by medera | Dec 2, 2022 | Press Release
Sardocor is a subsidiary fully owned by Medera Medera’s Sardocor Announces FDA Clearance of IND for First-in-Human Gene Therapy Clinical Trial for DMD Cardiomyopathy With modern therapeutic strategies to prolong life expectancy, an increasing number of Duchenne...by medera | Nov 22, 2022 | Press Release
Sardocor is a subsidiary fully owned by Medera Medera’s Sardocor Announces FDA Clearance of Investigational New Drug Application and Initiation of First-In-Human Gene Therapy Clinical Trial for Heart Failure with Preserved Ejection Fraction (HFpEF) Heart failure is a...by medera | Oct 27, 2022 | Press Release
Novoheart is a subsidiary fully owned by Medera Medera’s Novoheart partners with AstraZeneca 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...by mintywebs | Feb 20, 2020 | Press Release
Novoheart is a subsidiary fully owned by Medera Novoheart Named 2020 Venture 50 Company Ranked Among Year’s Top Performing Stocks in Life Sciences Novoheart Among Top 10 TSX-V Performers in Clean Technology & Life Sciences Sector Ranking based on share price...by mintywebs | Jan 21, 2020 | Press Release
Novoheart is a subsidiary fully owned by Medera Novoheart Contracts with Global Pharma to Develop Novel Microplate for High Throughput Drug Screening Using Engineered Human Heart Tissue Strips New 96-Well Microplates (hvCTS-96) to Further Advance MyHeartTM Platform...by mintywebs | Jan 7, 2020 | Press Release
Novoheart is a subsidiary fully owned by Medera Continued Success of Novoheart to Receive R&D Grants: Innovation Technology Fund for Developing Smart Cardiac Screening Technologies Grant will fund advanced R&D and incorporation of artificial intelligence...
Central Nervous System is the processing centre of the body and consists of the brain and the spinal cord. Both of these are protected by three layers of membranes known as meninges.
Liver is the largest internal organ in the body. It is essential for digestion of food and elimination of toxic substances from the body. Liver problems can be caused by a variety of genetic and non genetic factors such as viruses, alcohol use and obesity. Damage of the liver can lead to liver failure, and a build up of toxin in the blood leading to life threatening conditions.
Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system that are mostly attached by tendons to bones of the skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscle tissue, and are often known as muscle fibers. The muscle tissue of a skeletal muscle is striated – having a striped appearance due to the arrangement of the sarcomeres.
In 2017, Novoheart filed a patent application with the United States Patent and Trademark Office (USPTO) for a versatile bioreactor platform for culturing, stimulating, and monitoring the function of multiple engineered human-tissue organoids. The proprietary bioreactor system, combines hardware for organoid maintenance, intervention, and monitoring, together with customized software for seamless data processing and analysis. The system, is designed to increase throughput, deliver strengthened consistency, and extend stimulation and monitoring capabilities. The modular design of the bioreactor allows multiple organoids to be combined for increased throughput of the semi-automated culture and testing process. Ultimately, the new technology enhances Novoheart’s capacity and further expands its ability to identify promising bioactive therapeutics, classify toxicity of unknown drugs and pioneer innovative methods of addressing diseases or disorders.
This technology applies to other mini-organs such as mini-Liver, -Lungs, -Gut, -Vasculature, etc, with circulation powered by the mini-Heart, that forms the basis of our mini-Life Platform. (Learn more details for the mini-Life Platform)
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For more detailed press release, please click here.
To fully optimize the highly accurate, content-rich data generated from Novoheart’s mini-Heart Technology for detecting cardiac toxicity or efficacy, the Company has invested in developing machine learning capabilities to speed up the analysis of multiparametric drug screening data, enabling unbiased and automated drug classification. In doing so, it is able to facilitate new levels of automation and throughput in data analysis. This technology enables researchers to develop new and innovative ways for determining the effects of new as well as previously disregarded drugs on human subjects. The technology continues to advance and update as part of our software package for automation (Learn more details for the CTScreen ).
