Komzifti (ziftomenib) / Kura Oncology, University of Michigan, Kyowa Kirin - LARVOL DELTA

Kura Oncology to Host Virtual Investor Event to Discuss Data Presented at ASH 2025 on Triplet Combination of Ziftomenib (KOMZIFTI) with Venetoclax and Azacitidine in Newly Diagnosed and Relapsed/Refractory Acute Myeloid Leukemia (GlobeNewswire) - "Event Scheduled for December 8, 2025 at 12:30 PM ET."

P1 data • Acute Myelogenous Leukemia

Ziftomenib in combination with venetoclax and azacitidine in relapsed/refractory NPM1-m or KMT2A-r acute myeloid leukemia: Updated phase 1a/b safety and clinical activity results from KOMET-007 (ASH 2025) - P1 | "In the ongoing KOMET-007 study, ziftomenib RP2D of 600 mg QD + Ven/Aza was welltolerated with robust clinical activity in patients with R/R NPM1-m or KMT2A-r AML. No ziftomenib-relatedQTc prolongation was reported. One case of DS (NPM1-m, Gr 3) successfully resolved with protocol-specified mitigation."

Clinical • Combination therapy • P1 data • Acute Myelogenous Leukemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Leukemia • Neutropenia • FLT3 • KMT2A • NPM1

Trial in progress: A phase II study of ziftomenib monotherapy in unfit patients with newly diagnosed Acute Myeloid Leukemia with NPM1 mutation or KMT2A rearrangement (ASH 2025) - P2 | "While the standard treatment for less intensive inductionin AML consists of venetoclax and azacitidine, some patients are too frail for this regimen and maybenefit from targeted therapies in the frontline setting. Currently, the only targeted treatment approvedas a single agent in the frontline setting is ivosidenib for patients aged 75 years and older with IDH1-mutated AML, based on an open-label, single arm study...If at least 3patients achieve CR/CRh of these 18 patients, an additional 11 patients will be enrolled. For the NPM1-mcohort, if 2 patients achieve CR/CRh of an initial 10 patients, then 12 additional patients will be enrolled."

Clinical • Monotherapy • P2 data • Acute Myelogenous Leukemia • Hematological Malignancies • Infectious Disease • Leukemia • IDH1 • KMT2A • NPM1

Preliminary data from the ongoing Phase 1 study of the menin-MLL inhibitor enzomenib (DSP-5336) in combination with venetoclax and azacitidine in patients with relapsed or refractory Acute Myeloid Leukemia (ASH 2025) - P1/2 | "Median age was 50 yrs (21-76), 56% were female andmedian prior regimens was 2 (1-4); 3 pts (16.7 %) had prior allogeneic stem cell transplant (SCT), 6 pts(33.3%) had prior VEN, and 5 pts (27.8%) received prior menin inhibitor (2 ziftomenib, 1 revumenib, 2enzomenib). Preliminary data show ENZO up to 300 mg BID to be well tolerated in combination withVEN/AZA with no DLTs in 18 pts with R/R KMT2Ar or NPM1m AML. No QT prolongation was reported andthere was 1 report of non-serious DS. Promising preliminary clinical activity has been observed,particularly in pts without prior VEN or menin exposure (100% ORR and 67% CRc rate)."

Clinical • Combination therapy • P1 data • Acute Myelogenous Leukemia • Central Nervous System Leukemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Leukopenia • Neutropenia • Septic Shock • Thrombocytopenia • FLT3 • KMT2A • NPM1

The outcomes of patients who are relapsed or refractory to menin inhibitors is poor with a limited overall survival (ASH 2025) - "Prior to MENINi, 86% (n=72)received intensive chemotherapy (IC) and 77% (n=65) received venetoclax (VEN)-based therapy, including65% (n=55) who had received both. Thirty-eight percent (n=32) of pts previously underwent alloSCT.Revumenib was the most used MENINi (n=61, 73%), followed by bleximenib (n=12, 14%) and ziftomenib(n=9, %)...The most common therapiesafter MENINi failure were hypomethylating agent (HMA) and VEN (n=13; 15%), investigational agents(n=13, 15%), and gilteritinib-based regimens (GILT; n=9, 11%)... MENINi are promising in AML, but outcomes after failure are poor. VEN-based regimens,especially in VEN-naïve pts, and MENINi switching can yield responses associated with improved survival.Studies addressing optimal sequencing as well as preventing and overcoming resistance are needed."

