0:00
Awesome, thank you for that introduction.
0:01
So hopefully all the slides are set.
0:04
We promise to be experts in nano therapeutics and not on sharing slides.
0:09
But yeah, as he mentioned, my name is Jess Widman.
0:12
I'm the Senior product development scientist at NanoComposix, which is a branch of Fortis Life Sciences.
0:18
I'm really excited to talk to you today about maximising therapeutic impact through nanoparticle enabled delivery. At NanoComposix, where CDMO focused on nano material solutions, where we partner with you from development all the way through manufacturing of your nanotherapeutics.
0:36
To give you a brief outline of what we'll go over today, we'll start off with a quick background of what nanoparticles are, talk about some key challenges to conventional therapeutic delivery, and then move into how nanoparticles can help solve some of those current challenges that we're facing through nanoparticle engineering and a few real life case studies.
0:55
Then we'll again reiterate how NanoComposix can help expedite your time to clinic.
1:02
So let's talk about what nanoparticles are.
1:06
Nanoparticles are particles that have at least one dimension in the nanoscale range.
1:11
Most typically this is somewhere between about 5 to 500 nanometers or so. To talk about what that actually looks like with things that we work with every day.
1:19
So proteins and antibodies are on the scale of about one to 10 nanometers.
1:24
Viruses are closer to 100 nanometers, which is one of the most common size of nanoparticles for nanotherapeutics.
1:31
Whereas zooming out towards, as we approach the macro scale, we see that bacteria are close to about 1 Micron, eukaryotic cells are closer to 10 microns.
1:40
And then zooming out even further to something that we can see with the naked eye, a credit card thickness is about 1 millimetre, so about 1 millionth the size of a nanometer.
1:51
Nanoparticles can be synthesised from a wide range of different materials.
1:54
So at NanoComposix we focus on materials such as gold, all the way to biodegradable polymers like PLGI.
2:02
We also produce nanoparticles for a wide range of applications.
2:05
We'll focus on the medicine application today, but we've made nanoparticles for even defence applications or national security applications as well.
2:17
Let's look at biomaterials and nanomaterials, specifically in therapeutics.
2:21
They started coming on the scene about 30 to 40 years ago when doxorubicin was a very common treatment for different types of cancers.
2:29
One of the main challenges with it is that it's very cardio toxic.
2:33
So when you dose patients, they have cardiac side effects.
2:37
And this was really difficult, especially for patients with underlying diseases.
2:41
And so Doxil is a liposomal formulation of doxorubicin that actually reduce the cardio toxicity while still treating the patient.
2:49
And that was one of the first nano therapeutics that was FDA approved and it really elevated the standard of care for patients who otherwise couldn't be treated.
2:59
As we move to present day, we're all familiar with the COVID-19 vaccine, which is again a liposomal formulation of therapeutic.
3:06
And so as nanomedicine starts gaining more traction, we're really excited to see what comes next.
3:15
Like I mentioned in the previous slide, there's a lot of therapeutics that exist that either can't be delivered safely to patients or just not efficiently to patients.
3:24
And so we have a lot of medicines that work really well, but we need some sort of delivery vehicle to get them there because they have challenges like poor solubility and stability, nonspecific systemic distribution of macromolecules or small molecules that can diffuse more freely around the body and cause those off target effects, rapid clearance through your kidneys, biological barrier limitations such as not being able to cross the BBB and then lastly, dose limiting toxicity.
3:55
One potential solution to these challenges is to actually use a nanoparticle as a drug delivery vehicle.
4:01
At NanoComposix, we partner with you to find the right vehicle for your particular API and your particular needs.
4:07
However, I did want to highlight two platforms that we use quite frequently for Nano Therapeutics customers.
4:13
One is our mesoporous silica nanoparticles or MSNs, and below that is polymeric nanoparticles.
4:20
Really commonly we use PLGA, but we're familiar with a wide array of different polymers.
4:25
Both of these have their own unique advantages and disadvantages, and our experts are there to walk you through those advantages and help you choose the right platform for your needs.
4:34
Overall, both platforms are biocompatible, biodegradable, have high drug loading capacity, tuneable and controlled release, and then we can have really excellent control over the composition as well as surface modifications to both of these particle types.
4:51
So let's specifically put these two things together and understand how our nanoparticles can actually help solve some of the challenges we mentioned in the previous slide, starting with solubility and stability.
5:04
So poor drug solubility is a large issue because it limits the bioavailability of the compound in your patient.
