Open-label, Dose-escalating Trial to Evaluate the Tolerability, Toxicity, Safety, Pharmacokinetics, Pharmacodynamics and Activity of Volasertib Added to the Standard Intensive Salvage Chemotherapy Regimen With Liposomal Daunorubicine, Fludarabine and Cytarabine (DNX-FLA) Followed by Fludarabine and Cytarabine (FLA) in Children From 3 Months to Less Than 18 Years of Age With Acute Myeloid Leukaemia After Failure of the Front-line Therapy

This is an open-label, dose-escalating trial to evaluate the MTD and/or dose to be used for further development by evaluation of DLT in course 1 and the safety of volasertib when added to standard intensive salvage chemotherapy with DNX-FLA in paediatric patients with AML after failure of first-line therapy. Furthermore, data on efficacy and PK/PD of volasertib in paediatric patients with AML when added to standard intensive salvage chemotherapy will be collected.

开始日期2016-11-01

申办/合作机构

Boehringer Ingelheim GmbH

NCT02757248 / Withdrawn临床1期IIT

A Phase I Trial of Volasertib Plus Romidepsin in Patients With Relapsed/Refractory Peripheral T Cell and Cutaneous T Cell Lymphoma

This is a phase I study of the combination of volasertib and romidepsin in patients with relapsed/refractory peripheral T cell lymphoma (PTCL) or stage IIB-IV cutaneous T cell lymphoma (CTCL). This study will determine the maximum tolerated dose (MTD) of this combination by treating cohorts of patients at a certain dose combination. The investigators will use a Bayesian design to determine the dose combination for the next cohort of patients and to determine the MTD. Overall response rate as well as adverse events will be monitored and reported.

开始日期2016-11-01

申办/合作机构

Duke University

[+2]

NCT02527174 / Withdrawn临床1期IIT

A Phase I Study of Volasertib Combined With Standard Induction Chemotherapy for Previously Untreated Patients With Acute Myeloid Leukemia (VIAC)

This is a Phase I clinical trial to determine the maximum tolerated dose (MTD) of the polo-like kinase-1 inhibitor volasertib which can be safely combined with idarubicin plus cytarabine induction chemotherapy for previously untreated patients with acute myeloid leukemia. (AML).

开始日期2016-11-01

申办/合作机构

University of Alberta

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100 项与伏拉色替相关的专利（医药）

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180

项与伏拉色替相关的文献（医药）

2024-03-01·Molecular Oncology

PLK1 and FoxM1 expressions positively correlate in papillary thyroid carcinoma and their combined inhibition results in synergistic anti‐tumor effects

Article

作者: Siraj, Abdul K ; Padmaja, Divya ; Begum, Rafia ; Thangavel, Saravanan ; Al-Sobhi, Saif S ; Diaz, Roxanne ; Haqawi, Wael ; Parvathareddy, Sandeep Kumar ; Alobaisi, Khadija ; Poyil, Pratheesh Kumar ; Al-Kuraya, Khawla S ; Al-Dayel, Fouad

Polo‐like kinase 1 (PLK1; also known as serine/threonine‐protein kinase PLK1) serves as a central player in cell proliferation, exerting critical regulatory roles in mitotic processes and cell survival. We conducted an analysis of PLK1 protein expression in a large cohort of samples from papillary thyroid carcinoma (PTC) patients and examined its functional significance in PTC cell lines, both in vitro and in vivo. PLK1 overexpression was noted in 54.2% of all PTC and was significantly associated with aggressive clinicopathological parameters; it was also found to be an independent prognostic marker for shorter recurrence‐free survival. Given the significant association between PLK1 and forkhead box protein M1 (FoxM1), and their concomitant overexpression in a large proportion of PTC samples, we explored their correlation and their combined inhibitions in PTC in vitro and in vivo. Inhibition of PLK1 expression indeed suppressed cell proliferation, leading to cell cycle arrest and apoptosis in PTC cell lines. Significantly, the downregulation of PLK1 reduced the self‐renewal capability of spheroids formed from PTC cells. Immunoprecipitation analysis shows that PLK1 binds to FoxM1 and vice versa in vitro. Mechanistically, PLK1 knockdown suppresses FoxM1 expression, whereas inhibition of FoxM1 does not affect PLK1 expression, which suggests that PLK1 acts through the FoxM1 pathway. The combined treatment of a PLK1 inhibitor (volasertib) and a FoxM1 inhibitor (thiostrepton) demonstrated a synergistic effect in reducing PTC cell growth in vitro and delaying tumor growth in vivo. This study highlights the important role of PLK1 in PTC tumorigenesis and prognosis. It also highlights the synergistic therapeutic potential of dual‐targeting PLK1 and FoxM1 in PTC, unveiling a potential innovative therapeutic strategy for managing aggressive forms of PTC.

2024-01-01·European Journal of Pharmacology

Eph signal inhibition potentiates the growth-inhibitory effects of PLK1 inhibition toward cancer cells

Article

作者: Kuwajima, Hiroki ; Saito, Youhei ; Yuki, Ryuzaburo ; Ikeda, Yuki ; Ota, Ryoko ; Nakayama, Yuji

Anti-mitotic drugs are clinically used as anti-cancer treatments. Polo-like kinase 1 (PLK1) is a promising target against cancer cell division due to its importance in the whole process of mitosis, and thus PLK1-targeting agents have been developed in the last few decades. Clinical trial studies show that several PLK1 inhibitors are generally well-tolerated. However, the response rates are limited; therefore, it is needed to improve the efficacy of those drugs. Here, we show that NVP-BHG712, an erythropoietin-producing human hepatocellular (Eph) signaling inhibitor, potentiates the growth-inhibitory effects of the PLK1 inhibitors BI2536 and BI6727 in cancer cells. This combination treatment strongly suppresses cancer spheroid formation. Moreover, the combination drastically arrests cells at mitosis by continuous activation of the spindle assembly checkpoint (SAC), thereby inducing apoptosis. SAC activation caused by the combination of NVP-BHG712 and BI2536 is due to the inhibition of centrosome maturation and separation. Although the inactivation level of the PLK1 kinase is comparable between BI2536 treatment alone and combination treatment, the combination treatment strongly inactivates MAPK signaling in mitosis. Since inhibition of MAPK signaling potentiates the efficacy of BI2536 treatment, inactivation of PLK1 kinase and MAPK signaling contributes to the strong inhibition of centrosome separation. These results suggest that Eph signal inhibition potentiates the effect of PLK1 inhibition, leading to strong mitotic arrest via SAC activation and the subsequent reduction of cancer cell survival. The combination of PLK1 inhibition and Eph signal inhibition will provide a new effective strategy for targeting cancer cell division.

