ONO PHARMACEUTICAL : Two-Year Overall Survival Data from Two Pivotal Opdivo® (nivolumab) Trials Demonstrate Sustained Benefit In Patients with Advanced Non-Small Cell Lung Cancer (196KB)

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May 24, 2016

Two-Year Overall Survival Data from Two Pivotal Opdivo® (nivolumab) Trials Demonstrate Sustained Benefit In Patients with Advanced Non-Small Cell Lung Cancer

(PRINCETON, NJ, May 18, 2016) - Bristol-Myers Squibb Company (NYSE: BMY) announced two- year overall survival data from two pivotal Phase 3 studies evaluating Opdivo (nivolumab) versus docetaxel in previously treated metastatic non-small cell lung cancer (NSCLC). Opdivo continued to demonstrate improved overall survival (OS), the primary endpoint for both studies, at the landmark two-year time point. In CheckMate -057, a trial in previously treated non-squamous NSCLC, 29% of patients treated with Opdivo were alive at two years (n=81/292) versus 16% of those treated with docetaxel (n=45/290) (HR: 0.75 [95% CI: 0.63, 0.91]). In CheckMate -017, a trial in previously treated squamous NSCLC, 23% of patients treated with Opdivo were alive at two years (n=29/135) versus 8% of those treated with docetaxel (n=11/137) (HR: 0.62 [95% CI: 0.47, 0.80]). In CheckMate -057 and - 017, treatment-related adverse events (AEs) occurred in 71% and 61% of Opdivo-treated patients. The safety profile of Opdivo at two years was consistent with previous reports of data from both studies.

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 Head and Neck Cancer, Glioblastoma, Small Cell Lung Cancer, Urothelial Cancer, Hepatocellular Carcinoma, Esophageal Cancer, Hodgkin Lymphoma, Colorectal Cancer, Solid Tumors (Triple-Negative Breast Cancer, Gastric Cancer, Pancreatic 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. In addition, ONO has submitted supplemental applications for additional indications of Renal Cell Cancer and Hodgkin Lymphoma, and is conducting clinical development program including Head and Neck Cancer, Gastric Cancer, Esophageal Cancer, Small Cell Lung Cancer, Hepatocellular Carcinoma, Glioblastoma, Ovarian Cancer, Urothelial 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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ONO PHARMACEUTICAL CO., LTD.

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Two-Year Overall Survival Data from Two Pivotal Opdivo® (nivolumab) Trials Demonstrate Sustained Benefit In Patients with Advanced Non-Small Cell Lung Cancer

Opdivo demonstrated an overall survival benefit at the landmark two-year time point versus docetaxel in previously treated advanced non-small cell lung cancer, across histologies

Data show benefit with Opdivo in the overall population, with nearly double (CheckMate -057) and triple (CheckMate -017) the patients alive at two years compared to docetaxel

Safety profile of Opdivo at two years was consistent with previous reports of data from both studies

(PRINCETON, NJ, May 18, 2016) - Bristol-Myers Squibb Company (NYSE: BMY) announced today two-year overall survival data from two pivotal Phase 3 studies evaluating Opdivo (nivolumab) versus docetaxel in previously treated metastatic non-small cell lung cancer (NSCLC). Opdivo continued to demonstrate improved overall survival (OS), the primary endpoint for both studies, at the landmark two-year time point. In CheckMate -057, a trial in previously treated non-squamous NSCLC, 29% of patients treated with Opdivo were alive at two years (n=81/292) versus 16% of those treated with docetaxel (n=45/290) (HR: 0.75 [95% CI: 0.63, 0.91]). In CheckMate -017, a trial in previously treated squamous NSCLC, 23% of patients treated with Opdivo were alive at two years (n=29/135) versus 8% of those treated with docetaxel (n=11/137) (HR: 0.62 [95% CI: 0.47, 0.80]). In CheckMate - 057 and -017, treatment-related adverse events (AEs) occurred in 71% and 61% of Opdivo-treated patients. The safety profile of Opdivo at two years was consistent with previous reports of data from both studies.

These data will be presented at the 52nd Annual Meeting of the American Society of Clinical

Oncology (ASCO) Annual Meeting in Chicago, IL, June 3-7, during a poster session on Saturday, June 4, 8:00 AM - 11:30 AM CDT (Abstract #9025).

"These new data from CheckMate -057 and -017 are robust randomized Phase 3 data, with the longest published follow up of patients being on therapy available for a PD-1 inhibitor in lung cancer, across histologies," said Hossein Borghaei, DO, Chief, Thoracic Oncology, Fox Chase Cancer Center. "Data presented at ASCO underscore the potential of Opdivo to improve long-term outcomes for patients with this particularly challenging disease."

