(mellow music)
- So, you have you have the
best press releases recently.
Solid tumor, cell therapy,
advanced melanoma,
advanced cervical cancer.
If anyone hasn't heard
about these developments then
they should probably leave
the room right now.
But just to save them that embarrassment
give us the update on
LN-145 and Lifileucel
and where exactly Iovance
is in their trajectory.
- Okay, so Iovance
Biotherapeutics is a company
that manufactures tumor
infiltrating lymphocytes
for solid indications.
So, basically, in short,
we take a tumor biopsy,
we have a process or processes,
whereby we create an environment
for the tumor infiltrating lymphocytes
to emigrate out of the tumor,
and we get them to expand
and then we adaptively transfer
them back into the patient.
So it is a polyclonal
heterogeneous population of cells
that is specific to the patient.
We have several ongoing clinical trials,
phase two clinical trials
currently in progress.
We have LN-144 for metastatic melanoma,
which is also referred to as Lifileucel
as well as LN-145 that
we are using to treat
metastatic persistent cervical cancer.
In terms of our pipeline,
which we'll probably get into,
we have other things
that we're working on.
The press releases right now,
is that we've recently talked about
our most recent clinical
results in metastatic melanoma,
where we saw an overall
response rate of over 36%
in this highly refractory
population stage three,
stage four that have
exhausted all other treatments
including checkpoint inhibition.
Even more interestingly,
we've seen in cervical cancer,
highly refractory patients,
again, chemo-resistant,
and we have seen an overall
response rate of 44%.
What's interesting is not only
have we seen responsiveness
in both of these these populations,
we have not reached something
called the duration of response.
So in our metastatic melanoma cohort,
we have reached out to
approximately 15.5 months,
and we still see that these
responses are ongoing,
showing that they are include
indeed persistent and durable.
We have other things in the pipeline,
we're treating patients
with head neck cancer,
that's a fairly new indication
that we're looking into.
We're also getting a little
bit into liquid tumors
with CLL and a program that
we have with Ohio State.
Some of our other press releases recently
has been some collaborative relationships
with Novartis where we're retrying to,
where we have licensing now
to produce an IL-2 analog.
Part of our process involves
systemic administration
of IL-2, which can bring about
some significant adverse events.
And so we want to try to
decrease those adverse events
in our patient cohort.
We also have initiated the collaboration
with a company called Cellectis
for their TALEN technology
with the purpose of
genetically editing our TIL,
because currently our TIL product
is not genetically engineered.
It is expanded from the
actual tumor biopsy itself.
- So it's not hard enough
to just manufacture TILs,
you have to gene edit them as well
to introduce further
manufacturing challenges isn't it.
- Yes.
(laughing)
I think you can look at
it in the perspective
that in the pipeline, we're looking
at multiple types of strategies
to try to improve our current product.
So we've seen dramatic and
remarkable clinical efficacy
in the indications that we've looked at.
We wanna expand that repertoire
in terms of the indications
that we're treating.
Some that may be even more
difficult to generate TIL.
And we want to know that
we can actually produce
a population of TIL that
is persistent and durable.
- Though your clinical
numbers are reminiscent
of nothing more than
the trials like Eliana
in the earliest days of parties
where we saw crazy
numbers in the 80% range.
There was no mistake that
these numbers look amazing.
Let's talk a little bit more
about the manufacturing.
You start out with a with a tumor biopsy?
- Correct.
- And you have manufacturing operations
lasting over 20 days.
- Correct.
- How do you feel about the
the robustness of that process?
- So the initial process,
which was devised by Steve Rosenberg lab
at NCI 30 years of development
with this process initially
was a six week manufacturing process.
In terms of the ability to
commercialize the product,
it was going to be very
difficult to do so,
to manufacture something
that was going to take
that long in manufacturing.
So one of our first goals
at Iovance was to be able
to come up with a process
where we could expand the
TIL and in sufficient number
to see clinical efficacy but do so
in a much shorter manufacturing process
while cryopreserving the product.
So one of our first initiatives
that we generated as we call
it the generation two process.
So it is a 22 day process
and on average we're able
to expand TIL from a tumor biopsy
to approximately 28 billion
that's on average 28 billion cells
and still see fairly
significant clinical efficacy.
- 22 days.
Still a pretty long manufacturing process
for autologous medicine.
- It is when you have a patient population
that we're currently treating.
We're looking at patients
that essentially are towards
the end of their life.
