ONO PHARMACEUTICAL : Promising Response Rates with Opdivo® (nivolumab) Observed In Advanced Form of Bladder Cancer From Phase 1/2 Study CheckMate-032 (167KB)

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June 6, 2016

Promising Response Rates with Opdivo® (nivolumab) Observed In Advanced Form of Bladder Cancer From Phase 1/2 Study CheckMate-032

(PRINCETON, N.J., June 5, 2016) - Bristol-Myers Squibb Company (NYSE: BMY) announced the first presentation of results for Opdivo in the cohort of patients with metastatic urothelial cancer (n=78), the most common type of bladder cancer, after platinum-based therapy from CheckMate -032, a Phase 1/2 open-label trial. In the trial, the primary endpoint of investigator-assessed confirmed objective response rate (ORR), was 24.4% (95% CI: 15.3- 35.4) in patients treated with Opdivo, with a minimum follow-up of nine months. Response rates by tumor PD-L1 expression, evaluated as an exploratory endpoint, were similar regardless of PD-L1 expression levels. In patients with PD-L1 1%, the ORR was 24%. At one year, patients treated with Opdivo had an overall survival (OS, a secondary endpoint) rate of 45.6%, with a median OS of 9.72 months (95% CI: 7.26-16.16). The safety profile of Opdivo in CheckMate -032 was consistent with the known safety profile of Opdivo in other tumor types.

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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Promising Response Rates with Opdivo® (nivolumab) Observed In Advanced Form of Bladder Cancer From Phase 1/2 Study CheckMate -032

Confirmed objective response rate was 24.4% in these previously treated patients who received

Opdivo

Similar response rates were observed regardless of PD-L1 expression status; in patients with PD-L1 >1%, the objective response rate was 24% At one year, patients treated with Opdivo had an overall survival rate of 45.6%, with a median overall survival of more than nine months

(PRINCETON, N.J., June 5, 2016) - Bristol-Myers Squibb Company (NYSE: BMY) announced today the first presentation of results for Opdivo in the cohort of patients with metastatic urothelial cancer (n=78), the most common type of bladder cancer, after platinum-based therapy from CheckMate

-032, a Phase 1/2 open-label trial. In the trial, the primary endpoint of investigator-assessed confirmed objective response rate (ORR), was 24.4% (95% CI: 15.3-35.4) in patients treated with Opdivo, with a minimum follow-up of nine months. Response rates by tumor PD-L1 expression, evaluated as an exploratory endpoint, were similar regardless of PD-L1 expression levels. In patients with PD-L1 >1%, the ORR was 24%. At one year, patients treated with Opdivo had an overall survival (OS, a secondary endpoint) rate of 45.6%, with a median OS of 9.72 months (95% CI: 7.26-16.16). The safety profile of Opdivo in CheckMate -032 was consistent with the known safety profile of Opdivo in other tumor types.

These data will be presented today, Sunday, June 5, at the 52nd Annual Meeting of the American

Society of Clinical Oncology (ASCO) in an oral abstract session from 8:12 AM - 8:24 AM CDT (Abstract #4501).

Padmanee Sharma, M.D., Ph.D., study investigator and professor at The University of Texas MD Anderson Cancer Center, commented, "Urothelial carcinoma is the most common type of bladder cancer, accounting for approximately 90% of bladder cancer cases. Patients with advanced stages of the disease face high rates of disease recurrence and progression, making new research an extremely important factor to address this high unmet medical need. We are pleased with the findings from the Phase 1/2

study, CheckMate -032, which provide support for further study of Opdivo in patients with this cancer to assess outcomes and survival."

Bladder cancer is the ninth most commonly diagnosed cancer in the world, with an estimated 430,000 new cases diagnosed per year and over 165,000 deaths per year. 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 and type of the cancer and when it is diagnosed. For Stage IV bladder cancer, the five-year survival rate is 15%.

Jean Viallet, M.D., Global Clinical Research Lead, Oncology, Bristol-Myers Squibb, commented, "We are excited to present for the first time results for Opdivo in previously treated metastatic urothelial cancer, a type of bladder cancer. We are encouraged by the response rates and overall survival data observed with Opdivo in CheckMate -032, which supports the ongoing Phase 2 study in this cancer.

Through our Immuno-Oncology research across different tumor types, our goal is to help more patients achieve quality long-term survival, and we look forward to further study of our Immuno-Oncology agents, including the Opdivo and Yervoy combination, in advanced bladder cancer."

About CheckMate -032

CheckMate -032 is an ongoing Phase 1/2 open-label trial, evaluating the safety and efficacy of Opdivo monotherapy, or Opdivo combined with Yervoy in advanced or metastatic solid tumors. The trial enrolled patients regardless of PD-L1 expression. The primary endpoint was investigator-assessed confirmed objective response rate (ORR). Secondary endpoints included safety, duration of response, overall survival (OS) and progression-free survival (PFS).

Data presented at ASCO specific to metastatic or locally advanced urothelial cancer were from a cohort of 78 patients who have received one or more prior lines of platinum-based therapy. In this analysis, patients received Opdivo monotherapy (3 mg/kg administered intravenously every two weeks) until progression or discontinuation. Patients treated with Opdivo monotherapy were allowed to continue treatment beyond progression if Opdivo was tolerated and clinical benefit was noted, or patients could cross over to receive the combination of Opdivo and Yervoy if they met prespecified criteria.

In the trial, the investigator-assessed confirmed ORR was 24.4% (95% CI: 15.3-35.4) for the cohort of patients treated with Opdivo. Median duration of response was not estimable (9.92-NE). In addition, the one-year OS rate reported for the Opdivo-cohort was 45.6%, based on Kaplan-Meier

estimates, with a median OS of 9.72 months (95% CI: 7.26-16.16). Median PFS was 2.78 months (95% CI: 1.45-5.85).

Of randomized patients, 67 patients had quantifiable tumor PD-L1 expression, with 37.3% expressing PD-L1 at >1%. Objective response rate was 26.8% (14.2-42.9) in patients with PD-L1 >1%. Efficacy of Opdivo by PD-L1 expression was an exploratory endpoint in CheckMate -032.

The safety profile of Opdivo in CheckMate -032 was consistent with the known safety profile of Opdivo in other tumor types. Grade 3-4 treatment-related adverse events (AEs) occurred in 22% of patients receiving Opdivo, with the most frequent AEs of any grade reported in >10% of patients being fatigue (36%), pruritus (30%), maculopapular rash (18%), increased lipase (14%), nausea (13%), arthralgia (12%), and anemia (10%). Two Grade 5 treatment-related AEs occurred in patients treated with Opdivo (pneumonitis [n=1] and thrombocytopenia [n=1]). No Grade 3 or 4 pneumonitis or thrombocytopenia was reported.

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 leading to the first regulatory approval for the combination of two Immuno-Oncology agents, and continue to study the role of combinations in cancer.

We are also investigating other immune system pathways in the treatment of cancer including CTLA-4, CD-137, KIR, SLAMF7, PD-1, GITR, CSF1R, IDO, and LAG-3. These pathways may lead to potential new treatment options - in combination or monotherapy - to help patients fight different types of cancers.

Our collaboration with academia, as well as small and large biotech companies, to research the potential of Immuno-Oncology and non-Immuno-Oncology combinations, helps achieve our goal of providing new treatment options in clinical practice.