A PHASE II MULTICENTER OPEN -LABEL TRIAL OF TAGRAXOFUSP (TAG) IN COMBINATION WITH VENETOCLAX AND AZACITIDINE (VEN/AZA) IN ADULTS WITH PREVIOUSLY UNTREATED CD123+ ACUTE MYELOID LEUKEMIA (AML) WHO ARE INELIGIBLE FOR INTENSIVE CHEMOTHERAPY

This study will be divided into 2 parts (Part 1 and Part 2). Part 1 will evaluate 2 doses
of tagraxofusp (9 and 12 micrograms/kilogram/day [μg/kg/day]), used in combination with
venetoclax and azacitidine, to determine the dose for Part 2. This determined dose, in
combination with venetoclax and azacitidine, will then be further evaluated in Part 2 in
2 cohorts (TP53 mutated and TP53 wild type). Both parts will be conducted in participants
with previously untreated CD123+ AML who are ineligible for intensive chemotherapy.

Key Inclusion Criteria:

- Previously untreated with histological confirmation of AML by World Health
Organization 2022 criteria and are ineligible for treatment with a standard
cytarabine and anthracycline induction regimen due to age, or comorbidity.

- Participant has any level of CD123 expression on blasts.

- Participants must be considered ineligible for intensive chemotherapy, defined by
the following:

- ≥75 years of age; or

- ≥18 to 74 years of age with at least 1 of the following:

- Eastern Cooperative Oncology Group (ECOG) performance status of 2 or 3.

- Diffusing capacity of the lung for carbon monoxide of ≤65% or forced
expiratory volume in 1 second ≤65%.

- Baseline creatinine clearance ≥30 to <45 milliliters/minute calculated by
the Cockcroft Gault formula or measured by 24-hour urine collection.

- Hepatic disorder with total bilirubin >1.5 x upper limit of normal.

- Any other condition for which the physician judges the participant to be
unsuitable for intensive chemotherapy.

- ECOG performance status:

- 0 to 2 for participants ≥75 years of age, or

- 0 to 3 for participants ≥18 to 74 years of age.

Key Exclusion Criteria:

- Participant has received prior therapy for AML.

- Participant is willing and able to receive standard induction therapy.

- Participant has received treatment for an antecedent hematologic disease with a
hypomethylating agent, venetoclax, tagraxofusp, purine analogue, cytarabine,
intensive chemotherapy, SCT, chimeric antigen receptor-T therapy, or other
experimental therapies.

- Participant has AML with central nervous system involvement.

Note: Other inclusion/exclusion criteria may apply.