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- So I'm really happy to be here today
and provide you with an update
on our Spinal Cord Injury therapy with OPC1.
My name is Francois Binette.
I'm the Senior Vice President for Product Development
for Lineage Cell Therapeutics.
Let me get this out of the way quickly.
You know, we're a publicly traded companies,
I'll be making Forward-Looking Statement.
I'm sure you've seen this in other presentation as well,
so I direct you to our website in our 10-K filing
if you want to learn more about this exciting area.
So what is Lineage?
We are a Regenerative Medicine Company, obviously.
We're manufacturing "Off-the-Shelf" Cell Therapy
from our platform of pluripotent stem cell
to address severe disease and injury.
So those diseases that do not have approved
therapies or therapeutic solution right now.
So what we're doing is relatively simple.
We're taking pluripotent stem cells
and we're deriving from these pluripotent stem cell,
various lineages, various specialized cells.
And what we're putting in people
to treat their disease or injuries is
that we're not actually injecting people with stem cells.
We're really trying to replace
disease or dead tissue with specialized cell,
the cell that have been damaged
and hopefully provide a long term benefit.
So this is really a little bit different
than treating symptoms
and this is really what attracted me
to this area of regenerative medicine
is the potentially the promise
of bringing a cure to patient.
At least providing a long term benefit.
But that's easier said than done.
Obviously, you know, to be successful with
regenerative medicine, it's rather complex.
Not only do we need to understand well
the biology of the stem cells
as well as the specialized cells
that were are targeting,
we also need to consider where the cells
are placed in the body.
That is often requires specialized tools
and instrumentation that do not exist
prior to this therapy being delivered.
So we have to work with engineers
and develop creative solution for delivering ourselves
because they often time needs
to be placed in a very specific anatomical compartment.
Moreover, we need to have a strong partnership
with a surgeon that are enabling
with their new surgical procedure to place these cells
in the right anatomical location
using these new these new tools and devices.
So it's very exciting field, obviously,
you get to interact with a lot of different people
with a lot of different background,
but it's complex.
It's a little bit different
than traditional drug or biologic development.
So we have three ongoing programs at Lineage.
We have a retinal pigment epithelial cell
for macular degeneration.
We also have a dendritic cell program
as cancer vaccine, which I'm not gonna talk about.
Today, I'm gonna talk about the oligodendrocyte program
or the OPC1 program for spinal cord injury.
So Spinal Cord Injury as you know
is a very devastating condition, you know,
and what I want to show you on this slide
is obviously there's a lot of statistics on that
as far as cost to the patient, to the society in general
and burden on the healthcare system.
But what's important, I think, for you to understand is
depending on where the injury is on the spine,
it really affect the patient differently.
That is, the higher, the closer the injury is to the brain,
the more severe or impactful the injury is going to be.
So alternatively, if it's lower on the spine
or closer to the thoracic spine, it's less impactful
where there are fewer nerves
that are involved in this area of the spine.
But the problem is that most of the injuries
because of trauma
they occur in the neck region or cervical region
because that's the least protected area of the spine.
So this is the area that's more mobile,
obviously as you know
and it's the least protected you know,
because they're lower and the spine is protected
by the torso and the rest of your body.
Needless to say,
for a patient it's really impactful, it's devastating.
Oftentimes patients are wheelchair bound
after that paralyzed as you know.
Lots of pain, recurring pain,
chronic pain, re-hospitalization.
Oftentimes these patient need to have
breathing assist as well,
shortened life expectancy,
so it's just dreadful for this patient.
And it really became very personal quickly
for us at Lineage
because although we acquired this program
about a year and a half ago when we merged
with a company called Asterias Biotherapeutics
that was developing this particular program.
You know, just this year we had a colleague of us
and we're a small company, right?
So, you know, colleagues for us
are almost family members and friends.
So a colleague of us, one of his family member
actually got a spinal cord injury,
just an accident and broke his neck.
And what's happening is that, you know,
we got really frustrated in some ways
because although we might have had a therapy
that could have benefited this particular patient,
we couldn't do anything because it happened
that we finished enrollment in our trial
about two years ago, you know,
that I'm gonna talk about a little bit
and then we're not quite ready for the next stage trial
and I'm gonna tell you a little bit about, you know,
what we're doing in order to get ready
for the next stage trial.
So frustrating, obviously for everybody
so it became very, as I said, personal to us, as well.
So what is OPC1?
Our therapeutic candidate for spinal cord injury.
So OPC1 is a preparation of oligodendrocyte D cells.
What they do, they're not neurons or traditional nerve cell
that you know that that are part of the brain
and peripheral nervous system,
they're the cell that are wrapping the nerves
and the axon of these nerves
to really insulate these axons to conduct
the electrical current or the communication
between the brain and the periphery.
So not only these cells,
they allow, they accelerate this electrical current
to communicate between the brain to periphery,
they're also responsible to maintain
good health of the neuron and the brain in the periphery.
So they're very important cell
to just maintain and improve the health of a brain cell
if you will.
So what we found is the cells that we can derive
from pluripotent stem cells
that we derive into the specialized oligodendrocyte,
they do what we were hoping that they would do.
We have a lot of preclinical and vitro and animal studies,
that show that these cells can indeed remyelinate these axon
that is they can recoat these axon
and the neuron and insulate them,
but are also involved in general health.
They help in tissue remodeling,
that is they help healing of this condition,
when you have an injury to the spine.
They help bring new vasculature to the injury site,
and they prevents scar formation.
They also help neurons communicate
between one and another by enhancing
these neurite and these fibril that communicate
between the neurons
and more importantly,
they improve motor function.
So this is what we're trying to do
from a clinical perspective
is improve patient's motor function.
On this slide, what I want to show you is on this table,
you see on the left is a few function
or daily activities that people go through
or in general life, right?
And you have a series of these daily activities
and what's important to see here
is that if you have an injury to say,
at the cervical level four, C4
you can see in red here that you know,
if you're impacted at that level,
you're in red meaning that you need total assist
to execute all of these your normal daily activities,
whether it's eating, you know, combing your hair,
moving about, you know, on wheelchair or whatnot,
you need total assist for doing that.
But if you can heal and improve the motor function
by just to level in a neck.
Remember, one of the first slide I told you
that the higher the more impactful it is.
So if you can move this healing down
to just a little bit in the neck,
you can greatly improve functional recovery in this patient
and now instead of requiring total assist
they can actually be completely independent
and many of these functional require partial assist.
So, just to motor level improvement is really impactful
for this patient and their quality of life
and that's what we're trying to attend with our therapy.
So, we presented the data on our Phase 1/2 trial
before it's been made public.
This is the data at one years.
And this was the first time that this product was tested
in the cervical spine.
And we tested two things.
We tested three different doses
because we didn't know which dose
was gonna be optimal for our treatment.
So, we tested 210 and 20 million injection
and we tested two different of injury severity
(mumbles) what's called ASIA A and ASIA B.
And that's not really critical for now,
but what I'll tell you is that after one year,
you know, this was a trial mostly geared
to assess the safety of the therapy
and gain some at least preliminary insight
whether the product had activity.
So we're really happy that after one year
we got successful engraftment
that is the sales were able to stay in the spine
and do what they were supposed to do.
And we had no adverse event that was created
or originated from the product itself,
but more importantly, we saw that all of these patients
had at least one level of functional recovery,
and about third of the patient
had two or more functional recovery.
So it seemed to be you know, giving signs of activity
that were really promising to us.
And quickly, after two years were provided
that that update last year, you know,
continue very good safety profile
and all of the patient that received the product,
good engraftment as well sustain,
we can see the cell remain on site for a long term,
which is what we want to see.
But more importantly and one of the core to the patient
so one subgroup of the patient,
the group that's mostly similar to what we want to structure
the next trial to be.
We saw that five out of six patient
actually had two level of functional improvement
and one of them had three level of functional recovery.
So really promising, you know,
it's not powered to demonstrate efficacy,
but you know, really exciting signs of activity
for the product and again maintain safety.
So, what did we do moving forward?
So when we acquired this program,
we knew there were two things we needed to do
in order to take this to the next level
meaning that to provide material
for a large clinical trial
and ultimately get FDA approval
and start commercializing this product.
So we knew that we needed to improve
the manufacturing process for making this cell
because it was based on a rather old process
and we knew that, you know,
this process had irregularity
in the sense that it was difficult to control the cells
from pluripotent state to the specialized state
if you will and oftentimes we had impurities
in the final product.
We need to discard batches of product.
And also it was difficult to scale.
It was based on small scale,
small batches of product which is not really consistent
with, you know, large scale clinical trial
and certainly not with commercialization.
So I'll tell you a little bit what we did for that.
And finally, we knew also that,
remember when I told you that we needed
creative engineering solution.
We knew that the delivery system,
the rig or the device that was required to position
very accurately the cells in the spine
needed to be improved to make it more end user friendly
for the surgeon to manipulate this device more easily
as well as just the logistics of assembling this device
in the operating room
and then managing this device
from the patient as well as from the doctors perspective.
So I'll tell you a little bit about that.
So quickly, we did three things
to improve the process, right?
Starting with the pluripotent stem cells,
what we did is we generated new cell banks
that were much more potent, much healthier if you will.
They could grow and replenish themselves,
you know, much better.
Secondly, we develop a differentiation process
to the process from deriving
(mumbles) to the specialized stem cells
is now much better tightly control.
It's very easy for us to follow
where the cells are going
and how efficiently they're transitioning
from nonspecialized to specialize.
So much better control with better growth factors
and in process control
and at the end we ended up with a much pure product
that hopefully will be much more reproducible
and that we can actually scale to commercial scale.
And so right now we've done
all of these things successfully.
We're in the process of now making these cells
under a GMP that is to generate a material
that we can actually put in patient in a clinical trial.
Now the way to do that is we need to talk to FDA
as you as you know we're a regulated industry.
So we're talking to FDA about our plan
and how we want to introduce this process
into our next clinical trial.
Similarly for the delivery system
I've told you a little bit about some of the limitations
of the initial delivery device that we had.
We tested newer prototypes now that are much easier
to use and much easier to set up, to sterilize
and to distribute to the various site.
So we tested a few, we did some feasibility testing
and likewise, our process right now
is we're trying to discuss with FDA
about some of these changes
and how we're gonna introduce them
to the next clinical stage
so that we can do this safely
and hopefully we can get efficacy reading
from our next trial.
In conclusion, you know, from a development perspective,
what we need to do now,
we need to make clinical grade material under GMP
such that we can take this product
and take it to the patient.
We need to qualify a new delivery device.
That is we need to prove that it's compatible
with ourselves and surgeon at the end
can use this device effectively.
The process now is to work with FDA
and have conversation with them,
explain to them what we want to do and get their buy-in.
So, we're hopeful that in the next few month,
we'll be able to move a much better product
as well as a much better delivery system
to really facilitate the overall experience
from the surgeon perspective all the way down to the patient
with a much more robust product
that hopefully will provide
a functional benefit to the patient.
Thank you.
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