2024 from https://www.prnewswire.com/news-releases/arthex-biotech-receives-ind-clearance-from-fda-to-initiate-the-phase-i-iia-arthemir-trial-of-atx-01-for-myotonic-dystrophy-type-1-dm1-302073670.html[13] Spero Therapeutics Announces Clearance of IND for SPR206 to Treat MDR Gram-negative Bacterial Infections. Retrieved February 29, 2024 from https://www.globenewswire.com/news-release/2024/02/28/2836936/0/en/Spero-Therapeutics-Announces-Clearance-of-IND-for-SPR206-to-Treat-MDR-Gram-negative-Bacterial-Infections.html[14] PharmAust announces positive Phase 1 MEND Study Top-Line Results in MND / ALS. Retrieved February 29, 2024 from https://www.prnewswire.com/news-releases/pharmaust-announces-positive-phase-1-mend-study-top-line-results-in-mnd--als-302074155.html[15] Skyhawk Therapeutics Has Advanced to the Multiple Ascending Dose Portion of its Phase 1 Study evaluating SKY-0515, a RNA-Targeting Small Molecule for Huntington's Disease. Retrieved February 29, 2024 from https://www.prnewswire.com/news-releases/skyhawk-therapeutics-has-advanced-to-the-multiple-ascending-dose-portion-of-its-phase-1-study-evaluating-sky-0515-a-rna-targeting-small-molecule-for-huntingtons-disease-302074186.html[16] Atara Biotherapeutics Receives FDA Clearance of IND Application in Lupus Nephritis for ATA3219, an Allogeneic CAR T Therapy. Retrieved February 29, 2024 from https://www.businesswire.com/news/home/20240229015853/en[17] NeuroBo Pharmaceuticals Receives First Site IRB Approval for Its Phase 1 Clinical Trial Evaluating DA-1726 for the Treatment of Obesity. Retrieved February 29, 2024 from https://www.prnewswire.com/news-releases/neurobo-pharmaceuticals-receives-first-site-irb-approval-for-its-phase-1-clinical-trial-evaluating-da-1726-for-the-treatment-of-obesity-302075572.html[18] MaaT Pharma Announces Positive Review from the DSMB on the Ongoing Phase 1 Clinical Trial Evaluating MaaT033 in Amyotrophic Lateral Sclerosis (ALS). Retrieved February 29, 2024 from https://www.businesswire.com/news/home/20240229517711/en[19] S.BIOMEDICS completes brain transplant of hESC-derived dopaminergic progenitors (TED-A9) for Phase 1/2a study in patients with Parkinson’s disease. Retrieved February 29, 2024 from https://www.businesswire.com/news/home/20240229508525/en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

