A Phase 1/1b Study of AOH1996 Alone or in Combination With the BCL-2 Inhibitor Venetoclax +/- Azacitidine in Patients With Relapsed/Refractory Acute Myeloid Leukemia

This phase I trial tests safety, side effects, and best dose of AOH1996 alone or in combination with venetoclax with or without azacitidine for the treatment of patients with acute myeloid leukemia (AML) that has come back after a period of improvement (relapsed) or AML that has not responded to previous treatment (refractory). AOH1996 is in a class of medications called PCNA inhibitors. It inhibits cancer growth and induces deoxyribonucleic acid (DNA) damage. This may help keep cancer cells from growing and damage cancer cell DNA. 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. Azacitidine is in a class of medications called demethylation agents. It works by helping the bone marrow to produce normal blood cells and by killing abnormal cells in the bone marrow. Giving AOH1996 alone or in combination with venetoclax with or without azacitidine may be safe, tolerable and/or effective in treating patients with AML.

Start Date16 Aug 2025

Sponsor / Collaborator

City of Hope National Medical Center

[+1]

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]

NCT05554419

/ Not yet recruitingPhase 2IIT

Eradicating Measurable Residual Disease in Patients With Acute Myeloid Leukemia (AML) Prior to StEm Cell Transplantation (ERASE): A MyeloMATCH Treatment Trial

This phase II MyeloMATCH treatment trial compares cytarabine versus (vs.) cytarabine and venetoclax vs. liposome-encapsulated daunorubicin-cytarabine and venetoclax vs. azacitidine and venetoclax for treating patients who have residual disease after treatment for acute myeloid leukemia (AML). Cytarabine is in a class of medications called antimetabolites. It works by slowing or stopping the growth of cancer cells in the body. 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. Liposome-encapsulated daunorubicin-cytarabine is a drug formulation that delivers daunorubicin and cytarabine in small spheres called liposomes, which may make the drugs safer or more effective. Azacitidine is a drug that interacts with DNA and leads to the activation of tumor suppressor genes, which are genes that help control cell growth. This study may help the study doctors find out if the different drug combinations are equally effective to the usual approach of cytarabine alone while requiring a shorter duration of treatment. To decide if they are better, the study doctors will be looking to see if the study drugs lead to a higher percentage of patients achieving a deeper remission compared to cytarabine alone.

Start Date01 Apr 2025

Sponsor / Collaborator

National Cancer Institute

100 Clinical Results associated with Azacitidine

100 Translational Medicine associated with Azacitidine

100 Patents (Medical) associated with Azacitidine

9,168

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 Apr 2025·Non-coding RNA Research

DNA methylation of long noncoding RNA cytochrome B in diabetic retinopathy

Article

Author: Kumar, Jay ; Malaviya, Pooja ; Kowluru, Renu A

Diabetic retinopathy, a microvascular complication of diabetes, is the leading cause of blindness in adults, but the molecular mechanism of its development remains unclear. Retinal mitochondrial DNA is damaged and hypermethylated, and mtDNA-encoded genes are downregulated. Expression of a long noncoding RNA (larger than 200 nucleotides, which does not translate into proteins), encoded by mtDNA, cytochrome B (LncCytB), is also downregulated. This study aims to investigate the role of DNA methylation in the downregulation of LncCytB in diabetic retinopathy. Human retinal endothelial cells, incubated in 5 mM (normal) or 20 mM (high) D-glucose, in the presence/absence of Azacytidine (a DNA methyl transferase inhibitor) were analyzed for LncCytB DNA methylation by immunoprecipitation and methylation specific PCR techniques, and LncCytB transcripts by strand-specific PCR and RNA-FISH. Mitochondrial genomic stability was evaluated by quantifying protective mtDNA nucleoids by SYBR green staining and by flow cytometry, and functional stability by oxygen consumption rate using Seahorse analyzer. Results were confirmed in an in vivo model using retina from diabetic rat. While high glucose elevated 5 mC and the ratio of methylated to unmethylated amplicons at LncCytB and downregulated its transcripts, azacytidine prevented LncCytB DNA hypermethylation and decrease in its expression. Azacytidine also ameliorated decrease in nucleoids and oxygen consumption rate. Similarly, azacytidine prevented increase in retinal LncCytB DNA methylation and decrease in its expression in diabetic rats. Thus, DNA hypermethylation plays a major role in the downregulation of retinal LncCytB in diabetes, resulting in impaired mitochondrial homeostasis, and culminating in the development of diabetic retinopathy.

