A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study of Zilovertamab (an ROR1 Antibody) Plus Ibrutinib Versus Ibrutinib Plus Placebo in Subjects With Relapsed or Refractory Mantle Cell Lymphoma

This is a Phase 3 study to investigate the safety and efficacy of the investigational drug, zilovertamab, when given in combination with ibrutinib in patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL).

开始日期2023-03-01

申办/合作机构

Oncternal Therapeutics, Inc.

[+1]

NCT05156905 / Recruiting临床1期IIT

A Phase 1b Trial Investigating Docetaxel Combined With Cirmtuzumab in Patients With Metastatic Castration Resistant Prostate Cancer

The purpose of this study is to examine the safety and efficacy of cirmtuzumab in combination with standard of care docetaxel in patients with metastatic castration resistant prostate cancer. Docetaxel is a taxane chemotherapy which has been shown to prolong survival in men with castration resistant prostate cancer. Cirmtuzumab is a monoclonal antibody that targets the receptor called ROR1 of the non-canonical Wnt pathway and is suspected to contribute to prostate cancer growth and progression.

开始日期2022-06-16

申办/合作机构

University of California San Diego

NCT04501939 / Active, not recruiting临床2期IIT

Cirmtuzumab Consolidation for Treatment of Patients With Detectable CLL on Venetoclax

Single center, open-label, phase 2 study to determine the efficacy of cirmtuzumab consolidation in patients with measurable disease on venetoclax.

开始日期2020-08-06

申办/合作机构

University of California San Diego

[+1]

100 项与 Zilovertamab 相关的临床结果

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100 项与 Zilovertamab 相关的转化医学

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100 项与 Zilovertamab 相关的专利（医药）

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项与 Zilovertamab 相关的文献（医药）

2022-06-01·Leukemia

High expression level of ROR1 and ROR1-signaling associates with venetoclax resistance in chronic lymphocytic leukemia

Article

作者: Quijada-Álamo, Miguel ; Choi, Michael Y ; Ghia, Emanuela M ; Widhopf, George F ; Kipps, Thomas J ; Chu, Elvin ; Rassenti, Laura Z

Abstract:

Although the BH3-mimetic venetoclax is highly cytotoxic for chronic lymphocytic leukemia (CLL) cells, some patients with CLL fail to clear minimal residual disease (MRD). We examined the CLL cells of seven such patients (CLL1-7) and found each had high-level expression of ROR1. By examining the CLL cells from such patients prior to therapy at SC1 and then more than 1 year later (Sample Collection 2 (SC2)), when they had progressive increases in MRD despite continued venetoclax therapy, we found the levels of ROR1 expressed on CLL cells at SC2 were significantly higher than that on CLL cells collected at SC1. At SC2, we also observed upregulation of genes induced by Wnt5a-induced ROR1 signaling, including BCL2L1. Transduction of the CLL-cell-line MEC1 to express ROR1 enhanced expression of target genes induced by ROR1-signaling, increased expression of BCL-XL, and enhanced resistance to venetoclax, even in MEC1 made to express mutant forms of BCL2, which are associated with venetoclax resistance. Treatment of primary CLL cells with Wnt5a also increased their resistance to venetoclax, an effect that could be inhibited by the anti-ROR1 mAb (UC-961, zilovertamab). Collectively, these studies indicate that Wnt5a-induced ROR1-signaling can enhance resistance to venetoclax therapy.

2021-06-17·Blood1区 · 医学

ROR1 targeting with the antibody-drug conjugate VLS-101 is effective in Richter syndrome patient–derived xenograft mouse models

1区 · 医学

Article

作者: Vaisitti, Tiziana ; Allan, John N. ; Iannello, Andrea ; Braggio, Esteban ; Lannutti, Brian J. ; Di Napoli, Arianna ; Lee, Thanh-Trang ; Vitale, Nicoletta ; Deaglio, Silvia ; Miller, Langdon L. ; Chadburn, Amy ; Arruga, Francesca ; Furman, Richard R. ; Ko, Mira ; Jessen, Katti A.

Abstract:

Richter syndrome (RS) represents the transformation of chronic lymphocytic leukemia (CLL), typically to an aggressive lymphoma. Treatment options for RS are limited and the disease is often fatal. Receptor tyrosine kinase–like orphan receptor 1 (ROR1) is expressed on CLL cells and other cancers but not on healthy adult tissues, making it an attractive, tumor-specific therapeutic target. VLS-101 is being developed as an antibody-drug conjugate (ADC) for therapy of ROR1-expressing (ROR1+) cancers. VLS-101 comprises UC-961 (a humanized immunoglobulin G1 monoclonal antibody that binds an extracellular epitope of human ROR1), a maleimidocaproyl-valine-citrulline-para-aminobenzoate linker, and the antimicrotubule cytotoxin monomethyl auristatin E (MMAE). VLS-101 binding to ROR1 results in rapid cellular internalization and delivery of MMAE to induce tumor cell death. We studied 4 RS patient-derived xenografts (RS-PDXs) with varying levels of ROR1 expression (11%, 32%, 85%, and 99% of cells). VLS-101 showed no efficacy in the lowest-expressing RS-PDX but induced complete remissions in those with higher levels of ROR1 expression. Responses were maintained during the posttherapy period, particularly after higher VLS-101 doses. In systemic ROR1+ RS-PDXs, VLS-101 dramatically decreased tumor burden in all RS-colonized tissues and significantly prolonged survival. Animals showed no adverse effects or weight loss. Our results confirm ROR1 as a target in RS and demonstrate the therapeutic potential of using an ADC directed toward ROR1 for the treatment of hematological cancers. A phase 1 clinical trial of VLS-101 (NCT03833180) is ongoing in patients with RS and other hematological malignancies.

