Here's a run down of some events to expect in the next 2 1/2 weeks leading up to the 9/30 Annual General Meeting.

9/18 EASD: Oral presentation at European Association for the Study of Diabetes (EASD) in Stockholm, Sweden 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." Since 9 of the 13 countries currently disclosed to be sites for BETonMACE are in Europe, it seems quite apropos that RVX will be presenting at a meeting in Europe. Plus, this meeting is focused on Diabetes, which is the focus patient group of BETonMACE. See end of this message for the abstract, which is somewhat similar to the ESC 2015 abstract presented in London eariler this month. The ESC and EASD presentations seem to be a prelude to what Don will likely present to the lay non-science folk at the Yale Club and GCFF and hopefully to general shareholders at the AGM. These abstracts include the new microarray/pathway analysis data that emphasizes the multiple biological pathways that are beneficially affected by RVX-208 to synergistically provide the cardiovascular benefit. The EASD abstract is more diabetes focused than the ESC abstract.

9/22 and 9/23: 3rd Annual Targeting Epigenetic Readers and Chromatin Remodelers: Advances in Bromodomain Drug Discovery and Development in Boston. Norman Wong is on the schedule to moderate a discussion group "Examining the Basic Actions of BET Proteins" on the afternoon of 9/22 focusing on 1) Actions of BET proteins and specifically BRD4 in mediating actions of Pol II that differentiates it from BRD2/3 activity; 2) Actions of BET proteins in selective vs. pan inhibition; 3) Actions of BET proteins in inflammation. Then on 9/23 at 10:55 AM (Boston) Norman Wong is scheduled to present in a talk entitled "BET Proteins; Selective and Pan-Inhibition for Treating Human Diseases." However, this event never appeared on the Resverlogix events page. I inquired with Sarah at RVX about this and she indicated that "The presentation at that conference will be on behalf of Zenith by Eric Campeau." Sarah also confirmed that is was Eric who presented on behalf of Zenith at the July 2015 EpiCongress in Boston that Norman Wong/Resverlogix were originally scheduled for.

9/25: Yale Club presentation in NY. See recent posts on this Hub regarding this. Keep in mind that Don said yesterday at Rodman and Renshaw that the orphan indication will be disclosed in a couple of weeks. So we may hear about this on 9/25, which is 2 weeks after R&R.

9/26: GCFF (Global Chinese Financial Forum) in Toronto. Don McCaffrey is giving the keynote speech (40 minute time slot starting at 9:30 AM) entitled "How to structure a successful deal with Chinese Pharma?"

9/30: Annual General Meeting. Keep in mind that Don said at Rodman and Renshaw yesterday that they are a few short weeks away from starting enrollment. I always thing of "few" as at least 3. 3 weeks from yesterday is 10/1.

Here is the EASD abstract:

"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"

Exciting end to September! GLTA.

Best,

BDAZ