Ixico (LSE:IXI) — Capital Markets Day

0:00 So welcome everyone to the IXICO twenty twenty five Capital Markets Day. The usual disclaimer which I won't dwell on, but the exciting part of the day is we've got the entire C suite of IXICO here today. So we have Bram Gordon, who's the CEO, newly joined within the last year or so. We have Grant Nash, who's the Chief Operating Officer and Chief Financial Officer. We have Robin Walls, who is the Chief Scientific Officer and Chief Medical Officer. And we have Mark Austin, who is the Chief Technology Officer. And I guess the purpose of the day today is really to think about the sort of things that we can't necessarily or don't have time to communicate at the H1 or H2 trading, So this is about a deeper dive into the kind of growth trajectory of the company, the innovation strategy the company is actively employing, and then a deeper dive on the science and the technology.

0:54 As you can see, it is quite a busy packed agenda. We do have two external people dialing in, so we will be quite disciplined on time. As Mark said, please ask questions throughout. We do have sort of Q and A sections and for those in the room, we will also have the break, so if there's questions that you want to hold to the break, please do so.

1:17 But ask questions throughout please. The only thing I'd say is please don't be offended if I do have to move people on if we're getting stuck on questions, because as I said, we've got quite a tight schedule. But on that note, let me hand over, we're going to start off with Graham and Grant, who as you can see from the slide is going to start to talk you through where the company is going next, where it's just come from, the innovate leads scale strategy and a little bit of an insight into what we think the future might look like for the company. Well, thanks, James. James, chief business officer, who joined officially, I think, around six months ago. He's also the head of investor relations, so it's very comforting to have someone like him around for a day like today.

2:07 I'm delighted to be here. As James said, I have been with the company around a year now, a little bit over a year actually. I obviously met quite a few faces that I see in the room, so it's great to see these familiar faces. It's great also to see some faces that I don't know yet. And I'm hoping that quite a few people or we know that actually quite a few people are joining us also remotely. It is very exciting to be able to not just bring the results, and we're actually avoiding to talk about 25 results because you know those and we're very proud of them. But we're especially very excited about what's ahead. This is about the strategy going into '26, but also that more medium term strategy, as many of you may remember that we did to a quite recent capital raise. Obviously, we want to report out also on what have we been doing since we did that and how do we measure our progress.

3:01 Then, of course, after today, you can be the judge of that as well. So, to start with the opportunity, it's a problem which creates an opportunity. Sources indicate that forty three percent of the world population will at some stage be touched by a CNS disease. So that means that almost half of the world population will be facing that societal challenge which IXICO is all about. And so IXICO is very much a company that is mission driven, and you will hopefully hear that also from the experts that you're going to hear today. I want to point out especially Robin and Mark as Chief Scientific and Chief Technology Officer, but then also with their teams. You will see in a minute who is the team at IXICO and why have they chosen to be with IXICO.

3:50 It's a problem, obviously, for society, which we're trying to help to solve, but it's also an opportunity in terms of the economics around it, if you wish. The neurology market has a CAGR of 5% currently. In addition, for those who know the neurology, the CNS market a little bit, it has been sometimes qualified as a bit of a train wreck. It's hard to develop drugs that actually make it to market. But we've seen changes now, right? And we'll be talking about them. You'll also see Robin talk about Alzheimer's, for example, and some of the progress that has been made there. And so it's really a market now where we see a lot of progress happening as we speak. Having said that, it cannot be a one fit all solution. It will have to be through precision medicine where patients are identified that are eligible to treatment, where the right patients especially are also recruited into clinical trials.

4:41 And that is the business that IXICO is in. So a snapshot. I know quite a few people here probably don't need this, and you know as well, and you've been following and supporting us since quite a while. We are, what we call an imaging CRO, an imaging clinical research organization. We're considering ourselves almost the exclusive, definitely the leading one in CNS. In that neurology field, our competition is very much a group of generalists. And you may actually have seen in the news that one of our big competitors, Clario, just became a little bit bigger, as they are now going into the Thermo Fisher Group. We exist since twenty years, so we are an established player. Obviously, here based in The UK. And imaging is still very much that gold standard. So obviously, when you go and develop solutions in neurology, you will want to go to look in the brain.

5:34 Luckily, we don't have to do that anymore by opening the brain, so to speak, but we do that through imaging, and so that is the business we're in. I mentioned already more than 90 people. Over the past year, more than 10 people have been joining also following the capital raise, so we feel that we have a strengthened group again. Almost a third are PhDs, so I would say quite a few smart people in the building. Many of them here in The UK, but not only. Many different geographies and especially also at the other side of the pond. You see here 26 current studies ongoing. That may seem a lot or not a lot, depending on how you look at it. I think what's important to keep in mind is these are 26 potential solutions, blockbuster solutions that pharma or biotech are developing that might potentially come to the market. We think this is a very impactful number to be part of.

6:25 We rely on twelve fifty clinical centers, radiology, where the scans, the imaging is being done, and we very easily activate other centers as well. We are working with an even bigger network than that one. The core solutions are imaging, trial management, analytics, biomarker diagnostic, validation.

6:48 I already talked a little bit about the team. I'm actually very proud to present that team. Some of these people have been with the company since a long time, and I think that's our strengths. Especially, as I mentioned, Robin and Mark, who you will hear most of today, have been establishing the platform as it is today and have, of course, been further developing and enriching it. I did promote Mark to Chief Technology Officer a few months ago, and that is a very clear signal also from us as a company to make sure that the architect of the platform will be out there much more as we also start to work with partners. You'll hear Marc talk about that himself. Obviously, Grant as CFO and also Chief Operating Officer is instrumental and has been instrumental to the company since a long time. Robin, as mentioned, has always been the chief scientist, as we've now really built a platform that is serving many different disease areas.

7:42 The people to the left are people that you probably have never met, potentially not even heard of, but HANA, of course, as the head of talent is very important because there is a war on talent. Clearly, as I said, we've got these people in the building, so Hana's role is important. Then, Anna, legal, John, quality and regulatory are, of course, extremely important for an industry like ours as well, because everything we do is highly regulated. I already mentioned James. I'm very excited to have his strategic mind part of my C suite. And you will probably see more of James in the future as well, as we embark really more on a corporate development path as well.

8:20 We've got Mark and Kate with us today. Mark is my chair. Mark probably doesn't need introduction to some of you. He's well known and he's a CEO of ChemAI, so he's a good sparing partner for me, but at the same time also a great share to have as he obviously knows the investor ecosystem. Kate, who is a prior financial executive with GSK, so obviously invaluable in the discussions as well. I think Dipti has dialed in. She is a prior executive with IQVIA. As you can imagine, that is great to have as an input into our discussions with the Board as well. So a small board, a nimble board, but very much leaning in, as you see today as well.

9:10 I think this might actually be the most important slide that I wanted to show. We very rarely can share actually who we work with and what we do for them. We very much respect confidentiality. Often when you see these RNSs coming from us, we're talking about AFI's Phase II trial. We'll probably give you the indication and I will say with some maybe geographically situated biotech or biopharma. Those are actually three examples where we can actually clearly speak about who we're working with and what we're doing. I do want to pause here for a moment. The first one is the global Alzheimer's platform. You may have seen a few months ago that we announced that we actually invested. They're a client. They're actually a customer of ours, where we do the analytics for the entire BioHermes I and II trials, and they basically do biomarker research.

10:05 So they're front and center into what we do. But we've also invested in making sure that we are not necessarily an exclusive partner, but the imaging partner when it comes to accessing those data. And that is, of course, for us the gold which we sit on as an AI driven company. The second one is Unicure. You may have seen that in the newspapers here in The UK as well. The people on this picture are not people from Unicure. They're actually from our own University College London here, Sara Tabrizi, who's really a very well known figure in the Huntington's space. They brought out the news that the FDA has given a clear signal that despite the fact that they've got a Phase I or II trial, there may be endpoints allowing them to get to FDA approval.