临床1期临床结果细胞疗法

2024-02-01

·BioSpace

Purple Biotech Reaches Recommended Phase 2 Dose for NT219

REHOVOT, Israel, Feb. 01, 2024 (GLOBE NEWSWIRE) -- Purple Biotech Ltd. ("Purple Biotech" or "the Company") (NASDAQ/TASE: PPBT), a clinical-stage company developing first-in-class therapies that harness the power of the tumor microenvironment to overcome tumor immune evasion and drug resistance, today announced it has determined 100mg/kg is the recommended Phase 2 dose (RP2D) for NT219 in combination with cetuximab in the treatment of head and neck cancer based on its Phase 1/2 dose escalation study (NCT04474470). NT219 is a first-in-class small molecule dual inhibitor of IRS1/2 and STAT3. The RP2D was determined based on data from the open-label dose escalation study designed to assess the safety, pharmacokinetics, pharmacodynamics and efficacy of NT219 in combination with Erbitux® (cetuximab), in previously treated recurrent and/or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN) patients. The Company recently reported that NT219, in combination with cetuximab, demonstrated a dose dependent anti-tumor activity with confirmed partial responses. No dose-limiting toxicities were reported. The additional supporting data used for this determination was pharmacokinetics of NT219 across all dose levels. Further dose optimization is planned for future studies. The Phase 1 dose escalation study is being concluded and the remaining patients' data are expected to be reported during the first half of 2024. The Company is now advancing its upcoming Phase 2 Proof of Concept study of NT219 for the treatment of R/M SCCHN. Detailed clinical results from the dose escalation portion of the study are intended to be presented at the European Society of Medical Oncology Targeted Anticancer Therapies (ESMO TAT) Congress 2024 in Paris on February 26, 2024, in an Oral Presentation titled “Interim results of a Phase 1/2 trial of NT219 in combination with cetuximab in patients with advanced/metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN).” “This is a major milestone for the development of NT219 for an indication in need of more effective therapies. As we progress into a Phase 2 study, our goal is to establish NT219 as standard of care for squamous cell carcinoma of the head and neck for patients who have not responded to first line treatments,” stated Gil Efron, Chief Executive Officer of Purple Biotech. “We look forward to treating more patients with NT219 in a Phase 2 study.” About NT219 NT219 is a first-in-class, small molecule that promotes Insulin Receptor Substrates 1/2 (IRS) degradation and inhibits Signal Transducer and Activator of Transcription 3 (STAT3) phosphorylation, two major complementary signalling pathways that play a key role in the tumor and its microenvironment. IRS1/2 acts as scaffolds, organizing signalling complexes that mediate mitogenic, metastatic, angiogenic, and anti-apoptotic signals from IGF1R and other oncogenes, consisting of an important driver in multiple cancers and is highly involved in triggering drug resistance. STAT3 is a transcription factor that is broadly hyperactivated in many cancers, promoting proliferation, survival, angiogenesis, metastasis, and tumor immune evasion. Feedback activation of STAT3 plays a prominent role in mediating drug resistance to various anti-cancer therapies. As an inhibitor of both IRS1/2 and STAT3, NT219 has the potential to prevent the development of resistance to multiple approved therapies. About Purple Biotech Purple Biotech Ltd. (NASDAQ/TASE: PPBT) is a clinical-stage company developing first-in-class therapies that seek to overcome tumor immune evasion and drug resistance. The Company's oncology pipeline includes NT219, CM24 and IM1240. NT219 is a dual inhibitor, novel small molecule that simultaneously targets IRS1/2 and STAT3. A phase 2 study of NT219 at its recommended Phase 2 level in combination with cetuximab in patients with recurrent and/or metastatic SCCHN is planned. CM24 is a humanized monoclonal antibody that blocks CEACAM1, an immune checkpoint protein that supports tumor immune evasion and survival through multiple pathways. The Company is advancing CM24 as a combination therapy with anti-PD-1 checkpoint inhibitors in a Phase 2 study for the treatment of pancreatic ductal adenocarcinoma (PDAC). The Company has entered into a clinical collaboration agreement with Bristol Myers Squibb for the Phase 2 clinical trials to evaluate the combination of CM24 with the PD-1 inhibitor nivolumab in addition to chemotherapy. The Company is advancing a preclinical platform of conditionally-activated tri-specific antibody that engages both T cells and NK cells to mount a strong, localized immune response within the tumor microenvironment. The cleavable capping technology confines the compound's therapeutic activity