And so 22 days is still a long process.
So we are currently working
on further optimization
of our process and we're trying
to reduce the number of days
while not affecting
the product's efficacy.
That's important in terms of cell number
and the cell population
that we are deriving.
- How manual is the process?
- I'm sorry?
- How manual is the process?
- It's actually a fairly
streamlined process so much so
that when we were first working on it,
we had to have everybody in the laboratory
involved to make sure
that every single person
was able to do so.
Right now we don't have,
we are actually building our
own manufacturing facility,
that should be ready in about 2021, 2022.
Right now we have manufacturing facilities
generating our TIL product for us.
So we have a technology transfer team
and so the biggest
undertaking is at day zero,
but it's just basically we do it
in a very minimalized culture system
whereby basically you fragment the tumor,
you throw it into a flask,
you leave it for 11 days,
and at the end of that 11 days,
we add in something that
causes rapid expansion.
And then at day 16,
the cells are split into multiple flasks.
And day 22, you harvest.
So it's a fairly simplified process
compared to the initial process
where it was involving 24 wall plates
and multiple plates and
constantly splitting the cells.
- Still sounds really expensive.
- Yes.
- How much?
- That I can't necessarily speak to.
I can tell you in terms
of the fact that we have,
- Are we talking KIMRIAH expensive
or is all ZYNTEGLO expensive?
(laughing)
Or Maybe more?
- We're still working out the logistics
of how much it's going to cost.
The thought process
and having our own manufacturing facility
and being able to tweak the
process is to try to make it
as accessible to as
many patients as we can.
Being that the fact that
right now our current product
is not genetically
engineered and it is indeed
just expanding cells from
a pre-existing tumor biopsy
and doing so with really only
three days of a cell culture,
we're hoping that it's going
to be a reasonably derive product
in terms of time and in money.
So if you fold in gene editing,
it's going to be even more expensive.
- Likely likely.
But the thought of gene
editing it's further down
into the pipeline.
Again, with the gene editing approach,
we're trying to utilize
an approach with Cellectis
and with the talent
whereby we're going to do
as little manipulation as we possibly can.
But very much we're still
in the pre-clinical,
steps of that particular process.
- Yeah, I mean, you understand
the sensitivity here.
We saw the very manual
KYMRIAH process, which is,
to be polite about it as has
faulted on numerous occasions,
and then we see this inflation,
this apparent ongoing inflation
as we move up through
LUXTURNA just under a million,
you have ZYNTEGLO, we'll see.
And as all transfer over 2 million.
You could almost buy a house
in the Bay Area for that money,
but probably not quite.
- Our hope is to be that it's
going to be more affordable
than what we're seeing currently
with some of the cellular immunotherapy.
- More affordable than
CAR T type stuff therapy?
- Yes, yes.
That's the hope.
Now, our current product, as I said,
it's an unmanipulated product.
And again, we talk
about further generation
to try to make it more
potent, more antitumor,
but one of the strengths
of our current product
is that it's unmanipulated and we think
that that's the strength.
When you're thinking of solid malignancies
versus liquid tumors and you think
of the evolution of
CARS versus TIL, right?
If you look from the perspective
of a solid tumor microenvironment,
you have many, many tumor antigens.
It's a very heterogeneous population.
If you look on average,
there's potentially thousands
of TCRs 20,000 we'd be able to
see of TCRs that are present
within a tumor lesion.
You can think of the
number of tumor antigens.
We really don't know what tumor antigens,
or what T cells are tumor reactive.
Even with the evolution
of whole exome sequencing,
RNA sequencing, the
identification of neoantigens,
the strength of TIL is it's polyclonality.
In terms of CAR, it's difficult
because CARs are typically
to one antigen.
They work very well in hemalignancies.
- One cell, sometimes if
you believe Bruce Levine,
all you need is one cell.
If only my own, each
manufacturer one cell.
I think that is the great
strength and it's the,
there's two sides to every coin.
You know, what worries
me about manufacturer,
but I see is when I hear
about the polyclonality
of a product, what excites
me about the patients
that can be addressed with the product
is when I hear about the
polyclonality and that's just,
let's just reflect on, on
how exciting this is that
with advanced melanoma
and advanced cervical,
in the former case, my
understanding is that these patients
have failed both PD-1
and PDL one, therapies.
The outside of these four walls,
most physicians have
extremely excited about,
what you might call classical,
immuno-oncology involving,
checkpoint inhibitors of that nature.
