ONO PHARMACEUTICAL : Opdivo (nivolumab) Stabilized Patient-reported Outcomes in Patients With Previously Treated Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck in Pivotal Phase 3 CheckMate -141 Study (166KB)

October 11, 2016

(PRINCETON, NJ, October 9, 2016) - Bristol-Myers Squibb Company (NYSE: BMY) announced new patient-reported quality-of-life data from an exploratory endpoint in the pivotal Phase 3 CheckMate -141 trial evaluating Opdivo in patients with recurrent or metastatic squamous cell carcinoma of the head and neck after platinum therapy compared to investigator's choice of therapy (methotrexate, docetaxel or cetuximab). Outcome assessments showed Opdivo stabilized patients' symptoms and functioning, including physical, role and social functioning across three separate instruments. Both PD-L1 expressors and non-expressors treated with investigator's choice of therapy experienced statistically significant worsening of patient-reported outcomes from baseline to week 15 versus Opdivo. In addition, Opdivo more than doubled the time to deterioration for most functional domains measured and significantly delayed the time to worsening symptoms of fatigue, dyspnea and insomnia, compared to investigator's choice of therapy.

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

Opdivo (nivolumab) Stabilized Patient-reported Outcomes in Patients With Previously Treated Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck in Pivotal Phase 3 CheckMate -141 Study

Opdivo-treated patients exhibited stable functioning and symptoms, whereas those treated with investigator's choice of therapy exhibited statistically significant worsening of these outcomes

Opdivo more than doubled the time to deterioration for most functional domains

(PRINCETON, NJ, October 9, 2016) - Bristol-Myers Squibb Company (NYSE: BMY) announced today new patient-reported quality-of-life data from an exploratory endpoint in the pivotal Phase 3 CheckMate -141 trial evaluating Opdivo in patients with recurrent or metastatic squamous cell carcinoma of the head and neck after platinum therapy compared to investigator's choice of therapy (methotrexate, docetaxel or cetuximab).

Outcome assessments showed Opdivo stabilized patients' symptoms and functioning, including physical, role and social functioning across three separate instruments. Both PD-L1 expressors and non-expressors treated with investigator's choice of therapy experienced statistically significant worsening of patient-reported outcomes from baseline to week 15 versus Opdivo. In addition, Opdivo more than doubled the time to deterioration for most functional domains measured and significantly delayed the time to worsening symptoms of fatigue, dyspnea and insomnia, compared to investigator's choice of therapy.

These findings will be presented today, October 9, during a Presidential Symposium at the 2016 European Society for Medical Oncology Congress from 4:25-4:40 p.m. CEST (Abstract #LBA4) and will be simultaneously published in The New England Journal of Medicine.

"Patients living with this form of advanced head and neck cancer often experience debilitating physiological effects as well as emotional and social challenges brought on by the condition despite current treatment options," 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. "These patient-reported outcomes are encouraging, as they help us understand the potential for Opdivo to impact important quality-of-life measures for this patient population."

Squamous cell carcinoma of the head and neck accounts for approximately 90% of all head and neck cancers and may impact a patient's physiological function (e.g., breathing, swallowing, eating, drinking), personal characteristics (e.g., appearance, speaking, voice), sensory function (e.g., taste, smell, hearing) as well as psychological and social functioning.

John O'Donnell, Ph.D., M.A., vice president, head, Health Economics and Outcomes Research, Bristol-Myers Squibb, commented, "At Bristol-Myers Squibb, we are committed to improving outcomes in advanced cancers and are proud to apply our Immuno-Oncology science to study the way people live with squamous cell carcinoma of the head and neck. The quality-of-life data from CheckMate -141 are important because they provide additional insights into how Opdivo may help patients with this difficult-to-treat disease."

About CheckMate -141

CheckMate -141 is a Phase 3, open-label, randomized trial that evaluated Opdivo versus investigator's choice of therapy in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) with tumor progression within six months of platinum therapy in the adjuvant, primary, recurrent or metastatic setting.

Patient-reported outcomes (PRO) data were collected using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), EORTC Head and Neck Cancer-Specific Module (EORTC QLQ-H&N35) and the 3-level EQ-5D questionnaire (EQ-5D). The questionnaires were administered at baseline (cycle 1, day 1), week 9 and at six-week intervals thereafter while patients were on treatment. Clinical relevance was assessed using an established minimally important difference (MID) of ≥10 points for EORTC subscales.

Both the EORTC QLQ-C30 and EORTC QLQ-H&N35 questionnaires showed there were significant differences in PROs between patients treated with Opdivo and those treated with investigator's choice of therapy at 15 weeks. In the EORTC QLQ-C30, while patients treated with Opdivo had stable PROs relative to baseline, those treated with investigator's choice of therapy had significant and clinically meaningful worsening of physical, role and social functioning (pOpdivo), fatigue (pOpdivo), dyspnea (pOpdivo) and appetite loss (p=0.004 versus Opdivo). Opdivo more than doubled the median time to deterioration for global health status (7.7 versus 3.0 months), physical functioning (7.8 versus 3.6 months), role functioning (8.6 versus 3.8 months),

cognitive functioning (7.8 versus 3.3 months) and social functioning (7.7 versus 3.0 months), compared with investigator's choice of therapy. In emotional functioning, Opdivo

demonstrated a median time to deterioration of 6.7 months versus 4.7 months for investigator's choice of therapy. Opdivo also reduced the rate of clinically meaningful deterioration in fatigue, insomnia and dypsnea by 50% (p=0.008).

Responses to the QLQ-H&N35 questionnaire showed while patients treated with Opdivo reported stable PROs relative to baseline, those treated with investigator's choice of therapy had significant worsening in pain (p=0.022 versus Opdivo) as well as significant and clinically meaningful worsening in sensory problems (pOpdivo) and social contact problems (p=0.001 versus Opdivo). Compared with investigator's choice of therapy, Opdivo reduced the rate of clinically meaningful deterioration in pain by 74% (pp=0.002 versus investigator's choice of therapy) and opening mouth problems by 51% (p=0.029 versus investigator's choice of therapy).

Patients treated with Opdivo experienced stable health status, as measured by the EQ- 5D VAS, whereas those in the investigator's choice arm experienced worsening of health status, with a statistically significant difference at 15 weeks (p=0.037). Median time to deterioration of health status was nearly triple with 9.1 months for patients receiving Opdivo versus 3.3 months for those in the investigator's choice arm.

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, nose and throat. Head and neck cancer is the seventh most common cancer globally, with an estimated 600,000 new cases per year and 223,000-300,000 deaths per year. The global incidence of squamous cell carcinoma of the head and neck (SCCHN) is expected to increase by 17% between 2012 and 2022. The five-year survival rate is reported as less than 4% for metastatic Stage IV disease. Risk factors for SCCHN include tobacco and alcohol consumption. The Human Papilloma Virus (HPV) infection also is a risk factor leading to rapid increase in oropharyngeal SCCHN in Europe and North America.

Bristol-Myers Squibb: At the Forefront of Immuno-Oncology Science & Innovation

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.