to the local tumor microenvironment, and thereby potentially increases the anticipated therapeutic window in patients. The third arm specifically targets the Tumor Associated Antigen (TAA). The technology presents a novel mechanism of action by unleashing both Innate and adaptive immune systems to mount an optimal anti-tumoral immune response. IM1240 is the first tri-specific antibody in development that targets 5T4 expressed in a variety of solid tumors and is correlated with advanced disease, increased invasiveness and poor clinical outcomes. The Company's corporate headquarters are located in Rehovot, Israel. For more information, please visit . Forward-Looking Statements and Safe Harbor Statement Certain statements in this press release that are forward-looking and not statements of historical fact are forward-looking statements within the meaning of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements include, but are not limited to, statements that are not statements of historical fact, and may be identified by words such as "believe", "expect", "intend", "plan", "may", "should", "could", "might", "seek", "target", "will", "project", "forecast", "continue" or "anticipate" or their negatives or variations of these words or other comparable words or by the fact that these statements do not relate strictly to historical matters. You should not place undue reliance on these forward-looking statements, which are not guarantees of future performance. Forward-looking statements reflect our current views, expectations, beliefs or intentions with respect to future events, and are subject to a number of assumptions, involve known and unknown risks, many of which are beyond our control, as well as uncertainties and other factors that may cause our actual results, performance or achievements to be significantly different from any future results, performance or achievements expressed or implied by the forward-looking statements. Important factors that could cause or contribute to such differences include, among others, risks relating to: the plans, strategies and objectives of management for future operations; product development for NT219, CM24 and IM1240; the process by which such early stage therapeutic candidates could potentially lead to an approved drug product is long and subject to highly significant risks, particularly with respect to a joint development collaboration; the fact that drug development and commercialization involves a lengthy and expensive process with uncertain outcomes; our ability to successfully develop and commercialize our pharmaceutical products; the expense, length, progress and results of any clinical trials; the impact of any changes in regulation and legislation that could affect the pharmaceutical industry; the difficulty in receiving the regulatory approvals necessary in order to commercialize our products; the difficulty of predicting actions of the U.S. Food and Drug Administration or any other applicable regulator of pharmaceutical products; the regulatory environment and changes in the health policies and regimes in the countries in which we operate; the uncertainty surrounding the actual market reception to our pharmaceutical products once cleared for marketing in a particular market; the introduction of competing products; patents obtained by competitors; dependence on the effectiveness of our patents and other protections for innovative products; our ability to obtain, maintain and defend issued patents; the commencement of any patent interference or infringement action against our patents, and our ability to prevail, obtain a favorable decision or recover damages in any such action; and the exposure to litigation, including patent litigation, and/or regulatory actions, and other factors that are discussed in our Annual Report on Form 20-F for the year ended December 31, 2022 and in our other filings with the U.S. Securities and Exchange Commission ("SEC"), including our cautionary discussion of risks and uncertainties under "Risk Factors" in our Registration Statements and Annual Reports. These are factors that we believe could cause our actual results to differ materially from expected results. Other factors besides those we have listed could also adversely affect us. Any forward-looking statement in this press release speaks only as of the date which it is made. We disclaim any intention or obligation to publicly update or revise any forward-looking statement or other information contained herein, whether as a result of new information, future events or otherwise, except as required by applicable law. You are advised, however, to consult any additional disclosures we make in our reports to the SEC, which are available on the SEC's website, . CONTACTS: Company Contact: Lior Fhima Chief Financial Officer IR@purple-biotech.com

