[Fam]-Trastuzumab Deruxtecan Achieved a Tumor Response of 60.9% in Pivotal Phase II HER2-positive Metastatic Breast Cancer Trial

AstraZeneca and Daiichi Sankyo's [fam]-trastuzumab deruxtecan demonstrated an impressive 14.8-month median duration of response and 16.4-month median progression-free survival

AstraZeneca and Daiichi Sankyo Company, Limited (Daiichi Sankyo) today presented positive detailed data from the global pivotal Phase II single-arm DESTINY-Breast01 trial of [fam]-trastuzumab deruxtecan (DS-8201), an investigational HER2-targeting antibody drug conjugate (ADC) and potential new medicine, in patients with HER2-positive metastatic breast cancer who received two or more prior HER2-targeted regimens.

The primary endpoint of objective response rate (ORR), confirmed by independent central review, was 60.9% with [fam]-trastuzumab deruxtecan monotherapy (5.4mg/kg). Patients had a median of six prior therapies for metastatic disease (2-27).

Patients achieved a disease control rate (DCR) of 97.3% with a median duration of response (DoR) of 14.8 months (range: 13.8 - 16.9) and median progression-free survival of 16.4 months (range: 12.7 - not reached). The median overall survival (OS) has not yet been reached with an estimated survival rate for patients receiving [fam]-trastuzumab deruxtecan of 86% at one year. The results were consistent across subgroups of patients.

José Baselga, Executive Vice President, Oncology R&D, said: "The clinically meaningful and durable responses seen among these patients illustrate the potential of [fam]-trastuzumab deruxtecan to establish a new standard of care. These results are impressive, as women with this advanced stage of breast cancer have already endured multiple prior therapies for HER2-positive metastatic breast cancer."

Antoine Yver, Executive Vice President and Global Head, Oncology Research and Development, Daiichi Sankyo, said: "The strength of the pivotal results and the consistency with previously reported [fam]-trastuzumab deruxtecan data further underscore that this specifically engineered HER2-targeted antibody drug conjugate is delivering on its intent of enhancing efficacy for patients with HER2-positive metastatic breast cancer."

Ian E. Krop, a principal investigator of the DESTINY-Breast01 trial and Associate Chief, Division of Breast Oncology, Susan F. Smith Center for Women's Cancers, Dana-Farber Cancer Institute, said: "These results are particularly striking as [fam]-trastuzumab deruxtecan prompted a high level of durable tumor reduction among patients, the majority of whom had exhausted most, if not all, standard therapies for HER2-metastatic breast cancer. We are excited by these results and their potential to help patients with this advanced stage of breast cancer."

Summary of Resultsⁱ

The data were included as part of the press program at the 2019 San Antonio Breast Cancer Symposium (SABCS) and simultaneously published in The New England Journal of Medicine.

Prior therapies included ado-trastuzumab emtansine (T-DM1) (100%), trastuzumab (100%), pertuzumab (65.8%), other anti-HER2-therapies (54.3%), hormone therapies (48.9%) and other systemic therapies (99.5%). Median treatment duration was 10 months (range: 0.7 - 20.5 months) with a median duration of follow-up of 11.1 months (range: 0.7 - 19.9). As of data cut-off on August 1, 2019, 42.9% of patients remained on-treatment.

The safety and tolerability profile of [fam]-trastuzumab deruxtecan in DESTINY-Breast01 was consistent with that observed in the Phase I trial. The most common treatment- emergent adverse events (TEAEs), Grade 3 or higher, were decreased neutrophil count (20.7%), anemia (8.7%), nausea (7.6%), decreased white blood cell count (6.5%), decreased lymphocyte count (6.5%) and fatigue (6.0%). Overall, 13.6% of patients had confirmed interstitial lung disease (ILD) related to treatment as determined by an independent review. The events were primarily Grade 1 or 2 (10.9%) in severity with one Grade 3 (0.5%), no Grade 4 events. Four deaths (2.2%) were determined to be due to ILD.

