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Replies to post #85426 on Biotech Values
Katherine Sue - Wedbush Securities
Okay, great. Thanks for that. Another question is, more of a general strategy kind of question. What do you think of the approach of having a nuke in the combination apparently due to the high genetic barrier to resistant and also pangeotypic activity, versus your chosen combination of a PI and a non nuke?
Peter Mueller
Okay. So this is an interesting story that is somehow cruising around in the outer world. So, I think theoretically speaking, you can add everything to a combination, including a nuke. Now, I think I want to just say something about resistance pressure. I think the argument that a nuke is better because you have a different resistant pressure as compared to non-nukes, is in a way a mute point. And the reason why I’m saying that is because there’s tons of preclinical data in vitro data available right now that show that variants that are produced by one inhibition mechanism gets taken care of if you combine it by the other product that is combined into the mix. And so, for example, variants produced by telaprevir get taken care of 222 and vice versa. And what that means is at the end of the day that the entire resistant argument is sort of, I would say less of a problem. So I think this is the first thing I want to say.
And then the second thing what I want to say is in my life at least and this is happening in the biology field quite awhile, most nukes, and not necessarily always the case, but most nukes are more difficult to deal with because out of one simple reason that basically they act at the active site of polumerators which is the most concerned active site in the system on the planet. And that means electivity is a big issue. And polumerators are all over the body, in the gut, in the heart, in the eye, everywhere. And chances are that you will see more side effects and that’s what you’re seeing. And that’s why a lot of those nukes are never saw the light of the day. And they’re one of the other (inaudible), so yeah, there is a potential but I would say the resistant argument is sort of a mute point, okay. And when it comes down to safety and travel ability and I think the non-nukes are better. And any other mechanisms might be better. And so therefore I’m not a big fan. But it is a doable thing and if somebody will give me tomorrow a nuke that is clean, I would maybe try it. But I haven’t seen one.
It’s reasonable to infer that the second-gen protease inhibitors, VX-813 and VX-985 are effectively dead.
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