2024-01-01·Inflammation Research

Tangeretin attenuates acute lung injury in septic mice by inhibiting ROS-mediated NLRP3 inflammasome activation via regulating PLK1/AMPK/DRP1 signaling axis

Article

作者: Zhang, Zhongde ; Antonina, Kim ; Zan, Jie ; He, Zhipeng ; Shukhrat, Ziyadullaev ; Zheng, Danwen ; You, Guoxing ; Ding, Banghan ; Zhang, Yuting ; Guo, Wenjie ; Liu, Yuntao

OBJECTIVENLRP3 inflammasome-mediated pyroptosis of macrophage acts essential roles in the progression of sepsis-induced acute lung injury (ALI). Tangeretin (TAN), enriched in citrus fruit peel, presents anti-oxidative and anti-inflammatory effects. Here, we aimed to explore the potentially protective effect of TAN on sepsis-induced ALI, and the underlying mechanism of TAN in regulating NLRP3 inflammasome.MATERIAL AND METHODSThe effect of TAN on sepsis-induced ALI and NLRP3 inflammasome-mediated pyroptosis of macrophage were examined in vivo and in vitro using a LPS-treated mice model and LPS-induced murine macrophages, respectively. The mechanism of TAN regulating the activation of NLRP3 inflammasome in sepsis-induced ALI was investigated with HE staining, Masson staining, immunofluorescent staining, ELISA, molecular docking, transmission electron microscope detection, qRT-PCR, and western blot.RESULTSTAN could evidently attenuate sepsis-induced ALI in mice, evidenced by reducing pulmonary edema, pulmonary congestion and lung interstitial fibrosis, and inhibiting macrophage infiltration in the lung tissue. Besides, TAN significantly suppressed inflammatory cytokine IL-1β and IL-18 expression in the serum or bronchoalveolar lavage fluid (BALF) samples of mice with LPS-induced ALI, and inhibited NLRP3 inflammasome-mediated pyroptosis of macrophages. Furthermore, we found TAN inhibited ROS production, preserved mitochondrial morphology, and alleviated excessive mitochondrial fission in LPS-induced ALI in mice. Through bioinformatic analysis and molecular docking, Polo-like kinase 1 (PLK1) was identified as a potential target of TAN for treating sepsis-induced ALI. Moreover, TAN significantly inhibited the reduction of PLK1 expression, AMP-activated protein kinase (AMPK) phosphorylation, and Dynamin related protein 1 (Drp1) phosphorylation (S637) in LPS-induced ALI in mice. In addition, Volasertib, a specific inhibitor of PLK1, abolished the protective effects of TAN against NLRP3 inflammasome-mediated pyroptosis of macrophage and lung injury in the cell and mice septic models.CONCLUSIONTAN attenuates sepsis-induced ALI by inhibiting ROS-mediated NLRP3 inflammasome activation via regulating PLK1/AMPK/DRP1 signaling axis, and TAN is a potentially therapeutic candidate against ALI through inhibiting pyroptosis.

项与伏拉色替相关的新闻（医药）

2024-05-09

·PRNewswire

Fight Against Pancreatic Cancer Ramps Up as Market Size Revenues Expected to Exceed $36 Billion by 2036

