0:24
So thank you all for coming today.
0:27
I'll be talking about innovative strategies for long-acting parenteral drug delivery.
0:31
And during this presentation I'm going to be covering our vital dose EVA, which is a matrix copolymer used in as a reservoir or membrane in a number of different sustained delivery dose forms that kind of maximise on route of administration.
0:50
And so why tradition, why sustained delivery really matters to a lot of people in this room is that it gets over a lot of challenges posed by traditional dose forms.
0:59
And while there are a number of challenges to address, I just have three of them that I just want to highlight here.
1:06
And the first one is target sites.
1:08
So whether you have a physiological barrier in the target that you're going at or whether there's high convection in the tissue type that you're going at, or if there just isn't a ligand that allows you to effectively target that area of the body.
1:22
This is a significant limitation for oral and injectable type dose forms.
1:27
Then looking at efficacy.
1:29
So as a case study, looking at side effects, they come with a lot of drugs, but if you look at a non optimal route of administration, it's interesting that you have side effects associated with something that you have to take a higher dose for just to get over a low bioavailability.
1:46
So there's that kind of burden that happens on a patient as well as the fatigue that can happen with a different dose regime.
1:56
So those kind of come together and put a burden on the patient that lead to inconsistency in dosing.
2:02
And this is a problem across multiple therapy areas in the pharmaceutical industry.
2:08
And the last point is frequency.
2:10
So whether the drug is quickly metabolised or it just doesn't get into the cell type that you're really targeting or that just requires large loads in general, this is kind of another problem that really hits at not only it's a burden again on the patient, but it's a burden on the formulator as well.
2:33
So that's why we see a lot of pool in the market for a Vital Dose EVA.
2:37
This is an ethylene vinyl acetate copolymer that's used in as a matrix delivery system, as a reservoir or as a membrane in sustained delivery dose forms.
2:50
So this is a patent supported material meaning that we have background IP on the material itself in combination with different molecule types as well as in different dose form configurations.
3:01
So this will offer continuous tunable release from months to years and last in the middle it's in marketed products as well.
3:10
So this has over 2 decades of use in different delivery dose forms, EVA is listed on the inactive ingredients database and it has multiple administration routes in global markets.
3:22
So what's nice to point out from that is that if you look at products that are already on the market, they tend to have a higher efficacy and safety than other products that are substitutes.
3:38
And also since it is a, it is in use in market products, it's a low regulatory risk compared to other polymers that you might come across in the market.
3:47
And last, it has broad molecular compatibility.
3:51
So this has the capacity to deliver molecules regardless of their solubility as well as their molecular weight.
3:59
And so when you look at how EVA is used in the market, it's often through the lens of localised or systemic delivery.
4:05
And here are a number of TAs therapy areas that we're partnered with on external programmes and also in our own internal programmes.
4:14
And so pointing specifically at ophthalmology, oncology and Women's Health, these are great ways of looking at how EVA is used.
4:22
So by definition, ophthalmology is a localised delivery.
4:26
But what's relatively interesting is that depending on how you tailor the dose form allows you to see how you're getting efficacious delivery to the front of the eye or the back of the eye for different disease states.
4:40
And oncology and Women's Health have traditionally been dosed through a systemic dosing regime, but there's growing interest in placing these both on a localised delivery approach.
4:51
So for instance, if you have an intrauterine solid tumour, you can use a localised delivery approach to saturate that area to make sure that your therapeutic is getting to the targeted of interest.
5:06
And so looking at all of these different therapy areas, one thing to take away is that the material, once it's loaded with the API, can fit a number of different form factors, different shapes and different sizes to hit a variety of different applications.
5:23
And when we look at the number of molecules that the material can deliver, that also shows its versatility.
5:28
This 2D graph kind of demonstrates the different molecules that we've demonstrated tunable release in our lab, with the exception of mRNA, which is something that we're going after now.
5:38
But these are separated over different water solubilities, going from very poorly insoluble molecules to freely soluble molecules and going in different molecular weights from very small molecules up to very large molecules.
5:52
For instance, IgGs.
5:55
And also these nano encapsulated materials where we're looking at LNPs as well as other systems to show tunable release, as well as the ability to place these in different parts of the body to be proximal to different targets.