01 Apr 2025·INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES

The strigolactones-mediated DNA demethylation activates the phosphoinositide pathway in response to salt stress

Article

Author: Li, Changxia ; Cui, Jing ; Li, Shaoxia ; Yu, Wenjin ; Lu, Xuefang ; Qi, Jin

Salt stress severely affects the growth and development of tomato. Strigolactones (SLs) and DNA methylation have been shown to be involved in the growth and development and response to salt stress in tomato. However, the regulation of SLs on DNA methylation in tomato under salt stress remains unclear. In this study, the interaction between SLs and DNA methylation inhibitors 5-azacytidine (5-azaC) alleviate salt stress damage by increasing the plant height, stem diameter, leaf area, and root length of tomato, as well as enhancing the biosynthesis of chlorophyll, carotenoid and flavonoid. The transcriptome and genome-wide methylation analysis between NaCl and NaCl + GR24 treatment show that plant-pathogen interaction, MAPK signaling pathway, plant hormone signal transduction and phosphatidylinositol signaling system may be means for SLs in response to salt stress. Among, SLs strikingly up-regulate the pivotal genes related to phosphatidylinositol signaling system, and reduce CHG methylation level in promoter and body region of these genes under salt stress, implying that SLs mediated-demethylation may promote gene expression. The determination results of relevant metabolites and gene expression levels in the phosphatidylinositol signaling system suggest that PIP₂, DAG, IP₃, and PA are raised by co-treatment of SLs and 5-azaC under salt stress relative to NaCl + 5-azaC treatment. The same response pattern is also presented in the SlPLC2, SlNPC1, SlPLD-Z, SlPLD-B, SlDGK1, SlDGK5, SlDGK7 and SlPIP5K9 genes. These results strongly indicate that phosphatidylinositol signaling system response to salt stress is related to the SLs mediated-demethylation, and provide a potential means for defenses salt stress in tomato.

658

News (Medical) associated with Azacitidine

14 Feb 2025

·aptevotherapeutics.gcs-web.com

Aptevo Therapeutics Reports 2024 Financial Results And Provides A Business Update

