Hi, my name is Kate Timms, and today
I’m going to be talking to you about scaling EV isolation for the clinic. Clinical trials involving EVs have been
increasing year on year since 2010. But there has been a lag
in translation into the clinic. This has been particularly potent
for EV therapeutics and diagnostics, compared to other therapeutics
and diagnostics that aren’t EV-associated. But why is this the case? There are unique challenges found with EV
therapeutics and diagnostics. The first is
scale. For therapeutics, this means large volumes
from which EVs must be isolated. And for diagnostics, this means
a large number of tests done at once. Quality and reproducibility is also very important when it comes
to therapeutics and diagnostics. And this means making sure that EV isolations are as reproducible
and pure as possible. There is also a significant cost
and time associated with this, not just the in-production time
that it takes to isolate the EVs, but the significant amount of i
nvestment
in time and money that it takes to perfect the EV isolation process from your R&D all the way through
to your production scale. Finally, there are regulatory hurdles. These are going to be important when you
want to bring your product to market but you need to think about them
right from the beginning. Otherwise, you risk hitting a lag time
when you get closer to reaching the market. The challenges also diverge
for therapeutics and diagnostics. For EV therapeutics, as mentioned before,
the scale is in terms of volume. And this means that there needs
to be optimised concentration and EV isolation methods, which differ wildly
from those used regularly in the lab. There is also the problem of samples being identical, but not quite. They’re similar, but
there will be differences between batches. And making sure that the quality control
is in place to catch those differences will be integral to making sure that you
produce a safe and effective therapeutic. And on that point
steril
ity is really important in making sure that your end product
is safe for patients. This means that production
needs to be automated in a sterile space. Diagnostics has its own degree of challenges
which differ from that of therapeutics. When it comes to scale, here we’re talking about many tests
being run at once by busy diagnostic labs. And the samples will all be different. Be that differences
between individual plasma samples, or even larger differences
between different biofluids. Many sampl
es
will also need to be run concurrently so that a diagnostics lab can process them
in a timely and efficient manner. And the signal-to-noise
ratio will need to be low enough that your diagnostic marker
isn’t lost in the noise. This means that purity is especially
important when it comes to diagnostics. Finally, you must ensure that there’s
no carryover between patients which could lead to false positives
or false negatives. Introducing qEV PurePath, a customised workflow solution
for EV diagnos
tics and therapeutics. Due to the differing needs of therapeutics
and diagnostics, qEV PurePath comes in two distinct arms, the first
being qEVPurePath for Therapeutics. One of the things that many people say
when talking about size exclusion chromatography
in the realm of therapeutics, is that the technique just isn’t
applicable for large volumes. We’ve shown that that’s just not the case. We’ve created
qEV columns at a colossal scale, able to isolate from large volumes,
so many times larger th
an our qEVoriginal columns that as you can see
here, it’s completely dwarfed by it. For this column, we can start with
2000 L, which can then be concentrated and loaded onto this column
for a single isolation, truly bringing qEV columns
into the scale of therapeutics. Here you can see a qEVPurePath
for Therapeutics workflow, taking you through each
of the customisable steps from a crude sample all the way through to a clinic-ready EV isolate. The first step is the clarification step. Here, filt
ration or even centrifugation
can be used to remove large contaminants
such as cells or cell fragments. Then the sample will move on
to a concentration step which is required before isolation. For large therapeutics uses
this will most likely be tangential flow filtration, or TFF, with which we have great experience
within Izon. Here, there will be a great reduction
in the sample volume and a small reduction
in the amount of protein. Here it can then move on to the size
exclusion chromatography
with one of those colossal qEV columns. Here the EVs will be isolated
in their pure form. After this, it’s quality control.