临床1期临床2期免疫疗法ASCO会议

2023-12-09

·生物制品圈

从罗氏收购Carmot看药企并购红与黑

1罗氏收购Carmot挺身GLP-1大业罗氏日前与美国私人企业Carmot Therapeutics达成协议，以31亿美元的价格收购这家肥胖症药物开发公司，以期在寸土寸金的减肥药领域同诺和诺德和礼来进行角逐。Carmot Therapeutics是一家研发GLP-1受体激动剂药物的开发商。目前在减肥药和2型糖尿病领域叱咤风云的semaglutide和tirzepatide就是GLP-1受体激动剂类型的药物（更确切地说，tirzepatide是GLP-1/GIP双受体共激动剂）。此次收购使罗氏能够独家获得Carmot的三种临床阶段GLP-1受体激动剂产品组合，其中包括目前正在进行2期试验的两种皮下注射剂以及目前正在进行1期试验的每日片剂。Jefferies的分析师表示，Carmot管线产品的1期临床试验结果相当具有吸引力，尽管目前下定论还为时尚早，但他们的减肥药资产与罗氏肌肉保持药物的联手，是这笔31亿美元交易的关键促成因素。在这笔交易中，罗氏将先期支付27亿美元，后期支付最高4亿美元，具体取决于设定的里程碑的实现情况。预计罗氏将以诺和诺德与礼来的药物为参照进行 III 期试验，以获得市场准入。但虑到礼来和诺和诺德在减肥药物方面的巨大领先，罗氏仍然面临着争夺市场份额的挑战。礼来最近也以19.3亿美元收购了Versanis Bio，研究是否有可能将减肥和肌肉质量治疗结合起来。Versanis正在测试一种药物，希望这种药物能够促进肌肉质量的增加，同时指导身体代谢脂肪。从礼来与罗氏的这两笔交易来看，减肥药物开发可能很快就会从追求减重数量的层面，上升到在保持肌肉的前提下进行有质量减重的高阶层。制药企业的并购活动在全球范围内屡见不鲜，既有许多成功的案例，也存在一些令人深思的失败案例。2成功药企并购的背后药企的成功收购往往涉及收购者对目标公司主要资产项目的精准评估和整合。成功的药企收购存在一些先兆特征，包括研发项目、产品组合、知识产权等方面的因素。从大的角度来看，成功的企业并购需要注意战略契合、充分的尽职调查（due diligence包括财务状况、法律义务、知识产权、研发项目等方面的调查）、领导层支持和参与、有效的沟通和文化整合、人才和团队整合、明确的整合计划、对市场和法规的敏感性、技术和研发能力的整合等众多方面。我们着重从并购的重点研发项目和产品互补性两个角度来审视那些成功并购案例背后的共同点。1研发项目的质量成功的并购往往涉及到目标公司拥有的领先研发管线，包括处于不同研发阶段的候选药物。这为收购方提供了更多的创新机会和未来增长潜力。被并购的目标公司通常拥有进行中并取得了良好进展的临床试验项目，特别是那些朝着关键的治疗领域发展的项目，是成功收购的重要指标。研发项目质量的关键指标可以包括以下几个方面：• 临床试验成功率：成功被收购的企业，通常具备较高的临床试验成功率。这表明他们的研发项目经过有效筛选和优化，更有可能在后续临床试验中取得成功，减少产品研发失败的风险，并获得大型制药公司的青睐。• 创新性和独特性：优质的研发项目应具备创新性和独特性，即通过不同的机制或技术解决问题，使得产品更具竞争力。这种独特性有助于在市场上脱颖而出，提高产品的市场占有率。• 研发管线的多样性：成功的收购涉及到目标公司拥有多样性的研发管线，包括处于不同研发阶段的项目。这有助于降低市场风险，提高公司在不同治疗领域的覆盖率。降低了那种“一锤子买卖”的赌石风险。• 专业领域的专长：优质的研发项目通常反映了目标公司在某一特定领域具备的专业知识和经验。这种专长有助于提高产品的研发效率和成功率。这项特质几乎是放之四海而皆准的，在每笔成功的收购背后都存在。被收购的公司通常都是在某一领域做得非常突出的企业，而不是那种“万金油”的类型。• 研发项目的市场潜力：目标公司的研发项目应当具备良好的市场潜力，即具备满足市场需求、解决现有问题或填补市场空白的潜力。这有助于确保产品在未来市场上能够取得良好的销售业绩。• 研发项目的合规性：研发项目在合规性方面的表现也是关键因素。这包括项目符合法规的程度、相关道德规范的遵守等。合规性的高标准有助于降低未来法律风险。这一点可以在due diligence中得到体现。成功的并购案例，在研发项目质量方面存在一些先兆特征：• 项目进展和阶段达成：成功的药企收购案例通常涉及目标公司研发项目按计划推进，且项目在不同研发阶段取得了预期的进展。这表明项目的管理和执行水平较高。• 过往研发成功案例：目标公司过往的研发项目成功案例是一个重要的先兆特征。成功的研发历史显示公司具备科学实力和执行能力，增加了收购方对未来项目成功的信心。• 项目团队的专业素质：研发项目成功与否与项目团队的专业素质密切相关。目标公司拥有高素质、有经验的项目团队是一个积极的先兆，表明项目的科学基础和实施计划是可靠的。• 研发项目的战略契合度：目标公司的研发项目应当与收购方的战略方向相契合。这确保了整合后的公司能够更好地发挥各自的优势，形成协同效应。• 研发项目的知识产权：高质量的研发项目通常伴随着强大的知识产权支持，如有效的专利保护。这有助于保障产品在市场上的独特性，防范竞争风险。