A MENIN INHIBITOR STUDY

FOR PATIENTS WITH RELAPSED OR REFRACTORY ACUTE MYELOID LEUKEMIA

ABOUT KOMET-001

The goal of the Phase 2 registration-enabling expansion is to further evaluate the anti-tumor activity and tolerability of ziftomenib in patients with NPM1-mutant (NPM1-m) relapsed or refractory (R/R) acute myeloid leukemia (AML).

KURCOR_15223-001-045_Komet_Visual_Schema_001

ABOUT ZIFTOMENIB

Ziftomenib, an oral investigational drug candidate, is a novel compound targeting the menin-KMT2A (MLL) interaction for treatment of genetically defined AML patients with high unmet need. In preclinical models, ziftomenib inhibits the KMT2A (MLL) protein complex and has downstream effects on HOXA9/MEIS1 expression.

Epigenetic modifications by the menin-KMT2A (MLL) complex lead to expression of HOXA9/MEIS1, which leads to proliferation, stemness and differentiation block.¹
These KMT2A (MLL) rearrangements alter normal histone methyltransferase function of KMT2A (MLL), resulting in sustained high HOX levels and blockage of hematopoietic differentiation, ultimately leading to acute leukemia.^1-3
Mutant NPM1 is also dependent on the interaction between menin and wild-type KMT2A (MLL) to drive leukemogenic gene expression.¹
Ziftomenib is an investigational small molecule inhibitor of the menin-KMT2A (MLL) complex that may inhibit the survival, growth, and proliferation of certain kinds of leukemia cells as demonstrated in vitro.⁴

NPM1–m AML

have NPM1-m with or without other gene mutations^5,6

STUDY OVERVIEW

Phase 1 (dose escalation and expansion) is complete
Phase 2 will evaluate the RP2D (600 mg QD) in patients with NPM1-m R/R AML
Objectives are to assess evidence of anti-leukemic activity, clinical benefit, and safety/tolerability

PATIENT CRITERIA

OUTCOME MEASURES

STUDY LOCATIONS

All 35 /AIM 0 /Arizona 2 /Australia 0 /Austria 0 /Belgium 0 /California 0 /California 1 /California 0 /Currents 0 /Denmark 0 /Florida 0 /Florida 1 /Florida 0 /France 6 /Georgia 0 /Germany 0 /Global 0 /Global 14 /Greece 0 /Illinois 1 /Indiana 1 /Italy 0 /Italy 1 /Kansas 0 /Kentucky 0 /Komet 35 /Kurrent 0 /Leadership In The News 0 /Malaysia 0 /Maryland 0 /Maryland 1 /Maryland 0 /Massachusetts 0 /Massachusetts 1 /Massachusetts 0 /Michigan 0 /Michigan 2 /Minnesota 0 /Minnesota 1 /Missouri 0 /Missouri 0 /Netherlands 0 /New Jersey 1 /New York 0 /New York 3 /New York 0 /North Carolina 0 /North Carolina 1 /Norway 0 /Oklahoma 0 /Pennsylvania 0 /Pennsylvania 1 /Pennsylvania 0 /Republic of Korea 0 /Spain 0 /Spain 7 /Taiwan 0 /Tennessee 0 /Tennessee 1 /Texas 2 /Texas 0 /Thailand 0 /United Kingdom 0 /United States 0 /United States 21 /United States 0 /Washington 0 /Washington 1 /Wisconsin 0 /Wisconsin 0

For more information, please email: KO-MEN-001@kuraoncology.com.
To connect with a medical science liaison (MSL), please email: medicalaffairs@kuraoncology.com.

REFERENCES

1.Kühn MW, Song E, Feng Z et al. Targeting chromatin regulators inhibits leukemogenic gene expression in NPM1 mutant leukemia. Cancer Discov. 2016;6(10):1166-1181. 2. Klossowski S, Miao H, Kempinska K, et al. Menin inhibitor MI-3454 induces remission in MLL1-rearranged and NPM1-mutated models of leukemia. J Clin Invest. 2020;130(2):981-997. 3. Chan AKN, Chen CW. Rewiring the epigenetic networks in MLL-rearranged leukemias: epigenetic dysregulation and pharmacological interventions. Front Cell Dev Biol. 2019;7:81. 4. Burrows F, Wu T, Kessler L, et al. A novel small molecule menin-MLL inhibitor for potential treatment of MLL-rearranged leukemias and NPM1/DNMT3A-mutant AML [abstract]. In: Proceedings of the AACR EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther. 2018;17(1 Suppl): Abstract nr LB-A27. 5. Thiede C, Koch S, Creutzig E, et al. Prevalence and prognostic impact of NPM1 mutations in 1485 adult patients with acute myeloid leukemia (AML). Blood. 2006;107(10):4011-4020. 6. Prata PH, Bally C, Prebet T, et al. NPM1 mutation is not associated with prolonged complete remission in acute myeloid leukemia patients treated with hypomethylating agents. Haematologica. 2018;103(10):e455-e457.

A MENIN INHIBITOR STUDY

FOR PATIENTS WITH RELAPSED OR REFRACTORY ACUTE MYELOID LEUKEMIA

ABOUT KOMET-001

ABOUT ZIFTOMENIB

NPM1–m AML

STUDY LOCATIONS

Banner MD Anderson Cancer Center

Centre Hospitalier Lyon Sud

CHU de Bordeaux

CHU de Lille

CHU de Nantes

Duke Cancer Institute

Fred Hutchinson Cancer Research Center

Hackensack University Medical Center

Harold C. Simmons Comprehensive Cancer Center – UT Southwestern Medical Center

Hopital Saint Louis

Hospital Universitari i Politecnic La Fe

Hospital Universitari Vall d’Hebron

Hospital Universitario Central de Asturias

Hospital Universitario Sanchinarro

Hospital Universitario Virgen del Rocio

Indiana University Melvin and Bren Simon Comprehensive Cancer Center

Institut Gustave Roussy

Institute of Hematology and Medical Oncology “L. and A. Seragnoli”

Karmanos Cancer Institute

Massachusetts General Hospital

Mayo Clinic

Mayo Clinic

Mayo Clinic

MD Anderson Cancer Center

MD Anderson Cancer Center

Northwestern University

Roswell Park Comprehensive Cancer Center

The Mount Sinai Hospital

UCLA Bowyer Oncology Center

Universitat de Barcelona

University of Maryland Greenebaum Comprehensive Cancer Center

University of Michigan Hospitals

UPMC Hillman Cancer Center

Vanderbilt-Ingram Cancer Center

Weill Cornell

REFERENCES