Disclosures. Membership of Advisory Committees: Research Support/ PI: Celgene Corporation Millennium Pharmaceuticals Johnson & Johnson

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1 Randomized, Open-Label Phase 1/2 Study of Pomalidomide Alone or in Combination With Low-Dose Dexamethasone in Patients With Relapsed and Refractory Multiple Myeloma Who Have Received Prior Treatment That Includes Lenalidomide and Bortezomib: Phase 2 Results Paul Richardson 1, David Siegel 2, Ravi Vij 3, Craig Hofmeister 4, Sundar Jagannath 5, Christine Chen 6, Sagar Lonial 7, Andrzej Jakubowiak 8, Nizar Bahlis 9, Rachid Baz 10, Gail Larkins 11, Min Chen 11, Mohamed Zaki 11, Kenneth Anderson 1 1 Dana-Farber Cancer Institute, Boston, MA, USA; 2 Hackensack University Medical Center, Hackensack, NJ, USA; 3 Washington University School of Medicine, Saint Louis, MO, USA; 4 Ohio State University Medical Center, Columbus, OH, USA; 5 St Vincent s Comprehensive Cancer Center, New York, NY, USA; 6 Princess Margaret Hospital, Toronto, ON, Canada; 7 Emory University School of Medicine, Atlanta, GA, USA; 8 University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA; 9 University of Calgary, Calgary, AB, Canada; 10 H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA; 11 Celgene Corporation, Summit, NJ, USA

2 Disclosures Membership of Advisory Committees: Celgene Corporation Millennium Pharmaceuticals Johnson & Johnson Research Support/ PI: Celgene Corporation Millennium Pharmaceuticals

3 Background Pomalidomide () is a distinct oral immunomodulatory drug with significant anti-myeloma activity in vitro 1,2 has demonstrated promising activity in patients (pts ) with relapsed/refractory multiple myeloma (RRMM) 3 When combined with low-dose dexamethasone (LoDEX), has clinical efficacy in RRMM pts previously treated with lenalidomide (LEN) and/or bortezomib (BORT) 4 6 O N O N H O Pomalidomide NH 2 O 1. Hideshima T, et al. Blood. 2000;96: Mitsiades N, et al. Blood. 2002;99: Schey SA, et al. J Clin Oncol. 2004;22: Lacy MQ, et al. J Clin Oncol. 2009;27: Lacy MQ, et al. Leukemia. 2010;24: Lacy MQ, et al. Blood. 2011;118:

4 Phase 1 (MTD) MM-002 Study Design: ± LoDEX in RRMM therapy (once daily on days 1 21 of each 28-day cycle) Progressive disease or no response after completion of 4 cycles Option to add LoDEX (40 mg/week) Progressive disease Discontinue and follow up for survival and subsequent treatment Phase 2 (Randomized) Randomization (4 mg) + LoDEX (4 mg) Progressive disease Progressive disease Option to add LoDEX (40 mg/week) Discontinue and follow up for survival and subsequent treatment Concomitant medication: anticoagulants, granulocyte colony-stimulating factor use after cycle 1, erythroid growth factors, bisphosphonates, transfusions with platelets and/or red blood cells as clinically indicated MTD, maximum tolerated dose.

5 Aged 18 years Pts with RRMM: Key Eligibility Criteria measurable levels of M-paraprotein in serum or urine 2 prior therapies documented progression during or within 60 days of last treatment (i.e. relapsed and refractory disease) 1,2 prior therapy must have included 2 cycles of LEN and 2 cycles of BORT (separately or in combination) pts refractory to both LEN and BORT permitted 1. Anderson KC, et al. Leukemia. 2008;22: Richardson et al. N. Engl. J. Med. 2003;348:

6 Primary Endpoints MTD (phase 1) progression-free survival (phase 2) Secondary response (modified EBMT and IMWG/Uniform Criteria) 1 3 duration of response overall survival safety EBMT, European Group for Blood and Marrow Transplantation; IMWG, International Myeloma Working Group 1. Bladé J, et al. Br J Haematol. 1998;102: Richardson PG, et al. N Engl J Med. 2003;348: Durie BG, et al. Leukemia. 2006;20:

