1. New Findings in Hematology: Independent Conference Coverage* of ASH 2015, December 5-8, 2015, Orlando, Florida Venetoclax Monotherapy in R/R CLL With del(17p) *CCO is an independent medical education company that provides state-of-the-art medical information to healthcare professionals through conference coverage and other educational programs. This program is supported by educational grants from Amgen, Celgene Corporation, Merck, Incyte, Seattle Genetics, and Takeda Oncology.

2. Venetoclax in R/R CLL With del(17p): Background  Pts with R/R CLL with del(17p) have limited options and face poor prognoses –Median PFS < 12 mos with frontline chemotherapy  Venetoclax: oral selective BCL2 inhibitor [1] –Induces p53-independent apoptosis of CLL cells  Phase I study showed 79% response rate to venetoclax in pts with R/R CLL [2] –ORR for R/R CLL with del(17p): 71% (95% CI: 52% to 86%)  Current study evaluated the efficacy and safety of single-agent venetoclax for the treatment of R/R CLL with del(17p) [3] 1. Souers AJ, et al. Nat Med. 2013;19:202-208. 2. Roberts AW, et al. N Engl J Med. 2015;[Epub ahead of print]. 3. Stilgenbauer S, et al. ASH 2015. Abstract LBA-6. Slide credit: clinicaloptions.comclinicaloptions.com

3. Venetoclax in R/R CLL With del(17p): Study Design  Single-arm, multicenter phase II study  Risk-based TLS prophylaxis used  Primary endpoint: ORR (IRC assessment)  Secondary endpoints: CR/PR, time to first response, DoR, PFS, OS, safety  Exploratory endpoint: MRD Slide credit: clinicaloptions.comclinicaloptions.com Stilgenbauer S, et al. ASH 2015. Abstract LBA-6. R/R CLL with del(17p); ECOG PS 0-2; no major organ dysfunction,* prior alloSCT, RT, other malignancy, or uncontrolled AI cytopenia (N = 107) Response assessed by iwCLL 2008 criteria ‡ *ANC ≥ 1000/µL, plt ≥ 40,000/mm 3, Hb ≥ 8 g/L, creatinine clearance ≥ 50 mL/min. † Pts with electrolyte imbalance after first dose received 20 mg dose for 1 wk. ‡ Physical exam/blood counts (monthly); CT scans to confirm clinical response (prespecified at Wk 36); BM biopsy to confirm CR. Venetoclax 20 mg QD Day 1 † 50 mg QD Days 2-7 100 mg QD Wk 2 200 mg QD Wk 3 400 mg QD Wk 4+

4. Venetoclax in R/R CLL With del(17p): Baseline Characteristics Slide credit: clinicaloptions.comclinicaloptions.com Stilgenbauer S, et al. ASH 2015. Abstract LBA-6. Characteristic Pts (N = 107*) Median age, yrs (range) 67 (37-85) Male, % 65 Prior therapies, median n (range)  Prior bendamustine/refractory, %  Prior fludarabine/refractory, %  Prior CD20 mAb, % 2 (1-10) 50/70 73/44 84 ECOG PS 1/2, % 52/8 1 or more nodes ≥ 5 cm, % 53 ALC ≥ 25 x 10 9 /L, % 51 TLS risk category, %  High  Medium  Low 42 40 18 Rai stage III or IV, % 48 IGHV unmutated, % 81 *Includes 1 pt without del(17p).

5. Venetoclax in R/R CLL With del(17p): Pt Disposition Pts (N = 107) Time on study, median mos (range) 12.1 (0.03-21.5) Active on venetoclax, n (%) 70 (65) Discontinuations, n (%)  Disease progression Richter’s transformation CLL progression  Adverse events  Proceed to stem cell transplantation 37 (35) 22 (21) 11 (10) 9 (8) 3 (3) Deaths*, n (%)  Due to disease progression 18 (17) 14 (13) Slide credit: clinicaloptions.comclinicaloptions.com Stilgenbauer S, et al. ASH 2015. Abstract LBA-6. *n = 11, ≤ 30 days; n = 7, ≥ 30 days.

6. Venetoclax in R/R CLL With del(17p): Best Responses  25/48 pts (52%) had no evidence of CLL in bone marrow by IHC  18/45 pts assessed (40%) were MRD negative in peripheral blood samples  Among 87 pts with baseline lymphocytosis, only 4 failed to normalize ALC count to < 4 x 10 9 /L –Median time to normalization: 22 days (range: 2-122)  Among 96 pts with baseline lymphadenopathy, 89 had ≥ 50% reduction in nodal size of the largest target lesion (by SPD) –Median time to ≥ 50% reduction: 2.7 mos (range: 0.7-8.4) Slide credit: clinicaloptions.comclinicaloptions.com Stilgenbauer S, et al. ASH 2015. Abstract LBA-6. Response, %InvestigatorIRC Overall response  CR or CRi  nPR  PR 73.8 15.9 3.7 54.2 79.4 7.5 2.8 69.2 No response  Stable disease 26.2 22.4 20.6 NA

7. Venetoclax in R/R CLL With del(17p): Response Duration and Survival Slide credit: clinicaloptions.comclinicaloptions.com Stilgenbauer S, et al. ASH 2015. Abstract LBA-6. Parameter iwCLL response, median mos (range)  Time to first response  Time to CR/CRi 0.8 (0.1-8.1) 8.2 (3.0-16.3) Duration of response: 12-mo estimates, % (n = 85)  All responders  CR/CRi/nPR  MRD negative 84.7 100 94.4 Survival rates: 12-mo estimates, % (95% CI) (n = 107)  PFS  OS 72 (61.8-79.8) 86.7 (78.6-91.9)

8. Venetoclax in R/R CLL With del(17p): AEs  Neutropenia –Baseline (any grade): 22.4% –Manageable with dose interruption or reduction, G- CSF, and/or antibiotics  5 pts with laboratory TLS during dose escalation –2 dose interruptions (1 day each), but no clinical TLS  Serious AEs in 55% of pts –Most common SAEs: pyrexia, 7%; AIHA, 7%; pneumonia, 6%; febrile neutropenia, 5% Slide credit: clinicaloptions.comclinicaloptions.com Stilgenbauer S, et al. ASH 2015. Abstract LBA-6. Treatment-Emergent AE,* % Any Grade 3/4 Any9676 Neutropenia4340 Diarrhea290 Nausea291 Anemia2718 Fatigue220 Pyrexia201 Thrombocytopenia1915 Hyperphosphatemia161 Vomiting151 Infection  Upper respiratory  Nasopharyngitis  UTI 72 15 14 9 20 2 NR *Occurring in ≥ 15% of pts.

9. Venetoclax in R/R CLL With del(17p): Conclusions  Venetoclax active with deep responses in R/R CLL with del(17p) –> 10% had IRC-confirmed CR, CRi, or nPR –> 20% of responders MRD negative  Authors conclude that venetoclax toxicity and risk- benefit profiles are acceptable –Risk of TLS effectively mitigated; no clinical TLS –Similar incidence of neutropenia, infection as with frontline chemoimmunotherapy Slide credit: clinicaloptions.comclinicaloptions.com Stilgenbauer S, et al. ASH 2015. Abstract LBA-6.

10. Go Online for More CCO Coverage of ASH 2015! Short slideset summaries of all the key data Additional CME-certified analyses with expert faculty commentary on all the key studies in:  Acute leukemias/chronic leukemias  Myeloma/plasma cell disorders  Lymphomas  MDS and myeloproliferative neoplasms clinicaloptions.com/oncology