Replies to post #114941 on Biotech Values

[mcbio]

CYTK has gotten to interesting levels, but Zebra's law is possibly in play, as CYTK doesn't have a very advanced pipe.

AMGN's involvement kind of takes away Zebra's Law in my eyes though it obviously doesn't guarantee that the drug will work or that the approach is otherwise sound. Presumably AMGN's involvement can give some comfort on the latter point though. Note that RIGL I believe has a somewhat competing program, albeit at a much earlier stage (not even in clinic till end of 2012/early 2013) and they did note in their past presentation that their approach is a bit different than CYTK I do believe.

[tony111]

CYTK
The balance sheet is just horrible and they dun have much cash left (maybe 4 quarters). I was thinking to buy into their offering for a gamble However, since PGS is the expert in this field, if he says the drug is not going to work, I'll take his advice.

[poorgradstudent]

CYTK

Dunno how much you've kicked the tires in the CYTK garage. The theory is it increases output without increasing intracellular calcium, an effect of beta agonists. Thus you get the output without the increased velocity and shortened systolic ejection time. Interested to hear your take on how those parameters bear on progression to heart failure.

Actually, I'm very very familiar with the CYTK garage. I know two of the people on the SAB and have a couple of friends working there. The premise of the drug is that it actually allows the myosin in the cardiac sarcomeres to better progress through its force producing cycle. So as you say, it is indeed independent of Ca2+. The profs I know on the SAB are basically hard core, life long researchers working on myosin... so they come from a scientific curiosity angle rather than a clinical feasibility angle.

Anyways... I think the important point regarding this drug is to consider the various HF populations. To set the stage, remember that people with heart failure often have remodeled hearts. If they're lucky they're early stage hypertrophic and don't necessarily have an EF problem and their blood pressure is under control. But if patients do not have their blood pressure under control (often later stage hypertrophy), then increasing EF is not going to help. In fact it should increase afterload on the heart and make things worse. So the way I'm seeing it, in a population at early stages of hypertrophy, their hearts do a reasonable job of maintaining EF so the CYTK drug would not be useful. In later stage hypertrophy with poorly controlled BP I don't think you want to be increasing EF without having the BP under control

The best situation for this drug in my opinion would be in people with dilated cardiomyopathy. At that point their EF is low and they have low blood pressure. They'll feel better if their EF goes up with treatment (increased perfusion), but whether that is reflected by any other efficacy metric is doubtful. The dilated heart has some massive problems and requires remodeling, and this drug's MOA won't help in that regard.

I won't say this is Zebra's law or whatever. However it is pretty clear that increasing EF in end-stage patients with transient treatment of agonists (dopamine, dobutamine, epinephrine, etc...) results in those patients suffering poor outcomes. Granted these people are very sick and there isn't a great control group. But nonetheless, increasing EF in a chronic fashion doesn't strike me as the best idea.

All that said, I'm scientifically curious to see how this comes out. But I won't put any money on it.