Aptamer Group PLC (APTA) Earnings Call Transcript & Summary

Hello, everyone, and welcome to the Aptamer Group webcast presentation. We've prepared this webcast to follow on from our recent announcements and update you all on particular areas of work that we've been working on over the last couple of months. So the presentation will be broken into 3 areas. First, we'll give you some background to Aptamer Group and what we do as a company for those who are new to the story. We'll then give you a bit of an update on 2 significant areas of development within the business. Firstly, we'll focus on our recent work in the drug delivery space, focusing on the developments of our Optimer binders for delivery of treatments for fibrotic liver disease. We'll then move on to our new technology platform, the Optimer+ platform and tell you a little bit more about that and why it's exciting and how that could be applied, particularly in drug delivery. So firstly, a bit of background to the company. So Aptamer Group is a biotechnology company that's based in York in the U.K. We started trading in 2012 and have expanded the business and listed on AIM at the end of December in 2021. Now as a company, we've partnered with over 75% of the top 20 pharma companies across the globe. So we have projects with nearly 40 partners, ranging in all sorts of applications from therapeutics to diagnostics to research tools. And this really speaks to the power of our technology and the broad applicability of it. So first to put into context what we do as a company. So Aptamer Group operate in what is known as the affinity ligand market. Now an affinity ligand is a scientific way of saying a binder molecule. So as a company, we develop binder molecules that stick to other molecules. Now as you can imagine, with a description that's so broad, the applications of our technology are equally broad. So to give you an example that people will be familiar with, the COVID test that we all had to enjoy recently. Now that test was made possible by an affinity ligand, a binder that recognized the COVID virus. Now without that binder, that test would not have existed. So you can see how molecules of this nature are really important throughout the life sciences industry. Now the affinity ligand market space has been dominated by antibodies for many, many years. This was one of the first binder technologies to be commercialized. Unfortunately, there are problems with that platform. As many of you may know, antibodies are generated in animals. Now there's an issue with that system. Firstly, has obviously, the ethical concerns, but it's very difficult to control the conditions inside an animal, so that often means that you don't get a binder that meets all of your performance criteria. So there's a lot of development work and re-refinement that's needed to turn a preliminarily developed antibody into a functional product. And quite often, that isn't possible. So estimates suggest that about 50% of antibodies fail to meet their exact performance requirements. Now other technologies have emerged to try and address those unmet needs. So these have been developed by companies, for example, argenx, Molecular Partners and Avacta and indeed Bicycles. Now all of those platform technologies have been developed around protein scaffold, most of them being synthetic, but not all of them. Now Aptamers and Optimers are unique within the affinity ligand space because our binders are DNA or RNA-based. So we work with a nucleic acid scaffold. So it's a little different from the other platforms, but it has the ability to recognize the targets in a similar way. So our molecules are DNA- or RNA-based. They're made up of the 4 building blocks of DNA, and that gives us a reliable and scalable manufacturing process. I'll come back to that in the following slide. So here, we can see some of the advantages of our platform. So firstly, our binders are all isolated totally in a laboratory. There are no plants or animals involved in that development process. It's all done on robots. That actually means that we have the ability to target things that you can't put into an animal. So for example, we can work with toxic molecules that would lead to a sick bunny rabbit rather than an antibody. It also means that we can target whole cells or whole tissues you just can't do with antibody-based platforms. Now that's very important when it comes to developing binders against, for example, cancer cells or as we will show later on cells associated with fibrotic liver disease. The tunable selectivity of our process is also critically important. This means that we can generate binders that target one sort of protein specifically and not another one. Or in the case of diseases, we can target one type of cell, for example, cancer and make sure that they don't recognize noncancerous cells. So this is really important if you want to target your therapeutic, for example, to one cell type and not another. We'll come back to that point in a moment. Now as I mentioned, our Optimer binders are totally synthetic which gives a great advantage when it comes to the manufacturing and the quality control. So Optimers can be synthesized, they can be made synthetically through very well understood and very scalable chemical manufacturing processes. So this gives much better reproducibility from batch to batch. So that's really important in all sorts of applications, especially diagnostic and therapeutic uses where you want every batch to be exactly the same. Now as I mentioned, our processes are highly automated, which means our turnaround time can be very, very rapid. We have turned around Optimer binders in as little as 17 days. That was for our COVID project a number of years ago. Now this compares to anywhere from 4 to 18 months for antibody generation. So you can see there is a significant time advantage. And as I mentioned, the