FN Media Group News Commentary PALM BEACH, Fla., May 9, 2024 /PRNewswire/ -- The incidence of pancreatic cancer is increasing globally, which is driving the growth of the market. As of 2023, the American Cancer Society predicts that 64,050 Americans will be diagnosed with pancreatic cancer. It is estimated that 50,550 people will die from pancreatic cancer (26,620 men and 23,930 women). Pancreatic cancer is an aggressive form of cancer, and it is often not detected until it is in an advanced stage. Additionally, the treatment options for pancreatic cancer are limited, and the survival rate is low. These factors are contributing to the rise in pancreatic cancer cases, which in turn is driving the growth of the pancreatic cancer market. A recent report from Research Nester projected that the global pancreatic cancer market size is slated to expand at ~18% CAGR between 2024 and 2036. The market is poised to garner a revenue of USD 36 billion by the end of 2036, up from a revenue of ~USD 6 billion in the year 2023. The report said: "Advancements in diagnosis and treatment options for pancreatic cancer are also driving the growth of the market. As researchers gain a better understanding of the different types of pancreatic cancer, they are developing more targeted treatments that are more likely to be effective with fewer side effects. Additionally, new treatment options, such as immunotherapy and targeted therapies, are improving patient outcomes and extending survival rates." Active biotech and pharma companies in the markets this week include Oncolytics Biotech® Inc. (NASDAQ: ONCY) (TSX: ONC), Zai Lab Limited (NASDAQ: ZLAB), Notable Labs, Ltd. (NASDAQ: NTBL), Cardiff Oncology, Inc. (NASDAQ: CRDF), Johnson & Johnson (NYSE: JNJ). Research Nester concluded: "The pancreatic cancer market in North America is garner the largest revenue by the end of 2036 due to several demographic changes, including an aging population and increased incidence of obesity and diabetes. In the US, there are 37.3 million diabetics (11.3[R3] % of the population); 28.7 million are diagnosed with diabetes, including 28.5 million adults. As the population ages, there will be a higher prevalence of chronic diseases such as diabetes and obesity, which are risk factors for pancreatic cancer. Additionally, the aging population will lead to an increase in the number of people with pre-existing conditions that can increase the risk of developing pancreatic cancer. Obesity and diabetes are known risk factors for pancreatic cancer, and as these conditions become more prevalent, the number of cases of pancreatic cancer is expected to increase." Oncolytics Biotech® Inc. (NASDAQ: ONCY) (TSX: ONC) Receives Regulatory Clearance to Evaluate Pelareorep in Combination with Modified FOLFIRINOX +/- an anti-PD-L1 Inhibitor in Pancreatic Cancer US$5 million PanCAN grant provides important support for the fifth cohort of the GOBLET study Study of modified OLFIRINOX/pelareorep/atezolizumab (Tecentriq ®) combination expands existing pancreatic cancer program First patient expected to be enrolled in Q2 2024 Oncolytics Biotech ® Inc., a leading clinical-stage company specializing in immunotherapy for oncology, will commence enrollment into a new GOBLET study pancreatic cancer cohort following both German regulatory and ethics approvals. This cohort will evaluate pelareorep in combination with modified FOLFIRINOX (mFOLFIRINOX) with or without the PD-L1 immune checkpoint inhibitor atezolizumab (Tecentriq ® ) in newly diagnosed patients with pancreatic ductal adenocarcinoma (PDAC). It is supported by a US$5M Therapeutic Accelerator Award from the Pancreatic Cancer Action Network (PanCAN), an innovative program established to accelerate the development of new treatments for pancreatic cancer. The chemotherapy regimens of mFOLFIRINOX or gemcitabine + nab-paclitaxel are the two most common standards of care for pancreatic cancer. Oncolytics has already reported data with the combination of gemcitabine and nab-paclitaxel ( link to the PR , link to the poster ) that surpassed historical outcomes. Positive results from a combination with mFOLFIRINOX could greatly enhance pelareorep's potential in addressing pancreatic cancer. "Oncolytics is pleased to announce receipt of regulatory clearance to initiate the mFOLFIRINOX cohort in patients with newly diagnosed metastatic PDAC. We appreciate the opportunity to collaborate with PanCAN, Roche, and AIO on this cohort, which is expected to initiate enrollment in the second quarter," said Dr. Matt Coffey, President and Chief Executive Officer of Oncolytics. "We believe that working with PanCAN will help to further enrich Oncolytics' clinical relationships with the pancreatic cancer community. We are also grateful for PanCAN's Therapeutic Accelerator Award, which is enabling the evaluation of this combination therapy." "The Therapeutic Accelerator Award program has been an important part of PanCAN's approach to advancing innovative treatments for pancreatic cancer. We incorporated input from leading scientists and clinicians in the field of pancreatic cancer to select Oncolytics as a recipient of this award," said Anna Berkenblit , MD, MMSc, Chief Scientific and Medical Officer at PanCAN. "Increasing patient access to clinical trials is vital to developing improved treatment options, so we are pleased that Oncolytics has received regulatory clearance for the pelareorep/mFOLFIRINOX combination and is poised to enroll the first patient in this cohort. We hope that the results from this study lead to improved outcomes for patients with pancreatic cancer." Dirk Arnold , M.D., Ph.D., Director of Asklepios Tumorzentrum Hamburg and primary investigator of the GOBLET trial, commented, "Oncolytics has taken a very strategic approach to the development of pelareorep in pancreatic cancer by focusing its clinical studies on combinations with the most widely used treatment regimens. My experience to date with the GOBLET study, including the positive metastatic PDAC and encouraging anal cancer data reported last year, makes me enthusiastic to initiate enrollment in the mFOLFIRINOX cohort." "We previously reported very encouraging results in pancreatic cancer patients for the combination of pelareorep, gemcitabine/nab-paclitaxel, and atezolizumab, and we plan to begin a registration-enabling study of this regimen later this year. The new pelareorep/mFOLFIRINOX cohort offers the opportunity to expand pelareorep's role in pancreatic cancer. If the mFOLFIRINOX combination shows a compelling efficacy signal, this therapeutic approach could also be advanced to a registration-enabling study, providing two opportunities for pelareorep-based treatment to benefit pancreatic cancer patients," said Thomas Heineman , M.D., Ph.D., Chief Medical Officer at Oncolytics. "In addition, translational research studies planned for this cohort will help to further elucidate pelareorep's mechanism of action, including its ability to shape the tumor microenvironment (TME). Notably, we will evaluate the correlation between tumor responses and the expansion of tumor-infiltrating lymphocytes (TILs) in the blood, an effect that was observed in earlier pancreatic cancer studies. We look forward to initiating enrollment into the mFOLFIRINOX/pelareorep study cohort in the second quarter of this year." CONTINUED… Read these full press releases and more news for ONCY at: Other recent developments in the biotech industry of note for cancer events include: Zai Lab Limited (NASDAQ: ZLAB) recently announced financial results for the first quarter of 2024, along with recent product highlights and corporate updates. "Our first quarter results demonstrate strong commercial execution and pipeline progress across our potential first- and best-in-class product portfolio," said Dr. Samantha Du, Founder, Chairperson, and