A Phase 1 Study of Voruciclib in Subjects With B-Cell Malignancies or AML

This is a Phase 1, open-label, 3 + 3 dose escalation study to determine the safety and
preliminary efficacy of voruciclib in subjects with relapsed/refractory B cell malignancies
or AML after treatment with standard therapy.

There will be up to 5 dose level cohorts. Up to 6 subjects will be enrolled per dose cohort
and dose escalation will be allowed after 3 subjects have completed 1 cycle with no reported
dose limiting toxicities (DLTs) or 6 subjects completed 1 cycle with no more than 1 DLT.
Escalation to the next higher dose level will depend on demonstrated safety and tolerability.

Subjects may continue to receive voruciclib while there is evidence of clinical benefit and
acceptable toxicity as judged by the investigator.

Inclusion Criteria:

- Age ≥18 years

- Histologically-confirmed diagnosis of Follicular lymphoma (FL), mantle cell lymphoma
(MCL), marginal zone lymphoma (MZL), small lymphocytic lymphoma (SLL), chronic
lymphocytic leukemia(CLL), diffuse large B-cell lymphoma (DLBCL), or AML

a. Subjects must have disease that has relapsed or is refractory to 2 or more prior
regimens and in need of treatment due to progressive disease

- Presence of measurable disease defined per the 2008 International workshop on CLL
guidelines, or by 2014 Lugano criteria for non-Hodgkin lymphoma (does not apply for
AML subjects)

- Adequate hematologic parameters unless clearly due to the disease under study

- Adequate renal and hepatic function, per laboratory reference range at screening

Exclusion Criteria:

- For CLL subjects: only known histological transformation to an aggressive lymphoma

- For AML subjects:

1. Acute promyelocytic leukemia

2. Peripheral blast count > 25 × 10 9/L

- Known central nervous system involvement

- Significant cardiovascular disease

- Significant screening ECG abnormalities

- Subjects who require warfarin, anti-cancer therapeutics or investigational agents

- Evidence of an ongoing systemic bacterial, fungal, or viral infection (including upper
respiratory tract infections) at the time of start of voruciclib therapy

- Receipt of an allogeneic transplant within 6 months or an autologous transplant within
the preceding 3 months; evidence of ongoing graft-versus-host disease (GVHD)

- Prior therapy with a cyclin-dependent kinase (CDK9) inhibitor

- Ongoing immunosuppressive treatment at the time of the start of voruciclib therapy,
including systemic or enteric corticosteroids except as follows:

1. Prior to the start of voruciclib therapy, subjects may be using systemic
corticosteroids (≤20 mg/day of prednisone or equivalent), topical, or inhaled
corticosteroids

2. During study therapy, subjects may use systemic, topical, or enteric
corticosteroids, if needed