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

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

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

Ziftomenib in relapsed/refractory (R/R) NPM1-mutant acute myeloid leukemia (AML): Phase 1b/2 clinical activity and safety results from the pivotal KOMET-001 study. (ASCO 2025) - P1/2 | "Median age was 69 yrs (range 22–86), 56% female, 83% ECOG PS 0–1, median of 2 prior therapies (range 1–7), including 60% prior venetoclax (VEN) and 23% prior transplant... In the pivotal KOMET-001, the phase 2 primary endpoint was met: Ziftomenib achieved deep and durable responses in R/R NPM1-m AML, regardless of prior VEN. Ziftomenib was well tolerated with limited myelosuppression and only 3% ziftomenib-related discontinuations. Taken together, these data support the potential use of ziftomenib monotherapy as a new treatment option for R/R NPM1-m AML."

Clinical • P1/2 data • Acute Myelogenous Leukemia • Anemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Leukemia • Neutropenia • Oncology • Thrombocytopenia • KMT2A • NPM1

ZIFTOMENIB IN RELAPSED/REFRACTORY NPM1-MUTANT ACUTE MYELOID LEUKEMIA: PHASE 1B/2 CLINICAL ACTIVITY AND SAFETY RESULTS FROM THE PIVOTAL KOMET-001 STUDY (EHA 2025) - P1/2 | "In the pivotal KOMET-001 study, the phase 2 primary endpoint was met. Ziftomenib achieved deep and durable responses in R/R NPM1-m AML, with comparable clinical activity regardless of prior venetoclax exposure. Ziftomenib was well tolerated with limited myelosuppression and only 3% ziftomenib-related discontinuations."

Clinical • P1/2 data • Acute Myelogenous Leukemia • Anemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Leukemia • Neutropenia • Oncology • Thrombocytopenia • KMT2A • NPM1

ZIFTOMENIB COMBINED WITH INTENSIVE INDUCTION CHEMOTHERAPY (7+3) IN NEWLY DIAGNOSED NPM1-M OR KMT2A-R ACUTE MYELOID LEUKEMIA (AML): UPDATED PHASE 1A/B RESULTS FROM KOMET-007 (EHA 2025) - P1 | "KOMET-007 (NCT05735184) is an ongoing dose-escalation (ph1a) and expansion (ph1b) study of ziftomenib in combination with standard chemotherapies in NPM1-m or KMT2A-r AML.Aims: Here we present updated safety and clinical activity in all newly diagnosed AML patients (pts) treated at the recommended phase 2 dose (RP2D) of ziftomenib 600 mg once-daily (QD) in combination with standard doses of cytarabine and daunorubicin (7+3) across ph1a/b of KOMET-007.Adults (≥18y) with newly diagnosed NPM1-m or KMT2A-r AML received the ziftomenib RP2D of 600 mg QD in combination with 7+3 induction, followed by consolidation with cytarabine and/or hematopoietic stem cell transplantation. In the ongoing KOMET-007 study, ziftomenib RP2D of 600 mg QD combined with 7+3 was well tolerated and continued to demonstrate robust and evolving clinical activity in newly diagnosed AML: CRc of 94% in NPM1-m and 83% in KMT2A-r pts. No DS events were reported, with low rates of ziftomenib-related..."

P1 data • Acute Myelogenous Leukemia • Anemia • Bone Marrow Transplantation • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Leukemia • Neutropenia • Oncology • KMT2A • NPM1

Expected 2026 Key Milestones:…Ziftomenib Development (GlobeNewswire) - "(i) Present updated KOMET-007 data evaluating combination with 7+3 in newly diagnosed NPM1-m or KMT2A-r AML in the first half of 2026; (ii) Publish ven/aza combination data in R/R NPM1-m AML in the first half of 2026; (iii) Present preliminary data from KOMET-008 cohort evaluating combination with gilteritinib in R/R NPM1-m/FLT3-m AML in the second half of 2026; (iv) Advance enrollment of KOMET-017 Phase 3 trials for newly diagnosed AML, including combinations with intensive and non-intensive chemotherapy, in 2026; (v) Advance enrollment of KOMET-007 cohort evaluating combination with 7+3 and quizartinib in newly diagnosed NPM1-m/FLT3-m AML (quad) in 2026; (vi) Expand ziftomenib to non-AML indications in 2026, including ongoing Phase 1a dose escalation trial evaluating combination with imatinib in gastrointestinal stromal tumors."

Clinical data • Trial status • Acute Myelogenous Leukemia • Gastrointestinal Stromal Tumor

Launched KOMZIFTI (ziftomenib), first and only once-daily, oral menin inhibitor approved for adults with R/R NPM1-mutated AML (GlobeNewswire) - "$2.1 million of KOMZIFTI net product revenue in the five-week period of initial commercial availability ended December 31, 2025. Milestone payments of $195 million under collaboration agreement with Kyowa Kirin in the fourth quarter of 2025. Collaboration revenue (non-cash item) for the fourth quarter of 2025 estimated between $15 to $17 million."