Friedreich’s ataxia (FRDA) is a hereditary neuromuscular degenerative disease that affects over 1 in 50,000 people worldwide. FRDA patients have a defective Frataxin gene, which often leads to lethal heart complications. In 2016, Novoheart teamed up with Pfizer’s Rare Disease Unit to generate a species-specific, functional in vitro experimental models of FRDA using our mini-Heart technology. The new disease models were created using genetically modified as well as FRDA patient-derived cells, capturing both electrical and mechanical defects of the heart observed in FRDA patients. This new approach marks an important step away from using animals as traditional testing models which have limited predictive ability for drug discovery due to dramatic differences in both the genetics and physiology.
In 2018, Novoheart filed a patent application based on our proprietary mini-Heart Platform of human bioengineered heart tissues to create disease models for ataxia affecting the heart. The disease models will benefit patients and drug developers by providing a unique and robust platform for testing candidate therapeutics.
Novoheart and Pfizer subsequently co-published the result of the study in 2019.
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Based on the scientific invention made in Dr. Roger Hajjar’s laboratory, AskBio was granted an IND approval for a novel gene therapy with a re-engineered vector designed to inhibit phosphatase activity in heart failure with reduced ejection fraction (HFrEF). After injecting 8 patients in the clinical trial, AskBio was subsequently sold to Bayer for $4billion USD in 2020. The same delivery method in Celladon’s first-in-man gene therapy trial (Learn more details in 2007) was also used in this trial.
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In 2014, Novoheart collaborated with Pfizer’s Global Safety Pharmacology Unit to systematically examine the pharmacological responses of engineered human ventricular-like Cardiac Tissue Strips (hvCTS) and Organoid Chambers (hvCOC) of the mini-Heart technology, to 25 cardioactive compounds covering various drug classes. We further quantified the predictive capacity of our mini-Heart technology in a blinded screening, with accuracies for negative, positive, and null inotropic effects at 100%, 86%, and 80%. Our healthy “human heart-in-a-jar” confirmed the results and further revealed that the more adult-like heart characteristics result in a greater sensitivity to positive inotropic drugs that stimulate cardiac contractility. The findings led to a two-tiered screening strategy that can provide an improved drug discovery approach to better predict clinical outcomes. Since the publication of this study in 2019, the accuracy for all 3 classes of inotropes have now reached 100%.
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For more detailed press release, please click here.
In 2014, Drs. Ronald Li and Kevin Costa reported the first human ventricular Cardiac Tissue Strip (hvCTS). This published study helped advance the field of human cardiac tissue engineering by examining 3D hvCTS created from enriched human embryonic stem cell-derived cardiomyocytes obtained using an efficient small molecule-mediated directed differentiation. Expanding the characterization of hvCTS using multiple complementary testing platforms, known drug responses were validated with natural human cardiac muscle. (Learn more details)
Drs. Ronald Li, Kevin Costa, and Michelle Khine co-founded Novoheart to transform the drug development process using bioartificial human heart prototypes created with state-of-the-art stem cell and bioengineering approaches.
In 2006, Dr. Ronald Li’s group at Johns Hopkins published a series of studies which employed a complementary set of stem cell and gene transfer technologies to construct a biological pacemaker, that was tested in rats, guinea pigs and subsequently side-by-side with electronic pacemakers in mini-pigs. The study won American Heart Association’s Ground-breaking Study of the Year in 2006, and was highlighted in an editorial commentary by Harvard scientists. This effort evolved and a related NIH grant subsequently received a top 1% percentile ranking in the study section of Electrical Signaling, Ion Transport, and Arrhythmias Study Section (ESTA) in 2009, and formed the basis of Dr Li’s subsequent work in cardiac cell and tissue engineering.
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In 2005, Dr. Roger Hajjar further developed the gene delivery technique and subsequently translated it to a pig model of heart failure, showing a reversal of cardiac dysfunction after intracoronary delivery (i.e., directly into the heart through the coronary arteries) of a recombinant adeno-associated virus (AAV). The success in the pig model, whose cardiovascular system is similar to human, formed the basis of the FDA-approved delivery protocol that Sardocor is using today for patients.
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In 2000, Dr. Ronald Li and his colleagues at Johns Hopkins University directly injected an engineered adenovirus carrying two genes, SERCA1a and Kir2.1, into the heart of the guinea pig heart to simultaneously modulate cardiac excitability and contractility. The study demonstrates the feasibility of using a dual gene therapy to correct contractile abnormalities and prevent arrhythmias.
