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

2026 Strategic Priorities and Anticipated Milestones (GlobeNewswire) - "Continue enrollment in the pivotal KOMET-017 Phase 3 trials...Advance enrollment of KOMET-015 for ziftomenib and imatinib combination in gastrointestinal stromal tumors (GIST); Progress preclinical development of a next-generation menin inhibitor for use in combination therapy for solid tumors."

Enrollment status • Preclinical • Acute Myelogenous Leukemia • Gastrointestinal Stromal Tumor • Solid Tumor

2025 Highlights and Recent Developments (GlobeNewswire) - "Added to the FDA Orange Book, with listed patents extending up to July 2044, which support long-term market exclusivity in the United States."

Patent • Acute Myelogenous Leukemia

The Care and Cure of the Leukemias in 2026. (PubMed, Am J Hematol) - "Currently, most leukemias are effectively treated with immunotherapies (highly effective monoclonal antibodies targeting CD19 [blinatumomab], or CD22 [inotuzumab ozogamicin]), BCR::ABL1 tyrosine kinase inhibitors (TKIs; e.g., dasatinib, ponatinib), Bruton TKIs (e.g., ibrutinib, acalabrutinib), BCL-2 inhibitors (venetoclax), IDH1/2 inhibitors (ivosidenib, olutasidenib, and enasidenib), FLT3 inhibitors (e.g., midostaurin, quizartinib, and gilteritinib), menin inhibitors (revumenib, ziftomenib), and chimeric antigen receptor T-cell therapies. Herein, we provide a high-level overview of prominent clinical developments across all leukemias. In contemporary times, harnessing the benefits of novel targeted therapies and the evolving treatment landscape bolster the optimistic view that most, if not all, leukemias are curable."

IO biomarker • Journal • Review • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Chronic Lymphocytic Leukemia • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • Transplantation • ABL1 • CD22 • FLT3 • IDH1 • IDH2 • KMT2A • TP53

Differentiation Syndrome in Acute Myeloid Leukemia: Molecular Mechanisms, Clinical Spectrum, and Emerging Therapeutic Paradigms. (PubMed, Int J Mol Sci) - "While differentiation therapy revolutionized acute promyelocytic leukemia (APL) with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), its extension into non-APL AML has been limited until recent targeted agents...IDH1/2 inhibitors (ivosidenib, enasidenib, olutasidenib) yield overall response rates (ORRs) of 30-94% in AML with DS in 10-19%. Menin inhibitors (revumenib, ziftomenib, enzomenib, bleximenib) achieve ORRs of 33-88% in KMT2A-rearranged or NPM1-mutated AML, with DS in 10-25% and QT prolongation as key toxicities. FLT3 inhibitors (gilteritinib, quizartinib) improve survival in FLT3-mutated AML with DS in 1-5%...Improved recognition of DS and rational combination approaches will be essential to maximize the therapeutic benefit. Future research should address mechanisms of resistance and biomarkers to achieve cures beyond APL."

Journal • Review • Acute Myelogenous Leukemia • Acute Promyelocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • FLT3 • IDH1 • IDH2 • KMT2A • NPM1

Management of Acute Myeloid Leukemia: A Review. (PubMed, Cancers (Basel)) - "Targeted therapies have improved outcomes in molecularly defined subsets of AML, with menin, IDH and FLT3 inhibitors representing major advances. However, TP53-mutated AML continues to carry a dismal prognosis, underscoring the need for more effective therapeutic strategies. Continued biomarker-driven research, novel drug combinations, and mechanistic insights will be essential to further refine AML treatment and improve long-term survival across disease subsets."

Journal • Review • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • FLT3 • KMT2A • NPM1

Menin Inhibition in Acute Myeloid MLL Rearranged Leukemias: A New Target for Precision Care. (PubMed, Cancers (Basel)) - "Revumenib received approval in 2024-2025 for relapsed or refractory KMT2A-rearranged acute leukemia and NPM1-mutated AML...Several menin inhibitors, including ziftomenib, bleximenib, and enzomenib, are in clinical development...Combination therapies with azacitidine and venetoclax or intensive chemotherapy have achieved high response rates in newly diagnosed patients, supporting their potential use in frontline treatment...Approximately 30-40% of responders in relapsed or refractory trials proceeded to allogeneic transplantation, which remains a key pathway to potential cure. This review examines the molecular mechanisms of the menin-KMT2A interaction, and summarizes clinical trial data on the efficacy and safety of menin inhibitors as monotherapy and in combination."