10:58 We got quite a few phone calls actually from some of you as well. Are you involved in this? I think it is safe to say that when you see Huntington's disease in the news, you can assume that IXICO is involved. Obviously, in this case as well, we're sharing the pride of their progress. Then the third one is Fujirebio. That's a diagnostics company. You'll hear me talk about this a little bit more. I did say that we want to go into other verticals. This is one of these verticals where we now see blood based biomarkers come to market. This is the first one that was cleared by the FDA, and they used us together with the dataset from GAP to do that validation of their first diagnostic in Alzheimer's disease.

11:54 Why is it the right time for IXICO now? I've put our share price here. We try not to look at this too much. We try to focus on other things, such as the revenue increase. This is, of course, what happened over the past year. We're proud of this. It's double digit. I think it's what we promised. We even overachieved this a little bit. Importantly, as I mentioned, we did a capital raise, which means we're quite cash rich for the size that we are. But we didn't do that, as I always say internally as well, to fill the coffers. We do this to invest, to grow and to execute on what we said we were going to do. That's why you see that from an EBITDA perspective, we're still on that trajectory to profitability. I'm very confident and Grant will talk about what that horizon looks like. But I think we can say that we're very much on track when it comes to the execution of what we set out to do.

12:46 I leave it up to you to judge, of course, on the valuation and the share price of our company at the moment. I already mentioned it, the societal challenge. We are very much a mission driven company, which means that people in the building very much are there to help solve problems in Alzheimer's, Parkinson's, Huntington's and some of these other disease areas as well. And you see that that is very fertile ground. Over the past twenty years, we've actually seen an 18 fold increase in the number of trials that have been initiated in that arena. I already mentioned some of these numbers, 43 of the population, which is 3,400,000,000.

13:24 I mentioned 5% CAGR for the neurology market, which includes pharma, but it's also 7% growth for the imaging market, which is very much the one which we are operating in. And you see here, and I think Robin is going to come back to that and provide some more color around it, 138 new assets in Alzheimer's alone that are being researched as we speak.

13:48 So who are we and how do we make that impact and how is that evolving as well? We are first and foremost a technology platform. We operate as a clinical research organization. That's how we derive revenue most of the time. But it is very much driven by an AI driven platform that has been completely revamped. Actually, Mark will have an opportunity to really show that and even showcase that today, I think. Linked to that then are the experts. The people that are on our payroll are often thought leaders in their own right and will also interact on the global scientific platform. The business we're in is developing biomarkers or imaging biomarkers, managing trials from A to Z for our sponsors or clients, and then analytics deriving insights which we feed back to pharma.

14:35 The insights are largely around efficacy, safety and patient eligibility. I had quite a few discussions actually with some analysts lately as well. I think the fact that we are very clearly focusing on CNS and on neurology is very much confirmed now as the right choice. We could easily, as imaging, go into oncology, go into other areas as well. But we do very much feel that we are sitting on very fertile ground in CNS, and so specialization is definitely the name of the game. It's highly technological, it's highly scientific, but at the end of the day, as you see on the bottom, it's actually informing financial decisions of our clients in terms of progressing their assets through the pipeline or potentially failing fast if they need to.

15:28 About a year ago, I started to talk about the innovate, lead, scale strategy, and that's what I embarked on also together with the team. Just as a quick reminder, innovate, lead, scale is about product differentiation, so bringing novel innovation on our technology platform to make an impact, as you may remember, especially in Alzheimer's and Parkinson's. Lead is about making more noise on the scientific platforms, I should say, and working with key opinion leaders in that regard. Then scale, of course, is translating that into order book revenue and expanding that serviceable market into novel verticals. And so, at the end of the day, it's all about accelerating, especially revenue growth, and then from there, increasing the value of the company, which we do think relies also on its underlying technology.

16:15 But I would say the name of the game at the moment is very much the revenue increase. So how are we doing, or how do we think we're doing? As I mentioned, you can be the judges of that as you look at our results and about what we present. We do think that in terms of innovation, and I am definitely very happy with what I've seen the teams build in terms of new AD, Alzheimer's, Parkinson's product offerings, deployment of our next generation platform. We pulled the trigger on that around a year ago. That was under Mark's leadership and that is working very well now. Then the diversification in terms of therapeutic areas. I did put a little white box here because this is not necessarily something we set ourselves out to do. The new applications for our platform and how they could also penetrate revenues. I talked about that a little bit in a visionary fashion, but I do think over the past twelve months, I've really seen how this can actually be moving from a concept to reality. I think it's a bit early to start to make today about this, but I do think Mark is going to touch on that.

17:25 Lead. Again, people have come on board, key opinion leader. Relations have been built. Actually, one of the think we can almost call him I don't know if he's listening already Robin, but sort of the god of neuroimaging is dialing in today from San Francisco, Mike Weiner. Those are all relationships that we have forged over the past months. So then when it comes to scale, existing project revenue expansion. So that is again that thought leadership of our people with existing clients that has really led to, I think, quite an extraordinary year of upselling, if I can call it like that for a moment, and then new biomarker revenues, which sort of comes back to that diagnostic vertical as well in which we're operating. I did give pipeline order book partnerships an amber because I think it is a bit early to be satisfied. We've got an ambition. The ambition is clearly to move as rapidly as possible to double digit top line and of course also maintain that double digit growth. So I definitely don't want to make that green yet. And then in terms of company valuation, we give ourselves a red there. Again, I'll leave that up to you to be the judge.

18:37 With that, I'm going to let Grant keep me honest, if you wish, and then I'll come back and talk a little bit more about the future. Thank you, Bram. Good afternoon, everyone. I'm Grant Nash. I'm the Chief Financial Officer and Chief Operating Officer here at IXICO. It's a real pleasure to be here this afternoon. Bram has just given an overview, a reminder, an introduction to IXICO, who IXICO are, what we do, why what we do matters, what the market looks like, and why we are uniquely positioned to support the global pharmaceutical industry in addressing some of the world's most challenging neurodegenerative diseases. He's also provided a reminder and introduction to our Innovate, Lead, Scale strategy and provided that high level self appraisal of how we're doing.

19:31 What I want to do is just put a little bit more flesh onto the bones of what we've done over the last twelve months. I also want to talk about how that augments the position we've put ourselves in over the last few years, and then how those come together to focus on what we can do in the next twelve months. As a reminder, this isn't a results roadshow, so I'm not going to go into the detail of the financials. We'll do that in December once we've got our audited numbers out. But I will start with the trading updates that we released a couple of weeks ago, where we announced, as Bram said, that we have outperformed market expectations, 13% revenue growth in the last twelve months at 6,500,000 revenues, we've reduced our EBITDA losses, that is despite the fact that we've actually made a number of significant investments we'll come on to, off the back of the capital raise and in line with that innovate, lead, scale strategy.

20:31 And the impact of those investments have obviously yet to fully come through. Cash of 3,500,000, and then an order book of 13,800,000. So 13,800,000 of signed contracts, the revenues of which we'll be delivering over the coming few years. So those are the financials, but I also want to talk a little bit more about some of the other milestones, the other achievements that we've delivered across that same twelve month period. And obviously this started for us in terms of twelve months with that successful capital raise, 3,700,000 net of fees, almost exactly twelve months ago. Obviously, many of you were a key part and key supporters of that, so thank you very much.

