A Phase I Study of Oral ABL001 in Patients With CML or Ph+ ALL

This first-in-human trial with ABL001 is a dose escalation study whose primary purpose is to
estimate the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE) of
single agent ABL001 in CML or Ph+ ALL patients, and in combination with either Nilotinib or
Imatinib or Dasatinib in Ph positive CML patients. The safety, tolerability and
pharmacokinetic (PK) profile of ABL001 and ABL001+Nilotinib, ABL001+Imatinib and
ABL001+Dasatinib will be assessed together with an evaluation of pharmacodynamic (PD) changes
in peripheral blood mononuclear cells (PBMC) and bone marrow aspirates and all data may
contribute to the assessment of the RDE.

An understanding of the MTD/RDE, safety profile, PK/PD relationship, and preliminary evidence
of anti-CML and ALL activity will be used to inform future development in adults with CML and
Ph+ ALL. By virtue of its distinct pharmacological profile and by preclinical pharmacological
studies demonstrating an additive effect, a combination of ABL001 and a tyrosine-kinase
inhibitor (TKI) has the potential to achieve a deeper molecular response in a higher
proportion of CML patients as compared to single agent TKI therapy. Such a combination has
the added advantage of targeting the ABL kinase domain at two distinct locations,
theoretically preventing single point mutation-associated treatment resistance. The
prediction is that a nilotinib+ABL001, imatinib+ABL001 and/or dasatinib+ABL001 combination
will increase the percentage of patients who achieve a complete molecular response (CMR) and
decrease the time to CMR, thereby increasing the possibility of achieving sustained
treatment-free remissions in these patients. In addition, some patients may be intolerant of
therapy with TKIs or may develop mutations that promote resistance to TKI therapy. In these
patients, ABL001 may provide a novel therapeutic option.

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, respectivelyRadiotherapy
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

Other protocol-defined inclusion/exclusion criteria may apply