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Apabetalone Treatment Prevents COVID-19 Infection of Human Lung Cells

Apabetalone Inhibits SARS-CoV-2 Infection at Levels Comparable to Approved Antiviral

CALGARY, Alberta, March 15, 2021 (GLOBE NEWSWIRE) -- Resverlogix Corp. ("Resverlogix") (TSX:RVX) announced today the publishing of a new article titled: “Bromodomain and extraterminal protein inhibitor, apabetalone (RVX-208), reduces ACE2 expression and attenuates SARS-CoV-2 infection in vitro”, on the pre-print server, bioRxiv. The findings, made in collaboration with Dr. Dalia ElGamal’s research group at the University of Nebraska Medical Center (UNMC), Omaha, NE, provide a strong rationale for use of apabetalone, a bromodomain and extraterminal (BET) protein inhibitor, as a therapeutic for COVID-19.

The publication can be viewed using the following LINK.

“Our COVID-19 research program has yielded some truly extraordinary results, demonstrating apabetalone’s ability to prevent SARS-CoV-2 infection of human lung cells,” said Dr. Ewelina Kulikowski, Senior Vice President, Research & Development at Resverlogix. “Reducing cellular entry of virus particles into the lung tissue is one pillar of apabetalone’s unique dual-mechanism – alongside inhibiting damaging inflammation – in combatting COVID-19.”

“This work would not have been possible without the invaluable contribution of Dr. ElGamal and colleagues at UNMC,” said Donald McCaffrey, President and CEO of Resverlogix. “We are grateful to work with world-class scientific leaders to characterize apabetalone as a therapeutic for COVID-19 infection for the future benefit of patients.”

“Together with St. Patrick Reid, a prominent virologist at UNMC who's lab is dedicated to molecular pathogenesis of emerging viral pathogens, we found that apabetalone clearly inhibited SARS-CoV-2 infection of human lung epithelial cells,” said Dr. Dalia ElGamal, co-author and Assistant Professor at the Eppley Institute for Research in Cancer and Allied Diseases at UNMC. “Given apabetalone’s anti-inflammatory properties, and its favorable safety profile in human trails, I am excited to see apabetalone move forward in clinical trials for COVID-19.”

Publication Highlights include:

  • Angiotensin-converting enzyme 2 (ACE2) and dipeptidyl-peptidase 4 (DPP4) are key proteins used by SARS-CoV-2 to gain entry into human cells
  • Treatment with apabetalone reduces the expression of both ACE2 and DPP4 at the surface of human lung epithelial cells
  • Viral spike proteins, which bind ACE2 and initiate cell entry, adhere significantly less to apabetalone treated cells than control cells
  • Apabetalone prevents human SARS-CoV-2 infection of human lung epithelial cells at comparable levels to the antivirals remdesivir – a currently approved treatment for COVID-19 by the US Food and Drug Administration - and camostat mesylate
  • Cell viability is not impacted by drug treatment, the authors also note apabetalone’s well-established safety record in patients
  • Apabetalone’s observed dual mechanism of action on viral infection and inflammation support the use of apabetalone in clinical trials for COVID-19.

Program Update:

Apabetalone 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.

The results of the collaborative research efforts have uncovered that apabetalone has the potential to combat COVID-19 through a unique dual mechanism. First, apabetalone treatment prevents SARS-CoV-2 from infecting human cells (as highlighted in this work), and second it reduces the inflammation and cytokine storm response which can result in organ damage and long-term negative impacts. As a result of its dual mechanism and clinical safety record, several peer-reviewed publications have shortlisted apabetalone as a clinical candidate for COVID-19.

The work featured in this article is currently undergoing peer-review and is expected to be published in a scientific journal shortly.

About Resverlogix

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, the publishing of COVID-19 research in a scientific journals and the potential role of apabetalone in the treatment of 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. 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 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.

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