Last update 18 Dec 2024

Azacitidine

Last update 18 Dec 2024

Overview

R&D Status

Clinical Result

Translational Medicine

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

4-amino-1-beta-D-ribofuranosyl-s-triazin-2(1H)-one, 5-azacytidine, 5-AZC

+ [19]

Target

DNMT1

Mechanism

DNMT1 inhibitors(DNA (cytosine-5)-methyltransferase 1 inhibitors), DNA methylation inhibitors

Therapeutic Areas

NeoplasmsHemic and Lymphatic DiseasesOther Diseases+ [3]

Active Indication

Juvenile Myelomonocytic LeukemiaMyeloproliferative DisordersPhiladelphia chromosome positive chronic myelogenous leukemia+ [48]

Inactive Indication

Acute myeloid leukaemia with 11q23 abnormalityAcute Myeloid Leukemia with FLT3/ITD MutationAcute Promyelocytic Leukemia+ [59]

Originator Organization

Celgene Corp.

Active Organization

Bristol Myers Squibb Co.

Nippon Shinyaku Co., Ltd.

The University of Texas MD Anderson Cancer Center

+ [16]

Inactive Organization

Pfizer Inc.

Millennium Pharmaceuticals, Inc.Onyx Therapeutics, Inc.

+ [8]

Drug Highest PhaseApproved

First Approval Date

US (19 May 2004),

Myelodysplastic Syndromes

RegulationPriority Review (CN), Orphan Drug (JP), Orphan Drug (KR), Accelerated assessment (EU), Orphan Drug (US)

Structure

Molecular FormulaC8H12N4O5

InChIKeyNMUSYJAQQFHJEW-KVTDHHQDSA-N

CAS Registry320-67-2

801

Clinical Trials associated with Azacitidine

NCT06514261 / RecruitingPhase 1IIT

Phase 1 Trial of Iadademstat in Combination With Venetoclax and Azacitidine in Patients With Treatment Naive AML

This phase I trial tests safety, side effects and best dose of iadademstat with azacitidine and venetoclax for the treatment of patients with acute myeloid leukemia (AML) who have not receive treatment (treatment naive). Chemotherapy drugs, such as iadademstat and azacitidine work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Giving iadademstat with azacitidine and venetoclax may be safe and tolerable in treating patients with treatment naive AML.

Start Date15 Jul 2025

Sponsor / Collaborator

National Cancer Institute

ACTRN12624000738527 / Not yet recruitingPhase 2IIT

AMLM22/D4: The International AML Platform Consortium (IAPC) trial – is a randomised, 2-arm trial that will investigate the efficacy of oral Azacitidine combined with an allogeneic dendritic cell vaccine vididencel, compared with oral Azacitidine alone, in maintaining or inducing negativity for measurable residual disease (MRD) in AML patients in first complete remission (CR1) following intensive chemotherapy.

Start Date30 Jun 2025

Sponsor / Collaborator

The Australian Leukaemia & Lymphoma Group

[+1]

NCT06664879 / Not yet recruitingPhase 1/2IIT

ALLG AMLM26 INTERCEPT (Investigating Novel Therapy to Target Early Relapse and Clonal Evolution As Pre-emptive Therapy in AML): a Multi-arm, Precision-based, Recursive, Platform Trial

To demonstrate the efficacy of targeted and tailored sequential therapy in patients with AML.

Start Date01 Apr 2025

Sponsor / Collaborator

The University of Texas MD Anderson Cancer Center

[+1]

100 Clinical Results associated with Azacitidine

100 Translational Medicine associated with Azacitidine

100 Patents (Medical) associated with Azacitidine

6,246

Literatures (Medical) associated with Azacitidine

01 Dec 2025·CANCER CHEMOTHERAPY AND PHARMACOLOGY

Pharmacokinetic analysis of crushed venetoclax tablets combined with azacitizine for recurrent pediatric acute myeloid leukemia (AML)

Article

Author: Yasu, Takeo ; Yuza, Yuki ; Makimoto, Atsushi ; Matsui, Motohiro

BACKGROUND:

The efficacy of a combination therapy consisting of venetoclax (VEN) and azacytidine (AZA) for newly diagnosed acute myeloid leukemia (AML) has been confirmed in elderly patients. However, the clinical data on VEN for pediatric AML are limited. A combination therapy consisting of crushed VEN tablets and AZA (VEN/AZA) was administered to two children with recurrent AML. The pharmacokinetics of VEN were then analysed.