2产品组合的互补性除了研发项目的质量之外，产品组合的互补性也是成功并购的关键因素。这就像两个层次都很高的男女，未必一定适合组成家庭一样。产品的互补性也是药企并购过程中非常重要的契合点，产品组合的互补性对于整合后公司的市场竞争力和增长潜力至关重要。成功的药企收购中，目标公司通常具备强大的产品组合。这包括已上市的药物、市场潜力较大的候选药物以及符合公司战略方向的产品。收购方和被收购方的产品在市场上有一定的互补性，使得整合后的公司能够拓展市场份额，提高销售收入。• 治疗领域的多样性：产品组合的互补性首先体现在治疗领域的多样性。目标公司和收购方产品应在不同的治疗领域有所涉足，以实现整合后公司的市场覆盖面扩大。例如罗氏收购Carmot，就是希望将自己在肌肉保持药物方面的优势，结合后者GLP-1药物，实现更上一层楼的减肥药开发。• 不同产品类型的结合：互补性还表现在不同类型的产品的结合上，包括处方药、非处方药、生物制品、化学合成药物等。这种组合有助于满足不同患者群体的需求。• 产品生命周期的匹配：收购方和目标公司的产品生命周期应该相互匹配，以确保整合后公司有一个稳健和可持续的产品组合，不受特定产品过期的影响。• 市场份额的互补性：互补性还可以通过目标公司和收购方在市场上的份额结合来体现，从而实现整合后公司在市场上的强大地位。• 技术平台的互补：不同技术平台的产品结合也是互补性的一部分。这可以包括不同的制剂技术、新型给药途径等，为整合后公司提供更多的创新机会。3药企成功与失败并购案例分析• BMS收购Celgene，2019年，740亿美元百时美施贵宝2019年以740亿美元收购Celgene是制药业2019年具有里程碑意义的大型合并，也是制药行业历史上规模最大的合并之一，因此值得大书特书。虽然这起合并交易称不上完美，但在交易完成之后，BMS在2020年至2022年之间推出了九个新产品，其中包括两种CAR-T细胞疗法：用于B细胞淋巴瘤的 Breyanzi和Abecma，后者是第一个被批准用于多发性骨髓瘤的CAR-T疗法。两年内推出九款新产品，这是一个相当高产的数据，显示了并购后公司在创新和新产品上的积极表现。交易前公司设定了合并之后的战略目标，包括聚焦于变革性创新和在未满足医疗需求领域推出药物。公司在这些目标上取得了成就。合并后的新产品组合给BMS带来的收入从2022年的5.53亿美元增加到了2023年迄今为止的9.28亿美元，增长了68%。虽然这两家巨头公司的合并算不上完美无瑕，但从新产品创新和上市的角度来看，这笔交易可以算得成功。而这一点也对应了上文分析的组合产品的互补性与研发项目质量方面的讨论。表现在新产品的大量与快速推出，以及不错的市场表现。• 罗氏收购基因泰克，2009年，470亿美元当制药巨头罗氏于2009年以470亿美元收购基因泰克公司时，罗氏公司实际上已经是后者的投资人。而通过这场收购，罗氏获得了治疗癌症和湿性年龄相关性黄斑变性的重磅药物。在被收购后，基因泰克继续秉承初创公司精神，作为罗氏内部的一个独立业务部门运营。从罗氏的角度来看，基因泰克带来了强大的创新和显著的高回报产品组合。根据分析，仅4种基因泰克单抗药物，即贝伐珠单抗、利妥昔单抗、曲妥珠单抗和雷珠单抗，单在在2018年就赚了211亿美元。可想而知，罗氏为整个交易付出的470亿美元算不算物超所值。尽管其中一些药物已经失去了市场独占权，但基因泰克之后又贡献出了更多的新药，包括价值数十亿美元的重磅药物 Vabysmo。看过两起成功并购案例，再让我们把目光转向那些不怎么成功的药企M&A上：• 强生收购Actelion，2017年，300亿美元强生于2017年以300亿美元收购了Actelion，为他们的资产带来了一个新的治疗领域：肺动脉高压，这对于扩大企业的市场领域原本应该是有益处的，然而2018年，这笔交易已经开始朝着问题方向发展了。首先，2018年4月，强生停止了Actelion抗生素卡达唑胺（cadazolid）的开发，该药物当时正在用于治疗艰难梭菌相关腹泻的第三阶段项目中。接下来，就在几个月后的12月，Actelion同意支付3.6亿美元来解决回扣索赔问题。根据美国司法部报告，他们违反了《虚假索赔法案》，非法通过使用基金会，支付数千名使用Actelion肺动脉高压药物的医疗保险受益人的医疗保险赔付。强生从Actelion收购的另一项资产是多发性硬化症药物Ponvory，于2021年获得监管部门批准，但上市较晚，强生尚未公布其直接销售数据。• 拜耳收购孟山都，2018年，660亿美元拜耳今年表现糟糕已经是业界尽人皆知的事实，拜尔的问题，似乎从2018年那“伟大的一天”就有迹可循。2018年6月7日，拜耳时任CEO兼管理委员会主席Werner Baumann在一份公司公告中表示，“今天是伟大的一天”。在那一天，拜耳这家医药巨头斥660亿美元巨资收购了农业生物技术巨头孟山都公司（Monsanto）。一年后，《华尔街日报》将这笔诞生在“伟大一天”的收购评选为最糟糕的企业交易之一。而仅仅在五年之后，拜耳就面临着拆分公司的要求。尽管拜耳最初表现乐观，但孟山都多年来一直受到自身问题的困扰，拜耳似乎没有做好充分的due diligence调查（尽职调查）。Due diligence是一种商业和法律上的实践，指的是在签署合同、投资、收购或其他重要交易之前对特定事项进行仔细调查和评估的过程。