AstraZeneca partners with Medera’s Novoheart on
First Bioengineered Human Models of
Heart Failure with Preserved Ejection Fraction
- Heart failure is a global pandemic affecting at least 64 million people worldwide and costing over US$100B per year
- Heart failure with preserved ejection fraction (HFpEF) accounts for half of all heart failure cases, and is a growing problem with limited treatment options
- There is a lack of effective human-specific models for preclinical testing of targeted therapeutic candidates for HFpEF
- The AstraZenceca-Novoheart collaboration has successfully generated the world’s first bioengineered HFpEF miniature human heart models
- Forced expression of a down-regulated gene product identified in HFpEF reverses the disease phenotype in our bioengineered heart models
- HFpEF mini-hearts could provide a powerful tool for discovery, screening, and advancement to clinical trials of novel therapeutics for heart failure
Heart failure (HF) is a global pandemic2, with an increasing trend in prevalence3. The annual global economic burden of HF is estimated at over US$100 billion4. HFpEF accounts for approximately 50% of HF cases and is a major and growing public health problem worldwide. However, the pathological mechanisms and diverse causes of HFpEF remain poorly understood. Due to these complexities, previous models of the disease, including various investigational models, have shown limited ability to mimic the clinical presentation of HFpEF5. Therefore, drug developers have lacked predictive tools for preclinical testing of drug candidates for efficacy. As a result, clinical outcomes for HFpEF have hardly improved over the last several decades and limited treatment options are available to patients.
The Cardiovascular, Renal and Metabolism therapy area of AstraZeneca has worked with Medera’s Novoheart to use its proprietary mini-HeartTM Platform for human cardiac tissue engineering to successfully establish novel in vitro models that reproduce key phenotypic characteristics, including relaxation defects, fibrosis and hypertrophy, as seen in patients with HFpEF. Also known as “human heart-in-a-jar”, the 3-D human ventricular cardiac organoid chamber (hvCOC) is the only human engineered heart tissue available on the market that enables clinically informative assessments of human cardiac pump performance including ejection fraction and developed pressure.6 Unlike animal models, engineered human heart-in-a-jar can be fabricated with specific cellular and matrix compositions, and patient-specific human induced pluripotent stem cells (iPSCs), that allow control over the physical and mechanical properties to uniquely mimic those observed in HFpEF patient hearts. Novoheart has also developed human cardiac fibre-like HFpEF cardiac tissue strips (CTS) that recapitulate the effects of HFpEF on cardiac muscle stiffness and contractility.
To facilitate the research, Novoheart has also developed CTScreenTM proprietary hardware and software for automation that increases the throughput, accuracy and sensitivity of phenotypic and drug screening experiments using the engineered human heart-in-a-jar and hvCTS assays.
Collectively, these innovative HFpEF human heart models and related tools have provided a unique assay for understanding the mechanisms of HFpEF, identifying new therapeutic targets, and assessing novel therapeutics for treating HFpEF patients. Novoheart exclusively owns the intellectual property rights to the newly developed HFpEF models. This work is being submitted for publication in a peer-reviewed scientific journal.
Regina Fritsche Danielson, Senior Vice President, Head of Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, said, “At AstraZeneca, we recognize the urgent need to learn more about the underlying mechanisms of HFpEF in our ambition to develop targeted therapies for this population of patients. Our collaboration with Novoheart to build the first in vitro HFpEF models will help us bridge the gap between animal models and clinical trials to accelerate the drug discovery process by providing human-specific preclinical data.”
“These new HFpEF versions of our human heart-in-a-jar and hvCTS assays, developed in our ongoing collaboration with AstraZeneca, demonstrate the capability of Novoheart’s mini-HeartTM Platform for modelling complex acquired diseases such as heart failure, that are even more challenging than well-defined and rare genetic mutations,” said Novoheart CSO, Dr. Kevin Costa.
“The US FDA Modernization Act 2.0 aims to accelerate innovation and get safer, more effective drugs to patients more quickly by encouraging the use of scientifically superior, human-based technologies to animal testing while improving the human accuracy for better successes. Along this line, we are totally excited about the new HFpEF human mini-heart models. We are now focusing on their translation into tangible patient benefits,” said Medera CEO, Dr. Ronald Li.
1 Heart Fail Clin. 2014; 10(3):377–388.
2 Lancet 2017; 390(10100):1211–59.
3 Lancet. 2018; 392:1789-1858.
4 Int J Cardiol. 2014; 171(3):368-76.
5 JACC Basic Transl Sci. 2017; 2(6):770-789.
6 Biomaterials. 2018; 163:116-127.
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 www.astrazeneca.com and follow the Company on Twitter @AstraZeneca.
Founded in 2014, Medera is a leading clinical stage company with a mini-Heart-based drug discovery platform and a clinical pipeline focusing on the development of next-generation therapeutics for difficult-to-treat and incurable diseases. Medera has two subsidiaries, namely Novoheart and Sardocor. Novoheart capitalizes on the world’s first and award-winning “mini-Heart” Technology for revolutionary disease modelling and drug discovery. This platform enables us to uniquely model human-specific diseases and discover therapeutic candidates in the context of human cells and tissues, free from species-specific differences. Sardocor aspires to create the shortest regulatory path to clinic for advancing effective next-generation cell and gene therapies. Building upon Novoheart’s bioengineered human tissue-based assays for disease modelling and drug discovery, Sardocor has developed one of the world’s largest gene and cell-based therapeutic pipelines for a range of cardiac, vascular and muscular diseases such as heart failure with preserved ejection fraction, Duchenne muscular dystrophy and pulmonary hypertension, etc. For more information, please visit www.medera.bio