ONO PHARMACEUTICAL : Encouraging Survival Observed With Opdivo (nivolumab) Plus Yervoy (ipilimumab) With Longer Follow-up in First-line Advanced Non-small Cell Lung Cancer, in Updated Phase 1b CheckMate -012 Study (188KB)

December 8, 2016

(PRINCETON, N.J., December 5, 2016) - Bristol-Myers Squibb Company (NYSE: BMY) announced updated findings from the Phase 1b trial, CheckMate -012, in chemotherapy-naïve advanced non-small cell lung cancer patients evaluating Opdivo monotherapy, or in combination with Yervoy, at different doses and schedules. Data from this trial have been previously reported. These updated results, with a median follow-up of 16 months, include pooled efficacy findings for the Opdivo and Yervoy combination cohorts (Opdivo 3 mg/kg every two weeks plus Yervoy 1 mg/kg every six [Q6W] or 12 weeks [Q12W]). In the pooled combination cohorts, the median progression-free survival in patients with PD-L1 expression ≥1% (n=46) was 12.7 months (95% CI: 7.8, 23.0) and was not reached in patients with PD-L1 expression >50% (n=13; 95% CI: 7.8, NR). For patients with ≥50% PD-L1 expression (n=13), the one-year overall survival rate was 100% in the pooled combination cohorts. In addition, the confirmed objective response rates in all treated patients (n=77) was 43%, nearly double the response rate reported with Opdivo monotherapy (23%; n=52), with six patients (8%) achieving a complete response, three of which were in patients with PD-L1 expression

Bristol-Myers Squibb (BMS) has a robust clinical development program in Opdivo monotherapy and in combination therapy with other therapeutic drugs in a variety of tumor types overseas, including Glioblastoma, Small Cell Lung Cancer, Urothelial Cancer, Hepatocellular Carcinoma, Esophageal Cancer, Colorectal Cancer, Gastric Cancer, Blood Cancer, etc.

In Japan, Ono Pharmaceutical Co., Ltd. (ONO) launched Opdivo for the treatment of unresectable melanoma in September 2014. ONO received an approval for additional indication of unresectable, advanced or recurrent non-small cell lung cancer in December 2015, unresectable or metastatic renal cell cancer in August 2016 and relapsed or refractory classical Hodgkin lymphoma in December 2016. In addition, ONO has submitted supplemental application for additional indication of Head and Neck Cancer, and is conducting clinical development program including Gastric Cancer, Esophageal Cancer, Gastro-esophageal Junction Cancer and Esophageal Cancer, Small Cell Lung Cancer, Hepatocellular Carcinoma, Glioblastoma, Urothelial Cancer, Malignant Pleural Mesothelioma, Ovarian Cancer, Biliary Tract Cancer, etc.

In Japan, ONO and BMS (and BMS Japan subsidiary BMSKK) have formed a strategic partnership that includes co-development, co-commercialization, and co-promotion of multiple immunotherapies for patients with cancer.

Attached from the following page is the press release made by BMS for your information.

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In the pooled combination cohorts, median progression-free survival in patients with PD-L1 expression ≥1% was 12.7 months

With longer follow-up, the Opdivo plus Yervoy combination had a safety profile consistent with previous reports of this study

(PRINCETON, N.J., December 5, 2016) - Bristol-Myers Squibb Company (NYSE: BMY) announced today updated findings from the Phase 1b trial, CheckMate -012, in chemotherapy-naïve advanced non-small cell lung cancer patients evaluating Opdivo monotherapy, or in combination with Yervoy, at different doses and schedules. Data from this trial have been previously reported. These updated results, with a median follow-up of 16 months, include pooled efficacy findings for the Opdivo and Yervoy combination cohorts (Opdivo 3 mg/kg every two weeks plus Yervoy 1 mg/kg every six [Q6W] or 12 weeks [Q12W]).

