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And our speaker is going to be Darren Quinn, Head of Business Development at BDD. Darren earned his master's degree in Chemistry from the University of Strathclyde in Glasgow, Scotland, where his industry experience began with a placement as an organ chemist in Technology Surveyor.
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He further his career at Lonza and NextPharma where he specialised in oral solid dosage formulation development for BCS Class 2 and 4 molecules.
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At BDD, Darren leverages his commercial and scientific expertise to address complex drug development challenges for BDD’s partners and clients.
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Welcome to the stage.
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So thank you everyone for coming to my presentation.
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It's nice to see you're here.
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Handsome familiar faces too.
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My name is Darren Quinn.
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I'm the head of Business Development at BDD Pharma.
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In this presentation, I'm going to be discussing BDD’s auto modified release technology OralogiK, and I will delve a little bit into a case study where we applied OralogiK to overcome a specific therapeutic challenge.
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So a lot of you may not be familiar with BDD.
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We're a small to sort of mid-sized company, but we have been around for 25 years and in fact our 25th anniversary this year, so quite an important milestone.
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But we started back in the day as bioimages research and at that time we were a spin out from the University of Strathclyde founded by Professor Howard Stevens and I'm sure some of you have heard of before.
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And at that thing we specialised solely and gamma scintigraphic clinical image and study, which I'll touch on in a little bit.
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But we did that exclusively for 10 years before we then formed the sister company Drug Delivery International and started off a formulation development services and developed a patented technology OralogiK.
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The two companies then came together in 2025 to form BDD Pharma as we are today, but we're more than just OralogiK and gamma scintigraphy now, although those remain the backbone of our company.
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We now offer a full plethora of CRO and CDMO services, which we've coined as lean clinical development.
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And the idea behind lean clinical development is to offer our partners, whether they're pharma or biotech, an integrated accelerated solution to get the early phase clinical data, cost effectively.
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And the way that we do this is by combining formulation development, small scale GNP manufacturing and phase one clinical trial services, the full plethora of phase one services from scintigraphy first in human and bioequivalent studies.
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And we do this all on the one roof in a single project manager.
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So removes the complexity and the unnecessary steps from clinical development and allows us to accelerate our partners taking links towards that critical clinical data.
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And the case study that we'll discuss about later on is an example of how we put lean clinical development into action.
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They go from product concept to clinical study report in under a year.
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But as I said, gamma scintigraphy is really the foundation on which BDD has been built over the past two decades.
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For those of you who aren't familiar with it's a non-invasive clinical imaging technique which allows us to not only visualise but quantify the performance of drug delivery systems and modified release formulations and humans and real time.
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And the process is fairly simple.
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We take a formulation, and we add a small quantity of radio isotope to that, but that can be normally technetium, but we can use different isotopes depending on the length of time you need to image for.
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And when we dose these radio labelled products and volunteers or patients and image them with a gamma camera, we can follow the fate of the formulation and human and assess the critical performance parameters of that drug delivery system.
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And it isn't just the images that you get from scintigraphy because the rate of the radio label release is quantifiable as well.
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And we can image across the full plethora of roots of administration.
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And we've done many studies across many different types of formulations over the past 25 years.
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Inhaled formulations are popular for scintigraphy, particularly when you have something which may be acting locally in the lungs and isn't well absorbed.
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Gamma scintigraphy can be a good way to understand things like lung deposition, residence times in the lungs where you're sort of walking in a pharmacokinetic black box.
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And with the introduction of the new global warming potential propellants over the past few years, scintigraphy has also been the leading method by which the effect on mucociliary clearance of these propellants has been assessed as well.
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And we've trailblazed the way for those types of studies.
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We're actually doing a nasal formulation imaging study at the moment as well.
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We're looking at formulation residence time and the nose clearance rates, the actual efficiency of the drug delivery device or how much of the formulation stays and the device and how much is actually delivered.
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But you know, given that we're experts in oral modified release, the bulk of the scintigraphy studies that we do come from oral solid dose.
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And with oral dosage scintigraphy, you can gain a variety of different insights into product performance.
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Not only the critical performance parameters of your actual drug delivery system like the site and time of disintegration in the GI tract or the duration of an extended release.
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But you can also have an understanding of exactly how the gastrointestinal tract and the physiology of the body is having an impact on product performance, looking at things like gastric emptying, GI transit, food effects.
