And now we're going to have four shorter presentations by four
other outstanding speakers.
And the first one I'm going to invite on stage is Matt Wilsey.
And Matt is an entrepreneur and investor and adviser.
He has been an amazingly strong advocate and supporter
of medical research, drug discovery,
and the development of novel genomic approaches
for precision medicine.
He holds BA and an MBA from Stanford,
so he's a local person.
And he's on the board of multiple foundations,
including the Packard Foundation for Children's Health.
I don't want to say anything else about Matt
except that maybe you could call him a rare disease hunter.
And I think I'll tell you why in a second.
So Matt welcome.
Morning, everyone.
So I wanted to start my presentation actually
with my name tag from this conference.
Yesterday, I was looking at the back of it,
and my phrase on the back says I'm inspired by dot, dot, dot.
And I don't know if some of the others
have a similar phrase on the back,
but I thought that was a good place.
And what I'm inspired by are these patients here,
and what they all have in common is a rare genetic disorder
called NGLY1 deficiency.
And my daughter, Grace, is actually one of those patients.
She's 5 and 1/2 years old, and while she
looks perfectly normal, healthy, happy
here, a typical developing child,
she's in fact not normal.
And essentially, her metabolic engine is dysfunctional.
She has severe problems with her central nervous system,
her liver, her eyes, her muscle.
Essentially, NGLY1 is a critical gene
that's found almost in every organism in nature.
And what it does is it cleaves off a glycan off of a protein.
Oh, I see my timer's not working, but I'll be fast.
Don't worry.
And so what's it like having a child like Grace.
I get asked often what is it like.
It's like this.
It's like living on a deserted island.
It can be quite wonderful and beautiful,
like a typical parent-child relationship.
But it can be incredibly isolating.
You really don't have anybody that can understand
what you're going through.
You feel like you are in this world completely by yourself.
And in fact, a lot of friendships
disintegrate because people have trouble understanding it
and don't want to think about their kids falling
into a similar trap or that there's
a world that exists that this happens
to such innocent human beings.
But this analogy isn't quite right
because it looks actually pretty nice,
and so this is probably a better island.
And for those who have seen the movie Gravity,
it's really like being in space by yourself
with no escape hatch, no space shuttle, no space station.
Your oxygen is approaching e, and it's actually
accelerating down because you're breathing faster and faster.
And so what we found five years ago
when we started-- and we started here
at Packard with a stay in the NICU
with an amazing team of doctors--
we really had one relationship.
And these are the four main buckets
that I think about in terms of diagnosis,
but then also understanding the particular disorder
and developing a treatment and cure.
And I say cure, which not being a doctor myself,
often ruffles some feathers.
There's very few cures that have been developed.
But that's actually what we're trying to do.
We are trying to develop a real cure for this disorder.
And at the time, we essentially had amazing clinicians,
primarily led by Dr. Greg Enns here at Stanford,
who I view as one of the best biochemical geneticist
in the world.
But we didn't have a relationship with NIH.
We didn't have really relationship with researchers,
and we didn't have a relationship
with pharmaceutical companies.
And so to extrapolate the Gravity analogy
a little bit further, it was like we
were in one part of the solar system
and had to get to the opposite side.
And then once we were there, we had to combine solar systems.
And how we're going to do that in a world that just doesn't
like to change and certainly doesn't
like an outsider like myself?
I'm a Silicon Valley entrepreneur.
I've started three companies, and so I really
apply a lot of what I've learned here
in the valley to becoming a rare disease hunter.
And if you notice in Silicon Valley, there's often a hub
and spoke system where venture capitalists are
funding similar businesses that are
pushing products for consumers.
And I thought this would be a perfect way, this hub
and spoke system, to create an ecosystem of the best
medical minds in the world.
And then if I took that a little bit
further, what are some other examples?
Well, the interstate system that we've all
utilized across the United States is again another hub
and spoke system create-- basically
connecting these central hubs.
So what we started to do was assemble a world class team.
And this is actually our brain map of our team,
and it's very similar to the hub and spoke system
in Silicon Valley or the interstate system.
And what we would go-- we would go to a subject matter expert
like, Huda Zoghbi in Houston at Baylor,
and we say, who is the best at x or what is the first beachhead
that we should establish?
And from that we would do a Drosophila model.
Who's the best at that?
And that conversation would lead to three more people.
Those three conversations would lead to 7, those 7 to 15.
And essentially, what we had to do
was build the team ourselves.
