ONO PHARMACEUTICAL : Bristol-Myers Squibb Presents Results From CheckMate -026, a Phase 3 Study of Opdivo (nivolumab) Monotherapy Versus Chemotherapy as First-Line Therapy in a Broad PD-L1 Positive Population With Advanced Lung Cancer (165KB)

October 11, 2016

(PRINCETON, NJ, October 9, 2016) - Bristol-Myers Squibb Company (NYSE: BMY) announced the final primary analysis of CheckMate -026, a trial investigating the use of Opdivo (nivolumab) monotherapy as first-line therapy in patients with advanced non-small cell lung cancer (NSCLC) whose tumors expressed PD-L1 ≥1%. The study was powered to assess progression-free survival (PFS) for patients with ≥5% PD- L1 expression. The topline results from this study were previously disclosed and showed CheckMate -026 did not meet the primary endpoint of superior PFS compared to chemotherapy. In patients with ≥5% PD-L1 expression, the median PFS was 4.2 months with Opdivo and 5.9 months with platinum-based doublet chemotherapy (stratified hazard ratio [HR]=1.15 [95% CI: 0.91, 1.45, p=0.25]). Overall survival was 14.4 months for Opdivo versus 13.2 months for chemotherapy (HR=1.02 [95% CI: 0.80, 1.30]), and 60% of patients on the chemotherapy arm received subsequent Opdivo use after progression either through crossover or commercial access.

The safety of Opdivo was consistent with the known safety profile of the drug in previous studies. Among all-treated patients, treatment-related adverse events (AE) of any grade and Grade 3/4 occurred in 71% and 18% of Opdivo-treated patients and 92% and 51% of chemotherapy-treated patients, respectively.

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 and unresectable or metastatic renal cell cancer in August 2016. In addition, ONO has submitted supplemental applications for additional indications of Hodgkin Lymphoma and Head and Neck Cancer, and is conducting clinical development program including Gastric Cancer, Esophageal Cancer, Small Cell Lung Cancer, Hepatocellular Carcinoma, Glioblastoma, Ovarian Cancer, Urothelial Cancer, Malignant Pleural Mesothelioma, 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. Contact

ONO PHARMACEUTICAL CO., LTD.

Corporate Communications public_relations@ono.co.jp

(PRINCETON, N.J., October 9, 2016) - Bristol-Myers Squibb Company (NYSE: BMY) announced today the final primary analysis of CheckMate -026, a trial investigating the use of Opdivo (nivolumab) monotherapy as first-line therapy in patients with advanced non-small cell lung cancer (NSCLC) whose tumors expressed PD-L1 ≥1%. The study was powered to assess progression-free survival (PFS) for patients with ≥5% PD-L1 expression. The topline results from this study were previously disclosed and showed CheckMate -026 did not meet the primary endpoint of superior PFS compared to chemotherapy. In patients with ≥5% PD-L1 expression, the median PFS was 4.2 months with Opdivo and 5.9 months with platinum-based doublet chemotherapy (stratified hazard ratio [HR]=1.15 [95% CI: 0.91, 1.45, p=0.25]). Overall survival was 14.4 months for Opdivo versus 13.2 months for chemotherapy (HR=1.02 [95% CI: 0.80, 1.30]), and 60% of patients on the chemotherapy arm received subsequent Opdivo use after progression either through crossover or commercial access.

The safety of Opdivo was consistent with the known safety profile of the drug in previous studies. Among all-treated patients, treatment-related adverse events (AE) of any grade and Grade 3/4 occurred in 71% and 18% of Opdivo-treated patients and 92% and 51% of chemotherapy-treated patients, respectively.

"Opdivo has replaced the standard of care in previously treated metastatic NSCLC patients regardless of PD-L1 expression, and this study aimed to answer an important clinical question of whether this PD-1 inhibitor could provide superior benefit over chemotherapy in a broad patient population in the first-line setting," said Mark Socinski, M.D., executive medical director, Florida Hospital Cancer Institute, Orlando, and lead author of the study. "These findings provide additional understanding of the role of PD-1 monotherapy in treatment-naïve patients and confirm there is still a significant opportunity for improving outcomes for the majority of these patients."

These data will be presented today, October 9, during a Presidential Symposium at the 2016 European Society for Medical Oncology (ESMO) Congress from 5:35-5:50 p.m. CEST (Abstract #LBA7_PR).

"The CheckMate -026 trial results strengthen our belief that the majority of previously untreated NSCLC patients may require combination therapy in order to experience an improved benefit versus chemotherapy," said Fouad Namouni, M.D., head of development, Oncology, Bristol-Myers Squibb. "With our broad lung cancer development program, which includes a robust Phase 3 trial evaluating the combination of Opdivo and Yervoy as first-line therapy, we will continue to aim for transformative options for the majority of lung cancer patients."

About CheckMate -026

CheckMate -026 is a Phase 3, open-label, randomized study of Opdivo as monotherapy versus investigator's choice chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). Patients enrolled in the trial had received no prior systemic treatment for advanced disease and tested positive for PD-L1 expression (≥1%). The trial randomized 541 patients to receive either Opdivo 3 mg/kg intravenously every two weeks or investigator's choice platinum-based doublet chemotherapy in squamous patients (gemcitabine with cisplatin/gemcitabine with carboplatin/paclitaxel with carboplatin, followed by optional pemetrexed maintenance) and non-squamous patients (pemetrexed with cisplatin/pemetrexed with carboplatin) until disease progression, unacceptable toxicity or completion of six cycles. The primary endpoint is progression-free survival (PFS), as assessed by the Independent Radiology Review Committee, in patients with ≥5% PD-L1 tumor expression.

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 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, 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.

We understand making the promise of I-O a reality for the many patients who may benefit from these therapies requires not only innovation on our part but also close collaboration with leading experts in the field. Our partnerships with academia, government, advocacy and biotech companies support our collective goal of providing new treatment options to advance the standards of clinical practice.

About Opdivo

Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to uniquely harness the body's own immune system to help restore anti-tumor immune response. By harnessing the body's own immune system to fight cancer, Opdivo has become an important treatment option across multiple cancers.

Opdivo's leading global development program is based on Bristol-Myers Squibb's scientific expertise in the field of Immuno-Oncology and includes a broad range of clinical trials across all phases, including Phase 3, in a variety of tumor types. To date,

the Opdivo clinical development program has enrolled more than 25,000 patients. The Opdivo trials have contributed to gaining a deeper understanding of the potential role of biomarkers in patient care, particularly regarding how patients may benefit

from Opdivo across the continuum of PD-L1 expression.

In July 2014, Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world. Opdivo is currently approved in more than 57 countries, including the United States, the European Union and Japan. In October 2015, the company's Opdivo and Yervoy combination regimen was the first Immuno-Oncology