AstraZeneca presents advances in oncology research at ECC 2015 with data on AZD9291, durvalumab and lynparza™ (olaparib)

AstraZeneca, along with MedImmune, the company’s global biologics research and development arm, will illustrate the strength and depth of research underpinning its scientific leadership in oncology, at the European Cancer Congress (ECC) 2015 in Vienna, Austria (25-29 September 2015).

19 oral and poster presentations, including data on AZD9291, durvalumab and olaparib, will provide confirmation and complementary analysis of previously presented results, as well as new data on:

AZD9291: pooled Phase II efficacy and safety data in pre-treated patients with non-small cell lung cancer (NSCLC) (Abstract # 3113) and analysis of patients with and without brain metastases (Abstract # 3083)

Durvalumab (MEDI4736) monotherapy: preliminary results investigating tumour indicators of response in patients with NSCLC (Late Breaker Presentation Abstract # 15LBA)

Olaparib: tumour biomarkers to suggest potential treatment activity in women with ovarian cancer without a BRCA1/2 mutation (Abstract # 435)

Mondher Mahjoubi, Senior Vice President, Global Product Strategy for Oncology at AstraZeneca, said: “Data published at ECC 2015 confirm the strength and rapid progress of our development plan in oncology. Our large and growing dataset for AZD9291 is a great example of this, as it highlights the robustness and consistency of the results we are seeing across a broad population of pre-treated non-small cell lung cancer patients.”

AZD9291 in pre-treated patients with NSCLC

Data from an analysis of the AURA Phase II studies (AURA extension and AURA2) in pre-treated patients with NSCLC (Abstract # 3113) confirm findings already reported at previous congresses for AZD9291, a highly selective, irreversible inhibitor of both the activating epidermal growth factor receptor mutation (EGFRm) and the resistance mutation, T790M.Pooled data from over 400 pre-treated patients with EGFRm T790M showed an objective response rate (ORR) of 66% (95% confidence interval (CI) 61% to 71%). ORR was consistent across all sub-groups treated with AZD9291 including ethnicity, tumour mutation types and presence/absence of brain metastases. Preliminary median progression free survival (PFS) was 9.7 months (95% CI 8.3 months to non-calculable [NC]) and median duration of response (DoR) was non-calculable (95% CI 8.3 months to NC).

The safety profile was also in line with previous data readouts. The most common all-causality adverse events (AEs) were diarrhoea, 42% (1% ≥Grade 3) and rashes (grouped terms), 41% (1% ≥Grade 3).

Reported AEs of hyperglycaemia, interstitial lung disease (ILD) and QT prolongation remained consistent with data previously presented: ILD and pneumonitis 3% (2% ≥Grade 3), hyperglycaemia 1% (0% ≥Grade 3), QT prolongation 4% (1% ≥Grade 3). There was a low discontinuation rate:4% of patients discontinued AZD9291 due to drug-related AEs (as assessed by the investigator).

An analysis of AURA Phase II studies (Abstract # 3083) will demonstrate the consistent activity of AZD9291 in patients with EGFRm T790M NSCLC with and without brain metastases; clinical anecdotes suggest that AZD9291 may have activity in the brain. Pre-clinical data showing that AZD9291 penetrates the blood-brain-barrier were recently presented at the World Congress on Lung Cancer (WCLC Abstract # ID410). The BLOOM (NCT02228369) study is investigating further the potential activity of AZD9291 in the brain.

The AZD9291 ASTRIS study (NCT02474355)is recruiting pre-treated patients with advanced or metastatic EGFRm T790M NSCLC in a real-world setting at multiple sites in Europe. In the US, an expanded access programme (NCT02451852) for AZD9291 for patients with advanced or metastatic EGFRm T790M NSCLC is available. AZD9291 is an investigational therapy and is not yet approved for any indication in any market.

Immuno-oncology programme progresses at pace

MedImmune will demonstrate advances in biomarker research that may identify patients most likely to respond to immunotherapies. The research will demonstrate the potential association between increased tumour expression of programmed death ligand-1 (PD-L1) and gamma interferon and response to the PD-L1 mAb, durvalumab (MEDI4736) (Abstract # 15LBA).

The new research is part of the extensive durvalumab clinical development programme in NSCLC, which includes the PACIFIC (NCT02125461), ATLANTIC (NCT02087423), ARCTIC (NCT02352948), MYSTIC (NCT02453282) and NEPTUNE (NCT02542293) trials discussed recently at WCLC and other conferences this year.

Robert Iannone, Head of Immuno-Oncology, Global Medicines Development at AstraZeneca, said: “Advances in our biomarker development will enable us to effectively identify patients who could benefit most from durvalumab monotherapy as well as those for whom the combination with other immunotherapies such as our anti- CTLA-4 inhibitor (tremelimumab) would be more effective. These insights will support progress with our extensive late-stage immuno-oncology programme, which now includes 17 clinical studies and more than 9,000 patients in lung, bladder, head and neck, and other cancers.”

Olaparib shows activity beyond BRCA mutations

Exploratory biomarker data from a Phase II study of olaparib are contributing to an enhanced scientific understanding of why some women with ovarian cancer without a BRCA1/2 mutation demonstrate anti-tumour activity with poly ADP-ribose polymerase (PARP) inhibitor treatment (Abstract # 435). The data suggest that these women have tumours with mutations in other homologous recombination repair (HRR) genes that behave in a similar way to BRCA mutations.

The new biomarker analysis was carried out on tumour samples from 209 patients who took part in a Phase II trial of olaparib in platinum-sensitive relapsed serous ovarian cancer (NCT00753545, Study 19). In a sub-set of patients whose tumours did not carry the BRCA mutation, there was a trend towards greater olaparib efficacy in 21 women with other HRR gene mutations compared to 58 patients with no detectable mutations in other HRR genes.

