Inclusion Criteria:

- Participant must be at least 1 year old at the time the trial participant or legal guardian signs the informed consent form and will be assigned as follows:

• Adult arm: aged at least 12 years old.
• Pediatric arm: aged 1 to 17 years old.

For participants of the Escalation Part only:

- Adult and Pediatric Arms: Confirmed diagnosis of primary or secondary AML [any subtype except acute promyelocytic leukemia (APL) and juvenile myelomonocytic leukemia (JMML)] according to World Health Organization (WHO) 2022 classification. Participants with AML must meet one of the following criteria, a), b), c) or d) and are limited to those with no available (or are ineligible) therapy with known clinical benefit.

a) Primary Induction Failure (PIF) AML, defined as disease refractory to one of the following, i or ii.

i) An intensive induction attempt, per institution. Induction attempts include high-dose and/or standard-dose cytarabine ± an anthracyclines/anthracenedione ± an anti-metabolite, with or without growth factor or targeted therapy containing regimens.

Examples include but are not limited to:

• One cycle of high dose cytarabine (HiDAC) containing regimen
• One cycle of liposomal cytarabine and daunorubicin
• Two cycles of standard dose cytarabine containing regimen

ii) For adults who are age 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy; PIF is defined as AML refractory to one of the following less intensive regimens, 1 or 2: 1. 4 cycles of hypomethylating agents (HMA) or 2. 2 cycles HMA + venetoclax

b) Early relapse (ER) AML, defined as AML in relapse with CR duration < 6 months on prior induction treatment

c) Leukemia in first or higher relapse

d) For participants aged 1 to 17 years old, primary induction failure is defined as disease refractory after two cycles of induction therapy.

• Adult arm only: Confirmed diagnosis of cluster of differentiation 123 (CD123) + HR-MDS, with a Revised International Prognostic Scoring System (IPSS-R) risk category of intermediate or higher and are limited to those with no available (or are ineligible) therapy with known clinical benefit.

  • Not eligible for induction therapy and having completed ≥2 cycles of any of the following: hypomethylating agent (eg, 5 azacitidine or decitabine) and/or venetoclax, chemotherapy, or targeted agents.
  • Not eligible for autologous stem cell transplant (ASCT) and having completed ≥1 course of induction therapy.
• Adult and Pediatric arms and escalation part only: Confirmed diagnosis of CD123+ B-ALL without extramedullary lesions that have no available (or are ineligible) therapy with known clinical benefit.

For Participants in the Expansion Part Only (Adults only):

• For participants in Cohort A: Participants meeting inclusion criteria for AML participants that have been primary refractory (PIF) to prior induction treatment or who have had ER occurring 6 months or less after an initial remission on prior induction treatment.
• For participants in Cohort B: Participants meeting inclusion criteria for AML participants that have had late relapse (LR), occurring more than 6 months after an initial remission on prior induction treatment.
• Body weight at least 10 kg.
• Pediatric arm and escalation part only: Confirmed diagnosis of BPDCN according to World Health Organization (WHO) 2022 classification, who have relapsed or refractory disease with no available (or are ineligible) therapy with known clinical benefit.
• Pediatric arm and expansion part only: For participants in Cohort C: Participants with AML who have relapsed according to inclusion criteria for AML or have recurrent disease resistant or intolerant to available therapies.

Exclusion Criteria:

• Eastern Cooperative Oncology Group (ECOG) performance status >2 (≥18 years-old). Karnovsky Scale (16-17 years-old) <50% or Lansky Scale (<16 years-old) <50%.
• Ongoing or recent (within 5 years) evidence of significant autoimmune disease that requires or required treatment with systemic immunosuppressive treatments, which may suggest a risk for immune-related adverse events. The following are not exclusionary: vitiligo, childhood asthma that has resolved, residual hypothyroidism that required only hormone replacement or psoriasis that does not require systemic treatment.
• History of an invasive malignancy that requires active therapy (adjuvant hormonal therapy is allowed) other than the one treated in this study, with the exception of resected/ablated basal or squamous-cell carcinoma of the skin or carcinoma in situ of the cervix, or other local tumors considered cured by local treatment.
• Evidence of active central nervous system leukemia at the time of enrollment as evidenced by cytology or pathology. Except for participants aged 1 to 17 years, central nervous system 1 disease (CNS1) and CNS2 disease are allowed.
• Known acquired immunodeficiency syndrome (AIDS-related illnesses) or human immunodeficiency virus (HIV) disease requiring antiretroviral treatment, or having active hepatitis B or C infection, or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.
• Prior treatment with an anti-CD123-directed agent (except for participants with BPDCN in the pediatric arm).
• Prior HSCT with relapse beyond 3 months or prior CAR-T therapy in B-ALL with relapse beyond 2 months may be included only if off immunosuppression for a minimum of 4 weeks and no evidence of graft-versus-host disease (GVHD).
• Receiving at the time of first investigational medicinal product (IMP) administration corticosteroid as a concomitant medication with corticosteroid dose >10 mg/day of oral prednisone or the equivalent,
• AML, BPDCN, or HR-MDS participants with prior treatment with cellular therapy, eg, chimeric antigen receptor T cell (CAR-T) or chimeric antigen receptor NK cell (CAR-NK). Prior CAR-T therapy is allowed for participants with B-ALL.
• Concurrent treatment with other investigational drugs.
• Radiotherapy, even if palliative in intent, may not be given during the study.
• Prophylactic use of hematopoietic growth factors (eg, granulocyte-colony stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), erythropoietin) during the DLT observation period in the Dose Escalation Part only. - Individuals accommodated in an institution because of regulatory or legal order; prisoners or participants who are legally institutionalized.
• Pregnant and breast-feeding women.
• History of solid organ transplant, including corneal transplant.
• Average QTc (using the Fridericia correction calculation) greater than 470 milliseconds (msec) at screening. For pediatric arm participants only, inadequate ejection fraction as per institutional standards at screening or any clinically significant cardiac conditions (including but not limited to congestive heart failure, myocarditis, pericarditis, arrythmias).
• Pediatric arm only: Participants with known inherited bone marrow failure syndromes (e.g., bloom syndrome, ataxia-telangiectasia, Fanconi anemia, Kostmann syndrome, Shwachman syndrome). Participants with Down syndrome with adequate organ function as per Investigator discretion are allowed to participate in the study.

The above information is not intended to contain all considerations relevant to a potential participation in a clinical trial.