ONO PHARMACEUTICAL : Long-Term Data from Two Trials Evaluating the Opdivo® (nivolumab) and Yervoy® (ipilimumab) Regimen in Advanced Melanoma Continues to Validate Bristol-Myers Squibb's Immuno-Oncology Combination Approach (191KB)

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June 7, 2016

Long-Term Data from Two Trials Evaluating the Opdivo® (nivolumab) and Yervoy® (ipilimumab) Regimen in Advanced Melanoma Continues to Validate Bristol-Myers Squibb's Immuno-Oncology Combination Approach

(PRINCETON, NJ, June 6, 2016) - Bristol-Myers Squibb Company (NYSE: BMY) announced results from two trials evaluating the Opdivo and Yervoy combination regimen in advanced melanoma. In the pivotal Phase 3, CheckMate -067 trial, at a minimum follow-up of 18 months, the Opdivo and Yervoy combination demonstrated continued clinical benefit with a 58% reduction in the risk of disease progression versus Yervoy monotherapy (HR=0.42 [99.5% CI: 0.31-0.57; p

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.

Corporate Communications public_relations@ono.co.jp

Long-Term Data from Two Trials Evaluating the Opdivo® (nivolumab) and Yervoy® (ipilimumab) Regimen in Advanced Melanoma Continues to Validate Bristol-Myers Squibb's Immuno-Oncology Combination Approach

Significantly longer progression-free survival and higher objective response rates with Opdivo and Yervoy combination and Opdivo monotherapy versus Yervoy alone, with a minimum of 18-month follow-up, from CheckMate -067

In CheckMate -067, median duration of response had not been reached with the combination regimen, and was 22.3 months for Opdivo monotherapy and 14.4 months for Yervoy alone

With longer follow-up, the Opdivo and Yervoy combination regimen had a consistent safety profile with previously reported studies of the combination

(PRINCETON, NJ, June 6, 2016) - Bristol-Myers Squibb Company (NYSE: BMY) announced today results from two trials evaluating the Opdivo and Yervoy combination regimen in advanced melanoma. In the pivotal Phase 3, CheckMate -067 trial, at a minimum follow-up of 18 months, the Opdivo and Yervoy combination demonstrated continued clinical benefit with a 58% reduction in the risk of disease progression versus Yervoy monotherapy (HR=0.42 [99.5% CI: 0.31-0.57; pOpdivo monotherapy demonstrated a 45% risk reduction versus Yervoy alone (HR=0.55 [99.5% CI: 0.43-0.76; p

was 66%, and 20% achieved a complete response, with a minimum follow-up of two years. At two years, the median duration of response was not reached and 74% remain in response. The safety profile of the Opdivo and Yervoy combination regimen in both CheckMate -067 and -069 was consistent with previously reported studies of the combination, and most treatment-related adverse events were

managed using established algorithms.

"The data from CheckMate -067 provide new insights on the long-term durability of the progression-free survival benefit seen with the nivolumab and ipilimumab combination regimen in advanced melanoma relative to ipilimumab monotherapy," said Jedd D. Wolchok, M.D., Ph.D., Chief, Melanoma and Immunotherapeutics Service, at Memorial Sloan Kettering Cancer Center. "In addition,

in a post-hoc analysis from CheckMate -069, we observed that even for patients who discontinue treatment with the combination regimen due to toxicity, efficacy outcomes appeared consistent with that seen in the overall study population. These data are encouraging and provide additional important information about the efficacy and safety of the combination regimen in these patients."

The CheckMate -067 data will be presented at the 52nd Annual Meeting of the American Society

of Clinical Oncology (ASCO) in an oral abstract session on Monday, June 6, from 2:39 PM - 2:51 PM CDT (Abstract #9505). The CheckMate -069 data were presented in a poster discussion session on Saturday, June 4 (Abstract #9518).

Vicki Goodman, M.D., Development Lead, Melanoma and Genitourinary Cancers, Bristol- Myers Squibb, commented, "With the CheckMate -067 and -069 data presented at ASCO, we observe, with longer follow-up, the durability of progression-free survival and response for the Opdivo and Yervoy combination regimen in advanced melanoma. These findings further validate our research strategy to study the combination of Immuno-Oncology agents, and we remain committed to building on this research and evaluating more ways to improve long-term survival and patient outcomes in advanced cancers."