21:21 But that obviously was what drove us and allowed us to invest in this innovate, lead, scale strategy, the strategy that Bram brought to the organization just over twelve months ago. And we have, over the last twelve months, added eight new roles to the business, primarily in the areas of scientific and commercial, but also with this key focus on The US. Now, we've been supporting trials in The US for many years, but investing in The US and having people on the ground in The US in a market that is at least 50% of the market we're going after, we felt was very important to augment our global credentials and really show to that market the way we're there to support them in The US.

22:09 On top of that, as Fran mentioned, we've also invested in our key opinion leader resource base. This is something that Robin will talk more about, and you'll hear from Mike as well shortly. This is really important to us, firstly, in terms of getting the leading advice in our Innovate strand, where working with Robin to look at what are those things that we are looking to invest in and are those the right things? But also in that lead element, the innovate, lead, scale strategy, where we want to make sure that we're going out and we're talking to the market and augmenting that position of being the scientific leaders in neurodegenerative diseases. Having those experts who have that network able to support us for that has been very important.

22:58 We've then supported that with this acquisition of data rights. They're working with the global Alzheimer's platform to obtain access to this highly valuable AD dataset focused on MRI and PET, two different types of imaging protocol, and blood based biomarkers to support the developments that we're making. And the combination of those investments in people, the KOL support we're getting, access to data, has then meant that over the last twelve months, we have been able to develop and deploy new analysis pipelines that differentiate us in those areas of AD and PD. So, those have been the key focus of investments.

23:44 Alongside that, we've also launched our IXI platform. This was something that we've been investing in over a number of years before that, key to us in terms of our technology capability, and Mark will talk more about that shortly. We've supported 37 projects in the year. That, of course, drove that 13% revenue growth. And alongside that, we've signed 6,200,000 of new contracts in the year. Now, the key thing there is that of those 6,200,000 of contracts, 4,200,000 of those were actually signed in the second half, and then we've augmented that with a further 900,000 of contracts signed in the first two weeks of this year.

24:30 So that's important for us because in terms of developing our pipeline, developing our order book, gaining traction coming through off the back of the investments we're making are starting to show. So this is the next slide where I want to talk about the order book, but what I want to stop and just pause briefly is that we've had a solid year of delivery over the last twelve months, and we've made those investments. Over the next twelve months we're going to get the full benefit of the investments we've made over the last twelve months. But that builds on top of the order book that we already have. Our order book at 13,800,000 is not quite as high as we'd like it to be, but it is very well structured, and it's very well structured for growth. I want to use this slide to explain why that's the case.

25:19 This slide shows that order book, that $13,800,000 cut in two ways. On the right hand side of the slide, we've got the split by therapeutic indication, and on the left hand side, the split by clinical phase. I'm going to spend more time on the clinical phase, but just to touch on the therapeutic indication. You can see from our order book that our order book is still very much weighted towards HD and rare other neurological conditions. That's something that we've got a very strong reputation for, but the areas we're focusing on with those investments is in AD and PD, which is about 25% of our order book at this stage. We'd expect that to shift more to those AD and PD areas. But perhaps what's more relevant, I think, to today is the makeup of the order book in terms of phase.

26:08 With the bulk of our order book, about 6070% of order book being in phase one, phase two, that is very important in terms of the structural basis from which this organization can grow and how we can sustain that growth. And that is because most new trials that we'll win will tend to be in Phase I, Phase II. Once you're in a Phase I, Phase II, the CRO or the biopharmaceutical company will tend to stick with you as it moves to Phase III. So to win, you need to be in those Phase I's, Phase II's first. But by having a lot of phase ones, phase twos, that also provides a diversification of risk in terms of the order book and an increase in the opportunity. So the more early phase trials you have, because we know that we are working in an area where clinical trials don't always get all the way through Phase I, Phase II, Phase III, that we are well positioned to address any risk that arises should a trial fail.

27:06 But at the same time, by having that breadth of contracts, we have 25 projects in order book at the end of September, we are in a good position to follow those through as they move from phase one, phase two into phase three. And that's what will drive sustained revenue growth for this organization going forward. So, combining essentially the investments we've made over the last twelve months with an order book that is very well structured from a risk mitigation point of view and operational opportunity delivery structure, where we have an order book in a good position. So I'm just going to move on to my final slide before passing back to Bram. And what we've done here is we are bringing together the investments we've made over the last twelve months and why this put in a position to win more in AD and PD, with an order book that is already well structured for growth, and then looked at what is it that we will deliver over the next twelve months that really ensure that we sustain growth going forward.

28:15 And we've done some analysis work to look at what is the size of the opportunity that we can address today in the three markets of AD, PD, and rare Huntington's disease. So the dark gray bar in the middle of this slide, that is our estimated market. So an estimated market for us to service today of 40,000,000 in AD, 30,000,000 in PD, 13,000,000 in HD and Rare. So we can see that the big opportunities are in AD and PD beyond HD and Rare. And then the light blue bar beneath that is that element that we feel we have a good opportunity to address in the next twelve months. It's not the full bar because we know that some of these trials will already be in phase one or phase two, and the chance of winning the phase three, therefore, at this point is low.

29:08 Or we know that there are some biopharmas who work very closely with some of our competition, and getting those trials initially will be difficult. So we've done an assessment of those market opportunities, that 40,000,000, 30,000,000, 13,000,000 that we realistically can go after. But then we've brought that right down and said, Right, what are we going to win? What are the things we're definitely going to win in the next twelve months? We are saying that we will win at least 3,000,000 contracts in AD, at least 1,000,000 contracts in PD, and at least 6,000,000 contracts in HD and Rare. We feel very confident we can do that. When you total that up, that's obviously 10,000,000 of new bookings. We will also augment that with contract extensions. We have a good record of achieving that. We'll do at least 2,000,000 when we think of that. So with the investments we've made, building, hitting this level of bookings would put us in a very strong position in terms of our order book in twelve months' time. And this is what we want to be coming back to talking to you about in twelve months' time, having delivered this, because getting that level of bookings puts us in a position where we know that we can sustain the growth that we have delivered over the last twelve months.

30:25 We'll achieve that over the last twelve months. And working with the investments we've made and this order book, we will put ourselves in a position where in the next couple of years, we will drive up to 10,000,000 of revenues, which will then move us back to profitability as an organization. So that's, if you like, the here and now of the Innovate, Lead, Scale strategy. What I'm now going do is pass back to Bram, who's going to talk about some of the potential to take us beyond that 10,000,000. Thanks, Grant. I'll try to keep it short so we stay on our schedule. I think you heard Grant say this with a lot of confidence. Obviously, indeed, this is transformational for us as a business because it does bring us back to double digit top line, double digit growth, and eventually profitability as well. At the same time, these numbers may seem low. They seem low to me, to be honest, and it's not why I joined the company, to be honest, neither.

31:23 So really what we've set out to do but of course, need to make sure that we've got a solid basis where we start from, and I think that is what Grant has been presenting over the past minutes. Today, everything that we are enabling is happening in that upper right hand corner as a clinical research organisation supporting clinical trials. And of course, when a product, a drug is being approved by FDA or EMA, post marketing surveillance, which is following and making sure that further patient surveillance is happening for safety or efficacy reasons. But really, what is exciting is to start to see what else can the platform do. And again, I won't steal Mark's thunder and Robin's thunder, but we do believe that our platform can start to access other revenue streams that are not necessarily service or fee for service streams, and that will be through collaboration and through partnerships. And obviously, we need to equip our platform to do that. And so that's what we're working hard on. That's also why a CBO, for example, in the C suite is very important, as we're talking to these multi biomarker companies, large data analysis groups think of the VIVE as the metadata of this world large scale CROs, who already today are our partners: IQVIA, ICON, PPD and then imaging providers, of course, like the Siemens, the Philips and GE, who today, again, are already partners, but not necessarily the way we've been looking at them, sort of over the past months. And so

32:54 those are the discussions that we're having. And then the other pillar is, of course, clinical decision making, where we do have a platform that could very easily, in the hands of radiologists who today are using that already, you'll actually see that application from Merck. They could start to use that at the patient bedside as well. And so those are some of the, I think, exciting expansion areas, which will also be accessed through a different revenue model than what we are experiencing today. That is the work in progress that is happening as we speak. I know this is a little bit cartoon esque, but there is this confidence of this steel line of the company as is, and to make sure that we deliver on these promises within the timelines that we've set as an ICRO. But then there's really that excitement to potentially not necessarily completely walk away from who we are as a company, but to add that tech bio element, which is basically working through the technology, not necessarily through adding armies of people in the company as a service company, but really to start to look at licensing agreements and others with some of these bigger partners.

