"Have you seen the market cap of Esperion Therapeutics. $1.2 bill USd it was double that a few years ago and we have more of a proming drug IMO"

As an investor and close follower of both Esperion (ESPR) and Resverlogix, I'd like to offer my two cents on comparing the two companies.

ESPR's one and only drug in clinical development is ETC-1002 (bempedoic acid) that lowers LDL cholesterol via inhibition of ATP-citrate lyase. ESPR IPO'd on Nasdaq in summer 2013 with a share price of USD $14 and a market cap of $196 million after having passed Phase 1 and a couple Phase 2 trials with flying colors for LDL-C lowering. Fast forward to today and they have ~ twice as many outstanding shares due to dilution, a share price of USD $46, a market cap of about $1.2 billion and have completed several more Phase 2 and Phase 3 trials for LDL-C lowering with flying colors with two more Phase 3 safety/efficacy trials reading out in the next 1.5 months. NDA/MMA applications for LDL-C lowering on track for H1 2019. Ongoing cardiovascular outcomes trial (CVOT) reads out 2022, but FDA and EMA have given guidance that they can submit NDA/MMA applications for LDL-C lowering. Very likely bempedoic acid will be marketed and available for LDL-C lowering prior to completion of CVOT study. Based on other CVOT studies with statins, statin/ezetimibe, and PCSK9 drugs, the effects of bempedoic acid on RRR of MACE events are somewhat predictable and unlikely to be be outside of the 15-20% RRR range in my opinion. Like some statins, bempedoic acid not only lowers LDL-C but also lowers hsCRP. This added hsCRP benefit may boost the RRR beyond what is seen with other statin-alternatives like ezetimibe or PCSK9 drugs. Bempedoic acid has a consistent efficacy and safety(*) record for LDL-C lowering, and has been shown safe by itself, as well as in trials used as an add on to statins, statin/ezetimibe, and PCSK9 inhibitors. They also have an extended release formulation that may work better for NASH indications and first trial of this is set to read out Q4 2018. They have Phase 2 trial in type 2 diabetics that will read out H1 2019. Esperion has current funds to carry them through the NDA/MMA applications in H1 2019. *One Phase 3 trial that read out earlier this year did cause some alarm because there seemed to be an inbalance in patient deaths with more in the bempedoic acid group than the placebo group. However, mostly just analysts/investors had an issue with this, not the DSMB/clinical investigators/clinical experts who deemed it unrelated to study drug and chalked it up to just chance. Personally, I agree with this latter view. The additional Phase 3's that read out in the next 1.5 months may squash these safety concerns if no issues, but would definitely be cause for concern if these Phase 3 readouts do show imbalance in adverse events. If you want more info on this safety issue or other facets of ESPR, I refer you to their excellent investor day presentation from last month. ESPR has its current valuation based on its stellar and consistent performance in several clinical trials. There's an unmet need for this drug, and it can be a blockbuster. However, it may not have as high of a potential ceiling as apabetalone due to the smaller number of potential conditions for bempedoic acid and competitive environment with several other LDL-C lowering options on the market. If NASH indication pans out for extended release formulation, this could help. Esperion's company communications to investors are excellent, they leave very few black boxes with their communications, their projected timelines have been spot on, and they haven't over promised much in my opinion. Much of their recent history has been influenced by entry of PCSK9 drugs into market and the FDA reaction to PCSK9 and FDA's revised guidance on LDL-C as a continued clinical endpoint to use for marketing.

Now to our friend Resverlogix. As we all know, the ride has been bumpier. RVX-208/apabetalone used to be simply an orally available drug to raise apo-AI and HDL. It passed Phase 1 and 2 (ASSERT, SUSTAIN) for apo-AI/HDL raising with mostly flying colors with the exception of transient liver transaminase elevations in some patients. The HDL-C hypothesis was alive and well and valuations of Resverlogix somewhat followed the roller coaster ride of the CETP inhibitors in clinical development. Then CETP inhibitors were starting to flop for safety and lack of CVOT efficacy. Although the effects of apabetalone on apo-AI/HDL were modest, it raised apo-AI/HDL via a non-CETP mechanism and was still deemed viable. The mechanism of action of apabetalone as a BET inhibitor was announced in 2012. Then in summer 2013, Phase 2 ASSURE top-line readout happened (around same time as ESPR IPO). The modest effects of apabetalone on apo-AI/HDL didn't lead to plaque reduction. I won't narrate this sad time beyond that, as we all know (or should know) about this already. But thanks to post-hoc analyses of Phase 2 trials showing reduction in MACE events, especially in those with diabetes, low-HDL and high-hsCRP, as well as several pre-clinical studies showing that this orally available bromodomain-2 selective BET inhibitor not only raises apoAI/HDL but benefically effects several pathways related to cardiovascular disease, kidney function, and neurodegenerative diseases, the Phase 3 BETonMACE trial was born. BETonMACE's primary endpoint is reduction in 3-point MACE events, based strongly upon post-hoc analysis of failed Phase 2 ASSURE.  Along the way between ASSURE and now, there has been substantial dilution of Resverlogix seemingly always funding concerns. There are still questions as to what apabetalone will acutally be marketed for. "The exact indication to be sought by the Company, and to be reviewed by the FDA, would be driven by the study’s results." As with ESPR's bempedoic acid, there is a possibility that there may be an adverse event imbalance in Phase 3 readout that may impact the future of the drug. Resverlogix hasn't pursued marketing for an indication like apo-AI/HDL modulation and is banking everything on one Phase 3 trial. Other clinical trials have been discussed, but never materials. Two phase 2s have been approved for some time, but never started enrollment presumably to funding issues. Company communications have been average at best. Questions surrounding the timing an execution of interim analyses in BETonMACE (futility analysis/SSRA) have been left unanswered and because of this the timeline, target enrollment, target MACE and trial cost are left uncertain. The good news is that this drug has uber-blockbuster status it it shows the MACE RRR that is projected by the company and there is no other bromodomain inhibitor (or any epigenetic drug) in clinical trials for cardio, renal, or cognitive. So many potential indications, little competition. The current market cap reflects these aforementioned items and not the potential. The TSX and not Nasdaq for Resverlogix is likely also holding it back. 

So I view both as potential blockbusters. Ceiling higher for apabetalone but more risk remains for apabetalone.

All just my opinion. Not investment advice. Do your own due diligence. Yadda yadda yadda.

BearDownAZ