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And we can even evaluate the variability between patients across multiple arms of a study or indeed and a single individual across multiple different formulations on multiple arms.
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And scintigraphy isn't just about the images you get directly from that, but it's about how you correlate that with the pharmacokinetics as well.
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A lot of the time when companies are trying to decide upon a drug delivery strategy, they don't actually always have the necessary information they need to make the most informed approach.
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If you take a molecule, for example, which has a really short half-life and you need to therefore develop a sustained release to give coverage over a full day, but you don't know how well your molecule might be absorbed further down the GI tract, that's going to have an impact on your pharmacokinetics.
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So what you can do with scintigraphy is correlate the pharmacokinetic time points with the corresponding images in the site of your product in the GI tract to get a full picture and understanding of exactly where your molecule is and how it's being absorbed.
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At that point, you can use that data to optimise your drug delivery approach.
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And over the past 25 years with scintigraphy, we as a company have become experts in biopharmaceutics.
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We have a really great understanding of how formulations are likely to behave in humans.
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But across that period, we've also equally seen where formulations haven't necessarily behaved as our clients expected them to based on that in vitro method developments, enteric coats that are a really good example of this.
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So the image you can see on the screen is from an actual study where we were looking at a product which had been encapsulated and an off the shelf ready enteric coated capsule.
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And as you can see, the capsule had actually ruptured in the stomach after only 15 minutes just in one individual, but in multiple individuals.
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And obviously if you need to enteric coat a product, it's because it won't survive an acid then it will have an impact on the end product.
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So this was also catastrophic for that particular product.
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But on upside, we've also seen well enteric coated capsules have survived but have stayed in the stomach for upwards of 12 hours, which is also really good for the enteric coat, works great.
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But it calls into question the in vitro methods that we use to actually develop these because as you all know, the standard USP dissolution is 2 hours an acid.
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But if we know that the actual can sometimes stay in the stomach for 12 hours, how robust in representative actually as that test, and a similar vein that there are companies out there who market proprietary duodenal coatings which claim to achieve duodenal drug release.
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And for all of you in here, you'll know that is like the holy grail of drug delivery releasing in the duodenum.
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But the problem is the way that they can claim this is because they achieved disintegration between sort of pH 4.5 and 6.5 in vitro dissolution.
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But that disintegration takes normally over 20 minutes to take place.
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And through doing gamma scintigraphy studies, we know that passes through the duodenum is normally less than 5 minutes.
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So these core things just aren't going to work how they are marketed to work.
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And the reason I say this isn't to bash these products, per se, but it's to, you know, call into question then vitro methods that we use to develop products.
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And always take it with a grain of salt because a lot of the time they need not be protective of what will actually happen in humans.
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And that's where scintigraphy is great because as in humans, so the data is unequivocal and can't be misinterpreted.
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And so through doing these studies for such a long time, as I said, we'd seen a lot of the time where our clients’ formulations were failing, but we wanted to offer a solution to overcome that.
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And that's why we developed our patented modified release technology OralogiK.
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And this is an erosion based tamed drug delivery system.
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And the principle is that you have a core tablet containing your API.
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We then compress the OralogiK a loadable barrier layer around that and that protects the API from the of gastrointestinal physiology and we can fine tune how long it takes for the body layer to erode and therefore control the exact site and time of drug release.
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And a great thing about OralogiK and why we can do that is because it works independently of gastrointestinal variables.
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So it isn’t impacted by pH, agitation, or microbiome and that's what allows us to have that unparalleled control over the exact site and time drug release.
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And the beauty of OralogiK is actually in its simplicity because it's really just a combination of two key excipients.
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One is a wax; the other is a disintegration agent.
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But it's how we put them together which makes them unique because they're commonly used safe excipients.
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The erodible barrier layer, we can control the exact time before drug release just by changing the ratio of the excipients, the way that we process them and ultimately the thickness of the erodible barrier layer.
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And this is some in vitro and vivo correlation, what we've done in the past, which shows exactly how well OralogiK correlates, and dissolution compared to humans.
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So what we did here was developed to sustained, well, the same sustained release OralogiK formulation and manufactured 2 tablets and which we incorporated radio label.
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And we carried out two tests.
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The first was an in vitro dissolution just using standard dissolution methods.
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And then the second was putting that radio label tablet into a human and measuring the rate of radio label release through the GI tract.