33:59 To end, I hope I've shown that, and you'll actually hear more from Robin in a minute, that neurology, neurodegenerative diseases is the place to be in life sciences. It's a very exciting place to be. It's not always been like that, and IXICO, of course, has suffered from that. IXICO is still recovering from some of that, but we are really riding a wave. But at the same time, we don't just want to ride a wave. We wouldn't be masters of our own destiny. And so the strategy is, of course, also to make sure that we actually start to equip ourselves through our technology platform to better access that opportunity in the future. I'm going to let this one be on your retina for another few minutes. This is today where we are, but clearly growing revenues will be the name of the game for the next coming twelve months still and beyond that.

34:48 Moving to profitability is a promise that we've made, but then increasing value. And you will see, we think value does not just sit in revenues today, but sits also into what's sort of under the hood, which is our technology. So, with that, I'm going to end here and let's look a little bit under the hood. Thank you, Bram. So we're now gonna move on for a slightly deeper dive on the science, so I'm delighted to introduce Robin Waltz, who's our Chief Medical Officer and Chief Scientific Officer, who's gonna walk through a little bit more on the neurodegenerative market, and then particularly on the scientific roadmap and how we're addressing that market. Thank you James and good afternoon everyone. So as James said I'll build a little bit on what Brahm has been showing in his slides and hopefully give more color to why we really think this is the time to do precision medicine in neuroscience and it's actually happening as we will see in some of the following slides.

35:55 The chart on the left hand side you've seen in Pram's presentation, see this very systematic,

36:02 very nice increase in clinical trials that are being started and are being outsourced over the past years. What I'm particularly excited about is the graph on the right hand side that actually shows biomarker use in clinical trials over a period and the projection going into the future and that's what I want to dive into more detail. You'll hear the word biomarker a lot today, so I'll take a step back and briefly recap what we mean by that. So biomarker is a measure that tracks with disease progression that basically tells us biologically what is happening as the disease unfolds and therefore is a very important and very valuable tool to understand drug effects and essentially validate treatment in clinical trials.

36:54 What IXICO focuses on is biomarkers from imaging. So primarily brain imaging as we are a CNS focused company and for us that means basically looking at images taken from an MRI or a PET scanner, PET machine, position positron emission tomography. It's basically you will all have seen the imaging facilities and hospitals where a patient goes in and gets their scan taken in PET that means radio tracer being injected into the subject that then is used to image and display molecules or proteins in the brain that help us understand disease progress.

37:46 MRI on the other hand, magnetic resonance images, use strong magnetic fields to again display tissue properties of the brain in this case and that helps us visualize, for example structure and structural changes over time. I'd like to now go through the key therapeutic indications that we serve and you've heard Brahm and Koran refer to Alzheimer's disease, Parkinson's disease and Huntington's disease. I'd like to go through all of them and briefly discuss where we are with biomarker research, biomarker development and what role they play today in clinical trials already. So in Alzheimer's specifically we've come a long way over the past ten, fifteen years.

38:39 Many people today will have heard how the disease develops and builds up. It starts with accumulation of a protein called amyloid in the brain which then leads to build up of formation of tangles through another protein called tau. This then downstream leads to neuronal loss, essentially loss of brain cells and neurodegeneration which triggers the clinical symptoms that we all see in clinical dementia. If we think back ten, fifteen years when first trials that were targeting amyloid, which is the core protein triggering this disease, We had trials going into phase three ten, fifteen years ago that were designed to treat or essentially reduce amyloid levels.

39:36 These trials were designed in a way that we didn't actually check whether those subjects entering the trials have amyloid in the brain. So there's one phase three trial that was run by Pfizer and Janssen at the time on a track called Bapinuzumab. It's a monoclonal antibody targeting amyloid and after the trial concluded, looking at the data, it was confirmed that around thirty percent of the subjects actually don't have the pathology in the brain. So you are administering a truck to subjects that don't actually suffer from the disease. I think this is a very nice illustration that shows the power of biomarkers. If we now look at trials today they would all be testing for amyloid. But I want to briefly before getting into that more detail explain biomarker model that we see on the slide here. So you're not just looking at the slide, it's the ATN framework that was introduced in 2010.

40:38 It refers to amyloid tau neurodegeneration and what we see on the horizontal axis is essentially clinical stage of the disease and on the vertical axis we see biomarker abnormality and as I've just explained, we see A beta, so amyloid becoming abnormal first, followed by tau, followed by brain structure which is the neurodegenerative process which then leads to downstream cognitive impairment and clinical worsening. Fifteen years later this is implemented in every trial running in AD, specifically those targeting some of those underlying biomarkers like amyloid. So every trial would now be testing a subject for amyloid positivity before they enter the trial.

41:26 We also, as we will see later, these measurements are playing an increasingly important role in understanding treatment effects. So it really shows how we are doing precision medicine already in Alzheimer's disease today. The criteria are embedded in diagnostic criteria and we even see surrogate endpoints as we have approval of disease modifying therapy in Alzheimer's and I will come back to that later. I want to close by saying that imaging is central to all of this. All of those three categories that we have discussed can be measured through imaging, so we now have multiple radio tracers that allow us to image amyloid and tau. They are widely available, they are used in those trials and they are used for diagnostic purposes.

42:14 MRI on the other hand is a key measure to look at neurodegeneration and as Pram pointed out we see an emerging wave of measurements where some of this can now be measured through blood and IXICO is partnering with these companies to look at that multimodal aspect. Finally I want to say that we've seen a revision of those diagnostic criteria last year where a new set of measurements has been added, which is vascular as a co pathology in Alzheimer's disease. And the reason I'm mentioning this is because I'll come back to it later when I talk about IXICO's R and D roadmap. If we zoom out of Alzheimer's disease and look at the bigger picture here for one moment, we now see similar momentum in other therapeutic indications that we had in Alzheimer's ten, fifteen years ago.

43:12 So what I've explained at length on the previous slide is really the journey that Alzheimer's went through from first developing the biomarker models conceptually through developing the actual measurements and then implementing them into trials. And we see movement in Huntington's into the same direction where in 2022 a conceptual model was proposed that stages the disease into different stages using biomarkers and other measurements and the same has happened for Parkinson's only last year, so very recently. This now forms the foundation to go through similar steps that we've had in Alzheimer's in those indications in the coming years and I will touch on this in the following slides as we specifically zoom into the work that IXICO is doing to support those trends in those indications as we're developing those novel biomarkers and bring them onto platform.

44:13 I'd like to move on to, let's say, my second part of the presentation where I want to briefly look at each of those three indications, recap where we are in terms of drug development, how biomarkers are used today, to then go into my last part and talk about how IXICO is playing in this space. As many people will know, Alzheimer's disease is the most common cause of dementia. Currently we have more than fifty million people affected worldwide and crucially and critically this number is expected to increase by one hundred and fifty percent over the next twenty five years.