100% of Patients Achieved Remission Within 30 Days in Cohort 1 of the Mipletamig RAINIER Dose Optimization Trial for Frontline AML Patients, Trial Enrollment Continues Promising Data, including a 59% Stable Disease Rate, in ALG.APV-527 Phase 1 Trial for the Treatment of Multiple Solid Tumors Makes the Case for Continued Development of First-in-Class Anti-Cancer Agent SEATTLE, WA / ACCESS Newswire / February 14, 2025 / Aptevo Therapeutics Inc. (Nasdaq:APVO), a clinical-stage biotechnology company focused on developing novel immune-oncology therapeutics based on its proprietary ADAPTIR® and ADAPTIR-FLEX® platform technologies, today reported financial results for the year ended December 31, 2024 and provided a business update. Business Update "2024 was a successful year for Aptevo, as we've demonstrated the power of our science and our commitment to advancing oncology care. From the remarkable progress of mipletamig in AML, where 100% of patients in Cohort 1 of the RAINIER study achieved remission within 30 days, to the positive Phase 1 outcomes for ALG.APV-527 in solid tumors, we are delivering on the promise of our bispecifics to transform patient outcomes. These achievements are not just milestones-they're a testament to the ingenuity, dedication, and passion of our team. With every success, we are reinforcing Aptevo's position as a leader in the development of bispecific anti-cancer agents," said Marvin White, President and CEO of Aptevo. " The bottom line is that armed with the data and momentum of 2024, Aptevo is well poised for growth in 2025." Mipletamig AML bispecific highlights: Launched RAINIER, a dose optimization trial evaluating mipletamig in combination with venetoclax and azacitidine, the standard of care in frontline acute myeloid leukemia (AML) patients who are unfit to receive intensive high dose chemotherapy. RAINIER results reported to date include: 100% of patients in Cohort 1 of the trial achieved remission within 30 days One patient experienced complete remission with minimal residual disease (MRD)-negative status (100% elimination of cancer cells) Favorable safety profile consistent with prior trials, showing limited incidences of cytokine release syndrome (CRS), a common and often dose limiting side effect seen in similar therapies These results build on data from prior results, including: Phase 1b dose expansion combination therapy trial in which 100% of frontline patients also achieved remission (Remission = complete remission (CR) and, complete remission with blood markers that have not yet recovered (CRi)) Phase 1a dose escalation monotherapy trial in which 36% of evaluable patients experienced substantial leukemic blast reduction to a clinical meaningful degree compared to baseline (range of 17% to 88% reduction), providing evidence of the pharmacodynamic effect of the drug The Company anticipates providing multiple data readouts in 2025 and to present results at the American Society of Hematology meeting in the fourth quarter. ALG.APV-527 solid tumor bispecific highlights: Completed a readout from our ALG.APV-527 Phase 1 dose escalation study evaluating the drug for the treatment of multiple solid tumor types likely to express tumor antigen 5T4. ALG.APV-527 is being developed in partnership with Alligator Bioscience. Key trial data:10 of 17 efficacy evaluable patients (59%) achieved stable disease The longest duration of stable disease was in a breast cancer patient who entered the study with progressive disease, achieved stable disease and remained on study for >12 months. This patient successfully transitioned to a higher dose level twice One colon cancer patient achieved stable disease for more than six months One prostate cancer patient has been on study for at least four months and remains in stable disease Safety results include limited incidence, and no severe cases of liver toxicity, a common and often dose limiting side effect seen in similar treatments The data was presented at both the European Society for Medical Oncology Congress and the Society for Immunotherapy of Cancer Conference in 2024 10 of 17 efficacy evaluable patients (59%) achieved stable disease The longest duration of stable disease was in a breast cancer patient who entered the study with progressive disease, achieved stable disease and remained on study for >12 months. This patient successfully transitioned to a higher dose level twice One colon cancer patient achieved stable disease for more than six months One prostate cancer patient has been on study for at least four months and remains in stable disease "We are thrilled with the Cohort 1 RAINIER trial results that, taken together with data from our previously completed trials, demonstrate mipletamig's potential as a transformative therapy for the treatment of frontline AML in combination with standard of care venetoclax and azacitidine. Seeing all Cohort 1 patients achieve remission within 30 days, including a patient that reached MRD-negative status, is a testament to the strength of our science and commitment to addressing this devastating disease. These outcomes build on favorable data from our earlier trials, including monotherapy results where 36% of evaluable patients experienced substantial leukemic blast reduction to a clinically meaningful degree in a single agent setting, demonstrating clinical impact for patients. Together, these results reinforce our mission to develop innovative, life-changing treatments for patients in need," said Dirk Huebner, MD, Chief Medical Officer at Aptevo. "We are also pleased with the progress of the ALG.APV-527 clinical program. Of note, ALG.APV-527 treatment was not associated