A Phase I, Multicenter, Open-Label Study of Oral ABL001 in Patients with Chronic Myelogenous Leukemia or Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia

The design of a phase I, open label, dose finding study was chosen in order to establish a
safe and tolerated dose of single agent ABL001 in Chronic myeloid leukemia (CML) and
Philadelphia chromosome positive Acute lymphoblastic leukemia (Ph+ ALL) patients who are
relapsed or refractory to or are intolerant of Tyrosine kinase inhibitors (TKIs), and of
ABL001+Nilotinib, ABL001+Imatinib and ABL001+Dasatinib in Ph positive CML patients who are
relapsed or refractory to TKIs.

Inclusion Criteria:

For CML patients either:

- a. Patients with Ph+ CML in chronic or accelerated phase who were previously treated
with at least two different tyrosine kinase inhibitors prior to study entry and are
relapsed, refractory to or intolerant of TKIs as determined by investigators or

- b. Patients with CML in chronic or accelerated phase who exhibit relapsed disease
associated with the presence of the T315I "gatekeeper mutation" after at least one TKI
are also eligible provided that no other effective therapy exists

For ALL and CML-BP patients:

- Patients with CML BP or Ph+ ALL who have a cytopathologically confirmed diagnosis and
are relapsed or refractory to at least one prior TKI or intolerant of TKIs. TKI
failure for Ph+ ALL and CML-BP patients is defined as at least the loss of Molecular
Response (MR) 4.5 (BCR-ABL ≤ 0.0032%)

- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2

- Willingness and ability to comply with all study procedures

- Written informed consent obtained prior to any screening procedures

Exclusion Criteria:

Wash-out period:

- Systemic antineoplastic therapy (including cytotoxic chemotherapy, alfa-interferon and
toxin immunoconjugates) or any experimental therapy within 14 days or 5 half-lives,
whichever is shorter, before the first dose of study treatment

- Therapy with TKIs as single agent within 5 half-lives before the first dose of study
treatment

- Unconjugated monoclonal antibody therapies within 28 days or 5 half-lives, whichever
is shorter, before the first dose of study treatment

- For patients receiving ABL001 in combination with either nilotinib or imatinib or
dasatinib, intolerance to nilotinib, imatinib or dasatinib, respectively

- Radiotherapy with a wide field of radiation within 4 weeks or radiotherapy with a
limited field of radiation for palliation within 1 week of the first dose of study
treatment.

- CNS irradiation for meningeal leukemia, except if radiotherapy occurred > 3 months
previously. At least four weeks must have elapsed since prophylactic CNS irradiation
given as part of a front-line therapy regimen for ALL

- Major surgery within 2 weeks before the first dose of study treatment