SAN DIEGO, August 10, 2026
Kura Oncology, Inc. announced the publication of new research in Blood detailing the discovery and preclinical characterization of ziftomenib, a potent and selective menin inhibitor approved by the U.S. Food and Drug Administration in 2025 for adults with relapsed or refractory NPM1-mutated acute myeloid leukemia (AML). The publication describes ziftomenib’s differentiated binding profile, potency and selectivity against the menin-KMT2A interaction, as well as its activity across genetically defined leukemia models. The findings also provide evidence that ziftomenib retains activity against certain treatment-emergent MEN1 mutations associated with resistance to other menin inhibitors. The new scientific data add to the mechanistic understanding of ziftomenib and support Kura Oncology’s continued development of the therapy across molecularly defined AML populations.
Ziftomenib Demonstrates Broad Preclinical Activity in AML Models
The research published in Blood evaluated ziftomenib across multiple genetically defined leukemia models, including KMT2A-rearranged, NPM1-mutated and NUP98-rearranged leukemia. In these preclinical studies, ziftomenib demonstrated potent on-target activity by inhibiting the menin-KMT2A interaction and suppressing key KMT2A-regulated genes, including MEIS1 and HOXA9. The treatment also promoted leukemia-cell differentiation and reduced leukemia-cell viability. In multiple xenograft and patient-derived xenograft models, ziftomenib produced leukemia regression and extended survival, with durable responses reported in a patient-derived model even after treatment discontinuation. These findings provide mechanistic evidence for menin inhibition as a strategy against genetically driven acute leukemias and help explain the biological activity observed during the clinical development of ziftomenib. However, preclinical findings alone do not establish clinical efficacy across additional AML populations, making ongoing clinical studies important for determining the broader therapeutic potential of the drug.
Differentiated Binding Profile May Address Resistance Mechanisms
A key component of the publication was the evaluation of ziftomenib against MEN1 mutations that can emerge during treatment with menin inhibitors and potentially contribute to acquired resistance. Researchers found that ziftomenib maintained activity against certain resistance-associated menin mutations where other menin inhibitors did not demonstrate comparable activity. This result provides additional insight into the differentiated molecular binding profile of ziftomenib and the structural characteristics that may influence sensitivity to menin inhibition. Clinical observations have also indicated a relatively low frequency of treatment-emergent MEN1 resistance mutations with ziftomenib; in the KOMET-001 study, the MEN1-M3271 mutation emerged in one of 29 evaluable patients. These findings could become increasingly relevant as menin inhibitors move into broader clinical use, because understanding mechanisms of resistance may help guide treatment sequencing, combination strategies and the development of next-generation approaches for patients whose disease progresses following therapy.
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Kura Oncology Expands Ziftomenib Across AML Treatment Settings
Kura Oncology is continuing to develop ziftomenib (KOMZIFTI®) as a potential foundational therapy across the AML treatment continuum. The company is studying the once-daily oral menin inhibitor in combination with established standards of care across newly diagnosed and relapsed or refractory NPM1-mutated AML, as well as in KMT2A-rearranged and FLT3-mutated AML. The company is also investigating ziftomenib in additional oncology indications, including advanced gastrointestinal stromal tumors. The Blood publication provides further scientific validation for the mechanism and preclinical profile that supported ziftomenib’s progression from discovery into clinical development and regulatory approval. The next stage of development will depend on clinical evidence demonstrating whether the drug’s differentiated binding characteristics and activity against selected resistance-associated mutations translate into meaningful and durable benefits for broader groups of patients with menin-dependent acute leukemia.
Source:Kura Oncology press release
