May 29 - June 2, 2015 Borealis-1: Apatorsen + Gemcitabine/Cisplatin for Pts With Advanced Bladder Cancer CCO Independent Conference Highlights of the 2015 ASCO Annual Meeting* *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 AstraZeneca, Bayer, Bristol-Myers Squibb, Celgene Corporation, Genentech, Incyte, and Novartis.

clinicaloptions.com/oncology Borealis-1: Apatorsen in Advanced Bladder Cancer Apatorsen  Apatorsen (OGX-427): second-generation antisense oligonucleotide designed to inhibit Hsp27 by blocking translation  Hsp27: ATP-independent cytoprotective chaperone that inhibits cell death pathway signaling –Overexpression in high-grade bladder cancer –Expression level correlated with cancer stage and grade –Associated with poor survival prognosis in many cancers  Current study evaluated apatorsen combined with standard chemotherapy as first-line therapy for pts with advanced bladder cancer Bellmunt J, et al. ASCO Abstract 4503.

clinicaloptions.com/oncology Borealis-1: Apatorsen in Advanced Bladder Cancer Borealis-1: Study Design  Randomized, multinational, placebo-controlled phase II trial  Endpoints –Primary: OS –Secondary: Safety, dose for phase III, ORR, DCR, DoR, PFS Pts with advanced bladder cancer, either chemotherapy naive or neoadjuvant chemotherapy ≥ 12 mos ago (N = 179) Apatorsen 600 mg QW* + Gemcitabine/Cisplatin (n = 58) Apatorsen 1000 mg QW* + Gemcitabine/Cisplatin (n = 60) Stratified by PS score and presence or absence of visceral disease Placebo + Gemcitabine/Cisplatin (n = 61) Bellmunt J, et al. ASCO Abstract *After 600 mg IV x 3 loading dose

clinicaloptions.com/oncology Borealis-1: Apatorsen in Advanced Bladder Cancer Borealis-1: Pt Characteristics Characteristic Placebo + Gemcitabine/Cisplatin (n = 61) Apatorsen 600 mg + Gemcitabine/Cisplatin (n = 58) Apatorsen 1000 mg + Gemcitabine/Cisplatin (n = 60) Median age, yrs (range)64 (37-77)66 (52-78)64 (37-64) Male, % Karnofsky score ≤ 80%, % Visceral disease, %  Liver  Lung  Bone  Lymph node only Bellmunt J, et al. ASCO Abstract 4503.

clinicaloptions.com/oncology Borealis-1: Apatorsen in Advanced Bladder Cancer Borealis-1: Median Survival Not Increased With Apatorsen in ITT Population Bellmunt J, et al. ASCO Abstract Reprinted with permission. OS PFS Patients (%) Mos Gem/Cis (n = 61) 600 mg Apa + Gem/Cis (n = 58) 1000 mg Apa + Gem/Cis (n = 60) Patients (%) Mos Gem/Cis (n = 61) 600 mg Apa + Gem/Cis (n = 58) 1000 mg Apa + Gem/Cis (n = 60)

clinicaloptions.com/oncology Borealis-1: Apatorsen in Advanced Bladder Cancer Borealis-1: Analysis of Survival in Pts By Prognosis  A post hoc analysis of pts stratified by prognostic risk factors for progression  4 prognostic risk factors used to classify pts as “poor risk” or “good risk” –Karnofsky PS –Liver involvement –Low hemoglobin –High alkaline phosphatase Bellmunt J, et al. ASCO Abstract Reprinted with permission. OS Patients (%) Mos 600 mg (n = 31) Median 22.5 mo Placebo (n = 23) Median 21.9 mo 600 mg (n = 22) Median 11.9 mo Placebo (n = 32) Median 9.0 mo Good risk Poor risk Good risk: HR = 1.44 Poor risk: HR = 0.72

clinicaloptions.com/oncology Borealis-1: Apatorsen in Advanced Bladder Cancer Borealis-1: Select AEs (≥ Grade 3)  Discontinuation due to AE in 22% of apatorsen 600 mg arm and 38% of apatorsen 1000 mg arm vs 3% of placebo arm –30% of pts on apatorsen 1000 mg arm experienced infusion reactions despite steroid prophylaxis AE, % Placebo + Gemcitabine/Cisplatin (n = 61) Apatorsen 600 mg + Gemcitabine/Cisplatin (n = 58) Apatorsen 1000 mg + Gemcitabine/Cisplatin (n = 60) Neutropenia Anemia Thrombocytopenia Hypertension Pulmonary embolism13127 Urinary tract infection3315 Back pain3512 Bellmunt J, et al. ASCO Abstract 4503.

clinicaloptions.com/oncology Borealis-1: Apatorsen in Advanced Bladder Cancer Borealis-1: Conclusions  Apatorsen as part of first-line therapy for pts with advanced bladder cancer did not increase survival in ITT pt population –An exploratory subgroup analysis suggested a 2.9-mo survival benefit with apatorsen for pts with poor prognostic characteristics at baseline  Further development of apatorsen for bladder cancer should consider –Safety/tolerability in poor prognosis pts –Choice of chemotherapy regimen –Biomarker testing for pt selection Bellmunt J, et al. ASCO Abstract 4503.

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