path: root/transcripts/open-science-summit-2010/scott-johnson-myelin-repair-foundation.mdwn

Scott Johnson

Myelin Repair Foundation

Curentrepreneurs

Good morning. My name is Scott Johnson. I am president and founder of the
Myelin Repair Foundation. For those of you who have no idea what myelin is.
Myelin is the insullation of the nerves in your central nervous system and
peripheral nervous system. And in multiple scelerosis, it is damage to the
central nervous system, i.e. the brain and spinal cord that is the problem. I
will talk more about that in a minute. My quick overview today is to first of
all talk about how medical research is done, and what that process is, from
basic science to working with pharmaceutical industry, and making a case for
why that system is completely broken and not performing the way that people in
this room would like it to perform. Then talk about a solution that we're
implementing to deal with those that slow down the current process, then talk
about our results to date, and talk about what we see for the next few years.
That's a quick overview of what we'll talk about.

The title here- a new paradigm for medical research. The system is completely
broken, isn't providing treatments that we need, and a new way of doing it
cuold have a dramatic impact. We think taking 50 to 70% of the entier process
is doable. That's what we're about to demonstrate here. So, here's how it
works. Basic science is done in academic institutions all over the world,
driven by principal investigators in their lab. That work is funded primarily
by governments like the NIH, which provides $30B/year for medical research.
There's another $20B provided by other governments, agencies, by other private
foundations and individuals. So about $50B spent per year on academic medical
research. If anyone wants to take a guess, the tyypical way that output is
measured is either measured by dollars given, or how many papers are published
as a result of that $50B. Does anyone in the audience want to take a guess
about how many academic medical papers are published? 40k? 50k? 400M? 250k?
It's over 800k/year, that's how manyp apers are piublished every year. There
are some good news and bad news. That's a lot of great science discovery.
That's a lot of papers for industry to wade through for them to figure out if
they want to commercialize it. The reason why we show these circles.. is that
basic science is pretty random. There's no research plan. No disease
organization actually has a research plan. They put out a request for
proposals, they peer review those, and those that get the highest ratings,
that's what gets funded. Most academics would say that it should be random,
since you can't know where they are going. Well, in some cases you want to be
outcome directed. On the right hand side, you have the pharma industry, and
they $50B to $60B per year on R&D. In between the two, you have the valley of
death. There's a big gulf between the academic scientists and Big Pharma. This
gap has gotten larger as more science is moer narrowly focused, and Big Pharma
is increasingly removed from the academia.

On the right hand side of this diagram, there's a very small arrow coming out.
Between 1995 and 2005 the amount of money on academic research and on R&D in
Big Pharma doubled in real terms, and yet the number of new treatments coming
out the end, that right-hand arrow, actually declined. To me, that's insanity.
If you keep pouring more and more money at something, and you expect new
results, well, that's fucking crazy. You have to do something different.
Academic research is not equivalent to drug discovery. There's a huge
disconnect.

I talked about the peer review process for grant money. The end result of peer
review is that only incremental experiments will get through. They won't put
in a grant application for a breakthrough. THere's very little competition-
you have to have these narrow silos deveoped over the years, and there's no
mechanisms in academia for silos to work coordinated on a specific problem.
Without a research plan how are you going to coordinate your efforts to solve
a problem? Some of the issues we saw was that many academic things don't get
patented. Academia thinks that the information is free then. The problem for
industry is that if there's no protection of the IP,t hen they are reluctant
to spend hundreds of millions of dollars to develop something and move it
forward. The R&D has doubled, but the FDA approvals has not .. one thing that
is interesting is that that 50 or 60B per year that industry spends, it's for
R&D, but what has happened over the last few decades is that industry doesn't
do research, but they do tons of development. There's a policy called NURDO-
No research, development only. The industry over the past few decades has
relied on the biotech industry for research. Big Pharma would just buy the
promising ones. Unfortunately what has happened is that the returns on venture
capital in biotech, the amount of money going into venture capital for biotech
has declined, so that has gone away.

Another part of the issue in terms of the system, is that there are many
different players or participants in the value chain, and nobody is out there
thinking about how to coordinate that. One of the things that is unfortunate,
is that NPOs for the last 5 or 6 decades, they have patted themself out to the
NIH, like the American Cancer Society, they have adopted the NIH peer review
grant system as the gold standard so they give out the grant money in the same
way that the government does. That's too bad, because they are government
industry, you have to give out money in a completely unbiased way, because
their hands aer tied. Non-profits do not have this restriction. A key thing
that NPOs play a unique role, if they function this way, is to be this
coordinating unifying force across the entire value chain and across all of
the different participants. For all those reasons, we characterize it as a
completely broken system.

What I did, the reason why I got involved with this, I was diagnosed with MS
when I was 20 and an undergrad. I was able to pursue a business career. 8 or
10 years ago, after having the disease for 25 years, I was just assuming that
research was being undertaken at an organized fashion. What struck me was that
there had to be a simple and straightforward way to organize the science in a
rapid fashion. our mission as an organization is- it's great to have an idea
for a modle- unelss you prove it, nobody is going to believe it. We're
developing and demonstrating this model for myelin repair for multiple
scelerosis, so that we can show the model works. Our major goal is to change
the way that all medical research is done. We want this model that we're
pioneering to be adopted by every other disease organization out there. We
have raised $43M over the last 6 years, and almost exactly half of this money
has been from people funding us because of their interest in the model. Half
of the funds come from MS participants. It's how narrowly our research is-
myelin repair, $21M has come from people who jjust want to see this model
proven, because their disease for their family is Alzheimer's or Parkinson's,
and they want a model that will dramatically change things.