2021-06-01·Leukemia1区 · 医学

Wnt5a enhances proliferation of chronic lymphocytic leukemia and ERK1/2 phosphorylation via a ROR1/DOCK2-dependent mechanism

1区 · 医学

Article

作者: Kipps, Thomas J ; Ghia, Emanuela M ; Hasan, Md Kamrul ; Widhopf, George F ; Rassenti, Laura Z

Abstract:

Patients with chronic lymphocytic leukemia (CLL) have high plasma-levels of Wnt5a, which can induce phosphorylation of ERK1/2 and enhance CLL-cell proliferation. Such effects could be inhibited by treatment with an ERK1/2 inhibitor, ERK1/2-specific siRNA, or cirmtuzumab, an anti-ROR1 mAb. The CLL-derived line, MEC1, expresses Wnt5a, but not ROR1. MEC1 cells transfected to express ROR1 (MEC1-ROR1) had higher levels of phosphorylated ERK1/2 than parental MEC1, or MEC1 transfected with ROR1ΔPRD, a truncated ROR1 lacking the cytoplasmic proline-rich domain (PRD), or ROR1P808A a mutant ROR1 with a P→A substitution at 808, which is required for complexing with the Rac-specific-guanine-nucleotide-exchange factor DOCK2 upon stimulation with Wnt5a. We silenced DOCK2 with siRNA and found this repressed the capacity of Wnt5a to induce ERK1/2 phosphorylation in MEC1-ROR1 or CLL cells. CLL cells that expressed ROR1 had higher levels of phosphorylated ERK1/2 or DOCK2 than CLL cells lacking ROR1. Although we found ibrutinib could inhibit the phosphorylation of ERK1/2 and DOCK2 induced by B-cell-receptor ligation, we found that this drug was unable to inhibit Wnt5a-induced, ROR1-dependent phosphorylation of ERK1/2 or DOCK2. This study demonstrates that Wnt5a can induce activation of ERK1/2 and enhance CLL-cell proliferation via a ROR1/DOCK2-dependent pathway independent of BTK.

项与 Zilovertamab 相关的新闻（医药）

2024-09-12

·GlobeNewswire-Health Care

Oncternal Therapeutics Announces Termination of its Clinical Studies and Exploration of Strategic Alternatives

