ONO PHARMACEUTICAL : Bristol-Myers Squibb Receives Positive CHMP Opinion Recommending Approval of Opdivo (nivolumab) for the Treatment of Patients with Previously Treated Locally Advanced or Metastatic Urothelial Carcinoma, a Type of Bladder Cancer (149KB)

April 24, 2017

(PRINCETON, NJ, April 21, 2017) - Bristol-Myers Squibb Company (NYSE: BMY) announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has recommended the approval of Opdivo (nivolumab) for the treatment of locally advanced unresectable or metastatic urothelial carcinoma (mUC) in adults after failure of prior platinum- containing therapy. The CHMP recommendation will now be reviewed by the European Commission (EC), which has the authority to approve medicines for the European Union (EU).

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, relapsed or refractory classical Hodgkin lymphoma in December 2016 and recurrent or metastatic head and neck cancer on March 24, 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.

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Opdivo (nivolumab) for the Treatment of Patients with Previously Treated Locally Advanced or Metastatic Urothelial Carcinoma, a Type of Bladder Cancer

First positive CHMP opinion for an Immuno-Oncology agent for patients with locally advanced or metastatic urothelial cancer

CHMP opinion based on tumor response rate and duration of response demonstrated in Phase 2 CheckMate -275 trial

(PRINCETON, NJ, April 21, 2017) - Bristol-Myers Squibb Company (NYSE: BMY) announced today that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has recommended the approval of Opdivo (nivolumab) for the treatment of locally advanced unresectable or metastatic urothelial carcinoma (mUC) in adults after failure of prior platinum-containing therapy. The CHMP recommendation will now be reviewed by the European Commission (EC), which has the authority to approve medicines for the European Union (EU).

Opdivo is the first and only PD-1 immune checkpoint inhibitor for the treatment of patients with previously treated mUC to receive a positive CHMP opinion. Opdivo is already approved by the EC for six indications in four distinct tumor types.

"We view the CHMP recommendation of Opdivo for previously treated locally advanced or metastatic urothelial carcinoma as an important milestone for the patients. Bristol-Myers Squibb looks forward to collaborating with the European Commission as it considers this potential new indication for Opdivo," said Murdo Gordon, executive vice president and chief commercial officer, Bristol-Myers Squibb.

The CHMP adopted its positive opinion based on results from the Phase 2 clinical trial CheckMate -275 in patients with locally advanced unresectable or mUC that progressed after a platinum-containing therapy and were treated with Opdivo. The primary endpoint of CheckMate - 275 was objective response rate and additional efficacy measures included durability of response and overall survival. Data from CheckMate -275 were presented at the 2016 European Society for Medical Oncology Congress in October 2016 and published online in Lancet Oncology in January 2017.

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, 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 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 35 types of cancers with 13 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 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 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) as a single agent is indicated for the treatment of patients with BRAF V600 wild-type unresectable or metastatic melanoma.

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