CASE PRESENTATION:

[Patient 1] A 1-year-old, male patient who experienced an AML relapse following an allogeneic hematopoietic stem cell transplantation received three courses of VEN/AZA. At the initial dosage of VEN (8 mg/kg), the minimum plasma concentration (C_min) was only 0.44 µg/ml, which was far less than the optimal C_min of 1.2 µg/ml. Subsequent dose-escalation to 10 mg/kg only achieved C_min 0.42 µg/ml. [Patient 2] A 3-year-old, female patient in whom infantile acute lymphoblastic leukemia was originally diagnosed experienced a recurrence in the form of AML after lineage-switching. Three courses of VEN/AZA were administered with the same therapeutic drug monitoring as in Case 1. The C_min of VEN was 0.15 µg/ml at 8 mg/kg. Afterwards, voriconazole 16 mg/kg/day was begun for a concomitant fungal infection together with VEN 2 mg/kg. This combination finally achieved C_min 1.14 µg/ml probably through CYP3A4 inhibition by voriconazole. In terms of safety, only grade 4 hematological adverse events were observed in both patients. In terms of efficacy, patient 1 and patient 2 achieved stable disease status for two months and six months, respectively.

CONCLUSION:

Pediatric patients may scarcely achieve effective plasma concentration of VEN when crushed tablets are used at the same dosage as in adults.

01 Mar 2025·ANALYTICAL BIOCHEMISTRY

Development and validation of a sensitive and fast bioanalytical LC-MS/MS assay for the quantitation of venetoclax and azacitidine in Rat Plasma: Application to pharmacokinetic study

Article

Author: Alsegiani, Amsha ; Alsarhani, Emad ; El-Azab, Adel ; Hefnawy, Mohamed ; Alnasser, Abdulaziz ; Abdel-Aziz, Alaa ; Attwa, Mohamed ; Alrubia, Sarah ; El-Gendy, Manal ; Jardan, Yousef Bin

The combination of venetoclax plus azacitidine (VTX-AZA) is FDA-approved to treat patients with acute myeloid leukemia (AML) aged ≥75 years and has become the standard of care for AML patients. However, the literature has not reported an analytical method for determining VTX-AZA in plasma samples. Therefore, developing an accurate and sensitive bioanalytical assay to quantify VTX-AZA in plasma is important. For the first time, this study describes the development of a new liquid chromatography-tandem mass spectrometry method (LC-MS/MS) for the simultaneous determination of VTX and AZC in plasma samples with its application to pharmacokinetic study in rats. The assay employs repaglinide (RPG) as an internal standard. The chromatographic separations of VTX, AZC, and RPG are achieved within 2.5 min at 25 °C on an Eclipse plus C18 column (100 mm × 2.1 mm, 1.8 μm) and an isocratic mobile phase consisted of water with 0.1 % formic acid and acetonitrile (50:50, v/v, pH 3.2) at a flow rate of 0.30 mL/min. VTX and AZC have been extracted from rat plasma using the solid-phase extraction (SPE) procedure without interference from plasma endogenous. The FDA guidelines were followed in the validation of the developed assay, and linearity in rat plasma was observed for AZC and VTX, respectively, ranging from 5 to 3000 and 5-1000 ng/mL, with r ≥ 0.998. The lower limits of detection (LLOD) were 2 ng/mL for both drugs. In addition, the inter-day and intra-day accuracy were 0.8-6.6 % and 2.2-5.7 %; the inter-day and intra-day precision were 3-6.6 % and 1.5-7.1 %, respectively. The validated assay was effectively used in a pharmacokinetic investigation including the simultaneous oral administration of 40 mg/kg of AZA and 100 mg/kg of VTX to rats. The maximum plasma concentration (C_max) for AZC and VTX was 794 ± 99.6 ng/mL and 641 ± 96.9 ng/mL achieved at 0.5 ± 0.03 h and 6 ± 0.05 h, respectively. The AUC_0-∞ for AZC and VTX was 1253 ± 252.6 and 4881 ± 745.4 ng/mL.h; respectively.

