Imtesty,

It's been a while. Good to hear from you. I don't recall off the top of my head all of the inflammation/autoimmune markers that Resverlogix has disclosed as being modulated by RVX-208 or other BET inhibitors such as RVX-297. However, I think it is safe to say that Resverlogix and Zenith have many compounds with clinical potential for autoimmune and inflammation. RVX-208 is likely the most well understood, since they have plasma protein (proteomic) data from SomaScan analysis of ASSERT and ASSURE trial patients and have done extensive testing with microarray analysis of whole blood or primary hepatocytes exposed to RVX-208. I'd suggest taking a look back at their press releases and abstracts on their web page, as well as checking out the presentations at the NYAS Epigenetics: Cancer and Beyond ebriefing. This will be a good start. Also, check out their publication in Atherosclerosis from January.

As for RVX-297, here is a reply regarding RVX-297 I made to G1945V on the Stockhouse board recently. I hope this helps!

"G1945V,

When RVX-Therapeutics (now Zenith Epigentics) was spun out, the primary focus was to be on autoimmune and cancer. From the April 8, 2013 news release, "RVX Therapeutics will exclude Apolipoprotein A-1 ("Apo A-1") and RVX-208 technologies, rather focusing on multiple therapeutic indications including autoimmune diseases and cancer." As we know, the Zenith cancer program is active. The autoimmune program with RVX-297 and other compounds was initiated by Resverlogix and continued by Zenith and includes pre-clinical animal studies that have been presented at scientific conferences as well as in corporate updates. Autoimmune used to be a part of the Zenith website but they took that off at least a few months ago. Not sure why.

Is the RVX-297 molecule still "active"? I don't know for sure. What I do know is that in the March 2016 MD&A document, it was stated that as of January 31, 2015 that Zenith had terminated its license agreement with Resverlogix because Zenith intended to pursue its own IP and not the licensed IP. Read more about this here. So assuming that RVX-297 was a compound license to Zenith from Resverlogix, it would appear that Zenith has decided to not go forward with RVX-297 and instead pursue its own IP.

I have a copy of a July 2014 Zenith EpiCongress presentation and there is a slide entitled "Zenith’s robust platform has generated promising BET inhibitors for auto-immune disorders" that describes properties of ZEN-3118, ZEN-3309, ZEN-3228 and ZEN-3212, with ZEN-3118 seeming to be their lead molecule with in vivo efficacy in both rat collagen-induced arthritis (CIA) and mouse experimental autoimmune encephalomyelitis (EAE) models. Additionally, there is a slide that shows ZEN-297 (not RVX-297) being compared against ZEN-3118 in the EAE animal model. ZEN-297 is also referred to in another slide that emphasized Zenith's extensive BET inhibitor platform.

Long story short. Yes, autoimmune/RVX-297 was transerred to Zenith. Looks like Zenith referred to it as ZEN-297. Regardless of whether you call is RVX-297 or ZEN-297, it appears that Zenith has moved on to a next generation molecule. RVX-208 and RVX-297 are 200-series compounds. The ZEN-3000 series [including the ones mentioned above and also ZEN-3365 (former oncology lead compound), ZEN-3694 (current oncology lead compound) and ZEN-3717 (current oncology backup compound) likely represent years of improved understanding of BET inhibitors and epigenetics to develop better compounds. Remember, the BET inhibitor mechansim of action wasn't even announced until April 2012! So when Zenith talks about 2nd and 3rd generation BET inhibitors, likely their 3000 series compounds reflect these next generation improvements. I'd rather Zenith pursue an improved molecule than an older inferior one such as RVX-297.

Similar argument for pursuing ZEN-3694 and ZEN-3717 instead of ZEN-3365. While there may or may not have been patent problems with pursuing ZEN-3365, they decided to avoid this and go ahead and pursue a supposedly superior molecule from the 3600- and 3700- series and avoid potential patent problems (or at the very least delays) with using the earlier 3300-series ZEN-3365.

From Masila's notes from the January 2016 Zenith AGM: "The challenges with that in Oct 2014 were based around intellectual property. We had moved forward very fast with that, but prior to our publishing of our IP, another company had published a document that didn’t completely cover/block us, but would have made it difficult legally. We went back to the drawing board and, after bragging about our massive platform and extensive IP, we went back to that and developed two very good lead programs going forward – ZEN 3694 and ZEN 3717. There were actually about 7 or 8 that we had to choose from, all superior to our first one. We’ve very happy about having that depth."

Best regards,

BearDownAZ