Chief Executive Officer of Zai Lab. "The launch of VYVGART is off to an impressive start with $13.2 million of sales in the first quarter. Looking ahead, we expect to accelerate commercial performance for the remainder of the year and are preparing for three new potential launches in 2024. We are also excited by the progress of our late-stage pipeline and we are on track to achieve the objectives outlined in our five-year strategic plan, including significant revenue growth and profitability by the end of 2025." "Our net revenues grew 39% y-o-y or 43% y-o-y at CER in the first quarter, driven by strong execution with the launch of VYVGART and uptake of our existing portfolio," said Josh Smiley, President and Chief Operating Officer of Zai Lab. "With VYVGART's launch in gMG at the end of last year, and multiple new products and indications expected to launch over the near-term, we are now entering a period of robust growth for Zai Lab. Our significant growth, coupled with our focus on driving efficiencies and productivity across the organization, will drive the evolution of Zai Lab into a profitable, high growth business by the end of 2025. Furthermore, we will continue to focus on expanding our global portfolio through our internal discovery activities and strategic business development," Mr. Smiley concluded. Notable Labs, Ltd. (NASDAQ: NTBL), a clinical-stage precision oncology company developing new cancer therapies identified by its Predictive Precision Medicine Platform (PPMP), recently reported financial results for the year ended December 31, 2023 and provided a business update. "The last year has been a time of great accomplishment for Notable. We built a strong clinical validation dataset, starting with a poster presented at the American Association for Cancer Research (AACR 2023); became a publicly listed company, following the closing of a reverse merger in October 2023; and reported successful PPMP clinical data from the Phase 2 fosciclopirox study that showcased the ability of our platform to accurately predict patient outcomes for specific therapeutics," said Thomas Bock, M.D., Chief Executive Officer of Notable. "The performance of our platform in accurately predicting the outcome of the fosciclopirox study has enabled us to enhance the clinical trial plan for our lead product candidate, volasertib, in development for patients with relapsed/refractory acute myeloid leukemia (r/r AML). In our upcoming Phase 2 trial, we will be utilizing the platform to enrich the study's enrollment with patients predicted to respond to volasertib, which we believe will result in more rapid enrollment, shorter time to efficacy data and, ultimately, increased probability of success." Cardiff Oncology, Inc. (NASDAQ: CRDF), a clinical-stage biotechnology company leveraging PLK1 inhibition to develop novel therapies across a range of cancers, recently announced financial results for the first quarter ended March 31, 2024, and provided a business update. "During the start of 2024, we presented several important new data sets supporting our first-line RAS-mutated mCRC strategy and the broader opportunity for onvansertib," said Mark Erlander, Ph.D., Chief Executive Officer of Cardiff Oncology. "The data from the ONSEMBLE trial replicated, in a second independent and randomized dataset, the bev naïve signal from our earlier Phase 1b/2 KRAS-mutated mCRC trial. And the Phase 1b data published in the peer-reviewed journal Clinical Cancer Research, and the additional data we presented in one of our five posters at AACR, further substantiated our lead program in RAS-mutated mCRC. The additional AACR posters also point toward new indications for onvansertib in RAS wild-type mCRC, small cell lung cancer and ovarian cancer. Looking ahead, we believe that our upcoming data readout from our first-line trial in RAS-mutated mCRC has the potential to serve as a key value inflection point for our company and revolutionize the treatment of RAS-mutated mCRC, an area with no new treatments approved in over two decades." Johnson & Johnson (NYSE: JNJ) recently announced that the U.S. Food and Drug Administration (FDA) has approved CARVYKTI® (ciltacabtagene autoleucel; cilta-cel) for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least one prior line of therapy, including a proteasome inhibitor and an immunomodulatory agent, and are refractory to lenalidomide. With this approval, CARVYKTI® becomes the first and only B-cell maturation antigen (BCMA)-targeted therapy approved for the treatment of patients with multiple myeloma as early as first relapse. FDA approval is based on positive results from the Phase 3 CARTITUDE-4 study, which demonstrated that the earlier use of CARVYKTI® reduced the risk of disease progression or death by 59 percent compared to standard therapies—pomalidomide, bortezomib and dexamethasone (PVd) or daratumumab, pomalidomide and dexamethasone (DPd)—in adults with relapsed and lenalidomide-refractory multiple myeloma who received one to three prior lines of therapy. The study, which was presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting and published in The New England Journal of Medicine, also included and reported key secondary results such as overall response (OR) and overall survival (OS). About FN Media Group: At FN Media Group, via our top-rated online news portal at , we are one of the very few select firms providing top tier one syndicated news distribution, targeted ticker tag press releases and stock market news coverage for today's emerging companies. #pressreleases #tickertagpressreleases Follow us on Facebook to receive emerging news updates: Follow us on Twitter for real time Breaking News: Follow and us on Linkedin: DISCLAIMER: FN Media Group LLC (FNM), which owns and operates FinancialNewsMedia.com and MarketNewsUpdates.com, is a third party publisher and news dissemination service provider, which disseminates electronic information through multiple online media channels. FNM is NOT affiliated in any manner with any company mentioned herein. FNM and its affiliated companies are a news dissemination solutions provider and are NOT a registered broker/dealer/analyst/adviser, holds no investment licenses and may NOT sell, offer to sell or offer to buy any security. FNM's market updates, news alerts and corporate profiles are NOT a solicitation or recommendation to buy, sell or hold securities. The material in this release is intended to be strictly informational and is NEVER to be construed or interpreted as research material. All readers are strongly urged to perform research and due diligence on their own and consult a licensed financial professional before considering any level of investing in stocks. All material included herein is republished content and details which were previously disseminated by the companies mentioned in this release. FNM is not liable for any investment decisions by its readers or subscribers. Investors are cautioned that they may lose all or a portion of their investment when investing in stocks. For current services performed FNM was compensated forty nine hundred dollars for news coverage of the current press releases issued by Oncolytics Biotech® Inc. by a non-affiliated third party. FNM HOLDS NO SHARES OF ANY COMPANY NAMED IN THIS RELEASE. This release contains "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E the Securities Exchange Act of 1934, as amended and such forward-looking statements are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. "Forward-looking statements" describe future expectations, plans, results, or strategies and are generally preceded by words such as "may", "future", "plan" or "planned", "will" or "should", "expected," "anticipates", "draft", "eventually" or "projected". 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临床结果临床2期上市批准

