ONO PHARMACEUTICAL : Opdivo (nivolumab) Shows Durable Response in Longest Follow-up for a PD-1 Inhibitor in Previously Treated Advanced Non-Small Cell Lung Cancer (149KB)

October 11, 2016

(PRINCETON, NJ, October 9, 2016) - Bristol-Myers Squibb Company (NYSE: BMY) announced updated results from two pivotal Phase 3 studies, CheckMate -057 and CheckMate -017, which showed more than one-third of previously treated metastatic non-small cell lung cancer (NSCLC) patients in both trials experienced ongoing responses with Opdivo, compared to no ongoing responses in the docetaxel arm. The median duration of response (DOR) with Opdivo versus docetaxel in CheckMate -057 was 17.2 months (95% CI: 8.4, NE) and 5.6 months (95% CI: 4.4, 6.9), respectively, and in CheckMate -017 it was

25.2 months (95% CI: 9.8, 30.4) and 8.4 months (95% CI: 8.4, NE), respectively. In CheckMate -057, patients with PD-L1 ≥1% had a median DOR of 17.2 months (95% CI: 8.4, NE) and in patients with PD- L1

There were no new safety signals identified for Opdivo in the pooled safety analysis from both studies. No new treatment-related deaths occurred between one and two years' minimum follow-up despite the longer treatment exposure, and new events were observed in 11/418 patients with an additional one year of follow up..

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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Opdivo (nivolumab) Shows Durable Response in Longest Follow-up for a PD-1 Inhibitor in Previously Treated Advanced Non-Small Cell Lung Cancer

Updated data from CheckMate -057 and -017 show Opdivo-treated patients had tripled the duration of response compared to those treated with docetaxel, with a minimum follow-up of two years

In CheckMate -057, durable responses and complete responses were observed with Opdivo

in both PD-L1 expressors and non-expressors

Patient-reported outcomes from CheckMate -057 show favorable overall health status with

Opdivo versus docetaxel in previously treated advanced non-small cell lung cancer patients

(PRINCETON, NJ, October 9, 2016) - Bristol-Myers Squibb Company (NYSE: BMY) announced today updated results from two pivotal Phase 3 studies, CheckMate -057 and CheckMate -017, which showed more than one-third of previously treated metastatic non-small cell lung cancer (NSCLC) patients in both trials experienced ongoing responses with Opdivo, compared to no ongoing responses in the docetaxel arm. The median duration of response (DOR) with Opdivo versus docetaxel in CheckMate -057 was 17.2 months (95% CI: 8.4, NE) and 5.6 months (95% CI: 4.4, 6.9), respectively, and in CheckMate -017 it was

25.2 months (95% CI: 9.8, 30.4) and 8.4 months (95% CI: 8.4, NE), respectively. In CheckMate -057, patients with PD-L1 ≥1% had a median DOR of 17.2 months (95% CI: 8.4, NE) and in patients with PD-L1

There were no new safety signals identified for Opdivo in the pooled safety analysis from both studies. No new treatment-related deaths occurred between one and two years' minimum follow-up despite the longer treatment exposure, and new events were observed in 11/418 patients with an additional one year of follow up.

These findings were presented today, October 9, during a poster discussion session at the 2016 European Society for Medical Oncology Congress from 3:46-4:06 p.m. CEST (Abstract #1215PD).

"Further evaluation of Opdivo in previously treated non-small cell lung cancer showed continued superior survival and the potential for durable responses compared to

docetaxel across histologies in this patient population," said Martin Reck, M.D., Ph.D., head of thoracic oncology at the Hospital Grosshansdorf. "Notably, the median duration of response with Opdivo was more than three times that observed with docetaxel."

Patient-reported outcomes from CheckMate -057 were also presented today during a poster discussion session from 3:46-4:06 p.m. CEST (Abstract #1217PD). Findings show Opdivo provided better preservation of health status, health-related quality of life and symptom control versus docetaxel, as assessed by the EuroQoL-5 Dimensions (EQ-5D) visual analog scale (VAS) and the Lung Cancer Symptom Score (LCSS).

Nick Botwood, M.D., Development Lead, Lung and Head & Neck, Bristol-Myers Squibb, commented, "Opdivo, a standard of care in the second-line non-small cell lung cancer treatment setting continues to show durable survival based on updated findings from CheckMate -057 and -017. In addition, based on patient-reported outcomes data from CheckMate -057, Opdivo shows favorable overall health status compared to chemotherapy. These pivotal data continue to inform the scientific community on the use of Opdivo in previously treated NSCLC, a difficult-to-treat cancer."

About CheckMate -057 and CheckMate -017

CheckMate -057 is a landmark Phase 3, open-label, randomized clinical trial that evaluated patients with advanced non-squamous non-small cell lung cancer (NSCLC) who had progressed during or after one prior platinum doublet-based chemotherapy regimen. The trial included patients regardless of PD-L1 status. The study's primary endpoint was overall survival (OS), and secondary endpoints included objective response rate (ORR), progression-

free survival (PFS) and efficacy by tumor PD-L1 expression. Patients enrolled in the trial were administered Opdivo 3 mg/kg every two weeks versus docetaxel at 75 mg/m2 every three weeks.

CheckMate -017 was a Phase 3, open-label, randomized clinical trial that evaluated Opdivo 3 mg/kg every two weeks versus docetaxel 75 mg/m2 every three weeks in patients with advanced squamous NSCLC who had progressed during or after one prior platinum doublet-based chemotherapy regimen. The study's primary endpoint was OS, and secondary endpoints included PFS and response rate. The trial included patients regardless of PD-L1 expression status.

In pooled safety analyses of CheckMate -057 and CheckMate -017, after a minimum of two years of follow-up, treatment-related adverse events (AE) were reported in fewer Opdivo-treated patients than docetaxel-treated patients (any grade: 68% versus 88%; Grade

3/4: 10% versus 55%) and less frequently led to discontinuation (any grade: 6% versus 13%; Grade 3/4: 4% versus 7%). Frequencies of the most common treatment-related AEs were lower with Opdivo than docetaxel. The majority of treatment-related select AEs occurred within the first three months of Opdivo treatment and were resolved using standard management algorithms. Pooled Grade 3/4 treatment-related select AEs for Opdivo include skin (1%), gastrointestinal (1.2%), endocrine (0%), hepatic (1%), pulmonary (1.2%), renal

(0.2%) and hypersensitivity/infusion reaction (0%).

In CheckMate -057, patient-reported outcomes (PROs) were measured using the Lung Cancer Symptom Scale (LCSS) and European Quality of Life (EuroQol)-5 Dimensions visual analog scale (EQ-5D VAS) and EQ-5D utility index (UI). These PROs were assessed every other cycle for Opdivo and every cycle for docetaxel for the first six months of treatment and then every six weeks and at two post-treatment follow-up visits. The EQ-5D also was assessed during survival follow-up, including every three months for the first year and then every six months thereafter. While improvements were seen earlier with the LCSS than with the EQ-5D VAS, both PRO instruments indicated benefit before the separation of the survival curves, which also favored Opdivo.

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