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CETP History

This post is part 5 of a 16 part series of posts taken from the transcript of an interview I (JL) conducted with Resverlogix (RVX.TO) co-founders Dr. Norman Wong (NW) and Donald McCaffrey (DM).

Topics discussed include the history of Resverlogix, recent events at the American Heart Association meetings, and future plans for the company.

I'll be publishing two interview segments a day so not all of the links may be active if you are viewing this in the March 28-April 5, 2011 time frame (I currently own RVX.TO)

  1. Background of Dr. Norman Wong

  2. Early History of Resverlogix

  3. HDL Biology

  4. American Heart Association Meeting - 2010

  5. CETP History

  6. Importance of HDL Type

  7. AHA ASSERT Trial Response

  8. ALTs

  9. Investor Reaction

  10. The Next 2 Years

  11. David vs. Goliath

  12. Alzheimer's Therapy Potential

  13. Upcoming Assure Trial

  14. Volatility of Resverlogix

  15. Resverlogix is Expanding

  16. More on the sell-off

Part 5

NW: You've got to take a little step back and look at the history of this sort of thing. In 2007,

as Don has said, Torcetrapib bit the dust. It bit the dust because it killed more people than it
helped in their Phase Three clinical trial. It killed like . . . I can't remember how many.

DM: 61%.

NW: Yeah. More deaths . . .

JL: Which seems . . . kind of parallels . . .

DM: 27.5%.

NW: So since then, the HDL field has sort of wondered around and is now trying to recover.
And then the AHA hit. HDL people were looking for good news. They were looking for
something. They were looking for a revival of the HDL field, which it did. But they did it at
our expense. We never gave up after Torcetrapib. RVX continued and we said we're different
from CETP inhibitors. We actually make good particles of HDL. We don't raise it by a hundred
. . . Torcetrapib increased it by 61%, Anacetrapib, 138%.

DM: Dalcetrapib only does 30%.

NW: Yeah, that's right. And I asked these guys, I said, "Look. There's 30%. There's 138%.
Who's right?" And they're both the same types of compounds. They're CETP inhibitors.

DM: See what happens here is once this large filled HDL goes to the liver and dumps, most
of it exits through the liver, as I told you. Some of it cycles back to become LDL cholesterol,
and that's an important part of the Reverse Cholesterol Transport system. So stopping that
is stopping the formation of new LDL. They've interrupted the system. You've got your LDL
dropping in a short period of time in this study, to a point where 142 patients have to drop
out of the trial for risk of fatally low LDLs. 17.6%. If you run a two or three year trial, what's
that number going to be? And if somebody doesn't get off of it, where are they going to be?
They're going to be in the drain.

NW: They won't be left in the trial.

DM: So for us, what we have to do is we have our data show plaque regression before these
CETP trials fail, because these trials will fail. And if we've already shown HDL ApoA-1 does
work if you do it the right way, these CETP trials could fail all at once. We don't care. I'm glad
they didn't fail this week, because it would have been like three years ago with Torcetrapib
where it was nuclear winter for us for two or three years, because nobody was interested
in HDL anymore. HDL ApoA-1 is one hell of a good program if you're working in the right
category, and that's raising ApoA-1 and creating the production of new empty HDLs. Not
down here where you just have HDL numbers go up. We call this constipated HDL and
dysfunctional HDL. So for us, we know the science differences. We know what they're doing.

We know Anacetrapib is just playing the game of saying, "Oh, it's 138%. Isn't that great?"
No. It's not great. Yes, they got media off of it. Yes, their stock went up $3 billion. Is that
drug ever going to make it to the market? In my opinion this paper would strongly suggest
no and if it does it will not be used for plaque regression.

NW: We want to make sure that the audience and investors understand that we're different
from what CETP inhibitors do. I realize that our numbers are not 138%, but we're raising the
right particles of HDL. Biologically it makes sense. It's not the number . . . let's look at the
prime example, Torcetrapib.

DM: Quality versus quantity.

NW: Exactly. You look back at the Torcetrapib study. Phil Barter, who's on our clinical board,
did the post-hoc trial analysis which was to see if Torcetrapib worked or not, regardless of
the death issue. He divided it into quintiles of how high the HDL raised, and then he looked
at what that impact had on atherosclerosis.

In the first four quintiles, there was nothing. Nothing happened until that very, very end
quintile, which is like 100 and some odd percent more than the normal individual. They got
this little, little impact. So that's what CETP has to do. Ours? No. We can impact upon plaque
regression with even a small amount of the right particles of HDL, and that's what we do.
That's what we're going after. But it's what we call surgeon mentality. If your surgeon says
one gram of antibiotics is going to work, he's going to give you five, because that's the
surgeon mentality. Sprinkle more on it.

DM: When in doubt, cut it out.

NW: Give it more. Give it more and then it will work.

JL: Keep your life simple.

NW: Give one gram. One gram is enough.

DM: This chart kind of shows that. So in the old data, old meaning only 15 years. This is a
new field. HDL got its name the good cholesterol because of the Framingham study. So it
showed that if your HDL was one milligram per deciliter higher than mine, you have a 2%
or 3% less chance of cardiovascular disease. So that's what all the big pharmas based their
earlier programs off of. So let's just get bigger HDL numbers and we've won the game.

So 138% 10 years ago would have gotten them a multibillion dollar selling drug until they
figured out it maybe killing people. But then, the new studies here, the Framingham offspring
studies analyzed sub particles, because the technology is there now to do so. We now
understand there are different types of HDL.