2024-04-12

·BioSpace

Notable Labs Reports 2023 Financial Results and Provides a Business Update

FOSTER CITY, Calif., April 12, 2024 (GLOBE NEWSWIRE) -- Notable Labs Ltd. (Nasdaq: NTBL) (“Notable” or the “Company”), a clinical-stage precision oncology company developing new cancer therapies identified by its Predictive Precision Medicine Platform (PPMP), reported financial results for the year ended December 31, 2023 and provided a business update. “The last year has been a time of great accomplishment for Notable. We built a strong clinical validation dataset, starting with a poster presented at the American Association for Cancer Research (AACR 2023); became a publicly listed company, following the closing of a reverse merger in October 2023; and reported successful PPMP clinical data from the Phase 2 fosciclopirox study that showcased the ability of our platform to accurately predict patient outcomes for specific therapeutics,” said Thomas Bock, M.D., Chief Executive Officer of Notable. “The performance of our platform in accurately predicting the outcome of the fosciclopirox study has enabled us to enhance the clinical trial plan for our lead product candidate, volasertib, in development for patients with relapsed/refractory acute myeloid leukemia (r/r AML). In our upcoming Phase 2 trial, we will be utilizing the platform to enrich the study’s enrollment with patients predicted to respond to volasertib, which we believe will result in more rapid enrollment, shorter time to efficacy data and, ultimately, increased probability of success.” Dr. Bock commented further, “Looking ahead, we are on track to significantly advance the clinical program for volasertib in 2024 and further validate the potential for PPMP as a precision medicine tool. We are pleased that an abstract related to this program was presented this week at the AACR 2024 and look forward to providing additional data in the coming months.” Joseph Wagner, Ph.D., Chief Scientific Officer of Notable, added, “We are enthusiastic to initiate the Phase 2 volasertib/PPMP trial in the coming months. Our study will incorporate important learnings from prior studies conducted by volasertib’s originator, Boehringer Ingelheim, which suggest that standardizing best supportive care and introducing body surface area-based dosing are likely to enhance patient responses and tolerability. We plan to include and evaluate these refinements in a small all-comers dose optimization lead-in, prior to enrolling PPMP-predicted responders. The open label design of our Phase 2 trial will enable us to provide ongoing updates and initiate a subsequent Phase 3 trial at the earliest possibility.” Recent and Upcoming Milestones: Presentation of two posters at AACR2024: April 8 and 9, 2024 Volasertib: Advance the Phase 2 program, starting with the dose optimization prelude Year End December 31, 2023 Financial Results Total cash and cash equivalents(Cash) were $11.8 million as of December 31, 2023. As of April 1, 2024, Notable has cash and cash equivalents of $8.2 million. Based on its current cash position and the Company’s planned expense run rate, the Company believes that its current cash balance is sufficient to support its planned expenses, obligations and capital expenditure requirements into Q4 2024. Total net revenue includes revenue from diagnostic services performed on a limited basis as an outsourced provider. Total net revenue for the year ended December 31, 2023 was $0.3 million. Total cost of services relate to the costs of processing diagnostic tests of laboratory samples. Total cost of services for the year ended December 31, 2023 was $0.2 million. Research and development expenses for the year ended December 31, 2023 were $4.7 million, compared to $7.8 million in 2022, reflecting lower engineering costs necessary to support the PPMP platform, as well as lower laboratory costs for fosciclopirox and volasertib. General and administrative expenses for the full year 2023 were $10.1 million compared to 5.2 million in 2022, mainly reflecting increased third-party costs related to the merger completed in October 2023, as well as higher costs associated with being a public company, including Directors and Officers Insurance (D&O) and stock-based compensation. Other Income (Expense), Net for the full year 2023 increased to $3.4 million of other income, net, from an expense of $1.5 million in 2022. The increase was primarily due to the loss on the conversion of the Series D SAFEs, the increase in the derivative fair value of the Series C SAFE and redeemable convertible preferred stock warrant liability. Net loss for 2023 decreased to $(11.3) million, or a loss of $(3.41) per share on a basic and diluted basis, for the year ended December 31, 2023, versus a net loss of $(14.4) million, or a loss of $(21.97) per share on a basic and diluted basis, for the year ended December 31, 2022. Outstanding shares as of April 1, 2024 were approximately 9.0 million. About Volasertib Volasertib is a PLK-1 inhibitor with demonstrated activity in AML and other tumor types, including solid tumors, with significant unmet medical need. Building on the performance of volasertib on PPMP, an important and proprietary step during Notable’s targeted in-licensing strategy and decision making, Notable will utilize PPMP to predict volasertib-responsive patients prior to their treatment, with the goal of selectively enrolling and treating those predicted responders, increasing volasertib’s response rates and overall patient outcomes, and fast-tracking volasertib’s remaining clinical development in this patient population. Volasertib was originally developed and manufactured by Boehringer Ingelheim and previously granted breakthrough therapy designation by the FDA. Notable in-licensed volasertib and obtained exclusive worldwide development and commercialization rights, except for certain rare pediatric cancers. About Notable Labs, Ltd. Notable Labs, Ltd. Is a clinical-stage platform therapeutics company developing predictive precision medicines for patients with cancer. Through its proprietary Predictive Precision Medicines Platform (PPMP), Notable aims to predict whether or not a patient is likely to respond to a specific therapeutic. The PPMP is designed to identify and select clinically responsive patients prior to their treatment, potentially fast-tracking clinical development. By continually advancing and expanding the reach of the PPMP across diseases and predicted medical outcomes, Notable aims to be the leader in predictive precision medicine and revolutionize the way patients seek and receive treatments that work best for them. Notable believes it has created a targeted and de-risked in-licensing strategy to deliver a product’s medical impact and commercial value faster, with a greater likelihood of success, than traditional drug development. By transforming historical standards of care, Notable aims to create a dramatically positive impact for patients and the healthcare community. Notable is headquartered in Foster City, California. Learn more at our website and follow us @notablelabs. Forward Looking Statements This press release contains “forward-looking statements” within the meaning of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, including but not limited to, express or implied statements regarding Notable’s future operations and goals; the potential benefits of any therapeutic candidates or platform technologies of Notable; the timing of any clinical milestones of Notable’s therapeutic candidates; the cash runway of the company; and other statements that are not historical fact. All statements other than statements of historical fact contained in this communication are forward-looking statements. These forward-looking statements are made as of the date they were first issued, and are based on the then-current expectations, estimates, forecasts, and projections, as well as the beliefs and assumptions of management. Forward-looking statements are subject to a number of risks and uncertainties, many of which involve factors or circumstances that are beyond Notable’s control. Notable’s actual results could differ materially from those stated or implied in forward-looking statements due to a number of factors, including but not limited to (i) uncertainties associated with Notable’s platform technologies, as well as risks associated with the clinical development and regulatory approval of product candidates, including potential delays in the commencement, enrollment and completion of clinical trials; (ii) risks related to the inability of Notable to obtain sufficient additional capital to continue to advance these product candidates and any preclinical programs; (iii) uncertainties in obtaining successful clinical results for product candidates and unexpected costs that may result therefrom; (iv) risks related to the failure to realize any value from product candidates and preclinical programs being developed and anticipated to be developed in light of inherent risks and difficulties involved in successfully bringing product candidates to market; (v) risks associated with Notable’s future financial and operating results, including its ability to become profitable; (vi) Notable’s ability to retain key personnel; (vii) Notable’s ability to manage the requirements of being a public company; (viii) uncertainties relating to the Israel-Hamas war; (ix) Notable’s ability to obtain orphan drug designation, and the associated benefits, for any of its drug candidates; (x) Notable’s inability to obtain regulatory approval for any of its drug candidates; and (xi) changes in, or additions to international, federal, state or local legislative requirements, such as changes in or additions to tax laws or rates, pharmaceutical regulations, and other regulations. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties. These and other risks and uncertainties are more fully described in periodic filings with the U.S. Securities and Exchange Commission (“SEC”), including the factors described in the section titled “Risk Factors” in the Annual Report on Form 10-K of Notable Labs, Ltd. for the year ended December 31, 2023 as filed with the SEC, and in other subsequent filings with the SEC. You should not place undue reliance on these forward-looking statements, which are made only as of the date hereof or as of the dates indicated in the forward-looking statements. Notable expressly disclaims any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in its expectations with regard thereto or any change in events, conditions or circumstances on which any such statements are based. CONTACTS: Investor Relations: Daniel Ferry, LifeSci Advisors C: +1 (617) 430-7576 E: daniel@lifesciadvisors.com

