The Current Status of Immune Checkpoint Inhibitors: Arvin Yang, MD PhD Oncology Global Clinical Research Bristol-Myers Squibb

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1 The Current Status of Immune Checkpoint Inhibitors: A Global Overview of the Field Arvin Yang, MD PhD Oncology Global Clinical Research Bristol-Myers Squibb Immune Checkpoint Inhibitors Conference, March 25, 2015 Boston, MA

2 Agenda Discuss how checkpoint antibodies have changed the way we think about and treat cancer Identify the critical issues facing the development of cancer immunotherapies Discuss the importance of collaboration between industry, academia, regulators, payers and advocacy groups to advance cancer immunotherapies

3 How Immunotherapy and Checkpoint Inhibitors have Revolutionized Cancer Treatment

4 Proportion Alive Yervoy Improves Overall Survival in Advanced Melanoma Ipilimumab + DTIC Placebo + DTIC Years Estimated Survival Rate 1 Year 2 Year 3 Year* Ipilimumab + DTIC n= Placebo + DTIC n= *3-year survival was a post-hoc analysis Bristol-Myers Squibb Confidential For Consultant Use Only Not For Further Copying or Distribution Robert C NEJM 2011

5 Proportion alive Yervoy Treatments Results in Durable Long-Term Overall Survival in Pooled Analysis of Patients with Advanced Melanoma N = 1861 Patients Across 12 Studies Median OS: 11.4 mo (95% CI mo) year Survival Rate: 22% (95% CI 20 24%) Ipilimumab CENSORED Months Patients at Risk Ipilimumab Schadendorf et al; European Cancer Congress 2013; Amsterdam Bristol-Myers Squibb Confidential For Consultant Use Only Not For Further Copying or Distribution

6 Patients Surviving (%) Nivolumab Improves Overall Survival Compared to Dacarbazine in Previously Untreated Advanced Melanoma yr OS 73% Nivolumab (N=210) HR 0.42 (99.79% CI, ; P < ) (Boundary for statistical significance ) Patients who died, n/n Median OS mo (95% CI) Nivolumab 50/210 NR Dacarbazine 96/ ( ) 1-yr OS 42% Dacarbazine (N=208) Patients at Risk Nivolumab Dacarbazine Months Robert et al. NEJM 2014 NR=not reached. Based on 5 August 2014 database lock Bristol-Myers Squibb Confidential For Consultant Use Only Not For Further Copying or Distribution Follow-up since randomization: months

7 Aspirational Goal with Combination Bristol-Myers Squibb Confidential For Consultant Use Only Not For Further Copying or Distribution 7

8 OS (%) Phase 1 Nivolumab + Ipilimumab 1 & 2-Year Overall Survival Rates in Patients with Advanced Melanoma yr OS 94% 2-yr OS 88% yr OS 85% 2-yr OS 79% Censored Cohort 2 (Nivo 1 + Ipi 3) Concurrent Cohorts Month Patients at Risk Cohort 2 (Nivo 1 + Ipi 3) Concurrent Cohorts Cohort 2 dose is similar to the dose/schedule used in phase 3 clinical studies Kluger et al. ESMO 2014 based on June 2014 database lock Bristol-Myers Squibb Confidential For Consultant Use Only Not For Further Copying or Distribution

9 Patients Alive Without Relapse (%) Ipilimumab improves Recurrence-free Survival in Melanoma Median: 17.1 mo Ipilimumab 10 mg/kg Placebo Median: 26.1 mo Ipilimumab Placebo Events/patients 234/ /476 HR (95% CI)* 0.75 ( ) Log-rank P value* Year RFS rate (%) Year RFS rate (%)** *Stratified by stage. **Data are not yet mature Patients at Risk O Ipilimumab Placebo N Months Bristol-Myers Squibb Confidential For Consultant Use Only Not For Further Copying or Distribution

10 What is Beyond Melanoma?

11 Overall Survival (%) Overall Survival with Nivolumab in Advanced, Pretreated Squamous Cell Lung Cancer Median OS, months (95% CI) 8.2 (6, 11) 1-year OS rate, % (95% CI) 41 (32, 50) Number of events 72/117 Median OS = 8.2 months 1-year OS = 41% Overall Survival (Months) Number of Patients at Risk Nivolumab mg/kg Median follow-up for survival: 8 months (range, 0 17 months) Ramalingam CMSTO 2014 Bristol-Myers Squibb Confidential For Consultant Use Only Not For Further Copying or Distribution

12 Broad activity demonstrated with checkpoint blockade BMS Phase 3 Studies as an Example Untreated Melanoma RCC Lung Other OPDIVO* OPDIVO* OPDIVO* + YERVOY OPDIVO* + YERVOY YERVOY Sq NSCLC YERVOY SCLC Previously Treated OPDIVO* YERVOY OPDIVO* OPDIVO* OPDIVO* Head & Neck OPDIVO* Glioblastoma YERVOY Prostate Adjuvant YERVOY OPDIVO Additional BMS Studies Hodgkin Lymphoma Breast Cancer Bladder Cancer Gastric Cancer Pancreatic Cancer Hepatocellular Carcinoma Colon Cancer Non-Hodgkin Lymphoma Bristol-Myers Squibb Confidential For Consultant Use Only Not For Further Copying or Distribution

13 What Do We Still Need to Address?

14 Critical Issues Facing the Development of Cancer Immunotherapies Combination conundrum What are the appropriate endpoints? Understanding and finding biomarkers of response? Is PDL1 a relevant biomarker? Enrichment and response rate are not associated with survival PDL1 positive and negative patients benefit Temporal heterogeneity

15 The Future of Immunotherapy: Combinations and Collaboration

16 Aspirational Goal with Combination Bristol-Myers Squibb Confidential For Consultant Use Only Not For Further Copying or Distribution 1

17 Immuno-Oncology: Research & Preclinical Focus Bristol-Myers Squibb Confidential For Consultant Use Only Not For Further Copying or Distribution 17

18 Proportion alive What is the Appropriate Endpoint? Overall Survival Progression Free Survival Durable Response Ipilimumab CENSORED Months Patients at Risk Ipilimumab Schadendorf et al; European Cancer Congress 2013; Amsterdam

19 Nivolumab treatment in both PD-L1 Positive and Negative Melanoma patients improves Overall Survival Robert et al. NEJM 2014 NR=not reached. Based on 5 August 2014 database lock

20 II-ON: Industry-Academia Collaboration Facilitate translation of cancer research findings into clinical trials clinical practice Work to further advance innovation in drug discovery and development 20

21 An Example: Extending Leadership through Partnerships