This will differ between different therapeutics, but will most likely include
some kind of particle measurement. Here, size, zeta potential
and concentration will be important, not just for your own in-house monitoring, but also for meeting
regulatory requirements. After this, things will get a little bit
different between different therapeutics. You’ll either have a set of
markers
that you use to make sure that your therapeutic is the same
or similar enough between batches, or this could be
some kind of potency test. Either way, your isolate will need to pass
both quality control types to be able to move on to the clinic-ready isolate. But why these steps
and how are they customisable? Well, each step will be fully
customisable, meaning that we will work with you to find the best solution
for each step of the workflow, making sure that our expertise can be used
w
ith your own knowledge of your own therapeutic to make the workflow as efficient and pure as possible. Here we have some case study data
from a company that we have worked with. As you can see here, the purity in terms
of particles per microgram of protein is really low for that
crude conditioned media starting sample. TFF then increases the purity
by an almost imperceptible amount. But what it does
do is massively concentrate this volume. Then moving on to the qEV size
exclusion chromatography
step, you can see
there is a massive increase in purity, which is essential for making your product
as pure and reproducible as possible. Now you have an idea of what the workflow might look like
in terms of the actual EV isolation. What about our workflow together? Well, it will start with
some kind of consultation. We will discuss your needs and perhaps
brainstorm some ideas with you. After that, we’ll move on
to the optimisation and development step. Here we will look at each customisable
ste
p in the workflow individually, working on all of them to see whether we can optimise them
for your individual therapeutic. After that,
we will move on to the pilot study, which we will run in-house
being able to validate that the workflow works as a whole unit
for your particular samples. After that, and the validation
that follows we will move on to tech transfer,
where we will give you the knowledge and the technology
to be able to take your customised qEV PurePath for Therapeutics
workflow i
nto production. Whilst consultation
is just the first step of the process that will continue all the way through,
and should you encounter problems at any point, Izon will be there to help. The point of this is that
we can work with you to take your sample from a crude conditioned media all the way through to a clinic isolate
which is ready for use. More importantly,
giving us that burden to optimise EV isolation gives you the time
and the resources to work on making the most effective
therapeut
ic possible. Next up is qEV PurePath for Diagnostics. Here we have our own very different
set of needs and solutions. The first of these is processing speed. In a busy diagnostics lab, you need to be able to run
multiple samples simultaneously. For this we have solutions in development, which will allow you to isolate
from multiple samples simultaneously. Next is the cost effectiveness
of your diagnostic tests. It won’t be picked up at a large scale
if it’s too expensive. But we’ll make sure tha
t that’s
not a problem with the qEV isolation columns, we will make sure
that there will be a significant reduction in cost for bulk orders,
meaning that the qEV column costs will never be a significant barrier
to entry into the market. qEV columns are the market leaders when
it comes to purity and protein removal. And we have other things in development
to be able to increase this purity even more
when it comes to those tricky biofluids. Next is our expertise
those tricky biofluids I mentioned
we’ve worked with customers
who have used them all? Meaning that we’ll be here to answer
any questions that you have and adapt any processes, depending on what samples
you have, or your storage conditions or any other things that might impact
your particular diagnostic test. Finally, the
time to market will be drastically reduced because you don’t
have to do the messy business of developing
and optimising your EV isolation. We can be doing that for you whilst
you get on with doing the important
work of making sure that your diagnostic test
is as good as it can be. But what will the workflow look like? It looks similar but as you can see also different from that for therapeutics,
because different solutions are needed. We’ll be taking your crude biofluid and then the first step again
will be clarification. Though here, it’s most likely
to be some form of dead-end filtration. Though again, that’s customisable
depending on your own biofluid and your own diagnostic test. Next will be qEV i
solation
which will occur concurrently with more than one sample. As I said, we have products
in development to really speed up this aspect of the workflow,
meaning that you can rely on us to help you develop a diagnostic test
which is scalable for the clinic. After that comes concentration, which will be malleable depending
upon what your sample requires. And then after that we will move
onto the diagnostic test itself, which is your purview. We just need to make sure
that we deliver it to you
in a process where the signal-to-noise
ratio is most efficacious. But why use qEV technology at all? As you can see here, qEV columns make significantly purer EV isolates
than the competition. Precipitation, whilst
a popular choice in diagnostic studies is significantly less
pure than qEV columns, meaning that there will be
a much higher noise-to-signal ratio, which might hide your precious diagnostic,
not just in development, but when it comes to your patients
too. Ultracentrifugation, as you c
an see, is wholly unsuitable producing an EV isolate,
which is not pure enough for diagnostics. But what are those innovations
that we mentioned earlier? The first is the qEV Primera. This is a priming station,
which will allow you to prime multiple qEV columns simultaneously, massively reducing
the time it takes to isolate your EVs. After that, we will have the qEV Chimera. This will allow you to do the EV
isolation itself concurrently with different samples being isolated
from columns simultan
eously. The point of this is to help you increase your efficiency,
reducing the time it takes for individual samples to be isolated,
and speeding up the diagnostics process. But what will the process look like
when it comes to working with us for qEV PurePath
for Diagnostics. Again, we will start with a consultation,
where we will discuss your needs and propose solutions
that we think might help. Then we will move on to the development stage,
and following that the optimisation stage, making sur
e that the workflow that we work
together to create will isolate your EVs in the purest form possible, which again is super important for a diagnostics test. Next, we will move on to validation,
making sure that the processes that we’ve developed and optimised work in the real
world for your diagnostics test. After
that, we will turn to the tech transfer, where we will give you the knowledge
and the technology you need to be able to put your diagnostic test
into production. And again, we’ll be t
here to help you at that stage too
if there’s anything that you need. If problems
arise, Izon will be there to help. It’s our job to help
take you from that crude isolate all the way to a diagnostics-ready isolate. And that time it takes to work on
that will be taken away, you won’t have to focus on it. And instead, you can make sure
that you can make a diagnostics test that is as effective as possible. But why use qEV PurePath
and not just do it yourself? Well, the first major reason is time
an
d cost efficiency. You can offload
the complex business of research, development, optimisation
and piloting to us so that you have the time
to focus on working on what really matters:
your therapeutic or your diagnostic. We can also make your isolation
as customisable as possible. We can make custom columns and have access
to things that you may not have by yourself. Working with us means that you don’t
just have to settle for what’s out there. We can help make something
which works perfectly fo
r your product. And it’s that expert support
that will allow you to move forward in a timely manner to make sure
that you can move towards market before your competitors do
and make sure that not only that, but you’re doing so with the most
effective and safe product possible. Thank you for listening. If you want to get any more information
on qEV PurePath, you can visit our website where there are dedicated pages
for qEV PurePath for Therapeutics and qEV PurePath
for Diagnostics. Thank you.
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