0:01
Everyone just want to say thanks for attending the session here today.
0:05
Talk today here.
0:06
Just want to talk through some real basic info on sustained release drug delivery systems.
0:13
So for us these are polymeric implantable solid form implants that deliver drug for an extended period of time.
0:21
So just want to provide some early considerations here for anyone thinking about developing some of these therapies and the main things that we're looking at.
0:32
There's kind of three elements that we start with that I'll kind of talk through here today.
0:36
So that's some of the indication and drug selection considerations.
0:41
We'll cover some basics on polymer selection.
0:44
And then at the end, I'll talk just a little bit more about manufacturing process and what's capable with some of these technologies.
0:53
All right.
0:54
So just a quick overview here of the different types of delivery modalities.
1:02
And along the bottom here, I've kind of got a spectrum of, how long can we push the extension of these delivery systems based on what you're trying to achieve.
1:12
So you know, what's the greatest extent we can push these two?
1:15
So obviously oral, topical and inhaled therapies, we kind of see some of those operating starting at the multiple times daily and we can stretch those close to a once weekly style delivery.
1:30
There may be some exceptions to that rule.
1:32
I'm sure many of you are working on cool interesting things that may push the boundaries here.
1:38
But these are some general guidelines.
1:40
And then when it comes to auto injectors or injectables, this is where you kind of see this split of delivering drug for, a once daily to once weekly, that's more patients administering it themselves.
1:53
And then as we get into it, injectables, you can see that push to monthly.
1:56
And you know, we do have some that push into that multiple months delivery as well.
2:02
But at a certain point, once you get to roughly about 3 months or so, the only option that you have to deliver drug for that long a period of time isn't this implantable form.
2:14
And so this is really what's carving out a new and interesting space for us.
2:21
And so this is what we refer to as sustained release drug delivery applications or implantable drug delivery.
2:28
I'll come back to this point at the once which we get over to the polymer side as well.
2:35
But within that spectrum on the short end of delivery, you're typically gravitating towards more of the bioresorbable polymers.
2:43
Those that will break down in the body versus the longer term applications really have to be in a bio durable platform.
2:54
All right.
2:54
So as far as when we're looking at indications and where can we apply this technology, just a quick overview on what may be the drivers of those.
3:03
Obviously, since we just talked about the greatest possible extension of release is in these forms, if there's a real advantage to that's something that should be driving some consideration of that type of development, developing that kind of product.
3:21
A main driver of that may be high patient compliance risk.
3:26
And so we have these patient populations that are a little bit more prone to stopping their medication through, maybe some memory conditions there, but there's also other patient populations that are just higher risk of going off a once daily oral application.
3:45
And so those may also be an area where we can drive some real value in developing an implantable system.
3:54
Targeted delivery is also a good potential here.
3:58
There's a couple different forms of that.
4:00
This is more if you can place the drug within the anatomy where that drug is needed to be delivered, that is certainly possible with these implantable systems as well.
4:12
So if you think of a cancer application, being able to place that drug directly next to the tumour and through that you can actually minimise dosage and cut down on some of the side effects that the patient may experience.
4:26
So those may be also applications where you can consider these types of products.
4:33
Bioavailability, I know can also be challenges for some of the other delivery modalities as well.
4:40
So this is again where we're encapsulating that drug within the polymeric matrix and we're able to place it in the body so that we know that molecule is getting to where it needs to go and having the effect on the patient that's desired.
4:56
And then lastly, another thing that we're starting to hear quite a bit more about as well is just the strain that physicians may be dealing with the current therapy.
5:07
So we see this a lot in some of the ocular applications we work on.
5:11
We have doctors, physicians that are really only able to work with therapies that deliver drug for about a month or so.
5:21
And so their entire day is consumed by giving these ocular injections and they'll have some difficulty doing some of the other things that they really want to do with patients as far as, making them better and some of those sorts of things.
5:35
And so they've also been pushing some of the product developers to really be thinking about how can we extend the release of these therapies on these drug products.
5:46
So those will be some things that might drive you to consider coming up with some of these systems within certain indications.
5:57
As far as drug selection. So, if we just think about what are the right drug candidates for us to target with some of these, there aren't black and white rules, but as far as guidelines and where are you going to have the most flexibility?
6:09
And that will lead to, what are your chances of actually come out coming up with a viable product concept.
6:16
If you can have the drug products, if it's on the lower end of the molecular weight scale where we kind of draw that line is a good guideline is anything below 1000 for molecular weight is going to give you a lot of flexibility in design across polymers and you know system design some of those sorts of things.
6:37
So as you can identify a drug target that has something below that threshold again gives you options as you design some of these systems.
6:49
Obviously we're leveraging some of the more traditional manufacturing processes with these polymers to which some of them can be fairly heat intensive.
6:58
So another factor to consider as well as some of the melt temperature for that drug product as well.
7:04
So I'd say anything in the 1:20 to 1:40 C range is kind of where you start running into maybe some limitation of your options within those.
7:17
But as long as you're above that, you should have all of the flexibility across polymers as well.
7:24
Greater potency is also a fairly important consideration here as well.
7:29
Again, if you think about these implantable systems, it's something that you're delivering to a patient many times with maybe some of the larger gauge needles as they are a solid form.
7:40
And so you only have so much real estate to work with for being able to actually load these systems.
