1. 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.

2. 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 2014. Abstract 8080. 2. Powles T, et al. Nature 2014;515:558-562. 3. Petrylak DP, et al. ASCO 2015. Abstract 4501.

3. 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 2015. Abstract 4501.

4. clinicaloptions.com/oncology Atezolizumab (MPDL3280A) in Urothelial Bladder Cancer Atezolizumab in UBC: Baseline Characteristics Petrylak DP, et al. ASCO 2015. Abstract 4501. 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 79 5 10 5 Visceral metastasis, %  Liver 79 37 Characteristic Total (N = 92) Prior therapies, %  Cystectomy or nephroureterectomy  Platinum-based chemo  Cisplatin  Carboplatin  ≥ 2 prior systemic regimens 61 94 75 38 72 ≤ 3 mos from last chemo, %42* Hemoglobin < 10 g/dL, %17 GFR < 60 mL/min, %41 *n = 89.

5. 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 2015. Abstract 4501.

6. 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 13 0 13 19 0 19 44 15 29 67 33  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 2015. Abstract 4501.

7. 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 2015. Abstract 4501. Reprinted with permission. IC3 IC2 IC1 IC0 100 80 60 40 20 0 -20 -40 -60 -80 -100 Maximum SLD Reduction From Baseline, %

8. 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 2015. Abstract 4501. Reprinted with permission. Efficacy Outcome IC0/1 (n = 44) IC2/3 (n = 48) 1-yr OS, %3857 1-yr PFS, %1039 Median PFS, mos16 100 80 60 40 20 0 02468101214161820 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)

9. 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 2015. Abstract 4501.

10. 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