01 Jan 2025·NEW PHYTOLOGIST

Binding of PtoRAP2.12 to demethylated and accessible chromatin regions in the PtoGntK promoter stimulates growth of poplar

Article

Author: Xiao, Liang ; Du, Qingzhang ; Zhang, Deqiang ; Zhou, Jiaxuan ; Lv, Chenfei ; Zhang, Donghai ; He, Yuling ; Quan, Mingyang ; Zhong, Leishi ; Li, Peng ; Zhang, Jinhan ; Wang, Dan

Summary:

DNA methylation is an essential epigenetic modification for gene regulation in plant growth and development. However, the precise mechanisms of DNA methylation remain poorly understood, especially in woody plants.We employed whole‐genome bisulfite sequencing (WGBS), assays for transposase‐accessible chromatin using sequencing (ATAC‐seq), and RNA‐Seq to investigate epigenetic regulatory relationships in Populus tomentosa treated with DNA methylation inhibitor 5‐azacitidine. Expression‐quantitative trait methylation analysis (eQTM), epigenome‐wide association study (EWAS), and joint linkage‐linkage disequilibrium mapping were used to explore the epigenetic regulatory genes, and using CRISPR/Cas9 to identify the role of candidate genes.Plant developmental abnormalities occurred when DNA methylation levels were substantially reduced. DNA methylation regulated 112 expressed genes via chromatin accessibility, of which 61 genes were significantly influenced by DNA methylation variation at the population level. One DNA methylation‐regulated gene, PtoGntK, was located in a major quantitative trait locus (QTL) for poplar growth. Overexpression and CRISPR/Cas9 of PtoGntK revealed it affected poplar height and stem diameter. The PtoRAP2.12 was found to bind to the demethylated accessible region in the PtoGntK promoter, thereby promoting growth in poplar.This study identified key genes with epigenetic regulation for plant growth and provides insights into epigenetic regulation mechanisms in woody plants.

