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OK. Thank you for coming.
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And my name's Mike Sailor and I'm representing SiCare Bio here.
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And also in the audience here is Barry McDonough, who's the CEO of our company.
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We're going to talk about how we use nanoporous silicon and silicon oxides to deliver drugs.
0:24
And the typical reason that we go after this and the reason that this material exists for us and why our company is moving forward is basically the four bullets you see here, you know, trying to avoid the low loading that we see often with biologics like proteins and nucleic acids, which are two areas that we really focus on.
0:50
The first release of those, especially when we're talking about long acting injectables, which is one of the areas that we work on a lot.
0:58
Then the degradations of the payloads.
1:00
So especially important for biologics like proteins and nucleic acid therapeutics to protect that therapeutic long enough for it to actually do its thing.
1:12
And then also, you know, again from long acting, mostly it's duration of release, but also for in vivo applications where you say trying to target tumour or Alzheimer's plaques or things that are going to be injected and circulating for a fairly short period of time, a few hours.
1:29
Still the critical thing is to time the release.
1:32
So it releases the payload when you want it to release, you know, when it docks with the target.
1:37
So silicon has been an emerging material for drug delivery since probably before many of the people in this room were alive.
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And the basic idea is that, you know, we eat silicon every day in our diet.
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You actually, fun fact, you eat more silicon in your diet than you do iron, and your body knows how to handle it.
2:02
That's one of the real advantages of using silicon as a carrier.
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But the key to a lot of this is getting the material to dissolve a reliably similar to what you see with the polymer based delivery systems.
2:15
They have to go away once they've done their job.
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And that was really one of the big challenges with some of the early therapeutic carriers like MCM-41.
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This classic sol-gel derived silica say they were great.
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They had big pores they could hold a lot of, they carry a lot of drug, but they wouldn't dissolve away.
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And so this field has been going on for quite a while as I mentioned.
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But really there's been a couple of key pivot points and one of them is the approval a couple of human use cases and just recently the five about five years ago, the porous silicon, which I'll talk about more in the next slide was given its first approval for use in humans by FDA.
3:01
And so on the right hand side of the slide here you can see just a small collection of companies that are actively engaged in using Si and SiO2 as a carrier system for therapeutics.
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So why would you want to use this as a drug carrier?
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I've mentioned already one reason is its ability to be tolerated by the body.
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Again, the human body in your blood plasma right now you have about somewhere between 100 and 200 PPB of dissolved silica.
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So the body knows how to get rid of the dissolution product of the material.
3:43
It's very slow dissolving material if you don't engineer it properly.
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And that's one of the challenges in this field historically.
3:52
But you know, it's used a lot and actually, you know, there's silica used as a glidant in oral formulations for decades, and so it's generally considered a GRAS material if it's SiO2, so that's what I mean by silica.
4:07
And what's shown on the right hand side of the slide here, kind of critical, important step for delivery of biologics, especially proteins and peptides is that this carrier does not generate acid.
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There's no large pH excursions as it dissolves.
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So it's kind of typical degradation say of PLGA shown up here.
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Just generate, you know, carboxylic acids is your biproducts and there's local acidic conditions around your API.
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If it's a pH sensitive API that can be a challenge.
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Silica doesn't have that problem and it’s basically buffered, its dissolution product is neutral at pH 7.
4:51
You have to go all the way up to pH 10 before it'll ionise or take them to remove that proton.
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So it's not acidic.
5:00
So the type of silica that we work with at SiCare Bio is a very unique material.
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It's derived from single crystal silicon wafers.
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So this is a material that's etched from crystalline silicon.
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Why would we do that?
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Crystalline silicon is an expensive material compared to, you know, sand.
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The reason for that is performance, and we've developed technologies to define pore sizes programmatically in this material.
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Basically it's an electrochemically etched material.
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You dial a knob on a power supply to change the pore size.
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3 examples are shown here.
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These are all images shown on the same scale showing the pore texture for three different samples.
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And again, for biologics that getting a size up in the sort of, you know, 10 to 50 nanometre range is really important.
5:58
And being able to tune that size is important as well because to get a particle to hold the drug and not release it rapidly, the pore has to be a certain size.
6:09
If it's too big, the drug goes in, but it comes right back out.
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If it's too small, it never goes in the first place.
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But furthermore, what's critical about this type of silica, is it because of the way it's prepared, it's a non-equilibrium material.
6:23
When drugs, especially proteins go into it actually restructures the pores.
6:28
The API causes the pores to restructure, basically sealing the pores.
6:33
And that's really the key to getting the long-acting and flat release curves that we see with this material.
6:42
So kind of lastly is the basically there's this versatility of the material we have various different ways that we've developed and patented for trapping APIs that really again kind of trigger on this non-equilibrium phase of silica that we generate.
7:01
So this very distinct from say sol-gel derived silicas which are generated at room temperature by precipitation routes.
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They're thermodynamically stable.
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They're not physically strained in any way.
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Our material has that high strain and high non-equilibrium chemistry built into it.
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So that makes it dissolve quickly.
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It also allows it to trap APIs really effectively and on the left hand side or just four different methods that we used to load our APIs, and bottom line that these things will load very high.
7:36
The numbers shown in the bar here are mass percentage loading of proteins as well as nucleic acids.
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For a while we held the world record for siRNA loading in porous silicon or in any carrier up upwards of 30%.
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We can get nucleic acids to get in there to quite effectively.
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Also our proteins, generally we see between 20 and 40% mass loading of those.
8:05
So with that, I'll stop and answer any questions you might have.
8:10
Thank you.