6:11
And so when working with the material, I'm just going to show some levers about how easy it is to formulate with this product and how you can pull these different levers to get different formulation characteristics.
6:24
And so some of these I'm going to be looking at composition of the polymer itself, multi layer configurations, loading percentages and their effect as well as size alterations.
6:35
And so if we were to give you the basically the material in house, these are how you'd look at a formulation and how we look at a formulation in our lab when we work with customers like yourself.
6:48
So in the very first, on the left-hand side, we have a circular peptide cyclosporine.
6:53
And this is a great example of an insoluble molecule that's loaded in a very simple design.
7:00
So this is a monolayer design.
7:02
It just has basically one grade of the API with a different polymer, sorry, one grade of the one grade of the polymer with an API.
7:10
And so when you don't have when you only have a monolayer design, the amount of drug entirely depends on how fast it's coming out.
7:18
So increasing from 5 to 25, you get an increase in that jump.
7:23
And then also when the drug is diffusing through the polymer, playing with the amount of vinyl acetate also is how you provide tunable release in these different designs.
7:33
So with higher vinyl acetate, you have lower crystallinity of the polymer and that's a kind of a faster route for the molecule to diffuse out of that material.
7:43
But then on the right hand side looking at a much higher solubility drug, this is a sodium naproxen.
7:50
And so we're able to take that monolithic or monolayer design and it follows the same rule.
7:57
So as you go in, as you go down in vinyl acetate, you also go down in drug release.
8:02
So that's one way of tuning it.
8:04
But next, if you take that same dose form and now apply a membrane on that, what's very interesting is you get this effect of going into a different dosing regime where you entirely remove out that initial burst release and you get to a linear zero order release relatively quickly.
8:24
And by applying a membrane, it also detaches or decouples the release away from the drug loading.
8:29
So it doesn't matter what's happening in that reservoir.
8:32
Now you can tune it based off of things like thickness as well as the vinyl acetate because it still follows that same rule.
8:39
The lower the vinyl acetate, the lower the amount of drug release.
8:44
Next, we apply that same idea of taking a membrane or a multi-layer design and apply it to larger molecules.
8:52
On the left hand side we have a human serum IgG and in orange we have a that monolayer design.
9:01
And with the IgG being relatively soluble it comes out pretty freely.
9:05
But by applying different membrane characteristics, we can get to a very tunable release for that IgG over several months.
9:15
And looking at antisense oligonucleotides, these are one of the most soluble molecules that you know, we can see kind of coming out in today's therapeutics.
9:25
And this is kind of problematic for a lot of polymers out there is that if you have a simple design, these are so freely soluble that they can fly out of a lot of systems.
9:36
But by applying different configurations, we can now start to approach getting into a higher tunability for these very soluble molecules.
9:45
And this is a 21-mer antisense oligonucleotide just used in treating anti VEGF in an ocular application.
9:56
And then looking at coming back and revisiting that idea of drug load.
10:02
If you have any type of device that's implantable, you can take a very simple design and apply that same kind of methodology to put a drug loading on top of that device.
10:14
So for instance, if there's an ocular drainage device that now you want to either allow for to kind of improve implantability or allow for a complementation, a compliment of the what the drug, what the device is actually doing.
10:31
You can allow for drug loading to be a part of that device now by just coding the material or placing a cassette on top of that with different loadings.
10:40
And the last way that we look at tuning the releases, it's actually getting and playing with the amount of permeable surface area.
10:49
And you can see that going through different types of configurations.
10:54
You can also start to play it not only with the release rate, but what that release profile starts to look like.
11:02
And so when we generally work with a number of people who are looking to innovate on what they're currently doing, we, there's a couple of camps we tend to see.
11:12
There's a 505B2 or an LCM type opportunity coming in where they want to reformulate to have a higher efficacy or a better experience for the patient or there's the NCE type application.
11:28
And both of these tend to look for applying kind of currently use systems like a subcutaneous implant, intravaginal ring, IUDs or an ocular device.
11:40
But they really are just trying to leverage that existing device to get into the market.
11:45
But we also see a number of people that are looking to do really innovative things.
11:51
And we have the capability to, if you have an idea and also a constraint about where you need the dose, we have the ability to really create any type of shape or size to fit into those different applications.
12:06
And so the one way that we work with people is working in our prototyping lab.