5:11
And so by encapsulating your API that is hydrophobic, for example, within a polymeric nanoparticle and as a borosilicate nanoparticle, whatever nanoparticle platform you choose, you can actually increase the bioavailability of that compound for your patient.
5:25
Additionally, for drug stability, we have a lot of small molecules as well as macromolecules that are very sensitive to their environment.
5:33
Take nucleic acids for example.
5:35
There's a lot of nucleases in the environment.
5:37
And so putting a nucleic acid in a nanoparticle protects it from seeing that nuclease and allows it to remain stable for longer.
5:46
In this table you can see that we have a few example APIs that we have loaded into polymeric nanoparticles in this case to show you that we have a wide range of experience loading hydrophobic and hydrophilic drugs at nanoparticle sizes that are clinically relevant around that 100 to 200 nanometre range that's very commonly requested.
6:08
And this was actually one reason that a customer approached us was they were developing A polymeric nanoparticle for an immunotherapeutic application.
6:16
They were trying to co load both a protein and a nucleic acid.
6:20
And so right away we were excited to get them into a nanoparticle because we knew that we needed to protect the nucleic acid from nucleases.
6:27
They were also having difficulty co loading these two APIs.
6:30
And so we were able to work with them from the ground up on optimising their formulation.
6:35
We achieved about a 55% encapsulation efficiency for them which they were really excited about and retained functionality of both the protein and the nucleic acid throughout our formulation.
6:46
We then were able to scale up their batch size to multi gramme batches.
6:50
We actually moved the whole process under a quality management system for GMP manufacturing because we have produced material for this customer to be used in phase one and two clinical trials already.
7:05
Moving on to a few other challenges that I want to talk about somewhat together include non-specific systemic distribution, rapid clearance and biological barrier limitations.
7:15
So just by encapsulating our APIs we have a larger sized nanoparticle than we did our small molecule or macro molecule.
7:22
So we limit diffusion quite significantly and don't get nearly as much nonspecific distribution of our drug product.
7:30
However, we can also add on surface modifications to further extend circulation time and also enable targeted delivery.
7:39
I'll briefly go over a few of the most common surface modifications we do at nanocomposites.
7:44
The first being adding a polymer, most commonly PEG to the surface of your nanoparticle.
7:50
This prevents nonspecific protein absorption to the surface of your nanoparticle and helps reduce clearance by the immune system in the liver, which is how nanoparticles are mainly cleared.
8:00
Additionally, we can add a peptide protein or specifically antibody to the surface of the nanoparticle, which can provide active targeting.
8:08
It may be involved with your therapeutic response, and it can also help overcome those biological barriers we talked about as well.
8:16
Another common modification is adding a carbohydrate to the surface of the nanoparticle.
8:20
So this kind of mimics the sugars that are on the surface of bacteria.
8:25
And so this is a great targeting strategy for immune cells.
8:29
Lastly, gaining popularity again is adding lipids, which can again help promote stability, improve circulation time and potentially mediate cell membrane fusion.
8:43
An example where we modified the surface of our nanoparticles was for a customer who wanted to change their route of administration for a certain peptide.
8:52
We ended up using our mesoporous silica nanoparticle platform for this customer to deliver their peptide.
8:59
So we optimise the formulation by tuning the pore size and structure for their specific needs.
9:04
Loading the API into the pores of the mesoporous silicon nanoparticle as you see on the left hand side.
9:10
And then they wanted release of their API in acidic environments.
9:14
So we added a pH sensitive probe to cover the surface of the mesoporous silicon nanoparticles such that the API would only be released in those acidic environments.
9:25
So this was a really great challenge for us because we needed to make sure that we only released in those target environments which we were able to achieve through our optimization with our R&D team.
9:36
We also retained functionality throughout scale up and again produce large batch sizes for use in non-human primate studies for this customer.
9:48
Lastly, I know a lot of the strategies that I've mentioned so far can also help reduce dose limiting toxicity, but I want to highlight one of the main benefits of using polymeric nanoparticles, which is controlled release.
10:00
So typically when we dose a patient with a drug, we get something that looks like this yellow curve here, a burst release.
10:07
So we dose the patient really quickly.
10:10
They rise through the therapeutic window, potentially over the maximum tolerated dose, get some side effects, and then that quickly tapers down.
10:18
If we need to stay in that therapeutic window for longer, we again have to dose the patient.