7:47
And so typically you want to be in a microgram per day scale for a lot of these therapies.
7:56
You may be able to go up from that as well.
7:59
But that may limit really how long you can deliver drug for as you'll have some payload limitation as well there.
8:08
And then based on what we typically see, solid-state drug molecules that you can get to a micronized powder is going to make, again, a lot of flexibility there.
8:21
I'll talk a little bit later on and some of the design considerations about some alternatives if that's not possible for the drug product that you're targeting for some of these.
8:31
So all of these are really, again, like I said, they create some flexibility in the design, some of the polymer platforms that you can use, some of the manufacturing processes.
8:43
So as far as the polymer classes, again going back to I guess this is mainly where we work and some of the drug products that we see on the market today, they're either leveraging a bioresorbable platform or a biodurable.
8:58
So again difference there being whether it's breaking down within the body or not because the polymers that do breakdown are breaking down.
9:09
It's a surface erosion process that releases the drug.
9:12
You will have kind of a limitation there at the 6-ish month mark.
9:18
Some of those you can stretch to about nine months of delivery in these bioresorbable platforms.
9:24
But after you go, if you want to go beyond that, you will typically have to leverage a biodurable platform.
9:31
And again with that you're considering as well, something that's going to actually not breakdown within the body.
9:38
So another common consideration is what we have to have a follow up procedure to remove that implant at the end of that process.
9:46
So, but just a couple of the classes of materials within each of these PLGA very well established and is used in many different applications.
9:57
That's a very common one for a lot of our ocular delivery therapies that we work on.
10:04
But you also see polycaprolactone and PEG be used quite often as well in copolymer mixtures there.
10:13
And then on the biodurable side, you see silicone used quite commonly as well as EVA.
10:19
So those are the typical platforms that we'll see.
10:24
So this is maybe a bit of a map of those polymer classes and what products are on the market that leverage each of these.
10:33
Again, just kind of painting a picture of what's being used and where they're being applied on the left here you see, again, those biodurable polymers, each of these products is on the women's health side of things.
10:49
So whether they're contraceptives or other applications, that is a pretty common approach.
10:56
And again, you see a lot of value in being able to provide that therapy for as long as possible just so that there's not as much of a maintenance issue that's going on there.
11:09
On the right side, there's obviously are biodurable polymers and a lot of that is, as you see in the PLGA side, Durysta, Ozurdex, those ocular therapies that are well established in leveraging those platforms.
11:24
But we also see some more systemic administrations in those platforms as well.
11:33
Polycaprolactone and PEG also have each of their products.
11:37
I've got Propel and Sinuva in the middle as they're kind of leveraging all three of those platforms in a copolymer.
11:47
All right.
11:47
So as we get to how do, what form do these products typically take?
11:53
I think most products that we see on the market today, really the only function of this system is to deliver drug.
12:00
There isn't really any meaningful mechanical function to the product itself.
12:06
So a lot of these do take a rod shape.
12:08
It's going to be the most efficient process that you can really build to produce the product.
12:13
And so very well established within that form factor.
12:19
There's a couple different options here.
12:20
So single entity systems is where we're mixing the drug and the polymer together and then creating the finished state.
12:28
It's really just a matrix of drug and polymer in those and that works fantastic from an efficiency standpoint if you're able to really control what the chemistry of the polymer, the release rate for that drug product.
12:43
If we can't properly control it or we need to slow it down.
12:48
You may also see a membrane application as well.
12:50
And so this is where you might see a coextrusion approach taken where you have a different polymer that's outside of the drug and polymer mixture that effectively slows the release to the right rate that you'd like to see.
13:05
So that's the best way to efficiently come up with a membrane that would limit the rate.
13:14
You may also see a lumen approach.
13:16
So this is where you'd still create the rod shape, but you've got lumens available on the inside of that product.
13:24
This is where you may use if, for example, you can't get to that micronized state.
13:30
Maybe you've got a crystalline drug, or it takes some other form.
13:34
You can apply that drug into the lumen and then close off either the ends or this is where the vaginal ring approach would also be used, or you can actually join either end to fully encapsulate that drug product.
13:48
So this is another example where we can create sort of that membrane and then administer the drug into those systems in a different way if there's some kind of challenging form for that drug product.
14:04
So as far as alternative options here too, so if there is some need for mechanical function of the drug product itself, maybe it needs to hold its shape within the anatomy, you may want to create something that actually has a form to it.
14:22
And so this is where you'll see some of these alternative form factors.
14:27
This would drive us more down a moulding path to achieve more of an organic form factor.
14:34
Again, you see the same thing with a single entity system where you've got the drug and polymer in mixture and again you're going through that moulding process rather than extrusion to achieve that form.
14:47
Other alternatives are if you actually have an assembly process so we can create multiple components and put all of that together within a single system.
14:58
This is where you've got multiple components again where that assembly process is required, but that's an alternative that we can use as well.
15:09
And then we've also seen applications where our customers are really trying to challenge how quickly we can release a drug from these systems for some shorter term applications for the way that these systems work, the more that you can increase surface area of the product itself, the faster that drug will release.
15:31
And so we've also seen applications where our customers have asked us to look at a sheeting process so that we can really increase that service area and get that drug to release at a little bit faster rate.
15:46
That is everything I have happy to take any questions that may come up.