Commercial • Launch US • Acute Myelogenous Leukemia

Update on a Phase 1/2 First-in-Human Study of the Menin-KMT2A (MLL) Inhibitor Ziftomenib (KO-539) in Patients with Relapsed or Refractory Acute Myeloid Leukemia (ASH 2022) - P1/2 | "Clinical benefit with disease control (eg, decreasing blast counts [BC] or hydroxyurea requirement) occurred across dose levels. P1b results suggest that with appropriate DS management, ziftomenib is well tolerated. Additionally, the 600 mg dose demonstrates meaningful signs of efficacy in heavily pretreated R/R AML pts, warranting further investigation of ziftomenib as a monotherapy and in combination with rational therapeutic partners."

Clinical • P1/2 data • Acute Myelogenous Leukemia • Anemia • Bone Marrow Transplantation • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Inflammation • Leukemia • Leukopenia • Neutropenia • Oncology • Pneumonia • Respiratory Diseases • Septic Shock • Thrombocytopenia • Transplantation • KMT2A • NPM1 • RUNX1 • SETD2

ACTIVITY, TOLERABILITY, AND RESISTANCE PROFILE OF THE MENIN INHIBITOR ZIFTOMENIB IN ADULTS WITH RELAPSED/REFRACTORY NPM1-MUTATED AML (EHA 2023) - P1/2 | "Ziftomenib continues to demonstrate significant clinical activity in heavily pretreated and co-mutated R/R NPM1mAML pts where 35% of pts achieved CR. The safety profile remains consistent, and episodes of DS are clinicallymanageable. Data reveal that remissions are durable, with MRD clearance of NPM1 and key co-mutations.Resistance mutations develop infrequently, and ziftomenib remains effective against a common menin gatekeepermutation."

Clinical • Late-breaking abstract • Acute Myelogenous Leukemia • Anemia • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • Thrombocytopenia • Transplantation • FLT3 • IDH1 • IDH2 • KMT2A • MEN1 • NPM1

Ziftomenib in relapsed or refractory acute myeloid leukaemia (KOMET-001): a multicentre, open-label, multi-cohort, phase 1 trial. (PubMed, Lancet Oncol) - P1/2 | "Ziftomenib showed promising clinical activity with manageable toxicity in heavily pretreated patients with relapsed or refractory acute myeloid leukaemia. Phase 2 assessment of ziftomenib combination therapy in the upfront and relapsed or refractory setting is ongoing."

Journal • P1 data • Acute Myelogenous Leukemia • Cardiovascular • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Neutropenia • Oncology • Pneumonia • Respiratory Diseases • Septic Shock • Thrombocytopenia • KMT2A • NPM1

Ziftomenib Combined with Intensive Induction (7+3) in Newly Diagnosed NPM1-m or KMT2A-r Acute Myeloid Leukemia: Interim Phase 1a Results from KOMET-007 (ASH 2024) - P1 | "Following a rule-based approach, at least six dose-limiting toxicity (DLT) evaluable pts were assigned to each cohort where ziftomenib (200, 400, or 600 mg once daily) was escalated with standard doses of cytarabine and daunorubicin (7+3). Taken together, these data support the advancement of ziftomenib in combination with intensive chemotherapy. 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 • Leukemia • Neutropenia • Oncology • KMT2A • NPM1

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

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

Menin inhibitors for adult acute myeloid leukemia: 2025 update. (PubMed, Expert Opin Investig Drugs) - "Menin inhibitor approval/use is expanding into other HOX-driven subtypes (e.g. NPM1, NUP98r), as frontline option and in combination settings. Monitoring for differentiation syndrome, QT interval prolongation, recognizing pseudo-progression, and supportive care needs remains essential to maximize patient benefit."

Journal • Review • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • HOXA9 • KMT2A • MEIS1 • MEN1 • NPM1 • NUP98

KOMZIFTI (Ziftomenib). (PubMed, Clin Ther) - No abstract available

Journal

Revumenib for Relapsed/Refractory Acute Myeloid Leukemia with Susceptible NPM1 Mutation (ASH 2025) - "My presentation will review the FDA approvals for revumenib and ziftomenib for the treatment of patients with R/R AML with a susceptible NPM1 mutation without satisfactory alternative treatment options, discuss why the review teams arrived at these restricted indication statements, and implications for AML drug development."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • NPM1

Managing KOMZIFTI in Patients with R/R NPM1-m AML (ASH 2025) - "Supported By Kura Oncology For in-person participants only"

Clinical • Acute Myelogenous Leukemia • NPM1

Ziftomenib for Relapsed/Refractory Acute Myeloid Leukemia with Susceptible NPM1 Mutation (ASH 2025) - "My presentation will review the FDA approvals for revumenib and ziftomenib for the treatment of patients with R/R AML with a susceptible NPM1 mutation without satisfactory alternative treatment options, discuss why the review teams arrived at these restricted indication statements, and implications for AML drug development."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • 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

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

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

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