About CheckMate -067

CheckMate -067 is a Phase 3, double-blind, randomized study that evaluated the Opdivo and Yervoy combination regimen or Opdivo monotherapy versus Yervoy monotherapy in patients with previously untreated advanced melanoma, including both BRAF V600 mutation positive or BRAF wild- type advanced melanoma. A total of 945 patients were randomized to receive the Opdivo and Yervoy combination regimen (Opdivo 1 mg/kg plus Yervoy 3 mg/kg every 3 weeks administered intravenously for 4 doses followed by Opdivo 3 mg/kg every 2 weeks thereafter; n=314), Opdivo monotherapy (Opdivo 3 mg/kg every 2 weeks administered intravenously; n=316) or Yervoy monotherapy (Yervoy 3 mg/kg every 3 weeks administered intravenously for 4 doses followed by placebo every 2 weeks; n=315). Patients were treated until progression or unacceptable toxic effects. Co-primary endpoints were progression-free survival (PFS) and overall survival (OS); secondary endpoints included PFS and objective response rate (ORR), as well as safety and tolerability. The study is ongoing in its evaluation for OS.

At a minimum follow-up of 18 months, the Opdivo and Yervoy combination demonstrated a 58% reduction in the risk of disease progression versus Yervoy monotherapy in previously untreated patients with advanced melanoma (HR=0.42 [99.5% CI: 0.31-0.57; pOpdivo monotherapy

demonstrated a 45% risk reduction versus Yervoy monotherapy (HR=0.55 [99.5% CI: 0.43-0.76;

p

11.5 months (95% CI: 8.9-16.7) and 6.9 months (95% CI: 4.3-9.5) for Opdivo monotherapy versus 2.9 months (95% CI: 2.8-3.4) for Yervoy monotherapy. At 18 months, the PFS rate was 46% for the combination regimen (HR=0.42 [99.5% CI: 0.31-0.57; pOpdivo monotherapy (HR=0.55 [99.5% CI: 0.43-0.76; pYervoy.

The Opdivo and Yervoy combination regimen and Opdivo monotherapy also demonstrated a higher ORR (ORR: 58% and 44%, p Yervoy monotherapy (19%). There were 38 (12%) complete responses and 143 (46%) partial responses seen in patients treated with the combination regimen, and 31 (10%) complete responses and 107 (34%) partial responses seen in patients treated with Opdivo monotherapy, versus 7 (2%) complete responses and 53 (17%) partial responses seen in patients treated with Yervoy alone. The median duration of response had not been reached for those patients treated with the Opdivo and Yervoy combination regimen, and was 22.3 months for Opdivo monotherapy and 14.4 months for Yervoy alone. In the study, a change in tumor burden was seen with the Opdivo and Yervoy combination regimen and Opdivo monotherapy, with a median decrease of 51.9% and 34.5%, respectively, and 5.9% increase for Yervoy alone.

As part of a pre-planned, descriptive analysis of data from CheckMate -067, a greater improvement in PFS for the combination of Opdivo with Yervoy, relative to Opdivo monotherapy, was only observed in patients with low tumor PD-L1 expression. Overall response rates were higher for the combination of Opdivo and Yervoy relative to Opdivo monotherapy, regardless of tumor PD-L1 expression levels. In addition, efficacy of the Opdivo and Yervoy combination regimen and Opdivo monotherapy was observed, regardless of BRAF mutational status.

With longer follow-up, the safety of the Opdivo and Yervoy combination regimen in CheckMate

-067 was consistent with previously reported studies of the combination regimen and most treatment- related select adverse events (AEs) were managed with immune-modulating medications. Grade 3-4 treatment-related AEs were reported more frequently with the combination regimen (56.5%), relative to the Opdivo monotherapy (19.8%) versus Yervoy alone (27%). Treatment-related AEs of any grade led to discontinuation in 38.7% of patients treated with the combination regimen, 10.5% for patients treated with Opdivo monotherapy, and 15.4% of patients treated with Yervoy alone. No treatment-related deaths occurred in the Opdivo and Yervoy combination regimen arm. The most common treatment-related select AEs of any grade with the combination regimen versus Yervoy alone included increased ALT (17.9% vs. 3.9%), increased AST (15.7% vs. 3.9%), diarrhea (45.4 % vs. 33.8%), colitis (11.5% vs.