Enanta Pharmaceuticals Inc (ENTA)

[DaveAu]

Transcipt (Seeking Alpha)

Excerpt on the new NASH drug:

Sure. So shifting gears to FXR now. So 297 are follow-on FXR agonist. We spent a lot of time trying to optimize whatever characteristics of the molecule we could. Obviously looking at potency and selectivity and other kinds of things. What surprised us as you know with 305 in the ARGON study was that the doses that we used, we saw more pruritus than we would have expected from all the information we saw in Phase 1. And so for us thinking about how to use 305 in a way that gives better tolerability going forward is the path that we’re thinking about for 305, but 297 then it became clear that pruritus perhaps more so than lipids is the thing we needed to really try to figure out how to improve upon. The confounding part of that is that nobody -- nobody really understands what’s causing pruritus with these various FXRs that have seen it, is it on target, is it off target, is it on target in certain tissues, but not others and so absent having the sort of confirmed mechanistic understanding of how to reduce pruritus, what we did was took other approaches that we could do sort of independent of knowing the mechanism.

So number one is drill down the potency to as good a potency is you could possibly do. So we worked and worked and worked on that you’ve -- we put the data out at JP Morgan initially, we’ll have more at EASL, but it’s a very, very potent FXR. It is the most potent one based on the data that we’ve generated side by side versus any other FXR agonist that’s in development today. So number one, that’s good because you will reduce the amount of drug that it takes to deliver the punch. So we know that FXR receptors are in the intestine and also in the liver in terms of the sites of efficacy for a compound that we would be looking for in NASH. And so in addition to making these exquisitely potent for FXR and hopefully less potent for something else that we might not know, we aimed it directly at liver and intestine and not had plasma and skin, because obviously if you have high plasma levels you are going be circulating the drug around to all kinds of other tissues in the body and we specifically thought it would be interesting to minimize the skin exposure of the drug as well.

So it’s really the twofold combination of having very, very good potency. So that we’ll be dosing just very small amounts of drug and then having that drug go directly to the sites where we need the drug and hopefully not at the sites where we don’t need the drug were only -- were only -- were only other things could happen. So that’s our thesis and there is a scenario where it might not play out as we hoped, but that sort of narrow scenario of bad luck would be, if it is FXR mediated, the pruritus and if it’s FXR mediated by FXR receptors inside the liver or intestine, then we may only have achieved a super, super potent version of 305 or some of the other FXRs that are out there today. But if it’s any other scenario, we have the chance to come up with benefit and that’s what we’ll be exploring. We think we can learn actually, a fair amount in Phase 1 and we’re on track to start that Phase 1 study in the middle of this year with -- with the -- with the data coming in the first half of next year. So it’s a pretty straightforward plan, it looks like an excellent molecule chemical profile more at EASL, but it’s a -- it’s a polished entrant into the field.