ONO PHARMACEUTICAL : Opdivo (nivolumab) and Yervoy (ipilimumab) Regimen Shows Promising Efficacy and Safety in Previously Treated Patients With Advanced Form of Bladder Cancer (159KB)

November 15, 2016

Opdivo (nivolumab) and Yervoy (ipilimumab) Regimen Shows Promising Efficacy and Safety in Previously Treated Patients With Advanced Form of Bladder Cancer

(PRINCETON, N.J., November 12, 2016) - Bristol-Myers Squibb Company (NYSE:BMY) announced additional results from the Phase 1/2 open-label CheckMate -032 trial investigating two combination schedules of Opdivo (nivolumab) plus Yervoy (ipilimumab) in patients with locally advanced or metastatic urothelial carcinoma (mUC) previously treated with platinum-based therapy. In these preliminary data, the primary endpoint of investigator-assessed confirmed objective response rate (ORR) was 38.5% (95% CI: 20.2 - 59.4) in patients who received Opdivo 1 mg/kg plus Yervoy 3 mg/kg (n=26) compared to 26.0% (95% CI:, 17.9 - 35.5) in patients treated with Opdivo 3 mg/kg plus Yervoy 1 mg/kg (n=104). No new safety signals have been identified. The incidence of Grade 3-4 treatment-related adverse events (AEs) was 30.8% in the Opdivo 1 mg/kg plus Yervoy 3 mg/kg group, 31.7% in the Opdivo 3 mg/kg plus Yervoy 1 mg/kg group. Treatment-related AEs led to discontinuation of therapy in 7.7% of patients in the Opdivo 1 mg/kg plus Yervoy 3 mg/kg group, 13.5% in the Opdivo 3 mg/kg plus Yervoy 1 mg/kg group.

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 [e-mail]

Opdivo (nivolumab) and Yervoy (ipilimumab) Regimen Shows Promising Efficacy and Safety in Previously Treated Patients With Advanced Form of Bladder Cancer

Data from CheckMate -032 showed a confirmed objective response rate of 38.5% in previously treated metastatic urothelial carcinoma patients who received the Opdivo 1 mg/kg and Yervoy 3 mg/kg regimen

No new safety signals identified with the Opdivo and Yervoy regimen

Results support further development of Opdivo plus Yervoy regimen in patients with metastatic urothelial carcinoma

(PRINCETON, N.J., November 12, 2016) - Bristol-Myers Squibb Company (NYSE:BMY) announced today additional results from the Phase 1/2 open-label CheckMate

-032 trial investigating two combination schedules of Opdivo (nivolumab) plus Yervoy (ipilimumab) in patients with locally advanced or metastatic urothelial carcinoma (mUC) previously treated with platinum-based therapy. In these preliminary data, the primary endpoint of investigator-assessed confirmed objective response rate (ORR) was 38.5% (95% CI: 20.2 - 59.4) in patients who received Opdivo 1 mg/kg plus Yervoy 3 mg/kg (n=26) compared to 26.0% (95% CI: 17.9 - 35.5) in patients treated with Opdivo 3 mg/kg plus Yervoy 1 mg/kg (n=104). No new safety signals have been identified. The incidence of Grade 3-4 treatment-related adverse events (AEs) was 30.8% in the Opdivo 1 mg/kg plus Yervoy 3 mg/kg group and 31.7% in the Opdivo 3 mg/kg plus Yervoy 1 mg/kg group. Treatment- related AEs led to discontinuation of therapy in 7.7% of patients in the Opdivo 1 mg/kg plus Yervoy 3 mg/kg group and 13.5% in the Opdivo 3 mg/kg plus Yervoy 1 mg/kg group.

These data were presented at the 31st Annual Meeting and Associated Programs of the

Society for Immunotherapy of Cancer (SITC) in National Harbor, Md., during the Oral Late- breaking Abstract Session II today from 11:30 - 11:45 a.m. EST.

"Metastatic urothelial carcinoma is an area of significant unmet medical need, especially for patients in the advanced stages of the disease who have progressed on standard chemotherapy," said Padmanee Sharma, M.D., Ph.D., study investigator and professor at The University of Texas MD Anderson Cancer Center. "Earlier this year, we presented encouraging results from this trial for Opdivo monotherapy, and now we are seeing the promise of a combination regimen with Opdivo and Yervoy for previously treated patients with this common type of advanced bladder cancer. These findings support the need for

further study of combination therapy to assess outcomes and potential survival in patients with metastatic urothelial carcinoma."

Urothelial carcinoma is the most common type of bladder cancer, accounting for approximately 90% of bladder cancer cases. Bladder cancer is the ninth most commonly diagnosed cancer in the world, with an estimated 430,000 new cases diagnosed per year and more than 165,000 deaths annually. The majority of bladder cancers are diagnosed at an early stage, but rates of recurrence and disease 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%.

"These results from the CheckMate -032 study support further development of the Opdivo plus Yervoy regimen for treatment of metastatic urothelial carcinoma in platinum refractory patients," commented Vicki Goodman, M.D., development lead, Melanoma and Genitourinary Cancers, Bristol-Myers Squibb. "The findings also bolster our belief that combining our Immuno-Oncology agents, Opdivo and Yervoy, can potentially advance cancer care."

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 is investigator-assessed confirmed objective response rate (ORR), confirmed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Secondary endpoints include safety, duration of response (DOR), overall survival (OS) and progression-free survival (PFS).

Data presented at SITC is specific to a cohort of 208 patients with metastatic or locally advanced urothelial cancer (mUC) who have received one or more prior lines of platinum-based therapy. In the arms evaluating combination therapy, patients were treated with either one of two combination schedules - Opdivo 1 mg/kg plus Yervoy 3 mg/kg (n=26) or Opdivo 3 mg/kg plus Yervoy 1 mg/kg (n=104) every three weeks for four cycles, followed by Opdivo 3 mg/kg every two weeks. All patients were treated until disease progression or unacceptable toxicity. Patients were followed for a median of 7.8 months in the Opdivo 1 mg/kg plus Yervoy 3 mg/kg group (n = 26) and 16.7 months in the Opdivo 3 mg/kg plus Yervoy 1 mg/kg group (n = 104).

For the primary endpoint, the highest ORR was observed in the Opdivo 1 mg/kg plus

Yervoy 3 mg/kg group: 38.5% (95% CI: 20.2 - 59.4). The ORR was 26.0% (95% CI: 17.9 -

35.5) in the Opdivo 3 mg/kg plus Yervoy 1 mg/kg group.

The incidence of Grade 3-4 treatment-related adverse events (AEs) was 30.8% in the Opdivo 1 mg/kg plus Yervoy 3 mg/kg group and 31.7% in the Opdivo 3 mg/kg plus Yervoy 1 mg/kg group. Treatment-related AEs led to discontinuation of therapy in 7.7% of patients in the Opdivo 1 mg/kg plus Yervoy 3 mg/kg group and 13.5% in the Opdivo 3 mg/kg plus Yervoy 1 mg/kg group. One death was reported in the Opdivo 3 mg/kg plus Yervoy 1 mg/kg group due to pneumonitis.

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.

We are leading the scientific understanding of I-O through our extensive portfolio of investigational and approved agents, including the first combination of two I-O agents in metastatic melanoma, and our differentiated clinical development program, which is studying broad patient populations across more than 20 types of cancers with 11 clinical-stage molecules designed to target different immune system pathways. Our deep expertise and innovative clinical trial designs uniquely position us to advance the science of combinations across multiple tumors and potentially deliver the next wave of I-O combination regimens 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 inform which patients will benefit most from I-O therapies.

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.