Clinical • Leukemia • FLT3 • KMT2A • MEN1 • NPM1 • NUP98 • WT1

Ziftomenib in combination with venetoclax and azacitidine in newly diagnosed NPM1-m acute myeloid leukemia: Phase 1b results from KOMET-007 (ASH 2025) - P1, P3 | "In the ongoing KOMET-007 study, ziftomenib RP2D of 600 mg once daily combined withVen/Aza was well tolerated and demonstrated robust clinical activity in patients with newly diagnosedNPM1-m AML, including 84% CRc after a median of 3.5 weeks and 54% CRc MRD-negativity after amedian of 8.4 weeks. Low rates of ziftomenib-related cytopenia and no additional myelosuppressionwere observed with this combination. One case each of differentiation syndrome (grade 2) andinvestigator-assessed QTc (grade 3) were successfully resolved."

Combination therapy • P1 data • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • FLT3 • HEY1 • KMT2A • NPM1

Kura Oncology…announced the first U.S. commercial sale of KOMZIFTI (ziftomenib) has been completed (GlobeNewswire) - "Under Kura’s collaboration and license agreement with Kyowa Kirin Co. Ltd. and Kyowa Kirin, Inc. (collectively, 'Kyowa Kirin'), this milestone triggers a $135 million payment from Kyowa Kirin to Kura, which Kura expects to receive prior to year-end."

Commercial • Acute Myelogenous Leukemia

Blood Cancer United—formerly The Leukemia & Lymphoma Society—will celebrate new data presented by Blood Cancer United funded grantees at the upcoming American Society of Hematology (ASH) Annual Meeting & Exposition (December 6-9, 2025). (PRNewswire) - "At the meeting, two oral presentations on combination studies of ziftomenib, venetoclax and azacitidine in newly diagnosed and relapsed/refractory AML will be presented."

Clinical data • Acute Myelogenous Leukemia

Menin inhibitors as targeted therapy in KMT2A-Rearranged acute leukemia: A comprehensive review of current advances and therapeutic implications. (PubMed, Med Oncol) - "Among them, revumenib and ziftomenib have advanced furthest in clinical testing. Ongoing trials are now evaluating menin inhibitors in rational combinations, frontline regimens, and maintenance therapy. Collectively, these advances highlight menin inhibition as a transformative strategy in acute leukemia, reshaping therapy through precision-targeted epigenetic intervention."

Journal • Review • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Gene Therapies • Hematological Malignancies • Leukemia • Oncology • HOXA9 • KMT2A • MEIS1 • MEN1 • NPM1

Identifying novel 'druggable' targets via Npm1A-turboid fusion and mass spectrometry to overcome genetic or adaptive resistance to menin inhibitors in mtNPM1 AML (ASH 2025) - "Treatment with revumenib may also cause emergenceof hot spot mutations in menin (e.g., S160T, M327V, M327I, G331D, G331R, and T349M) exhibitingreduced affinity to MI-binding...OCI-AML3 MEN1-M327I cells were resistant toSNDX-50469, ziftomenib, and DS1594b, but sensitive to the second-generation MI, bleximenib, aspreviously reported.To identify novel 'druggable' targets in mtNpm1 AML cells either sensitive or resistant to MI, we knockedin TurboID by CRISPR/Cas9 into the C-terminus of the mtNpm1 gene in OCI-AML3 cells...When combined with a BET inhibitor (pelabresib) ora novel dual BET/HAT inhibitor (NEO2734/EP31670), both RocA and talazoparib induced synergisticlethality in the sensitive OCI-AML3 and OCI-AML2-Npm1A KI, as well as the MI-resistant (OCI-AML3-Menin-M327I or the OCI-AML3 MITR) cells...Exvivo treatment with EP31670 and RocA or talazoparib induced synergistic loss of viability in MI (SNDX-50469)-resistant, patient-derived (N = 3) mtNpm1 AML cells. In the..."