SAN DIEGO, Sept. 12, 2024 (GLOBE NEWSWIRE) -- Oncternal Therapeutics, Inc. (Nasdaq: ONCT) (the “Company”) today announced its decision to discontinue its clinical trials evaluating ONCT-534, its dual action androgen receptor inhibitor for the treatment of patients with metastatic castration resistant cancer, and ONCT-808, its ROR1-targeting autologous CAR T program for the treatment of patients with aggressive B-cell lymphoma, and to explore strategic alternatives. In the current study, interim Phase 1 results of ONCT-534 did not show clinically meaningful improvements of disease, including prostate-specific antigen (PSA) levels, in the 20 patients treated in eight dosing cohorts with various doses and schedules of administration of ONCT-534. ONCT-534 was generally well tolerated, with dose limiting toxicity observed in 2 of 3 patients at the highest dose tested, 1200 mg given orally once per day. The results with ONCT-808 at an interim Phase 1 analysis showed anti-tumor activity at every dose tested, including a complete metabolic response lasting eight months and long-term persistence of the CAR-T cells, with expected treatment emergent adverse events for a CAR-T therapy, and one death due to complications of shock at the highest dose tested. Based on the available clinical data and capital requirements for continued development, the Company has decided to terminate these studies. The Company will focus on exploring strategic alternatives with the goal of maximizing value for its stockholders, which may include asset sales, licensing or other strategic transactions relating to the Company’s development programs or a merger, reverse merger, acquisition, or other business combination involving the Company. While this strategic exploration is ongoing, the Company will discontinue all product development activities and will take other steps to reduce costs, including a reduction in its workforce to preserve cash resources. “The early results during dose escalation in the Phase 1/2 studies of ONCT-534 in heavily pretreated patients are disappointing, as the study was supported by extensive preclinical data and was designed to address important unmet medical needs for patients with advanced prostate cancer,” said James Breitmeyer, M.D., Ph.D., Oncternal’s President and CEO. “In light of these data and the challenging financing environment, we intend to explore strategic options with the hope of advancing and realizing value from our pipeline including ONCT-534, ONCT-808, zilovertamab and ONCT-216.” About Oncternal TherapeuticsOncternal Therapeutics is a clinical-stage biopharmaceutical company focused on the development of novel oncology therapies for the treatment of patients with cancers that have critical unmet medical need. Oncternal pursues drug development targeting promising, yet untapped biological pathways implicated in cancer generation or progression, focusing on hematological malignancies and prostate cancer. More information on our company and programs is available at https://oncternal.com/. About ONCT-534 ONCT-534 is an investigational dual-action androgen receptor inhibitor (DAARI) with demonstrated preclinical activity in prostate cancer models against both unmutated androgen receptor (AR), and against multiple forms of AR mutation and aberration. It is a potential treatment for patients with mCRPC with unmet medical need because of resistance to androgen receptor pathway inhibitors, including those with AR amplification, mutations in the AR ligand binding domain (LBD), or splice variants with loss of the AR LBD. It is being investigated in Study ONCT-534-101 (NCT05917470) for the treatment of patients with mCRPC who are resistant to current AR pathway inhibitors. About ONCT-808ONCT-808 is an investigational autologous chimeric antigen receptor T (CAR T) cell therapy that targets Receptor Tyrosine Kinase-Like Orphan Receptor 1 (ROR1) using the binding domain from zilovertamab. ONCT-808 has demonstrated activity in preclinical models against multiple hematological malignancies and solid tumors and has been shown to be specific for cancer cells expressing ROR1. Oncternal has developed a robust and reproducible manufacturing process that has the potential to reduce the time patients must wait for their individual CAR T therapy to be produced compared with currently approved CAR T products. Oncternal has dosed patients under Study ONCT-808-101 (NCT05588440) with relapsed or refractory aggressive B-cell lymphoma, including patients who have failed previous CD19 CAR T treatment. About zilovertamabZilovertamab (previously called cirmtuzumab and UC-961) is an investigational monoclonal antibody designed to inhibit the function of ROR1. Zilovertamab has been evaluated in Phase 1/2 Study CIRM-0001 (NCT03088878) in combination with ibrutinib for the treatment of patients with mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL) and marginal zone lymphoma (MZL), which resulted in 100% progression free survival (PFS) at 48 months in CLL patients whose tumors harbored p53 mutation/del(17p), a population underserved by current treatment options. The U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation to zilovertamab for the treatment of CLL and MCL. The results of an investigator-sponsored, Phase 1b clinical trial of zilovertamab in combination with paclitaxel for the treatment of women with HER2-negative metastatic or locally advanced, unresectable breast cancer were recently published (Shatsky 2023). Zilovertamab is being evaluated in an investigator-initiated Phase 1b study of zilovertamab in combination with docetaxel in patients with metastatic castration-resistant prostate cancer (NCT05156905), and an investigator-initiated Phase 2 clinical trial of zilovertamab in combination with venetoclax, a Bcl-2 inhibitor, in patients with relapsed/refractory (R/R) CLL (NCT04501939). About ONCT-216ONCT-216 (previously called TK216) is an investigational targeted small-molecule inhibitor of the E26 transformation-specific (ETS) family of oncoproteins including fusion proteins. Tumorigenic fusion proteins involving the EWS protein and an ETS protein can be found in most cases of Ewing sarcoma. ETS-related translocations or overexpression are also found in many other tumors such as acute myeloid leukemia (AML), diffuse large B cell lymphoma (DLBCL), and prostate cancer. In preclinical models, ONCT-216 was observed to bind to EWS-FLI1, blocking the interaction between this fusion protein and other transcriptome proteins such as RNA helicase A, leading to tumor cell apoptosis and inhibiting tumor growth in animal models. The U.S. Food and Drug Administration (FDA) has granted Rare Pediatric Disease Designation, Orphan Drug Designation and Fast Track Status to ONCT-216 for the treatment of Ewing sarcoma. The results of a Phase 1/ 2 clinical trial of ONCT-216 in patients with Ewing sarcoma (NCT02657005) were recently published (Myers 2024). Forward-Looking Information Oncternal cautions you that statements included in this press release that are not a description of historical facts are forward-looking statements. In some cases, you can identify forward-looking statements by terms such as “may,” “will,” “should,” “expect,” “plan,” “anticipate,” “could,” “intend,” “target,” “project,” “contemplates,” “believes,” “estimates,” “predicts,” “potential” or “continue” or the negatives of these terms or other similar expressions. These statements are based on Oncternal’s current beliefs and expectations. Forward-looking statements include statements regarding: Oncternal’s ability to complete a strategic transaction or continue as a going concern even if a strategic transaction is completed; anticipated benefits of strategic transactions; and Oncternal’s ability to preserve cash during the strategic alternatives process. Forward-looking statements are subject to risks and uncertainties inherent in Oncternal’s business, including: Oncternal may not realize the benefits expected from the workforce reduction and discontinuation of product development activities, including its ability to conserve cash; Oncternal’s ability to retain remaining key personnel; whether Oncternal will be able to secure and complete or achieve the anticipated benefits from any potential strategic transactions on acceptable terms or at all; Oncternal may use its capital resources sooner than it anticipates, resulting in a liquidation and dissolution of the Company; Oncternal’s common stock may be delisted from Nasdaq; and other risks described in Oncternal’s filings with the U.S. Securities and Exchange Commission. All forward-looking statements in this press release are current only as of the date hereof and, except as required by applicable law, Oncternal undertakes no obligation to revise or update any forward-looking statement, or to make any other forward-looking statements, whether as a result of new information, future events or otherwise. All forward-looking statements are qualified in their entirety by this cautionary statement. This caution is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Contact Information: InvestorsRichard Vincent 858-434-1113rvincent@oncternal.com Business DevelopmentPablo Urbaneja 415-316-8276 purbaneja@oncternal.com

