AstraZeneca aims to transform the oncology treatment landscape with diverse early pipeline and novel combinations at AACR

28 March 2022 07:05 BST (Updated 30 March 2022) Clinical data in immuno-oncology and DNA damage response illustrate potential of next-wave medicines to advance cancer care First data for novel molecules show promising anti-cancer activity and showcase strategy to attack cancer from multiple angles AstraZeneca will present new data underscoring the breadth of the Company’s early oncology portfolio at the American Association for Cancer Research (AACR) Annual Meeting in New Orleans, 8 to 13 April 2022. Data from 60 presentations, including 5 oral and 3 mini-oral presentations, will feature the Company’s next wave of potential cancer medicines spanning its immuno-oncology (IO), DNA Damage Response (DDR) and Antibody Drug Conjugate (ADC) scientific platforms. This includes key data shared from three potential new medicines that illustrate the Company’s innovative approach to designing molecules that address key challenges in treating cancer, including the ability to target different, complementary mechanisms. Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “We are serious about leading a revolution in oncology, which is why we continue to pioneer new ways to target cancer earlier and with greater precision, for the benefit of patients. Our data at AACR from next-wave Immuno-Oncology medicines, PARP inhibitors and antibody drug conjugates demonstrate the potential of our diverse portfolio and reflect our vision to target cancer from every angle." Introducing the next wave of IO therapies The first clinical results will be shared for MEDI5752, a novel bispecific antibody, that simultaneously targets the immune checkpoint proteins PD-1 and CTLA-4, in solid tumours. Bispecific antibodies are a promising IO approach that combines the potential benefits of two medicines in one. MEDI5752 was engineered to achieve combined blockade of CTLA-4 and PD-1, to improve the therapeutic index when compared to targeting these proteins using two separate medicines. A presentation from the NeoCOAST randomised Phase II trial in resectable, early-stage non-small cell lung cancer will highlight improved disease responses with novel Imfinzi (durvalumab) combinations including with oleclumab, an anti-CD73 monoclonal antibody, and with monalizumab 1 , an anti-NKG2A checkpoint inhibitor, when compared to Imfinzi alone. Additionally, four presentations will describe novel molecules targeting interleukin-12 (IL-12) and leukaemia inhibitor factor (LIF) and illustrate the potential of targeting non-redundant mechanisms to modulate the immune tumour microenvironment. Building the next generation of PARP inhibitors The first data will be presented from the PETRA Phase I clinical trial investigating AZD5305, a next-generation PARP1-selective inhibitor, in patients with tumours harbouring specific homologous recombination repair gene mutations. AZD5305 is designed to selectively target PARP1, killing cancer cells by targeting tumour cell DNA damage repair mechanisms. This approach could allow PARP inhibitors to expand into new settings and offer new opportunities for combinations with DNA damage pathway activating agents such as ADCs. Preclinical data will be presented that support this hypothesis showing the activity of Enhertu (trastuzumab deruxtecan) in combination with DDR agents including PARP1-selective inhibitors. AstraZeneca is collaborating with Daiichi Sankyo Company, Limited (Daiichi Sankyo) to develop and commercialise Enhertu globally. Additionally, four presentations will describe the discovery of AZD9574, a novel PARP1 selective inhibitor designed to cross the blood brain barrier to enable the targeting of primary and secondary brain malignancies. Innovative approaches to deliver a next-wave ADC The first preclinical data will be shared on AZD8205, a novel ADC targeting B7-H4, a protein overexpressed in a range of solid tumours. This molecule is the first ADC to incorporate AstraZeneca’s proprietary linker technology, demonstrating the Company’s progress in establishing in-house ADC expertise and building leadership in this field. Key AstraZeneca presentations during AACR 2022 Presenting author Abstract title Presentation details IO Tran, B MEDI5752, a novel PD-1/CTLA-4 bispecific checkpoint inhibitor for advanced solid tumors: First-in-human study Abstract #CT016 Oral Session CTPL04 - Combination Immunotherapy Clinical Trials 12 April 2022 11:46 – 12:01 CDT Cascone, T NeoCOAST-2: a randomized, open-label, phase 2 study of neoadjuvant durvalumab plus novel immunotherapies and chemotherapy (CT) followed by adjuvant durvalumab plus novel agents, in patients with resectable non-small-cell lung cancer (NSCLC) Abstract #CT124 / 6 Poster – Trial in progress (TiP) Session PO.CT02.03 - Phase II Trials in Progress 11 April 2022 09:00 – 12:30 CDT Cascone, T NeoCOAST: open-label, randomized, phase 2, multidrug platform study of neoadjuvant durvalumab alone or combined with novel agents in patients (pts) with resectable, early-stage non-small-cell lung cancer (NSCLC) Abstract #CT011 Oral Session CTPL03 - Neoadjuvant and Perioperative Immunotherapy Clinical Trials 11 April 2022 11:16 – 11:31 CDT Shrestha, P Durvalumab (D) + platinum-etoposide (EP) in 1L extensive-stage small-cell lung cancer (ES-SCLC): Exploratory analysis of SCLC molecular subtypes in CASPIAN Abstract #CT024 Mini-oral Session CTMS01 - Biomarker Advances in Clinical Trials 10 April 2022 15:50 – 160:00 CDT Reinmuth, N Durvalumab (D) plus tremelimumab (T) in platinum-refractory/resistant extensive-stage small cell lung cancer (ES-SCLC): Efficacy, safety and ctDNA dynamics from Arm A of the phase 2 BALTIC study Abstract #CT533 Poster – Clinical Trial Session OPO.CT02.01 - Phase II Clinical Trials 8 April 2022 12:00 – 13:00 CDT Fayette, J INTERLINK-1: A phase 3, randomized, double-blind, placebo-controlled, multicenter, global study of monalizumab in combination with cetuximab in patients with recurrent or metastatic head and neck squamous cell carcinoma previously treated with an immune checkpoint inhibitor Abstract #CT236 / 7 Poster – TiP Session PO.CT03.02 - Phase III Trials in Progress 12 April 2022 13:30 – 17:00 CDT Carneiro, BA First-in-human study of MEDI1191 (mRNA encoding IL-12) plus durvalumab in patients (pts) with advanced solid tumors Abstract #CT183 / 8 Poster – Clinical Trial Session PO.CT01.02 - Phase I Clinical Trials 2 12 April 2022 09:00 – 12:30 CDT O’Kane, G A phase 2 trial of first-line AZD0171 + durvalumab and chemotherapy (CT) in patients with metastatic pancreatic ductal adenocarcinoma (PDAC) and CD8+ T cell infiltration Abstract #CT126 / 9 Poster – TiP Session PO.CT02.03 - Phase II Trials in Progress 11 April 2022 09:00 – 12:30 CDT Purroy, N First-in-human trial of intravenous MEDI9253, an oncolytic virus, in combination with durvalumab in patients with advanced solid tumors Abstract #CT218 / 18 Poster – TiP Session PO.CT01.03 - Phase I Trials in Progress 1 12 April 2022 09:00 – 12:30 CDT Candido, J AZD0171 (anti-LIF) combines productively with chemotherapy and anti-PD-L1 in mouse models of cancer Abstract #1293 / 3 Poster Session PO.IM02.08 - Immune Mechanisms Invoked by Other Therapies 11 April 2022 09:00 – 12:30 CDT DDR Yap, TA PETRA: First in class, first in human trial of the next generation PARP1-selective inhibitor AZD5305 in patients (pts) with BRCA1/2, PALB2 or RAD51C/D mutations Abstract #CT007 Oral Session CTPL02 - Clinical Trials Targeting the DNA Damage Response and KRAS 10 April 2022 16:01 – 16:16 CDT Pike, A Evaluation of the CNS penetration of a next generation PARP inhibitor, AZD9574, in cynomolgus monkey using positron emission tomography Abstract #5076 Poster Session OPO.CH01.01 - Drug Discovery, Design, and Delivery 8 April 2022 12:00 – 13:00 CDT Davies, BR AZD9574 is a novel, brain penetrant PARP-1 selective inhibitor with activity in an orthotopic, intracranial xenograft model with aberrant DNA repair Abstract #2609 / 22 Poster Session PO.ET04.02 - DNA Damage Response and Repair 12 April 2022 09:00 – 12:30 CDT Ghosh, A Structure-based and property-based drug design of AZD9574, a CNS penetrant PARP1 selective inhibitor and trapper Abstract #6302 Poster Session OPO.CH01.01 - Drug Discovery, Design, and Delivery 8 April 2022 12:00 – 13:00 CDT Schou, M Discovery and preclinical validation of [ 11 C]AZ3391: A first in class blood-brain barrier permeable, subtype selective PARP-1 PET radioligand Abstract #5977 Poster Session OPO.TB07.01 - In Vivo Imaging 8 April 2022 12:00 – 13:00 CDT Shapiro, GI Ceralasertib and olaparib in the treatment of homologous recombination repair (HRR)-deficient platinum-sensitive ovarian cancer after progression on PARP inhibitors Abstract #CT201 / 1 Poster – TiP Session PO.CT01.03 - Phase I Trials in Progress 1 12 April 2022 09:00 – 12:30 CDT ADCs Kinneer, K Discovery and first disclosure of AZD8205, a B7-H4-targeted antibody-drug conjugate utilizing a novel topoisomerase I linker-warhead Abstract #1765 / 17 Poster Session PO.ET01.04 - Antibody-Drug Conjugates 11 April 2022 13:30 – 17:00 CDT Wortmann, P Development and implementation of image analysis-based Quantitative Continuous Score (QCS) for B7-H4 IHC to understand AZD8205 pharmacodynamics Abstract #452 / 3 Poster Session PO.BCS02.02 - Artificial Intelligence and Digital Pathology 10 April 2022 13:30 – 17:00 CDT Wallez, Y Activity and tolerability of combinations of trastuzumab deruxtecan (T-DXd) with inhibitors of the DNA damage response in preclinical models Abstract #5298 Poster Session OPO.ET07.01 - Biological Therapeutic Agents 8 April 2022 12:00 – 13:00 CDT Mettetal, J Activity and tolerability of combination of trastuzumab deruxtecan with the next generation PARP1-selective inhibitor AZD5305 in preclinical models Abstract #1142 / 6 Poster Session PO.ET05.02 - Preclinical and Clinical Pharmacology 11 April 2022 09:00 – 12:30 CDT 1 AstraZeneca obtained full oncology rights to monalizumab from Innate Pharma in October 2018 through a co-development and commercialisation agreement initiated in 2015 Notes AstraZeneca in oncology AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients. The Company’s focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyse changes in the practice of medicine and transform the patient experience. AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death. AstraZeneca AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on Twitter @AstraZeneca . 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