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Part II: Lou-Ellen Barkan interviews
Elemer Piros
Part I of our Reflections interview with Dr. Piros was
featured in our Fall 2009 issue.
L OU-ELLEN BARKAN (LEB): We’ve had an ongoing
concern that there may be too much investment in the
amalyoid hypothesis. Is this the right hypothesis? We’ve
been looking for the renegades.
Elemer Piros (EP): It’s probably a reasonable hypothesis,
but it shouldn’t be the only one because we know how
different the disease is in different people, both in the age
of onset and the length and course of the disease. The
manifestations of the disease are also different. We should
entertain other hypotheses.
The sad part of this story is that for decades, the
mavericks weren’t funded by the NIH because there was
a cult-like following of the amyloid theory. Everything
else was seen as unreasonable. There are still two groups
that disagree about the pathway of the disease and I don’t
think they’ve come to a point where they each accept
each other’s ideas.
The remaining argument is a chicken or egg problem.
In other words, if the amyloid is at the root of the problem and the tau follows, then it makes sense to inhibit the
amyloid and break plaque buildup. However, if we
approach the tau first, the amyloid problem may cause
other issues, which are not addressed. Tau treatment
might only treat the symptoms rather than the cause. Each
one is a different value proposition. What comes first?
Nevertheless, it is nice to see these opponents talking and
acknowledging that each has valid points.
LEB: Last summer one scientist suggested that there are
two kinds of amyloid, soluble and non-soluble. Why has
no one thought of this before? It seems so obvious.
EP: What we are actively working on is what’s harmful for
the brain versus what helps the brain’s functionality. You
could be too aggressive and clean up amyloid needed for
normal function. If we are too aggressive on one pathway,
it leads to severe side effects. One vaccine trial was halted
because the treatment may have been too aggressive. If
we were more refined in our thinking and could attack
multiple targets, that would be ideal.
LEB: Amyloid protein exists throughout the body. Have
we learned anything from amyloidosis research?
EP: There are a number of common features, but we are
much more advanced in our understanding of Alzheimer’s
disease and we have more treatment options available. It’s
ironic that the same company that developed Alzhemed
(Neurochem), which failed to show efficacy for Alzheimer’s
disease, also failed with a similar approach for amyloidosis.
Amyloidosis is not as prevalent, so we haven’t spent that
much time and effort on it.
LEB: If you’re interested in investing in Alzheimer’s
disease, either in a public company or a privately funded
laboratory, what’s the very best way to locate a good
opportunity?
EP: The best strategy for the non-specialist investor
— one who doesn’t have the training to understand the
underlying technology being developed — is to find a
technology that’s been validated by an investment from
big “pharma.” This reassures the investor that someone
has done the due diligence. For example, before they
invested in Medivation’s Dimebon, Pfizer spent six months
understanding the program, the science and the intellectual
property protection. And they took their translators to Russia, where the trials were conducted, and interviewed
those sites. They understood how the clinical trial was
conducted, what sort of scrutiny was placed on the study,
and then they agreed that this was a program worth taking
a risk on.
LEB: Some time ago, I learned that there is investor profit
to be made in good news, which raises the stock price,
even if the drug has just advanced from Phase I to Phase
II. Then when you advance from Phase II to Phase III, you
get another bump, but it’s in this last step that the investor
has real risk.
EP: That’s correct. And every one of these steps usually
leads to some sort of a risk mitigation — value increase
— but the biggest inflection point is probably between
Phase II and Phase III. Phase II is where we prove that
a concept could make sense. Phase III is confirmation.
The problem is, especially in Alzheimer’s disease, Phase
II trials are relatively skimpy. Therefore, the Phase III
confirmation studies do not work out as well as in other
fields. Alzheimer’s research is a unique example where
the biggest bang for the buck has been in the Phase II
setting.
LEB: One company reached out to us just as they were
going into Phase III. There was tremendous excitement
when they rang the bell at the NASDAQ. Unfortunately,
we were also watching when their disappointing Phase III
results came back and the company went into bankruptcy.
As an investor, it would have been better to be invested
during their Phase II period.
EP: This is where it gets complicated for the average
investor. The most advantageous time might be just
before a small company takes a partner. It’s advisable not
to do the huge Phase III program all alone since a small
company won’t have the resources — capital, time or
human — to conduct the study alone. Once the Phase
II data is available, it’s very likely that in the ensuing 6-12
months there is going to be a transaction.
LEB: The real reason that I’m interested is not to advise
our readers on investing, but because I think everyone is
worried about the reduction in NIH and NIA funding. If
there are fewer government funds then the money has to
come from private partnerships and investments.
EP: Fortunately for Alzheimer’s disease — and I’m not
sure if other therapeutic areas enjoy this luxury – there is
so much interest from the private sector that the slack in government funding is being picked up, at least so far. The
private companies see that they can make an investment
in a condition which has 5 million potential patients, who
will be taking the drug for a long period of time. It’s
difficult to predict that we are going to cure the disease
soon, so people will need the drugs for a long time.