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And as you can see, there's a great correlation between both the in vivo and the in vitro data, which allows us to really optimise the drug development from an early stage because we know there's great correlation.
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But the really interesting thing to note here and it goes back to what I said before is how consistent OralogiK erodes in the GI tract.
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By 5 hours, as you can see on that graph there in vivo, the tablet is in the colon, but the rate of erosion hasn't changed.
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So irrespective of where that product is in the stomach, where there's low pH, you know, a lot of water agitation or whether it's in the colon, which is a really dry environment with only small pockets of water, erosion is going to happen at the exact same rate.
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And that allows us to really fine tune exactly how we want OralogiK to work.
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And that consistent performance allows us to develop a plethora of different modified release options with OralogiK.
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So if you take the example that I used before with the core tablet and a single layer of the audible barrier layer wrapped around that, we can achieve a delayed release.
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We can use this for two key reasons.
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First of all, because we have such a great understanding of gastrointestinal transit teams, through doing scintigraphy studies, we can fine tune the OralogiK or erodible barrier layer to deliver to a certain part of the GI tract just through time.
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And you can also use a delayed release mechanism for chronotherapeutic enhancement.
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So if you have a condition, rheumatoid arthritis is always a good example, where patients often suffer from early morning pain and stiffness as soon as they wake up.
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Well, if you took a tablet at nighttime, well the release of the API occurred corresponding with the peak of pro inflammatory cytokines, and you can dampen that effect and help these patients with the early morning pain.
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You then look at the one, just one to the right, which is a pulsatile release.
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And that's the same sort of mechanism of the tablet erodible barrier layer.
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But by adding an extra layer of API on top of that, you can achieve a pulsatile release.
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And you can take that even one step further and have up to three separate pulses of API and a single tablet.
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And you can do this with one API perhaps to take something that's a twice or three times daily product and create a once daily product and a single tablet with three or two separate doses.
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Or you can do it with two separate APIs to create a complex fixed dose combination product.
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And that's particular really useful when you have two APIs with different dosing requirements.
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Maybe they need to be separated by time and because there's a drug-drug interaction or maybe one as a pretreatment of the other.
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So OralogiK gives not only the physical separation of the drugs, but also the time separation of the drugs as well.
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And as I mentioned then the last slide with OralogiK, we can also do sustained release to a slightly different mechanism where we actually incorporate the API throughout the OralogiK erodible barrier layer.
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And because that erodes consistently through the GI tract, it means that the API is also released at the exact same rate.
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And it's an interesting approach to take for large molecules like peptides, enzymes, which we've done in the past because these types of molecules don't necessarily always disintegrate so well from standard HPMC matrix type systems.
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So with OralogiK approach allows you to do exactly that.
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And ultimately the technology is really modular.
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You can take a delay, a sustain, a second pulse, put it all together to achieve exactly what you want and create a product that is tailored to a specific therapeutic profile.
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And this is sort of just expanding on the delayed release and targeted drug delivery members.
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We can achieve colonic delivery with OralogiK.
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As I said, we have a really good understanding of typical GI transit teams and humans both in healthy volunteers and different disease states.
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So because of that, we can fine tune OralogiK to deliver to the colon either via a pulsatile release or through a sustained release throughout the entire colon. And when you image that's per scintigraphy, it's really great because you get these really distinct heart shapes where you can see the radio label actually moving throughout the colon.
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And what we do is we take the OralogiK delayed release, and we enteric coat that using a coat that we've developed obviously.
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So we know it will work.
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And that removes the variability of gastric emptying.
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So the OralogiK clock, for lack of a better term, doesn't start until it's actually released from the stomach.
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And OralogiK is a really good approach for colon targeting because a lot of the time the diseases that we actually need to target the colon for, such as Crohn's, colitis.
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But these patients often have variable pH and microbiome.
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So or the logic works based off time only.
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So the variability and pH and microbiome won't make a difference because we deliver just purely based on a timed release.
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Well, something I think is always important to know when talking about drug delivery technologies is the scalability, because there are a lot of great modified release technology and drug delivery systems out there.
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But the issue sometimes comes when you're then evaluating that to actually create a product that's commercially viable.
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Now with OralogiK that's absolutely the case because we've already had that manufactured commercial scale for one of our long standard partners and it is probably the most complex product that we'll ever develop.
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It's a triple pulse dexmethylphenidate product.
