A Dose Optimisation Study of ASLAN003 in Acute Myeloid Leukemia

ASLAN003-003 is a multi-center, Phase IIA study to determine the optimum dose of ASLAN003
based on the safety, efficacy, and tolerability of varying doses of ASLAN003 (100 mg QD, 200
mg QD, 100 mg BID, and possibly 200 mg BID) administered to AML subjects daily for a
continuous 28-day treatment cycle until disease relapse, disease progression, unacceptable
toxicity, or withdrawal of consent.

The study has 2 parts and plans to enroll a total of 44 to 56 patients with 18 to 24 patients
in Part 1 and 26 to 32 patients in Part 2 (comprising Parts 2A and 2B). The Overall Complete
Remission Rate will be evaluated in AML patients not eligible for standard treatment (Part 1)
and in relapsed and refractory AML patients (Part 2A) using the optimum dose of ASLAN003
established in Part 1 of the study. In Part 2B of the study, the appropriate dose of ASLAN003
in combination with azacitidine in older (more than or equal to 60 years) AML patients who
have exhausted any approved and available treatment options will be determined.

Inclusion Criteria:

1. Patients who are of or older than 18 years old in the United States or are of or older
than the legal age in the respective countries at the time when written informed
consent is obtained

2. Patients who are able to understand and willing to sign the informed consent form
(ICF)

3. Patients who are diagnosed with AML according to the 2016 revision to the World Health
Organization classification of myeloid neoplasms and acute leukemia (refer to Appendix
1: WHO Classification of Acute Myeloid Leukemia)

4. Patients who have a sufficient archival or fresh BM aspiration sample for the
evaluation of relevant exploratory endpoint.

Note: Patients who do not have sufficient archival BM aspiration sample and refuse to
repeat the procedure may be enrolled in the trial only after written confirmation by ASLAN
5. Part 1: Patients who are ineligible for standard treatment of AML including to the
following conditions:

- Patients who are ineligible for chemotherapy, and have exhausted any approved and
available treatment options. More details on patients who are considered as ineligible
or unfit for chemotherapy as per Ferrara et al, Leukemia, 2013 can be found in
Appendix 4.

- Patients who have relapsed from prior remission;

- Patients who have failed to respond to prior therapy including chemotherapy,
hypomethylating agents, and bone marrow transplantation.

5. Part 2A: Patients who have relapsed or refractory AML to treatments including
chemotherapy, hypomethylating agents, bone marrow transplantation, and other
anti-leukemic agents

- Relapsed patients who have bone marrow blasts ≥5%; or reappearance of blasts in
the blood; or development of extramedullary disease after prior CR or CRi

- Refractory patients who have no CR or CRi after 2 courses of intensive induction
treatment 5. Part 2B: Older patients (more than or equal to 60 years) AML
patients who have exhausted any approved and available treatment options.

6. Patients who have an ECOG performance status of ≤ 2 7. Patients with adequate
renal and hepatic function, as defined below:

- Estimated Glomerular Filtration Rate (eGFR) or creatinine clearance (CrCl) (CrCl
calculated by the Cockroft and Gault method) ≥ 40 ml/min/1.73 m2

- Total bilirubin, AST, and ALT ≤ 1.5 × ULN

Exclusion Criteria:

1. Patients who are diagnosed with de novo myeloid sarcoma without BM involvement

2. Patients who are diagnosed with acute promyelocytic leukemia/retinoic acid receptor
alpha (PML-RARA)

3. Patients who received any other standard or investigational treatment for their
leukemia within the last 7 days before starting the first dose of study drug, with the
exception of leukapheresis and hydroxyurea

4. Patients with unresolved serious toxicity (≥ CTCAE 4.03 Grade 2) from prior
administration of standard or investigational treatment for their leukemia

5. Patients who have a positive test for human immunodeficiency virus (HIV), viral
hepatitis C infection (patients with sustained viral response are not excluded),
active viral hepatitis B infection (positive hepatitis B surface antigen [HBsAg]) with
hepatitis B virus deoxyribonucleic acid (DNA) exceeding 2000 IU/ml

6. Patients who have a known history of liver cirrhosis Child-Pugh score B or C

7. Patients who have any history of other malignancy unless in remission for more than 1
year (skin carcinoma and carcinoma-in-situ of uterine cervix treated with curative
intent is not exclusionary)

8. Female patients who are pregnant or breast-feeding

9. Patients with a known history of alcohol or drug addiction on the basis that there
could be a higher risk of non-compliance to study treatment

10. Patients with a history or presence of a clinically significant condition which in the
opinion of the Investigator could jeopardize the safety of the patient or the validity
of the study results

11. Patients who have been previously treated with ASLAN003