尽职调查旨在确保相关各方在做出决策时有充分的信息，并且能够了解交易的各个方面。自交易完成以来，这些困境一直困扰着拜耳。最近，陪审团下令拜耳向华盛顿州立一所学校的员工支付1.65亿美元，理由是孟山都化学物质从灯具中泄漏并导致他们生病。再加上拜耳因缺乏功效而停止血液稀释剂asundexian的3期研究的消息，导致股价暴跌，市值缩水 83 亿美元。42023年1亿美元以上的药企并购（截止2023年11月22日）• T3 Pharmaceuticals日期：11月22日买家：勃林格殷格翰价格：最高5.08亿美元主要交易目标：一期实体瘤候选药T3P-Y058-739• Mitokinin日期：10月5日买家：艾伯维价格：1.1亿美元主要交易目标：临床前帕金森病候选药物• Point Biopharma Global日期：10月3日买家：礼来价格：14亿美元主要交易目标：放射性配体治疗产品线• Decibel Therapeutics日期：8月9日买家：再生元价格：1.09亿美元主要交易目标：Decibel的主要听力损失候选药物DB-OTO，针对因otoferlin基因突变导致听力损失的个体进行1/2期试验。• DTx Pharma日期：7月17日买家：诺华价格：5亿美元主要交易目标：脂肪酸配体缀合寡核苷酸（FALCON）平台以及三个临床前项目• Qpex Biopharma日期：6月26日买家：盐野义价格：1亿美元主要交易目标：抗生素项目• Dice Therapeutics日期：6月20日买家：礼来价格：24亿美元主要交易目标：口服IL-17抑制剂DC-806 and DC-853，针对银屑病。• Chinook Therapeutics日期：6月12日买家：诺华价格：32亿美元主要交易目标：两个针对罕见、进行性慢性肾病的后期项目• VectivBio日期：5月22日买家：Ironwood Pharmaceuticals价格：10亿美元主要交易目标：3期药物apraglutide，用于治疗伴有肠衰竭的短肠综合征。• Iveric Bio日期：5月1日买家：Astellas Pharma价格：59亿美元主要交易目标：补体C5蛋白抑制剂avacincapad pegol，降低地理萎缩进展的速度。• Bellus Health日期：4月18日买家：葛兰素史克价格：20亿美元主要交易目标：3期慢性咳嗽治疗药物camlipixant• Prometheus Biosciences日期：4月17日买家：默沙东价格：108亿美元主要交易目标：肠道疾病候选药物PRA023• Immunorizon日期：2月2日买家：Purple Biotech价格：1亿美元主要交易目标：实体瘤候选药NT219和胰腺导管腺癌候选药CM24• Concert Pharmaceuticals日期：1月19日买家：Sun Pharmaceuticals售价：5.76亿美元主要交易目标：治疗脱发症的JAK抑制剂• CinCor Pharma日期：1月9日买家：阿斯利康价格：18亿美元主要交易目标：3期产品醛固酮合成酶抑制剂baxdrostat，治疗不受控制的高血压参考文献:1.Bayer closes Monsanto acquisition. Bayer Press Release. 07. 06. 2018.https://www.bayer.com/media/en-us/bayer-closes-monsanto-acquisition/2.Roumeliotis, G. et al. Bayer clinches Monsanto with improved $66 billion bid. Reuters. 15. 09. 2016.3.Bender, R. How Bayer-Monsanto Became One of the Worst Corporate Deals—in 12 Charts. The Wall Street Journal. 28. 08. 2019.4.Armstrong, A. et al. Fierce Biotech M&A Tracker 2023: Boehringer buys T3 Pharmaceuticals; Syncona throws lifeline to British biotech. FierceBiotech. 22. 11. 2023.5.Pecci, A. The fortunes and flops of pharma M&A. PharmaVoice. 04. 12. 2023.6.Clark, A. Roche Strikes $3.1 Billion Deal for Obesity Drugmaker. It’s Hoping to Compete with Eli Lilly, Novo Nordisk. Barron’s. 04. 12. 2023.识别微信二维码，添加生物制品圈小编，符合条件者即可加入生物制品微信群！请注明：姓名+研究方向！版权声明本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观点，不代表本站立场。