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And so we know that if that can be manufactured and scaled up, there's nothing that can't be in.
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The processes are fairly simple.
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You need hot melt extrusion and a tablet and tablet press, both of which are continuous and scalable processes.
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So now I just want to touch briefly on a specific case study where OralogiK was actually applied to treat a very specific therapeutic need.
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So our partners, Synchronicity Pharma identified an opportunity where OralogiK could be applied to help treat children with autism spectrum disorder.
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Now, up to 80% of children with autism unfortunately suffer from sleep disturbance, and because of that, 40% of those children also receive a pharmacological treatment.
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Although there isn't actually an FDA or MHRA approved treatment for sleep disturbance at the moment.
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But a typical treatment regimen would normally be a low dose of a hypnotic about 3 hours before sleep.
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In this case, it was melatonin, followed by a second dose of hypnotic about 3 hours after that, just at the time of sleep.
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In this case, it was Clonidine, which is typically used in migraine prophylaxis and hypertension.
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But because one of the side effects is drowsiness, it's an appropriate API in this case.
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Now, obviously, anyone who has children with autism in the family know that can be a difficult thing to deal with already.
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But haven't they actually, you know, give your children treatment just to help them go to sleep and stay asleep.
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Makes that exponentially more difficult, especially when it's a very strict dosing measurement like that.
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So in collaboration with Synchronicity, we identified an opportunity where we could hopefully improve patient compliance and therefore have better therapeutic outcomes and ultimately a better quality of life, not only for the children, but for the parents and the caregivers of these children who have to administer the treatments.
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And so we developed a fixed dose combination of both melatonin and Clonidine, and the product was designed exactly like this.
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So what we did was we developed the core tablet to contain Clonidine just using, you know, everyday standard tablet and methods.
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We then optimised the OralogiK at erodible barrier layer to achieve a release time between 3 to 4 hours.
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And then that immediate release that you can see on the top contained melatonin and that was for immediate release and the stomach upon ingestion.
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So not only did we develop the product, but we also ran the proof of concept clinical study as well.
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So that was a two way crossover in healthy volunteers at our phase one clinical unit in Glasgow.
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And the objectives of the study were twofold primarily: firstly, to compare the pharmacokinetics of the OralogiK formulation with the two individually dosed comparators, melatonin and Clonidine.
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And secondly, to evaluate the absorption of each of the APIs and correlate that with the site and time or drug release using gamma scintigraphy.
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So what you can see on the screen here are actual examples of the scintigraphic images that we got from that clinical study.
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And then that's instance what we did was we only radio labelled the core containing Clonidine because we knew that the immediate release layout would release right away as the table says.
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But theoretically if you had two different drugs releasing at different times in the GI tract or different sites, then you could radio label both of those layers to showcase distinct release with scintigraphy.
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But in this case, it was just the clonidine.
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So after 45 minutes going from left to right, you can see that the core tablet is still very much intact.
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And that's showcased by the concentrated area of radiation.
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Gastric emptying then happened by about 2.5 hours, and we see the tablet still very much intact in the proximal small intestine.
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And then after about 3.25 hours exactly where we wanted it, we can see the onset of radio label release, which correlates with the onset of tablet disintegration and the beginning of release of Clonidine.
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And that was an approximate small intestine.
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And you can see after four hours of formulation has moved around and it's in the sort of distal small bowel and disintegration has fully completed at that stage.
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And this is a snapshot of the pharmacokinetic results from that study as well.
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So what you see is with the solid lines and blue and red, those are the individually dosed comparators.
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And then the dashed lanes are from the OralogiK formulation.
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And the study was set up that in one arm the volunteers received the OralogiK product and then the next arm they received the two individually dosed products 3 hours apart to mimic the treatment regimen and the OralogiK formulation.
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As you can see, there's really great correlation between both the immediate release and the delayed release of the exact time that we wanted up.
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So ultimately we were able to achieve this for Synchronicity.
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And it's just one example of where we've used OralogiK to fit a very specific therapeutic profile.
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But hopefully what's come across is how modular and versatile the technology is and how it can be applied across many different molecule types in different therapeutic areas.
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And I'm using our lean clinical development approach, combining formulation, manufacturing and clinical services.
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We were able to go from product concept to the final clinical study report and just under a year.
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So that's me.
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Thank you for listening.
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Happy to take any questions.