Journal • Review • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Transplantation • KMT2A • MEN1 • 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

KO-MEN-017: Studies testing Ziftomenib together with standard treatments in adults with newly diagnosed acute myeloid leukemia (AML) that has specific genetic changes (NPM1 or KMT2A) (clinicaltrialsregister.eu) - P2/3 | N=144 | Not yet recruiting | Sponsor: Kura Oncology Inc.

New P2/3 trial • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • FLT3 • 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

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

KO-MEN-017: Studies testing Ziftomenib together with standard treatments in adults with newly diagnosed acute myeloid leukemia (AML) that has specific genetic changes (NPM1 or KMT2A) (clinicaltrialsregister.eu) - P2/3 | N=411 | Not yet recruiting | Sponsor: Kura Oncology Inc.

New P2/3 trial • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • FLT3 • KMT2A • NPM1

Targeting menin in T-lineage acute lymphoblastic leukemia. (PubMed, Mol Cancer Ther) - "We tested menin inhibitors (ziftomenib, revumenib, VTP-50469) in 14 primary T-ALL samples and 8 cell lines, representing HOXA-high and HOXA-low genotypes. In conclusion, a subset of T-ALL, defined by high p-MEF2C S222, is sensitive to menin inhibition. Combining ziftomenib with CDK or ERK inhibition offers synergistic efficacy, supporting biomarker-driven clinical trials of this strategy in relapsed/refractory T-ALL."

Journal • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • T Acute Lymphoblastic Leukemia • CDK1 • KMT2A • MEF2C • MEIS1

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

CLEC12A-CAR-T Cell Therapy of NPM1m and KMT2A-r AML Can Be Improved by Combination with Menin Inhibition (EHA-EBMT-CART 2026) - "Notably, early clinical trials with heavily pretreated patients reported a dramatic efficacy of the men-i-therapy culminating in the FDA approval of the men-i revumenib for relapsed/refractory KMT2A -r and NPM1 m AML...Methods : In our work, treatment of KMT2A -r and NPM1 m AML cells with different men-i (MI-503, ziftomenib or VTP-50469), revealed a substantial upregulation of CLEC12A at the transcriptome level...To evaluate men-i as an AML priming treatment for CLEC12A-directed immunotherapy, we designed a second-generation, 4-1BB-based chimeric antigen receptor (CAR) based on the anti-CLEC12A scFv derived from Tepoditamab...Conclusions : Taken together, the efficacy of our combinatorial approach based on men-i pre-treatment and CLEC12A-CAR-T cell therapy provides a novel treatment concept for therapy of NPM1 m and KMT2A -r AML and should soon be available for clinical investigation. Clinical Trial Registry : -"

CAR T-Cell Therapy • IO biomarker • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • CLEC12A • IFNG • 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

Phase 1/1b Trial Of Olutasidenib And Ziftomenib For NPM1 And IDH1 Co-Mutated Acute Myeloid Leukemia (clinicaltrials.gov) - P1 | N=20 | Not yet recruiting | Sponsor: M.D. Anderson Cancer Center

New P1 trial • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • IDH1 • NPM1

201: It's Raining Menin Inhibitors: Exploring the Menin Inhibitor Pipeline in AML (HOPA 2026) - "The presentation will also evaluate ongoing clinical trials for emerging menin inhibitors, highlighting potential roles in therapy for KMT2A- and NPM1-mutated AML. UAN: 0465-0000-26-031-L01-P Knowledge or Application Based: Application Learning Objectives: Analyze the prognostic significance and treatment implications of KMT2Ar and NPM1m in AML Appraise the clinical impact of literature leading to the FDA approval of ziftomenib and revumenib Apply key clinical pearls and evidence-based management of adverse effects to optimize menin inhibitor therapyEvaluate safety and efficacy data on agents in the menin inhibitor pipeline"

Acute Myelogenous Leukemia • Hematological Malignancies • KMT2A • NPM1

Ziftomenib: First Approval. (PubMed, Drugs) - "Ziftomenib received its first approval on 13 Nov 2025 in the USA for the treatment of adults with relapsed or refractory AML with a susceptible NPM1 mutation who have no satisfactory alternative treatment options. This article summarises the milestones in the development of ziftomenib leading to this first approval for relapsed or refractory AML associated with an NPM1 mutation."

Journal • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Sarcoma • 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 + Mezigdomide in Adolesc. and Adults w/ R/R AML (clinicaltrials.gov) - P1 | N=24 | Not yet recruiting | Sponsor: Massachusetts General Hospital

New P1 trial • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Targeted Protein Degradation • FLT3 • KMT2A • NPM1

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