Study of ACY-241 Alone and in Combination With Pomalidomide and Dexamethasone in Multiple Myeloma

During phase 1a, patients will receive 1 cycle of ACY-241 monotherapy. Patients who complete
the ACY-241 monotherapy cycle without a dose limiting toxicity (DLT) and are clinically
stable may continue to phase 1b combination therapy, beginning with Cycle 2. During phase 1b,
patients will receive ACY 241 in combination with pomalidomide and low dose dexamethasone at
the currently approved pomalidomide dose and schedule. Each cohort of patients in phase 1a
and phase 1b will consist of at least 3 patients. The first patient enrolled in each cohort
of phase 1a will be observed for 1 week before enrollment of subsequent patients in the
cohort. Patients who withdraw consent before entering phase 1b will be replaced. (Replacement
patients must complete phase 1a prior to continuing to phase 1b.) Patients who experience a
DLT or other unacceptable toxicity in Cycle 1 of phase 1a monotherapy or Cycle 2, the first
cycle of phase 1b combination therapy, will be removed from study treatment. An assessment of
the safety of treatment will be completed by the Safety Review Committee (SRC) prior to
dose-escalation.

Key Inclusion Criteria:

- Must have a documented diagnosis of MM and have relapsed or relapsed-and-refractory
disease. All patients must have relapsed after having achieved at least stable disease
(SD) for at least 1 cycle of treatment to at least 1 prior regimen and then developed
progressive disease (PD). Relapsed-and-refractory patients also have documented
evidence of PD during or within 60 days of completing last treatment

- Must have undergone prior treatment with at least 2 cycles of lenalidomide and at
least 2 cycles of proteasome inhibitor unless not a candidate.

- May have undergone prior treatment with pomalidomide if patient is not refractory to
pomalidomide and has previously achieved a response of MR or better to pomalidomide.

- Must have measurable disease (serum M-protein or urine M-protein).

- Must have Eastern Cooperative Oncology Group (ECOG) Performance score of 0, 1, or 2.

- Must be able to take low-dose aspirin, low molecular weight heparin, or other
equivalent antithrombotic or anticoagulant daily as prophylactic anticoagulation.

Key Exclusion Criteria:

- Prior therapy with pomalidomide with best response of PD or SD.

- Prior therapy with histone deacetylase (HDAC) inhibitor.

- Any of the following laboratory abnormalities: Absolute neutrophil count(ANC) <
1,000/µL, Platelet count < 75,000/µL or < 50,000/µL for patients in whom ≥ 50% of bone
marrow nucleated cells are plasma cells, Hemoglobin < 8 g/dL, Creatinine clearance <
45 mL/min according to Cockcroft-Gault formula. If creatinine clearance calculated
from the 24 hour urine sample is ≥ 45 mL/min, patient will qualify for the trial,
Aspartate transaminase (AST) or Alanine transaminase (ALT) > 3.0 × Upper Limited
Normal (ULN), Serum total bilirubin > 2.0 mg/dL or > 3.0 × ULN for patients with
hereditary benign hyperbilirubinaemia.

- Hematologic growth factors are not allowed at screening or during the first cycle of
phase 1a or 1b.

- Nonsecretory myeloma or free light chain detected in serum only (ogliosecretory).

- Hypersensitivity to thalidomide, lenalidomide, pomalidomide, or dexamethasone

- Patients who received an allogeneic bone marrow or allogeneic peripheral blood stem
cell transplant less than 12 months prior to initiation of study