ONO PHARMACEUTICAL : New Data on Opdivo (nivolumab) Indicate Benefit in Heavily Pre-Treated Classical Hodgkin Lymphoma Patients in Phase 2, Single-Arm Pivotal Trial (167KB)

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June 15, 2016

New Data on Opdivo (nivolumab) Indicate Benefit in Heavily Pre-Treated Classical Hodgkin Lymphoma Patients in Phase 2, Single-Arm Pivotal Trial

(PRINCETON, N.J., June 10, 2016) - Bristol-Myers Squibb Company (NYSE: BMY) announced results from CheckMate -205, a multi-cohort, non-comparative, single-arm, Phase 2 registrational trial evaluating Opdivo (nivolumab) in patients with classical Hodgkin lymphoma (cHL). These results, from cohort B of the trial, included patients who had relapsed or progressed after autologous hematopoietic stem cell transplantation (auto-HSCT) and post-transplantation brentuximab vedotin (n=80). The primary endpoint of objective response rate (ORR) per an independent radiologic review committee (IRRC) was 66.3% (95% CI: 54.8-76.4). Median time to response was 2.1 months, and estimated median duration of remission was 7.8 months (95% CI: 6.6-NE). The majority of responses (62.3%) were ongoing at the time of analysis. In an exploratory analysis, the authors observed more than two-thirds (72.1%) of patients who did not respond to most recent prior brentuximab vedotin treatment did respond to Opdivo. The safety profile of Opdivo in CheckMate -205 was consistent with previously reported data in this tumor type.

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, 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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New Data on Bristol-Myers Squibb's Opdivo (nivolumab) Indicate Benefit in Heavily Pre- Treated Classical Hodgkin Lymphoma Patients in Phase 2, Single-Arm Pivotal Trial

Opdivo demonstrated objective response rate of 66.3% in classical Hodgkin lymphoma patients who had relapsed or progressed after auto-HSCT and subsequent brentuximab vedotin, as assessed by an independent radiologic review committee

Among patients who responded to Opdivo, estimated median duration of remission was 7.8 months

(PRINCETON, N.J., June 10, 2016) - Bristol-Myers Squibb Company (NYSE: BMY) announced results from CheckMate -205, a multi-cohort, non-comparative, single-arm, Phase 2 registrational trial evaluating Opdivo (nivolumab) in patients with classical Hodgkin lymphoma (cHL). These results, from cohort B of the trial, included patients who had relapsed or progressed after autologous hematopoietic stem cell transplantation (auto-HSCT) and post-transplantation brentuximab vedotin (n=80). The primary endpoint of objective response rate (ORR) per an independent radiologic review committee (IRRC) was 66.3% (95% CI: 54.8-76.4). Median time to response was 2.1 months, and estimated median duration of remission was 7.8 months (95% CI: 6.6-NE). The majority of responses (62.3%) were ongoing at the time of analysis. In an exploratory analysis, the authors observed more than two-thirds (72.1%) of patients who did not respond to most recent prior brentuximab vedotin treatment did respond to Opdivo. The safety profile of Opdivo in CheckMate -205 was consistent with previously reported data in this tumor type.

These data will be presented at the 21st Congress of the European Hematology

Association (EHA) in Copenhagen, Denmark on Sunday, June 12 from 8:00 - 8:15 a.m. CEST (Abstract #S793) and is in press with The Lancet Oncology.

"There is currently no standard treatment option for classical Hodgkin lymphoma patients who have relapsed or whose disease has progressed after auto-HSCT and post-transplantation brentuximab vedotin," said Andreas Engert, M.D., lead investigator and professor of Internal Medicine, Hematology and Oncology, University Hospital of Cologne, Cologne, Germany. "We are encouraged by the objective response rates and that the majority of responses were ongoing

at the time of analysis in the CheckMate -205 trial evaluating Opdivo in these heavily pre-treated patients."

"Classical Hodgkin lymphoma is a disease that disproportionately impacts young people, and there is a significant unmet need for patients who are not cured by the current standard-of- care treatments and who have a poor prognosis and very limited options," said Jean Viallet, M.D., Global Clinical Research Lead, Oncology, Bristol-Myers Squibb. "The data presented at EHA demonstrate that Opdivo is an important treatment option for patients whose disease has progressed after auto-HSCT and post-transplantation brentuximab vedotin."

Opdivo recently received its first U.S. Food and Drug Administration approval in hematology on May 17, 2016, which also marks the first approval of a PD-1 inhibitor in a hematological malignancy. It was granted accelerated approval based on overall response rate for the treatment of patients with cHL who have relapsed or progressed after auto-HSCT and post- transplantation brentuximab vedotin based on a combined analysis of data from the Phase 2 CheckMate -205 trial, which were more limited than the data being presented at EHA, and the Phase 1 CheckMate -039 trial. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. Opdivo also is currently under regulatory review for cHL in the European Union and Japan.

About CheckMate -205

CheckMate -205 is a Phase 2, single-arm, open-label, international, multicenter, multi- cohort study that included the evaluation of Opdivo in adult patients with cHL. All patients in cohort B had failed both auto-HSCT and subsequent brentuximab vedotin. The median number of prior lines of therapy was four, and 49% had received at least five previous lines of therapy. Patients enrolled in this trial were treated with Opdivo 3 mg/kg intravenously every two weeks until disease progression or unacceptable toxicity.

The primary endpoint was ORR by IRRC assessment. Secondary endpoints based on IRRC assessment included duration of objective response, complete and partial remission rates, duration of complete and partial remission, and based on investigator assessment, objective response and duration of objective response. Exploratory endpoints included IRRC-assessed progression-free survival (PFS), overall survival (OS), safety and tolerability, and quality of life. Investigator-assessed ORR was 72.5% (95% CI: 61.4-81.9). Best overall response was complete

and partial remission in 27.5% and 45.0%. At six months, the IRRC-assessed PFS rate was 76.9% (95% CI: 65-85), and the OS rate was 98.7% (95% CI: 91.0-99.8), whereas median PFS was 10 months (95% CI: 8.41-NA). The safety profile of Opdivo in CheckMate -205 remained consistent with previously reported data in this tumor type.

Classical Hodgkin lymphoma is characterized by Reed-Sternberg cells, which exhibit 9p24.1, resulting in overexpression of PD-1 ligands PD-L1 and PD-L2 on the tumor cell surface. Increased PD-L1 and PD-L2 expression by Reed-Sternberg cells may enable these cells to evade detection by the immune system. An exploratory analysis evaluated the association between the 9p24.1 genetic alteration, programmed death 1 (PD-1) ligand expression and IRRC-assessed ORR. Responses were reported in patients with any level of 9p24.1 alteration.

The most common drug-related adverse events were fatigue (25%; 20/80), infusion- related reaction (20%; 16/80), rash (16%; 13/80), arthralgia (14%; 11/80), pyrexia (14%; 11/80), nausea (13%; 10/80), diarrhea (10%; 8/80), and pruritus (10%; 8/80). Grade 3/4 adverse events occurred in 32 patients (40%), and one Grade 5 event occurred (1%; multi-organ failure). Serious adverse events of any cause were reported in 20 patients (25%; 20/80), the most common being pyrexia (4%; 3/8), and drug-related serious adverse events in five patients (6%), the most common being infusion-related reaction (3%). Extended safety follow-up of cHL patients treated in the nivolumab clinical trial program subsequently treated with allogeneic HSCT (N=17) identified complications, including fatal events.

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.