Olaparib is the cornerstone of AstraZeneca’s industry-leading pipeline of personalised treatments targeting DNA damage and repair mechanisms in cancer cells. The potential of olaparib to target tumours with HRR mutations beyond those in BRCA genes is under investigation in ongoing clinical trials.

AstraZeneca delivering on oncology strategy

ECC marks another successful milestone for AstraZeneca and MedImmune in 2015, following the launch of LYNPARZA™ (olaparib) in the U.S. and Europe, the approval of IRESSAÒ (gefitinib) in the US, rapid US and EU filings for AZD9291, key regulatory designations for further investigational compounds, and encouraging datasupporting the company’s focus on combinations across immuno-oncology and small molecules.

As progress continues, the company is deepening its understanding of cancer biology and extending its research into a wider range of tumour types, with new data expected at congresses throughout 2016. AstraZeneca remains on track to achieve its bold ambition of delivering six new cancer medicines to patients by 2020.

– ENDS –

NOTES TO EDITORS

Key ECC data presentations

About AZD9291

AZD9291 is a highly selective, irreversible inhibitor of both activating sensitising EGFRm and the resistance mutation, T790M, while sparing the activity of wild type EGFR.AZD9291 is designed to achieve minimal or no activity against two biological receptors, known as the

insulin receptor (IR) and insulin-like growth factor receptor (IGFR), in order to minimise the potential for hyperglycaemia (high blood sugar). Hyperglycaemia can lead to patients requiring treatment with additional medications.

Patients who have the EGFRm form of NSCLC, which occurs in 10-15 percent of NSCLC patients in Europeand 30-40 percent of NSCLC patients in Asia,are particularly sensitive to treatment with currently available EGFR-TKIs, which block the cell signalling pathways that drive the growth of tumour cells. However, tumours almost always develop resistance to treatment, leading to disease progression. In approximately two-thirds of patients treated with the approved EGFR-TKIs, gefitinib or erlotinib or afatinib, this resistance is caused by the secondary mutation, T790M. There are currently no targeted therapies approved for the treatment of tumours with this resistance mutation.

Marketing authorisation applications for AZD9291 for the treatment of EGFRm T790M NSCLC have been submitted to the US Food and Drug Administration (FDA), the European Medical Agency (EMA) and other regulatory authorities. Recently, the FDA granted Priority Review to AZD9291, adding to the Breakthrough Therapy designation, Orphan Drug and Fast Track status already assigned by the regulatory body. AZD9291 has also been granted Accelerated Assessment by the EMA.

About durvalumab (MEDI4736)

Durvalumab is an investigational human monoclonal antibody directed against programmed death ligand-1 (PD-L1). Signals from PD-L1 help tumours avoid detection by the immune system. Durvalumab blocks these signals, countering the tumour's immune-evading tactics. Durvalumab is being developed, alongside other immunotherapies, to empower the patient's immune system and attack the cancer. Durvalumab is being investigated in an extensive clinical trial programme, as monotherapy or in combination with tremelimumab, in NSCLC, head and neck, gastric, pancreatic, bladder and blood cancers.

About LYNPARZA™

Olaparib is an innovative, first-in-class oral poly ADP-ribose polymerase (PARP) inhibitor that exploits tumour DNA repair pathway deficiencies to preferentially kill cancer cells. This mode of action gives olaparib the potential for activity in a range of tumour types with DNA repair deficiencies.

Olaparib is the first PARP inhibitor to be approved for patients with germline BRCA-mutated advanced ovarian cancer, and has been launched in the U.S. and Europe, with ongoing regulatory submissions across multiple markets.

In Europe, ovarian cancer is the fifth most commonly diagnosed cancer in women and the sixth leading cause of cancer death among women. Up to 15% of women with ovarian cancer have a BRCA mutation, which is the most common cause of homologous repair deficiency (HRD).

In addition to ovarian cancer, AstraZeneca is investigating the full potential of olaparib in multiple tumour types, with Phase III studies in second line gastric cancer, BRCA-mutated pancreatic cancer and adjuvant and metastatic BRCA-mutated breast cancers underway.

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 medicines is focused on four main disease areas - lung, ovarian, 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 visitwww.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

CONTACTS

Media   Enquiries
Esra Erkal-Paler	UK/Global	+44 20   7604 8030
Vanessa Rhodes	UK/Global	+44 20   7604 8037
Ayesha Bharmal	UK/Global	+44 20   7604 8034
Karen Birmingham	UK/Global	+44 20   7604 8120
Jacob Lund	Sweden	+46 8 553 260 20
Michele Meixell	US	+1 302 885 2677
Investor Enquiries
UK
Thomas Kudsk Larsen	Oncology	+44 20 7604 8199	+44 7818 524185
Eugenia Litz	RIA	+44 20 7604   8233	+44 7884 735627
Nick Stone	CVMD	+44 20 7604 8236	+44 7717 618834
Craig Marks	Finance	+44 20 7604   8591	+44 7881 615764
Christer Gruvris		+44 20 7604   8126	+44   7827 836825
US
Lindsey Trickett	Oncology, ING	+1 301 398   5118	+1   240 543 7970
Mitch Chan	Oncology	+1 301 398 1849	+1   301 398 1849
Dial / Toll-Free		+1 301 398 3251	+1 866 381 7277

Key: RIA - Respiratory, Inflammation and Autoimmunity, CVMD - Cardiovascular and Metabolic Disease,

ING - Infection, Neuroscience and Gastrointestinal