临床1期孤儿药临床结果快速通道临床2期

2024-09-10

·药融圈

ADC元老创始人掌舵，新转型Biotech能否实现弯道超车？

▲10月26-27日成都中国临床试验产业发展大会免费报名注：本文不构成任何投资意见和建议，以官方/公司公告为准；本文仅作医疗健康相关药物介绍，非治疗方案推荐（若涉及），不代表平台立场。任何文章转载需得到授权。从药融云数据库获悉，2024年5月20日，Immunome宣布完成对 Atreca的抗体和相关资产的收购，通过此次收购，Immunome获得28款抗体，拟用于ADC药物研发。Immunome是一家成立于2008年的专注于开发靶向肿瘤疗法的生物技术公司，公司现任总裁兼首席执行官Clay Siegall博士表示：Immunome打算通过具有成本效益的业务开发、严格的发现和开发工作来进一步扩展其ADC产品组合。 ADC元老再出手，能否续写传奇是的，你没看错，该公司现任的总裁兼CEO就是创建了Seagen的Clay Siegall博士。虽然Clay Siegall博士在2022年因为私人事务辞去了Seagen（1997年创立，2023年被辉瑞以430亿美元的价格收购）的CEO职务，但在处理好私人事务之后几个月就出任了美国普渡大学衍生的新公司Morphimmune的CEO，任职仅四个月，Morphimmune就与成立于2006年的Immunome合并（以Immunome的名字继续运行），还是由Clay Siegall博士担任CEO。 Clay Siegall博士两司合并之后，Immunome就注定不会再像之前一样默默无闻，公司进入了高度活跃的状态。2023年10月，在Clay Siegall博士个人资源的加持下，公司完成了1.25亿美元私募投资（2024年2月又完成了2.3亿美元的公开募股）；而后Clay Siegall博士通过公司一系列合作收购向同行展示了ADC元老的冲击力。2023年年底，Immunome宣布收购Atreca的一系列抗体资产（该笔交易在2024年5月份完成），同时还将Seagen的前高管Bob Lechleider博士任命为首席医疗官；2024年1月，Immunome从Zentalis Pharmaceuticals获得了ROR1 ADC药物和ADC平台技术；2024年7月份，Immunome宣布再次扩大在ADC研发上的投入，将从Nectin Therapeutics、Bluefin Biomedicine、OncoResponse三家公司引进多款针对实体瘤以及未公开靶点的用于ADC药物开发的抗体。截止2024年9月4日，Immunome公司市值8.83亿美元。基于现有体系的3+N策略研究表明，Notch通路对细胞增殖、存活、迁移、侵袭、耐药性和转移扩散等过程具有关键的促进作用，而这些过程与癌症预后较差相关，γ分泌酶参与诱导Notch受体的水解，使其细胞内结构域（NICD）释放，NICD进入细胞核后启动相关基因转录。因此，γ分泌酶是激活Notch通路的关键蛋白酶，其被抑制时，Notch通路无法激活。γ分泌酶抑制剂是最早发现和最大的一类Notch通路靶向药物，能阻止Notch受体的第3次酶切，从而阻止NICD的释放。AL102是一种口服γ分泌酶抑制剂，目前正进行针对硬纤维瘤的临床试验3期研究中。 2024年3月，Immunome与Ayala Pharmaceuticals（后面简称“Ayala”）签订资产购买协议，收购了Ayala的AL102和AL101（2017年，Ayala与BMS就γ分泌酶抑制剂签订了全球独家许可协议，根据协议，Ayala获得了包括AL102在内的γ分泌酶抑制剂的全球独家开发和商业化权利，而后两公司共同合作进行γ分泌酶抑制剂管线的的研发活动），根据协议条款，Immunome在交易完成时向Ayala支付2000万美元现金和3000万美元的Immunome普通股，并额外支付高达3750万美元的开发和商业里程碑付款。但是在与Immunome交易之后，Ayala就公开宣布其已经向SEC提交不再公开定期报告的表格，此表格生效的话，其就不再是公开报告公司，其向SEC提交其他报告的义务也将暂停，不知后续是否会有其他动向。 2024年2月，AL102针对硬纤维瘤的临床试验3期研究（也称RINGSIDE研究）宣布已完成患者招募，RINGSIDE被设计为一项注册研究，以支持硬纤维瘤的NDA，该研究分为Part A和Part B。其中Part A为临床试验2期研究，是一项开放标签的剂量方案探索研究，2023年7月，AL102的临床试验2期研究结束会议已经完成；Part B是临床试验3期研究，是一项双盲、多中心试验，招募了156名疾病进展患者，将AL102每天一次用药1.2 mg与安慰剂进行对比。主要终点是无进展生存期（PFS），次要终点包括客观缓解率（ORR）、缓解持续时间（DOR）和患者报告的生活质量（QOL）指标。药融云数据库：药品研发信息 2023年11月，OGSIVEO（nirogacestat）已成为FDA批准用于硬纤维瘤的首个治疗方法，临床试验数据显示，AL102在治疗硬纤维瘤方面可能会比前者更有效。Immunome预计在2025年下半年报告RINGSIDE Part B的顶线数据，与此同时，公司还在评估和执行支持AL102 NDA提交所需的额外生产和药理学工作。其实AL102还在Ayala手中时除了开展针对硬纤维瘤的研究外，还在研究其与诺华的BCMA靶向剂WVT078联合治疗复发/难治性多发性骨髓瘤（MM），2021年4月，报道了该临床试验1期研究的首位患者已经给药，但目前为止，尚未报道最新研究情况。