ONO PHARMACEUTICAL : First Presentation of Efficacy Data from CheckMate -204 Evaluating the Combination of Opdivo (nivolumab) and Yervoy (ipilimumab) Demonstrates Anti-tumor Activity in Advanced Melanoma Patients with Brain Metastases (168KB)

June 5, 2017

(PRINCETON, N.J., June 4, 2017) - Bristol-Myers Squibb Company (NYSE: BMY) announced efficacy and safety data from CheckMate -204, the first Phase 2 study to evaluate Opdivo plus Yervoy as a potential treatment for patients with melanoma metastatic to the brain. The primary endpoint of intracranial (IC) clinical benefit rate (CBR), defined as complete response plus partial response plus stable disease ≥ 6 months, was 60% (95% CI: 48 to 71) at the median follow-up of 9.2 months among the 75 evaluated patients. These data will be presented during an oral session today from 10:12 - 10:24 a.m. CDT during the Melanoma/Skin Cancers session in the Arie Crown Theater at the American Society of Clinical Oncology (ASCO) Annual Meeting 2017.

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.

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Over half of patients (55%) experienced an intracranial objective response with 21% achieving a complete intracranial response

(PRINCETON, N.J., June 4, 2017) - Bristol-Myers Squibb Company (NYSE: BMY) today announced efficacy and safety data from CheckMate -204, the first Phase 2 study to evaluate Opdivo plus Yervoy as a potential treatment for patients with melanoma metastatic to the brain. The primary endpoint of intracranial (IC) clinical benefit rate (CBR), defined as complete response plus partial response plus stable disease ≥ 6 months, was 60% (95% CI: 48 to 71) at the median follow-up of 9.2 months among the 75 evaluated patients. These data will be presented during an oral session today from 10:12 - 10:24 a.m. CDT during the Melanoma/Skin Cancers session in the Arie Crown Theater at the American Society of Clinical Oncology (ASCO) Annual Meeting 2017.

"More than 60 percent of patients with stage IV melanoma eventually develop brain metastases, which are a major cause of illness and death among these patients," said Hussein Tawbi, M.D., PhD, Associate Professor, Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center. "These results from the CheckMate -204 trial are the first efficacy data investigating the use of an Immuno-Oncology combination for the treatment of patients with untreated melanoma brain metastases. The use of upfront systemic therapy is a novel approach in this population where radiation therapy is the norm."

A complete IC response was achieved by 21% (n=16) of patients; 33% (n=25) had partial responses; and 5% (n=4) experienced stable disease. The IC objective response rate (ORR) was 55% (95% CI: 43 to 66) with a safety profile consistent with previously reported data in melanoma patients without brain metastases. Treatment-related grade 3/4 adverse events (AEs) occurred in 52% of patients (n=39), with 8% (n=6) being neurologic in nature, including headaches. Three treatment-related deaths were reported as cardiogenic shock, IC hemorrhage and malignant neoplasm progression.

"The CheckMate -204 trial is important because research about therapies for advanced melanoma patients with brain metastases is somewhat limited. Until recently, these patients have been excluded from clinical trials," said Vicki Goodman, M.D., development

lead, Melanoma and Genitourinary Cancers, Bristol-Myers Squibb. "These data add to the body of scientific knowledge on Opdivo and Yervoy and highlight our continued commitment to researching the potential benefits of this combination in a diverse set of patient groups."

CheckMate -204 is a Phase 2 open-label study in 75 patients with melanoma that had spread to the brain, resulting in one or more asymptomatic brain metastases of 0.5 to 3.0 cm. The trial evaluated the efficacy and safety of Opdivo in combination with Yervoy followed by Opdivo monotherapy. The primary endpoint was IC CBR. Secondary objectives included overall survival, extracranial CBR and safety.

Enrolled patients received Opdivo 1 mg/kg plus Yervoy 3 mg/kg every three weeks for four doses, followed by Opdivo 3 mg/kg every two weeks until disease progression or toxicity. Patients who experienced severe AEs during the combination treatment could receive Opdivo monotherapy when their toxicity resolved, and stereotactic radiotherapy was permitted for patients experiencing brain oligo-progression if an assessable brain metastasis remained. The median number of combination doses was three (range 1 to 4), and 28 patients (37%) received four combination induction doses and 42 patients (56%) began Opdivo maintenance (median 12 doses, range 1 to 36).

About Metastatic Melanoma

Melanoma is a form of skin cancer characterized by the uncontrolled growth of pigment-producing cells (melanocytes) located in the skin. Metastatic melanoma is the deadliest form of the disease and occurs when cancer spreads beyond the surface of the skin to other organs. The incidence of melanoma has been increasing steadily for the last 30 years. In the United States, 87,000 new diagnoses of melanoma and more than 9,700 related deaths are estimated for 2017. Globally, the World Health Organization estimates that by 2035, melanoma incidence will reach 388,262, with 98,288 related deaths. Melanoma is mostly curable when treated in its early stages. However, patients in the United States diagnosed with advanced melanoma classified as Stage IV historically have a five-year survival rate of 15% to 20% and 10-year survival of about 10% to 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