临床2期突破性疗法财报引进/卖出AACR会议

2024-04-09

·BioSpace

Notable Labs Presents the Design Plan for the PPMP-Enabled Phase 2 Trial with Volasertib for Relapsed/Refractory AML at AACR 2024

Poster outlines the parameters for developing a flow-cytometry-based PPMP as a companion diagnostic to predict volasertib responders, based on a proof-of-concept study using 41 primary acute myeloid leukemia (AML) samples Plans to incorporate a dose optimization prelude to enhance patient response and tolerability also outlined in the poster FOSTER CITY, Calif., April 09, 2024 (GLOBE NEWSWIRE) -- Notable Labs, Ltd. (Nasdaq: NTBL) (“Notable” or the “Company”), a clinical-stage precision oncology company developing a new class of cancer therapies identified by its Predictive Precision Medicine Platform (PPMP), today presented the design for the PPMP-enabled Phase 2 trial with volasertib, in combination with decitabine, in patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) at the American Association for Cancer Research (AACR 2024) being held in San Diego, CA (Poster abstract 5178). “We are very pleased to share more data regarding our clinical program and proprietary platform with the oncology community at AACR 2024. Presenting a summary of the Phase 2 volasertib study design in AML provides us with an opportunity to highlight the potential for the PPMP to effectively predict responders, and enroll an responder-enriched patient population, in our upcoming clinical program. Our clinical program will incorporate the co-development of a companion diagnostic test,” said Thomas Bock, M.D., Chief Executive Officer of Notable. Joseph Wagner, Ph.D., Chief Scientific Officer of Notable, commented, “The abstract highlights technical features of volasertib on Notable’s PPMP, including our method to develop a companion diagnostic test and define a cut-off value to predict responders. Based on the robust results of a 41-sample proof-of-concept study summarized in the poster, we are optimistic about the potential for PPMP to improve patient selection and lead to a strong Phase 2 study. In addition, we look forward to implementing a dosing optimization plan, including standardized use of best supportive care and introduction of body surface area-based dosing, to enhance patient responses and tolerability.” Poster Highlights: Guided by a predictive ex vivo test: Bringing the PLK1 inhibitor volasertib back into the clinic for venetoclax-HMA relapsed/refractory acute myeloid leukemia patients Overview: While prior studies of volasertib demonstrated an approximately 30% complete response/complete response with incomplete count recovery (CR/CRi) rate in de novo AML patients in combination with cytarabine, development was halted in part due to toxicity potentially related to the use of a flat dose, rather than patient-specific, body-surface area (BSA) dosing. Notable Labs provided an updated plan for the design of an open label Phase 2 study, including a dose optimization plan aimed at reducing toxicity while maintaining efficacy and an overview of study objectives and endpoints. As part of the study, a companion diagnostic assay to predict responders will be co-developed utilizing the Company’s proprietary flow-cytometry-based PPMP. Method: Ex vivo flow cytometry experiments evaluated the treatment of volasertib on 41 primary acute myeloid leukemia (AML) samples collected from peripheral blood or bone marrow. Dose-response profiles consistent with volasertib’s role as a cell cycle inhibitor were observed. To obtain a preliminary concentration of volasertib for patient stratification, Notable compared the ex vivo resistant blast fractions (leukemic cells surviving ex vivo treatment with volasertib) at several concentrations with the areas under the volasertib dose-response curves (AUCs), assuming that AUCs would correspond most accurately with the clinical responses. Results: The results suggest a strong correlation between volasertib resistant fractions treated with 31.6 and 100 nM of volasertib and AUCs, which could represent a suitable metric to stratify patients into responders and non-responders. These preliminary metrics predict that 32-33% of de novo patients and 25% of R/R AML patients would be predicted to be responders if they were treated with volasertib. Poster information: Session Category: Clinical Research Session Title: Predictive Biomarkers Session Date and Time: Tuesday Apr 9, 2024, 9:00 AM - 12:30 PM PT Location: Poster Section 45 Poster Board Number: 19 Published Abstract Number: 5178 The full poster will be posted to the company’s website in the Scientific Presentations & Publications page in the News section of the website shortly after the event. About Volasertib Volasertib is a PLK-1 inhibitor with demonstrated activity in AML and other tumor types, including solid tumors, with significant unmet medical need. Building on the performance of volasertib on PPMP, an important and proprietary step during Notable’s targeted in-licensing strategy and decision making, Notable will utilize PPMP to predict volasertib-responsive patients prior to their treatment, with the goal of selectively enrolling and treating those predicted responders, increasing volasertib’s response rates and overall patient outcomes, and fast-tracking volasertib’s remaining clinical development in this patient population. Volasertib was originally developed and manufactured by Boehringer Ingelheim and previously granted breakthrough therapy designation by the FDA. Notable in-licensed volasertib and obtained exclusive worldwide development and commercialization