We've got, they are
themselves, they're not cheap.
They're certainly not
without side effects.
Do you see any prospect of
you marching up the standard
of care to a point where
you're competing with PD-1
and PDL one inhibitors or even, being used
prior to their prescription?
- Yeah, so right now if
you look at our repertoire,
basically all of our
metastatic melanoma patients
have failed PD-1.
And 40 to 65% of patients,
metastatic melanoma patients
that are put on anti PD-1,
whether it's Pembro or Nivo,
essentially fail at some point
there right away or they, they respond
and then they become refractory.
So all of our patient
cohort has failed PD-1
and we still see this
good clinical efficacy
with our TIL product.
That being said, we're
still investigating.
It's difficult to get a population
of metastatic melanoma
patients that is naive to PD-1
at this point.
But we do have a small
cohort in a basket trial
where we are looking at
joining up with checkpoints
where we're looking at
patients that are naive
to checkpoints, giving them
TIL and then following up
with checkpoint therapy.
So I think we can exist
in the environment.
I don't think that we need to compete
because we can exist post
checkpoint inhibition failure
and we could potentially be in,
we can work with checkpoint inhibitors.
And that's really something
that we're looking at
in the pipeline down the road
is the unmet medical need
of those patients that
have failed all treatments
and also thinking that we would like
to be much earlier aligned
and in combination with checkpoints.
- That sounds like a
lot of clinical trials.
- It is.
And so we have of course our LM-144 trial
where we have just our
metastatic melanoma patients
that have failed PD-1,
actually most of them
have been on three to six prior therapies.
And then we do have another part
of our clinical trial,
and a basket trial that we are looking
at naive patients from cervical
head, neck and melanoma
that are naive to checkpoints
that we're then treating
with TIL end checkpoint.
- So BLA 2020?
- Yes.
- Two BLA's 2020?
- So definitely with Lifileucel
and 145 for metastatic melanoma,
we're projecting the submission of the BLA
and Q-3 and Q-4 of this year.
We've also had the end
of phase two meeting
with the FDA and they were very favorable
on the single arm registration trial.
And with our preexisting cervical cohort
and just expanding that cohort,
we can go ahead with BLA submission.
So we're going to prepare
for BLA submission
this year and hopefully
by 20 the beginning of 2021 we're hoping.
- So shipping jog in 2021.
- Well the hope is that once we submit,
depending upon the FDA
that we get approval, but
we're hoping that both BLAs
will be submitted within 2020 to 2021
are manufacturing
facility is scheduled to,
- Rolling submissions?
- Pardon me?
- Rolling submissions?
- Yes, basically.
- And how many patients
are you going to be treating in 2021?
- So we just finished
treating our last patient
on our cohort four, which was
our pivotal registration trial
for metastatic melanoma.
We started in March of 2019
and we treated 75 patients
between March of 2019
and January 15th of 2020 to complete,
the registration cohort.
We're going to continue
on the cervical trial
to try to, bring that cohort up to 75.
We currently have reported
about 27 patients on that,
but those treatments
are ongoing right now.
We also have the head and
neck cohort that's ongoing,
where we need to increase
the patient number,
but we also have some, we've submitted
some further IMDs, and
as such as for the CLL,
which is a he malignancy
with our PBL product,
we also have some selection strategies,
PD-1 selection that we're hoping
that we can initiate clinical trials
in the very near future.
- Yup, well, so that's a two BLAs,
a new manufacturing facility,
in licensing, gene editing,
and an aisle two analog as well.
- As well as selection.
- What else are you gonna do?
- Whatever,
(laughing)
but the options are endless.
Right?
I think that one of the things
that when you see about
Iovance and you think
of cellular immunotherapy, you
spoke to it at the beginning,
is that they're waiting for that bell
to ring with cellular immunotherapy.
We thought a couple of years ago,
and we've been sitting around at Iovance
doing our jobs, trying to get to the point
where we can actually
treat solid malignancies.
And so what we know
is that there's no cellular immunotherapy,
product for solid malignancies.
And we believe that we will be the first,
but Lifileucel is only
going to be one component
of what Iovance can bring to solid tumors.
That is the hope.
We want to expand in a
multiple indications.
We want to continue to
perfect our current product
that has clinical efficacy
so that we can see greater
durability, greater persistence,
and we can treat more indications.
- Good luck.
You've got a lot of work to do.
We're all waiting for that bell to ring.
Thank you very much.
(applauding)
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