with serious liver toxicities, which can be treatment limiting and are commonly seen in similar drugs. We believe this safety feature could provide significant differentiation among competitors.We also believe this drug has the potential to impact patients in large patient populations that are significantly underserved by available treatment options." About Mipletamig and RAINIER Aptevo's wholly owned lead proprietary drug candidate, mipletamig, targeting AML, MDS and other leukemias, is differentiated by design to redirect the immune system of the patient to destroy leukemic cells and leukemic stem cells expressing the target antigen CD123, which is a compelling target for AML due to its overexpression on leukemic stem cells and AML blasts. This antibody-like recombinant protein therapeutic is designed to engage both leukemic cells and T cells of the immune system and bring them closely together to trigger the destruction of leukemic cells. Mipletamig is purposefully designed to reduce the likelihood and severity of CRS by use of a unique CD3 binding domain derived from CRIS-7 vs. the CD3 binding domain used by competitors (which is derived from SP34). Mipletamig has received orphan drug designation ("orphan status") for AML according to the Orphan Drug Act. Mipletamig has been evaluated in over 100 patients to date. RAINIER, Aptevo's Phase 1b/2 frontline AML program, was initiated in 3Q24 and is ongoing. RAINIER, a frontline AML study, is a two part Phase 1b/2 trial. Part one is an ongoing dose optimization, multi-center, multi-cohort, open label study of up to 39 patients who are being treated across five dose levels ranging from 9 mcg - 140 mcg in combination with venetoclax and azacitidine Subjects will be adults aged 18 or older, newly diagnosed with AML who are not eligible for intensive induction chemotherapy. Phase 1b consists of 28-day cycles of treatment in five sequential cohorts. RAINIER will be conducted in two parts. First, a Phase 1b dose optimization study in frontline AML patients followed by a Phase 2 study. About ALG.APV-527 and The Phase 1 Dose Escalation Trial ALG.APV-527 is a bispecific conditional 4-1BB agonist, only active upon simultaneous binding to 4-1BB and 5T4. This has the potential to be clinically important because 4-1BB can stimulate the immune cells (antitumor-specific T cells and NK cells) involved in tumor control, making 4-1BB a particularly compelling target for cancer immunotherapy. 5T4 is an oncofetal tumor associated antigen overexpressed on numerous solid tumors including non-small-cell lung carcinoma (NSCLC), breast, head and neck, cervical, renal, gastric, and colorectal cancer. The ALG.APV-527 Phase 1 trial was a multi-center, multi-cohort, open-label dose-escalation trial that involved the administration of ALG.APV-527 in up to six escalating dose levels. The trial enrolled adult patients with multiple solid tumor types/histologies likely to express the 5T4 antigen. ALG.APV-527 will be given intravenously once every two weeks. The trial is assessing the safety and tolerability, pharmacokinetics, pharmacodynamics and preliminary anti-tumor activity of ALG.APV-527. 2024 Summary Financial Results Cash Position: Aptevo had cash and cash equivalents as of December 31, 2024, totaling $8.7 million. Research and Development Expenses: Research and development expenses decreased by $2.7 million, from $17.1 million for the year ended December 31, 2023 to $14.4 million for the year ended December 31, 2024. The decrease was primarily due to lower preclinical spending and lower mipletamig trial costs as we concluded our Phase 1b dose expansion study and initiated the Phase 1b/2 dose optimization study in Q3 of 2024. General and Administrative Expenses: General and administrative expenses decreased by $1.6 million, from $11.8 million for the year ended December 31, 2023 to $10.2 million for the year ended December 31, 2024. The decrease is primarily due to lower employee and consulting costs. Other Income (Expense) Net: Other Income from Continuing Operations, Net consists of other income, net of $0.5 million for the year ended December 31, 2024 and other income, net of $0.6 million for the year ended December 31, 2023. The change was primarily due to lower interest income from our money market funds. Gain Related to Sale of Non-FinancialAsset consists of a $9.7 million gain recorded in 2023 related to the sale of all of the deferred payments and a portion of the milestone payments from Medexus to XOMA. Discontinued Operations: Income from discontinued operations was $1.2 million for the year ended December 31, 2023, which related to contingent gain consideration from previous discontinued operations. Net Income (Loss): Aptevo had a net loss of $24.1 million or $87.38 per share for the year ended December 31, 2024, compared to a net loss of $17.4 million or $2,316.83 per share for the corresponding period in 2023. Aptevo Therapeutics Inc. CONSOLIDATED BALANCE SHEETS (in thousands, except share and per share amounts) Aptevo Therapeutics Inc. CONSOLIDATED STATEMENTS OF OPERATIONS (in thousands, except share and per share amounts) About Aptevo Therapeutics Aptevo Therapeutics Inc. (Nasdaq:APVO) is a clinical-stage biotechnology company focused on developing novel bispecific immunotherapies for the treatment of cancer. The Company has two clinical candidates. Mipletamig is currently being evaluated in RAINIER, a two part Phase 1b/2 trial for the treatment of frontline acute myeloid leukemia in combination with standard-of-care venetoclax + azacitidine. Mipletamig has received orphan drug designation ("orphan status") for AML according to the Orphan Drug