Dr. Roger Hajjar’s laboratory demonstrated that cardiac myocytes isolated from human explanted hearts of cardiac transplant that were exhibiting depressed contractility can be rescued by increased SERCA2a activity either by gene transfer of SERCA2a or by decreasing phospholamban expression.
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In 2018, Novoheart contracted with Amgen to further expand its current testing capabilities of the mini-Heart Technology by designing and developing a new versatile High-Throughput microplate which allows the screening of hundreds of drugs using engineered human ventricular Cardiac Tissue Strips (hvCTS). Termed the 96-well μCTS, the disposable microplate is a custom-designed plate with 96 “wells” used to simultaneously cultivate 96 individual miniature hvCTS. The first prototype of 96-well μCTS was completed in 2020. The Company is now continuing this work to develop a next-generation version of the 96-well μCTS to increase its compatibility with robotic plate handling and automated high-throughput screening technologies that have become industry-standard facilities in big pharma laboratories. (Learn more details for the CTScreen).
For more detailed press release, please click here.
In 2008, inspired by the children’s toy Shrinky Dinks, Dr. Ronald Li and Dr. Michelle Khine co-invented a new micropatterning technology for systematically aligning human heart cells to reproduce their pattern in the native heart. This technology lays the foundation for the human ventricular Cardiac Anisotropic Sheet (hvCAS) (Learn more details for the mini-Organs Products). Dr. Khine’s inventions won her numerous honours including Innovators Under 35 by MIT Technology Review and Marie Claire Women on Top Award, and Fellow of the National Academy of Inventors.
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In 2007, Dr. Ronald Li’s team patented an invention for driving the maturation of stem cell-derived human heart cells. Like a molecular time tunnel, this invention facilitates the use of these heart cells for drug screening and heart regeneration.
In 2014, the team patented another technology for driven maturation of stem cell-derived human heart cells without the need for genetic manipulation. These two inventions form the basis of our collaboration with Stanford University and AstraZeneca today.
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Medera’s human ventricular Cardiomyocytes (hvCMs) are terminally differentiated cardiomyocytes derived from human pluripotent stem cells (hPSCs) using Medera’s proprietary differentiation method. These cells have been extensively characterized for their electrophysiology, calcium homeostasis, transcriptome, microRNAome, and proteome.
They exhibit ventricular-like action potentials and express ventricular-specific myosin light chain MLC2v. With virtually homogeneous ventricular properties, these cells provide the consistency necessary to achieve reliable and reproducible results in downstream applications.
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Li, R. A. Cardiovascular regeneration. Stem Cell Res Ther. 5, 141 (2014).
Contractile performance is an essential function of the human heart, yet conventional 2-D cardiomyocyte cultures are inadequate for assessing contractility as they cannot perform physiological contractions on rigid plasticware. Tissue engineering offers a superior contractile assay in the form of Medera’s human ventricular Cardiac Tissue Strip (hvCTS), which is structurally and functionally similar to native trabecular muscle. This assay consists of aligned hvCMs in 3-D hydrogel mixture that is constructed using Medera’s custom-designed bioreactor with integrated force-sensing posts at the ends. This model has been validated as a sensitive and reliable predictor of clinical effects of drugs or pathologies on cardiac contractility.
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Effective modelling of arrhythmias in vitro is challenging: by definition they are multicellular events that can only be recorded by monitoring conduction patterns in electrically coupled cardiomyocytes. Conventional assays can only use surrogate markers for arrhythmia: the hERG assay, standard in the industry, for example, uses inhibition of a single potassium channel exogenously expressed in non-cardiac cell lines as an indicator for proarrhythmic risk. Although these remain the standard tests for arrhythmogenicity, global drug regulators recognize their pitfalls and are actively seeking better alternatives, notably in the Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative of the FDA. Human pluripotent stem cell-derived cardiomyocytes are inherently prone to arrhythmic events when cultured as randomly oriented monolayers. Medera’s human ventricular Cardiac Anisotropic Sheet (hvCAS) assay utilizes specially designed microgrooved substrates that physically guide hvCMs to align in a similar manner to that in the native human ventricle. The aligned cells show anisotropic electrical conduction which has been validated to reduce the baseline arrhythmogenicity compared to monolayers without a cardiomimetic preferential conduction axis.