639

News (Medical) associated with Azacitidine

17 Dec 2024

·www.globenewswire.com

AB Science provides a summary of the webcast held on December 16, 2024

PRESS RELEASE AB SCIENCE PROVIDES AN UPDATE ON AB8939, A NOVEL MICROTUBULE DESTABILIZER ESCAPING MULTIDRUG RESISTANCE AND STEM CELL TARGETED ALDH INHIBITOR, CURRENTLY IN PHASE 1 Paris, 17 December 2024, 7pm CET AB Science SA (Euronext - FR0010557264 - AB) today provides an update on its AB8939 program in acute myeloid leukemia (AML). The webcast presentation is available on the company’s website, in the section « Press Releases »: https://www.ab-science.com/news-and-media/press-releases/ Highlights of the presentation are the following: AB8939 target product profile AB8939 is a next generation synthetic microtubule destabilizer and stem cell targeted ALDH1/2 inhibitor with key differentiating factors for treatment of refractory/relapsing acute myeloid leukemia (AML). AB8939 blocks proliferating leukemia cells through microtubules AB8939 destabilizes microtubule, is not subjected to multidrug resistance as it does not bind to PgP, responsible of efflux outside the cells and AB8939 is not degraded by the enzyme myeloperoxidase. AB8939 targets leukemia cancer stem cells though inhibition of ALDH AB8939 inhibits ALDH1/2 and favors the bone marrow repopulation of normal progenitors. AB8939 is well suited for the treatment of relapsed or refractory AML AB8939 has activity seen across refractory AML cell lines, has an additive effect with referenced first line treatment for AML, namely cytarabine, azacitidine and venetoclax. AB8939 has a potential use in AML with MECOM AB8939 has shown a signal of efficacy in AML with MECOM gene rearrangement, a subset of patients that show extreme resistance to chemotherapies and exhibit the worst survival prognosis AB8939 shows absence of hematological toxicity based on clinical data Addressable market with AB8939 in relapsed/refractory AML Treatments in relapsed or refractory AML represent an estimated market size potential above EUR 2 billion per annum. Region Incidence Case(1) % Relapse or Refractory (2,3) % Insured Patients (4) Drug Price (€) Market Size(per in Mio EUR) USA / CANADA 23,700 50% 90% 100,000(5) 1 000 000 EUROPE 27,600 90% 60,000 770 000 APAC 27,800 30% 60,000 250 000 INDIA 11,000 30% 60,000 100,000 LATAM 7,200 30% 60,000 65 000 MENA 3,900 30% 60,000 35 000 TOTAL 90,200 2 200 000 EUROPE = EU27 + Norway + United Kingdom + Switzerland ; APAC = Australia, People’s Republic of China , Japan, New Zealand, Singapore, Taiwan ; LATAM = Argentina, Brazil, Chile, Colombia, Costa Rica, Mexico ; MENA = Algeria, Bahrain, Egypt, Israel, Kuwait, Morocco, Oman, Qatar, Saudi Arabia, Tunisia, United Arab Emirates(1) Zhou, Y et al. Global, regional, and national burden of acute myeloid leukemia, 1990–2021: a systematic analysis for the global burden of disease study 2021. Biomark Res 12, 101 (2024). (2) Ravandi F. Relapsed acute myeloid leukemia: Why is there no standard of care Best Pract Res Clin Haematol. 2013;26(3):253-9(3) Walter RB et al. Resistance prediction in AML: analysis of 4601 patients from MRC/NCRI, HOVON/SAKK, SWOG and MD Anderson Cancer Center. Leukemia (2015) 29:312–20. .(4) Estimated(5) Choi M. et al. Costs per patient achieving remission with venetoclax-based combinations in newly diagnosed patients with acute myeloid leukemia ineligible for intensive induction chemotherapy. Journal of Managed Care & Specialty Pharmacy Volume 28, Number 9. https://doi.org/10.18553/jmcp.2022.22021 Non clinical pharmacology Animal experiments have shown the following properties for AB8939 relevant for the treatment of AML: AB8939 is active against chemotherapy naive or chemotherapy refractory/relapsing patient’s AML cancers cells ex vivoAB8939 eradicates blasts in Blood and Bone Marrow in 5-AraC-resistant (Cytarabine) PDXAB8939 increases survival and has an additive effect in combination with reference treatment Azacitidine and VenetoclaxALDHs expression is a hallmark of cancer stem cells (CSCs) and AB8939 is an inhibitor of ALDH1/2. Therefore, AB8939 is a targeted therapy for leukemia cancer stem cells AB8939 eradicates Leukemia Cancer Stem Cells in a human PDX AML model Phase 1 preliminary safety The objective of the phase 1 is to determine the maximum tolerated dose (MTD) for three different cycles of AB8939. The first step of the phase 1 has been completed with 28 patients enrolled, evaluating the maximum tolerated dose after 3 consecutive days of AB8939 treatment. The second step of the phase 1 is close to completion and enrolled 10 patients, evaluating the maximum tolerated dose after 10 consecutive days of AB8939 treatment. The next step is to evaluate the maximum tolerated dose after 14 consecutive days of AB8939 treatment in combination with venetoclax or azacitidine and in combination with venetoclax plus azacitidine, both drugs being widely used on AML and for which AB8939 has shown an additive effect. Preliminary activity in MECOM MECOM is associated with a dismal outcome, with almost all patients dying within 12 months after relapse. AB8939 is a stem cell ALDH targeted therapy with potential use in AML with MECOM. ALDH gene expression is a marker of survival prognosis in AML. The higher the expression, the worse the prognosisMECOM is associated with the worst prognosis in AMLMECOM is a rearrangement or a mutation of the chromosome 3 locus Q26 that codes for the transcription factor gene EVI1 (Ecotropic virus integration site-1)The expression of ALDH1A1 is regulated by EVI1 and has an outstanding role in the formation and transformation of hematopoietic cells and in particular leukemia stem cellsThe hypothesis is that in MECOM, the rearrangement of chromosome 3 Q26 leads to EVI1 over-expressing ALDH1A and induces high resistance of leukemia stem cells, and AB8939 should have an impact on leukaemia stem cells by inhibiting ALDH1 AB8939 has shown activity on MECOM rearrangement, based on non-clinical data and early clinical data in relapsing/refractory line of treatment, with 50% response rate observed. Planned phases 2 The next steps in the clinical development will be discussed with FDA and EMA. The first intended step is to develop AB8939 in patients with MECOM AML, through a single arm study with less than 60 patients supporting an accelerated approval based on response rate. The second objective is to position AB8939 in broader forms of AML and position AB8939 in relapsed or refractory AML. The third objective is to capture the full market potential of AB8939 and position AB8939 in first line in combination with standard of care. Intellectual property AB8939 intellectual property rights in AML are secured until 2036 through a ‘composition of matter’ patent and potentially until 2044 in AML with chromosome abnormality, including MECOM, through a ‘second medical use’ patent. AB Science is the sole proprietary holder of AB8939 and its family of compounds. About AB ScienceFounded in 2001, AB Science is a pharmaceutical company specializing in the research, development and commercialization of protein kinase inhibitors (PKIs), a class of targeted proteins whose action are key in signaling pathways within cells. Our programs target only diseases with high unmet medical needs, often lethal with short term survival or rare or refractory to previous line of treatment. AB Science has developed a proprietary portfolio of molecules and the Company’s lead compound, masitinib, has already been registered for veterinary medicine and is developed in human medicine in oncology, neurological diseases, inflammatory diseases and viral diseases. The company is headquartered in Paris, France, and listed on Euronext Paris (ticker: AB). Further information is available on AB Science’s website: www.ab-science.com. Forward-looking Statements - AB ScienceThis press release contains forward-looking statements. These statements are not historical facts. These statements include projections and estimates as well as the assumptions on which they are based, statements based on projects, objectives, intentions and expectations regarding financial results, events, operations, future services, product development and their potential or future performance. These forward-looking statements can often be identified by the words "expect", "anticipate", "believe", "intend", "estimate" or "plan" as well as other similar terms. While AB Science believes these forward-looking statements are reasonable, investors are cautioned that these forward-looking statements are subject to numerous risks and uncertainties that are difficult to predict and generally beyond the control of AB Science and which may imply that results and actual events significantly differ from those expressed, induced or anticipated in the forward-looking information and statements. These risks and uncertainties include the uncertainties related to product development of the Company which may not be successful or to the marketing authorizations granted by competent authorities or, more generally, any factors that may affect marketing capacity of the products developed by AB Science, as well as those developed or identified in the public documents published by AB Science. AB Science disclaims any obligation or undertaking to update the forward-looking information and statements, subject to the applicable regulations, in particular articles 223-1 et seq. of the AMF General Regulations. For additional information, please contact: AB ScienceFinancial Communication & Media Relations investors@ab-science.com Attachment CP AB8939 Update 16122024 VENG VF