Act. ALG.APV-527, a bispecific conditional 4-1BB agonist, only active upon simultaneous binding to 4-1BB and 5T4, is being co-developed with Alligator Bioscience and is being evaluated in a Phase 1 clinical trial for the treatment of multiple solid tumor types likely to express 5T4. The Company has three pre-clinical candidates with different mechanisms of action designed to target a range of solid tumors. All pipeline candidates were created from two proprietary platforms, ADAPTIR®and ADAPTIR-FLEX®. The Aptevo mission is to improve treatment outcomes and transform the lives of cancer patients. For more information, please visit www.aptevotherapeutics.com . Safe Harbor Statement This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements, other than statements of historical fact, including, without limitation, Aptevo's expectations about the activity, efficacy, safety, tolerability and durability of its therapeutic candidates and potential use of any such candidates, including in combination with other drugs, as therapeutics for treatment of disease, its expectations regarding the effectiveness of its ADAPTIR and ADAPTIR-FLEX platforms, statements related to the progress of Aptevo's clinical programs, including statements related to anticipated clinical and regulatory milestones, whether further study of mipletamig in a Phase 1b dose optimization trial focusing on multiple doses of mipletamig in combination with venetoclax + azacitidine on a targeted patient population will continue to show remissions, let alone at a rate of 100%, whether Aptevo's final trial results will vary from its earlier assessment, whether Aptevo's strategy will translate into an improved overall survival in AML, especially among patient subgroups with poor prognosis, whether further study of ALG.APV-527 across multiple tumor types will continue to show clinical benefit, the possibility and timing of interim data readouts for ALG.APV-527, statements related to Aptevo's cash position and balance sheet, statements related to Aptevo's ability to generate stockholder value, whether Aptevo will continue to have momentum in its business in the future, and any other statements containing the words "may," "continue to," "believes," "knows," "expects," "optimism," "potential," "designed," "promising," "plans," "will" and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based on Aptevo's current intentions, beliefs, and expectations regarding future events. Aptevo cannot guarantee that any forward-looking statement will be accurate. Investors should realize that if underlying assumptions prove inaccurate or unknown risks or uncertainties materialize, actual results could differ materially from Aptevo's expectations. Investors are, therefore, cautioned not to place undue reliance on any forward-looking statement. There are several important factors that could cause Aptevo's actual results to differ materially from those indicated by such forward-looking statements, including a deterioration in Aptevo's business or prospects; further assessment of preliminary or interim data or different results from later clinical trials; adverse events and unanticipated problems, adverse developments in clinical development, including unexpected safety issues observed during a clinical trial; and changes in regulatory, social, macroeconomic and political conditions. For instance, actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including the uncertainties inherent in the results of preliminary or interim data and preclinical studies being predictive of the results of later-stage clinical trials, initiation, enrollment and maintenance of patients, and the completion of clinical trials, the availability and timing of data from ongoing clinical trials, the trial design includes combination therapies that may make it difficult to accurately ascertain the benefits of mipletamig, expectations for the timing and steps required in the regulatory review process, expectations for regulatory approvals, the impact of competitive products, our ability to enter into agreements with strategic partners or raise funds on acceptable terms or at all and other matters that could affect the availability or commercial potential of Aptevo's product candidates, business or economic disruptions due to catastrophes or other events, including natural disasters or public health crises such as the coronavirus (referred to as COVID-19), geopolitical risks, including the current war between Russia and Ukraine and the war between Israel and Hamas, and macroeconomic conditions such as economic uncertainty, rising inflation and interest rates, continued market volatility and decreased consumer confidence. These risks are not exhaustive, Aptevo faces known and unknown risks. Additional risks and factors that may affect results are set forth in Aptevo's filings with the Securities and Exchange Commission, including its Annual Report on Form 10-K for the fiscal year ended December 31, 2024, and its subsequent reports on Form 10-Q and current reports on Form 8-K. The foregoing sets forth many, but not all, of the factors that could cause actual results to differ from Aptevo's expectations in any forward-looking statement. Any forward-looking statement speaks only as of the date of this press release, and, except as required by law, Aptevo does not assume any obligation to update any forward-looking statement to reflect new information, events, or circumstances. CONTACT: Miriam Weber Miller Head, Investor Relations & Corporate Communications Aptevo Therapeutics Email: [email protected] or [email protected] Phone: 206-859-6628 SOURCE: Aptevo Therapeutics

