Phase Ib MMY1001: Daratumumab Plus Pom/Dex for Patients With R/R MM New Findings in Hematology: Independent Conference Coverage* of ASH 2015, December 5-8, 2015, Orlando, Florida *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. MM, multiple myeloma; Pom/Dex, pomalidomide, dexamethasone; R/R, relapsed/refractory. This program is supported by educational grants from Amgen, Celgene Corporation, Incyte, Merck; Seattle Genetics, and Takeda Oncology.

Daratumumab + Pom/Dex in R/R MM: Background Daratumumab: anti-CD38 IgG1 MAb Activity mediated by direct antitumor effects, ADCC and other immune-mediated apoptosis, and immunomodulation Safe, active as single agent or in combination with Rd in R/R MM Approved November 2015 for use in MM pts with ≥ 3 prior therapies Potential synergy with pomalidomide + dexamethasone Pomalidomide increases CD38 expression in MM cells[1] Current phase Ib study sought to determine efficacy, safety of daratumumab plus pom/dex in heavily pretreated and highly refractory pts with R/R MM[2] ADCC, antibody-dependent cell-mediated cytotoxicity; MM, multiple myeloma; Pom/Dex, pomalidomide, dexamethasone; Rd, lenalidomide/dexamethasone; R/R, relapsed/refractory. 1. Boxhammer R, et al. ASCO 2015. Abstract 8588. 2. Chari A, et al. ASH 2015. Abstract 508. Slide credit: clinicaloptions.com

Phase Ib MMY 1001: Study Design Open-label, multicenter trial of daratumumab with various backbone therapies Current analysis: daratumumab plus pomalidomide/dexamethasone Treat 6 pts; if ≤ 1 DLT enroll additional 6 pts; followed by expansion Primary endpoints: safety, tolerability Secondary endpoint: ORR Pts with R/R MM after ≥ 2 prior therapies including ≥ 2 cycles len/bort; no prior pom (N = 98) Daratumumab 16 mg/kg IV* + Pomalidomide 4 mg Days 1-21 + Dexamethasone 40 mg† Days 1,8,15,22 in 28-day cycles Until PD *QW cycles 1-2, Q2W cycles 3-6, Q4W cycles 7+. †20 mg in pts older than 75 yrs of age. DLT, dose-limiting toxicity; len/bort, lenalidomide, bortezomib; MM, multiple myeloma; PD, progressive disease; pom, pomalidomide. Slide credit: clinicaloptions.com Chari A, et al. ASH 2015. Abstract 508. Reproduced with permission.

MMY1001: Baseline Characteristics Daratumumab + Pom/Dex (N = 98) Median age, yrs (range) 70 yrs or older, % 64.5 (35.0-86.0) 29 Male, % 56 Median time since diagnosis, yrs (range) 5.2 (0.4-16.0) Median no. prior therapies, n (range) Prior ASCT, % Prior PI, % Bortezomib, % Carfilzomib, % Prior IMiD, % 4 (2-13) 75 100 98 32 Refractory to, % PI Lenalidomide PI + IMiD 76 66 30 89 67 ASCT, autologous stem cell transplantation; IMiD, immunomodulatory drug; PI, proteasome inhibitor; Pom/Dex, pomalidomide/dexamethasone. Slide credit: clinicaloptions.com Chari A, et al. ASH 2015. Abstract 508. Reproduced with permission.

MMY1001: Pt Disposition 61% of pts (n = 61) remain on treatment 39% of pts (n = 38) discontinued treatment Due to PD: 19% Due to AEs: 8% Due to death: 5% Due to investigator decision or refusal: 3% AE, adverse event; PD, progressive disease. Slide credit: clinicaloptions.com Chari A, et al. ASH 2015. Abstract 508.

MMY1001: Pt Safety and Tolerability No new safety signals with combination vs pom/dex alone Grade ≥ 3 AE incidence similar to pom/dex 17 deaths on trial, mostly due to disease progression 46% pts required G-CSF and 25% required blood transfusions during treatment Few grade ≥ 3 infusion-related reactions (6%) Managed with premedication and reduced infusion rates AEs in > 20% of Pts, % Pts (N = 98) Any Grade Grade ≥ 3 Any grade 97 91 Neutropenia 63 60 Anemia 42 25 Fatigue 41 8 Thrombocytopenia 34 15 Leukopenia 32 20 Cough 31 Diarrhea 30 1 Dyspnea 28 6 Nausea Constipation 22 AE, adverse event; G-CSF, granulocyte-colony stimulating factor; pom/dex, pomalidomide/dexamethasone. Slide credit: clinicaloptions.com Chari A, et al. ASH 2015. Abstract 508. Reproduced with permission.

MMY1001: Efficacy Outcome Evaluable Pts (n = 75) ORR, % Stringent CR VGPR PR 71 5 4 33 28 MR 3 SD 23 ORR in double-refractory pts, % 67 Median time to first response, mo 1.2 M-protein reduction ≥ 50% from baseline, % 77 6-mo PFS, % 66 MR, minor response; SD, stable disease; VGPR, very good PR. Chari A, et al. ASH 2015. Abstract 508. Reprinted with permission. Slide credit: clinicaloptions.com

MMY1001: Change in Paraprotein From Baseline -25 25 50 75 -50 -75 -100 N = 75 Relative Change in Paraprotein From Baseline (%) Urine M-protein Serum M-protein Free light chain Chari A, et al. ASH 2015. Abstract 508. Reprinted with permission. Slide credit: clinicaloptions.com

MMY1001: Conclusions In early analysis, daratumumab plus pom/dex shows promising activity in heavily pretreated R/R MM Rapid initial responses that are deepening over time 71% ORR overall; 67% ORR in pts double-refractory to PI/IMiD Combination has tolerable safety profile similar to pom/dex alone No new safety concerns Authors conclude that these results support further study of this combination in phase III trial IMiD, immunomodulatory drug; MM, myeloma; PI, proteasome inhibitor; pom/dex, pomalidomide, dexamethasone; R/R, relapsed/refractory. Slide credit: clinicaloptions.com Chari A, et al. ASH 2015. Abstract 508.

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