Study of APVO436 in Patients With AML or MDS

Phase 1 - Open-label, Dose Escalation: The dose escalation stage of the study will test
weekly doses from 0.3 mcg to 100 mcg over 10 dose levels (cohorts). Cohorts 1 to 3 consist of
single patients and Cohorts 4 - 10 will consist of a minimum of 3 patients; an additional 3
patients may be added to the cohort if adverse events possibly related to APVO436 or
dose-limiting toxicities (DLTs) occur. The next dose level is started after patients in the
previous dose cohort have completed the first cycle of dosing and an evaluation for
dose-limiting toxicities (DLTs) during the first cycle has been completed.

Phase 1b - Expansion: The recommended-dose from Phase 1 will be further examined in 2
expansion cohorts consisting 24 AML patients (Cohort 1) and 24 MDS patients (Cohort 2).
Patients will receive APVO436 intravenously weekly for six 28-day cycles, unless disease
progression, intolerable toxicity, or withdrawal of consent occurs earlier. Patients with
evidence of clinical benefit at the end of Cycle 6 in the absence of unacceptable toxicity
may also continue on study for up to 12 total cycles at the discretion of Investigator (6
cycles in addition to the initial 6 cycles).

Inclusion Criteria:

1. Signed informed consent. Consent must be obtained prior to any study-related
procedure.

2. Age ≥ 18 years

3. Histologically confirmed AML or MDS:

1. AML - relapsed or refractory AML and refuses or is not a candidate for intensive
chemotherapy (due to prior failure or not eligible due to expected intolerance)
or allogeneic transplant

2. MDS - relapsed or refractory MDS with > 5% blasts in the marrow or any blasts in
the peripheral blood. Patients must have failed prior treatment with an HMA
(azacitidine, decitabine, or other HMA agent); failure is defined as intolerance
to HMA, lack of response [no complete remission (CR) by at least 6 cycles], or
have IWG-defined progressive disease during or after treatment with an HMA.

4. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

5. Life expectancy of > 2 months in the Investigator's opinion

6. White blood cells (WBC) ≤ 25,000 cells/mm3 (may receive hydroxyurea to bring WBC count
down prior to and during the first cycle of treatment with study drug if necessary)

7. Creatinine ≤ 2 × upper limit of normal (ULN)

8. Adequate liver test parameters: total bilirubin < 2.5 × ULN (if disease related or
secondary to Gilbert's disease, then total bilirubin < 3.5 mg/dL), aspartate
aminotransferase (AST), and alanine aminotransferase (ALT) < 3 × ULN

9. Prothrombin time (PT) / international normalized ratio (INR) and partial
thromboplastin time (PTT) < 1.5 × ULN

10. Patients and partners of childbearing potential must be willing to use adequate
contraception during the study and for 2 months after last study drug administration.
Adequate contraception means less than 1% chance of pregnancy may occur with proper
use of the method(s).

Exclusion Criteria:

1. Any central nervous system (CNS) (cerebral/meningeal) disease related to underlying
malignancy

2. History of seizures

3. Acute promyelocytic leukemia

4. Prior anti-CD123 therapy outside of this study

5. Prior allogeneic or solid organ transplant (with the exception of cornea or hair
transplant)

6. Any therapy or experimental treatment for MDS or AML within 7 days of the first dose
of study drug. Must have recovered to Grade ≤ 1 from any Grade 2 to 4 toxicity from
previous treatment. The use of hydroxyurea is acceptable and does not exclude the
patient.

7. Active, uncontrolled infection requiring systemic therapy. If the infection is
controlled or has resolved, maintenance and/or prophylactic systemic antimicrobials
are permitted.

8. Major surgery within 3 weeks prior to first dose of study drug

9. Known to be positive for HIV, hepatitis B virus surface antigen (HBsAg), hepatitis B
core antibody (HBcAb), or hepatitis C virus (HCV)

10. Pregnant or breast feeding

11. Any other active systemic malignancies. Exceptions: noninvasive non-melanoma skin
cancer, in situ carcinoma, cervical intraepithelial neoplasia, and breast or prostate
cancer that is well controlled with anti-hormonal therapy

12. Any current autoimmune disorder requiring immunosuppressive therapy

13. Requires more than a replacement dose of corticosteroids (i.e., > 10 mg/day of
prednisone or equivalent)

14. Any uncontrolled medical condition, including but not limited to:

1. Symptomatic congestive heart failure ≥ Class III (New York Heart Association
Functional Classification)

2. Uncontrolled hypertension

3. Unstable angina

4. Myocardial infarction within previous 6 months

5. Clinically significant arrhythmias not controlled by medication

6. Uncontrolled metabolic disorders such as hypercalcemia

15. Substance use disorder, psychiatric, cognitive, or any other condition that, in the
opinion of the Investigator, would pose a risk to the patient's safety, may compromise
the patient's ability to understand and comply with the protocol or provide informed
consent, or interfere with the study evaluation

16. Any difficulty complying with protocol requirements that may increase the risk
associated with study participation or study drug administration, or may cause a
safety concern for the patient