10:22
And overall, this reduces patient compliance because they need to have the medicine more than once and then also potentially have side effects.
10:31
What we want to move towards is what's in this green line 0 order release, where we never go above that maximum tolerated dose and we stay within that therapeutic window for as long as possible.
10:43
What's often achievable is somewhere closer to this purple curve where we have sustained release, where we're in the therapeutic window for longer and we don't reach that maximum tolerated dose either.
10:53
So how do we actually accomplish this?
10:55
One way is to encapsulate our drugs in polymeric nanoparticles that slowly degrade over time, slowly releasing the API.
11:04
And so to tune this release, we can choose a different polymer identity based on how long you want your API to release over.
11:11
We can also alter co-polymer ratios.
11:13
If you're using something like PLGA, we can add those surface modifications and coatings as well that we talked about on the previous slide.
11:21
And lastly, particle size is really important here as well because this dictates how much drug you can load overall.
11:29
And again, route of administration is very important here.
11:31
If you are doing something IV, you have a size limitation, whereas if you're doing something IP or sub Q, you might be able to inject a drug depot that's micron sizes, which we have experience working with nanoparticles on the 10 nanometre all the way to 10 Micron size range there as well.
11:53
With mesopore silica nanoparticles, we can get some controlled release again by making those surface modifications and tuning that pore size as well.
12:01
But really it's the polymeric nanoparticles that have this slow release over time.
12:09
So we talked a lot about a lot of great benefits that nanoparticles have.
12:13
Why aren't there more that are FDA approved?
12:15
So one of the main challenges we see with our customers is that it's really difficult to scale nanoparticles really reproducibly and also do so with a GMP compliant facility.
12:27
So that's exactly why this next customer approached us.
12:30
They had developed an enzyme encapsulating polymeric nanoparticle for a specialised cosmeceutical application.
12:38
So they had a process that was working OK for them, but they had sort of maxed out the scale they could reach on their current equipment and couldn't further scale with their expertise.
12:47
And so they approached us.
12:49
We were able to actually transfer over their process really well.
12:53
We achieved the same release and enzyme function that they had seen and got the green light to go ahead and do some process development for them.
13:01
We were able to transfer their process to more scalable equipment and start the scale up process retaining enzyme functionality.
13:09
And I think all of us can appreciate how difficult it is to work with enzymes.
13:12
So this was a really great challenge for us and glad to say that we succeeded.
13:17
We develop a lyophilized formulation for them.
13:20
That's what they requested for integration into their final cosmeceutical formulation and again retained that API release and function throughout that whole LYO process as well.
13:31
And overall, they were really happy with their results because not only were they able to produce a larger lot size of their final cosmeceutical, but also decrease the price per gramme of their active.
13:45
To really highlight what a challenge this is, we had another customer recent recently approached us for the same reason.
13:51
They were having trouble further scaling their formulation that was a small molecule encapsulated in a polymeric nanoparticle as well.
13:59
And again for a specialised cosmetic application that had some regulatory requirements that we could fit as well.
14:06
Similarly to the last one, we were able to transfer the process.
14:10
We really simplified it and optimised it significantly and we're able to achieve scales over 100 times what they were previously working with and process really large volumes of batches for them, over 100 litres of batches.
14:24
And we have produced batches for this customer for their commercial use already.
14:33
So again, really to highlight our expertise at NanoComposix, translation of nanoparticle therapeutics can be very challenging.
14:42
You have a lot of requirements you need to meet that we meet at all stages from development and R&D all the way through manufacturing.
14:50
We have technical experts that are that have niche expertise in different nano therapeutics, and we work with our customers very collaboratively.
14:58
We're known to have a very nimble approach to working with our customers.
15:03
We also get our process development team working with us very early on.
15:06
So that way we've truly expedite your time to clinic.
15:10
And lastly, in addition to this niche nanoparticle expertise, we have GMP compliant and ISO certified facilities as well.
15:25
At NanoComposix and across our Fortis life science portfolio we're really excited to work with whatever complex challenges you have, I mentioned earlier that we are, we're part of Fortis Life Sciences, which is a portfolio that includes antibody solutions, molecular diagnostics, lyophilization services.
15:41
So we work well together across the board to help solve the most complex challenges.
15:49
And with that, I'd like to thank you for your time.
15:51
You can come find us at booth #62.
15:53
I have my colleagues here, Diana, our Programme Manager, as well as Kimberly, our Business Development Manager and we'd love to take any questions you might have now or at our booth.