IO biomarker • Acute Myelogenous Leukemia • AURKA • CDK9 • CDKN1A • EIF4A1 • EIF4A2 • FLT3 • HOXA9 • IL7R • IRAK4 • KMT2A • MEIS1 • MEN1 • MYC • NPM1 • PLK1 • S100A8 • SF3B1 • SMARCA2 • TP53

Outcome of Infants Treated on Total Therapy for Infants with Acute Lymphoblastic Leukemia I: Results from a Non-Randomized Multi-Center Study (ASH 2023) - P1/2 | "In this study, bortezomib and vorinostat were incorporated into an ALL chemotherapy backbone containing dexamethasone, mitoxantrone, and pegasparaginase during induction and reinduction chemotherapy cycles...Following induction intensification with cyclophosphamide, cytarabine, and mercaptopurine, 77% and 66% of all patients and KMT2Ar patients respectively were MRD negative at the time of count recovery...Although the study was not powered to evaluate outcomes, EFS and OS in KMT2Ar patients suggest a clinical signal worth pursuing given the low proportion of patients transplanted in first remission. The successor study, TINI 2 (NCT05848687), will build upon the bortezomib/vorinostat backbone by incorporating 2 cycles of blinatumomab and the menin inhibitor ziftomenib in combination with chemotherapy during reinduction."

Clinical • Acute Lymphocytic Leukemia • Anorexia • Cardiovascular • Dyslipidemia • Febrile Neutropenia • Hematological Malignancies • Hypertension • Hypertriglyceridemia • Infectious Disease • Pneumonia • Respiratory Diseases • Septic Shock • AFF1 • KMT2A • MLLT3

Preclinical activity of investigational menin inhibitor DSP-5336 (Enzomenib)-based combinations against MLL1-rearranged (MLL-r) or mutant-NPM1 AML models (ASH 2025) - "Previously reported preclinical data showed that treatment with Menin inhibitor (MI),e.g., SNDX-5613 (revumenib) or KO-539 (ziftomenib), disrupts binding of Menin to MLL1/2 and MLL1-FP,leading to reduced MLL1/2 and MLL1-FP target gene expression, as well as induction of differentiationand apoptosis in AML cells expressing MLL-FP or mtNPM1c...Notably, in the cell lines and PD AML cells with MLLr ormtNPM1c AML, in vitro treatment with DSP-5336 in combination with CDK9 inhibitor (CDK9i) AZD4573 orBAY1251152 for 48 to 96 hours induced synergistic apoptosis or loss of viability, as discovered by the ZIPmethod with SynergyFinder...In vivo co-treatment with DSP-5336 and BAY1251152 showedsignificantly greater reduction in AML burden than treatment with each agent alone (p< 0.05), withoutinducing weight loss or other toxicities. These preclinical findings underscore the anti-AML activity of DSP-5336 and its molecular correlates, aswell as demonstrate synergistic in vitro and..."

IO biomarker • Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • BCL2 • CASP3 • CD123 • CD33 • CD99 • CDK6 • CLEC12A • FLT3 • HOXA9 • IFNG • IL3RA • ITGAM • KMT2A • MEF2C • MEIS1 • NPM1 • PBX3

Roswell Park Experts Share Latest Hematology Research at 67th ASH Annual Meeting (Roswell Park Comprehensive Cancer Center)

Clinical data • Acute Myelogenous Leukemia • B Acute Lymphoblastic Leukemia • Blastic Plasmacytoid Dendritic Cell Neoplasm • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Multiple Myeloma

Protein degradation of MYC/GSPT1 combined with menin inhibition overcomes resistance to menin inhibition in KMT2A-rearranged Acute Myeloid Leukemia (ASH 2025) - "Pharmacological inhibition of the menin-KMT2A interaction using revumenib andziftomenib has shown encouraging efficacy in clinical trials, and revumenib has been FDA-approved(Aldoss & Issa, 2023)...By targeting the MYC-GSPT1 axis, GT19715, the first-in-class MYC/GSPT1degrader, has shown promising activity in c-MYC-driven hematological malignancies through disruptionof MYC/GSPT1 protein translation (Nishida, biorxiv 650490, in revision)... The proposed combinatorial approach of menin inhibition and MYC/GSPT1 proteindegradation induces highly synergistic cell death in KMT2A-r AML cells in vitro and in vivo, effectivelyovercoming resistance by MCL-1 overexpression and RAS pathway activation. Investigations usingKMT2Ar AML patient-derived xenograft models are ongoing and will be presented."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Targeted Protein Degradation • ANXA5 • GSPT1 • KMT2A • MCL1 • MYC • NRAS