And while a diagnosis is quite hard,
this is even more challenging to really put this team together
that can tackle an ultra rare genetic disease
like NGLY1 deficiency.
So actually, just two weeks ago in Palo Alto,
we held our first scientific conference.
We had 50 scientists from around the world fly
in from Asia, all over the US, and Europe.
This disease only has 30 patients worldwide confirmed.
So we have more scientists working on this
than we do number of patients.
We outlined what our keys to a successful approach have been.
And this is all from a scientist perspective.
It's the speed at which they're researching
can get off the ground.
They're not relying on traditional funding,
especially from the government.
Although, there is a place for that of course.
They're not waiting a long time for a funding decision,
so when we receive a proposal, we're
very fast at getting back to them.
There's no uncertainty what parts are liked or disliked
by our committee, which is led by our scientific advisory
board.
We're combining subject matter experts in various fields.
I often say that it's a Manhattan-like Project
for rare disease.
So there's no NGLY1 deficiency expert.
We have to take the best in gene therapy, the best at iPSCs,
the best at Drosophila, the best at mitochondrial diseases,
and put them together.
And then we're taking a business approach.
We require objectives and milestones.
Again, drawing from my history is an entrepreneur,
we needed a lean, efficient start-up, and, of course,
you need a business to do that.
And how do we add a new teammate?
We delineated that in a similar manner.
We evaluate our gaps with our scientific advisory board
and our existing team, and I think that's key.
It's not like they aren't a part of the unit deciding.
We triangulate again on who is the best
and the best in the world.
We will go anywhere to find that person.
We initiate contact.
That's often a cold call or cold email from myself.
We explain what we're doing.
We develop a plan again, objectives, milestones,
and budget.
We also have to agree to quarterly check-ins
and reviews.
We review the plan with our scientific advisory board.
We make sure it doesn't overlap with existing work.
I think that's important that we're not
limiting people's runway and, obviously,
publishing potential.
And then we fund and assimilate the team.
So essentially what we've done is we've turned
this, where we really weren't connected, to something
that's more like this.
And of course, it's a simplistic drawing
where we know that NIH is communicating with pharma.
But on a particular disease like this,
I don't think anybody has been able to assemble and accelerate
research quite like this from the disease being discovered
three years ago to having 50 scientists working on it
with some real possibilities for therapy.
And if you take a look at our collaboration
map-- I'm just focusing on the US
here-- this gives you a little bit a snapshot
of where all of our researchers are.
And again, it looks very similar to the interstate map
that I showed you earlier, and I think it's pretty cool.
I didn't show all the different permutations of Stanford
talking to Baylor or Baylor talking to Florida or vice
versa, but those lines are all there,
and it would be a jumbled mess if I did.
I also think it's important to note that NGLY1, or any disease
be it rare or common, will only be
solved with open collaboration across institutions.
And I focus here primarily on the academic centers,
but we could also have two more slides
on industry or governmental agencies
from around the world that are working together
on this particular disease.
And we hope this is the model moving forward
for other conditions.
We have some lessons learned, and I'll be quite quick here.
Patients and parents have great intuition,
create an open partnership with them.
I've sensed a new trend in the clinic
where there's more of a firewall between research and clinic.
Thankfully we, got in before those firewalls closed.
But I would encourage them to come back down.
A good idea can come from anywhere.
We often tell people to collaborate,
and they say, oh no, I'm collaborating.
I'm working with the person that the bench next to me
or down the hall.
That's not what we're talking about.
We're talking about collaborating
across institutions, across departments, with competitors.
Move fast and break things.
This is the phrase that was made famous by Mark Zuckerberg
the CEO of Facebook.
Essentially, jump into the deep end and see what happens.
It does not have to be perfect.
The plan does not have to be perfect.
Share often, including negative results.
And then objectives and milestones,
like I mentioned earlier, they are critical.
We know science will take random paths,
and you're going to hit roadblocks,
but you have to develop a game plan and have goals.
Really quickly, this is the NGLY1 mascot.
It's Remy from the Disney Pixar movie Ratatouille,
so thank you to Disney for letting us borrow this image.
I love it because he looks so darn cute,
but also because it looks like he has a brown top phlebotomist
tube, which we have seen a fair share of.
But really what that movie speaks to me,
and I think to the NGLY1 team, is
that a good idea can come from anywhere at any time.
Be open to unexpected.
Be open to serendipity.
Don't be close minded about possibilities.
And thank you so much for having me here today.