Study of PTC299 in Relapsed/Refractory Acute Leukemias

Inclusion Criteria:

- Participant must have relapsed/refractory AML and exhausted standard available
therapies known to provide clinical benefit.

- Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to (≤)
2

- Women of childbearing potential must be practicing a highly-effective method of birth
control for up to 50 days after the last dose of study drug.

- A man who is sexually active with a woman of childbearing potential and has not had a
vasectomy must agree to use a barrier method of birth control for up to 50 days after
the last dose of study drug.

- Participants must be willing to participate to the study, have the ability to
understand and adhere to study visit schedule and other protocol procedures, and be
able and willing to sign a written informed consent form.

Exclusion Criteria:

Medical history:

- Women who are or plan to become pregnant, or who are currently breastfeeding.

- Persistence of any clinically relevant (Common Terminology Criteria for Adverse Events
[CTCAE] Grade 2 or above) toxicities from previous therapy.

- Active alcohol or drug abuse.

- Previous drug-induced liver injury.

Cardiac assessments:

- Uncontrolled congestive heart failure, unstable angina pectoris.

- History or current evidence of a myocardial infarction during the last 6 months.

- QTc prolongation greater than (>) 500 milliseconds (msec) (Fridericia formula).

- Congenitally long QT syndrome or has received any marketed or experimental compound in
the last 4 weeks or 5 half-lives (whichever is shorter) prior to entering the study
with possible or known effects of QT prolongation. (If equivalent medication is not
available, QTc will be closely monitored.)

Laboratory assessments:

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) greater than or
equal to (≥) upper limit of normal (ULN).

- Serum bilirubin ≥ ULN (except those known to have Gilbert's syndrome).

- Creatinine clearance ≤ 45 milliliters per minute (mL/min).

- Any laboratory abnormality, which in the opinion of the investigator, places the
subject at an unacceptably high risk for toxicities.

Gastrointestinal (GI) assessments:

- Liver malignancy (including metastases) or chronic liver disease.

- History of GI surgery or procedures or conditions that might interfere with the
absorption or swallowing of the study drug.

Immunologic:

- Known hypersensitivity to study drug or its excipients.

Miscellaneous:

- Any sign of active uncontrolled infections; any severe chronic disease potentially
interfering with the protocol, including human immunodeficiency virus (HIV) infection,
or active hepatitis B or C or those with a positive screen for hepatitis A
Immunoglobulin M (IgM).

- Any other malignancies within the past 2 years other than basal cell skin cancer or
carcinoma in situ of the cervix.

- Participant concomitantly receiving any other investigational agents.

- Systemic chemotherapy within 2 weeks or investigational therapy within 5 half-lives
prior to first dose of study drug, unless there is evidence of rapidly progressive
disease; persistent chronic clinically significant toxicities from prior chemotherapy
must not be >Grade 1. For monoclonal antibodies, the washout from prior therapy will
be 4 weeks. Use of hydroxyurea (Hydrea) is permitted up to 24 hours prior to start of
study drug for control of proliferative disease.

- Participant with central nervous system (CNS) involvement.

- Participant is pregnant or breastfeeding or expecting to conceive or father children
within the projected duration of the study.

- Participant is receiving CYP2B6 substrates such as bupropion and methadone.

- Participant is receiving strong CYP3A4 inducers such as carbamazepine, enzalutamide,
mitotane, phenytoin, rifampin, and St. John's wort (hypericin) or drugs that are
exclusively substrates of CYP3A4.

- Participant is receiving moderate or strong CYP3A4 inhibitors.