45:00 This is the thing to keep in mind, that this problem is becoming bigger and bigger every year, and that is primarily driven by the aging population. So the single biggest risk factor to get Alzheimer's is age. And with aging population globally, we see this significant increase in people being affected. I don't wanna I'm not gonna go into detail about this. You've heard Graham talk about 138 trucks being in development. Not going to go through them, obviously. I want to show the graph on the right because it does illustrate the diversity we now see in targets, in approaches for drug development. It shows a good spread across clinical phases of development, really illustrating the significant momentum we have in that space.

45:59 I cannot present about Alzheimer's without emphasizing the significant highlights of the past couple of years for the field where we now have three disease modifying therapies approved for treatment. All those drugs are targeting amyloid. We have drugs from Lilly, Biogen, and AISI and this is the first time we have disease modifying therapy that actually treats the underlying biology of the disease as opposed to just addressing the symptoms which is a major breakthrough we have gone through and which is driving significant hope and also excitement in the field.

46:47 I have mentioned already the increasing value that biomarkers are playing in that space and that is reflected in the recent update to the FDA guidelines that recommend or encourage biomarker use across clinical stages of development. We see that happening. We have seen a biomarker of surrogacy in amyloid PET, which means amyloid PET has been considered a proxy for clinical benefit in those accelerated approvals we have had. So that is exactly where we want to get to with precision medicine. And I want to close by pointing to a potentially very exciting and transformational topic for the field, which is the development of GLP-one receptor agonist.

47:36 Many people will have witnessed the significant impact those group of drugs is having on the diabetes and also obesity market. We now see trials read out on GLP-1s being applied into Alzheimer's. We have Novo Nord isk present in a couple of weeks most likely on their top line results and we have Lilly also focusing in that space. We'll come back to the topic as a deep dive in our fireside chat later on. Now moving on to Parkinson's disease, where similar, as I've shown on the previous slides, see now Parkinson's developing similar models of disease pathology and biomarker and biological staging as we have had in Alzheimer's several years ago and that is reflected in the drug development landscape as well. To briefly recap, Parkinson's disease is a progressive neurodegenerative disorder that manifests in motor as well as non motor symptoms including clinical dementia.

48:51 It is again, it's affecting twelve million people at the moment but is expected to double over the coming twenty-twenty five years, again similar to Alzheimer's driven by the aging population. It is driven by an aggregation of a protein called alpha synuclein in the brain, which downstream leads to the loss of dopaminergic neurons and then leading to the cascade of clinical events. Imaging is another critical biomarker in this space. So molecular imaging techniques like PET, as I've explained earlier, are the gold standard assessment of dopaminergic loss and therefore critical for disease modifying therapy trials. And we see recent progress in developing radio tracers to image alpha synuclein, which would then put us in a position similar to what we have in Alzheimer's that we can actually identify subjects that suffer from the underlying pathology that we're treating in in the trial as opposed to doing a one size fits all approach.

49:59 Similar numbers, more than 130 drugs in development. Currently no disease modifying therapy on the market, but the field is cautiously optimistic after not least an announcement that Roche put out several months ago about entering their anti alpha synuclein acid into phase three following positive trends in clinical benefit as well as some trends on biomarker effect and I'll come back to that when I talk about IXICO's roadmap which is quite closely linked to these observations. Finishing off this part of the presentation with an overview on Huntington's disease. As Prahm has outlined, it's an area that IXICO is very strong in, where we are running most of the trials, where we have differentiated product portfolio and where we continue to innovate as well.

50:56 Huntington's disease is a progressive neurodegeneration. Again, it's caused by a gene modification in this case. It leads to motor cognition decline and also psychiatric decline. It is driven by neuronal loss in the brain region, specifically in the stratum, which again puts MRI in particular at the forefront of biomarker research just because that technology can capture the neuronal loss early on. It's an early onset disease affecting often subjects between 35 and 50 years of age. Oops, update required. And it's a rare disease, again as Brahm said, affecting around five to ten subjects out of 100,000 in Europe.

51:46 We had, I'm not going go into detail based because Brahm has mentioned it, Great results by UniCure, really driving optimism in the field. First therapy slowing the disease, a fast track pathway with the FDA. In other news we've seen Novartis announce a license arrangement with PTC Therapeutics worth up to close to $30,000,001,000,000,000, moving PTC's asset into phase three development. Wave Life Sciences have announced plans to do a registrational trial on their asset and interestingly they have publicly announced to consider MRI based measurements as circuit endpoints in that trial.

52:32 At IXICO we are very proud and also excited to be working with all of these companies. And we can say this because it's public knowledge that Uniqlo PTC and also Novartis and also Wave, apologies, are part of the HDIH consortium which is a pre competitive consortium that IXICO has co founded and that is working on implementing those biomarker protocols, biomarker criteria I've explained earlier in Huntington's use for clinical trial use and I'll come back to that in a minute. So with this, I'm gonna be moving to the last part of my presentation where I talk about an update on our roadmap. So as Param said, twelve to eighteen months ago we went out to present our Innovate lead scale strategy and here I'm gonna give a brief update on the progress specifically on the Innovate part when it comes to development of differentiated product solutions in Alzheimer's and Parkinson's.

53:38 Before I go there, briefly mentioning a milestone in Huntington's. As I just mentioned on the previous slide, we are active in this consortium with biopharma and non profit organizations and we have reached a significant milestone this year where we have analyzed on the IXI platform the biggest MRI data set in Huntington's disease. This now forms the foundation for the commercial partners to inform their trial planning, but it also together with our academic and commercial partners we are working on essentially using this data set to defining the criteria that allow us to implement emerging biomarker staging criteria into clinical trial use.

54:24 And this then allows sponsors to directly make those decisions through the IXICO platform because we've essentially calibrated it to be able to do that. I now will only spend another two or three minutes, because I know I am behind time, to briefly dive into an update on the vascular and the neuromelanin biomarker work that we've been doing over the past years. To set the scene, more than fifty percent of 80 subjects do show pathology of cerebrovascular disease. So they show some vascular pathology in their brain which is contributing potentially, most likely, to the clinical dementia we are observing. Really, as I said earlier, this has been integrated into the diagnostic framework now and underlies the important to understand those comorbidities as we plan clinical trials in Alzheimer's disease.

55:23 Neuromelanin MRI on the other hand in Parkinson's disease has been proposed as a potentially sensitive and early marker of dopamine deficiency. As I mentioned earlier, this is a key hallmark of Parkinson's disease and being able to measure that in vivo sensitively through a non invasive method like MRI opens up new opportunities in drug development and we've just seen how Roche has actually presented promising result on an early version of that biomarker in their trial. So starting with vasculature, I'm not going to spend too much time on this, but what we see on the top hand, on the top part of this slide, in the black box essentially, is is called the STRiVE criteria.

56:09 It's not important what that means. What it stands for, what it is is an expert consensus paper essentially that was proposed ten years ago to visually interpret, look visually at MRI scans and then grade the severity of vascular pathology in individual subject. As you might see this involves more than a handful of different MRI images that an expert then reviews and assesses different types of pathology which then gives a noble picture of a subject's vascular state. What we see in the bottom part is progress we've made over the past months before to put those measurements into our IXI platform. On the top hand, on the top top blue row we see that all of those measurements are now available through an expert reader in the regulatory compliant streamlined fully accessible platform and I'll leave it to Mark to explain in more detail what value data offers to clients.

57:20 What I'm also excited about is the progress we see in the bottom part of the slide where we are increasingly now moving to automating those measurements through AI based tools. So this will then not rely on visual interpretation by a trained expert which comes with all caveats around reproducibility, training, cost and so on. This is an automated AI tool that provides a quantitative interpretation of those scans. And this is what we set out to develop in our innovate and lead scale strategy and we're now seeing progress as these different assessments that are surrounded by the blue dots are now going on platform. We have another set of tools that will be coming off platform later this year actually and going into 2026.