rights, except for certain rare pediatric cancers. About Notable Labs, Ltd. Notable Labs, Ltd. Is a clinical-stage platform therapeutics company developing predictive precision medicines for patients with cancer. Through its proprietary Predictive Precision Medicines Platform (PPMP), Notable aims to predict whether or not a patient is likely to respond to a specific therapeutic. The PPMP is designed to identify and select clinically responsive patients prior to their treatment, potentially fast-tracking clinical development. By continually advancing and expanding the reach of the PPMP across diseases and predicted medical outcomes, Notable aims to be the leader in predictive precision medicine and revolutionize the way patients seek and receive treatments that work best for them. Notable believes it has created a targeted and de-risked in-licensing strategy to deliver a product’s medical impact and commercial value faster, with a greater likelihood of success, than traditional drug development. By transforming historical standards of care, Notable aims to create a dramatically positive impact for patients and the healthcare community. Notable is headquartered in Foster City, California. Learn more at our website and follow us @notablelabs. Forward Looking Statements This press release contains “forward-looking statements” within the meaning of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, including but not limited to, express or implied statements regarding Notable’s future operations and goals; the potential benefits of any therapeutic candidates or platform technologies of Notable; the timing of any clinical milestones of Notable’s therapeutic candidates; the cash runway of the company; and other statements that are not historical fact. All statements other than statements of historical fact contained in this communication are forward-looking statements. These forward-looking statements are made as of the date they were first issued, and are based on the then-current expectations, estimates, forecasts, and projections, as well as the beliefs and assumptions of management. Forward-looking statements are subject to a number of risks and uncertainties, many of which involve factors or circumstances that are beyond Notable’s control. Notable’s actual results could differ materially from those stated or implied in forward-looking statements due to a number of factors, including but not limited to (i) uncertainties associated with Notable’s platform technologies, as well as risks associated with the clinical development and regulatory approval of product candidates, including potential delays in the commencement, enrollment and completion of clinical trials; (ii) risks related to the inability of Notable to obtain sufficient additional capital to continue to advance these product candidates and any preclinical programs; (iii) uncertainties in obtaining successful clinical results for product candidates and unexpected costs that may result therefrom; (iv) risks related to the failure to realize any value from product candidates and preclinical programs being developed and anticipated to be developed in light of inherent risks and difficulties involved in successfully bringing product candidates to market; (v) risks associated with Notable’s future financial and operating results, including its ability to become profitable; (vi) Notable’s ability to retain key personnel; (vii) Notable’s ability to manage the requirements of being a public company; (viii) uncertainties relating to the Israel-Hamas war; (ix) Notable’s ability to obtain orphan drug designation, and the associated benefits, for any of its drug candidates; (x) Notable’s inability to obtain regulatory approval for any of its drug candidates; and (xi) changes in, or additions to international, federal, state or local legislative requirements, such as changes in or additions to tax laws or rates, pharmaceutical regulations, and other regulations. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties. These and other risks and uncertainties are more fully described in periodic filings with the U.S. Securities and Exchange Commission (“SEC”), including the factors described in the section titled “Risk Factors” in the Quarterly Report on Form 10-Q of Notable Labs, Ltd. as filed with the SEC on November 14, 2023, and in other subsequent filings with the SEC. You should not place undue reliance on these forward-looking statements, which are made only as of the date hereof or as of the dates indicated in the forward-looking statements. Notable expressly disclaims any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in its expectations with regard thereto or any change in events, conditions or circumstances on which any such statements are based. CONTACTS Investor Relations: Daniel Ferry, LifeSci Advisors +1 (617) 430-7576 daniel@lifesciadvisors.com

临床2期突破性疗法AACR会议

100 项与伏拉色替相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D10182	伏拉色替	-	DB12062

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
急性髓性白血病	临床3期	比利时	Boehringer Ingelheim GmbH	2013-01-29
急性髓性白血病	临床3期	加拿大	Boehringer Ingelheim GmbH	2013-01-29
急性髓性白血病	临床3期	意大利	Boehringer Ingelheim GmbH	2013-01-29
急性髓性白血病	临床3期	墨西哥	Boehringer Ingelheim GmbH	2013-01-29
急性髓性白血病	临床3期	葡萄牙	Boehringer Ingelheim GmbH	2013-01-29
急性髓性白血病	临床3期	美国	Boehringer Ingelheim GmbH	2013-01-29
急性髓性白血病	临床3期	挪威	Boehringer Ingelheim GmbH	2013-01-29
急性髓性白血病	药物发现	中国台湾	Boehringer Ingelheim GmbH	2013-01-29
急性髓性白血病	药物发现	-	Boehringer Ingelheim GmbH	2013-01-29
急性髓性白血病	药物发现	巴西	Boehringer Ingelheim GmbH	2013-01-29

