Positive Phase IIa results from the EPICCURE trial demonstrated that AZD8601 met the primary endpoint of safety and tolerability in patients with heart failure. In the trial, researchers injected mRNA encoding vascular endothelial growth factor (VEGF-A) ? known as AZD8601 ? directly into the myocardium of patients undergoing elective coronary artery bypass surgery (CABG) surgery. AZD8601 is being co-developed with Moderna. In the study of 11 patients, seven were treated with AZD8601 and four received placebo injections. Trends were observed in the three exploratory efficacy endpoints: left ventricular ejection fraction (LVEF); NT-proBNP (a biomarker which measures the level of a hormone and is elevated in patients with heart failure); and functional patient reported outcomes, compared with placebo. VEGF-A is a paracrine factor important for new blood vessel formation. In addition, it has been shown to stimulate progenitor cell division, descendants of stem cells that when stimulated differentiate to create specialised cell types that contribute to repair and regeneration of the heart. Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, AstraZeneca, said: ?Over one billion heart cells can be lost during a heart attack. These early results indicate the potential of mRNA therapeutics in stimulating VEGF-A production to provide reparative and disease-modifying options for patients with heart failure and other ischaemic vascular diseases.? St?phane Bancel, Chief Executive Officer, Moderna, said: ?mRNA is a compelling therapeutic modality because of its ability to act locally and transiently, while driving dose-dependent protein expression. The results presented today are a result of pushing new boundaries in the treatment of cardiovascular and other ischaemic vascular diseases and address serious unmet needs with the goal of improving patients? lives.? Results from the EPICCURE trial were presented on 15 November 2021 at the American Heart Association?s Scientific Sessions 2021. Notes Heart failure Heart failure (HF) affects approximately 64 million people worldwide (at least half of whom have a reduced ejection fraction),^1,2?including approximately 15 million in the EU, six million in the US,^3,4?and seven million treated adults in China.⁵?It is a chronic disease where half of patients will die within five years of diagnosis.⁶?There are two main categories of HF related to ejection fraction (EF), a measurement of the percentage of blood leaving the heart each time it contracts: heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF).⁷?HFrEF occurs when the left ventricle muscle is not able to contract adequately and therefore, expels less oxygen-rich blood in to the body.^8,9?HF remains as fatal as some of the most common cancers in both men (prostate and bladder cancers) and women (breast cancer).¹⁰?Chronic HF is the leading cause of hospitalisation for those over the age of 65 and represents a significant clinical and economic burden.¹¹ EPICCURE EPICCURE is a Phase IIa randomised, double-blinded, multi-centre, placebo-controlled study in patients with stable coronary artery disease and moderately decreased LVEF who are undergoing CABG surgery. The primary endpoint was safety and tolerability of AZD8601. Seven patients received AZD8601 and four received placebo; all 11 were followed for six months to assess primary safety and exploratory efficacy endpoints. There were no deaths or treatment-related serious adverse events and no infections were observed related to the treatment of AZD8601. Exploratory efficacy endpoints included LVEF, NT-proBNP, and functional patient reported outcomes resulted in a positive trend for the treated group. Although the data is limited to show significant effect, it provides opportunity for AstraZeneca to move to further trials with AZD8601. AZD8601 AZD8601 is a novel, investigational mRNA-based therapy, with mRNA formulated in a citrate saline buffer in the absence of lipid encapsulation, that encodes for VEGF-A for local administration in patients undergoing CABG. mRNA is responsible for carrying genetic instructions transcribed from DNA, which cells then translate to produce proteins. Proteins are responsible for directing the body?s biological functions. Moderna?s pioneering mRNA therapeutics are designed to trigger the cellular machinery to produce specific proteins. In this application, AZD8601 may enable the delivery of mRNA instructions to spur the production of VEGF-A protein. AstraZeneca and Moderna Therapeutics collaboration AstraZeneca and Moderna Therapeutics have an exclusive agreement to discover, develop and commercialise pioneering messenger RNA therapeutics for the treatment of serious cardiovascular, metabolic and renal diseases as well as cancer. AstraZeneca brings unparalleled depth of understanding of cardiovascular disease biology and the discovery and development of medicines in this area, while Moderna brings advanced mRNA technology and the ability to engineer multiple different mRNAs into therapeutic proteins. AstraZeneca in CVRM Cardiovascular, Renal and Metabolism (CVRM), part of BioPharmaceuticals, forms one of AstraZeneca?s main disease areas and is a key growth driver for the Company. By following the science to understand more clearly the underlying links between the heart, kidneys and pancreas, AstraZeneca is investing in a portfolio of medicines for organ protection and improve outcomes by slowing disease progression, reducing risks and tackling co-morbidities. The Company?s ambition is to modify or halt the natural course of CVRM diseases and potentially regenerate organs and restore function, by continuing to deliver transformative science that improves treatment practices and CV health for millions of patients worldwide. 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 Disease, 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. Contacts For details on how to contact the Investor Relations Team, please?click here. For Media contacts,?click here.

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