58:09 This really sets us up into a prime position to start engaging with those companies that are now looking at treatment linked to vasculature of the brain. That includes, for example, the GLP-one receptor agonists I've mentioned and we'll again come back to that topic as we have Mike in the fireside chat. Just wrapping up very quickly because I want to give you a glimpse into another exciting R and D project we are running at IXICO and that is part of the INOVAIT strategy. So neuromelanin, it's a pigment in the brain that is visible in brain structures like the substantia nigra. Just putting some names out there. But what it essentially does, if those cells get lost or retuse as kind of like dopamine retuses during the disease stage, so if we measure neuromelanin, it basically gives us a direct measurement of dopamine deficiency. And you can see this here with the naked eye in this slide. So if you look to the normal healthy subjects on the left, see these white rims in the center of the image. This is neuromelanin in the substantia nigra. If you look to the Parkinson's subject you see a marked reduction intensity illustrating the reduction in neuromelanin linked to dopaminergic loss. Being able to measure this on an MRI scan gives a direct measure of dopamine deficiency.

59:39 The challenge is to do this accurately, robustly in clinical trials and that's exactly what IXICO is focusing on. I want to leave you with this slide again. If you look to the left, this is an image as it comes out of the MRI scanner. The arrow points to the substantia nigra and I think you will agree that it's difficult to see structure at all just because of the noise in the image. At IXICO, over the past year we've developed a dedicated processing algorithm, like an AI based tool that analyzes the image and essentially creates the image that we see on the right where even if the naked eye, we can now see those small rims of the substantia nigra neomelanin appear. And this now forms the basis of an image that can be fed into an AI tool and then quantified automatically, and this is what we're working on with one of the leading academic centers in this space and looking forward to presenting more results on that in the near term.

1:00:44 Just before we move on, I'll wanna finish with this. I wanna maybe take a quick step back and emphasize again the excitement that I see personally and that I hope I've been able to bring across to some extent at least to the audience today about the significant momentum we see across those therapeutic indications towards the adoption and implementation of precision medicine approaches in CNS clinical trials. We are proud and we are pleased to see that almost the bets we took a couple of twelve to eighteen months ago in investing in specific innovation areas are starting to show to be the right ones because we are seeing traction in that direction. We are seeing momentum towards the increased requirement for markers of vascular pathology which is one of the innovation areas as well as the value that a non invasive measurement of dopamine deficiency like neuromelanin imaging can bring to PE trials. So in that we are well positioned to enter this phase of precision medicine and looking forward to it. And that's my last slide. I'm going to hand back to James.

1:02:05 Thank you Robin. We're now gonna move on to a fireside chat, we're gonna have 15 with Mike Weiner, so I'll just let Mike join. Hello everyone. Hi Mike. So So just to introduce Mike very briefly. So Mike is a medical doctor. He is a world renowned expert in neuroscience. In fact, he's a professor at University of California, San Francisco and he's a professor in neurology, in radiology, in biomedical imaging. He's a medical doctor, as I've just said, and also a professor in psychiatry. And what's also interesting about Mike's background is he is, the founder and the lead on a huge initiative in AD, which is the Alzheimer's Disease Neuroimaging Initiative, which is the largest study of its kind in Alzheimer's currently.

1:03:05 And with that, I welcome back, Robin to come and conduct the fireside chat. Then after this, just to remind everyone on the agenda, we go to a break, oh, sorry, go to a Q and A and then we go to a break. James. Hi, Mike. Thanks for joining. It's it's great to have you here, and I'm I'm really looking forward to to this discussion. You you heard me point a couple of times to some topics that I think will be interesting for the audience and get into later in the discussion. But before we go there, really like to hear your reflection almost on what we've seen in the presentation here on the exciting progress that we have in biomarker development over the past years. What impact that has on drug development, what the opportunity is for the next phase not least since acne I want to say this year has played such a pivotal role in achieving all of the things that I've tried to present about the roles of biomarkers and they're playing now. I'm really honored to hear your perspective here on that.

1:04:14 Well, thanks Robin. The progress in the last fifteen years has been incredibly transformational. It's been revolutionary because prior to about fifteen years ago, the only way that you could make a diagnosis with certainty of any neurologic disease was by autopsy. The reason for that is that in contrast to all the other tissues of the body, you can't biopsy the brain. So the only way that you can get brain tissue for pathology is to wait for the person to die and then, you know, look at the tissue. So the diagnosis of Alzheimer's disease and Parkinson's disease and all of these other conditions were basically made on clinical symptoms, but the clinical symptoms were not specific and they were not sensitive.

1:05:07 This really changed with the development of amyloid PET scanning, which allowed the measurement of amyloid in the brain in people who are alive. That happened about fifteen years ago and that has really broken the whole field wide open because if you have a lot of amyloid in your brain, you have Alzheimer's disease. As Robin has mentioned, Alzheimer's disease is amyloid leading to the spread of tau protein, which causes neurodegeneration. And after the development of amyloid PET scanning, then tau PET scanning was developed. And MRI measures neurodegeneration. So with amyloid PET, tau PET and MRI, we can measure the sequence of amyloid to tau to neurodegeneration.

1:05:57 And all of these are now used in all the clinical trials. They're used clinically and this has now also led to the blood tests, which are really gonna have a huger impact because they can be used for millions of people. So initially the blood tests were for measuring changes of amyloid in the brain and they were validated using the amyloid PET scan. Then blood tests came out measuring various species of tau in the blood. And now the blood test field is also just getting very exciting. There are various new platforms being developed, measuring a wide variety of proteins. So this is really just opening up the whole field of neurodegeneration in a very exciting way.

1:06:47 Great, thanks. And I know that you've been closely involved in many of the trials that were run over the past probably decades. So I'm really keen to also hear your thoughts on how these technical developments have changed the way we run and execute clinical trials and therefore how it has helped to the successes we've seen over the past years and how it has also potentially likely contributed to a renewed interest. We, I believe see in AD truck development today. Well, all of these developments have had huge impact on clinical trials. More than fifteen years ago, clinical trials only were measuring symptoms.

1:07:37 Symptoms are obviously very important. What's most important to patients and their families is how they're progressing, how well they're doing. And we continue to have to measure things, clinical measurements, activities of daily living. These are extremely important, but the ability to measure the actual disease process in the brain is extremely important because the treatments are aimed at a specific disease process. So all clinical trials use amyloid PET these days. Many clinical trials use tau PET to some extent. All clinical trials are using MRI because MRI is important at a variety of stages. It's important at the inclusion stage to make sure that people don't have other significant disease. For example, you don't want somebody with a brain tumor or with multiple sclerosis in an Alzheimer's disease trial.

1:08:33 But they also measure side effects, because, these, treatments, that pull amyloid out of the brain are sometimes associated with what's called area that is a swelling of the brain or bleeding in the brain. And those are sometimes serious side effects. So repeated MRI scans have to be done during the trials and performing, imaging over, hundreds of various sites with different scanners, some are GE, some are Siemens and some are Philips. Some of the scanners are new, some of the scanners are old, gathering the data from various sites and various scanners and being able to get a high quality longitudinal data that is harmonized is a very specific art and IXICO really has developed this to a very high degree.

1:09:28 Great, thanks Mike. So with that context, where do you see the field go next? So what is next in Alzheimer's? From a biomarkers perspective but also from a a drug development perspective, more generally, obviously keeping in mind that we do have treatment now, where do we take it next? Well, the next is also incredibly exciting. It's basically in a bunch of different buckets. The first is it's been shown that pulling amyloid out of the brain with monoclonal antibody slows progression, but number one, there are side effects. And number two, the rate of progression, the amount of progression slowing is significant, but we need to do better. So there's a lot of work going on just in amyloid removal. And there are new antibodies using something called the brain shuttle, which gets them into the brain more quickly They seem to be more effective at removing amyloid and they seem to be associated with less side effects. So there's gonna be a whole bunch of clinical trials ongoing and starting right now. Roche is a leader in this and there are other companies doing this. So that's one big area, just better amyloid removal.

