0:30 Thanks, everybody, for taking the time this morning to come listen to a little bit about silica-based drug delivery.
0:37 My intention today is to put the coordinates in place on who DelSiTech is, who we are, and a little bit about the technology.
0:46 I want to explain how the technology works, how we utilize it, and give you a couple of examples that demonstrate the paradigms that need to be taken into account with this particular type of technology.
1:04 DelSiTech is a small company based in Finland.
1:08 There are about 50 of us now, mostly young scientists coming from a material science background.
1:16 Everything we do is based on biodegradable amorphous silicon dioxide.
1:20 We use silica or silicon dioxide to encapsulate a variety of molecules.
1:27 The aim is to produce microparticles that can control the release of various molecules.
1:37 It is a proprietary technology, and we work hard to keep growing our patent portfolios, currently up to 2036.
1:44 The technology is extremely versatile in terms of release duration.
1:55 With the same technology, we can go from a 24-hour release to one year and everything in between.
2:08 Silica is effectively inert, giving us a unique ability to apply this technology to very sensitive entities.
2:24 Silica works very well with nucleic acids, and we recently announced work on mRNA.
2:35 This inert carrier is very suitable for biological entities, which is why we're here today.
2:46 We generally work with partners and also on our internal pipeline.
2:50 Currently, we're developing about 30 different products, with around 70% being biological entities.
3:04 We see a clear shift in finding the most value for silica as a drug delivery technology within the scope of biologics.
3:13 Peptides and up make up about 70% of the work we do.
3:25 This is a reasonably affordable technology, and we aim to apply it to global health challenges. While we can do ASO over long term, its important to note that our technology can be used in developing countries.
3:34 We work with Unitaid, Gates Foundation, Conrad, and others in various therapeutic areas and indications.
3:55 Let's get into the technology itself.
3:59 The technology is based on a microparticle that we can tune for release, but that's only half of the story.
4:15 We build the microparticle around the drug substance.
4:20 Instead of first producing a microparticle and then loading a protein into it, we build the silica microparticle around the protein.
4:34 Once we have the microparticle, we combine it with a silica hydrogel.
4:43 We bind the silica particle with the silica hydrogel into a silica-silica composite.
4:57 This is an irreversible composite, which is important for injectability and stability.
5:07 The main advantage is that we can apply the controlled release biologic of choice to various routes of administration.
5:16 These include intraocular injections, subcutaneous, intramuscular, topical administration, and more.
5:49 The basic principle is that combining the particle with hydrogel creates an irreversible composite that's easy to administer.
6:05 The chemistry behind this technology is well-characterised sol-gel chemistry.
6:15 It's a water-based process, using tetraethyl orthosilicate (TIOS) as a precursor. We don’t use toxic solvents or other harsh catalysts.
6:34 When TIOS is introduced to water and the pH is adjusted, silica is hydrolyzed out of the TIOS.
6:50 Silica forms short cyclic chains rather than long chains, that aggregate into nanostructures, which are efficient at entrapping molecules.
7:31 When a protein is introduced to these nanostructures, it becomes entrapped between the silica chains.
7:59 The protein is continuously encased by more nanoaggregates of silica.
8:22 We spray dry the solution to produce a dry solid silica microparticle containing the protein of a D50 value of three to seven microns.
8:42 The particle is combined with the hydrogel to form the final technology.
9:00 The material coming out of the syringe is the actual silica composite.
9:23 The composite is a non-flowing gel, which prevents sedimentation and maintains dose consistency over time.
9:57 When the plunger is pushed, the gel becomes a highly shear-thinning liquid that can flow through thin gauge needles.
10:48 This property is maintained at high particle density, allowing for easy injection through thin gauge needles.
11:19 After administration, the gel structure reforms, creating an unbreakable depot in the tissue. The value of this is highly dependent on the therapeutic area.
12:06 For example, this is important for subcutaneous treatments, as the entire dose can be removed in one go. It is really bound to this composite form.
12:43 The high load of protein-containing microparticles meets dose requirements for longer durations of controlled release.
13:23 Now that it’s been administered how does the silica release? Silica dissolves into water, and the solubility of the silica holding the protein is moderated during the chemistry stage. So we can choose if it dissolves very quickly or very slowly. What we want to determine is how quickly does silica dissolve in body fluids. We can figure out what an in vivo profile will look from the in vitro profile.
14:03 The body doesn't metabolize silica; it dissolves into silicic acid, which is a weak acid and doesn't cause local pH changes or tolerability issues.
15:06 The final composition of the product contains trace amounts of water, the API, and silica.
15:52 Silica acts as a stabilizing agent for sensitive molecules like mRNA. So it offers a protective and stable environment for these biological entities.
16:07 The technology provides controlled release strictly dependent on silica biodegradation.
17:02 A formulation for a paediatric patient population showed no burst and a stable release profile.
17:45 If you have an API we can create stable release profiles. The release profile is consistent with silica controlling the release, not diffusion.
18:18 A CD40L antibody formulation for six months by subcutaneous administration showed a stable release profile. The formulation strategy involved microparticle with hydrogel and then it was administered by a pre-filled syringe.
19:14 The release profile is erosion-based, not diffusion-based.
19:58 The technology can introduce a tuned burst for rapid onset of action if needed. One should note that this technology is inclined to steady release but we can introduce a tuned-burst.
20:26 Tolerability data from posterior segment ophthalmology showed no abnormalities or harm to the eye.
22:10 We observed how quickly intraocular pressure recovered to baseline within 30 minutes after administration.
22:52 Proteomics analysis showed no significant changes in inflammatory proteins.
23:08 The technology achieves linear release profiles with no burst and is applicable to small and large molecules.
23:50 The technology is well-tolerated in various routes of administration and has been tested with biologics.
24:04 Thank you very much.