药融云数据库：药品研发信息此外Immunome还在开发IM-1021和IM-3050，其中IM-1021是一种靶向ROR1的临床前开发阶段的ADC，是公司在2024年1月从Zentalis Pharmaceuticals获得的独家许可。在临床前研究中，IM-1021在三阴性乳腺癌小鼠模型中显示持续的肿瘤消退，在该模型中，IM-1021每周以2.5 mg/kg或5.0 mg/kg给药三周，与相同剂量的Zilovertamab Vedotin（默克公司的，也称MK2140，当前进行到临床试验2期）有效载荷ROR1ADC相比，肿瘤体积明显减少，未观察到有意义的体重减少。预计Immunome将于2025年第一季度向FDA提交IM-1021的IND。公司初步计划在获得IND后，IM-1021临床研究旨在有效评估实体瘤或淋巴瘤患者的剂量递增，然后将实体瘤临床方案潜在扩展为目标适应症，其中可能包括以下任何或所有内容：非小细胞肺癌、乳腺癌、前列腺癌、胰腺癌和胃癌，以及淋巴瘤方案可能扩展到弥漫性大B细胞淋巴瘤，套细胞淋巴瘤，或其他被认为合适的适应症。在剂量递增和扩展研究的同时，Immunome还计划进行非临床研究，评估IM-1021与其他疗法的联合治疗，并评估和开发潜在的伴随诊断，以帮助识别最有可能对IM-1021做出反应的患者。药融云数据库：药品研发信息 IM-3050是一种靶向FAP的Lu-177 RLT（放射配体疗法），目前正在开发用于治疗实体瘤，是合并前Morphimmune的管线，来源于普度大学的Philip Low实验室。预计在2025年第一季度向FDA提交IM-3050的IND。 FAP（成纤维细胞活化蛋白）是一种在正常组织中低表达的细胞表面蛋白酶，在癌症相关成纤维细胞（最常见的肿瘤基质细胞）上过表达，在75%的实体瘤中表达。IM-3050可以将放射性177Lu直接递送至表达FAP的细胞，具有针对肿瘤细胞的旁观者效应，可能会损伤或杀死附近的肿瘤细胞，该RLT有望克服FAP不适合ADC的靶点的局限性，例如肿瘤细胞的内化不良和低表达。除了以上已经确定的管线外，Immunome预计还会继续投资扩大公司的产品管线，包括ADC和RLT。在ADC的背景下，针对新型或未充分开发的靶点的优质抗体，不管是通过公司的专有平台开发还是通过收购获得，都是差异化疗法的起点。通过将这些抗体与适合每个靶点生物学特性的连接子和有效载荷配对，相信Immunome最终可以开发出为患者带来实质性益处的疗法。此外，公司还计划扩大知识产权资产和基础设施，以发现和推进平台和计划。财务状况 2023年度Immunome的合作收入1400万美元；研发费用为2310万美元；一般和管理费用为1970万美元；年度净亏损为1.068亿美元，或归属于普通股股东的基本和摊薄每股净亏损为5.38美元。 2024年上半年研发费用为4450万美元；一般和行政费用为1300万美元；净亏损1.65亿美元。分季度来看，第一季度研发费用为1540万美元，其中包括40万美元的股票薪酬成本。在制品研发费用为1.12亿美元。这些费用与Immunome从Ayala Pharmaceuticals收购AL101和AL102、从Zentalis Pharmaceuticals收购IM-1021和相关ADC平台技术的独家许可有关，这两项交易均于2024年第一季度完成。一般和行政管理费用为600万美元，其中包括180万美元的股票薪酬费用。净亏损为1.295亿美元，或归属于普通股股东的基本和摊薄每股净亏损为2.51美元。 2024年第二季度的研发费用为2910万美元，其中包括100万美元的股票薪酬成本；一般和管理费用为700万美元，其中包括220万美元的股票薪酬费用；季度净亏损为3610万美元。截至2024年6月30日，Immunome的现金、现金等价物和有价证券总计2.784亿美元，目前的现金预计将继续支持公司运营至2026年。参考：NMPA/CDE 药融云数据，www.pharnexcloud.com FDA/EMA/PMDA；相关公司公开披露（除标注外，正文图片均来自企业官网） https://immunome.com/ https://mp.weixin.qq.com/s/RcglELtOJ8lebL2vyCxPwg https://ir.ayalapharma.com/news-events/news-releases?a9d908dd_items_per_page=10&a9d908dd_year%5Bvalue%5D=2024&op=%E6%BB%A4%E6%B3%A2%E5%99%A8&a9d908dd_widget_id=a9d908dd&form_build_id=form-NbWaVtNpJg_Q2uBTbE3SRFGVNAKhrDJfX-7ba4_yvO8&form_id=widget_form_base https://ir.ayalapharma.com/news-releases/news-release-details/ayala-pharmaceuticals-enters-exclusive-worldwide-license；等等【关于药融圈】药融圈PRHub旨在帮助生物医药科技型企业进行品牌推广及商务拓展服务，针对客户的真实需求制定系统化解决方案，通过“翻译-降维-场景化”将客户的品牌信息以直白易懂的方式被公众知悉，同时在流量渠道覆盖100万+垂直用户基础上实现合作目的，帮助合作伙伴完成从品牌开始到商务为终的闭环营销服务。我们已经完成了数十场线下1000人规模的生物医药研发类会议，涵盖小分子新药，大分子新药，改良型新药，BD跨境交易等多个领域，服务了百余家上市/独角兽/生物技术/制药企业。

