Main Inclusion Criteria:

1. CP-CML and AP-CML patients previously treated with and resistant or intolerant to
imatinib, dasatinib and nilotinib or those who developed the T315I mutation after any
TKI therapy. BP-CML and Ph+ ALL patients previously treated with and resistant or
intolerant to imatinib and dasatinib or those who developed the T315I mutation after
any TKI therapy.

2. Patients must be ≥ 18 years old.

3. Provide written informed consent.

4. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.

5. Men and women of childbearing potential must agree to effective contraception from the
time of signing informed consent through the Follow-up Visit, approximately 30 days
after last dose of ponatinib.

Main Exclusion Criteria:

Patients are not eligible for participation in the study if they meet any of the following
exclusion criteria:

1. Are eligible for an ongoing and accessible clinical trial of ponatinib

2. Have not adequately recovered from AEs due to agents previously administered

3. Require concurrent treatment with immunosuppressive agents, other than corticosteroids
prescribed for a short course of therapy.

4. Have previously been treated with ponatinib.

5. Have significant or active cardiovascular disease, specifically including, but not
restricted to:

- Myocardial infarction within 3 months prior to first dose of ponatinib,

- History of clinically significant atrial arrhythmia or any ventricular
arrhythmia,

- Unstable angina within 3 months prior to first dose of ponatinib,

- Congestive heart failure within 3 months prior to first dose of ponatinib.

6. Have abnormal QTcF (> 450 ms for males or > 470 ms for females)

7. Have a significant bleeding disorder unrelated to CML or Ph+ ALL.

8. Have a history of pancreatitis or alcohol abuse

9. Have elevated amylase or lipase (> 1.5 x ULN for institution) at entry.

10. Have inadequate hepatic function or any of the following:

- Total bilirubin > 1.5 x ULN for institution at entry

- Alanine aminotransferase and aspartate aminotransferase > 2.5 x ULN for
institution at entry

- Prothrombin time >1.5 x ULN for institution at entry

11. Have inadequate renal function or serum creatinine > 2.5 x ULN for institution at
entry

12. Have uncontrolled hypertriglyceridemia or triglycerides > 450 mg/dL at entry.

13. Have malabsorption syndrome or other gastrointestinal illness that could affect
absorption of orally administered ponatinib.

14. Women who are pregnant or lactating.

15. Underwent major surgery within 14 days prior to the first dose of ponatinib.

16. Have ongoing or active infection (including known history of human immunodeficiency
virus [HIV], hepatitis B virus [HBV], or hepatitis C virus [HCV]).

17. Suffer from any condition or illness that, in the opinion of the Investigator would
compromise patient safety or interfere with the evaluation of the safety of the study
drug.