1:10:35 The second area is what are called prevention trials with amyloid removing drugs. The current studies that are approved are on people who had symptoms, people who have a memory problem who are progressing, they obviously need treatment. But the ideal thing is to find a way to prevent the development of symptoms. Because we know that about twenty to thirty percent of the population over the age of 65 has amyloid in the brain and they have no symptoms, but they are very high risk to develop symptoms. So those of you in the audience, just remember that about half of the population 90 has dementia from Alzheimer's disease. And that about thirty percent of people 65 have amyloid in the brain, which puts them at very high risk.

1:11:25 So both Lilly and AISI are currently in major prevention trials where people who are completely normal over the age of, I think 55 or so, who have amyloid in the brain are being treated with these monoclonal antibodies to pull amyloid out of their brain to see if that delays onset of mild cognitive impairment and dementia. There's a lot of hope that these are gonna be successful. I think we have a reasonable expectation, but we have to wait to see the results of the trials. I just learned yesterday that Roche has also announced that they're gonna go ahead and do a prevention trial with their brain shuttle thing. So that's amyloid. Then there are treatments against tau which are very promising. And that's a very, very exciting area because it's in fact the tau protein that really does the damage. So that's the, so there's the amyloid bucket, there's the tau bucket, and now we have the GLP-one agonists.

1:12:25 And that's, I think really hugely impactful. The GLP-one agonists like Ozempic and Wegovy and Zepound are certainly very effective of controlling diabetes. They cause a lot of weight loss, but people lose 20%, obese people can lose up to 20% of their body weight if they're on these medications. It results in better control of hypertension. So there's basically all better control of diabetes, reduction of obesity, hypertension control. It just makes for better vascular health. And there's a lot of evidence that these improve brain health. There are studies already showing that people treated with these medications have less strokes and appear to have less dementia.

1:13:16 Novo Nordisk has now completed a phase three study in people with symptomatic Alzheimer's disease and the results of that will be announced very, very soon in the next few weeks. But even if those trial is negative, I think the real impact of the GLP-one agonist is going to be prevention. That is people who are cognitively normal, who are diabetic, who are obese. Just remember in The United States, almost fifty percent of the adult population is obese. So these medications are gonna be used on millions of people. Up till now they have to be injected, but Lilly seems to have a good oral pill. I think there's more than a 100 companies developing GLP-one agonist right now. So I think there's gonna be huge numbers of clinical trials and these are gonna be focused on, a lot of them are gonna be focused on reducing or slowing the development of cerebral vascular disease.

1:14:16 And this is an area where IXICO has really got a phenomenal, highly automated platform to quantify all the different ways that cerebrovascular disease affects the brain. So between amyloid and tau and the GLP-one agonist, and then the work that's going on in Parkinson's and Huntington's and all these other neurodegenerative areas, this is a hugely exciting area for growth. That's great. Thanks so much, Mike, for giving your perspective. I think we're coming up to time. Is there anything you'd like to add from your side, Mike, before we go into q and a? No. Except that this is just a hugely exciting time. I see lots of new trials coming on. Everybody who comes to the meetings is very, very excited. AI is gonna have a big impact on this. IXICO is really taking advantage of that.

1:15:08 There's gonna this is just this is gonna make our lives better. Great. Thanks so much. I'll I'll hand it back to James. Thanks Mike and I think you're staying on for a few minutes Anja for Q and A. So we do have a little bit of time now for Q and A if anyone has any immediate questions you'd like to ask and then we have a break in about ten minutes time and then we're back at 03:35. Chris, yeah. Thanks, thanks for that. So just, let's see, a couple of questions. Just one on science leadership, and obviously, you're you're you're got all the data that you're you're you're pulling through. Is there anything that IXICO ICICO can do on its own that could possibly, you know, present some of that data as as IXICO or or is it all tied up into your your your client's data sets and you're not really allowed to use that?

1:16:03 Because obviously, you know, IXICO publishing its own results and its data would obviously put your name out there. So is is that an opportunity for you or are you completely locked out by by your competitors? And then maybe just on, you know, the accelerated approvals in the Huntington's disease, is there a risk that those trials accelerate and therefore they're not doing the phase threes and so you know, you actually, you know, by being able to produce the data that you do, you're blocking your phase threes in a sense? Good question. Shouldn't you go in first and then Prem, you want to probably add to that? Yeah, thanks. I'll have a go at both. Thanks, Chris. So on data side, we are publishing, I mean, you're right, the data that we produce as part of clinical trials is owned by the pharma companies, so we're not typically publishing on those.

1:16:55 We are sometimes in collaboration with pharma sponsors publishing on their results, but we also the key part of our R and D strategy is the engagement in research consortia like the one we mentioned with GAP, global Alzheimer's platform, the Huntington's Consortia, and this is typically where we produce the scientific presentations that we provide. Second question on Huntington's disease accelerated approval. I think we would all be very happy to see those drugs coming to patients. And I think, but to answer your questions directly, I think we've seen in Alzheimer's that having one accelerated approval doesn't mean everything else is stopping. So firstly there's different mechanisms that may be suitable for different types of patients.

1:17:43 What UniQ are doing is actually a very involved praying surgery for administration. So this is a very complicated way of administering the drug and what for example PTC Novartis are developing in the Phase three is an oral pill. So there's different mechanisms that we will be testing and there's different ways of administration as well to justify further trials. Don't know if anyone wants Maybe just to add, and especially as we've got Mike here as well. Yes, we don't publish the data of our customers. It's their data and it's their publications. Having said that, we can be coauthors or we can be part of it depending on whether biomarkers are really sort of the central theme also in those. Having said that, today, see Mike for fifteen minutes here talking a little bit about what's going on. But actually, Robin and Mike are doing a lot of work together and will actually be together at CETA at the Clinical Trials on Alzheimer's Disease Conference in a couple of weeks' time, as Mike said, in San Diego, which Mike is co organizing, where there will be work groups around this.

1:18:51 And it is my expectation that Robin, together with other leaders, industry leaders, so across companies, if you wish, and, of course, with key opinion leaders like Mike, he's going to then start to generate more insights, for example, around vascular. And those, of course, can be published as well across sort of the various industry players. A quick question just on the role of non image based biomarkers. Mike referred to the increased use of blood tests, for example. Do we see that as a potential threat in terms of IXICO's specialism in imaging? Will that be displaced in any way by the use of blood tests or is it complementary? Can I ask that question? And I think Mike might have an opinion on that while we still have him as well.

1:19:42 I don't think so. And I think as soon as I entered the company, also said, let's embrace this. And so we're validating those, and and that's why we're so proud of being instrumental in Fujirebio coming with the first, blood based biomarker. And now you see these others rapidly coming to market as well. First of all, as you know, our current business model is not in the clinic. These products are being developed for the clinic. And I think as Mike actually alluded to it, they will give access to a whole group of patients that today does not have access to other diagnostic modalities or where it would just not be economically viable to start to put everyone in an MRI or a PET scanner, to at least early diagnosis. So I think I'm using a lot of words to say I think it brings diagnosis potentially earlier in the disease, and I think that's a new market.

