1. New Findings in Hematology: Independent Conference Coverage* of ASH 2015, December 5-8, 2015, Orlando, Florida TOURMALINE-MM1: Improved PFS With Ixazomib + Len/Dex in R/R MM *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. TOURMALINE-MM1: Background  Feasible long-term therapy options needed for MM because of significant improvements in pt survival with PI- and IMiD-based treatment regimens  All-oral combination of PI ixazomib with lenalidomide/dexamethasone (Rd) showed promising efficacy and tolerability in newly diagnosed MM [1] –Safety profile encouraging for long-term use  Phase III TOURMALINE-MM1 trial: first interim analysis (with final PFS) reported here [2] 1. Kumar SK, et al. Lancet Oncol. 2014;15:1503-1512. 2. Moreau P, et al. ASH 2015. Abstract 727. Slide credit: clinicaloptions.comclinicaloptions.com

3. TOURMALINE-MM1: Study Design  Randomized, double-blind, placebo-controlled phase III trial [1]  Primary endpoint: PFS by IRC per IMWG criteria [2]  Secondary endpoints (data not yet mature): OS, OS in del(17p) pts 1. Moreau P, et al. ASH 2015. Abstract 727. 2. Rajkumar SV, et al. Blood. 2011;117:4691-4695. Ixazomib 4 mg PO D1,8,15 + Lenalidomide 25 mg* D1-21 + Dexamethasone 40 mg D1,8,15,22 (n = 360) R/R MM pts with measurable disease; 1-3 prior treatments; CrCl ≥ 30 mL/min; not refractory to PIs or lenalidomide (N = 722) Placebo D1,8,15 + Lenalidomide 25 mg* D1-21 + Dexamethasone 40 mg D1,8,15,22 (n = 362) 28-day cycles until PD or unacceptable toxicity Stratified by prior therapy (1 vs 2-3), ISS stage (I-II vs III), and prior PI exposure (yes vs no) *10 mg for pts with CrCl ≤ 60 or ≤ 50 mL/min. Slide credit: clinicaloptions.comclinicaloptions.com

4. Characteristic Ixazomib + Rd (n = 360) Placebo + Rd (n = 362) Median age, yrs (range)66 (38-91)66 (30-89) Male, %5856 Stratification factors, %  ISS stage I or II/III  Lines of prior tx, 0-1 or 2  PI exposed 87/13 59/41 69 88/12 59/41 70 High-risk cytogenetics,* %2117 Prior regimen, %  Bortezomib  Thalidomide  Lenalidomide  Carfilzomib  Melphalan  Stem cell transplantation 69 44 12 <1 81 59 69 47 12 1 80 55 TOURMALINE-MM1: Baseline Characteristics *t(4;14), t(14;16), del(17p). Moreau P, et al. ASH 2015. Abstract 727. Slide credit: clinicaloptions.comclinicaloptions.com

5. TOURMALINE-MM1: PFS Moreau P, et al. ASH 2015. Abstract 727. Slide credit: clinicaloptions.comclinicaloptions.com  Addition of ixazomib to Rd resulted in 35% improvement in PFS vs Rd alone  PFS benefit with ixazomib seen in all prespecified subgroups, including cytogenetic high risk, PI and IMiD exposed 100 80 60 40 20 0 Log-rank P =.012 HR (95% CI): 0.742 (0.587-0.939) Number of events: IRD 129; placebo-Rd 157 Median PFS: IRd: 20.6 mos Placebo-Rd: 14.7 mos 024681012141618202224 Time from randomization (mos) Probability of PFS (%)

6. TOURMALINE-MM1: Response Moreau P, et al. ASH 2015. Abstract 727. Characteristic Ixazomib + Rd (n = 360) Placebo + Rd (n = 362) P Value ORR, %  CR  VGPR  PR 78.3 11.7 36.4 66.7 71.5 6.6 32.3 64.9.035.019 Median time to response, mos1.11.9 Median DoR, mos20.515.0 Median TTP, mos21.415.7.007* *HR: 0.712. Slide credit: clinicaloptions.comclinicaloptions.com

7. TOURMALINE-MM1: Safety Moreau P, et al. ASH 2015. Abstract 727. AE, % Ixazomib + Rd (n = 361)Placebo + Rd (n = 359) Any gradeGrade 3-4Any gradeGrade 3-4 AEs attributed to ixazomib and/or lenalidomide  Diarrhea  Constipation  Nausea  Vomiting  Rash  Back pain  Upper respiratory infection  Thrombocytopenia 45 35 29 23 36 24 23 31 6 < 1 2 1 5 <1 19 39 26 22 12 23 17 19 16 3 < 1 0 < 1 2 3 0 9 AEs attributed to ixazomib  Peripheral neuropathy  Peripheral edema 27 28 2121 22 20 0000 AEs attributed to lenalidomide  Thromboembolism  Neutropenia 8 33 < 3 23 11 31 < 4 24 Slide credit: clinicaloptions.comclinicaloptions.com

8. TOURMALINE-MM1: Safety  Median number of treatment cycles: ixazomib + Rd, 17 (range: 1-34); Rd, 15 (range: 1-34)  Other infrequent AEs included cardiac, renal, liver, and lung impairment but no safety concerns were identified  Similar QoL (EORTC-QLQ-C30 health score) in each arm Moreau P, et al. ASH 2015. Abstract 727. AE, % Ixazomib + Rd (n = 361) Placebo + Rd (n = 359) Any AE9899 Any grade ≥ 3 AE7469 Serious AEs4749 Discontinuation due to AEs1714 On-study* death46 *Death ≤ 30 days from last dose. Slide credit: clinicaloptions.comclinicaloptions.com

9.  Addition of ixazomib to Rd improved clinical outcomes with fast/durable responses in R/R MM –Significantly prolonged PFS vs placebo, including del(17p) pts –Significantly improved TTP and response rates vs placebo  Ixazomib plus Rd has tolerable safety profile with limited additional toxicity over Rd alone –Quality of life preserved vs placebo  Study investigators conclude that this all-oral triplet combination regimen could represent new standard of care for R/R MM pts [1] –Ixazomib approved by FDA on November 20, 2015, for use in previously treated MM [2] TOURMALINE-MM1: Conclusions 1. Moreau P, et al. ASH 2015. Abstract 727. 2. FDA.gov. Accessed December 8, 2015. Slide credit: clinicaloptions.comclinicaloptions.com

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