ONO PHARMACEUTICAL : First Presentation of Phase 2 CheckMate-142 Study Evaluating Opdivo® (nivolumab) Alone or in Combination with Yervoy® (ipilimumab) Demonstrates Encouraging Clinical Activity in MSI-High Metastatic Colorectal Cancer (186KB)

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June 9, 2016

First Presentation of Phase 2 CheckMate-142 Study Evaluating Opdivo® (nivolumab) Alone or in Combination with Yervoy® (ipilimumab) Demonstrates Encouraging Clinical Activity in MSI-High Metastatic Colorectal Cancer

(PRINCETON, N.J., June 5, 2016) - Bristol-Myers Squibb Company (NYSE: BMY) announced the first presentation of interim data from the Phase 2 CheckMate-142 trial evaluating Opdivo alone or in combination with Yervoy in patients with previously treated metastatic colorectal cancer, including those with high microsatellite instability (MSI-H). In these first-time clinical results, the primary endpoint of investigator-assessed objective response rate (ORR) was 25.5% (95% CI: 15.4-38.1) for Opdivo monotherapy and 33.3% (95% CI: 18.6-50.9) for the Opdivo and Yervoy combination regimen. The six- month progression-free survival (PFS) rates were 45.9% (95% CI: 29.8-60.7) for Opdivo monotherapy and 66.6% (95% CI: 45.5-81.1) for the Opdivo and Yervoy combination. MSI-H, a specific tumor biomarker, is present in approximately 15% of early stage metastatic colorectal cancers, and 4% of Stage IV colorectal cancers. The safety profile of Opdivo alone or in combination with Yervoy was consistent with other tumor types and prior combination studies. These data will be presented today during an oral presentation at the 52nd Annual Meeting of the American Society of Clinical Oncology (ASCO) from 8:12 AM - 8:24 AM CDT in Chicago, IL (Abstract #3501).

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 Head and Neck Cancer, Glioblastoma, Small Cell Lung Cancer, Urothelial Cancer, Hepatocellular Carcinoma, Esophageal Cancer, Hodgkin Lymphoma, Colorectal Cancer, Solid Tumors (Triple-Negative Breast Cancer, Gastric Cancer, Pancreatic 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. In addition, ONO has submitted supplemental applications for additional indications of Renal Cell Cancer and Hodgkin Lymphoma, and is conducting clinical development program including Head and Neck Cancer, Gastric Cancer, Esophageal Cancer, Small Cell Lung Cancer, Hepatocellular Carcinoma, Glioblastoma, Ovarian Cancer, Urothelial 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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ONO PHARMACEUTICAL CO., LTD.

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First Presentation of Phase 2 CheckMate -142 Study Evaluating Opdivo® (nivolumab) Alone or in Combination with Yervoy® (ipilimumab) Demonstrates Encouraging Clinical Activity in MSI-High Metastatic Colorectal Cancer

Investigator-assessed objective response rate for MSI-high metastatic colorectal cancer patients was 25.5% for Opdivo monotherapy and 33.3% for Opdivo in combination with Yervoy Six-month progression-free survival rates were 45.9% for Opdivo monotherapy and 66.6% for

Opdivo in combination with Yervoy in patients with MSI-high metastatic colorectal cancer

Findings underscore potential of Immuno-Oncology combination therapy in this subset of metastatic colorectal cancer

(PRINCETON, N.J., June 5, 2016) - Bristol-Myers Squibb Company (NYSE: BMY) announced today the first presentation of interim data from the Phase 2 CheckMate -142 trial evaluating Opdivo alone or in combination with Yervoy in patients with previously treated metastatic colorectal cancer, including those with high microsatellite instability (MSI-H). In these first-time clinical results, the primary endpoint of investigator-assessed objective response rate (ORR) was 25.5% (95% CI: 15.4- 38.1) for Opdivo monotherapy and 33.3% (95% CI: 18.6-50.9) for the Opdivo and Yervoy combination regimen. The six-month progression-free survival (PFS) rates were 45.9% (95% CI: 29.8-60.7) for Opdivo monotherapy and 66.6% (95% CI: 45.5-81.1) for the Opdivo and Yervoy combination. MSI-H, a specific tumor biomarker, is present in approximately 15% of early stage metastatic colorectal cancers, and 4% of Stage IV colorectal cancers. The safety profile of Opdivo alone or in combination with Yervoy was consistent with other tumor types and prior combination studies. These data will be presented today during an oral presentation at the 52nd Annual Meeting of the American Society of Clinical Oncology (ASCO) from 8:12 AM - 8:24 AM CDT in Chicago, IL (Abstract #3501).

Michael J. Overman, M.D., Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, commented, "It is exciting to see these results for nivolumab, and nivolumab in combination with ipilimumab, in the subset of metastatic colorectal cancer patients that are characterized by deficient mismatch repair or microsatellite instability. The response and survival data reported today suggest that this subset of colorectal cancer is responsive to immune therapy and support further investigation into the potential of immune checkpoint inhibition to provide benefits to patients with this type of metastatic colorectal cancer."

"Through our deep scientific expertise in Immuno-Oncology research, we have a growing understanding of how our combination approach could stimulate anti-tumor activity in a variety of hard- to-treat cancers," said David Feltquate, M.D., Ph.D., Development Lead, Oncology Life Cycle Management, Bristol-Myers Squibb. "We believe the data presented at ASCO support our hypothesis that the combination of Opdivo with Yervoy has the potential to lead to greater clinical activity than Opdivo monotherapy in patients with MSI-H metastatic colorectal cancer. We are encouraged by the preliminary results from our ongoing efforts to evaluate the full potential of this combination regimen across a range of malignancies."