并购抗体药物偶联物高管变更

2024-08-08

·GlobeNewswire-Health Care

Oncternal Therapeutics Provides Business Update and Announces Second Quarter 2024 Financial Results

No dose-limiting toxicities or concerning side effects in our Phase 1/2 study with ONCT-534, our dual-action androgen receptor inhibitor (DAARI), for patients with advanced prostate cancer who are resistant to approved androgen receptor pathway inhibitors; 1200 mg cohort for ONCT-534 given orally once daily enrolled and treated; initial data readout expected in the third quarter of 2024Phase 1/2 study for ONCT-808, our ROR1-targeting autologous CAR T cell therapy, for patients with relapsed or refractory aggressive B-cell lymphoma is open and enrolling patients; clinical data update expected in the fourth quarter of 2024Cash, cash equivalents and short-term investments totaled $21.4 million as of June 30, 2024; cash runway projected into Q1 2025Management to host webcast today at 5:00 pm ET SAN DIEGO, Aug. 08, 2024 (GLOBE NEWSWIRE) -- Oncternal Therapeutics, Inc. (Nasdaq: ONCT), a clinical-stage biopharmaceutical company focused on the development of novel oncology therapies, today provided a business update and reported second quarter 2024 financial results. “Our Phase 1/2 study of ONCT-534 in patients with R/R mCRPC continues to advance through dose escalation cohorts without dose-limiting toxicities or concerning side effects. We are encouraged by the high pace of enrollment in the study and look forward to sharing initial clinical and biomarker data later in the third quarter,” said James Breitmeyer, M.D., Ph.D., Oncternal’s President and CEO. “Our Phase 1/2 study of ONCT-808, our autologous ROR1 CAR T, is open and enrolling patients. We remain encouraged we will find the optimal dose to address the high unmet need of patients with relapsed or refractory aggressive B cell lymphoma, including those who have relapsed after CD19 CAR T treatment.” Recent Highlights In July 2024, we announced that enrollment was complete and three patients dosed in the sixth cohort of our Phase 1/2 study of ONCT-534 for the treatment of patients with advanced prostate cancer who are relapsed or refractory to approved androgen receptor pathway inhibitors (ARPI). Patients in the sixth dosing cohort are being given 1200 mg of ONCT-534 orally once per day.Our dose escalation/dose expansion Phase 1/2 Study ONCT-808-101, evaluating our ROR1-targeting autologous CAR T cell therapy, ONCT-808, for the treatment of patients with relapsed or refractory aggressive B-cell lymphoma, including patients that have failed prior CD19 CAR T treatment, is open and enrolling patients. Protocol changes that include modified eligibility criteria, increased monitoring for early infection, and evaluating lower doses of ONCT-808 have now been implemented. Expected Upcoming Milestones ONCT-534, our dual-action androgen receptor inhibitor Initial clinical data in the third quarter of 2024Additional clinical data readouts in the fourth quarter of 2024 ONCT-808, our autologous ROR1-targeted CAR T cell therapy Clinical data update in the fourth quarter of 2024 Second Quarter 2024 Financial ResultsOur grant revenue was $0.8 million for the second quarter ended June 30, 2024. Our total operating expenses for the second quarter ended June 30, 2024 were $9.7 million, including $1.4 million in non-cash stock-based compensation expense. Research and development expenses for the quarter totaled $6.6 million, and general and administrative expenses for the quarter totaled $3.1 million. Net loss for the first quarter was $8.6 million, or a net loss of $2.89 per share, basic and diluted. As of June 30, 2024, we had approximately 3.0 million shares of common stock outstanding, $21.4 million in cash, cash equivalents and short-term investments and no debt. These funds are expected to be sufficient to fund our operations into the first quarter of 2025. About Oncternal TherapeuticsOncternal Therapeutics is a clinical-stage biopharmaceutical company focused on the development of novel oncology therapies for the treatment of patients with cancers that have critical unmet medical need. Oncternal pursues drug development targeting promising, yet untapped biological pathways implicated in cancer generation or progression, focusing on hematological malignancies and prostate cancer. ONCT-534 is an investigational dual-action androgen receptor inhibitor (DAARI) with demonstrated preclinical activity in prostate cancer models against both unmutated androgen receptor (AR), and against multiple forms of AR aberration. It is a potential treatment for patients with mCRPC with unmet medical need because of resistance to androgen receptor pathway inhibitors, including those with AR amplification, mutations in the AR ligand binding domain (LBD), or splice variants with loss of the AR LBD. Study ONCT-534-101 (NCT05917470) has completed enrollment and dosing in six dose cohorts for the treatment of patients with mCRPC. ONCT-808 is an investigational autologous chimeric antigen receptor T (CAR T) cell therapy that targets Receptor Tyrosine Kinase-Like Orphan Receptor 1 (ROR1) using the binding domain from zilovertamab. ONCT-808 has demonstrated activity in preclinical models against multiple hematological malignancies and