Safety, PK, PD, and Antitumor Activity of SNS-062 (Vecabrutinib) in B Lymphoid Cancers

Phase 1b (Dose Escalation) This portion of the study will evaluate the safety and
pharmacology of a range of SNS-062 (vecabrutinib) dose levels administered to subjects with
previously treated B-lymphoid malignancies, including: chronic lymphocytic leukemia/small
lymphocytic lymphoma (CLL/SLL), lymphoplasmacytoid lymphoma/Waldenström's macroglobulinemia
(LPL/WM), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), diffuse large B-cell
lymphoma of the activated B-cell subtype (DLBCL-ABC), and follicular lymphoma (FL).

All subjects will self-administer SNS-062 orally BID. The dose-limiting toxicity (DLT) window
will be 4 weeks (1 cycle in length). Assessments on study will be performed in 4-week cycles.
Cohorts of 3 to 6 subjects will be sequentially enrolled at progressively higher dose levels
of SNS-062 using a standard 3+3 dose-escalation design.

Based on the pattern of dose-limiting toxicities (DLTs) observed in the first cycle (4
weeks), escalation will proceed to define a maximum tolerated dose (MTD) and/or a recommended
dose (RD) that may be the MTD or a lower dose. An additional 6 subjects may be accrued at the
MTD or the RD to confirm SNS-062 safety and pharmacology as a prelude to further clinical
evaluation. Assessments regarding DLTs and dose escalation will be performed by a Safety
Review Committee (SRC) comprising, but not limited to, the principal investigators, the
medical monitor and the study sponsor drug safety representative.

Phase 2 (Cohort Expansion) This portion of the study provides cohort expansion to further
explore the clinical activity, safety, and pharmacology of SNS-062 monotherapy. Accrual will
occur independently for each of the 4 disease and mutation-specific cohorts. Subjects will
self-administer SNS-062 orally at the RD of SNS-062 identified in the Phase 1b portion of the
study. The SRC will meet regularly to assess the efficacy and safety for each cohort.

Inclusion Criteria (Key factors listed):

- Eastern Cooperative Oncology Group Performance Status of ≤2.

- Confirmed malignancy with relapsed/refractory disease after ≥2 lines of standard
systemic therapy including prior BTK inhibitor therapy having CLL, LPL/WM, MCL or MZL
and for DLBCL-ABC and FL, after ≥2 lines of standard systemic therapy.

- Presence of measurable disease through various assessments depending on specific
cancer type.

- Current medical need for therapy of the B-lymphoid malignancy due to disease-related
symptoms, lymphadenopathy, organomegaly, extranodal organ involvement, or PD.

Exclusion Criteria (Key factors listed):

- Active central nervous system involvement.

- History of second primary malignancy that has progressed or required systemic
treatment in the past 2 years. Exceptions include: local cancers of the skin, cervix
or breast cancers, non-invasive bladder cancer, hormone sensitive prostate cancer with
stable PSA ≥3 months, and other localized solid tumors in situ/other low risk cancers.

- Significant cardiovascular disease or electrocardiogram (ECG) abnormalities

- Ongoing risk for bleeding due to bleeding diathesis, platelet function disorder,
uncontrolled peptic ulcer disease, oral anticoagulation medications.

- Evidence of uncontrolled systemic bacterial, fungal or viral infections at the start
of drug therapy.

- Demonstrated intolerance to BTK inhibitor as shown by discontinuation due to adverse
effects.

- Use of a moderate or strong inhibitor or inducer of CYP3A4 within 7 days prior to
start of study therapy (e.g., some antibiotics, antifungals, anticonvulsants,
grapefruit).