Phase 1Phase 2

17 Dec 2024

·www.prnewswire.com

Expert Systems Celebrates Milestone in Clinical Development of Lonitoclax, a Best-in-Class BCL-2 Inhibitor, Developed in Partnership with Lomond Therapeutics

ROCKVILLE, Md., Dec. 17, 2024 /PRNewswire/ -- Expert Systems, a leader in AI-powered drug discovery, proudly celebrates the promising clinical results of oral once-daily lonitoclax, a next-generation BCL-2 inhibitor developed in collaboration with Lomond Therapeutics. The results of the single ascending dose Phase 1 studies demonstrate important advantages of lonitoclax over venetoclax and venetoclax-like molecules for chronic lymphocytic leukemia (CLL), acute myeloid leukemia (AML), and potentially other oncology indications. Lonitoclax demonstrated no significant safety signals at exposures sufficient to achieve robust inhibition of BCL-2, as measured via ex vivo activation of caspase in primary CLL cells. Importantly, the co-administration of itraconazole—a potent CYP 3A4 inhibitor—did not significantly alter lonitoclax exposures. These results highlight a key differentiation from venetoclax and similar molecules, which require complex dose titration and ritonavir co-administration, and emphasize important advantages in safety, tolerability, and feasibility of outpatient treatment. "Lonitoclax's promising Phase 1 results highlight the strength of our AI-enabled platform in driving the development of next-generation therapies," said Bill Farley, Chief Business Officer at Expert Systems. "Our platform de-risks early-stage drug development by reducing time and costs while delivering data-driven insights to optimize safety and efficacy. We are proud to support Lomond Therapeutics in advancing this innovative BCL-2 inhibitor, which has the potential to transform the treatment landscape for CLL and AML patients." About Lonitoclax Lonitoclax is a next generation BCL-2 inhibitor that has demonstrated best-in-class molecular pharmacology with the highest selectivity against BCL2, a key pro-survival protein that is overexpressed in many cancers. To mitigate the hematologic and immune toxicities observed with venetoclax, lonitoclax was designed with a unique binding mode to improve selectivity for BCL-2 over BCL-XL. In addition, a shorter half-life and reduced P4503A4 inhibition properties were built into the molecule to mitigate tumor lysis syndrome and drug accumulation risk, respectively. Lonitoclax has demonstrated monotherapy activity in pre-clinical models, as well as synergistic activity when combined with azacitidine, FLT3 inhibitors, and menin inhibitors in AML xenograft models. Unlike venetoclax, lonitoclax had minimal immunosuppressive activity on B cells, CD8 T cells, and NK cells in preclinical models. About Expert Systems Expert Systems, Inc., an advanced accelerator platform, is equipped with a comprehensive, hybrid AI-based system that covers the entire spectrum of preclinical drug discovery and early development phases. This includes target identification, virtual screening, non-clinical and clinical pharmacology, chemical liability assessment, and toxicology. Utilizing a unique combination of proprietary and public databases, Expert Systems employs specialized software tools to evaluate the intellectual property landscape and construct a competitive drug intelligence strategy to de-risk candidate selection for rapid transition from in silico to first-in-human trials. Expert Systems has been pivotal in establishing Seed and Series A companies, organizing and managing over 30 research and development programs across various financial investors and strategic partners in North America, Europe, and Australia. To learn more visit Media Contact: Bill Farley CBO [email protected] SOURCE Expert Systems, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Phase 1Clinical Result