Findings to be presented at the meeting will also include additional research to explore biomarkers that may help predict outcomes with Opdivo.

Nick Botwood, M.D., Development Lead, Lung and Head & Neck, Bristol-Myers Squibb, commented, "Our fundamental goal for Immuno-Oncology research is to redefine the expectation of long-term, quality survival for all patients with lung cancer. We will seek to continue to leverage our deep scientific expertise and our unwavering commitment to patients to deliver transformative cancer care. Today, these data from CheckMate -057 and -017 expand our understanding of the potential for Opdivo to provide a meaningful, durable survival benefit to patients with previously treated metastatic NSCLC."

About CheckMate -057 & CheckMate -017

CheckMate -057 is a landmark Phase 3, open-label, randomized clinical trial that evaluated patients with advanced non-squamous non-small cell lung cancer (NSCLC) who had progressed during or after one prior platinum doublet-based chemotherapy regimen. The trial included patients regardless of their PD-L1 status. The study's primary endpoint was overall survival (OS) and secondary endpoints included objective response rate (ORR), progression-free survival (PFS) and efficacy by tumor PD-L1

expression. Patients enrolled in the trial were administered Opdivo 3 mg/kg every two weeks versus standard of care, docetaxel, at 75 mg/m2 every three weeks.

At two years, 29% of patients treated with Opdivo were alive (n=81/292) versus 16% of those treated with docetaxel (n=45/290) (HR=0.75 [95% CI: 0.63, 0.91). Median overall survival (OS) was

12.2 months with Opdivo (95% CI: 9.7, 15.1) versus 9.5 months with docetaxel (95% CI: 8.1, 10.7).

CheckMate -057 also evaluated the efficacy of Opdivo by tumor PD-L1 expression. Of randomized patients, 78% (455/582) had tumor samples allowing the assessment of PD-L1 expression. Rates of PD-L1 expressing tumors were balanced between groups. Across pre-specified expression levels (1%, 5%, and 10%), PD-L1 status was associated with enhanced magnitude of benefit

from Opdivo. In patients who did not express PD-L1, OS was similar between Opdivo and docetaxel. The chart below describes the OS results based on PD-L1 expression levels.

Hazard Ratio (HR) for Opdivo vs. docetaxel (2 year OS rate)
	HR=0.91 [95% CI: 0.67-1.22] 25% vs. 18%
≥1% PD-L1 expression level	HR=0.62 [95% CI: 0.47-0.83] 37% vs. 17%
≥5% PD-L1 expression level	HR=0.48 [95% CI: 0.34-0.68] 44% vs. 14%
≥10% PD-L1 expression level	HR=0.43 [95% CI: 0.30-0.62] 45% vs. 13%

CheckMate -017 was a Phase 3, open-label, randomized clinical trial that evaluated Opdivo 3 mg/kg every two weeks versus standard of care, docetaxel 75 mg/m2 every three weeks, in patients with advanced squamous NSCLC who had progressed during or after one prior platinum doublet-based chemotherapy regimen. The study's primary endpoint was OS and secondary endpoints included PFS and response rate. The trial included patients regardless of their PD-L1 expression status.

In CheckMate -017, 23% of patients treated with Opdivo were alive at two years (n=29/135) versus 8% of those treated with docetaxel (n=11/137) (HR=0.62 [95% CI: 0.47, 0.80]). Median OS was

9.2 months with Opdivo (95% CI: 7.3, 12.6) versus 6.0 months with docetaxel (95% CI: 5.1, 7.3). The safety profile of Opdivo remained consistent with previous reports of data from both

CheckMate -057 and CheckMate -017 trials, and treatment-related adverse events (AEs) of any grade and grade 3/4 were less frequent with Opdivo versus docetaxel. The frequencies of the most common treatment-related AEs across the two trials remained lower with Opdivo than with docetaxel. In CheckMate -057 the most common treatment-related AEs for Opdivo and docetaxel included fatigue (17%, 29%, respectively), nausea (12%, 26%, respectively), decreased appetite (11%, 16%, respectively), and asthenia (10%, 18%, respectively). In CheckMate -017, the most common treatment- related AEs Opdivo and docetaxel included fatigue (16%, 33%, respectively), decreased appetite (11%, 19%, respectively), asthenia (11%, 14%, respectively) and nausea (9%, 23%, respectively).

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 & Immuno-Oncology: Advancing Oncology Research

At Bristol-Myers Squibb, we have a vision for the future of cancer care that is focused on Immuno-Oncology, now considered a major treatment choice alongside surgery, radiation, chemotherapy and targeted therapies for certain types of cancer.

We have a comprehensive clinical portfolio of investigational and approved Immuno-Oncology agents, many of which were discovered and developed by our scientists. Our ongoing Immuno-