ONO PHARMACEUTICAL : European Medicines Agency Validates Bristol-Myers Squibb's Type II Variation Application for Opdivo (nivolumab) in Advanced Form of Bladder Cancer (189KB)

September 21, 2016‌

(PRINCETON, NJ, September 20, 2016) - Bristol-Myers Squibb Company (NYSE: BMY) announced that the European Medicines Agency (EMA) validated its type II variation application, which seeks to extend the current indications for Opdivo to include the treatment of locally advanced unresectable or metastatic urothelial carcinoma (mUC) in adults after failure of prior platinum-containing therapy. Validation of the application confirms the submission is complete and begins the EMA's centralized review process.

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

Results from Phase 2 study CheckMate -275 evaluating Opdivo in metastatic urothelial carcinoma serve as basis for application

(PRINCETON, NJ, September 20, 2016) - Bristol-Myers Squibb Company (NYSE: BMY) announced today that the European Medicines Agency (EMA) validated its type II variation application, which seeks to extend the current indications for Opdivo to include the treatment of locally advanced unresectable or metastatic urothelial carcinoma (mUC) in adults after failure of prior platinum-containing therapy. Validation of the application confirms the submission is complete and begins the EMA's centralized review process.

"The high frequency of metastatic urothelial carcinoma and its relapsing nature highlight the substantial need for new treatment approaches with high and durable responses," said Fouad Namouni, M.D., head of development, Oncology, Bristol-Myers Squibb. "We

look forward to working with EMA to potentially extend the use of Opdivo and bring the science of Immuno-Oncology to help patients in Europe fight this difficult-to-treat, advanced form of bladder cancer."

The application primarily included data from CheckMate-275, a Phase 2, open-label, single arm study assessing the safety and efficacy of Opdivo in patients with locally advanced unresectable or mUC that has progressed after a platinum-containing therapy. The primary endpoint in CheckMate-275 trial is objective response rate, and additional efficacy measures included durability of response and overall survival. Data from this study will be presented at the 2016 European Society for Medical Oncology Congress.

About Bladder Cancer

Bladder cancer, which typically begins in the cells that line the inside of the bladder, is the fifth most commonly diagnosed cancer in Europe, with an estimated 151,000 new cases diagnosed per year and over 52,000 deaths per year. Urothelial cancer is the most common type of bladder cancer, accounting for approximately 90% of cases. The majority of bladder cancers are diagnosed at an early stage, but rates of recurrence and progression are high and approximately 78% of patients will experience a recurrence within five years. Survival rates vary depending on the stage and type of the cancer and when it is diagnosed. For Stage IV bladder cancer, the five-year survival rate is 15%.

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-Oncology clinical program is looking at broad patient populations, across multiple solid tumors and hematologic malignancies, and lines of therapy and histologies, with the intent of powering our trials for overall survival and other important measures like durability of response. We pioneered the research leading to the first regulatory approval for the combination of two Immuno-Oncology agents, and continue to study the role of combinations in cancer.

We are also investigating other immune system pathways in the treatment of cancer including CTLA-4, CD-137, KIR, SLAMF7, PD-1, GITR, CSF1R, IDO, and LAG-3. These

pathways may lead to potential new treatment options - in combination or monotherapy - to help patients fight different types of cancers.

Our collaboration with academia, as well as small and large biotech companies, to research the potential Immuno-Oncology and non-Immuno-Oncology combinations, helps achieve our goal of providing new treatment options in clinical practice.

At Bristol-Myers Squibb, we are committed to changing survival expectations in hard-to-treat cancers and the way patients live with cancer.

About Opdivo

Cancer cells may exploit "regulatory" pathways, such as checkpoint pathways, to hide from the immune system and shield the tumor from immune attack. Opdivo is a PD-1 immune checkpoint inhibitor that binds to the checkpoint receptor PD-1 expressed on activated T-cells, and blocks the binding of PD-L1 and PD-L2, preventing the PD-1 pathway's suppressive signaling on the immune system, including the interference with an anti-tumor immune response.

Opdivo's broad global development program is based on Bristol-Myers Squibb's understanding of the biology behind Immuno-Oncology. Our company is at the forefront of researching the potential of Immuno-Oncology to extend survival in hard-to-treat cancers. This scientific expertise serves as the basis for the Opdivo development program, which includes a broad range of Phase 3 clinical trials evaluating overall survival as the primary

endpoint across a variety of tumor types. The Opdivo trials have also contributed toward the clinical and scientific understanding of the role of biomarkers and how patients may benefit from Opdivo across the continuum of PD-L1 expression. To date, the Opdivo clinical development program has enrolled more than 18,000 patients.

Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world in July 2014, and currently has regulatory approval in 54 countries including the United States, Japan, and in the European Union.

U.S. FDA APPROVED INDICATIONS FOR OPDIVO®

OPDIVO® (nivolumab) as a single agent is indicated for the treatment of patients with BRAF V600 wild-type unresectable or metastatic melanoma.

OPDIVO® (nivolumab) as a single agent is indicated for the treatment of patients with BRAF V600 mutation-positive unresectable or metastatic melanoma. This indication is approved under accelerated approval based on progression-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of patients with unresectable or metastatic melanoma. This indication is approved under accelerated approval based on progression-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

OPDIVO®(nivolumab) is indicated for the treatment of patients with metastatic non- small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving OPDIVO.

OPDIVO®(nivolumab) is indicated for the treatment of patients with advanced renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy.

OPDIVO® (nivolumab) is indicated for the treatment of patients with classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and post- transplantation brentuximab vedotin. This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.