ONO PHARMACEUTICAL : Five-Year Survival Observed With Opdivo (nivolumab) in Patients With Previously Treated Advanced Non-Small Cell Lung Cancer (NSCLC), in Phase 1 Study CA209-003 (152KB)

April 5, 2017

(PRINCETON, NJ, April 3, 2017) - Bristol-Myers Squibb Company (NYSE: BMY) announced the first report of five-year overall survival (OS) data from the Phase 1 dose-ranging study CA209-003 evaluating Opdivo in patients with previously treated advanced non-small cell lung cancer (NSCLC; n=129). Overall survival was an exploratory endpoint in this study. The estimated OS rate at five years was 16% in heavily pre-treated NSCLC patients; survival was observed across PD-L1 expression levels and tumor histologies. The safety profile of Opdivo from this study was previously reported; no new safety signals were identified in this analysis. These data were featured today during the official press program at the American Association for Cancer Research (AACR) Annual Meeting 2017 in Washington, D.C.

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, relapsed or refractory classical Hodgkin lymphoma in December 2016 and recurrent or metastatic head and neck cancer on March 24, 2017. In addition, ONO has submitted supplemental application for additional indication of gastric cancer, and is conducting clinical development program including esophageal cancer, gastro-esophageal junction cancer, small cell lung cancer, hepatocellular carcinoma, glioblastoma, urothelial cancer, malignant pleural mesothelioma, ovarian 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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Estimated five-year overall survival rate in previously treated advanced NSCLC patients who received Opdivo was 16%; survival was observed across PD-L1 expression levels and tumor histologies

Data represent the longest survival follow-up with an anti-PD-1 therapy in advanced NSCLC

(PRINCETON, NJ, April 3, 2017) - Bristol-Myers Squibb Company (NYSE: BMY) today announced the first report of five-year overall survival (OS) data from the Phase 1 dose-ranging study CA209-003 evaluating Opdivo in patients with previously treated advanced non-small cell lung cancer (NSCLC; n=129). Overall survival was an exploratory endpoint in this study. The estimated OS rate at five years was 16% in heavily pre-treated NSCLC patients; survival was observed across PD-L1 expression levels and tumor histologies. The safety profile of Opdivo from this study was previously reported; no new safety signals were identified in this analysis. These data were featured today during the official press program at the American Association for Cancer Research (AACR) Annual Meeting 2017 in Washington, D.C.

Scott N. Gettinger, M.D., a senior author of CA209-003 and associate professor of medicine, Yale Cancer Center, New Haven, Conn., commented, "Historically, five-year survival rates for patients with advanced NSCLC have been less than 5%. With new data emerging from the NSCLC cohort of CA209-003, we observe that the estimated five-year overall survival rate in Opdivo-treated patients in the study was 16%. In addition, based on investigator assessments, the majority of these patients showed no evidence that their lung cancer had progressed at the time of their last follow-up. These findings offer important new insights into the long-term clinical profile of Opdivo in this patient population."

These results also will be presented today at AACR from 4:05 - 4:20 p.m. during the Update, Novel Indication, and New Immuno-Oncology Clinical Trials session (Late-Breaking Abstract CT077).

Nick Botwood, M.D., development lead, Lung, Bristol-Myers Squibb, commented, "Opdivo is a standard of care for second-line NSCLC and has been an important treatment option for these patients. CA209-003 represents the longest follow-up analysis of data from a clinical trial testing an anti-PD-1 immunotherapy, and it is encouraging to observe that a subset of these heavily pre-treated patients experienced, at minimum, five years of survival. We look forward to further evaluating our Immuno-Oncology agents, including Opdivo-based combinations, with the goal of improving long- term survival for lung cancer patients."

About CA209-003

CA209-003 (NCT00730639) is a Phase 1b, open-label, multicenter, multidose, dose- escalation study of Opdivo in patients with select advanced or recurrent malignancies, including previously treated non-small cell lung cancer (NSCLC). In this study, patients received one to five prior systemic therapies for advanced NSCLC (n=129) and were treated with Opdivo (1, 3 or 10 mg/kg) intravenously once every two weeks for less than 96 weeks. The primary objectives were measures of safety and tolerability. Secondary objectives include antitumor activity. Overall survival (OS) and analysis by PD-L1 expression levels were exploratory objectives. The data reported at AACR 2017 represent pooled data across the three doses for the NSCLC cohort.

At five years, the estimated OS rate for patients treated with Opdivo at all doses was 16%, and the median OS was 9.9 months (95% CI: 7.8, 12.4), with a minimum follow-up of 58 months. The five-year OS rates were consistent across histologies (squamous = 16% [n=54]; non-squamous = 15% [n=74]). In patients with evaluable PD-L1 expression (n=68/129), five-year OS rates increased as the PD-L1 expression level increased. Five-year OS rates were 20%, 23% and 43% in patients with PD-L1 expression >1% and >50%, respectively. PD-L1 status was not evaluable in 47% of patients (n=61/129); the estimated five-year OS rate in patients with unknown PD-L1 status was 10%. Based on investigators' assessment, 75% (n=12/16) of patients remained without evidence of progressive disease at their last follow-up. In the study, five-year survivors had variable length of time and disease course from diagnosis to Opdivo treatment initiation. The median time from initial diagnosis to start of Opdivo was 1.2 years (range, 0.4 to 6.1 years).

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

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 35 types of cancers with 13 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.

About Opdivo

Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to uniquely harness the body's own immune system to help restore anti-tumor immune response. By harnessing the body's own immune system to fight cancer, Opdivo has become an important treatment option across multiple cancers.

Opdivo's leading global development program is based on Bristol-Myers Squibb's scientific expertise in the field of Immuno-Oncology and includes a broad range of clinical trials across all phases, including Phase 3, in a variety of tumor types. To date, the Opdivo clinical development program has enrolled more than 25,000 patients. The Opdivo trials have contributed to gaining a deeper understanding of the potential role of biomarkers in patient care, particularly regarding how patients may benefit from Opdivo across the continuum of PD-L1 expression.

In July 2014, Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world. Opdivo is currently approved in more than 60 countries, including the United States, the European Union and Japan. In October 2015, the company's Opdivo and Yervoy combination regimen was the first Immuno-Oncology combination to receive regulatory approval for the treatment of metastatic melanoma and is currently approved in more than 50 countries, including the United States and the European Union.

U.S. FDA-APPROVED INDICATIONS FOR OPDIVO®

OPDIVO® (nivolumab) as a single agent is indicated for the treatment of patients with BRAF V600 mutation-positive unresectable or metastatic melanoma. This indication is approved under accelerated approval based on progression-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

OPDIVO® (nivolumab) as a single agent is indicated for the treatment of patients with BRAF V600 wild-type unresectable or metastatic melanoma.

OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of patients with unresectable or metastatic melanoma. This indication is approved under accelerated approval based on progression-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.