About CheckMate -142

CheckMate -142 is an international Phase 2, open-label, non-comparative trial evaluating Opdivo as a single-agent or in combination with Yervoy in recurrent or metastatic colorectal cancer, including patients with and without high microsatellite instability (MSI-H). The MSI-H patients received Opdivo 3 mg/kg every two weeks (n=70) or Opdivo 3 mg/kg and Yervoy 1 mg/kg (n=30) for four doses followed by Opdivo 3 mg/kg every two weeks until an unacceptable toxicity occurred, or until disease progression. Enrollment of MSI-H patients to Opdivo 3 mg/kg and Yervoy 1 mg/kg every two weeks is ongoing. Twenty-three microsatellite stable (MSS) patients received one of three doses of the Opdivo and Yervoy combination.

The primary endpoint was investigator- assessed objective response rate (ORR) in MSI-H patients, and the secondary endpoint was independent radiology review of ORR in MSI-H patients. Exploratory endpoints included safety and tolerability, progression-free survival (PFS) and overall survival (OS) in MSI-H patients, as well as investigator-assessed ORR in MSS patients. Interim results for both MSI-H and MSS patients will be presented.

The investigator-assessed ORR for MSI-H patients receiving Opdivo 3 mg/kg with at least 12 weeks of follow up was 25.5% and 33.3% for the Opdivo 3 mg/kg and Yervoy 1 mg/kg combination. Median duration of response was not reached in either group. The six-month PFS rates were 45.9% (95% CI: 29.8-60.7) for Opdivo 3 mg/kg and 66.6% (95% CI: 45.5-81.1) for the Opdivo 3 mg/kg and Yervoy 1 mg/kg combination. Survival data are also reported, with nine-month OS rates of 75.0% (95% CI: 58.5-85.7) for Opdivo 3 mg/kg and 85.1% (95% CI: 65.0-94.2) for the Opdivo 3 mg/kg and Yervoy 1 mg/kg combination. At the time of analysis, 67.1% of MSI-H patients in the Opdivo 3 mg/kg arm and 60.0% of those in the Opdivo 3 mg/kg and Yervoy 1 mg/kg combination arm remained on treatment.

In MSI-H patients, treatment-related adverse events (AEs) of any grade occurred in 58.6% of patients in Opdivo 3 mg/kg group and 83.3% of patients in the Opdivo 3 mg/kg and Yervoy 1 mg/kg group. The most common AEs of any grade occurring in >15% of MSI-H patients were fatigue (18.6% with Opdivo 3 mg/kg; 20.0% with Opdivo 3 mg/kg and Yervoy 1 mg/kg), diarrhea (14.3% with Opdivo 3

mg/kg; 43.3% with Opdivo 3 mg/kg and Yervoy 1 mg/kg), pruritus (11.4% with Opdivo 3 mg/kg; 16.7%

with Opdivo 3 mg/kg and Yervoy 1 mg/kg), nausea (7.1% with Opdivo 3 mg/kg; 20.0% with Opdivo 3 mg/kg and Yervoy 1 mg/kg), and pyrexia (4.3% with Opdivo 3 mg/kg; 23.3% with Opdivo 3 mg/kg and Yervoy 1 mg/kg). Grade 3/4 AEs occurred in 14.3% of patients in the Opdivo 3 mg/kg group and 26.7% of patients in the Opdivo 3 mg/kg and Yervoy 1 mg/kg group. One patient in the Opdivo 3 mg/kg group died due to a Grade 5 treatment-related AE of sudden death. In MSS patients, AEs of any grade occurred in 80% of the patients with diarrhea (30%), nausea (25%), pyrexia (25%), fatigue (20%), vomiting (20%), and pruritus (10%) being the most common.

About Colorectal Cancer

Colorectal cancer, or CRC, is the third most commonly diagnosed cancer, with worldwide incidence expected to increase from 1.4 million cases diagnosed in 2012 to 2.4 million cases by 2036. High microsatellite instability (MSI-H) tumors are present in approximately 15% of early stage metastatic colorectal cancers and 4% of Stage IV colorectal cancers, and are known to have an exceptionally high mutation burden. MSI-H CRC occurs when there are DNA mismatch repair deficiencies, which is a change that occurs in the DNA of certain cells. Survival rates of CRC vary depending on the stage and type of the cancer when it is diagnosed. Globally, the five-year survival rate for Stage I CRC is about 92%, and 11% for Stage IV.

Bristol-Myers Squibb & Immuno-Oncology: Advancing Oncology Research

At Bristol-Myers Squibb, we have a vision for the future of cancer care that is focused on Immuno-Oncology, now considered a major treatment choice alongside surgery, radiation, chemotherapy and targeted therapies for certain types of cancer.

We have a comprehensive clinical portfolio of investigational and approved Immuno-Oncology agents, many of which were discovered and developed by our scientists. Our ongoing Immuno- Oncology clinical program is looking at broad patient populations, across multiple solid tumors and hematologic malignancies, and lines of therapy and histologies, with the intent of powering our trials for overall survival and other important measures like durability of response. We pioneered the research