Clinical ResultPhase 1ASHFinancial StatementOrphan Drug

12 Feb 2025

·www.aptose.com

Aptose’s Frontline Triple Drug Therapy with Tuspetinib Achieves Notable Responses in Newly Diagnosed AML Patients in the Phase 1/2 TUSCANY Trial

TUS+VEN+AZA triplet achieves Cycle 1 complete remission (CR) in TP53-mutated/CK AML TUS+VEN+AZA triplet achieves Cycle 1 complete remissions in FLT3-wildtype AML patients TUS+VEN+AZA triplet shows favorable safety with no alteration of VEN and AZA dosing PK levels of TUS in the triplet remain equivalent to levels as TUS or TUS+VEN therapy SAN DIEGO and TORONTO, Feb. 12, 2025 (GLOBE NEWSWIRE) -- Aptose Biosciences Inc. (“Aptose” or the “Company”) (NASDAQ: APTO, TSX: APS), a clinical-stage precision oncology company, today reported promising early safety and response results from newly diagnosed acute myeloid leukemia (AML) patients dosed in Aptose’s Phase 1/2 TUSCANY trial with a 40 mg dose of tuspetinib in combination with standard of care dosing of venetoclax and azacitidine (TUS+VEN+AZA triplet). The TUS+VEN+AZA triplet is being developed as a frontline therapy to treat large, mutationally diverse populations of newly diagnosed AML patients who are ineligible to receive induction chemotherapy. In January 2025, Aptose announced the initiation of the TUSCANY trial and dosing in the first cohort of newly-diagnosed AML patients with the lowest starting dose (40 mg) of TUS as part of the TUS+VEN+AZA triplet, and the early data reveal promising clinical safety and antileukemic activity. To date, four newly diagnosed AML patients have received the lowest dose of TUS (40 mg) as part of the (TUS+VEN+AZA) combination. Three patients with unmutated (wildtype) FLT3 (FLT3-WT) completed Cycle 1 of treatment with no dose-limiting toxicities (DLTs) and no dose adjustments. Two FLT3-WT patients achieved complete remissions (CR and CRh) by the end of Cycle 1. Notably, a patient with biallelic TP53 mutations and a complex karyotype obtained CR. The third FLT3-WT patient experienced significant reductions in bone marrow leukemic blasts during Cycle 1 and remains on therapy in Cycle 2. The fourth patient, harboring FLT3-ITD and NPM1 mutations, is currently dosing in Cycle 1 and is not yet eligible for response evaluation Pharmacokinetic (PK) analyses for TUS show plasma levels unaffected by the addition of AZA, providing predictability and avoiding the need for dose alterations due to PK interactions. Two FLT3-WT patients achieved complete remissions (CR and CRh) by the end of Cycle 1. Notably, a patient with biallelic TP53 mutations and a complex karyotype obtained CR. The third FLT3-WT patient experienced significant reductions in bone marrow leukemic blasts during Cycle 1 and remains on therapy in Cycle 2. “These are very promising early results from the TUSCANY trial of TUS+VEN+AZA and the first indicators of the safety and efficacy we expected to see in newly diagnosed AML patients,” said Rafael Bejar, M.D., Ph.D., Chief Medical Officer of Aptose. “To achieve a complete remission (CR) in Cycle 1 in a subject harboring a TP53 mutation – one of the most adverse forms of AML – is particularly encouraging. With enrollment ongoing in the TUSCANY study, we look forward to reporting additional data as it becomes available.” “TUS+VEN+AZA triplet therapy has the potential to treat large AML patient populations, including those with traditionally difficult-to-treat mutations, and improve patient outcomes right from the outset of treatment,” said William G. Rice, Ph.D., Chairman, President and Chief Executive Officer of Aptose. The ability to treat such diverse AML populations – including FLT3 wildtype patients – with a favorable safety profile and without having to alter the standard of care dosing, differentiates our drug from many AML drugs in development.” TUSCANY: TUS+VEN+AZA Triplet Phase 1/2 Study Tuspetinib based TUS+VEN+AZA triplet therapy is being advanced in the TUSCANY Phase 1/2 trial with the goal of creating an improved frontline therapy for newly diagnosed AML patients that is active across diverse AML populations, durable, and well tolerated. Earlier APTIVATE trials of TUS as a single agent and in combination as TUS+VEN demonstrated favorable safety and broad activity in diverse relapsed or refractory (R/R) AML populations that went beyond the more prognostically favorable NPM1 and IDH mutant subgroups. Responses to TUS were also observed in those with prior-VEN and prior-FLT3 inhibitor (FLT3i) therapies, those with highly adverse TP53 and RAS mutations, and those with mutated or unmutated (wildtype) FLT3 genes. The TUSCANY triplet Phase 1/2 study is designed to test various doses and schedules of TUS in combination with standard dosing of AZA and VEN for patients with AML who are ineligible to receive induction chemotherapy. A convenient, once daily oral agent, TUS will be administered in 28-day cycles, beginning at 40mg once daily, with dose escalations planned after a safety review of each dose level. Multiple U.S. sites are enrolling in the TUSCANY trial with anticipated enrollment of 18-24 patients by mid-late 2025. Data will be released as it becomes available. More information on the TUSCANY Phase 1/2 study can be found on www.clinicaltrials.gov (here). 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 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 and safety profile of tuspetinib (including the triplet therapy) and its clinical development, the anticipated enrollment rate in the TUSCANY trial and the timing thereof, 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 Pietropaolo Corporate Communications & Investor Relations 201-923-2049 spietropaolo@aptose.com Released February 12, 2025