12 Dec 2024

·www.globenewswire.com

Aptose Announces Publication of Preclinical Data in AACR Journal Demonstrating Tuspetinib’s Unique Mechanism of Action and Synthetic Lethality on AML Cells When Combined with Venetoclax

Peer-reviewed publication details unique TUS mechanism of action TUS+VEN combination synthetic lethality overcomes resistance to VEN Tuspetinib prolongs survival in multiple AML models resistant to other drugs Findings suggest TUS will demonstrate broad antileukemic activity across AML patients TUS+VEN+AZA Triplet Frontline Therapy in Newly Diagnosed AML Patients Now Enrolling SAN DIEGO and TORONTO, Dec. 12, 2024 (GLOBE NEWSWIRE) -- Aptose Biosciences Inc. (“Aptose” or the “Company”) (NASDAQ: APTO, TSX: APS), a clinical-stage precision oncology company developing highly differentiated targeted agents to treat hematologic malignancies, today announced the publication of preclinical data for Aptose’s lead hematology compound tuspetinib (TUS) in Cancer Research Communications, a journal of the American Association for Cancer Research (AACR), available online now (link). The publication, entitled “Preclinical development of tuspetinib for the treatment of acute myeloid leukemia,” is the first preclinical profiling of tuspetinib, a well-tolerated, once daily, oral kinase inhibitor currently in clinical development for treatment of acute myeloid leukemia (AML). The publication defines TUS activities on select oncogenic signaling targets, demonstrates enhanced activity and safety of TUS when combined with other agents, and illustrates synthetic lethality when combined with venetoclax (VEN). Pharmacokinetic and toxicology studies revealed that TUS is readily absorbed and achieves plasma concentrations sufficient to inhibit the target kinases, it has a plasma half-life that supports once daily dosing, and it demonstrates a favorable safety profile. Aptose is now enrolling newly diagnosed AML patients in a Phase 1/2 clinical study to receive the tuspetinib + venetoclax + azacitidine (TUS+VEN+AZA) triplet combination (NCT03850574). Clinical studies in patients with relapsed or refractory AML receiving TUS single agent or the TUS+VEN combination have been completed. “The non-clinical findings presented in the publication suggest that TUS will demonstrate favorable safety and a breadth of antileukemic activity across AML patient populations with a diversity of adverse mutations, and the initial clinical data is bearing that out,” said William G. Rice, Chairman, President and Chief Executive Officer. “We are eager for the next set of data in our triplet combination trial of TUS+VEN+AZA.” Key findings: Tuspetinib inhibits a defined cluster of oncogenic signaling kinases operative in AML TUS inhibits SYK, JAK1/2, RSK2, mutant KIT, and wild type and mutant forms of FLT3TUS potently killed AML lines (GI50 = 1.3 to 5.2 nM) and Ba/F3 cells expressing wildtype (GI50 = 9.1 nM) or various mutant forms of FLT3 (GI50 = 2.5 – 56 nM)TUS dampens stroma-induced activation of FLT3-ITD signaling in AML cells TUS prolongs survival in multiple AML models Oral TUS markedly extended survival in subcutaneously and orthotopically inoculated xenograft models of FLT3 mutant human AML, was well tolerated, and delivered enhanced activity when combined with venetoclax or 5-azacytidine TUS combines effectively with other classes of agents to kill AML cells with mutations in RAS and other difficult-to-treat adverse mutationsTUS was 2.1-15-fold and a 4.5-13-fold more potent than gilteritinib at blocking fibrinogen and immunoglobulin-mediated activation of SYK in KG-1a cellsThe most notable observation was the marked and unexpected synthetic lethal vulnerability to venetoclax and two MCL1 inhibitors in the TUS-resistant cells About Aptose Aptose Biosciences is a clinical-stage biotechnology company committed to developing precision medicines addressing unmet medical needs in oncology, with an initial focus on hematology. The Company's small molecule cancer therapeutics pipeline includes products designed to provide single agent efficacy and to enhance the efficacy of other anti-cancer therapies and regimens without overlapping toxicities. The Company’s lead clinical-stage, oral kinase inhibitor tuspetinib (TUS) has demonstrated activity as a monotherapy and in combination therapy in patients with relapsed or refractory acute myeloid leukemia (AML) and is being developed as a frontline triplet therapy in newly diagnosed AML. For more information, please visit www.aptose.com. Forward Looking Statements This press release may contain forward-looking statements within the meaning of Canadian and U.S. securities laws, including, but not limited to, statements relating to the therapeutic potential of tuspetinib, its clinical development and safety profile, including that it combines effectively with other classes of agents and will demonstrate a favorable safety profile and a breadth of antileukemic activity across an AML patient population with a diversity of adverse mutations, as well as statements relating to the Company’s plans, objectives, expectations and intentions and other statements including words such as “continue”, “expect”, “intend”, “will”, “should”, “would”, “may”, and other similar expressions. Such statements reflect our current views with respect to future events and are subject to risks and uncertainties and are necessarily based upon a number of estimates and assumptions that, while considered reasonable by us are inherently subject to significant business, economic, competitive, political and social uncertainties and contingencies. Many factors could cause our actual results, performance or achievements to be materially different from any future results, performance or achievements described in this press release. Such factors could include, among others: our ability to obtain the capital required for research and operations and to continue as a going concern; the inherent risks in early stage drug development including demonstrating efficacy; development time/cost and the regulatory approval process; the progress of our clinical trials; our ability to find and enter into agreements with potential partners; our ability to attract and retain key personnel; changing market conditions; inability of new manufacturers to produce acceptable batches of GMP in sufficient quantities; unexpected manufacturing defects; and other risks detailed from time-to-time in our ongoing quarterly filings, annual information forms, annual reports and annual filings with Canadian securities regulators and the United States Securities and Exchange Commission. Should one or more of these risks or uncertainties materialize, or should the assumptions set out in the section entitled “Risk Factors” in our filings with Canadian securities regulators and the United States Securities and Exchange Commission underlying those forward-looking statements prove incorrect, actual results may vary materially from those described herein. These forward-looking statements are made as of the date of this press release and we do not intend, and do not assume any obligation, to update these forward-looking statements, except as required by law. We cannot assure you that such statements will prove to be accurate as actual results and future events could differ materially from those anticipated in such statements. Investors are cautioned that forward-looking statements are not guarantees of future performance and accordingly investors are cautioned not to put undue reliance on forward-looking statements due to the inherent uncertainty therein. For further information, please contact: Aptose Biosciences Inc.Susan PietropaoloCorporate Communications & Investor Relations201-923-2049spietropaolo@aptose.com

