Well, next up on the RVX schedule of events is this:

European Society of Cardiology (ESC) Congress 2015, London, England, August 29 - September 2.

Norman Wong is listed as having an August 30th poster presentation in the poster session entitled: Lipids in atherosclerosis.

08:30P1585"RVX-208, an orally active BET inhibitor, lowers CVD risk by activities beyond raising ApoA-1/HDL."

Then in September, they list 17th Annual Global Investment Conference Rodman & Renshaw 2015, New York City, NY, September 8-10 and the 22nd Annual BioCentury NewsMakers 2015, New York City, NY, September 10. They are listed as a presenting company at Rodman & Renshaw but not on the BioCentury Newsmakers page as of this afternoon.

Finally, in mid-September, at the European Association for the Study of Diabetes in Stockholm, Sweden, September 14-18, looks like RVX is presenting an abstract entitled "RVX-208 acts via an epigenetic mechanism to lower Major Adverse Cardiovascular Events (MACE) in patients with atherosclerosis and especially in those with diabetes mellitus." You should be able to access the abstract with the link, but I will paste the text at the end of this message in case the link fails.

I couldn't find a posted abstract for the ESC presentation, but in the EASD abstract, there is something new: Microarrays from human whole blood exposed ex-vivo to RVX-208. Previously in the ACC2015 abstract, they only indicated that "The microarray studies were performed using primary human liver cells exposed to RVX-208. This treatment demonstrated significant changes in cellular pathways or networks characterized by: an attenuation in inflammation, coagulation, complement and cholesterol synthesis." Now in the newer EASD abstract, it appears that they are looking at both primary hepatoctyes AND human whole blood treated with RVX-208.

The language regarding the human hepatocyte microarrays sounds similar between the ACC2015 and EASD2015 abstract. But the language on the whole human blood is new: "Microarrays from HWB exposed ex-vivo to RVX-208 identified pathways with known roles in atherogenesis including: pro-inflammatory signaling, cell-cell interactions and extracellular matrix organization. RVX-208 significantly downregulated several pro-atherogenic genes (43/56) but upregulated anti-atherogenic genes (9/17), that control monocyte recruitment, migration and activation, macrophage function, inflammatory signaling and plaque stability to suggest an overall antiatherosclerotic benefit."

At both the ESC and EASD conferences, hopefully Dr. Norman Wong presents more about the recent Emerald Logic FACET analysis. It is unclear from the EASD abstract as well as this ACC2015 presentation in March 2015 by Jan Johansson whether the Emerald Logic FACET analysis was included. From the Emerald Logic news release: "Emerald Logic analyzed Resverlogix's complete clinical dataset including all measurements obtained from each of 798 patients who participated in the Company's Phase 2 clinical trials ASSERT, SUSTAIN and ASSURE........The complete dataset, containing approximately 650,000 data points, was analyzed using Emerald Logic's FACET software. This unique approach combines medical history, epidemiology, demographics, patient vital signs, and clinical lab measures in order to identify explanatory factors for efficacy and adverse events and to produce discriminatory models without bias or guidance."

Both the ACC2015 and EASD2015 abstract indicate looking at plasma biomarkers, and furthermore the ACC2015 abtract indicated that "levels of more than 60 biomarkers were collected in the aforementioned trials." However, did the Emerald Logic FACET analysis include more that 60 biomarkers? I really wish we new more about this FACET analysis.

Then after that, there's nothing scheduled until the September 30th AGM.

One more note. I noticed on the RVX homepage that if you mouse over the Clinical Cardiovascular panel on the left, the text that appears reads "RVX-208 (“Apabetalone”) is a first-in-class small molecule that inhibits BET bromodomains. Phase 3 clinical trial “BETonMACE” is expected to be launched this fall with a primary endpoint of relative risk reduction of Major Adverse Cardiac Events (MACE) in high-risk cardiovascular and diabetes mellitus patients." I added the bolding. By some definitions, Fall begins in September.........

