Preclinical Study Highlights Ziftomenib Activity Across Genetically Defined Leukemia Models and Certain Resistance-Associated MEN1 Mutations – Kura Oncology
10 August 2026 – Kura Oncology, Inc. announced the publication of a manuscript in Blood, the flagship journal of the American Society of Hematology, detailing the discovery and preclinical development of ziftomenib, a potent and selective menin inhibitor approved by the U.S. Food and Drug Administration in 2025 for adult patients with relapsed or refractory NPM1-mutated acute myeloid leukemia (AML).
The publication describes the scientific foundation underlying ziftomenib’s development, including its differentiated binding profile, potent and selective inhibition of the menin-KMT2A interaction, activity across multiple genetically defined leukemia models, and activity against certain treatment-emergent MEN1 mutations associated with resistance to other menin inhibitors.
“The publication in Blood captures the remarkable scientific journey that led to ziftomenib, from identifying the menin-KMT2A interaction as a compelling therapeutic target to designing a potent and selective inhibitor with the properties needed for clinical development. The findings also provide important insight into the molecular properties that distinguish ziftomenib and supported its advancement from discovery through clinical development.” – Francis Burrows, Ph.D., Chief Scientific Officer of Kura Oncology.
Researchers from the University of Michigan pioneered the discovery of small molecules that target the interaction between menin and KMT2A, which plays an important role in leukemias with genetic changes such as NPM1 mutations and KMT2A rearrangements. A collaboration between the University of Michigan and Kura Oncology, initiated in 2014, ultimately led to the development of ziftomenib, a menin inhibitor that Kura Oncology subsequently advanced through clinical development and FDA approval.
Study findings in preclinical leukemia models
As reported in Blood, across KMT2A-rearranged, NPM1-mutated and NUP98-rearranged leukemia models, ziftomenib demonstrated potent on-target activity, including suppression of key KMT2A-regulated genes such as MEIS1 and HOXA9, induction of differentiation, and reduced leukemia cell viability.
Ziftomenib also was shown to induce leukemia regression and extended survival in multiple xenograft and patient-derived xenograft models, including durable responses observed after treatment discontinuation in a patient-derived model.
The research further evaluated ziftomenib against treatment-emergent MEN1 mutations associated with resistance to menin inhibition. Researchers found that ziftomenib retained activity against certain resistance-associated menin mutations while other menin inhibitors did not, providing additional insight into ziftomenib’s differentiated binding profile and the molecular determinants of resistance. Clinical studies have shown a low frequency of treatment-emergent MEN1 resistance mutation with ziftomenib; in KOMET-001, MEN1-M3271 emerged in only 1 of 29 evaluable patients.i
“Ziftomenib represents the culmination of years of discovery, development, and dedication from an extraordinary team of scientists, clinicians, and colleagues who share a common goal: making a meaningful difference for patients. This publication provides important scientific validation of the properties that enabled ziftomenib to advance from an early discovery program to an approved medicine for adult patients with relapsed or refractory NPM1-mutated AML. More importantly, these findings reinforce our conviction in ziftomenib’s potential as a foundational therapy across the AML treatment continuum as we continue to pursue combination strategies with established standards of care and development across molecularly defined patient populations.” – Troy E. Wilson, Ph.D., J.D., President and Chief Executive Officer of Kura Oncology.
Kura continues to advance ziftomenib as a potential foundational therapy across the AML treatment continuum by combining it with multiple standards of care in molecularly defined patient populations. These efforts are designed to build upon ziftomenib’s established activity in NPM1-mutated AML and expand its potential benefit to additional patients with menin-dependent acute leukemias, which represent up to 50% of eligible patients.
