Quantcast

Jim Letourneau's Blog

Investing, Technology, Travel, Geology, Music, Golf. I think that covers it.

ALTs

This post is part of 8 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).

What follows is a lengthy and candid interview about 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 near the end of March 28-April 5, 2011.

  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 8

Now, this chart is where these panel guys got all huffy about these ALTs. What an ALT is,

is not liver damage, as they stated on a stage. What these ALTs are, are signals. An ALT is
an enzyme in the liver, kind of a marker. If something different is going on in your liver,
ALT’s kind of wake up, turn on a little bit. That's how doctors measure it. Can it be a sign of
something bad? Yes, definitely, especially in conjunction with something called bilirubin. ALT
means change is going on. Bilirubin means death, cell death is going on. So what changed in
those livers? Well, you just flushed a whole load of plaque through the liver, and this is what
is showing. This is showing that increase in plaque out of the arteries, and it goes to the liver
and flushes it. So you've just flushed an enormous amount of plaque through the liver. That
is normal. That is 100% normal. That is what is supposed to happen if our drug is working.
So they point to this as a safety issue for us – a total of three, eight, and seven – 18 and then
the AHA panel totally ignore 142 patients in the Merck study. Also, three of these actually
had nothing to do with our drug. They had to do with surgeries they had and other things
that were known.

JL: Were you expecting to see that?

NW: We wanted to see that. In designing a clinical trial, which is an experiment with humans,
we needed to know the boundaries.

DM: Yeah. So I'll tell you one thing. In all the due diligence we continue to do with all these
pharmas, about a year ago in some of our studies, one of the pharmas said, "Are you seeing
ALT increases without bilirubin?" We said, "Yes." And they said, "Good, because if you're not
seeing them, nothing is happening."

NW: You're not working if ALT signals were absent.

JL: Okay.

DM: So then the AHA panel turns this into some big negative for us. That is total garbage.
Any liver expert out there . . . we had a board meeting last week, and I brought in such a liver
expert. I brought a liver expert who used to work for Merck and worked on their simvastatin
drug. I brought him in to talk to the board about his opinion of what was going on in our
livers. And he had zero concern. Totally normal. The board seemed thrilled with that, by
the way.

NW: I mean, even if you look at it, what is the most common cause of ALT increases? Statins.
Guess what our patients were on. Everybody was on a statin. So why are we looking at 208?
The answer is right in front of us. They were on statins.

DM: Out of the 15 ALTs that were related, every one of them was on high dose or old statin.
Every one of them.

NM: Every one of them.

DM: This is good news, not bad news for us.

DM: Also two of those three extra’s were on high dose Tylenol. Tylenol is a bad drug for high
ALT’s. So they don't want to see ALTs of over eight by the FDA. We set our limit at three. So
we started counting them at three. We leave patients on drug until eight. We only had five of
those. We set our own low limit because we're new, and we're trying to prove how safe it is.
Tylenol, if you take Tylenol two days in a row, you'll be at 11, 11 times over the normal.

NW: With alcohol, you'd be even higher.

DM: So, let's now do the same thing we did with the other chart. Let's break down these
patients. Where are these patients? So if you take your low to mid dose statins, only one
of those 18 ALT patients are even in there. One. We're just not going to use high dose in
the next trial. We will in the future, because we feel it's not a problem. We feel it's a sign of
efficacy, not negative. But to make the scientific community happier, we can show that we
can limit ALT’s. Look at the difference.

You look at the ASSERT sub population analysis of the low, mid dose statin and the low
HDL population that we're planning to enroll for our next trial, ASSURE. This would total 85
patients, not a small group. That's how many ALTs you would have had versus what we saw
in ASSERT, one. And this was blown up as a problem? Give me a break. Especially when
they were sitting on this information of their own. It was incredible. And all those good news
reports on Merck came out before the journalists had even read the accompanying Journal
article. It's just ridiculous.

So let's look at this yet another way. Here's the increases of HDL, and all those problem
patients with ALTs over three times, look at their HDL increase. This is the large HDL that's
taking the plaque out. They're not a problem. They're hyper responders. These guys had so
much plaque going through the liver, the ALT is just turning on and saying, "Hey, what's all
this? I haven't seen this in a while." Then they calm down, and we've already showed they
calm down. They drop right down afterwards. While this is the chart showing that the Apo-AI
and HDL increases are still going up at some significant rates.

JL: So your trial was 90 days?

DM: This was 90 days.

JL: And if you did 120 days, you'd probably be . . .

DM: Sure. If we had done 91 days, we would have been statistically significant. It takes a
while to get going, about eight weeks.

JL: So at eight weeks, you don't see anything hardly.

DM: Sure. But if you ran a statin trial for only 12 weeks, you'd see nothing, because it takes
16 weeks for statins to start working. So you'd see a flat line, and then you'd see a slight
increase. 16-20 weeks before they start working. Niacin takes eight to nine months before it
starts working.

JL: Really?

DM: Yeah. Your body's been designed a certain way. The chemistry inside of us has been set
that way for a million years. And now you're putting a drug in and saying change. Sometimes

the change is slow. You've got to get it the right way. If you crank it up too fast, well then,
eight to nine months out, it could be toxic. So you have to do it slowly and get there safely.

We couldn't have done a study longer than 12 weeks anyway, because we only had animal
safety testing for 12 weeks. Now, our animal safety testing is out a year, which allows us to
do anything. We can do two and three years off of that. So we have our full animal toxicity
work complete now, and all the monkeys have been . . .

JL: The monkeys are doing well.

DM: No.

NW: No. They're dead now.

DM: The monkeys aren't doing very well.

NW: We sacrificed them per government protocol.

JL: Oh really?

DM: You have to do liver biopsies, brain biopsies, cardiovascular biopsies. So the monkeys
did very well. But they're not doing so well right now.