AstraZeneca to update on progress with Immuno-Oncology pipeline and combination treatments at ASCO 2015

• 61 data abstracts - with 6 oral presentations - to be featured from across AstraZeneca’s broad pipeline, including in lung, ovarian and breast cancers.
• Increased confidence in the potential of anti-PD-L1 MEDI4736 as a cornerstone for combination treatments with other immuno-oncology and small molecule investigational medicines.
• Updated data will be presented on the safety and clinical activity of MEDI4736 + tremelimumab in patients with NSCLC.
• Data will also be presented on the safety of MEDI4736 in combination with EGFR inhibitors gefitinib and AZD9291, as well as the triple combination with trametinib (MEK inhibitor) + dabrafenib (BRAF inhibitor)¹.
• In small molecule combinations, data will be presented on AZD9291 with savolitinib (cMET inhibitor) or selumetinib (MEK inhibitor), being investigated as potential treatments for overcoming newly-identified forms of resistance in EGFR mutated lung cancer.

AstraZeneca and MedImmune, the Company’s global biologics research and development arm, will demonstrate rapid progress with their combination-focused oncology pipeline at the American Society of Clinical Oncology (ASCO) Annual Meeting, 29 May-2 June 2015. 61 scientific abstracts² will be presented at the meeting, reinforcing the significant progress in immuno-oncology through combination therapies and innovative companion diagnostics.

Briggs Morrison, Executive Vice President, Global Medicines Development and Chief Medical Officer at AstraZeneca, said: “We are pleased to update on the breadth and depth of our oncology pipeline at ASCO. Our small molecule and biologic treatments target multiple areas of tumour biology across a diverse range of cancers, alone or in combination. It is especially encouraging to see the potential impact of our work in non-small cell lung cancer at different stages of the disease pathway and for different types of patients.”

“In immuno-oncology, we are starting to see the transformational potential of combination therapies, which are at the heart of our vision of redefining cancer treatment. The maturing data reinforce our confidence in this strategy, and, in particular, in MEDI4736, which is showing durable activity across multiple tumour types and in different combinations. This progress offers the possibility of helping patients who don’t respond to standard of care or current monotherapies.”

Bahija Jallal, Executive Vice President, MedImmune, said: “Our understanding of the potential of immuno-oncology is fast evolving as we begin to unlock its benefits for a greater number of patients – however we have only scratched the surface so far. Our comprehensive, combination-focused development programme aims to rapidly deepen our scientific understanding, exploring all the critical areas of the immune system that cancer can hijack to escape destruction. Through the use of companion diagnostics, we can also fully understand the clinical value of our investigational immunotherapies, both as monotherapy and in combination, for different types of patients and across many different types of cancer.”

Highlights at the ASCO Annual Meeting will include data from across the Company’s broad pipeline of next-generation investigational medicines, which target cancer through key areas of tumour biology including immunotherapy, the genetic drivers of cancer and acquired resistance and DNA damage repair.

Immuno-oncology

Immunotherapies use the body's own immune system to help fight cancer. There are three major components to an effective cancer immune response:priming and activation of T-cells (white blood cells that play a central role in immune response) through cancer antigen presentation; optimising T-cell mediated cancer cell killing by overcoming inhibitory mechanisms employed by the cancer; and overcoming immune suppressive mechanisms in the tumor microenvironment to further enhance an effective anti-tumour immune response.

At the ASCO Annual Meeting AstraZeneca will provide an update on its comprehensive immuno-oncology development programme, which

includes 31 ongoing clinical trials targeted across this cycle of anti-tumour immunity. Data to be presented at ASCO are supported by a number of recent milestones including:

• Start of the combination arm of the Phase III ARCTIC study of MEDI4736 with tremelimumab in non-small cell lung cancer (NSCLC) patients who have received at least two prior systemic treatment regimens.

• Start of the Phase II CONDOR study of MEDI4736 and tremelimumab as monotherapies and in combination in patients with recurrent squamous cell carcinoma of the head and neck (SCCHN).

Fast-Track designation granted by the FDA for the investigation of MEDI4736 as a monotherapy treatment for patients with advanced NSCLC, who have received at least two prior systemic-treatment regimens, who do not have EGFR mutations or anaplastic lymphoma kinase (ALK) alterations, and have tumours that are determined to be PD-L1 positive.

In addition to testing the potential of immunotherapies in solid tumours, AstraZeneca recently entered into a strategic collaboration with Celgene, a global leader in haematological cancers, on a broad development programme for MEDI4736, both as monotherapy and in combination with other molecules, across a range of blood cancers including multiple myeloma, non-Hodgkin’s lymphoma and myelodysplastic syndrome.

Presentations to include:

• Safety and efficacy of MEDI4736in combination with tremelimumabin patients with NSCLC [Abstract #3014]. Updated data on additional patients and activity in both PD-L1 positive and negative patients to be presented.

• Safety and efficacy of the triple combination of MEDI4736 with BRAF (dabrafenib) and/or MEK (trametinib) inhibitors in patients with advanced melanoma [Oral Abstract #3003].

• An open-label study of MEDI4736 in combination with MEDI0680 (anti-PD-1) in patients with advanced malignancies [Trials in Progress Poster #TPS3087].

• Updates reinforcing the clinical activity of MEDI4736 as monotherapy in patients with NSCLC [Abstract #8032], in patients with recurrent or metastatic SCCHN [Abstract #3011], and on the development of a PD-L1 companion diagnostic assay [Abstract #8033].

