Resverlogix' RVX-208 is the First BET Bromodomain Inhibitor in Clinical Trials
News Jul 24, 2012
Resverlogix Corp. has announced the "Mechanism of Action" (MoA) by which RVX-208 increases apolipoprotein A-I (ApoA-I) production. Our data shows RVX-208 to be an inhibitor of the Bromodomain and Extraterminal Domain (BET) proteins.
RVX-208 acts on BET proteins, including BRD4, a member of the BET-protein family, leading to increased transcription of the ApoA-I gene followed by production of more ApoA-I protein.
ApoA-I is the major protein component of HDL, a class of lipoproteins believed to reduce atherosclerosis through reverse cholesterol transport (RCT).
The ability of RVX-208 to increase ApoA-I makes it the lead candidate in Resverlogix' pipeline for treating atherosclerotic cardiovascular disease.
RVX-208 is an orally active small molecule, the first in a new class of compounds to enter into human clinical trials more than 4 years ago.
Clinical benefits of RVX-208 are currently being explored in two concurrent Phase 2b clinical trials (SUSTAIN and ASSURE), led by Cleveland Clinic.
"The finding that RVX-208 inhibits BET proteins is an important discovery for a wide scientific and medical audience," stated Dr. Norman Wong, Chief Scientific Officer of Resverlogix.
"This discovery is important because BET proteins are key players in 'epigenetics', a critical mechanism for regulating the expression of genes. Epigenetic processes are mediated by proteins, including the BET-proteins, that act in concert with the DNA to make it transcriptionally active or dormant. This epigenetic control of gene expression plays a key role in the development and progression of many human diseases. The knowledge gained from studies of RVX-208 will guide Resverlogix in its search for additional compounds to treat some of these diseases," added Dr. Wong.
"The MoA of RVX-208 has allowed the company to expand the scope of its technology and the potential of its pipeline significantly," stated Donald McCaffrey, President and Chief Executive Officer of Resverlogix. "We have been generating and filing new intellectual property since our discovery, and see the opportunity to initiate licensing and partnering discussions in the areas of atherosclerosis, oncology, autoimmune and Alzheimer's diseases where the MoA plays a pivotal role."
Mr. McCaffrey added that, "the value of this discovery was further validated when Dr. James Watson, in his first solo scientific publication since 1972, highlighted the promise of BRD4 as a therapeutic target and in particular, against untreatable cancers."
In treating inflammatory bowel disease (IBD), physicians can have a hard time telling which newly diagnosed patients have a high risk of severe inflammation or what therapies will be most effective. Now researchers report finding an epigenetic signature in patient cells that appears to predict inflammation risk in a serious type of IBD called Crohn’s disease.