May 29 - June 2, 2015 Atezolizumab (MPDL3280A) Shows Favorable Tolerability, Promising Activity in Urothelial 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 Atezolizumab (MPDL3280A) in Urothelial Bladder Cancer Atezolizumab in UBC: Background  UBC characterized by very high mutation rates and immunogenicity –Metastatic UBC associated with poor outcomes, with no FDA-approved therapy options following platinum-based therapy (OS: 5 to 7 months)  Atezolizumab (MPDL3280A): humanized anti–PD-L1 antibody that inhibits the PD-1 immune checkpoint pathway –Blocks PD-L1/PD-1 and PD-L1/B7.1 interactions, restoring antitumor T-cell activity and boosting T-cell priming –In UBC: PD-L1 expression on immune cells, but not tumor cells, predictive of response [1,2]  Current report details updated safety and efficacy data from phase Ia dose- expansion study of atezolizumab in pts with previously treated metastatic UBC [3]  PD-L1 expression measured in tumor cells and immune cells using SP142 assay with 4 IHC levels 1. Bellmunt J, et al. ESMO Abstract Powles T, et al. Nature 2014;515: Petrylak DP, et al. ASCO Abstract 4501.

clinicaloptions.com/oncology Atezolizumab (MPDL3280A) in Urothelial Bladder Cancer Atezolizumab in UBC: Phase Ia Study Design  Ongoing dose-expansion phase in multiple cancer cohorts, including cohort with UBC –UBC cohort includes pts based on PD-L1 expression, as well as all-comers (N = 92) –PD-L1 expression by SP142 assay categorized into 4 IHC scoring levels –IC3 ≥ 10% of IC PD-L1+; IC2 ≥ 5% < 10% of IC PD-L1+; IC1 ≥ 1% < 5% of IC PD-L1+; IC0 < 1% of IC PD-L1+  Key eligibility criteria: previously treated, metastatic UBC with measurable disease by RECIST and ECOG PS 0-1  Atezolizumab administered at 15 mg/kg IV q3w or 1200-mg flat dose  Primary endpoint: safety and tolerability  Secondary endpoints: ORR, OS, PFS Petrylak DP, et al. ASCO Abstract 4501.

clinicaloptions.com/oncology Atezolizumab (MPDL3280A) in Urothelial Bladder Cancer Atezolizumab in UBC: Baseline Characteristics Petrylak DP, et al. ASCO Abstract Characteristic Total (N = 92) Median age, yrs (range)66 (36-89) Male, %75 ECOG PS 0/1, %40/60 Site of primary, %  Bladder  Renal pelvis  Ureter  Urethra Visceral metastasis, %  Liver Characteristic Total (N = 92) Prior therapies, %  Cystectomy or nephroureterectomy  Platinum-based chemo  Cisplatin  Carboplatin  ≥ 2 prior systemic regimens ≤ 3 mos from last chemo, %42* Hemoglobin < 10 g/dL, %17 GFR < 60 mL/min, %41 *n = 89.

clinicaloptions.com/oncology Atezolizumab (MPDL3280A) in Urothelial Bladder Cancer Atezolizumab in UBC: Safety  No treatment-related deaths  1 pt discontinued due to treatment- related AE  Grade 3/4 immune-related AEs observed in 5% of pts –Elevated AST (n = 3) –Elevated ALT (n = 2) –Elevated bilirubin (n = 1) –Hypophysitis (n = 1) Treatment- Related AEs All Grades in ≥ 5% of Pts, % Grade 3/4 in ≥ 2 Pts, % Any658 Fatigue160 Asthenia131 Nausea110 Decreased appetite 100 Pruritus100 Pyrexia70 Rash80 Diarrhea50 Increased AST22 Petrylak DP, et al. ASCO Abstract 4501.

clinicaloptions.com/oncology Atezolizumab (MPDL3280A) in Urothelial Bladder Cancer Atezolizumab in UBC: Response by PD-L1 Expression Level Efficacy Outcome, % IC0 (n = 15) IC1 (n = 26) IC2 (n = 34) IC3 (n = 12) ORR  CR  PR  Combined ORR 50% in IC2/3 groups, 17% in IC0/1 groups  Responses also observed in pts with visceral metastases at baseline –IC2/3 (n = 32): 38% ORR; IC0/1 (n = 36): 14% ORR  Median time to response: 62 days; median duration of response: NR  66% of responding pts had ongoing responses at time of data cutoff  10 pts treated ≥ 1 yr, including 3 re-treated following protocol amendment Petrylak DP, et al. ASCO Abstract 4501.

clinicaloptions.com/oncology Atezolizumab (MPDL3280A) in Urothelial Bladder Cancer Atezolizumab in UBC: Response by IC Status  55% (44/80) evaluable pts showed tumor burden reduction –Decreased tumor (CEA, CA19-9) and inflammatory (CRP) markers also seen in pts who responded to atezolizumab Petrylak DP, et al. ASCO Abstract Reprinted with permission. IC3 IC2 IC1 IC Maximum SLD Reduction From Baseline, %

clinicaloptions.com/oncology Atezolizumab (MPDL3280A) in Urothelial Bladder Cancer Atezolizumab in UBC: Survival  SP142 IHC assay for PD-L1 IC expression is a potential predictive biomarker for benefit from atezolizumab Petrylak DP, et al. ASCO Abstract Reprinted with permission. Efficacy Outcome IC0/1 (n = 44) IC2/3 (n = 48) 1-yr OS, % yr PFS, %1039 Median PFS, mos Mos OS Median OS: 7.6 mos (95% CI: 4.7-NE) IC2/3 IC0/1 Median OS: NR (95% CI: 9.0-NE) Median survival follow-up: 14 mos (IC2/3) 12 mos (IC0/1)

clinicaloptions.com/oncology Atezolizumab (MPDL3280A) in Urothelial Bladder Cancer Atezolizumab in UBC: Conclusions  Atezolizumab demonstrated pattern of improved outcomes with increasing PD-L1 expression in metastatic UBC –In IC2/3 tumors (highest PD-L1 expression), ORR: 50%; 1-yr OS: 57% –In IC0/1 tumors (lowest PD-L1 expression), ORR: 17%; 1-yr OS: 38%  Atezolizumab well tolerated with manageable toxicity profile –No treatment-related deaths –Rate of grade 3/4 immune-related AEs: 5%  Phase II and III studies of atezolizumab in UBC ongoing Petrylak DP, et al. ASCO Abstract 4501.

Go Online for More CCO Coverage of ASCO 2015! clinicaloptions.com/oncology Short slidesets of all the key data Additional CME-certified analyses with expert faculty commentary on all the key studies in:  Gastrointestinal cancers  Genitourinary cancer  Hematologic malignancies  Immunotherapy  Lung cancer