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Message: Critique rvx-208 Science

I just posted the following on SH re can anyone see any holes in rvx-208 science?

Over the years I have been very critical of RVX management and what up until the last year I considered less than adequate communications.

Both of these functions have improved dramatically in the past 2 years with continuous scientific discoveries on the cascading epigenetic effects of rvx-208 (apabetalone) and on the business side the Hepalink deal is an indications of good things to come.

On the scientific side I have heard criticisms (mostly by Poc/CTW/OTH) about poor experimental design because of the ASSURE trail failure and that the trial was underpowered he claimed (hind sight is 20:20). There has also been criticism about lack of FDA approval but we know that RVX is working on this and probably trying to get a paradigm shift in their thinking. There is also the orphan trial which could result in apabetalone going to market much sooner.

The post hoc analysis from ASSURE/SUSTAIN has lead to a brilliant trial design called BETonMACE which is adaptive, focused and has wide geographical coverage thus providing genetic variation to the findings. It is lead by an advisory board of top scientists in these fields.

So here is an except from their website;

From the RVX website

The most advanced BET inhibitor in clinical development is apabetalone (RVX-208). This compound was originally discovered in a screen for Apolipoprotein (Apo) A-I mRNA inducers in hepatocyte cell cultures, and has been shown to raise ApoA-I and high-density lipoprotein (HDL) in humans. Apabetalone binds preferentially to the second bromodomain of BET family members, with a 20-fold or higher selectivity for the second bromodomains of BRD2, BRD3 and BRD4 versus the first bromodomain. This inhibition modulates the expression of a variety of genes including ApoA-I, the core protein component of HDL. Beneficial effects were also observed on CVD biomarkers, such as high-sensitivity C-reactive protein, a marker for systemic inflammation, alkaline phosphatase, a reported key driver for vascular calcification, and components of the complement and coagulation cascades, as well as other mediators of vascular inflammation.

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My question to scientific posters and others is "what, if any" are the perceived scientific barriers or pitfalls to rvx-208 a.k.a. apabetalone?".

I think we need more critical thinking on these boards even though I am "high" on this stock and long. I am biased because I think it is going to be a blockbuster. Therefore I would appreciated anyone out there who could sober me up on the science.

Cheers

Toinv

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