Product Indication Date Developments Opdivo CRC March 2019 Ono, our alliance partner for  Opdivo  in Japan, announced the submission of a supplemental application of  Opdivo  in Japan for additional indication of MSI-H unresectable advanced or recurrent CRC that has progressed following chemotherapy for a partial change in the approved items of the manufacturing and marketing approval. This is mainly based on the result from Phase II CheckMate-142 study evaluating  Opdivo  in patients with MSI-H or dMMR recurrent or metastatic CRC that has progressed on or after, or been intolerant of, at least one previous line of treatment with chemotherapy including fluoropyrimidine anticancer drugs. ESCC September 2019 Announced results from the Phase III ATTRACTION-3 trial evaluating  Opdivo  versus chemotherapy for the treatment of patients with unresectable advanced or recurrent ESCC refractory or intolerant to combination therapy with fluoropyrimidine and platinum-based drugs. For the primary endpoint of overall survival,  Opdivo  demonstrated a statistically significant improvement over chemotherapy, with a 23% reduction in risk of death and a 2.5-month improvement in median overall survival compared to patients treated with chemotherapy. The safety profile for  Opdivo in this trial was consistent with previously reported studies in ESCC and other solid tumors. May 2019 Ono, our alliance partner for  Opdivo  in Japan, announced the submission of a supplemental application of  Opdivo  for indication of unresectable advanced or recurrent esophageal cancer in Japan for a partial change in approved items of manufacturing and marketing approval. GBM September 2019 Announced Phase III CheckMate-548 trial evaluating the addition of  Opdivo  to the current standard of care (temozolomide and radiation therapy) versus the standard of care alone did not meet one of its primary endpoints, progression-free survival, in patients with newly diagnosed GBM that is MGMT- methylated. The data monitoring committee recommended that the trial continue as planned to allow the other primary endpoint, overall survival, to mature. The Company remains blinded to all study data. May 2019 Announced Phase III CheckMate-498 trial evaluating  Opdivo  plus radiation versus temozolomide plus radiation in patients with newly diagnosed MGMT-unmethylated GBM did not meet its primary endpoint of overall survival at final analysis. HCC June 2019 Announced topline results from CheckMate-459, a randomized Phase III study evaluating Opdivo  versus sorafenib as a first-line treatment in patients with unresectable HCC. The trial did not achieve statistical significance for its primary endpoint of overall survival per the pre-specified analysis. Melanoma October 2019 Announced the EC approval of  Opdivo  flat dosing schedule of 240 mg infused over 30 minutes every two weeks or 480 mg infused over 60 minutes every four weeks for the adjuvant treatment of adult patients with melanoma with involvement of lymph nodes or metastatic disease who have undergone complete resection. September 2019 Announced results of a three-year analysis of efficacy data from the Phase III CheckMate-238 study evaluating adjuvant use of  Opdivo 3 mg/kg versus  Yervoy 10 mg/kg in patients with Stage III or Stage IV melanoma who were at high risk of recurrence following complete surgical resection. At three years of follow-up,  Opdivo  continues to demonstrate superior recurrence-free survival compared to  Yervoy , the active control, with recurrence-free survival rates of 58% and 45%, respectively. August 2019 Announced, with our alliance partner Nektar, that the FDA has granted Breakthrough Therapy Designation for investigational agent bempegaldesleukin (NKTR-214) in combination with  Opdivo  for the treatment of patients with previously untreated unresectable or metastatic melanoma. The Breakthrough Therapy Designation is based on clinical data which were recently reported in the 2019 American Society of Clinical Oncology Annual Meeting from the cohort of patients with metastatic melanoma that were treated with the doublet therapy in the ongoing PIVOT-02 Phase I/II clinical study. NSCLC September 2019 Announced long-term pooled efficacy and safety results from the Phase III CheckMate-017 and CheckMate-057 studies in patients with previously treated advanced NSCLC. At five years, patients treated with  Opdivo  continued to experience long-term overall survival (“OS”) benefit versus docetaxel. OS rate at five years were 13.4% for  Opdivo  and 2.6% for docetaxel. The OS benefit for  Opdivo -treated patients was observed across all subgroups. April 2019 Announced results from pooled analyses of survival data from four studies (CheckMate-017, -057, -063 and -003) in patients with previously-treated advanced NSCLC who were treated with  Opdivo . In the pooled analysis of the four studies, 14% of all  Opdivo -treated patients were alive at four years. Notably, in patients with PD-L1 greater than or equal to 1% and less than 1%, four-year overall survival rate were 19% and 11%, respectively. SCCHN September 2019 Received approval in China for  Opdivo , as a monotherapy in treatment of patients with SCCHN with disease progression on or after platinum-based therapy, and whose tumors have PD-L1 positive expression (defined as ≥1% of tumor cells expressing PD-L1) January 2019 Acceptance in China of sBLA filing for patients who had previously been treated for metastatic or recurrent SCCHN. 53