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100 项与 NT-219 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
大肠腺癌	临床2期	美国	Tyrnovo Ltd.	2020-09-03
大肠腺癌	临床2期	以色列	Tyrnovo Ltd.	2020-09-03
晚期恶性实体瘤	临床2期	美国	Tyrnovo Ltd.	2020-09-03
晚期恶性实体瘤	临床2期	以色列	Tyrnovo Ltd.	2020-09-03
转移性实体瘤	临床2期	美国	Tyrnovo Ltd.	2020-09-03
转移性实体瘤	临床2期	以色列	Tyrnovo Ltd.	2020-09-03
复发性实体肿瘤	临床2期	美国	Tyrnovo Ltd.	2020-09-03
复发性实体肿瘤	临床2期	以色列	Tyrnovo Ltd.	2020-09-03
头颈部鳞状细胞癌	临床2期	美国	Tyrnovo Ltd.	2020-09-03
头颈部鳞状细胞癌	临床2期	以色列	Tyrnovo Ltd.	2020-09-03

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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


NCT04474470 (ESMO_TAT2024) 人工标引	临床1/2期	头颈部鳞状细胞癌	17	NT219+cetuximab	願選衊夢範淵願夢獵襯(憲鏇繭願獵蓋醖積積獵) = 觸夢遞齋網積鬱選鹽鬱蓋壓簾鹹鑰願餘襯糧鹽 (鹹顧選齋選構廠觸襯夢 ) 更多	积极	2024-02-26
NCT04474470 (Biospace) 人工标引	临床1/2期	头颈部肿瘤	49	NT219	鏇艱淵蓋築願糧襯膚網(願製鏇網構醖顧襯鬱糧) = No dose-limiting toxicities (DLTs) were reported in either cohort. 觸製夢選觸餘網艱衊衊 (願鬱餘鑰構積簾鬱窪繭 ) 更多	积极	2023-10-03
NCT04474470 (Biospace) 人工标引	临床1/2期	头颈部肿瘤	49	NT219+cetuximab		积极	2023-10-03