Results of a Randomized Phase III Trial (MPACT) of Weekly nab-Paclitaxel Plus Gemcitabine vs Gemcitabine Alone for Patients With Metastatic Adenocarcinoma of the Pancreas With PET and CA19-9 Correlates Daniel D. Von Hoff,1 Thomas Ervin,2 Francis P. Arena,3 E. Gabriela Chiorean,4 Jeffrey Infante,5 Malcolm Moore,6 Thomas Seay,7 Sergey A. Tjulandin,8 WenWee Ma,9 Mansoor N. Saleh,10 Marion Harris,11 Michele Reni,12 Ramesh K. Ramanathan,1 Josep Tabernero,13 Manuel Hidalgo,14 Eric Van Cutsem,15 David Goldstein,16 Xinyu Wei,17 Jose Iglesias,18 Markus F. Renschler 17 1TGen, Scottsdale Healthcare, AZ, USA; 2Florida Cancer Specialists/Sarah Cannon Research Institute, Englewood, FL; 3Arena Oncology Associates, Lake Success, NY, USA; 4University of Washington, Seattle, WA, USA; 5Sarah Cannon Research Institute/Tennessee Oncology, PLLC, Nashville, TN; 6Princess Margaret Hospital, Toronto, Canada; 7Atlanta Cancer Care, GA, USA; 8Blokhin Cancer Research Center, Moscow, Russia; 9Roswell Park Cancer Institute, Buffalo, NY, USA; 10Cancer Specialists, Atlanta, GA, USA; 11Southern Health, East Bentleigh, VIC, Australia; 12San Raffaele Scientific Institute, Milan, Italy; 13Vall d'Hebron University Hospital, Barcelona, Spain; 14Centro Integral Oncológico Clara Campal, Madrid, Spain; 15Leuven University, Belgium; 16Prince of Wales Hospital, Sydney, NSW, Australia; 17Celgene Corporation, Summit, NJ, USA; 18Bionomics, Thebarton, Australia

Disclosures This study was sponsored by Celgene Corporation Von Hoff: consultant or advisory role, honoraria, and research funding, Celgene; Ervin: research funding, Celgene; Arena: research funding, Clinical Research Alliance and Celgene; Chiorean: research funding, Celgene; Moore: consultant or advisory role and research funding, Celgene; Seay: research funding, Celgene; Tjulandin: research funding, Celgene; Ma: research funding, Celgene; Saleh: research funding, Celgene; Reni: consultant or advisory role, honoraria, and research funding, Celgene; Ramanathan: consultant or advisory role, honoraria, and research funding, Celgene; Tabernero: consultant or advisory role and honoraria, Celgene; Hidalgo: consultant or advisory role, honoraria, and research funding, Celgene; Van Cutsem: research funding, Celgene; Goldstein: consultant or advisory role and research funding, Celgene; Wei: employment or leadership position and stock ownership, Celgene; Iglesias: employment or leadership position at Bionomics and stock ownership, Celgene; Renschler: employment or leadership position and stock ownership, Celgene; Infante, Harris: nothing to disclose. Von Hoff et al. ASCO 2013. 2

nab-Paclitaxel + Gemcitabine in Pancreatic Cancer 1. Preclinical models1,2: nab-Paclitaxel (nab-P) active as single agent Synergizes with gemcitabine (Gem) 2. In a 67-patient phase I/II trial of nab-P + Gem1 MTD: nab-P 125 mg/m2 + Gem 1000 mg/m2 on days 1, 8, and 15 every 28 days Promising activity at MTD ORR: 48% Median PFS: 7.9 months Median OS: 12.2 months Von Hoff DD, et al. J Clin Oncol. 2011;29:4548-4554. Frese KK, et al. Cancer Discov. 2012;2:260-269. Von Hoff et al. ASCO 2013. 3

Study Design nab-P Planned N = 842 Gem Gem 125 mg/m2 IV qw 3/4 + Gem 1000 mg/m2 IV qw 3/4 Planned N = 842 Stage IV No prior treatment for metastatic disease KPS ≥ 70 Measurable disease Total bilirubin ≤ ULN No age limitation 1:1, stratified by KPS, region, liver metastasis Gem 1000 mg/m2 IV qw 7/8 then qw 3/4 Primary endpoint OS Secondary endpoints PFS and ORR by independent review (RECIST) Safety and tolerability By NCI CTCAE v3.0 With 608 events, 90% power to detect OS; HR = 0.769 (2-sided α = 0.049) Treat until progression CT scans every 8 weeks PET scans in an initial cohort of patients at baseline and weeks 8 and 16 CA19-9 measurements at baseline and every 8 weeks Von Hoff et al. ASCO 2013. 4

