NOVOHEART TIMELINE
2005
First genetically engineered human heart muscle cells derived from human embryonic stem cell by Dr. Ronald Li’s team
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.
Relevant Publications:
Ion channels in human pluripotent stem cells
Mass production of cardiomyocytes
Calcium handling of human pluripotent stem cell-derived cardiomyocytes
2007
Patented technology for driving maturation of human heart cells by Dr. Ronald Li’s team
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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Other Related Publications:
2008
First lab grown rat “heart-in-a-jar” by Dr. Kevin Costa
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)
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2008
Invention of Alignment technology – groundwork for the human ventricular Cardiac Anisotropic Sheet (hvCAS) by Drs. Ronald Li and Michelle Khine
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.
Relevant Publications:
2010
Rat engineered cardiac tissue – Precursor to human ventricular Cardiac Tissue Strip (hvCTS) by Dr. Kevin Costa
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)
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2013
First human “heart-in-a-jar” prototype created and tested by Dr. Ronald Li and Dr. Kevin Costa
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)
2014
Novoheart, was established in 2014 as a Medera’s subsidiary, to focus on Disease Modelling and Drug Discovery
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.
2014
First hvCTS published by Drs. Ronald Li and Kevin Costa
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)
Relevant Publications:
2014
Pfizer and Novoheart undertook a double-blinded drug screening study using the mini-Heart technology
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.
2015
First human “heart-in-a-jar” created in Li and Costa lab
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.
Relevant Publications:
For more detailed press release, please click here.
2016
First demonstration of gene editing to correct inherited cardiomyopathy in an engineered cardiac tissue strip model by Drs. Kevin Costa and Roger Hajjar
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.
Relevant Publications:
2016
First human mini-Heart models of Friedreich’s Ataxia was created by the collaboration of Novoheart and Pfizer
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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Relevant Press Releases:
2017
Novoheart was dual listed on Toronto and Frankfurt Stock Exchanges
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.
2017
Landmark Study Demonstrating the Use of Machine Learning to Accelerate Drug Screening
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 ).
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2017
Patent on Pioneering New Multi-organoid Bioreactor Platform
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)
Relevant Publications:
For more detailed press release, please click here.
2018
Development of a high-throughput cardiac contractility screening system with Amgen
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.
2019
Partnership with AstraZeneca to co-develop a human mini-Heart model of Heart Failure with preserved Ejection Fraction (HFpEF)
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
2020
Novoheart Named 2020 Venture 50 Company Ranked Among Year’s Top Performing Stocks in Life Sciences
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:
- 1. Share price: one-year share price change as of December 31, 2019
- 2. Trading: one-year trading volume as of December 31, 2019
- 3. Market capitalization: one-year market capitalization change as of December 31, 2019
2020
Novoheart was privatized, moved to the U.S. and restructured for tighter strategic relationship with Sardocor for creating a one-stop platform for disease modelling and drug discovery all the way to clinical trials
2021
An open IND from the FDA was granted to start First-In-Human gene therapy clinical trial for Heart Failure with preserved Ejection Fraction (HFpEF) based on Novoheart's human mini-heart data
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.
1997
First gene therapy proof-of-concept study performed in a rat model of heart failure by Dr. Roger Hajjar at Harvard University
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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1999
First translational gene therapy proof-of-concept study performed in cardiac cells isolated from failing human hearts isolated at the time of cardiac transplant by Dr. Roger Hajjar
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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2000
Dual gene therapy modulates excitability and contractility in guinea pig by Dr. Ronald Li and his colleagues
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.
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2005
Intracoronary delivery in pre-clinical pig models of heart failure by Dr. Roger Hajjar
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.
Relevant Publications:
Kawase Y, Ly HQ, Prunier F, Lebeche D, Shi Y, Jin H, Hadri L, Yoneyama R, Hoshino K, Takewa Y, Sakata S, Peluso R, Zsebo K, Gwathmey JK, Tardif JC, Tanguay JF, Hajjar RJ. Reversal of cardiac dysfunction after long-term expression of SERCA2a by gene transfer in a pre-clinical model of heart failure. J Am Coll Cardiol. 2008 Mar 18;51(11):1112-9. doi: 10.1016/j.jacc.2007.12.014. PMID: 18342232.
2006
Gene-Based Biological Pacemaker by Dr. Ronald Li’s team
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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Commentary:
Commentary:
2007
First-in-man gene therapy trial for heart failure in the U.S. by Dr. Roger Hajjar
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.
Relevant Publications:
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.
2016
IND approval for novel gene therapy to inhibit phosphatase activity in heart failure
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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2019
Drs. Roger Hajjar and Ronald Li co-founded Sardocor to develop next-generation gene therapies for heart failure and other difficult-to-treat diseases
2020
1000 doses of Sardocor’s gene therapy drug SRD001/2 are available for patient injection
2021
Sardocor was granted an open IND from the FDA to start gene therapy clinical trials for Heart Failure with preserved Ejection Fraction (HFpEF) and reduced Ejection Fraction (HFrEF)
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 Sardocor’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.
2022
Sardocor was granted another open IND from the FDA to start gene therapy clinical trials for DMD-related Cardiomyopathy