Genetic drivers of cancer and resistance

AstraZeneca has a strong legacy in research into the genetic drivers of cancer and resistance. Iressa (gefitinib) was the first epidermal growth factor receptor (EGFR) inhibitor, providing the first truly targeted treatment for advanced lung cancer. Data to be presented at ASCO will focus on AZD9291, an investigational, highly selective, irreversible inhibitor of both the activating sensitising EGFR mutation (EGFRm) and the activating resistance mutation, T790M.

Patients with EGFRm NSCLC are particularly sensitive to treatment with currently available EGFR tyrosine kinase inhibitors (TKIs), which block the cell signalling pathways that drive the growth of tumour cells. However, tumour cells almost always develop resistance to treatment, leading to disease progression. In approximately two thirds of patients, this resistance is caused by the secondary mutation, T790M. No currently targeted therapies are approved for the treatment of tumours with this resistance mutation.

AZD9291 presentations at ASCO to include:

• Early efficacy and safety data from the multi-arm Phase Ib TATTON study, testing AZD9291 in combination with one of three treatments in patients with advanced, EGFR-mutant NSCLC who have progressed on prior EGFR TKI therapy [Abstract #2509]. The treatments are MEDI4736; savolitinib (AZD6094), an investigational, highly potent and selective c-MET inhibitor; or selumetinib, a potent, selective inhibitor of MEK1/2 kinases.

• Detail on the Phase III FLAURA clinical trial testing AZD9291 versus standard doses of gefitinib or erlotinib in treatment-naïve patients with EGFR-mutant advanced NSCLC [Trials in Progress Poster #TPS8102].

• Data from the Phase I AURA study testing AZD9291 as first-line therapy for patients with NSCLC, compared against currently approved EGFR medicines [Abstract #8000].

Data presented at ASCO build on the updated progression-free survival (PFS) data for AZD9291 as second line therapy for patients with EGFR-mutated NSCLC, who also have the T790M resistance mutation, which was presented at the recent European Lung Cancer Conference. The data demonstrated a median PFS of 13.5 months (95% confidence interval (CI) 8.3 months to not calculable (NC)).These PFS findings relate to independently reviewed data from 63 patients with T790M tumours treated with AZD9291 at a dose of 80mg per day, and are based on only 38% of patients having tumour progression. In patients treated with AZD9291 80mg, the most common all-cause adverse events (AEs) of any grade were rash, 38% (0% Grade ≥3) and diarrhea, 36% (1% Grade ≥3). Investigator-determined treatment-related Grade ≥3 AEs occurred in 14% of patients.

DNA Damage Repair

AstraZeneca has the largest portfolio of potential medicines targeted at DNA damage repair, including the recently launched Lynparza (olaparib), an oral poly ADP-ribose polymerase (PARP) inhibitor, for BRCA-mutated ovarian cancer.

During ASCO, new data will be presented on Lynparza and on AZD1775, a small molecule designed to inhibit the tyrosine kinase called Wee1, which helps to regulate the cell-division cycle, and is undergoing testing for the treatment of ovarian cancer. AZD1775 is designed to cause certain tumour cells to divide without undergoing the normal DNA repair processes, ultimately leading to cell death. Preclinical evidence suggests that the combination of AZD1775 and DNA damage-inducing chemotherapy agents can enhance anti-tumour properties, in comparison to chemotherapy alone.

• Data on the genomic characterisation of long-term responders to Lynparza will provide further insight into the physiology of ovarian cancer patients seeing benefit from the medicine [Abstract #5566].

• Data from an international biomarker-directed randomised Phase II trial of AZD1775 used in combination with paclitaxel and carboplatin for the treatment of women with platinum-sensitive, TP53 mutated ovarian cancer [Oral Abstract #5506].

• Data from a Phase II study of AZD1775 plus carboplatin in patients with TP53 mutated ovarian cancer refractory or resistant (three or fewer months) to standard first line therapy [Oral Abstract #2507].

Key AstraZeneca abstracts to be featured at ASCO

– ENDS –

NOTES TO EDITORS

¹Novartis medicines for treatment of patients with metastatic melanoma.

² Data included in abstracts are preliminary only and do not represent full data sets.

About AstraZeneca in Oncology

Oncology is a therapeutic area in which AstraZeneca has deep-rooted heritage. It will be potentially transformational for the Company’s future, becoming the sixth growth platform. Our vision is to help patients by redefining the cancer treatment paradigm and one-day eliminate cancer as cause of death. By 2020, we are aiming to bring six new cancer medicines to patients.

Our broad pipeline of next-generation investigational medicines is focused on four main disease areas - ovarian, lung, breast, and haematological cancers. These are being targeted through four key platforms – immuno-oncology, the genetic drivers of cancer and resistance, DNA damage repair and antibody drug conjugates.

About MedImmune

MedImmune is the worldwide biologics research and development arm of AstraZeneca. MedImmune is pioneering innovative research and exploring novel pathways across key therapeutic areas, including respiratory, inflammation and autoimmunity; cardiovascular and metabolic disease; oncology; neuroscience; and infection and vaccines. The MedImmune headquarters is located in Gaithersburg, Md., one of AstraZeneca’s three global R&D centres. For more information, please visit www.medimmune.com.

About AstraZeneca

AstraZeneca is a global, innovation-driven biopharmaceutical business that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of cardiovascular, metabolic, respiratory, inflammation, autoimmune, oncology, infection and neuroscience diseases. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information please visit: www.astrazeneca.com.

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