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Medera’s fluid-ejecting 3-D human ventricular Cardiac Organoid Chamber (hvCOC), a.k.a. “human heart-in-a-jar” is the only technology available to date that enables the clinically informative assessment of human cardiac pump performance which no other human engineered heart tissues on the market are capable of. Combined with complementary custom-designed hardware and software, the best-in-class “human heart-in-a-jar” allows drug screening and disease modelling with unprecedented biofidelity.
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In 2021, an open IND is granted from the FDA for Sardocor to start gene therapy clinical trials for Heart Failure with reduced Ejection Fraction (HFrEF) and preserved Ejection Fraction (HFpEF) in the US.
Sardocor’s HFpEF gene therapy trial will be the first-in-class.
The first patient with severe HFrEF was injected by intracoronary means with Medera’s first gene therapy drug SRD-001/2 in Dec 2021. As of April 2022, there have been no adverse events or safety concerns, as assessed by the Safety Committee.
Novoheart was named a 2020 Venture 50 Company, ranked among the TSX Venture Exchange’s top 50 best performing companies.
The ranking comprises ten companies from each of five key industry sectors. Novoheart is one of the ten best performers within the Clear Technology and Life Sciences sector.
Ranking was based on three equally weighted criteria:
There are two main types of heart failure – Heart Failure with reduced Ejection Fraction (HFrEF) and Heart Failure with preserved Ejection Fraction (HFpEF) which accounts for roughly half of all new cases of heart failure. In recent years, new therapies have been introduced for HFrEF which reduce deaths and hospitalization due to the disease. But these drugs do not work as well in HFpEF. Research is much needed to identify alternative strategies for treating HFpEF, and reliable animal models of the disease are lacking. To achieve this goal, Novoheart has teamed up with AstraZeneca to build preclinical human models of HFpEF designed to understand the disease mechanism, and predict the effects of potential medicines, bringing the most promising agents into clinical trials. This in vitro model builds on Novoheart’s heart-in-a-jar from the mini-Heart technology and will be used to test new therapies.
For more detailed press release, please click here.
AstraZeneca Testimonial
https://www.astrazeneca.com/what-science-can-do/topics/disease-understanding/making-the-connection-targeting-multiple-mechanisms-in-heart-failure.html
In 2019, Novoheart announced an exclusive licensing agreement with Harvard University’s Office of Technology Development to combine its state-of-the-art mini-Heart Platform with Harvard’s pioneering tissue-engineered scale model of the heart ventricle and related bioreactor technology. By integrating Harvard’s valved bioreactor technology with Novoheart’s proprietary human heart-in-a-jar, Novoheart will advance its disease modelling capabilities including modelling of highly prevalent heart diseases such as dilated cardiomyopathy and hypertrophic cardiomyopathy, for improved discovery of new therapeutics targeting such diseases.
For more detailed press release, please click here.
Novoheart was selected as one of “The Top 50 of Innovative Biotechnology Enterprises in Guangdong-Hong Kong-Macau Greater Bay Area 2018”, as one of 5 enterprises from Hong Kong on the list.
The award ceremony was held in Guangzhou on September 7, 2018. The selection is co-organized by ZDVC Research, KPMG China and the Guangdong Medical Valley. The selection process lasted for three months, led by a panel of advisors from government agencies, third-party research organizations, professional investment entities and medical institutions.
Novoheart Holdings Inc., was listed in Canada on TSX Venture Exchange (NVH:V) on October 3, 2017. The company announced its dual listing in Germany on Tradegate Exchange under ticker 3NH (ISIN: CA67011V1076) on October 18, 2017.
Drs. Kevin Costa and Roger Hajjar published a study in the European Heart Journal demonstrating for the first time that gene editing to correct the PLN-R14del mutation in iPSCs from patients carrying this variant of the phopholamban gene was able to restore contractile function of engineered cardiac tissue strips to match tissues from healthy donors. This could lead to new gene therapy strategies for these patients who suffer severe and early onset dilated and arrhythmogenic cardiomyopathy.
In 2015, the first human “heart-in-a-jar” was successfully created and measured in the Li and Costa Labs. This ground-breaking technology received much attention from global news media, including BBC World, Bloomberg, CNBC etc. To this day, Novoheart remains the only company on the market with the “human heart-in-a-jar” technology.
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For more detailed press release, please click here.
