∙ Patients with refractory or relapsed AML defined as the reappearance of ≥ 5% blasts in the bone marrow and who have also failed or are ineligible for any approved standard of care therapies, including HSCT.

• Phase 1b:

‣ Patients with a documented lysine\[K\]-specific methyltransferase 2-rearrangement (KMT2A-r), or

⁃ Patients with a documented nucleophosmin 1 mutation (NPM1-m)

• Phase 2:

‣ Patients with a documented nucleophosmin 1 mutation (NPM1-m)

• Sub-studies:

‣ Sub-studies 1 and 2: Patients with R/R AML with NPM1-m or other mutations associated with MEIS1 overexpression.

⁃ Sub-study 3: Patients with R/R Acute Lymphoblastic Leukemia (ALL) with KMT2A-r.

⁃ Sub-study 4: Patients with R/R AML with mutations associated with MEIS1 overexpression.

• ≥ 18 years of age.

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2, and a life expectancy of at least 2 months.

• Adequate liver and kidney function according to protocol requirements.

• Peripheral white blood cell (WBC) counts ≤ 30,000/μL. Patients may receive hydroxyurea to control and maintain white blood cell count prior to enrollment.

• Women of childbearing potential must be willing to use a highly effective method of contraception throughout the study and for at least 187 days after the last dose of study treatment.

• Males with female partners of childbearing potential must agree to use a highly effective method of contraception throughout the study and for at least 97 days after the last dose of study treatment.