Anyways, here's the abstract if the link didn't work.

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RVX-208 acts via an epigenetic mechanism to lower Major Adverse Cardiovascular Events (MACE) in patients with atherosclerosis and especially in those with diabetes mellitus. N.C.W. Wong1, E. Kulikowski1, L. Tsujikawa1, D. Gilham1, S. Wasiak1, C. Halliday1, K. Lebioda1, J.O. Johansson2, M. Sweeney2; 1Clinical Development, Resverlogix Corporation, Calgary, Canada, 2Clinical Development, Resverlogix Corporation, San Francisco, USA.

Background and aims: RVX-208 binds selectively to the second ligand domain of Bromodomain and Extra-Terminal (BET) proteins and inhibits their activity. Each BET protein has two bromodomains that bind acetylated lysines in histones. When a BET protein binds ligand, it recruits transcriptional machinery to DNA and thereby modifies gene activity. Analysis of pooled data from two phase 2b trials; SUSTAIN and ASSURE revealed a 55% relative risk reduction (RRR) of MACE in RVX-208 treated patients (n=331) vs. placebo (n=168). But in those with diabetes mellitus (DM) RVX-208 treatment lead to a 77% RRR of MACE vs. placebo. RVX-208 increased production of ApoA-I yielding more high-density lipoprotein (HDL) particles. While these effects should lower MACE, the magnitude was more than expected, prompting studies to identify properties of RVX-208 beyond its effects on ApoA-I/HDL.

Materials and methods: Plasma biomarkers from SUSTAIN and ASSURE trials were analyzed. Microarray data from RVX-208 treated primary human hepatocytes (PHH) or human whole blood (HWB) were used to identify differentially expressed genes, and guide measurements of specific proteins in clinical samples to confirm key findings.

Results: Biomarkers from the trials showed significant increases (p<0.05, unless specified) between RVX-208 vs. placebo in: HDL-c (+3mg/dL), ApoA-I (+7.5mg/dL), large HDL (+0.7umol/L), HDL size (+0.1nm), and total HDL particles (+1.8umol/L, p<0.07). Glucose in all patients (n=499) or in those with DM (n=192) given RVX-208 or placebo was unchanged vs baseline. In patients with DM (n=119) and low HDL (<40mg/dL), RVX-208 reduced glucose by -0.3 mmol/L but in placebo it increased +0.9 mmol/L. These modest changes do not predict the MACE reductions. Thus microarrays were used to survey PHH and HWB exposed to RVX-208. In PHH, RVX-208 decreased expression of genes in pathways for cholesterol & fatty acid synthesis, innate immunity and glucose processing. Most profound were effects on complement and coagulation pathways, where RVX-208 downregulated expression of 19/26 and 20/33 genes respectively. These data were confirmed by RT-PCR of key mRNAs. Furthermore, specific complement and coagulation proteins were found to be decreased in plasma from the trials (range 7-12% vs. baseline). Microarrays from HWB exposed ex-vivo to RVX-208 identified pathways with known roles in atherogenesis including: pro-inflammatory signaling, cell-cell interactions and extracellular matrix organization. RVX-208 significantly downregulated several pro-atherogenic genes (43/56) but upregulated anti-atherogenic genes (9/17), that control monocyte recruitment, migration and activation, macrophage function, inflammatory signaling and plaque stability to suggest an overall antiatherosclerotic benefit.

Conclusion: RVX-208 treatment is associated with marked MACE reductions in SUSTAIN and ASSURE patients and especially in those with DM. RVX-208 modifies cellular epigenetics to impact multiple biological processes that underlie CVD. Combined effects of RVX-208 on reverse cholesterol transport, vascular inflammation, innate immunity, atherosclerosis and thrombosis may explain its efficacy in reducing MACE.

Clinical Trial Registration Number: NCT01423188, NCT01067820