Apabetalone treatment reduces SARS-CoV-2 infectivity and completely prevents cardiac damage in a cytokine-storm model
CALGARY, Alberta, March 03, 2021 (GLOBE NEWSWIRE) -- Resverlogix Corp. ("Resverlogix") (TSX:RVX) and QIMR Berghofer Medical Research Institute (“QIMR Berghofer”), one of Australia’s most successful medical research institutes, announced today the publishing of a new article providing evidence of apabetalone’s potential benefit on SARS-CoV-2 (COVID-19). The article, titled: “Bromodomain and Extraterminal Inhibition Blocks Inflammation-Induced Cardiac Dysfunction and SARS-CoV-2 Infection (Pre-Clinical)”, was published on the pre-print server, bioRxiv, at the request of the reviewing scientific journal.
The publication can be viewed using the following LINK.
“We are excited that we can finally share publicly some of the incredible early results of our collaborative COVID-19 research program,” said Donald McCaffrey, President and CEO of Resverlogix. “Not only does apabetalone treatment reduce SARS-CoV-2 infection in cardiomyocytes, but it also prevents cardiac dysfunction induced by cytokine-storm. These findings showcase the unique dual-mechanism of apabetalone as a potential therapeutic for COVID-19 and provide strong support for human trials.”
“I would like to commend our collaborators at QIMR Berghofer whom it has been a pleasure to work with,” said Dr. Ewelina Kulikowski, Senior Vice President, Research & Development at Resverlogix and a co-author of the article. “Collaborations such as this serve to quickly move our research forward for the benefit of patients.”
Repurposing Drugs to Treat COVID-19
“Many re-purposed drugs have failed in clinical trials for COVID-19,” said Associate Professor James Hudson, head of the Cardiac Bioengineering Research Group at QIMR Berghofer. “We sought a different approach to firstly understand mechanistically how COVID-19 could be driving cardiac dysfunction seen in many patients. After detailed studies we identified bromodomain-containing protein 4 as a key mediator of dysfunction and BET inhibitors were very effective at blocking this response. In the pursuit to translate these findings to the clinic, we formed a very exciting collaboration with Resverlogix to test apabetalone, which we also found was very effective in our models. It was a pleasure to work with Resverlogix and truly share information both ways, and contribute data for the basis of their clinical trials.”
Collaborative Support From Alberta Government
“This is another great example of an Alberta-based biotech company taking the fight to COVID-19,” said Doug Schweitzer, Minister of Jobs, Economy and Innovation for Alberta. “We have world-class researchers in our province that are creating internationally recognized products to save lives around the world. It is exciting to see this growing industry create solutions and jobs for Albertans.”
Publication Highlights include:
- Cardiac dysfunction is known to result from COVID-19 infection, increasing risk of mortality and serious complications
- BET inhibitors, including apabetalone, were evaluated for their ability to protect cardiac tissue from damage induced by COVID-19
- State-of-the-art models were employed, including human cardiac organoids and mouse models of cytokine-storm
- Apabetalone treatment was found to prevent cardiac dysfunction caused by inflammation
- Apabetalone treated heart cells showed decreased SARS-CoV-2 infectivity, and reduced expression of ACE2 (a receptor linked to the virus’ entry into human cells)
- In mouse models, BET inhibitors reduced cardiac injury resulting from cytokine-storm which translated to survival of all animals in the treatment group, compared to 75% mortality among the control group
Apabetalone, a FDA granted Breakthrough Therapy Designation (BTD) drug is an investigational, phase 3 clinical candidate with safety data in more than 4,000 subjects. Resverlogix has announced plans for an open-label study to assess the safety and efficacy of apabetalone in the treatment of COVID-19.
As previously announced, an article published on March 23, 2020 revealed the interaction between SARS-CoV-2 (COVID-19) protein E with BET proteins. Following this finding, Resverlogix put out a call for collaborations, resulting in multiple partnerships, and in parallel initiated in-house preclinical research to further characterize and investigate apabetalone’s efficacy in treating COVID-19 infection.
The work featured in this article is currently undergoing peer-review and is expected to be published in a scientific journal shortly. Additional publications are expected to result from ongoing COVID-19 research in the months to come.
About QIMR Berghofer
QIMR Berghofer is a world-leading, translational medical research institute based in Brisbane, Australia. Its research focuses on cancer, infectious diseases, mental health and a range of chronic disorders. Working in close collaboration with clinicians, other research institutes and the biotech sector, QIMR Berghofer’s aim is to improve human health by developing new and better diagnostics, treatments and prevention strategies.
Resverlogix is developing apabetalone (RVX-208), a first-in-class, small molecule that is a selective BET (bromodomain and extra-terminal) inhibitor. Apabetalone is the first therapy of its kind to have been granted US FDA Breakthrough Therapy Designation – for a major cardiovascular indication – to help facilitate a time-efficient drug development program including planned clinical trials and plans for expediting the manufacturing development strategy.
BET inhibition is an epigenetic mechanism that can regulate disease-causing genes. Apabetalone is a BET inhibitor selective for the second bromodomain (BD2) within the BET proteins. This selective inhibition of apabetalone on BD2 produces a specific set of biological effects with potentially important benefits for patients with high-risk cardiovascular disease, diabetes mellitus, chronic kidney disease, end-stage renal disease treated with hemodialysis, neurodegenerative disease, Fabry disease, peripheral artery disease and other orphan diseases, while maintaining a well described safety profile.
Resverlogix common shares trade on the Toronto Stock Exchange (TSX:RVX).
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This news release may contain certain forward-looking information as defined under applicable Canadian securities legislation, that are not based on historical fact, including without limitation statements containing the words "believes", "anticipates", "plans", "intends", "will", "should", "expects", "continue", "estimate", "forecasts" and other similar expressions. In particular, this news release includes forward looking information related to apabetalone as a potential therapeutic for COVID-19 and the potential role of apabetalone in the treatment of patients with cognitive disorders, high-risk cardiovascular disease, diabetes mellitus, chronic kidney disease, end-stage renal disease treated with hemodialysis, Fabry disease, peripheral artery disease and other orphan diseases. Our actual results, events or developments could be materially different from those expressed or implied by these forward-looking statements. We can give no assurance that any of the events or expectations will occur or be realized. By their nature, forward-looking statements are subject to numerous assumptions and risk factors including those discussed in our Annual Information Form and most recent MD&A which are incorporated herein by reference and are available through SEDAR at www.sedar.com. The forward-looking statements contained in this news release are expressly qualified by this cautionary statement and are made as of the date hereof. The Company disclaims any intention and has no obligation or responsibility, except as required by law, to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise.