(upbeat music)
- I direct you to my disclosure statement,
I do have a financial interest in what I'm going to present.
Retinal degenerations include a number
of very differing diseases.
One is retinitis pigmentosa, RP,
which will be of particular interest for this talk.
Another is age-related macular degeneration,
which is a more common disease but less severe.
RP starts as night blindness progresses to tunnel vision
and eventually results in total blindness for the patients.
But both of these diseases in all retinal degenerations
have in common, the loss of photoreceptors,
which are the rods and cones at the back of the retina.
And these cells are lost
over the course of disease progression
and this results in the inability to see.
Now from a treatment perspective,
as a cell treatment person,
I have to ask the question,
am I going to try to replace these photoreceptors
or am I going to try to use the cells
to employ neuroprotection?
And in our case, we decided to go with neuroprotection.
So that's the idea that we can rescue the photoreceptors
that are in the host eye.
And here, I wanna divide between the rods and the cones.
It's the rods that are expressing the mutant disease genes,
and these are the cells that degenerate first.
However, rods are mainly just important for night vision,
so if the disease stopped with rod degeneration,
the patients would not actually go completely blind.
Eyes later involvement of the cone photoreceptors
which subserve the majority of human visual function
that are critical to the disease progression
when the cones, which do not express the mutant gene
are lost late in the course of RP,
this results in severe visual deficits for the patients.
Now, if we could protect these cones
that are not expressing the mutant gene,
then we could have a huge impact on the problem.
Now, which cells are we gonna employ?
We could use true stem cell such as you see on the left,
such as the embryonic stem cells
and induced pluripotent stem cells that are very popular.
However, we've focused on the use of the retinol progenitor,
which is a tissue specific cell
found only in the developing retina.
These cells are restricted to making cell types
that are found later in the retina
they do not make other cell types
such as blood, muscle or pancreas,
but that's okay for our purposes.
Now here's proof of principle in an animal model
on the left you see an image of the treatment paradigm,
where the cells seen in red are injected
into the vitreous cavity of the eye.
That's the large gel filled space behind the lens
and in front of the retina.
The cells clustered to form these neurospheres
that survive for a period of time in the retina,
and from there they can exude their trophic factors,
which are gonna have the therapeutic effect
on the photoreceptors.
Now, a retina taken from our raw RCS rat
is seen in the central image.
These rats undergo a photoreceptor degeneration,
much as seen in RP.
And now we segregate our rats into treated and untreated
and at the upper right is the on false image from a retina
of our control animal and you just don't see anything.
And that's because the photoreceptors have all died
and gone away.
Whereas in the lower right,
you see lot of a red and green dots.
These are profiles that correspond to rods
and middle wavelength cone, photoreceptors, respectively.
So by comparing the two you can see
that the treated eyes have considerably
more residual photoreceptors, than do the untreated.
So that's the evidence of a treatment effect.
We back up this evidence with evidence
of a functional improvement in these animals
and that scene both through something called
optomotor response in the upper image,
as well as electroretinogram seen in the lower image.
Now we move on to our patients
and here I give you a overview of
what we're attempting to do in the patients
and pointing some of the highlights
of this therapeutic approach
versus other potential approaches.
Now we're gonna use these retinal progenitor cells.
These are an allogeneic product,
they can be taken from one unrelated donor
and given to multiple recipients
as seen with these frozen vials here.
The disease target is retinitis pigmentosa,
the delivery is through intraarticular injection,
just as was seen in the rats, into the vitreous cavity.
This can be performed in the office setting
using topical numbing drops.
And despite the fact that this is an allogeneic product,
it can be given without immune suppression.
That's the equivalent of getting a blood transfusion
without the need to tissue type the blood.
On the mechanism of action here is neurotrophic,
as opposed to cell replacement as I previously described.
Here's the setting of the initial clinical trial,
this is when Kristin was getting treated.
We enrolled our patients starting in June of 2015,
the trial was completed by August of 2017
and all of the 28 patients in the initial trial
completed that study.
This product was well tolerated,
and importantly, there were no immune issues.
Here's the visual output from these patients.
We've segregated the data in terms of the different doses
and compared to the fellow eye,
the point is the treated looked somewhat better
and was particularly prominent for the highest dose,
the 3 million dose.
We had a benefit of nine letters on average,
in treated eyes over untreated eyes,
now that's quite a large response.
Again, this was an open label study
and small group of patients,
but the FDA encouraged us to explore a higher dose.
So we entered the people who had completed the first trial
in an extension trial,
and here you see Rosie,
we've followed these patients for a longer term,
and these patients were allowed the option
of being redosed in the fellow eye,
24 out of 28 of the patients were redosed,
and again, despite being dosed in a second eye,
there was still no immune related issues
related to this treatment.
That allowed us to move into phase two B.
This was a much larger study
involving a total of 84 patients.
They were divided into three different dose types,
6 million cells, 3 million cells and mock injection,
which was essentially the equivalent of a placebo effect.
Again, we were looking at visual acuity at 12 months,
although we included some other end points
and we completed the first aspect of this trial
in fall of last year,
although patients have crossed over
into the treatment effect
from the mock injection following completion.
But looking at these initial data
from the initial 12 month study,
we see that there was again a very well tolerated products,
good safety, consistent with what we saw in the first trial.
We also saw a prominent response in the highest dose
that being the 6 million dose
and looked at more carefully,
we see a nice relationship
between the proposed mechanism of action,
the retinal anatomy,
and test performance across the different other endpoints.
So taken together there's a nice amount of information
we got from this that positions us very well
to embark on our phase three study.
I'd like to thank everybody, particularly CIRM,
who's been an excellent partner
at every step of the process,
as well as the people from MyLab and the clinical folks
who carried out the clinical trials testing
as well as people on the corporate side at JSA.
Thank you very much for your attention.
(upbeat music)