0:00
Thank you for the kind introduction and thank you for coming.
0:06
Yes, so I will talk about innovative dosage forms for large molecules like peptides, antibodies and RNA.
0:13
And I will start with giving you an introduction about our drug delivery technology.
0:19
And that drug delivery technology is called VitalDose and our drug delivery technology is based on polyethylene vinyl acetate, which is a low melting thermoplastic.
0:34
It's non resolvable, but it is very inert.
0:37
And what you can do with it is basically you can compound it with a drug component and form a drug eluting implant.
0:48
And the benefit of that is that you have a continuous release over time and you can tune that continuous release over weeks, but you can also have a release over months and even years.
1:02
So our technology is a commercially established since over 20 years.
1:09
It's used in vaginal rings and also in subcutaneous implants.
1:14
And yes, and that you can see we are coming really from the women's Health space, but now we are evolving really into the oncology space and CNS and endocrinology.
1:32
So what is really beneficial about our technology is it accommodates really a broad range of drug components.
1:42
Commercially established as I mentioned are small molecules like Etonogestrel, but now we've tested much more components over the recent years and our technology is also feasible to deliver peptides, antisense oligonucleotides and even larger compounds like antibodies.
2:09
And in addition to yes, that it can basically release a lot a large variety of compounds, you can actually have different configurations which allow you to tune the release from slow release to faster release.
2:32
This slide I like or I like the graph because it shows basically what drugs components, APIs we've tested so far in house in our lab and it should show you basically that there's no limitation in terms of hydrophilicity or hydrophobicity.
2:52
And also like I just mentioned in terms of molecular weight.
2:56
So we tested small molecules as well as large molecules.
3:03
So how do you get actually to drug eluting implant?
3:07
Basically what is done is you take our VitalDose, ethylene vinyl acetate and you compound it with the API.
3:18
The API needs to be in a dry powdered state and that is how you blend it and then extrude it.
3:26
And you get small pellets and from these smaller pellets you can create any form factor that you would like to achieve.
3:33
That can be rods, but that can also be rings or any other kind of shape.
3:42
And from our experience with the different APIs, we basically gained the knowledge that there is actually a different kind of release depending really what drug component you integrate in our polymer system.
4:04
So if you have a small molecule and very low loading you the API is actually very good dispersed in our ethylene vinyl acetate and then the drug is released by diffusion.
4:20
So basically it diffuses through the ethylene vinyl acetate.
4:23
That is what you see on the upper side of the graph.
4:27
On the lower side, that is what happens if you have a large molecule and high loading.
4:34
In that case, really a porous network is generated and then if you place the implant into an aqueous solution, the drug is solvated through the porous network.
4:52
What you can imagine is if you have a very hydrophilic compound, the drug is released really fast.
5:03
And therefore we came up with a variety of systems how you can actually control a release and really slow down release.
5:16
And this is done actually with membranes.
5:21
So rate control membranes, that is what I want to show you here.
5:27
What you see here in this graph is the and the release of lysozyme.
5:33
So we added 60% of lysozyme into our ethylene vinyl acetate.
5:41
And if you look here on the right, on the left-hand side, you see that if you have just a simple system, a monolithic system, the drug is eluted very fast.
5:53
So within one two days, the drug is eluted.
5:56
However, if you apply membranes, the membrane can adjust the release and then it's really slowing down the release.
6:07
And it really depends on what kind of membrane you attach basically to the core.
6:13
So in that way you can optimise the drug release.
6:20
Now switching gears a little bit, I want to bring up some product concepts mainly to give you some ideas how our drug delivery technology can at the end be used in other therapeutic areas.
6:35
And I will start with cancer treatment, so and looking into therapy with monoclonal antibodies.
6:45
So what is the current challenge?
6:47
Monoclonal antibodies are usually infused.
6:51
So basically the whole body is treated with the monoclonal antibody.
6:59
And what is the limitation?
7:01
The limitation is toxicity, toxicity to the healthy cells and that limits the therapeutic outcome.
7:09
What can be a solution is moving from that intravenous delivery to a localised delivery.
7:18
So you could basically place an implant adjacent or intratumoral into the cancer cells.
7:27
What you achieve with that is you reduce the side effects and you of course you need much less drug load.
7:37
And further by using [unclear] implant and not just injecting it into tumour, you can increase the drug retention at the tumour.