By combining the joint expertise of Drs. Ronald Li and Kevin Costa in cell and tissue engineering, and electrophysiology and mechanobiology, respectively, and after 4 years of effort, the world’s first human mini-heart prototype was successfully created and tested. The scientific work was published in 2015. (Learn more details in 2015)
In 2010, Dr. Kevin Costa began his research in creating engineered cardiac tissues with rat neonatal ventricular cardiomyocytes. In 2012, he reported these results together with a system that was created to examine the contractile function of these rat cell-derived Engineered Cardiac Tissues (ECTs), a precursor to human ventricular Cardiac Tissue Strip (hvCTS). (Learn more details in 2014)
At Columbia University, Dr. Kevin Costa embarked on the development of a rat mini-heart. In 2007, he was awarded funding from the National Institutes of Health (NIH) in the US as the top 1% percentile ranked grant of the year. In 2008, he published on the first-generation rat mini-heart, a precursor to the human “heart-in-a-jar”. A year later, he started collaborating with Dr. Ronald Li to design the world’s first human “heart-in-a-jar” by combining their expertise in cardiac cell and tissue engineering, mechanobiology, electrophysiology and human stem cell derived cardiomyocytes. (Learn more details in 2015)
Using the delivery technique invented by Dr. Roger Hajjar at Massachusetts General Hospital/Harvard (Learn more details in 1997), Celladon obtained a US FDA approval in 2007 to launch the world’s first-in-man gene therapy trial to target heart failure by directly injecting an engineered adeno-associated virus (AAV) containing the SERCA gene into the coronary arteries. Having been used by Celladon, Asklepios Biopharmaceutical (AskBio, which was later acquired by Bayer), (Learn more details in 2016) and Sardocor, this delivery method has been proven both safe and effective in human.
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Celladon’s trial did not succeed to meet the clinical endpoints, however, because they were using doses, as allowed by FDA at the time, that were as much as 30-100X lower than what are typically used by today’s gene therapy companies. In general, the gene therapy field has advanced very significantly from the lessons learned in the past 20 or so years.
In the beginning of the Millennium, Dr. Ronald Li’s group at the Johns Hopkins University produced the world’s first genetically engineered human embryonic stem cells (hESC)-derived heart cells via lentivirus-mediated bioengineering. This was later awarded the American Heart Association’s Best Basic Study of the Year Award (2005). However, the efficiency of deriving heart cells from hESCs at the time was only 0.5%. This seminal report formed the basis for subsequent studies, including the first to discover the central importance of calcium handling in stem cell-derived cardiomyocyte function, the presence of ion channels in human pluripotent stem cells, the development of methods for mass production of cardiomyocytes, etc.
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Ion channels in human pluripotent stem cells
Mass production of cardiomyocytes
Calcium handling of human pluripotent stem cell-derived cardiomyocytes
At Harvard University, Dr. Roger Hajjar published his first study on gene therapy in 1997. Dr. Hajjar tested the effect of adenovirus-mediated transfer of the SERCA2a gene to modify calcium handling and contraction in isolated myocytes of a rat model of heart failure.
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Restenosis is when a part of the artery that was previously treated for blockage becomes narrow again.
Arteriovenous Fistula Failure occurs when the fistula surgically created for hemodialysis treatments is never usable or fails within the first three months of its use.
Pulmonary hypertension is high blood pressure in the blood vessels that supply the lungs (pulmonary arteries). It occurs when walls of the pulmonary arteries become thick and stiff, and cannot expand as well to allow blood through. The reduced blood flow makes it harder for the right side of the heart to pump blood through the arteries, causing damage to the right heart.
Pulmonary fibrosis means scarring in the lungs. Over time, the scar tissue blocks the movement of oxygen from inside the tiny air sacs in the lungs into the bloodstream, causing people who have pulmonary fibrosis to feel short of breath, particularly when walking and exercising.
Heart failure with preserved ejection fraction (HFpEF) is a form of heart failure with high left ventricular (LV) filling pressure despite normal or near normal LV ejection fraction.
Heart failure with reduced ejection fraction (HFrEF) occurs when the left ventricular ejection fraction (LVEF) is 40% or less and is accompanied by progressive left ventricular dilatation and adverse cardiac remodelling.
Duchenne muscular dystrophy (DMD) is a genetic disorder characterized by progressive muscle degeneration and weakness due to the alterations of a protein called dystrophin that helps keep muscle cells intact.
