ONO PHARMACEUTICAL : European Commission Approves Bristol-Myers Squibb’s Opdivo (nivolumab) for Squamous Cell Cancer of the Head and Neck in Adults Progressing On or After Platinum-based Therapy (192KB)

May 8, 2017

European Commission Approves Bristol-Myers Squibb's Opdivo (nivolumab) for Squamous Cell Cancer of the Head and Neck in Adults Progressing On or After Platinum-based Therapy

(PRINCETON, NJ, April 28, 2017) - Bristol-Myers Squibb Company (NYSE: BMY) announced that the European Commission (EC) has approved Opdivo (nivolumab) as monotherapy for the treatment of squamous cell cancer of the head and neck (SCCHN) in adults progressing on or after platinum-based therapy. Opdivo is the first and only Immuno-Oncology (I-O) treatment that demonstrated in a Phase 3 trial a significant improvement in overall survival (OS) for these patients.

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 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.

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European Commission Approves Bristol-Myers Squibb's Opdivo (nivolumab) for Squamous Cell Cancer of the Head and Neck in Adults Progressing On or After

Platinum-based Therapy

Opdivo is the first and only Immuno-Oncology agent to receive European approval for the treatment of squamous cell cancer of the head and neck in adults progressing on or after platinum-based therapy

Opdivo is now approved by the EC for seven indications in five distinct tumor types

(PRINCETON, NJ, April 28, 2017) - Bristol-Myers Squibb Company (NYSE: BMY) today announced that the European Commission (EC) has approved Opdivo (nivolumab) as monotherapy for the treatment of squamous cell cancer of the head and neck (SCCHN) in adults progressing on or after platinum-based therapy. Opdivo is the first and only Immuno- Oncology (I-O) treatment that demonstrated in a Phase 3 trial a significant improvement in overall survival (OS) for these patients.

"Adult patients with squamous cell cancer of the head and neck that progresses on or after platinum-based therapy are fighting a debilitating and hard-to-treat disease that is associated with a very poor prognosis," said Kevin Harrington, M.D., Ph.D., professor in Biological Cancer Therapies at The Institute of Cancer Research, London, and a consultant clinical oncologist at The Royal Marsden NHS Foundation Trust in London. "As an oncologist who helps patients deal with navigate this terrible disease, I hope that nivolumab will now be made available as widely as possible, offering this group of patients a new treatment option that can potentially improve their overall survival."

The approval was based on results from CheckMate -141, a global Phase 3, open- label, randomized trial, first published in The New England Journal of Medicine last October, which evaluated Opdivo versus investigator's choice of therapy in patients aged 18 years and above with recurrent or metastatic, platinum-refractory SCCHN who had tumor progression during or within six months of receiving platinum-based therapy administered in the adjuvant, neo-adjuvant, primary or metastatic setting. Investigator's choice of therapy included methotrexate, docetaxel, or cetuximab. The primary endpoint was OS. The trial's secondary endpoints included progression-free survival (PFS) and objective response rate (ORR).

"The European Commission's approval of Opdivo marks not only the first new treatment option in 10 years for patients with advanced cancers of the head and neck, but also the first Immuno-Oncology treatment for SCCHN," said Murdo Gordon, executive vice

president and chief commercial officer, Bristol-Myers Squibb. "Bristol-Myers Squibb remains committed to redefining survival for patients with cancer, and now that Opdivo is approved in Europe, we will work collaboratively with EU health authorities to ensure it is available for these patients as quickly as possible."

In the interim analysis of the pivotal trial, Opdivo demonstrated statistically significant improvement in OS with a 30% reduction in the risk of death (HR=0.70 [95% CI: 0.53-0.92; p=0.0101]), and a median OS of 7.5 months (95% CI: 5.5-9.1) for Opdivo compared with 5.1 months (95% CI: 4.0-6.0) for the investigator's choice arm. There were no statistically significant differences between the two arms for PFS (HR=0.89; 95% CI: 0.70, 1.13) or ORR (13.3% [95% CI: 9.3, 18.3] vs 5.8% [95% CI: 2.4, 11.6] for Opdivo and investigator's choice, respectively. The EC approval was based on updated study results, which will be presented at the 53rd Annual Meeting of the American Society of Clinical Oncology (ASCO).

Patient reported outcomes (PROs) were evaluated using the following European Organization for Research and Treatment of Cancer (EORTC) quality-of-life assessments: EORTC QLQ-C30, EORTC QLQ-H&N35, and 3-level EQ-5D instruments. Patients treated with Opdivo exhibited stable PROs, while those assigned to investigator's choice therapy exhibited significant declines in functioning (e.g., physical, role, social) and health status as well as increased symptomatology (e.g., fatigue, dyspnoea, appetite loss, pain and sensory problems).

The safety profile of Opdivo in CheckMate -141 was consistent with prior studies in patients with melanoma and non-small cell lung cancer. Serious adverse reactions occurred in 49% of patients receiving Opdivo. The most frequent serious adverse reactions reported in at least 2% of patients receiving Opdivo were pneumonia, dyspnea, aspiration pneumonia, respiratory failure, respiratory tract infection, and sepsis.

About Head & Neck Cancer

Cancers that are known as head and neck cancers usually begin in the squamous cells that line the moist mucosal surfaces inside the head and neck, such as inside the mouth, the nose and the throat. Head and neck cancer is the seventh most common cancer globally, with an estimated 400,000 to 600,000 new cases per year and 223,000 to 300,000 deaths per year. The five-year survival rate is reported as less than 4% for metastatic Stage IV disease.

Squamous cell cancer of the head and neck (SCCHN) accounts for approximately 90% of all head and neck cancers with global incidence expected to increase by 17% between 2012 and

2022. Risk factors for SCCHN include tobacco and alcohol consumption. Human Papilloma Virus (HPV) infection is also a risk factor leading to rapid increase in oropharyngeal SCCHN in Europe and North America.

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.

U. S. FDA APPROVED INDICATIONS FOR OPDIVO®

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