scalability and manufacturability of Optimers is also a significant advantage. If you go to the right manufacturer, you can have Optimers made on the kilogram scale. So that's a lot of drug before you need to make a new batch. So at Aptamer Group, we see ourselves as an enabler of technologies. We use our Optimer platform, shown in the hexagon in the middle of the slide there to address intractable problems for our customers, collaborators and partners. So those partners often come to us with a target molecule. You can see on the left-hand side of the slide, that's something that they want a binder against. So that could be a small molecule, for example, a food additive or an environmental contaminant, something of that nature. It could be a protein, so something that they want to study, something that they want to purify or it could be a more complicated system like a whole cell or a tissue or indeed a virus. So in those cases, the end application is often therapeutic in nature. So they have a target molecule. They also have something that they want to do with that target molecule, so that's their application. Now this could be a therapeutic. They may want to stop that protein doing something it isn't supposed to do, but they may also want to deliver a therapeutic. So they might want to target, for example, a cancer cell. Their applications may also include bioprocessing, it's a purification of a molecule that they're interested in or a diagnostic. It could be a detection of something that they're interested in, again, using COVID as an example. Their applications may also be research tools, so they might want to use a binder to study a molecule. The point here is that they have an application and a target, but without the affinity ligand, without the binder, there's no way to make those 2 things marry up, which is where we, as a company, come in. So today, we're going to focus on therapeutic applications. Now as I mentioned, over the last 5 years, there's been an increasing demand for targeted delivery vehicles. So that's a molecule that is able to take a drug to a specific site of action. So for example, a delivery system to take a chemotherapeutic only to cancerous cells. I'll come back to that in a minute. So the idea of targeting drugs is a major challenge within the market. So there's a lot of interest in this space, as you can see by some of the announcements that we've put out over recent months and years. So you can see some examples down the left-hand side of the slide of some of the announcements and partnerships that we've engaged in this space. So why do we need a drug delivery system at all? So I'll take a moment to explain this. So everyone at some point in their life is going to be touched by cancer, if you don't get cancer yourself and you're fortunate, you all know somebody who has. Now most of the time those patients end up having a treatment regime of chemotherapeutic. Now chemotherapeutics are very effective molecules, but they're highly toxic. And that means that you get a lot of unwanted side effects associated with that treatment. So for example, with chemotherapeutics, you often treat the cancer, you kill the cancer, but you also kill off, for example, your hair follicles, some of your stomach lining. So that's why you lose your hair, you feel sick all of the time and so on and so forth. Those are all off-target effects because the drug is going to cells that you don't really need it to go to. Now if you could take that drug specifically to your cancer and stop it going to your hair follicles, for example, you can have the benefit without those side effects. Now when it comes to gene therapies, a lot of gene therapies are very, very effective indeed, Unfortunately, it's also very difficult to get those gene therapies exactly where they need to be in sufficient doses for them to have an effect before they get degraded. So here, the targeting is really needed to get that gene therapy to its site of action. Now in both of those cases, if you can get your drug to where it needs to be, you can increase the potency so you can increase how effective that drug is, you can increase the safety and the tolerability by stopping some of those off-target effects. And it also means that you can better tailor the dose rather than having to deliver a very high dose to have any sort of effect, you can tailor that and get the dose just right to have the effect that you need without those off-target effects. So you can see that this is a real important area in therapeutic development. And this is why we've looked at this as a company. Now the idea of developing a therapeutic delivery vehicle is not a new one. Antibodies have been used as the gold standard for this in the form of antibody drug conjugates for quite some time. And you can see an example of that in the slide on the left-hand side. So the antibody is that Y-shaped molecule. And then you can see the drug, the little blue pill, attached to that antibody through some sort of linker here represented by the little chain. Now it's not just antibodies you can do that with, we can do that as well with our Optimer binders. So you can see the Optimer represented by the blue helix on the left-hand side, again, attached to the linker, the chain to a drug molecule, the blue pill on the right-hand side. Now there's a number of advantages to using Optimers in this context. First of all, as you can see by the slide, Optimers are a lot smaller. On average, they're about 10x smaller. Now that gives a number of advantages in and of itself. Firstly, the Optimer binders can get to sites that antibodies are just too big to get to. So certain binding sites on the surface of, for example, a cancer cell might be buried inside a day cleft or a crevice on the surface of that cell. If the antibody can't get to it, it can't deliver the drug, the Optimers being smaller can. But