Hi Tada,

Very good points.  BET proteins have now been unequivocally identified as master regulators of inflammatory disease, and virtually all diseases associated with ageing and chronic diseases without a simple genetic basis or infectious agent have been shown to have an inflammatory basis. The list of diseases for which BET inhibitors can be expected to be modulatory is now likely close to a thousand, not under 100.  For a glimpse of the potential, download the pdf associated with this patent application of one Zenith BETi:  https://patents.google.com/patent/US9278940B2/en

You can see that this patent application outlines the known actions of BETis and then lists (not even exhaustively) the types of diseases that may be amenable to treatment with BETis.  I am not sure that Resverlogix and Zenith have a 6-8 yr lead time anymore given the amount of research and development being poured into BET inhibition.  But they are in the lead and that's the best place to be!  They also have an excellent science program to elucidate the mechanisms underlying the observed effects of their BETis.

Reduction of toxicity is going to open the field to thousands of disease applications, a key will be to not lose too much efficacy in the process.  For example, the Picard et al 2013 publication that was discussed yesterday showed that JQ1 (a BETi with affinity for both BD1 and B2) downregulated significantly trancription of 754 genes in liver cancer cells whereas apabetalone, which is selective for BD2, downregulated signficantly only 46 genes under the same conditions. This may help reduce side-effects but may also reduce efficacy.   

Also, some BETs interact directly with the upregulated protein Transcription Factors in the immune system, so that they can not only diminsh the production of the TFs by displacing BETs from DNA, but can also prevent existing TFs from assembling the cell machinery to produce other inflammatory molecules (breaking some of the cascading effects seen in inflammation). Lots of (exciting)work to be done.

You can bet (sorry) that RVX will be a buy-out target soon, possibly even in the absence of stellar Phase III results.  Only my humble opinion, of course.

Jupe