This is a graphic of what our system to try to speed up the basic sciencei s.
What we do is we have a narrowly defined problem, we have- we then try to set
out to figure out, what expertise do we need to solve this. My background was
startups, so I approached this like a startup, you want a small team of the
very best people in the area of expertise, instead of an army of mediocricy,
and then we found the best scientists in each of those areas, we had 5 PIs
from 5 different universities, we then sat down with those guys, put together
a research plan. This was a brand new experience. You think they would think
broadly about the overall scope, that's just not the case. We're working over
the course of a week and said, let's list out all about what is known about
myelin formation, damages, and what questions. We had about 100 questions that
we had, and if we cuold answer them, we could fix things. So every 3mo we
update the research plan. We didn't want to move the scientists to a new
building, they were all at great places, like UCSF, etc., the idea was to
ccreate a virtual lab, we have a Data Cloud where every student and PI has to
immediately put the data from their experiments in their system so that
everyone across the entire team can see it. We have 45 full-time scientists
that we're funding.

The next element was this green box, which is what we call a boundary
condition which is the research plan. The other key element is the management
process. The current system of all this time up front for evaluating grant
system is "Fund and Forget". All this time up front, the assumption is that a
paper will get published. the right approach is to pick greatp eople, and talk
with them on a daily basis, by phone, email, webinar, in-person meetings, and
through that process, much better science is resulted. Much of the scientists
that you are talking with here, tenured and so on, they are doing better
science here than they ever have, because of dealing with really brilliant
people. We do protect the intellectual property, we do negotiate agreements
with the uuniversities. WE pay for the patents. The universities own them, but
we have exclusive licensing rights, so we can go to, for each invention, what
company out there would be the best, because of their expertise to move it
forward. Our idea is .. mitrition rate in drug development is incredibly high,
so we want to push as many things in the pipeline as possible so at least one
thing would emerge as a treatment.

It's compherensive- all of the inforamtion responsine,. biology, the blood-
brain barrier, all of these are pieces of solving the overall problem. This
slide is to say that the mitrition rate is so high. The high cost of clinical
trials. When you look at the entire value chain of ioPharma. The majority of
the cost- 2/3rds is before the clinical trials. For every 260 targets, there's
one thing that emerges as a treatment. You make many small investments
initially. Our objective was- after showing up the front end, was to how can
we speed up the translational portion and what can we do to address that issue
as well. So what's happened in the first five years? When we started in 2004,
myelin repair was not even on the radar screen of a single company. It was not
considered therapeutically possible, and all of the expenditures in MS
research was on immunosuppression idea, they didn't think you could repair it,
and just supress the immune system. Five years later, 30 companies now review
myelin repair as the next generation of MS treatment- that shows how much the
dial has shifted, and that's big. We've identified about 150 targets that we
can take to companies to try to have them move forward. Some of them are
already in trials for other indications, and those comapnies.. myelin repair
possibilities. We invest in tools and models. It's very difficult to get NIH
to fund that, and it's critical. So we've invested heavily in that, we've had
companies come to us now who view the models we've developed as better than
anything else they have, and they want to runt heir compounds through our
assays to see how well they wokr.

We operate like a virtual biotech. Unlike most nonprofits, we have 5 PhDs, all
from the biotech pharma world, they have drugs on the market. So we can manage
the overall process. That's very different. The first 5 years will cost $25M
to execute. We were able to do that for $21M. When you're talking about
hundreds of billions of dollras on R&D, it doesn't take a lot to do it
differently to have a dramatic impact. This graphic across the top is the
various steps in the value chain. So in terms of what we seei n the second 5
years, we need to keep identifying new targets, so we'er going to continue to
fund the basic science team, but we're going to validate targets as well to
industry standards (which other NPOs don't do) to the point where industry can
pick them up. And our next step is forming partnerships with companies to take
these targets and move them forward. The costs raise dramatically each step in
the chain, the sooner we can offload these the sooner the better. I only have
two slides left.

This is our description of our research plan for the second 5 years. That what
was what we did in the first five years, basic biology discovery. This
translational part is really key, biomarkers and so on. And setting up
netwroks and contracts with research organizations to take our discoveries and
validate them to industry levels, and then work closely with partners. It
turns out that strategies for doing this- there might be some things for
spinning out companies, partnerships will form, how we can fund the validation
work by others, and so lastly, the point I will leave yuo with- we believe we
are the only non-profit that is focused on the entire value chain, in every
step of the process and how to accelerate them. There are many oragnizations
focused on curing a disease, we are the only non-profit focused on developing
a replicable model that can be applied to any disease research. There is
nothing in our process that is specific to myelin repair. Everything we're
doing, we're doing as much as we can to develop modules that we can hand off
to other people. Half of our money is coming frmo people who just want to back
this moel. They want to see this model replicated, they want to see this
change in biomedical research and the way research is done.