Regulatory submission of [fam]-trastuzumab deruxtecan for the treatment of patients with HER2-positive metastatic breast cancer was recently accepted by the US Food and Drug Administration.

– ENDS –

NOTES TO EDITORS

About HER2-Positive Breast Cancer

Approximately one in five breast cancers are HER2 positive. Despite recent improvements and approvals of new medicines, there remain significant clinical needs for patients with HER2-positive metastatic breast cancer. This disease remains incurable with patients eventually progressing after available treatment. Additionally, there are currently no approved HER2-targeted medicines for HER2 FISH negative, IHC 2+ or IHC 1+ tumors.

About HER2

HER2 is a tyrosine kinase receptor growth-promoting protein found on the surface of some cancer cells that is associated with aggressive disease and poorer prognosis in patients with breast cancer. To be considered HER2 positive, tumor cancer cells are usually tested by one of two methods: immunohistochemistry (IHC) or fluorescent in situ hybridization (FISH). IHC test results are reported as: 0, IHC 1+, IHC 2+, or IHC 3+. A finding of IHC 3+ and/or FISH amplification is considered positive.

About DESTINY-Breast01

DESTINY-Breast01 is a pivotal phase II, single-arm, open-label, global, multicenter, two-part trial evaluating the safety and efficacy of DS-8201 in patients with HER2-positive unresectable and/or metastatic breast cancer previously treated with trastuzumab emtansine. The primary endpoint of the trial is objective response rate, as determined by independent central review. Secondary objectives include, duration of response, disease control rate, clinical benefit rate, progression-free survival, and overall survival. Enrollment into DESTINY-Breast01 was completed in September 2018 with 184 patients at more than 100 sites across North America, Europe, Japan and other countries in Asia.

About [Fam]-trastuzumab deruxtecan

[Fam]-trastuzumab deruxtecan, (DS-8201), is the lead product in the investigational ADC Franchise of the Daiichi Sankyo Cancer Enterprise and the most advanced program in AstraZeneca's ADC Scientific platform. ADCs are targeted cancer medicines that deliver cytotoxic chemotherapy ("payload") to cancer cells via a linker attached to a monoclonal antibody that binds to a specific target expressed on cancer cells.

A comprehensive development program is underway in North America, Europe and Asia, including five pivotal trials in HER2-expressing metastatic breast and gastric cancers, including a trial in patients with metastatic breast cancer and low levels of HER2 expression. Phase II trials are underway for HER2-expressing advanced colorectal cancer, as well as metastatic non-squamous HER2-overexpressing or HER2-mutated non-small cell lung cancer. Trials in combination with other anticancer treatments, such as immunotherapy, are also underway.

About the collaboration between AstraZeneca and Daiichi Sankyo

In March 2019, AstraZeneca and Daiichi Sankyo entered into a global collaboration to jointly develop and commercialize [fam-] trastuzumab deruxtecan as a potential new medicine worldwide, except in Japan where Daiichi Sankyo maintains exclusive rights. Daiichi Sankyo is solely responsible for manufacturing and supply.

About AstraZeneca in Oncology

AstraZeneca has a deep-rooted heritage in Oncology and offers a quickly-growing portfolio of new medicines that has the potential to transform patients' lives and the Company's future. With at least six new medicines to be launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, we are committed to advance New Oncology as one of AstraZeneca's five Growth Platforms focused on lung, ovarian, breast and blood cancers. In addition to our core capabilities, we actively pursue innovative partnerships and investments that accelerate the delivery of our strategy, as illustrated by our investment in Acerta Pharma in hematology.

By harnessing the power of four scientific platforms – Immuno-Oncology, Tumor Drivers and Resistance, DNA Damage Response and Antibody Drug Conjugates – and by championing the development of personalized combinations, AstraZeneca has the vision to redefine cancer treatment and one day eliminate cancer as a cause of death.

About AstraZeneca

AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines, primarily for the treatment of diseases in three therapy areas - Oncology, Cardiovascular, Renal & Metabolism and Respiratory. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information, please visit www.astrazeneca-us.com and follow us on Twitter @AstraZenecaUS.

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12/19

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