AACR

100 Deals associated with Azacitidine

External Link

KEGG	Wiki	ATC	Drug Bank
D03021	Azacitidine	L01BC07	DB00928

R&D Status

Approved

10 top approved records.

to view more data

Indication	Country/Location	Organization	Date
Juvenile Myelomonocytic Leukemia	US	Bristol Myers Squibb Co.	20 May 2022
Myeloproliferative Disorders	EU	betapharm Arzneimittel GmbH	24 Mar 2020
Myeloproliferative Disorders	IS	betapharm Arzneimittel GmbH	24 Mar 2020
Myeloproliferative Disorders	LI	betapharm Arzneimittel GmbH	24 Mar 2020
Myeloproliferative Disorders	NO	betapharm Arzneimittel GmbH	24 Mar 2020
Philadelphia chromosome positive chronic myelogenous leukemia	CN	Bristol-Myers Squibb Pharma EEIG	24 Apr 2017
High Risk Myelodysplastic Syndrome	AU	Celgene Pty Ltd.	30 Nov 2009
Acute Myeloid Leukemia	EU	Bristol-Myers Squibb Pharma EEIG	17 Dec 2008
Acute Myeloid Leukemia	IS	Bristol-Myers Squibb Pharma EEIG	17 Dec 2008
Acute Myeloid Leukemia	LI	Bristol-Myers Squibb Pharma EEIG	17 Dec 2008
Acute Myeloid Leukemia	NO	Bristol-Myers Squibb Pharma EEIG	17 Dec 2008
Chronic Myelomonocytic Leukemia	EU	Bristol-Myers Squibb Pharma EEIG	17 Dec 2008
Chronic Myelomonocytic Leukemia	IS	Bristol-Myers Squibb Pharma EEIG	17 Dec 2008
Chronic Myelomonocytic Leukemia	LI	Bristol-Myers Squibb Pharma EEIG	17 Dec 2008
Chronic Myelomonocytic Leukemia	NO	Bristol-Myers Squibb Pharma EEIG	17 Dec 2008
Myelodysplastic Syndromes	US	Bristol Myers Squibb Co.	19 May 2004