LEB: Clearly, the economic opportunity is extraordinary.
We know the numbers of people that are going to become
ill are shocking.
EP: And we haven’t seen a slowdown. Nevertheless, I
think individuals should continuously push for government
funding and support research by contributing to
organizations like yours. The advantage of the Alzheimer’s
Association is that you have a nice mechanism in place to
determine how to distribute the money.
LEB: We’re very proud of our peer review process.
Scientists know that the funds are being allocated to
folks who are doing real research in areas that will make
a difference.
EP: So like private equity, you pick up the slack where the
federal government leaves off. And the private companies
continue to renew their commitment. The Medivation
deal underscores Pfizer’s commitment to Alzheimer’s.
Wyeth declared war on Alzheimer’s. I think you read
those headlines. Hopefully, they’ll also continue to fight
the battle.
For these reasons, I’m not worried, at least in the near
term. But if government funding is cut in half, or worse,
then the next generation of knowledge will be handicapped
because large pharmaceuticals rely on academic findings.
Academics are the ones who champion new areas that
don’t seem to be all that rational at first, or may not be in
line with the amyloid hypothesis. If the funding for these
scientists dries up, they won’t receive grants and we’ll miss
that component sometime down the road.
LEB: I’ve been convinced for years that the person who
will cure Alzheimer’s disease is now a junior at Bronx
High School of Science. My fear is that there will not be
adequate funding to engage this young person to go into
Alzheimer’s research, which is such an exciting field.
We won’t make real progress until the general public gets
behind our agenda. Look at what happened in breast
cancer research and HIV/AIDS, which was transformed
from a death sentence to a chronic disease. These diseases had very strong support from the general public.
EP: I think they’ll have a wakeup call soon. The Baby
Boomer numbers speak for themselves.
LEB: Given where we are today, when do you think we’ll
really see an effective drug?
EP: I think we’ll be able to impact the course of the disease,
modify it, but not cure it, within the next five years. There
are approaches out there including Medivation’s drug,
Dimebon. But we don’t have ultimate proof yet. We are
getting much closer.
Until now, we’ve been trying to put out a fire when
three-quarters of the house is already burned down. Now
the picture has changed, and we are at the moment when
the Fire Department is right at the door and the fire is
just about to begin. We still cannot prevent the fire from
happening, but we have a much better chance with what
we have in the pipeline.
We have to learn much more about Alzheimer’s to
even fantasize about a cure. But a more reasonable goal is
to delay the onset so we only have to tackle it in one’s 80s
and 90s. That is a more manageable target than hoping to
eliminate it.
LEB: That supports the current actuarial statistics that
suggest that fifty percent of us will live past the age of
85. If you only have to deal with that fifty percent, you’ve
already eliminated a large portion of the problem for
the health care system. We are hoping that since the
Boomers are such a large target for the disease, they will
raise their voice to help us.
EP: I hope the population with early-onset Alzheimer’s
will be targeted more aggressively, because the impact on them is even more significant than an 85-year old.
LEB: Approximately 10% of the people with Alzheimer’s
are under the age of 60. Do you think early-onset is the
same disease that we see in those who are over eighty
five?
EP: It is probably the same since it has some commonalities
with the sporadic version and because the end result and
the symptoms towards the end tend to be the same. The
speed is faster, so it may have more toxic components than
the late onset version. We don’t fully understand this, which
is why you won’t hear me giving you specific differences
between the two.
LEB: What can we do? I know we can heighten
awareness, I know we can raise money for research.
What can we tell people about how they can help move
faster, more readily, more steadily?
EP: We all need to keep reminding ourselves and our
legislators that a train wreck is coming. A train wreck that
could bankrupt the healthcare system. Maybe we need
to say the train is right here in our backyards, because the
numbers speak for themselves. We should use these statistics
when our elected officials allocate the funding and remind
them priorities need to be clear. Industry will take care of
itself because they are motivated to keep on marching.
LEB:My hope is the politicians will start to worry about
themselves, and regardless of where they sit on the age
spectrum, I hope they’ll understand our issues and the
urgency.
Elemer Piros, Ph.D., Senior Biotechnology Analyst — Previously, Dr. Piros was a buy-side biotechnology analyst at Spear, Leeds & Kellogg, now
a wholly-owned subsidiary of Goldman Sachs. From 1990 to 2000, Dr. Piros conducted academic research in the field of neuroscience, focusing on
understanding the molecular mechanism of communication in the nervous system. He has published his findings in peer-reviewed scientific journals.
Dr. Piros earned degrees in mathematics and biology, and a Ph.D. in neuroscience at the University of California at Los Angeles. He then completed
post-doctoral training at Cornell University Medical College in New York. Dr. Piros was named the #1 stock-picker in biotechnology in The Wall Street
Journal’s annual “Best on the Street” survey in 2007. In 2008, the Financial Times ranked Dr. Piros amongst the top three earnings estimators in the
pharmaceutical industry. Currently, Dr. Piros’ research universe includes emerging biotechnology companies that develop products addressing the
nervous system and cancer.
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