ONO PHARMACEUTICAL : Results From CheckMate-275 Validate Further Study of Opdivo (nivolumab) in Patients With Advanced Form of Bladder Cancer (167KB)

October 11, 2016

(PRINCETON, NJ, October 8, 2016) - Bristol-Myers Squibb Company (NYSE: BMY) announced results from the CheckMate -275 trial, in which Opdivo had a confirmed objective response rate (ORR), the primary endpoint, of 19.6% (95% CI 15.0 - 24.9) in platinum-refractory patients with metastatic urothelial carcinoma. Responses were observed in both PD-L1 expressors and non-expressors. The confirmed ORR in patients expressing PD-L1 ≥1% was 23.8% (95% CI 16•5-32•3) and 16.1% (95% CI 10.5-23.1) in patients expressing PD-L1

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.

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• Confirmed overall response rate of 19.6% in all previously treated patients who received

  Opdivo

• Durable responses observed in PD-L1 expressors and non-expressors

• The safety profile of Opdivo in this study was consistent with previously reported studies

(PRINCETON, NJ, October 8, 2016) - Bristol-Myers Squibb Company (NYSE: BMY) announced today results from the CheckMate -275 trial, in which Opdivo had a confirmed objective response rate (ORR), the primary endpoint, of 19.6% (95% CI 15.0 - 24.9) in platinum-refractory patients with metastatic urothelial carcinoma. Responses were observed in both PD-L1 expressors and non-expressors. The confirmed ORR in patients expressing PD-L1 ≥1% was 23.8% (95% CI 16·5-32·3) and 16.1% (95% CI 10.5-23.1) in patients expressing PD-L1

Opdivo in this study was consistent with the safety profile of Opdivo in other tumor types.

These data will be presented today, October 8, at the 2016 European Society for Medical Oncology (ESMO) Congress during an oral proffered paper session from 9:15 - 9:30

a.m. CEST (Abstract #LBA31_PR).

"The prognosis for patients with metastatic urothelial carcinoma progressing despite platinum-based chemotherapy is poor, and treatment options have historically been quite limited," said Matthew Galsky, M.D., professor of medicine and director of Genitourinary Medical Oncology, The Tisch Cancer Institute at Icahn School of Medicine at Mount Sinai. "In the CheckMate -275 study, we observe that with Opdivo, patients who responded experienced rapid and durable responses, including patients with PD-L1 expressing and non- expressing tumors. These results are encouraging and provide new information to the scientific community on the potential of Opdivo as a treatment option for this type of advanced bladder cancer."

Urothelial carcinoma, a common type of bladder cancer, accounts for approximately 90% of cases. The majority of bladder cancers are diagnosed at an early stage, but approximately 78% of patients will experience a recurrence within five years.

Vicki Goodman, M.D., development lead, Melanoma and Genitourinary Cancers, Bristol-Myers Squibb, commented, "There is a significant unmet need for new treatment approaches for progressive metastatic urothelial carcinoma. The results from CheckMate - 275 show treatment with Opdivo resulted in durable and clinically meaningful objective response of 19.6% in all-treated patients. Based on these findings, we believe Opdivo has the potential to become an important new treatment option for patients with platinum-refractory advanced bladder cancer."

About CheckMate -275

CheckMate -275 is a Phase 2, single-arm clinical trial evaluating the safety and efficacy of Opdivo in 270 patients with metastatic or unresectable urothelial cancer who have progressed or recurred following treatment with a platinum-based agent in the metastatic setting or within one year after neoadjuvant/adjuvant platinum therapy. The trial enrolled patients regardless of PD-L1 expression. The primary endpoint was confirmed objective response rate (ORR) based on assessments by the blinded independent review committee in all treated patients and in patients with tumor PD-L1 expression ≥1% and ≥5%. Key secondary endpoints included progression-free survival (PFS), overall survival (OS), safety and quality of life. Patients received Opdivo 3 mg/kg administered intravenously every two weeks and were assessed for response beginning eight weeks from randomization and continuing every eight weeks for 48 weeks, then every 12 weeks until progression or discontinuation.

The confirmed ORR was 19.6% (95% CI: 15.0 - 24.9) for all treated patients. About half of the overall patient population (46%) had a PD-L1 expression of ≥1%, and approximately 30% had a PD-L1 expression of ≥5%. Higher responses observed among patients with PD-L1 expression ≥1% (23.8%; 95% CI: 16.5 - 32.3) and ≥5% (28.4%; 95% CI: 18.9 - 39.5). Responses to Opdivo were also observed in patients with PD-L1

Among the 52 patients who responded to treatment, the median time to a response was 1.9 months (1.6 - 5.9 months). Median duration of response was not reached, with an ongoing response among 77% of the responders at the time of the analysis.

The median PFS was 2.0 months in all treated patients (95% CI: 1.87 - 2.63), 1.87 months for patients with PD-L1

11.3 months in patients with PD-L1 expression ≥1% (95% CI: 8.74 - N.A.). In addition, quality of life is maintained for patients remaining on study over 41 weeks on two quality of life measures - the EORTC (European Organisation for Research and Treatment of Cancer) QLQ-C30 and the EQ-5D Visual Analog Scale.

The safety profile of Opdivo in CheckMate -275 was consistent with the safety profile of Opdivo in other tumor types. Among the 270 patients who received Opdivo, 64.4% experienced a treatment-related adverse event (AE) of any grade, with grade 3 or 4 in 17.8%. The most frequently reported treatment-related AEs of any grade included fatigue (16.7%), pruritis (9.3%), diarrhea (8.9%), decreased appetite (8.1%), hypothyroidism (7.8%), nausea

(7.0%), asthenia (5.9%), rash (5.9%) and pyrexia (5.6%). The most frequent treatment-related

grade 3-4 AEs were fatigue (1.9%), diarrhea (1.9%), asthenia (1.5%) and rash (1.1%). Overall, 4.8% of patients discontinued therapy due to treatment-related AEs of any grade, and 3.0% discontinued therapy due to grade 3-4 treatment-related AEs.

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.