Developing

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Immunoblastic Lymphadenopathy	Phase 3	JP	Celgene Corp.	06 Nov 2018
Thrombocytopenia	Phase 3	US	Celgene Corp.	26 Apr 2013
Thrombocytopenia	Phase 3	AU	Celgene Corp.	26 Apr 2013
Thrombocytopenia	Phase 3	BE	Celgene Corp.	26 Apr 2013
Thrombocytopenia	Phase 3	BR	Celgene Corp.	26 Apr 2013
Thrombocytopenia	Phase 3	CA	Celgene Corp.	26 Apr 2013
Thrombocytopenia	Phase 3	CZ	Celgene Corp.	26 Apr 2013
Thrombocytopenia	Phase 3	DK	Celgene Corp.	26 Apr 2013
Thrombocytopenia	Phase 3	FI	Celgene Corp.	26 Apr 2013
Thrombocytopenia	Phase 3	FR	Celgene Corp.	26 Apr 2013

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ASH2024	Phase 3	Acute Myeloid Leukemia	70	Azacitidine+HAG regime	dhvmasjkau(zobcyggdoi) = lnpvidpdam dijfrgivxj (jsoevtlkmf ) View more	Positive	09 Dec 2024
ASH2024	Not Applicable	Relapsing acute myeloid leukemia	-	Venetoclax	cxnsnwxohe(ndlxlzkipl) = sosqchsjqr wqzlldwfen (wlcvjcyzgj, 6.2 - 16.0)	-	09 Dec 2024
735Phase 1b/2 Study (ASH2024)	Phase 1/2	Refractory acute myeloid leukemia TP53mutation	110	Magrolimab (Magro) + Azacitidine (AZA) + Venetoclax (VEN)	rpkomrbezm(dtbchsmlaf) = falipsbyva ctpjhgiucv (cbvnxeaooj, 7 - 13) View more	Positive	09 Dec 2024
ASH2024	Not Applicable	Myelodysplastic Syndromes	-	Azacitidine + Durvalumab	gxklxsbrbe(txukkpseag) = duxusgdovi omhvjzphpv (ukkuwtncib ) View more	-	09 Dec 2024
				Azacitidine	gxklxsbrbe(txukkpseag) = zxhbrsvvmb omhvjzphpv (ukkuwtncib ) View more
ASH2024	Not Applicable	Acute Myeloid Leukemia	-	Azacitidine + Venetoclax	ttmxhihyqh(fhjvfuohoh) = unqobpiwsk tnlwytzpde (yylbgcugnt ) View more	-	09 Dec 2024
NCT04501120 (APG2575AC101, ASH2024) Manual	Phase 1/2	Myelodysplastic Syndromes	49	Lisaftoclax Azacitidineazacitidine (R/R MDS)	eqyeihtxnp(ohxwsrkubt) = yqdzfymynd vciezskgcl (gixqdqwody ) View more	Positive	08 Dec 2024
				Lisaftoclax Azacitidineazacitidine (TN MDS)	bomphffmtl \| eqyeihtxnp(lcbciltydr) = offbsdwjbx afdkobcvhw (qboalafjht, 61.5 - 89.2) View more
NCT02719574 (ASH2024) Manual	Phase 1/2	IDH1 Mutation Acute Myeloid Leukemia IDH1 Mutation	67	Olutasidenib 150 mg + azacitidine	zlqdehvlzm(ofobmnnjbu) = gcahuufrid ifbzzbzpka (ttcugiijtt, 21 - 44) View more	Positive	08 Dec 2024
				Olutasidenib 150 mg + azacitidine (prior OLU exposure)	zlqdehvlzm(ofobmnnjbu) = axddgsirhv ifbzzbzpka (ttcugiijtt, 24 - 52) View more
ASH2024	Not Applicable	-	-	Ziftomenib 200 mg	eelsoiyjko(sycsdgtjbt) = qspdhcdkqe qypotwsora (twwupgmctu ) View more	-	08 Dec 2024
				Ziftomenib 400 mg	eelsoiyjko(sycsdgtjbt) = nlexolksku qypotwsora (twwupgmctu ) View more
ASH2024	Not Applicable	Acute Myeloid Leukemia	-	Venetoclax+Azacitidine+LDAC	oehxgmraid(muqdcqvotf) = All the 39 experience patients had anemia and thrombocytopenia, which controlled after therapy, without severe infection and bleeding complications poyiguipbh (deqmopptxe ) View more	-	08 Dec 2024
				Venetoclax+Azacitidine
ASH2024	Not Applicable	Acute Myeloid Leukemia	-	Venetoclax-Azacitidine	ihqugseqjj(tsrpvlfytp) = significantly lower in blasts from refractory patients syjgstfopb (nbhhuutkvp ) View more	-	08 Dec 2024
				Navitoclax

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