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT01121406 (Pubmed \| J Urol) 人工标引	临床2期	卵巢癌三线	109	Volasertib	(構製範積壓鹽襯網鏇製) = 蓋積鏇鏇壓繭鑰衊醖顧範遞獵醖簾膚範壓鬱願 (鹹窪繭夢餘願簾獵壓窪, 18.0 ~ 43.2) 更多	积极	2016-03-01
				Chemotherapy	(構製範積壓鹽襯網鏇製) = 簾窪糧積糧蓋觸範築鹽範遞獵醖簾膚範壓鬱願 (鹹窪繭夢餘願簾獵壓窪, 29.6 ~ 56.7) 更多
NCT01721876 (Pubmed) 人工标引	临床3期	急性髓性白血病	666	cytarabine+Volasertib	(餘膚膚網餘蓋齋艱築糧) = 獵積醖築簾廠繭齋淵艱顧鹹獵夢網蓋衊醖願繭 (齋選遞艱顧鏇築醖願網 ) 更多	不佳	2021-08-02
				cytarabine+Placebo	(餘膚膚網餘蓋齋艱築糧) = 鏇齋艱窪觸鬱艱衊艱窪顧鹹獵夢網蓋衊醖願繭 (齋選遞艱顧鏇築醖願網 ) 更多
NCT00824408 (WCLC2013)	临床2期	非小细胞肺癌二线	131	Volasertib monotherapy	(鹹憲夢鬱範觸鏇餘積觸) = 願鏇積積壓製遞遞鏇築廠醖鏇繭觸鹹鬱簾獵衊 (顧構鏇糧築憲廠壓壓鬱 ) 更多	不佳	2013-10-30
				Volasertib + Pemetrexed	(鹹憲夢鬱範觸鏇餘積觸) = 築範選網憲構築淵醖顧廠醖鏇繭觸鹹鬱簾獵衊 (顧構鏇糧築憲廠壓壓鬱 ) 更多
NCT00804856 (Pubmed \| Circulation)	临床2期	急性髓性白血病	180	Low-dose cytarabine	簾艱鬱餘壓鬱積鏇鑰鑰(淵獵醖襯蓋膚鹹衊壓範) = LDAC + volasertib led to an increased frequency of adverse events that was most pronounced for neutropenic fever/infections and gastrointestinal events 齋襯淵製選築鑰鑰淵膚 (廠艱鑰鹽積憲齋憲鹹網 ) 更多	-	2014-08-28
				Low-dose cytarabine + volasertib
NCT01022853 (Pubmed \| Ann Oncol) 人工标引	临床1期	HR阳性/HER2低表达实体瘤	30	Volasertib+Nintedanib	(繭艱蓋繭築夢夢構齋衊) = 2 pts treated with the MTD experienced grade 3 increased ALT (both) and AST 夢構膚鏇淵網鹽齋觸鬱 (艱膚鹽願築襯顧鏇淵簾 ) 更多	积极	2015-11-01
NCT00824408 (Pubmed \| Clin Lung Cancer)	临床2期	非小细胞肺癌二线	143	Volasertib monotherapy	(廠築簾鏇鏇鏇鹹膚鏇範) = 14 [31%]/13 [28%]/2 [6%] 範廠顧鹹鑰鏇夢製鹹蓋 (蓋壓鬱壓鏇窪壓遞齋衊 ) 更多	不佳	2015-11-01
				Volasertib with pemetrexed
NCT01022853 (ASCO2013)	临床1期	HR阳性/HER2低表达实体瘤	30	Volasertib	衊衊壓網窪鹽顧齋餘鑰(遞構襯繭遞膚醖鏇繭襯) = 繭夢鹹衊窪觸範窪壓艱築選遞窪獵獵憲艱鏇鹹 (鹹築構窪廠構鹽顧鏇築 ) 更多	-	2013-05-20
				Nintedanib	(製鑰夢鹹蓋夢鏇獵膚餘) = 願窪築齋鏇觸積蓋齋築壓齋鬱餘觸醖築鹹鏇願 (積範艱範範製憲範憲廠 ) 更多
NCT01121406 (ASCO2013)	临床2期	铂耐药性卵巢癌	109	Volasertib 300 mg IV	淵願鑰顧觸觸獵築壓鬱(艱衊繭製顧遞夢鹹壓網) = 膚鹹齋齋壓觸艱製觸齋蓋鑰膚膚廠選壓製繭膚 (築鹹壓鹹糧願製遞築廠, 18–43) 更多	-	2013-05-20
				Chemotherapy (pegylated liposomal doxorubicin, topotecan, paclitaxel, gemcitabine)	淵願鑰顧觸觸獵築壓鬱(艱衊繭製顧遞夢鹹壓網) = 範築鹽壓積簾襯廠顧憲蓋鑰膚膚廠選壓製繭膚 (築鹹壓鹹糧願製遞築廠, 30–57) 更多
NCT01206816 (Pubmed \| Cancer Chemother Pharmacol) 人工标引	临床1期	晚期恶性实体瘤	57	volasertib+afatinib (Schedule A)	(願餘鹹廠築齋夢齋糧獵) = The MTDs were volasertib 300 mg plus afatinib 30 mg days 2-21 and 70 mg days 2-6 of a 3-week cycle for Schedules A and B, respectively. 願淵膚鹹糧夢蓋遞淵獵 (築遞蓋積顧願鏇網觸襯 ) 更多	不佳	2015-10-01
				volasertib+afatinib (Schedule B)
NCT01348347 (Pubmed \| Invest New Drugs)	临床1期	HR阳性/HER2低表达实体瘤	15	Volasertib	(築繭鹽製獵糧膚鑰積繭) = 夢範範鹽鏇艱築齋齋鹽齋鹽獵顧網淵鹽淵簾襯 (顧顧遞餘築鬱鏇糧獵觸 ) 更多	-	2016-02-01