Clinical ResultPhase 1

12 Feb 2025

·mendus.com

Mendus AB Year-end Report 2024

Preparations for pivotal-stage readiness of vididencel in AML on trackThe hard work of the Mendus team to advance the company’s lead product vididencel in acute myeloid leukemia (AML) continued to pay off during the fourth quarter of 2024. In December, we presented positive updated survival data of the ongoing ADVANCE II Phase 2 trial at ASH, demonstrating that the majority of patients treated remained alive at 41.8 months median follow-up. Also in Q4, we received positive EMA and FDA feedback endorsing our registration trial preparations. We successfully advanced our manufacturing alliance for the large-scale production of vididencel. The progress realized during the quarter keeps us on track to achieve pivotal-stage readiness of vididencel in AML as our lead program in the second half of 2025. Erik Manting, Ph.D.Chief Executive Officer Significant events of Q4 2024 Net sales for the period amounted to KSEK – (-) Result for the period amounted to KSEK -31,515 (-41,165) Earnings and diluted earnings per share totalled SEK -0.63 (-0.95*) Cash runway extended until beginning of 2026 versus earlier guidance until Q4 2025 Mendus presented preclinical data supporting the combination of its intratumoral primer ilixadencel with the immune checkpoint inhibitor avelumab at the 39th annual meeting of the Society for Immunotherapy of Cancer (SITC). Mendus announced that the members of the Nomination Committee for the 2025 Annual General Meeting were appointed. The Nomination Committee consists of Erik Esveld, appointed by Van Herk Investments B.V, Karl Elmqvist, appointed by Flerie Invest AB, and Mats Andersson, appointed by Holger Blomstrands Byggnads AB. Mendus presented positive survival data from the ongoing ADVANCE II Phase 2 trial at the ASH 2024 conference. The data showed that the majority of AML patients treated with vididencel remain alive and disease-free in long-term follow-up, with a median follow-up of 41.8 months. Mendus also presented two preclinical abstracts during the ASH 2024 conference. The first abstract demonstrated synergies between vididencel and the combination of venetoclax and azacitidine, two backbone drugs in the treatment of AML, with venetoclax having a direct synergistic effect on vididencel’s mode of action. The second abstract supports the potential use of vididencel in the treatment of chronic myeloid leukemia (CML). Mendus reported positive topline data from the ALISON Phase 1 clinical trial with vididencel in ovarian cancer. The data confirmed that vididencel stimulates immune responses against ovarian cancer antigens, as a potential basis for an effective anti-tumor response, and the strong safety profile for vididencel. Mendus announced that Institut Bergonié was no longer in a position to study Mendus’ intratumoral immune primer ilixadencel in soft tissue sarcomas as part of the REGOMUNE trial, because third party funding for the trial had been terminated. Significant events after end of reporting period Mendus announced a summary of the feedback received from FDA and EMA in the fourth quarter of 2024. The feedback is supportive of the preparations for a registration trial with vididencel in AML. Financial summary * The comparative numbers recalculated taking into account the reverse split, 20:1 The full report is attached as PDF and is available on the company’s website: https://mendus.com/investors/financial-reports/ Webcast investor call, February 13, 08.30 CETThe company will host a live presentation and business update today at 08.30 CET. The presentation will be held in English and includes a Q&A session. If you wish to participate via webcast please use the link below.https://mendus.events.inderes.com/q4-report-2024/register If you wish to participate and ask questions via teleconference, please register on the link below. After registration you will be provided phone numbers and a conference ID to access the conference.https://conference.inderes.com/teleconference/?id=5004794 For more information, please contact:Erik MantingChief Executive OfficerE-mail: ir@mendus.com About Mendus AB (publ) Mendus is dedicated to changing the course of cancer treatment by addressing tumor recurrence and improving long-term survival for cancer patients, while preserving health and quality of life. We leverage our understanding of dendritic cell biology to develop an advanced clinical pipeline of immunotherapies which combine clinical efficacy with a benign safety profile. Based in Sweden and The Netherlands, Mendus is publicly traded on the Nasdaq Stockholm under the ticker IMMU.ST. https://www.mendus.com/ AttachmentsMendus Q4 2024 ENG 02 13 FinalMendus AB Year-end Report 2024

Clinical ResultPhase 1ImmunotherapyPhase 2Executive Change

100 Deals associated with Azacitidine

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KEGG	Wiki	ATC	Drug Bank
D03021	Azacitidine	L01BC07	DB00928

R&D Status

Approved

10 top approved records.