7 Phase 1: Patient Characteristics 2 mg (n = 6) 3 mg (n = 8) 4 mg (n = 14) 5 mg (n = 10) Total (N = 38) Median age, years (range) 66 (55 72) 72 (61 78) 69 (45 80) 64 (38 83) 67 (38 83) Median number of prior 7 (5 11) 7 (2 11) 6 (3 17) 6 (3 10) 6 (2 17) therapies (range) Prior LEN and BORT % Prior DEX % Prior THAL % Prior SCT % Prior Carfilzomib % Refractory to LEN and BORT % BORT, bortezomib; DEX, dexamethasone; LEN, lenalidomide; SCT, stem cell transplantation; THAL, thalidomide. Richardson PG, et al. Blood. 2010;116:[abstract 864].

8 Phase 1: Dose-limiting Toxicities Median number of completed Dose-limiting toxicity, n cycles (range) 2 mg (n = 6) 1.5 (1 12) 1* (grade 3 fatigue) 3 mg (n = 8) 5.0 (2 13) 1 (grade 4 neutropenia) 4 mg (n = 14) 5.5 (1 30) 2 (grade 4 neutropenia) 5 mg (n = 10) 8.0 (1 26) 4 (grade 4 neutropenia) MTD determined to be 4 mg, when given on days 1 21 of each 28- day cycle pts received a median of 5 cycles of (range 1 20) All but one dose-limiting toxicity due to grade 4 neutropenia *Grade 3 fatigue in the second group of 3 pts enrolled in 2 mg cohort. Grade 4 neutropenia in the second group of 4 pts enrolled in 3 mg cohort. One grade 4 neutropenia occurred in first group of 3 pts, and one grade 4 neutropenia occurred in the next group of 6 pts enrolled in 4 mg cohort. One grade 4 neutropenia occurred in first group of 5 pts, and three grade 4 neutropenias occurred in the next group of 5 pts enrolled in 5 mg cohort. Richardson PG, et al. Blood. 2010;116:[abstract 864].

9 Phase 1: Best Response* and Clinical Outcomes MR PR CR PR: 29% MR: 71% Evaluable Pts (%) PR: 33% MR: 33% PR: 14% MR: 29% 33% 14% 14% 36% 18% 2 mg (n = 3) 3 mg (n = 7) 4 mg (n = 11) 5 mg (n = 7) Total (N = 28) 29% 43% PR: 29% MR: 50% Patients who received 4 mg or 5 mg achieved higher response rates and remained longer on treatment ( months) compared with those who received 2 mg or 3 mg ( months) 25% 21% 4% *Efficacy results presented using investigator assessment. Discrepancies in totals due to rounding. CR, complete response; MR, minor response; PR, partial response; Pts, patients. Richardson PG, et al. Blood. 2010;116:[abstract 864].

10 Randomized Phase 2 Schema and Patient Disposition Randomization (N = 221) (n = 108) +LoDEX (n = 113) Discontinued (n = 86) AEs (n = 13) PD (n = 47) UPD (n = 6) Discontinued (n = 90) AEs (n = 8) PD (n = 58) UPD (n = 7) PD Added LoDEX (n = 61) Continued treatment (n = 22) Continued treatment (n = 23) 219 pts received 1 dose of treatment; 191 were evaluable for response Median number of cycles: 5 (range 1 17) Median treatment duration: 5.0 months Median treatment duration for alone before addition of LoDEX: 2.3 months AE, adverse event; PD, progressive disease; UPD, unconfirmed PD.

11 Patient Characteristics (n = 108) + LoDEX (n = 113) Total (N = 221) Median age years (range) 61 (37 88) 64 (34 88) 63 (34 88) Male % Baseline MM stage % I II III Baseline ECOG PFS % Median number of prior therapies (range) 5 (2 12) 5 (2 13) 5 (2 13) Prior LEN and BORT % Prior DEX % Prior THAL % Prior SCT % Prior Carfilzomib % Refractory to LEN % Refractory to BORT % Refractory to LEN and BORT % ECOG, Eastern Cooperative Oncology group.