In the pooled combination cohorts, the median progression-free survival in patients with PD-L1 expression ≥1% (n=46) was 12.7 months (95% CI: 7.8, 23.0) and was not reached in patients with PD-L1 expression >50% (n=13; 95% CI: 7.8, NR). For patients with

≥50% PD-L1 expression (n=13), the one-year overall survival rate was 100% in the pooled combination cohorts. In addition, the confirmed objective response rates in all treated patients (n=77) was 43%, nearly double the response rate reported with Opdivo monotherapy (23%; n=52), with six patients (8%) achieving a complete response, three of which were in patients with PD-L1 expression

Scott N. Gettinger, M.D., associate professor of medicine, Yale Cancer Center, New Haven, Conn., commented, "With longer follow-up in the CheckMate -012 trial, we observe that the Opdivo and Yervoy combination resulted in encouraging progression-free survival. We are also excited to see the consistent near doubling of response rates with the combination relative to Opdivo alone in both PD-L1 expressors and non-expressors, and the previously reported response rates of over 50% and 90%, respectively, among patients with at least 1% and 50% tumor PD-L1 expression. We look forward to further evaluating Opdivo plus Yervoy in the first line treatment setting for advanced lung cancer."

Results from CheckMate -012 will be presented today at the International Association for the Study of Lung Cancer 17th World Conference on Lung Cancer (WCLC) in Vienna, Austria, during an Oral Session at 11:00 a.m. CET.

Nick Botwood, M.D., development lead, Lung, Bristol-Myers Squibb, commented, "The updated results from CheckMate -012 continue to be promising, and we look forward to advancing the Opdivo and Yervoy combination in the ongoing CheckMate -227 Phase 3 trial for first-line advanced lung cancer, with the hope of confirming these findings."

CheckMate -012 is a multi-arm Phase 1b trial evaluating the safety and tolerability (primary endpoints) of Opdivo as monotherapy or in combination with Yervoy at different doses and schedules in patients with chemotherapy-naïve advanced non-small cell lung cancer. The secondary endpoints include confirmed objective response rate (ORR) and progression-free survival (PFS) rates at 24 weeks. Exploratory endpoints include overall survival (OS) and efficacy by PD-L1 expression.

The updated data presented at WCLC include a median follow-up of 16 months for the two combination cohorts - Opdivo 3 mg/kg every two weeks plus Yervoy 1 mg/kg every six weeks (Q6W) (n=39) and 12 weeks (Q12W) (n=38). In the study, both PD-L1 expressors

>1% and non-expressors >1%, including 72% in the Q6W cohort and 70% in the Q12W cohort.

The pooled PFS and OS findings for the combination cohorts in all-treated patients and by tumor PD-L1 expression are reported below.

Additional efficacy findings were reported for the Q6W and Q12W cohorts in patients with tumor PD-L1 expression >1% at WCLC. These findings are summarized below.

The rates of treatment-related adverse events (AEs) with Opdivo plus Yervoy remained similar to those previously reported. Treatment related AEs of any grade were 84% and 74% for the Q12W and Q6W combination cohorts, respectively. The Grade 3/4 AEs were 42% and 31% for the Q12W and Q6W combination cohorts, respectively. Treatment- related AEs of any grade led to discontinuation in 18% of patients in Q12W and Q6W combination cohorts. Treatment-related Grade 3/4 AEs led to discontinuation in 8% of patients in the Q12W and Q6W combination cohorts.

About Lung Cancer

Lung cancer is the leading cause of cancer deaths globally, resulting in more than 1.5 million deaths each year, according to the World Health Organization. Non-small cell lung cancer (NSCLC) is one of the most common types of the disease and accounts for approximately 85% of cases. About 25% to 30% of all lung cancers are squamous cell carcinomas, and non-squamous NSCLC accounts for approximately 50% to 65% of all lung cancer cases. Survival rates vary depending on the stage and type of the cancer when it is diagnosed. Globally, the five-year survival rate for Stage I NSCLC is between 47% and 50%; for Stage IV NSCLC, the five-year survival rate drops to 2%.

Bristol-Myers Squibb: At the Forefront of Immuno-Oncology Science & Innovation

At Bristol-Myers Squibb, patients are at the center of everything we do. Our vision for the future of cancer care is focused on researching and developing transformational Immuno- Oncology (I-O) medicines that will raise survival expectations in hard-to-treat cancers and will change the way patients live with cancer.

We are leading the scientific understanding of I-O through our extensive portfolio of investigational and approved agents, including the first combination of two I-O agents in metastatic melanoma, and our differentiated clinical development program, which is studying broad patient populations across more than 20 types of cancers with 11 clinical-stage molecules designed to target different immune system pathways. Our deep expertise and innovative clinical trial designs uniquely position us to advance the science of combinations across multiple tumors and potentially deliver the next wave of I-O combination regimens with a sense of urgency. We also continue to pioneer research that will help facilitate a deeper understanding of the role of immune biomarkers and inform which patients will benefit most from I-O therapies.