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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.

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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

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Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05428969 (BEXMAB, ASH2024) Manual	Phase 1/2	Myelodysplastic Syndromes TP53 Mutation	14	Bexmarilimab+Azacitidine	atnvydcfyf(edorzxdcup) = kuuuapgido fgbajgjunx (pulevshuxl ) View more	Positive	09 Dec 2024
ASH2024	Phase 3	Acute Myeloid Leukemia	70	Azacitidine+HAG regime	ylycgehjzr(nsjsrudfas) = ddtphzuate bdyqvucnjw (ekrteycjhy ) View more	Positive	09 Dec 2024
735 (ASH2024)	Phase 1/2	Acute Myeloid Leukemia TP53mutation	110	Magrolimab (Magro) + Azacitidine (AZA) + Venetoclax (VEN)	jttucsomqu(sdpsnrdsuc) = odwvctjtjf wlcrgtemmx (htnzlmqxvf, 7 - 13) View more	Positive	09 Dec 2024
ASH2024	Not Applicable	Myelodysplastic Syndromes	-	Azacitidine + Durvalumab	ukotybkryk(iszimyayru) = uqgnpfkocg epvllhawzl (gwiifcppxx ) View more	-	09 Dec 2024
				Azacitidine	ukotybkryk(iszimyayru) = twfnculndb epvllhawzl (gwiifcppxx ) View more
ASH2024	Not Applicable	Acute Myeloid Leukemia	-	Azacitidine + Venetoclax	oplbepjkix(pmhkvricfq) = bjeqohhfcj rvlutplkog (wejcjgoahq ) View more	-	09 Dec 2024
NCT03013998 (BAMT, ASH2024)	Phase 1/2	Acute Myeloid Leukemia	1,096	Non-Intensive (Off-Protocol)	ebgdmtpxnn(mxvbroazyr) = isnirpllqr bcvhlgnexq (lbaqzomwip, 6.9 - 13.4) View more	Positive	09 Dec 2024
				Ven/HMA (Off-Protocol)	ebgdmtpxnn(mxvbroazyr) = yxnfnyqxez bcvhlgnexq (lbaqzomwip, 2.2 - 10.7) View more
ASH2024	Not Applicable	Relapsing acute myeloid leukemia	-	Venetoclax	kngfsjsrxg(mzgntjofoo) = biptgfuqhx scbnonmyiy (zmvciqegdu, 6.2 - 16.0)	-	09 Dec 2024
NCT02719574 (ASH2024) Manual	Phase 1/2	IDH1 Mutation Acute Myeloid Leukemia IDH1 Mutation	67	Olutasidenib 150 mg + azacitidine	enrarxdqvk(mbtljgayki) = frfuywhboh ylscfolozt (maeebqntpo, 21 - 44) View more	Positive	08 Dec 2024
				Olutasidenib 150 mg + azacitidine (prior OLU exposure)	enrarxdqvk(mbtljgayki) = vzwpqauyjw ylscfolozt (maeebqntpo, 24 - 52) View more
NCT04550442 (ASH2024) Manual	Phase 1/2	High Risk Myelodysplastic Syndrome \| Chronic Myelomonocytic Leukemia	33	AzacitidineVenetoclax	qbdzvttzmr(wbzqusrvha) = eqcaeduseb bagwfrukjj (ayjduhvnit ) View more	Positive	08 Dec 2024
				Azacitidine and Venetoclax (TP53 mutation)	wwmvdojlll(owpppbzjoo) = bgjomhhuxs lyyzjsfudj (jxrctmsplx, 0.9 - 5)
NCT04501120 (APG2575AC101, ASH2024) Manual	Phase 1/2	Myelodysplastic Syndromes	49	Lisaftoclax Azacitidineazacitidine (R/R MDS)	riyjdktcmu(bioyxpftwr) = uaehfnfoeh cvwykeyfbn (mhqempuomx ) View more	Positive	08 Dec 2024
				Lisaftoclax Azacitidineazacitidine (TN MDS)	kgnifxvwrc \| riyjdktcmu(lwdvzdmocg) = fmvcruxicl qemxzkxeka (biqzzriaec, 61.5 - 89.2) View more

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