ONO PHARMACEUTICAL : European Commission Approves Bristol-Myers Squibb's Opdivo (nivolumab) for Previously Treated Locally Advanced Unresectable or Metastatic Urothelial Carcinoma in Adults After Failure of Prior Platinum-Containing Therapy (186KB)

June 5, 2017

(PRINCETON, N.J., June 2, 2017) - Bristol-Myers Squibb Company (NYSE: BMY) announced that the European Commission (EC) has approved Opdivo (nivolumab) for the treatment of locally advanced unresectable or metastatic urothelial carcinoma (mUC) in adults after failure of prior platinum-containing therapy. Today's decision makes Opdivo the first Immuno-Oncology agent approved in the European Union for the treatment of patients with this common type of bladder cancer.

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, relapsed or refractory classical Hodgkin lymphoma in December 2016 and recurrent or metastatic head and neck cancer in March 2017. In addition, ONO has submitted supplemental application for additional indication of gastric cancer, and is conducting clinical development program including esophageal cancer, gastro-esophageal junction 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. Contact

ONO PHARMACEUTICAL CO., LTD.

Corporate Communications public_relations@ono.co.jp

(PRINCETON, N.J., June 2, 2017) - Bristol-Myers Squibb Company (NYSE: BMY) announced today that the European Commission (EC) has approved Opdivo (nivolumab) for the treatment of locally advanced unresectable or metastatic urothelial carcinoma (mUC) in adults after failure of prior platinum-containing therapy. Today's decision makes Opdivo the first Immuno- Oncology agent approved in the European Union for the treatment of patients with this common type of bladder cancer.

"Bladder cancer has an estimated 151,000 new cases diagnosed annually in Europe, yet there have been few advancements in treatment for advanced bladder cancer during the last few decades," said Prof. Dr. Margitta Retz, Director of the Division Uro-Oncology of the Department of Urology, Technical University Munich, Germany. "The European Commission's approval of nivolumab marks a significant advancement, with a notable objective response rate, and provides an important option to help patients with previously treated locally advanced unresectable or metastatic urothelial cancer."

The approval was based on results from CheckMate -275, a Phase 2, open-label, single-arm, multicenter study evaluating Opdivo in patients with locally advanced or mUC who have disease progression during or following treatment with a platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. In this study, 270 patients received Opdivo 3 mg/kg administered intravenously every two weeks until disease progression or unacceptable toxicity. The primary endpoint of the trial was objective response rate (ORR). Secondary endpoints included progression free survival (PFS) and overall survival (OS). In the trial, 20.0% (95% CI: 15.4, 25.3; 54/270) of patients responded to treatment with Opdivo. The percentage of patients with a complete response was 3.0% (8/270) and the percentage of patients with a partial response was 17% (46/270).

"We are pleased with the European Commission's approval of Opdivo for patients with previously treated locally advanced unresectable or metastatic urothelial carcinoma, many of whom have been in need of an additional treatment option," said Murdo Gordon, executive vice president and chief commercial officer, Bristol-Myers Squibb. "With this second EU approval for Opdivo in as

many months, Bristol-Myers Squibb is demonstrating our commitment to help address unmet needs for cancer patients. We intend to work closely with EU health authorities to make Opdivo available for patients with this common form of bladder cancer as soon as possible."

Half of the overall patient population (46%) in CheckMate -275 had a tumor PD-L1 expression of ≥1% and efficacy was observed across tumor PD-L1 expressors and non-expressors. The response rate was 25% in patients with tumor PD-L1 expression ≥1% (95% CI: 17.7, 33.6) and 15.8% (95% CI: 10.3, 22.7) in those with tumor PD-L1 expression

Among the 270 patients who received Opdivo in CheckMate -275, 17.8% experienced a grade 3 or 4 treatment-related adverse event (AE). The most frequently reported treatment-related AEs of any grade included fatigue (16.7%), pruritis (9.3%), diarrhea (8.9%), decreased appetite (8.1%),

hypothyroidism (7.8%), nausea (7.0%), asthenia (5.9%), rash (5.9%) and pyrexia (5.6%). The most

frequent treatment-related grade 3-4 AEs were fatigue (1.9%), diarrhea (1.9%), asthenia (1.5%) and rash (1.1%). Overall, 4.8% of patients discontinued therapy due to treatment-related AEs of any grade, and 3.0% discontinued therapy due to grade 3-4 treatment-related AEs. Treatment-related death occurred in four patients due to pneumonitis or cardiovascular failure.

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 carcinoma 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, 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, 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 for hard-to-treat cancers that could potentially improve outcomes for these patients.

We are leading the scientific understanding of I-O through our extensive portfolio of investigational compounds and approved agents. Our differentiated clinical development program is studying broad patient populations across more than 50 types of cancers with 14 clinical-stage

molecules designed to target different immune system pathways. Our deep expertise and innovative clinical trial designs position us to advance I-O/I-O, I-O/chemotherapy, I-O/targeted therapies and I- O/radiation therapies across multiple tumors and potentially deliver the next wave of therapies 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 how patients' individual tumor biology can be used as a guide for treatment decisions throughout their journey.

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 60 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 combination to receive regulatory approval for the treatment of metastatic melanoma and is currently approved in more than 50 countries, including the United States and the European Union.

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