7:49
What we've done to check for feasibility, we tested a monoclonal antibody.
7:58
In our case we use trastuzumab as it was available and we did drug release testing and we checked for stability and that is what you see here on the lower graphs.
8:11
So apparently a monoclonal antibody survives the extrusion process and also stays stable over the first months.
8:21
So actually it's really an option really to move into an implant solution.
8:33
Staying with cancer treatments, I want to show you here a peptide therapy, Goserelin, is not only used as a cancer treatment itself, but also as an adjuvant treatment.
8:48
And there it needs to be taken for a very long time.
8:53
And yes, what is the challenge?
8:56
The challenge is the adherence.
8:59
And if patients are not adherent, the risk of reoccurrence is highly increasing.
9:07
So what could a long acting implant do?
9:12
What could it be as a solution?
9:15
If you use a long-acting implant, it reduces the dosing frequency.
9:19
And of course it here, it increases adherence.
9:25
What we've done is that we tested Goserelin in our drug release system and what you see here is a fairly nice curve already with our monolithic design.
9:40
And we checked also for stability and Goserelin stays stable over six months.
9:46
So you can easily go for a six months or even a one year release implant with Goserelin.
9:59
Then moving into ophthalmology, so long-acting implants can be used for retinal disorders.
10:06
That addresses the high treatment burdened also currently coming with retinal disorders.
10:13
Usually, for example, TKIs are given via injections and you could overcome that by moving into or changing the route of administration to an intravitreal implant or to a suprachoroidal implant.
10:32
And what we've done to check for feasibility is we tested TKIs mainly axitinib and we tested the release over time and you can extrapolate it and then come up basically with a six months implant.
10:53
Our system can not only be used for the back of the eye but also to the front of the eye.
10:59
This is an example for treating glaucoma.
11:02
The current standard treatment are eye drops and also here the main issue is non compliance.
11:11
And yeah, what you could do is basically use an implant, put it in the front of the eye and then have for example, like here displayed timolol released over an extended period of time, like a six months release implant would be an option.
11:29
You could also use it in combination with, yes, a drainage device.
11:37
So have a drug eluting component to the drainage device attached.
11:47
In the light of time, I will move to RNA therapeutics.
11:52
So drug eluting implants can also address the challenges for RNA therapeutics.
12:00
So what are the current challenges with RNA therapeutics?
12:05
It's really the delivery to the side of action is one challenge.
12:10
The short half lives and yeah, that at the current stage you need to in check very frequently and that it is really a treatment burden for patients and an implant could be a solution.
12:26
RNA therapeutics have evolved over the last decades and looking at the current treatments today actually for siRNA we really have a solution.
12:40
So the dosing is only every six months.
12:48
However, for example for antisense oligonucleotides you still have very frequent injections.
12:58
VitalDose can be basically a solution to deliver antisense oligonucleotides.
13:07
You can take a localised approach.
13:09
So you can use it for intravitreal delivery, you can use it for intratumoral delivery or even intrathecal delivery.
13:19
So basically use an implant to cross the physiological barrier or you can use it for systemic treatment if you want to treat cardiovascular or inflammation mainly to reduce the administration frequency.
13:38
And this is the data I can show you today.
13:42
We checked an antisense oligonucleotide which was phosphorylated, so and we checked it for stability over a longer period of time.
13:55
So actually antisense oligonucleotide is very stable.
14:00
So it's a good fit to our implant solution.
14:05
What you can see here in that graph is the release and as we loaded the implant was 50% and we only used a monolithic system and antisense oligonucleotides are fairly hydrophilic.
14:21
They will come out very fast.
14:24
So the next step is really to find an appropriate membrane and this is where we are starting and where we are working on to reduce basically the drug release at the beginning and to change it to a more continuous release.
14:44
Yes, I quickly want to highlight our feasibility lab.
14:51
So what we can do in house is we can do design development, we can do formulation development, we do prototyping and drug release testing in house.
15:05
And with that, I really want to thank our collaborations and partners with them.
15:14
We have really exciting projects.
15:17
So I want to take that moment and thank these collaborations.
15:24
And yeah, ending here, I hope I could show you that our direct delivery technology is a really versatile technology, but you can use for really a broad range of molecules and it is also really tuneable.
15:41
So you can really adjust it according to your needs.