12:12
And so when you in these types of arrangements, we have the ability to take your idea from our, your, we can bring in your API and work from an idea stage the whole way up into having a finished prototype that's up to about a preclinical setting.
12:31
So that you'd have something in hand to take forward into a CDMO to go into clinical studies or even into further analysis.
12:41
And during this time, we work with you in an iterative standpoint to find out what works best for you and how to help develop this dose form.
12:50
And we have a number of customers that come to us and say we don't even know what sustained delivery would look like for our molecule.
12:57
And this is very common in the RNA space where, you know, if you say sustained delivery, that's like going down a one way street in the wrong direction in most people's minds.
13:05
So we work with you to give you prototypes that can range in different release rates that you can apply to an animal model and then see what that really means in your setting.
13:16
And so just in these we really did this investment because a lot of people don't have these in house capabilities to do this.
13:26
We can do relatively precise work and just getting a prototype out for you to evaluate.
13:33
And then in the larger scheme, how we work with customers is either we can give you the material for your in house development.
13:40
And I will say that Celanese does have our pharma and medical division, but we're a very large company who applies just works over a lot of different industries, including automotive and kind of some other things along that side.
13:56
We have a great in-house facility for helping to do technical Support.
14:03
So if we give you the material, we can help you to do that Technical Support in how you either develop the prototype or even how you can do GMP or how you can do your scale up.
14:15
And as I mentioned, we also do that co-development, bringing that idea from the just the idea stage into the actual prototype.
14:23
And we also work on a strategic partnering where we do a master service agreement to help you to apply this type of strategy to different APIs in your portfolio or just to create a platform type device that can be applied to multiple different APIs.
14:42
And just to give you an idea of where we are going as a company, Celanese really I think that it doesn't have like a really high resonance in the pharma industry.
14:55
Where is it as a dozen maybe other industries.
14:58
But we have a polymer, it's been around for quite some time.
15:01
It's very recognised in a number of different dose forms and these collaborations that we've been able to publicly disclose really show just a little bit of a summary of where we're kind of going.
15:12
So the first couple give an idea of just in applications in either sexual health as well as contraception looking at advanced routes of administration with an oncology.
15:25
And then these three get at work, we've done in ocular whether it's looking at advanced formulations to get precision delivery even with very simple small implants in the eye, looking at super coital delivery to get it more efficacious route of administration to the retina in the eye as well as just an innovative approach, a platform that's doing some good stuff.
15:52
And then Secarna as well as we're looking at different routes of administration for ASOs in a number of different therapy areas.
16:01
And last, this is just a list of our partnered programmes looking at a couple of different therapy areas over oncology, ocular, CNS, Women's Health and just some other ones that fall in there.
16:14
And this will give you an idea of that therapy area, the different disease states that we're going after and some of the different molecules that we're playing within that.
16:25
And so we do have a number of feasibility programmes that are coming off going from feasibility into a marketed product.
16:33
And again, this is just a little bit of a summary that these are kind of growing as we go.
16:41
And so just to give a summary of the material, Vital Dose EVA is great for a patient centric delivery.
16:53
So whether you're reducing dosing frequency, you're reducing side effects, you're trying to place a set and forget type approach to a chronic disease.
17:01
This is a great, this is a great system.
17:04
It's been proven out in the number of different APIs that set and forget is kind of better for a patient.
17:11
And it's, it can be also beneficial to the formulator as well, where once that's placed in from weeks to months to years, depending on the application, you'll get a very consistent delivery over that period of time.
17:24
And our material has been used for over 2 decades.
17:27
So we have experienced working with people going into commercialised products and we support all of our materials with DMF.
17:35
And whether you're in oncology, ophthalmology, CNS, rare diseases, Women's Health, we're looking to do anything that would help you in your programme, whether it's leveraging existing dose forms to help you get to a better release profile or doing something relatively innovative and trying to push the envelope, looking at intracranial delivery, intrathecal and anything along those lines that are kind of outside of the box, but that would benefit the patient.
17:59
And we also look towards working towards any type of 505B2 as well as life cycle management and over this over the rest of the conference.
18:12
I know it sounds like a maybe a sitcom, but please come find Brian, Brian or Rob and we'd be happy to help you out.
18:20
And please connect with us over any of these other conferences going forward as well.