Optimers are also small enough to penetrate deeper into tissues. So if you think about a cancer, you think about a tumor with an antibody that may only be able to affect the surface of that tumor, whereas the Optimer is small enough to penetrate much deeper into the tumor. So you're not just going to kill the surface of the tumor, you actually have the possibility of treating the entire tumor and killing the whole thing. So you can see there's a lot of advantages in using Optimers as delivery vehicles in that context. Now obviously, the use of delivery vehicles, as I mentioned, has a lot of advantages, and this is really highlighted on this slide. So over recent years, there have been a number of high-value partnerships between companies that have a therapeutic payload and partners of those who have a delivery system. So by forming a partnership, you can take a drug molecule that's very effective and conjugate it, attach it to a delivery system to make sure that drug goes exactly where it needs to be. So you can see the value in this platform and how we can generate revenues from this going forward. So I will now move on and talk about some of the work that we've been doing using our Optimer binders in this example to target fibrotic liver disease. So liver disease kills on average around 2 million people per year. So that's quite a lot of patients. Of those, about 115 million suffer from a disease known as NASH. Now NASH currently has no effective treatment so this gives a opportunity for us to develop a delivery system to take for example, a gene therapy to those disease-associated cells. Now there are treatments available for treatments of all sorts of diseases within the liver, an example of a delivery system for the liver is GalNAc. Now GalNAc actually targets all sorts of active cells within the liver. It doesn't specifically target, for example, fibrotic liver disease associated cells. Now that said, GalNAc in itself generated over $170 million in revenues in 2022. So you can see the value of platforms such as that. But if we can develop something that's even better and target those disease-associated cells, you can see the potential of the platform. So let's look at some example data that we've generated recently. So on the left-hand side of the slide, first, we're going to look at just our Optimer on its own. So the Optimer represented again by the little blue helix at the top of the slide. Now in this case, we've attached our Optimer binder to a red fluorescent dye. So we can see that Optimer, and we can see where it's binding. Now on the left-hand side of that panel at the top, you can see very clearly that the red fluorescently dyed aptamer is binding to these activated disease-associated cells. So we've got a very good binding response. Underneath that, you can see an example of healthy cells. And you can see no red staining there at all. So the Optimer is not binding to those healthy cells, but it is binding to the fibrotic liver disease associated cells. So that's great. We have specific targeting. On the right-hand side of the slide, we've taken our Optimer binder and attached a therapeutic payload. In this case, it's a gene therapy. Now again, you can see the top left-hand panel of that right-sided diagram that the Optimer binder is still binding to those cells. So this is great. The Optimer binder is binding to those disease-associated cells when it has that therapeutic payload attached. So the attachment of that payload has not affected the Optimer's ability to bind to its target. On the right-hand side of the slide, you can see that we still do not target the healthy cells of the liver. So we've still got our selective binding. Now as a control, at the bottom of that diagram, you can see that we've taken a scrambled sequence as we call it. So this a binder that we have deliberately muddled up to knock out its ability to bind to its target. So on the bottom left, you can see that, that binder no longer recognizes the activated disease-associated cells. So this is good. This shows that the binding that we're seeing is a function of our Optimer and it's not just a nucleic acid effect and it's not because of the cargo that we've attached to our Optimers. So this is great. This shows that our Optimer binder works, and it will take a therapeutic payload just to the cells that we need it to. Now on this slide, I appreciate there's a lot of data here, so we'll go through it a step at a time. Here, we're looking for a therapeutic effect from our binder. So if we look at the data on the left-hand side of the slide, first of all. So this is using our Optimer binder to target those disease-associated cells. So what you can see here is, as we increase the dose of our Optimer with that gene therapy attached, you can see in the yellow, pink and blue as we increase the dose we have an increasing effect. So we can see a reduction in the amount of gene activity. That's the reduction in the bar sizes because we've delivered this gene therapy and reduce that gene activity. So the Optimer is doing exactly what we need it to do. It's delivering that therapeutic to those cells. Now in the data set in the middle, this is the healthy cells that we showed on the previous slide, the Optimer does not recognize. And as you can see here, as we increase the dose, again, from the yellow to the pink to the dark blue bars, we have no effect. So the Optimer is not binding to those cells. So it's not taking that gene therapy into them, and therefore, we're having no effect. So that's great. We combined and delivered to the cells that we want, but not to the rest of the liver. Now it's important to show that the therapy is being delivered in an active form. So we wanted to make sure that the results that we're seeing in the normal liver cells were not because we've actually knocked out that therapeutic molecule. So that's the data on