MPACT (CA046) Phase III Trial Country nab-P + Gem, n Gem, n All, n (%) USA 235 241 476 (55) Australia 61 59 120 (14) Russia 50 100 (12) Canada 33 30 63 (7) Italy 21 16 37 (4) Ukraine 14 12 26 (3) Spain 6 10 16 (2) Germany 3 5 8 (1) Austria 6 (1) France 4 2 Belgium 1 3 (< 1) Total 431 430 861 (100) Table 14.1.4.1 - Demographic and Baseline Characteristics - Intent-to-Treat Population Total of 151 sites enrolled 861 patients between May 8, 2009, and April 17, 2012 Von Hoff et al. ASCO 2013. 5

Baseline Characteristics Variable nab-P + Gem (n = 431) Gem (n = 430) All Patients (N = 861) Age Median years (min, max) 62 (27, 86) 63 (32, 88) 63 (27, 88) ≥ 65 years old, % 41 44 42 Sex Male, % 57 60 58 KPS 90-100, % 62 70-80, % 38 40 Pancreatic primary location Head, % 43 Body, % 31 32 Tail, % 24 26 25 Current site(s) of metastasis Lung, % 35 39 Liver, % 85 84 No. of metastatic sites 1, % 8 5 6 2, % 47 48 ≥ 3, % 45 46 Previous Whipple Yes, % 7 Biliary stent 19 16 17 CA19-9a Normal, % 14 13 > ULN-< 59 ×ULN, % 28 ≥ 59 × ULN, % ULN, upper limit of normal. a CA19-9 at baseline was unknown in 13% of patients. Table 14.1.4.1 Demographic and Baseline Characteristics, Intent-to-Treat Population Table 14.1.5.1 Cancer History Von Hoff et al. ASCO 2013. 6

Proportion of Survival Overall Survival 1.0 OS, months Events/n (%) Median (95% CI) 75th Percentile 333/431 (77) 8.5 (7.89-9.53) 14.8 359/430 (83) 6.7 (6.01-7.23) 11.4 0.9 0.8 nab-P + Gem Gem 0.7 0.6 Proportion of Survival 0.5 0.4 HR = 0.72 95% CI (0.617-0.835) P = 0.000015 0.3 0.2 0.1 Table 14.2.1.1.1 Overall Survival –Stratified Analysis by Randomization Strata, Intent-to-Treat Population 0.0 3 6 9 12 15 18 21 24 27 30 33 36 39 Months Pts at risk nab-P + Gem: Gem: 431 430 357 340 269 220 169 124 108 69 67 40 26 27 15 16 7 9 3 4 1 Subsequent therapy: 38% for nab-P + Gem and 42% for Gem OS censored at time of secondary therapy: 9.4 vs 6.8 months; HR 0.68; P = 0.00007 Trial conclusions not impacted by secondary therapies Von Hoff et al. ASCO 2013. 7

Overall Survival Rate nab-P + Gem Gem Time Points, months Survival, % Increase, % P Value 6 67 55 22 0.00074 9 48 36 33 0.00067 12 35 59 0.00020 18 16 78 0.00803 24 4 125 0.02123 Table 14.2.1.1.1 Overall Survival –Stratified Analysis by Randomization Strata, Intent-to-Treat Population Von Hoff et al. ASCO 2013. 8

OS—Prespecified Subgroups nab-P + Gem Events/n Gem HR 333/431 359/430 0.72 188/254 209/242 0.65 145/177 150/188 0.81 138/186 141/173 195/245 218/257 142/179 146/161 0.61 187/248 212/268 0.75 142/191 155/180 0.59 188/237 201/246 0.80 290/365 309/360 0.69 43/66 50/70 0.86 21/33 16/21 0.41 159/202 163/206 104/136 121/140 0.79 49/60 59/63 0.50 47/60 43/56 1.07 96/122 95/120 0.83 151/197 171/195 50/61 53/59 0.67 62/64 59/62 0.84 14/38 17/38 207/268 230/271 0.68 Group HR All patients Age < 65 years Age ≥ 65 years Female Male KPS 70-80 KPS 90-100 Primary tumor location: head Primary tumor location: other No liver metastases Liver metastases Normal CA19-9 CA19-9 ULN to < 59 x ULN CA19-9 ≥ 59 x ULN > 3 metastatic sites 1 metastatic site 3 metastatic sites 2 metastatic sites Will be redone with log scale Australia Western Europe North America Eastern Europe 0.125 0.25 0.5 1.0 2.0 Favors nab-P + Gem Favors Gem Von Hoff et al. ASCO 2013. 9

PFS by Independent Review Proportion of Progression-Free Survival PFS, months Events/n (%) Median (95% CI) 75th Percentile 277/431 (64) 5.5 (4.47-5.95) 9.2 265/430 (62) 3.7 (3.61-4.04) 5.9 1.0 0.9 0.8 nab-P + Gem Gem 0.7 0.6 Proportion of Progression-Free Survival 0.5 HR = 0.69 95% CI (0.581-0.821) P = 0.000024 0.4 0.3 0.2 0.1 0.0 3 6 9 12 15 18 21 24 Pts at Risk nab-P + Gem: Gem: 431 430 281 209 122 51 62 23 24 10 8 6 4 2 Months PFS Rate at nab-P + Gem Gem Increase 6 months 44% 25% 76% 12 months 16% 9% 78% Von Hoff et al. ASCO 2013. 10