12 Best Response EBMT/Uniform Criteria, Intent-to-treat Population Disease control ( SD) observed in 81% of overall pts Discrepancies in totals are due to rounding. ORR, overall response rate; SD, stable disease. (n = 108) + LoDEX (n = 113) ORR ( PR) % MR % CR % 1 1 PR % VGPR % 2 9 MR % SD % PD % 10 6 NE % Median time to response, months Median duration of response, months

13 Patients Refractory to LEN, and LEN + BORT Best Overall Response (n = 85) LEN refractory* + LoDEX (n = 87) (n = 64) LEN and BORT refractory * + LoDEX (n = 69) ORR ( PR) % MR % CR % PR % VGPR MR % SD % Median time to response, months Median duration of response, months *Refractory defined as progression while on the last LEN- or BORT containing regimen, or within 60 days after the last dose of that therapy

14 Survival Outcomes: Overall Population LoDEX 80 + LoDEX Patients (%) Patients (%) Progression-free survival (months) Overall survival (months) Median PFS: + LoDEX 4.7 months; alone 2.7 months Median OS: + LoDEX 16.9 months; alone 14 months ~ Median OS: for pts with PD as best response 5.4 months PFS, progression-free survival; OS, overall survival.

15 Patients Refractory to LEN + BORT Survival Outcomes LoDEX 80 + LoDEX Patients (%) Patients (%) Progression-free survival (months) Overall survival (months) Median PFS: + LoDEX 3.9 months; alone 2.0 months Median OS: + LoDEX 13.7 months; alone 12.7 months ~ Median OS: for pts with PD as best response 4.6 months

16 Grade 3 4 Adverse Events ( 5% of Patients) Hematologic AEs % (n = 107) + LoDEX (n = 112) Neutropenia Leading to Dose Reduction 7 4 Thrombocytopenia Leading to Dose Reduction 9 5 Anemia Non-hematologic AEs % Pneumonia 8 19 Fatigue 8 10 Discontinuation due to AEs % 12 6 No Grade 3/4 Peripheral Neuropathy Grade 3/4 Thromboembolic events 4% in +LoDEX: 3% in alone

17 Conclusions/Future Directions (4 mg/day, on days 1 21 of a 28-day cycle) with or without LoDEX demonstrates promising efficacy in advanced MM pts who have received multiple prior therapies (median 5) and are refractory to both LEN and BORT + LoDEX exhibits synergistic activity and is generally well tolerated with PR 34% (including VGPR+CR 13%) + LoDEX produces consistent and durable response rates regardless of prior therapy and refractoriness, with favorable PFS and encouraging median OS (16.9 months) + LoDEX is being investigated in phase 3 trials and as part of combination treatments, including Bortezomib Phase 3 study evaluating efficacy and safety of + LoDEX vs. highdose DEX in RRMM currently enrolling in Europe Phase 3 study of +Bortezomib/Dex vs. Bortezomib/Dex in RRMM planned in USA

18 Acknowledgements Phase 2 investigators including: Kevin Song, Andrew Belch, Noopur Raje, Joseph Mikhael, Martha Lacy, Suzanne Lentzsch, Jeffrey Matous, Chaim Shustik The Cancer Center Hackensack University Medical Center H. Lee Moffitt Cancer and Research Institute Massachusetts General Hospital Mayo Clinic Arizona Mayo Clinic Minnesota Roswell Park Cancer Institute The Ohio State University James Cancer Hospital University of Michigan Comprehensive Cancer Center Washington University Siteman Cancer Center Institutions/Study sites Our Patients and their Families St. Vincent's Comprehensive Cancer Center University of Pittsburgh Cancer Institute Emory University Princess Margaret Hospital UHN Cross Cancer Center University of Calgary Tom Baker Cancer Center Vancouver General Hospital, Diamond Health Care Centre Royal Victoria Hospital McGill University Multiple Myeloma Research Consortium Clinical Research Staff Celgene Corporation