solid tumors and has been shown to be specific for cancer cells expressing ROR1. Oncternal has developed a robust and reproducible manufacturing process that has the potential to reduce the time patients must wait for their individual CAR T therapy to be produced, compared with currently approved CAR T products. Oncternal has dosed patients under Study ONCT-808-101 (NCT05588440) with relapsed or refractory aggressive B-cell lymphoma, including patients who have failed previous CD19 CAR T treatment. Zilovertamab is an investigational monoclonal antibody designed to inhibit the function of ROR1. Zilovertamab has been evaluated in a Phase 1/2 Study CIRM-0001 (NCT03088878) in combination with ibrutinib for the treatment of patients with mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL) and marginal zone lymphoma (MZL), which resulted in 100% progression free survival (PFS) at 42 months in CLL patients expressing a p53 mutation/del(17p), a population underserved by current treatment options. Zilovertamab is also being evaluated in an investigator-initiated Phase 1b study of zilovertamab in combination with docetaxel in patients with metastatic castration-resistant prostate cancer (NCT05156905). More information on our company and programs is available at https://oncternal.com/. Forward-Looking Information Oncternal cautions you that statements included in this press release that are not a description of historical facts are forward-looking statements. In some cases, you can identify forward-looking statements by terms such as “may,” “will,” “should,” “expect,” “plan,” “anticipate,” “could,” “intend,” “target,” “project,” “contemplates,” “believes,” “estimates,” “predicts,” “potential” or “continue” or the negatives of these terms or other similar expressions. These statements are based on Oncternal’s current beliefs and expectations. Forward-looking statements include statements regarding Oncternal’s expected cash runway and statements regarding Oncternal’s development programs, including the anticipated timing for study enrollment and announcing clinical data. Forward-looking statements are subject to risks and uncertainties inherent in Oncternal’s business, including risks associated with the clinical development and process for obtaining regulatory approval of Oncternal’s product candidates, such as potential delays in the commencement, enrollment and completion of clinical trials; the risk that interim results of a clinical trial do not predict final results and that one or more of the clinical outcomes may materially change as patient enrollment continues, following more comprehensive reviews of the data, as follow-up on the outcome of any particular patient continues, and as more patient data become available; and other risks described in Oncternal’s filings with the U.S. Securities and Exchange Commission. All forward-looking statements in this press release are current only as of the date hereof and, except as required by applicable law, Oncternal undertakes no obligation to revise or update any forward-looking statement, or to make any other forward-looking statements, whether as a result of new information, future events or otherwise. All forward-looking statements are qualified in their entirety by this cautionary statement. This caution is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Contact Information: InvestorsRichard Vincent 858-434-1113rvincent@oncternal.com MediaCorey Davis, Ph.D. LifeSci Advisors 212-915-2577 cdavis@lifesciadvisors.com Oncternal Therapeutics, Inc.Condensed Consolidated Balance Sheets Data(Unaudited; in thousands) June 30,2024 December 31,2023 Cash, cash equivalents and short-term investments $21,429 $34,255 Total assets 23,859 36,729 Total liabilities 8,105 6,677 Accumulated deficit (214,726) (197,779)Total stockholders' equity 15,754 30,052 Oncternal Therapeutics, Inc.Condensed Consolidated Statements of Operations Data(Unaudited; in thousands, except per share data) Three Months EndedJune 30, Six Months EndedJune 30, 2024 2023 2024 2023 Grant revenue $801 $106 $1,370 $309 Operating expenses: Research and development 6,612 6,577 12,671 15,608 General and administrative 3,052 3,074 6,341 6,389 Total operating expenses 9,664 9,651 19,012 21,997 Loss from operations (8,863) (9,545) (17,642) (21,688)Interest income 304 579 695 1,235 Net loss $(8,559) $(8,966) $(16,947) $(20,453)Net loss per share, basic and diluted $(2.89) $(3.05) $(5.73) $(6.98)Weighted-average shares outstanding, basic and diluted 2,960 2,936 2,960 2,931

临床1期细胞疗法财报免疫疗法临床结果

100 项与 Zilovertamab 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	Zilovertamab	-	-

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
B细胞淋巴瘤	临床3期	-	Oncternal Therapeutics, Inc.	2023-03-01
难治性套细胞淋巴瘤	临床3期	-	Oncternal Therapeutics, Inc.	2023-03-01
套细胞淋巴瘤	临床3期	美国	University of California	2022-01-04
套细胞淋巴瘤	临床3期	美国	Oncternal Therapeutics, Inc.	2022-01-04
慢性淋巴细胞白血病	临床2期	美国	Oncternal Therapeutics, Inc.	2020-08-06
边缘区B细胞淋巴瘤	临床2期	美国	University of California San Diego	2018-01-03
边缘区B细胞淋巴瘤	临床2期	美国	Oncternal Therapeutics, Inc.	2018-01-03
小淋巴细胞淋巴瘤	临床2期	美国	University of California San Diego	2018-01-03
小淋巴细胞淋巴瘤	临床2期	美国	Oncternal Therapeutics, Inc.	2018-01-03
去势抵抗性前列腺癌	临床1期	美国	Oncternal Therapeutics, Inc.	2022-07-14