Response Rates Variable nab-P + Gem (n = 431) Gem (n = 430) P Value Overall response rate Independent review, % (95% CI) Investigator assessment, % 23 (19.1-27.2) 29 (25.0-33.8) 7 (5.0-10.1) 8 (5.3-10.6) 1.1 x 10−10 3.3 x 10−16 Disease control rate by independent review,a % 48 (43.0-52.6) 33 (28.4-37.5) 7.2 x 10−6 Table 14.2.4.1 Overall Response Rate by Independent Radiological Review, Intent-to-Treat Population Table 14.2.4.5 Overall Response Rate by Investigator Review, Intent-to-Treat Population Table 14.2.4.6 Disease Control Rate by Independent Radiological Review, Intent-to-Treat Population a Includes CR + PR + SD ≥ 16 weeks. Von Hoff et al. ASCO 2013. 11

Treatment Exposure Variable nab-P + Gem (n = 421) Gem (n = 402) Treatment duration, median months (min, max) ≥ 6 months, % 3.9 (0.1, 21.9) 32 2.7 (0.1, 21.5) 15 Relative dose intensity (%), median (min, max) nab-P 80.6 (16.7, 100.0) 75.2 (14.3, 97.7) -- 84.6 (14.1, 100.0) Cumulative dose, median mg/m² 1425.0 11,400.0 9000.0 nab-P doses at 125 mg/m², n (%) Gem doses at 1000 mg/m², n (%) 4116.0 (71) 3731.0 (63) 3762.0 (79) Table 14.3.1.1 Table 14.3.1.5 Table 14.3.1.6 Von Hoff et al. ASCO 2013. 12

Safety Preferred Term nab-P + Gem (n = 421) Gem (n = 402) Pts with at least 1 AE leading to death, % 4 Grade ≥ 3 hematologic AEs,a % Neutropenia Thrombocytopenia Anemia 38 13 27 9 12 Pts who received growth factors, % 26 15 Febrile neutropenia,b % 3 1 Grade ≥ 3 nonhematologic AEsb in > 5% pts, % Fatigue Peripheral neuropathyc Diarrhea 17 6 7 < 1 Grade ≥ 3 neuropathy Time to onset, median days Time to improvement by 1 grade, median days Time to improvement to grade ≤ 1, median days Pts who resumed nab-P, % 140 21 29 44 113 -- Hematologic values: table. 14.3.4.1.1 Nonhematologic: table 14.3.2.3.5 Febrile neutropenia: 14.3.2.9.1 AE leading to death: 14.3.2.1 Neuropathy time: table 14.3.3.4 a Based on laboratory values; b Based on investigator assessment of treatment-related events; c Grouped term. Von Hoff et al. ASCO 2013. 13

Metabolic Response by PET by Independent Review PET scans were performed in the first 257 patients randomized to receive treatment at PET-equipped centers Outcome nab-P + Gem (n = 130)a Gem (n = 127)a HR P Value Metabolic response by PET,b % 63 38 - 0.000051 ORR by CT scan, % 31 11 0.0001 Median OS in PET cohort, mo 10.5 8.3 0.71 0.0096 a Follow-up scans at 8 weeks (n = 222) and 16 weeks (n = 134). b PET evaluated by EORTC criteria (Young H, et al. Eur J Cancer. 1999;35:1773-1782). Von Hoff et al. ASCO 2013. 14

CA19-9 Best Response and Landmark OS Analyses Best Decrease in CA19-9 During Study Decrease in CA19-9 level nab-P + Gem (n = 379) Gem (n = 371) P Value Patients with a ≥ 20% decrease, n (%) 230 (61) 162 (44) < 0.0001 Patients with a ≥ 90% decrease, n (%) 117 (31) 51 (14) Predictive Value of CA19-9 Response at Week 8 on OS: Landmark Analyses Decrease in CA19-9 Level at Week 8 HR n Median OS, mo ≥ 20% 197 13.2 141 9.4 0.59 ≥ 90% 59 13.4 34 9.8 0.47 0.0053 Detailed analysis presented by Chiorean et al. (abstract 4058) Von Hoff et al. ASCO 2013. 15

Conclusions from MPACT MPACT study – a large, multi-center, international study performed at community and academic centers OS, PFS, and ORR were superior for nab-P + Gem vs Gem Improvement in OS across the entire curve, including median, 1-year, and 2-year survival rates Metabolic response rate by PET and CA19-9 response rates were higher for nab-P + Gem vs Gem alone Both were predictors for longer OS Von Hoff et al., ASCO 2013 16

Conclusions from MPACT (cont) Serious life threatening toxicity not increased; AEs acceptable and manageable 5. nab-P + Gem, a new standard for the treatment of patients with metastatic pancreatic cancer, is superior to Gem alone and could become the backbone for new regimens A phase III study of nab-P + Gem in the adjuvant setting is currently in development Von Hoff et al., ASCO 2013 17

MPACT Team Von Hoff et al. ASCO 2013. 18