Resverlogix Corp shows RVX-208 demonstrates increase in functional HDL particles

Resverlogix Corp. has announced key scientific data was presented in an oral presentation highlighting the novel features of RVX-208 at the American Heart Association Scientific Meeting. The presentation titled "Compound RVX-208 Modulates HDL-C Levels and Function in Non-human Primates and in Early Human Trials" was presented by Dr. Jacques Genest.

Dr. Jacques Genest, MD, Director of the Division of Cardiology at McGill University Health Centre/Royal Victoria Hospital said, "We continue to be excited about the data that is being generated for RVX-208. It is important that our colleagues have access to this promising data which is why we have presented at this prominent conference. Resverlogix's novel drug demonstrated the ability to increase the production of ApoA-I and functional HDL. Notably we saw increases in prebeta-HDL particles, which improve HDL's ability to mediate cholesterol efflux."

"Today we presented interesting and consistent data from African Green monkey studies and our Phase 1a human clinical trial at the AHA," stated Dr. Jan Johansson, MD, Ph.D., Senior Vice President, Medical Affairs of Resverlogix. "The pharmacodynamic data from human healthy volunteers of which the majority had low HDL demonstrated that we have seen significant increases in ApoA-I production and HDL functionality, consistent with previous findings in the African Green monkey studies. Further investigation of the effect of RVX-208 on the HDL metabolic pathway is ongoing in humans and animals to establish the mechanisms of action and therapeutic potential in treating atherosclerotic cardiovascular disease."

During the presentation Dr. Genest reported that in an African Green monkey study treatment with RVX-208 resulted in a highly significant increase in the average of serum ApoA-I and HDL-C levels (57% and 92%, respectively). It was noted that RVX-208 treatment modified the distribution of HDL particle size causing a significant increase in prebeta-HDL and the larger alpha-HDL particles. The ability of serum to promote cholesterol efflux via ABCA1, ABCG1 or SR-BI-dependent pathways in a cell culture model was significantly increased by RVX-208.

Data was also presented for Resverlogix's Phase 1a safety and pharmacokinetic human study which was comprised of a total of 80 subjects. RVX-208 was found to be well tolerated and had good oral absorption meeting the objectives of safety and pharmacokinetics.

In the multiple ascending dose arms, 24 participants were randomly assigned to 3 cohorts of 8 healthy volunteers (6 active and 2 placebo), and received oral administration of RVX-208 at 2, 3 and 8 mg/kg/day or placebo for 7 days. ApoA-I, HDL-C, HDL particle size distribution and ABCA1-dependent cholesterol efflux were assessed on day 1 (pre-dose) and day 7. Following administration for 7 days, treatment with RVX-208 increased the change for ApoA-I by 11% (P=0.03) in treated subjects compared with placebo. Interestingly, the corresponding prebeta-HDL change was 42% (P=0.007) in the actively treated group compared to control. Furthermore, sera from subjects were assessed for ABCA1 mediated cholesterol efflux as a predictive marker for reverse cholesterol transport. Again, ABCA1-dependent cholesterol efflux change increased by 10% (P=0.03) and was found to correlate with increased prebeta-HDL. Taken together these data demonstrate the ability of RVX-208 to generate prebeta-HDL, improve HDL functionality, which clearly differentiates RVX-208 from other HDL therapies, and making it the first of a new drug class.

RVX-208, a novel small molecule therapeutic that facilitates endogenous ApoA-I production, is positioned to be one of the most promising emerging drugs in the treatment of atherosclerosis. Apolipoprotein A-I (ApoA-I), the main component of high-density lipoprotein (HDL) represent the bodies natural defense system against atherosclerosis by mediating reverse cholesterol transport, i.e. transport of peripheral cholesterol including that of the vessel wall to the liver for processing. To the Company's knowledge RVX-208 is the only novel small molecule that is specifically designed to increase ApoA-I production and thereby raise prebeta-HDL levels thus enhancing HDL functionality to augment reverse cholesterol transport (RCT). RCT is a pathway by which accumulated cholesterol is transported from the arterial wall to the liver for excretion, thus preventing atherosclerosis. Major constituents of RCT include acceptors such as high-density lipoprotein (HDL) and apolipoprotein A-I (ApoA-I). A critical part of RCT is cholesterol efflux, in which accumulated cholesterol is removed from macrophages. The American Heart Association estimates that almost 80 million American Adults have one or more types of cardiovascular disease. CVD remains the number one killer of developed nations. Nearly 2400 Americans die each day from cardiovascular disease.