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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


NCT03088878 (CIRM-0001, GlobeNewswire) 人工标引	临床1/2期	套细胞淋巴瘤 \| 慢性淋巴细胞白血病 \| 边缘区B细胞淋巴瘤 TP53	-	Zilovertamab (CLL)	廠簾蓋製鏇製夢鏇網蓋(糧顧鹽淵膚獵築網夢網) = 夢範選獵蓋製壓衊蓋顧鹽獵顧築艱遞餘鑰糧衊 (齋淵簾夢鏇選餘齋糧膚 )	积极	2024-02-29
ICML2023	临床1/2期	套细胞淋巴瘤 \| 慢性淋巴细胞白血病 \| 边缘区B细胞淋巴瘤 TP53 mut/del(17p)	99	Zilovertamab 600 mg IV q4wks + Ibrutinib 420 mg (CLL) or 560 mg (MCL) daily	糧醖構觸艱憲積範築蓋(餘鑰淵廠鹹廠鹹蓋獵憲) = 9.4% of all pts treated 廠鏇夢觸糧廠淵積鑰鹹 (獵製遞淵觸鬱憲鑰廠願 ) 更多	积极	2023-06-09
NCT03088878 (ASCO2022)	临床1/2期	套细胞淋巴瘤 \| 慢性淋巴细胞白血病	102	Zilovertamab	範鏇醖襯膚艱艱醖衊淵(鏇鹽鏇範衊窪襯餘觸艱) = 構鏇築鏇齋顧壓鏇齋醖觸窪壓襯糧蓋鬱構積鑰 (觸艱鹽壓網鹹積製鏇膚 ) 更多	-	2022-06-02
NCT03088878 (ASCO2021)	临床1/2期	套细胞淋巴瘤 \| 慢性淋巴细胞白血病	102	Cirmtuzumab	齋繭夢構淵膚襯遞襯簾(淵選鹹鹹範選築憲繭築) = 壓衊繭蓋網顧鑰觸夢夢觸襯壓網觸膚鬱遞壓鹹 (夢糧餘願觸範壓醖鏇壓 ) 更多	-	2021-05-28
NCT02222688 (CTgov)	临床1期	慢性淋巴细胞白血病	26	cirmtuzumab (Cirmtuzumab 0.015 - 0.03 mg/kg)	憲衊顧獵憲夢構蓋顧簾(艱遞鹽廠積襯壓構網廠) = 襯繭鬱窪糧鏇築網積餘襯積壓範鹽壓夢構廠選 (範鑰糧築積憲鹽蓋鑰簾, 繭醖鹹淵醖鏇遞壓簾鏇 ~ 鏇繭糧夢糧鑰顧繭簾鬱) 更多	-	2020-08-13
NCT02222688 (CTgov)	临床1期	慢性淋巴细胞白血病	26	cirmtuzumab (Cirmtuzumab 0.06 - 0.12 - 0.24 mg/kg)	憲衊顧獵憲夢構蓋顧簾(艱遞鹽廠積襯壓構網廠) = 壓襯鹹製壓壓襯獵膚繭襯積壓範鹽壓夢構廠選 (範鑰糧築積憲鹽蓋鑰簾, 積鑰獵齋顧鹽淵網願願 ~ 獵齋夢觸壓築齋衊餘鹽) 更多	-	2020-08-13
NCT03088878 (ASCO2020)	临床2期	套细胞淋巴瘤 \| 慢性淋巴细胞白血病	46	Cirmtuzumab + Ibrutinib	願糧糧鬱繭鑰窪餘餘範(憲夢餘蓋壓簾窪鹹醖餘) = only grade 1/ 2 AEs were reported as possibly related to Cirm alone, whereas the safety profile attributed to Ibr or Ibr / Cirm was similar to published data, with no new or unexpected events 衊壓膚壓範窪鏇艱積膚 (繭鬱願鹹構簾糧蓋遞遞 )	积极	2020-05-25
NCT02776917 (AACR2020) 人工标引	临床1期	局部晚期乳腺癌 HER2 Positive \| ROR1 Positive	15	paclitaxel +cirmtuzumab	繭願遞顧製膚餘餘簾衊(選淵鬱鬱遞壓簾獵壓艱) = none 膚築齋齋齋襯選築遞簾 (夢夢鬱糧餘繭鹹願製窪 ) 更多	积极	2020-02-15
ASCO2019	临床1/2期	慢性淋巴细胞白血病	-	Cirmtuzumab	夢憲鏇壓衊獵蓋願憲糧(鹹願遞窪願夢鹹衊繭襯) = 1 atrial fibrillation event 製築艱蓋觸鬱淵壓鹽憲 (積鹹衊窪壓觸齋壓廠醖 ) 更多	积极	2019-05-26