the right-hand side. So if we take our Optimer drug conjugate and force it into those healthy cells, we can see that we do have a knockdown effect. So the bars are greatly reduced on the right-hand side. So this shows that even though the Optimer is not delivering to these cells, if we force it in, we do have an effect. So we know that our gene therapy is still active. So all in all, this data shows us that on the left, we can target the cells that we want and deliver a therapeutic payload and the data in the middle shows that the nontarget cells, the healthy cells are not touched. Now everyone who can see the little asterisks above each of the data sets, this is basically highlighting that we can say that this data is 99% likely to be due to the actual effect. So this is not really due to chance. So we're very confident in this data and the fact that it is genuine. So to summarize, we've demonstrated that the Optimer platform can be used to develop binders for drug delivery and specifically in the data that we presented here to fibrotic liver disease. We've actually got a number of projects going in this sort of area, looking at developing Optimer binders for a whole range of different diseases. And as you may have seen from a recent announcement, a top 15 pharma partner has actually requested a sample of our Optimer binder to test in their own liver disease models. So that work will be ongoing in the near future. We've also developed a number of advancements in the Optimer delivery vehicle space and shown how we can use that for potential treatment of fibrotic liver disease. So that's quite unique within this space. So we're now going to move on to our next-generation Optimer+ platform. So first of all, I'll reshow this slide, but there's now an added section in our Optimer+. You can see that towards the right-hand side of the top there. So the Optimer+ platform really represents the best of both worlds. So we've taken the advantages of our Optimer platform, being the flexibility and the scalability of manufacture. And we've added into that some of the benefits of protein-based scaffolds in that they have these additional functional groups to engage with the target. I'll come back to that in a moment. So you can see a schematic of our new Optimer+ binders at the bottom of the slide. So they're really broken into 3 regions. So we have the variable region at the top. So this is the part of the molecule that will engage with the target. We have a scaffold region. That's essentially to space that binding region away from the bottom of the molecule where we have an attachment region. So that's the region as the name suggests, where we can put all sorts of different cargoes. So we could attach gene therapies, we could attach [ flora ]. We can attach anything that the customer may need. So as you can see here, a little comparison between the Optimer binder on the left-hand side of the diagram, and our hybrid molecule, the Optimer+ on the right-hand side. So as I mentioned very early in the presentation, the Optimer binders are made of the 4 building blocks of DNA, whereas our new Optimer+ platform has the potential for over 20 different sorts of building blocks. So this really expands the way in which our new binders can engage with their targets. So we're expecting this to improve the performance in our new platform. And that's summarized on the slide here. So you can see each of the colored circles, we expect that our Optimer+ platform will outperform either antibodies or other platform technologies and indeed, our own binder technologies. Now this isn't to say that the Optimer platform doesn't work really well. I've shown you in the early slides it does, but we're always looking for the next best thing. So for example, when it comes to targeting, there are some molecules that we've not been able to generate binders too with our existing Optimer platform. We expect the additional functionalities that we've added to the Optimer+ platform will allow us to be successful in those projects as well. The discovery and development time frame is expected to be better for our Optimer+ platform. There are fewer steps in the isolation of these molecules. So we expect the turnaround to be even faster. We still expect to retain the manufacturing and scalability of the binders compared to our existing Optimer platform because they still rely on the scalable, solid phase chemical manufacturing process. So those advantages will be retained. The deployment and shipment advantages of Optimers will also be retained. So we don't expect that these new molecules will need cold chain storage, for example. So we can ship them dry. We don't need to have them transported through specialist cold chain manufacturers. So now to look at some data for our Optimer binders. So one of the earliest molecules that we tested here was a binder that we already had developed and Optimer, too. So it was something we knew that we could develop. So you can see the performance of our existing Optimer binder shown in orange. Now what this data is showing you is the Optimer attached on a biosensor interacting with that target molecule. So you can see very clearly a nice clean response, so the Optimer is binding to that target molecule and then not letting go of it. Now when we used our new platform to generate a binder, you can see already it outperformed our Optimer binder. So we got a much bigger response. It bound much more tightly and it stayed [ stock ]. So it grabbed hold of that target molecule and kept hold of it. Now that's obviously really important when it comes to developing diagnostics or indeed therapeutics. And you can see from the numbers at the top of the slide, the new Optimer+ binder is about tenfold better. So it binds 10x more strongly than our existing platform. Now we also did a parallel test where we removed those new side chains from our Optimer+ binder. And you can see when we do that, we completely knock out the function. So we know that the new -- the improved performance from our new Optimer+ platform is because of these modified [ side ] chains that we've added to our binders. So that was a great example of how well this new platform is expected to perform. Now obviously, if we want to use that platform in cell targeting or drug delivery, we need to be able to recognize those targets in the context of a cell. So what you can see on the left-hand side of the slide, we took that same Optimer binder and attached a green fluorescent dye to it. And what you can see is that when we interact those Optimer binders with the target cells up at the top, they interact with it, so you can see those cells lighting up in green. Now at the bottom of the slide, when we take non-target cells, so that cells that do not have that marker associated with them, we don't see any binding at all. So this shows that our new Optimer binder is able to bind to its target as it's presented on the surface of cells. So that's going to be really important for the application in drug delivery. And on the right-hand side, you can see some biosensor data, where we've attached again our Optimer binder. It shows very good binding to the therapeutic protein but doesn't bind to a nontarget. So something we don't want it to stick to. Another example, we've generated some Optimer+ binders against the dengue virus. Now dengue is a nasty disease associated with mosquitoes. It affects a huge number of people. So it's really important with dengue to actually determine the type of dengue that's been infected. So the different sort of dengue virus you've been infected with. So here, we generated a binder against dengue type 2, and you can see very clearly from the data on the slide that our binder recognizes dengue Type 2, but doesn't recognize dengue Type 1, 3 or 4. So again, we've got excellent selectivity in this binder. Now if we're looking to develop these binders as novel therapeutics, there are 3 basic tests that we need to be able to demonstrate First of all, on the left-hand side of the slide, we need to show that our new binders are stable. So what we've done here is taken one of our Optimer+ binders and introduced it into serum, 100% serum, so essentially blood. And what you can see by comparing the blue bar, that's the Optimer+ on its own to the pink bar or the purple bar in the middle, that's the Optimer incubated in 100% serum, so in blood essentially, there is no difference in the signal there at all. So what that's showing us is that we haven't lost any of the Optimer+ binder after incubating it in the blood for 120 hours. So it's a stable molecule. Then on the right-hand side of the slide, it's important to show that the Optimer+ binders are not toxic. So in this case, we've added different amounts of Optimers that's the different colored bars to a cell culture model. And what you can see here is looking at the viability from these cells or the number of cells that have survived, in the control, on the left, so just treatment with a solution that doesn't have an Optimer in it, you can see the cells all survived. So that's as expected. When we put the Optimer+ into that, so that's the data set in the middle, we see no difference in response at all. So again, the cells are all surviving even though they've had Optimers added to them. So this demonstrates that the Optimer+ is not toxic to these cells. Now in order to make sure that this assay was done correctly, we also introduced a toxin. That's the data on the right-hand side of the slide. And you can see very clearly that there's a reduction in cell activity and cell viability. So we know that these cells can be killed when they're introduced to a toxic molecule, so this is great. We've demonstrated that our Optimers are stable and that they're not toxic to cells. The next thing to demonstrate is that they're not harmful to animals because at the end of the day, if we're to develop these into a therapeutic, they're going to go into animals, patients like you and me. So first of all, we did a study in some mice, and we were delighted to see that even at higher doses of our Optimer+ binders there were 100% survival rate in these mice. So this is great. We've shown that our Optimer+ are stable. We've shown that they're not toxic to cells. And we've shown that they're not harmful to mice. So that's a great start. So in summary, we've demonstrated our novel Optimer+ platform and shown that we can generate binders that have improved performance compared to our existing Optimer platform. We've shown that those binders have improved affinity, so they bind better. We've shown that they can bind to their target in the context of a protein and in the context of cells. So that's going to be really important for future therapeutic developments. And we've shown that they are stable and well tolerated in both cell and animal models. So just to summarize. In the presentation today, we've shown that we can generate Optimer binders and demonstrated the performance of those in precision medicine and in this case, in the potential treatment of fibrotic liver disease. We've also shown that our Optimer+ platform has the potential for a next-generation affinity ligand. So we're expecting this to help us to push into that affinity ligand space and take a greater share of that market. We've also demonstrated the performance of the Optimer+ platform in terms of binding and its potential as a therapeutic in that they're stable and they're not harmful to either cells or to animals. So we're continuing to advance our Optimer platforms, especially in the area of fibrotic liver disease, and we'll be continuing to develop the Optimer+ platform and use that to add additional value to Aptamer Group. So thank you for your time and attention, and hope you have a good day.