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Resverlogix Corp
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Resverlogix talks BD2-selective BET inhibitor safety

2022-06-08 10:20 ET - News Release

Dr. Ewelina Kulikowski reports


Resverlogix Corp. has published an article entitled "Breaking boundaries: Pan BETi disrupt 3D chromatin structure, BD2-selective BETi are strictly epigenetic transcriptional regulators" in the journal Biomedicine & Pharmacotherapy. The article uncovers a clear mechanism for the improved safety and reduced off-target effects seen with BD2-selective BET (bromodomain and extraterminal) inhibitors in comparison with non-selective BET inhibitors.

"This research helps us better understand the important differences between selective and non-selective BET inhibition as therapeutic strategies," said Dr. Ewelina Kulikowski, senior vice-president, research and development, and the senior author of the article. "BD2-selective inhibitors, such as apabetalone, can inhibit the expression of disease-causing genes without disrupting the fundamental functions of cells."

Publication highlights include:

  • A new role for BET protein BRD4 was discovered, in maintaining the higher-order structure of chromatin at topologically associating domain (TAD) boundaries.
  • Maintaining the structure of TAD boundaries is critical for the basic functioning of cells, and disrupting the boundaries can lead to cell death.
  • As a result of differing interactions with BRD4, non-selective BET inhibitors disrupt TAD boundaries, while BD2-selective BET inhibitors do not.
  • These findings contribute to a potential mechanism underlying the differences in clinical safety outcomes observed between BD2-selective and non-selective BET inhibitors.

Other recent publications

Another article, entitled "Inhibition of epigenetic reader proteins by apabetalone counters inflammation in activated innate immune cells from Fabry disease patients receiving enzyme replacement therapy," was recently published in the journal Pharmacology Research & Perspectives. The article details the beneficial impacts of apabetalone treatment on inflammatory pathways in immune cells from Fabry disease patients. These findings suggest that apabetalone is a promising therapeutic candidate for the rare disorder.

About apabetalone

Apabetalone (RVX-208) is a first-in-class, small-molecule, therapeutic candidate with an epigenetic mechanism of action. It is a BD2-selective BET inhibitor that works in preventing and treating disease progression by regulating the expression of disease-causing genes.

Due to the extensive role for BET proteins in the human body, apabetalone can simultaneously target multiple disease-related biological processes while maintaining a well-described safety profile -- leading to a new way to treat chronic disease. Apabetalone received breakthrough therapy designation from the U.S. Food and Drug Administration (FDA) and is the only drug of its class with an established safety record in human clinical trials, with well over 4,200 patient-years of safety data across 10 clinical trials.


Studies -- published in prestigious scientific journals (including Cell) -- demonstrate that apabetalone has the potential to act against COVID-19 with a unique dual mechanism: first by preventing viruses from entering the cells and replicating; and second by averting excessive inflammatory reactions that can cause severe and lasting organ damage. The investigational treatment could potentially reduce the severity and duration of COVID-19. Apabetalone's unique dual mechanism also means that it has the potential to show efficacy against new COVID-19 variants and may even help fight other viruses.

Resverlogix has partnered with Eversana, the pioneer of next-generation commercial services to the global life sciences industry, to support the rapid commercialization of apabetalone for COVID-19 in Canada and the United States. Eversana is currently leading clinical outreach and advocacy for apabetalone in the Canadian market.


Apabetalone is the first therapy of its kind to receive breakthrough therapy designation from the FDA -- for a major cardiovascular indication -- following the groundbreaking findings from the BETonMACE phase 3 study. Data from BETonMACE showed apabetalone can potentially prevent major adverse cardiac events among high-risk cardiovascular disease patients who also have Type 2 diabetes mellitus.

About Resverlogix Corp.

Founded in 2001, Resverlogix is a Calgary-based late-stage biotechnology company and the world leader in epigenetics, or gene regulation, with the goal of developing first-in-class therapies for the benefit of patients with chronic disease.

Resverlogix is developing a new class of epigenetic therapies designed to regulate the expression of disease-causing genes. The company aims to improve patients' lives by restoring biological functions -- altered by serious illnesses such as cardiovascular disease -- back to a healthier state.

The company's clinical program is focused on evaluating the lead epigenetic candidate apabetalone for the treatment of cardiovascular disease and associated co-morbidities as well as COVID-19.

Resverlogix's common shares trade on the Toronto Stock Exchange.

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