Menin inhibition as a new therapeutic option for the myeloproliferative neoplasms (ASH 2025) - "Of note, ziftomenib, astructurally distinct menin inhibitor currently in clinical trials, similarly affected megakaryopoiesis in vitro,indicating this is a class effect...Importantly, revumenib as a single agent and in combination with ruxolitinib also resulted inmarked, significant improvement in overall survival. Finally, revumenib was well tolerated in a 12-weekstudy of healthy mice. Together these findings demonstrate that revumenib suppressesmegakaryopoiesis both in vitro and in vivo in MPN models and highlight menin inhibition as a potentialdisease-modifying strategy capable of reversing key pathological features of MPNs."

Acute Myelogenous Leukemia • Fibrosis • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Myeloproliferative Neoplasm • Thrombocytopenia • Thrombocytosis • CALR • CD34 • ITGA2B • KMT2A • MEIS1 • NPM1

NCCN has published updates to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines), NCCN Guidelines Navigator, and the NCCN Drugs & Biologics Compendium (NCCN Compendium) for Acute Myeloid Leukemia, Version 3.2026. (NCCN)

NCCN guideline • Acute Myelogenous Leukemia

KOMZIFTI (ziftomenib) Added to National Comprehensive Cancer Network (NCCN) Guidelines for Acute Myeloid Leukemia (AML) (GlobeNewswire) - "KOMZIFTI received full approval by the U.S. Food and Drug Administration on November 13, 2025, for the treatment of adults with relapsed or refractory AML with a susceptible NPM1 mutation who have no satisfactory alternative treatment options."

NCCN guideline • Acute Myelogenous Leukemia

ZIFTOMENIB IN COMBINATION WITH IMATINIB IN ADVANCED GASTROINTESTINAL STROMAL TUMORS (GIST) AFTER IMATINIB FAILURE: PHASE 1A/B STUDY OF SAFETY, PHARMACOKINETICS, AND ANTITUMOR ACTIVITY (CTOS 2025) - P1 | "n/a"

Clinical • Combination therapy • Metastases • P1 data • PK/PD data • Stroma • Gastrointestinal Cancer • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • KIT • KMT2A

Phase l dose escalation and expansion of ziftomenib in combination with quizartinib in AML (ASH 2025) - P1 | "Secondary objectives include assessment of the composite complete remission rate, duration ofresponse, event-free and overall survival and concordance of genetic (NGS, Invivoscribe, USA) and flowMRD. This trial includes longitudinal collection of samples, with exploratory objectives focused onimproving MRD detection, and understand of response and resistance using cytometry by time of flight.This study, currently enrolling patients at MD Anderson, could lead to a novel all-oral targeted therapycombination for the largest subset of patients with AML."

Combination therapy • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • FLT3 • KMT2A • MEIS1 • NPM1 • NUP98

A baseline transcriptomic signature predictive of clinical response to menin inhibitors in AML : The PRE-men retrosprospective Study (ASH 2025) - P1/2 | "In this study, we assessed thetranscriptomic profiles of R/R AML patients at baseline and during early MENi therapy to: (1) develop agene expression signature predictive of treatment response, and (2) gain insight into the molecularfeatures distinguishing sensitive from primary resistant patients.MethodsIn this monocentric retrosprospective study, patients treated with MENi monotherapy (revumenib (n=15),ziftomenib (n=3), bleximinib (n=1), enzomenib (n=1)) either in French revumenib compassionate useprogram or in dedicated clinical trials (2020-004104-34, 2023-510509-17, 2023-505584-36, 2022-502741-10-00) were included. Most of the DEG found were involved in immune signalingpathways. A transcriptomic signature predictive of response to MENi therapy is currently evaluated in anindependent external validation cohort and will be presented at the meeting."

Clinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • ADNP • CD14 • HIF1A • HOXA9 • KMT2A • MEIS1 • NUP98

Menin-inhibition boosts CAR-T cell therapy against NPM1 mutated and KMT2A-rearranged acute myeloid leukemia (ASH 2025) - "Here, we discovered that men-i uniformly induces the expression of theimmunotarget CLEC12A (also known as CLL-1) on both leukemia entities, thereby sensitizing these cellsfor chimeric antigen receptor (CAR)-based immunotherapy.Initially, RNAseq revealed CLEC12A to be consistently upregulated in KMT2A-r and NPM1m AML cellsupon pharmacological inhibition with different men-i, including MI-503, ziftomenib, or VTP-50469 (closehomologue to revumenib). Combined in vivo men-i (14 days) and CLEC12A-directed CAR-T celltreatment resulted in significantly enhanced eradication of engrafted KMT2A-r MOLM-13 cells asassessed 9 days after CAR-T cell injection.To our knowledge, this is the first preclinical study demonstrating that men-i induces the immunotargetCLEC12A to overcome the limitations of CAR-based immunotherapy against AML. Combined men-i andCLEC12A-directed CAR-T cell treatment had dramatic anti-leukemic effects in vitro and in vivo and shouldsoon be available for clinical..."

CAR T-Cell Therapy • IO biomarker • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • CLEC12A • HAVCR2 • IFNG • ITGAM • KMT2A • LAG3 • MEIS1 • NPM1 • PD-1 • TIGIT

Targeting the compass complex to overcome resistance in KMT2A-rearranged Acute Myeloid Leukemia (ASH 2025) - "Methods To this note, we aimed to establish an in-vitro resistant model in KMT2Ar leukemia cell lines (MV4-11 andMOLM-13) by chronically exposing them to sequentially escalating, sub-therapeutic doses of a menininhibitor (ziftomenib, Selleckchem, cat.no:E1290)...An ATP-based cell proliferation assay was performed to assess cell viabilityand growth inhibition following SiRNA KD and by using WDR5 inhibitor (OICR-9429, Selleckchem,cat.no:S7833) to pharmacologically target the complex...CRISPR knockdowns and patient cells will be tested in xenografts fortherapeutic response.ConclusionASH2L and WDR5 are critical mediators of COMPASS-dependent therapy resistance in KMT2A-r AML.Targeting this complex, particularly ASH2L and WDR5, represents a promising strategy to possibly reverseresistance and improve therapeutic outcomes in resistant KMT2A-r AML. Our preliminary data indicateother components of the COMPASS complex to possibly cause resistance in KMT2A-r AML, and..."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • HOXA10 • HOXA9 • KMT2A • MEIS1 • WDR5

Onco360…has been selected as a pharmacy partner by Kura Oncology for Komzifti (ziftomenib), indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with a susceptible nucleophosmin 1 (NPM1) mutation who have no satisfactory alternative treatment options (GlobeNewswire)

Commercial • Acute Myelogenous Leukemia

Lintuzumab-Ac225 Exerts Mutation Agnostic Antileukemic Activity in Preclinical Models of AML (ASH 2024) - "In clinical trials, lintuzumab-Ac225 has demonstrated promising therapeutic responses when added to CLAG-M chemotherapy in heavily pretreated relapsed/refractory AML patients, including high risk populations with venetoclax failures and TP53 mutations...Although the single agent cytotoxicity of FLT3 inhibitors (gilteritinib, quizartinib) and KMT2A inhibitors (revumenib, ziftomenib) was observed with varied sensitivity in both MV-4-11 and MOLM-13 FLT3/KMT2A mutation-carrying cells, the combinations with lintuzumab-Ac225 were additive at all studied dose levels (p<0.01)...CD33-targeted radiation-induced damage improves AML control in adverse-risk settings, and further potentiates response durability when added to standard-of-care, including molecularly targeted therapy. Collectively, these data support the backbone therapy potential of lintuzumab-Ac225 in a mutation agnostic manner, warranting further clinical evaluation in difficult to treat relapsed/refractory AML."

Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD33 • CDKN1A • FLT3 • IDH1 • IDH2 • KMT2A • NPM1 • TP53

Ziftomenib Combined with Venetoclax/Azacitidine in Relapsed/Refractory NPM1-m or KMT2A-r Acute Myeloid Leukemia: Interim Phase 1a Results from KOMET‑007 (ASH 2024) - P1 | "Based on these encouraging initial results, a dose expansion phase evaluating this triplet combination in newly diagnosed and R/R NPM1-m and KMT2A-r AML patients is underway. Updated results will be presented, as data from the 400 mg cohorts continue to mature and 600 mg cohorts are enrolling."

P1 data • Acute Myelogenous Leukemia • Anemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Neutropenia • Oncology • Pneumonia • Respiratory Diseases • KMT2A • NPM1