1:20:28 And secondly, I think it's really sort of complementary to what imaging does, keeping in mind also that our market is very much in that research space, where I do think blood based biomarkers are probably going to start to become part of the protocols of some of these trials. I also do think that we're not entirely there yet. But I don't know, Mike, Robin, you guys are the experts in the room. Yeah, think it's the complementary value we see and I think there's so much need for diagnosis that being able to align those measurements in the right way, it really opens up opportunity to be able to assess more subjects. Last but not least, of course, we're working with diagnostic companies in refining those biomarkers as well, so we can increasingly deploy them in clinical trials. I think one thing that Ram didn't touch on is the added value of imaging that we currently don't have in blood based biomarkers, specifically from MRI, which as Mike said, a safety, it's a key safety measurement that cannot be replicated from a blood test at the moment. We talked a lot about vasculature, specifically in the context of GLP-1s that are coming up. Again, this is something we're taking from an MRI where there are currently no developed blood based biomarkers.

1:21:51 So I think there's a role for both and we have embraced working with those companies early on, which I think puts us into a quite nice position now because it helps us on kind of like playing a role in this area where it's multimodal, we're basically looking at both, right, and building up expertise on how the two interact with each other is actually something that has helped quite a lot now working with those diagnostic companies to validate them. Don't know, Mike, any Another way to answer the question is that what blood tests are going to do is that they're going to just hugely expand the target population. In some circumstances, may be that blood tests would replace, for example, amyloid PET. There's still a lot of debate as to whether or not a blood test is good enough to replace an amyloid PET scan for inclusion.

1:22:44 One thing we know for certain, the blood tests are not good at measuring amyloid removal effectively. The only way to know whether amyloid has been pulled out of the brain is to do an amyloid PET scan. So you need to have a longitudinal amyloid PET scan to show that the treatment is working. Blood tests are so far are not very good at predicting the tau level in the brain. And certainly the only way to measure the strip of vascular disease, bleeds, white matter disease, all of the things that happen from cerebral vascular disease that has to be done with MRI. Mike, thank you very much for your comments, especially about the fact that over the last fifteen years, there's been a huge advance in the way we're starting to understand brain disease.

1:23:41 I was fortunate enough to work in Parkinson's with Eli Lilly in the nineties. In those days, we called it witchcraft. We had no idea what was going on. I'm sure you remember. Looking to the future, we got these GLP one data coming out. I think it'd be really interesting to hear your and, you know, obviously talk to your peers on what you think the outcome of the GLP data will be on Alzheimer's and how it will have or maybe have no impact on the amyloid and tau trials which are ongoing. Well, that's nobody knows the answer to this question. But basically, what we all care about is reducing cognitive decline and dementia in the population.

1:24:26 Now, if you look at autopsies, if you look at the autopsy data, probably eighty percent of the people that have dementia have Alzheimer's pathology in the brain, but they're very unusual if it's only Alzheimer's pathology. Usually when people have dementia, there's a mixed picture, which includes amyloid, tau, but it also very commonly includes some element of cerebrovascular disease. We know that these GLP-one agonists are good for brain health. There's no question that they're good for brain health and they're gonna reduce the number of strokes and so forth. Whether the GLP-one agonists are gonna slow the effect of amyloid accumulation or tau accumulation is very uncertain, but to me, I don't think that's really gonna be necessary. I think they're gonna be very impactful to really improve brain health, reduce the development of mild cognitive impairment and dementia in the population. And there's one other thing, Most of the work that's been done, most of the research that's been done on Alzheimer's disease has been done on highly educated, affluent people who have health insurance.

1:25:50 And in that population, amyloid and tau clearly are the major causes of dementia. We have much less data on poor people, on people with lower education because they don't volunteer for clinical research. It's very likely that cerebral vascular disease is a much bigger cause of mild cognitive impairment and dementia than we think, because most of our studies haven't been done on the population that is obese as poorly controlled hypertension, has more diabetes. The GLP-one agonists are gonna have a hugely impactful in that population. But there's just gotta be a lot of clinical trials done on this.

1:26:36 This is a huge growth industry and IXICO is perfectly situated for this, especially because of its beautiful platform to measure cerebrovascular disease. So thank you very much. I'm delighted now to introduce Johannes Streffer to you, is SVP Global Clinical Development at Lundbeck. Johannes, can you hear me? Yes very well. Good afternoon. Johannes has got a very strong academic background in both neurology and psychiatry, but he's also spent a long time in pharma at a very senior level, both at clinical and leadership levels, notably at J and J, at UCB and AC Immune.

1:27:28 And what's interesting actually, and hopefully Johannes is gonna touch on it a bit today, throughout his entire career, he spent a lot of time dedicated to focusing on how artificial intelligence can play a role, where data plays a role, and where technology plays a role in furthering drug development. And so on that note, I'm delighted to also welcome back Bram, who's gonna have a fireside chat with Stefan. Also Johannes. Hey Johannes. No worries. Good afternoon. Are you dialing in from Copenhagen or are you dialing in from from Germany? Copenhagen. Copenhagen. That's where the music plays for me. Good. Good. Well, welcome to London. I want to start, I think James already gave the introduction, right? But when we spoke a couple of days ago as we were preparing for this day, I think we sort of discovered or you actually uncovered, so I hope I'm not stealing your thunder here, but how our organizations have some similarities as well. I think that struck me right. So you said that we're both focused on CNS. Obviously, I've made it very clear to the audience today as well that we do feel being in CNS means being in very fertile ground. It is sort of a very opportune time. And I think you said, well, that's very much what Lundbeck is about as well. And secondly, we're priding ourselves in having done that for twenty years. We're celebrating our twenty years anniversary, and I think you sort of said, well, we've been doing this for seventy plus years in the more than one hundred years history

1:28:59 of Lundbeck. So I think there's clear consistency. Then I think James already alluded to it, I will invite you to sort of chime in where you see fit. Obviously, we have an AI driven platform. We pride ourselves in being born out of AI. But as you said, Lundbeck has always been embracing digital and AI very much as a cornerstone. And You can maybe allude to it, but I think quite a few people in the audience probably also read even the most recent news where there was strengthened collaboration between Lundbeck and OpenAI. Obviously, I invite you to comment on that if you see that fit. But maybe starting with the sort of more generic first question. Obviously, we're in the business of precision medicine. We've been saying today how that is very important in some of these big disease areas, but also in rare disease areas, obviously something that you're very close to as well. So how important is precision medicine, according to you indeed, in CNS today?

1:29:56 And then more specifically, also how does imaging fit in there? First of all, thanks a lot for having me. I think it's great to put a focus on neuroscience and precision medicine. When we look at neuroscience and I think you spoke about your tenure in neuroscience. Lundbeck, as well, is committed to neuroscience. And we have said that we stay in neuroscience, have done that for a long time. There is a huge change. And I think this is really breaking a lot of things open. We do understand biology better. And while neuroscience, specifically large psychiatry indications, have always been very strong on phenomena. And in truth, that is critical for patients, right, the symptoms.

1:30:42 We now get more and more into understanding biology, and understanding what the underlying pathophysiology for diseases. And that is fantastic for precision medicine, right? Because here again, now we can understand the disease and then go about it with very targeted mechanisms. That has, I think, helped to break the neuroscience arena open. And I think this is, as well, strengthening the focus in neuroscience. And here you come in play. In contrast to dermatology, they can do biopsies. Other organs are easily accessible. The brain isn't, right? So we have to be much more inventive in the sense of how we go about looking at our diseases. And this is where it's obviously great to see an organization being dedicated to that, and specifically with the focus you're having on brain imaging, which makes things accessible to us. We have, as neuroscientists, the opportunity to see symptoms very easy. But unfortunately, to see pathology is sometimes difficult. And this is where we come together. And I think where it is great to see your focus on neuroscience.

1:32:04 Great, thank you. So maybe homing in for a moment on that relationship that we have, and obviously, James made that introduction already that you've got extensive experience. You've got extensive experience in different organizations. What has been your experience with IXICO so far? And is there anything you would like to call out? No, obviously Good question. Now, I and I think what as well where my path is with IXICO, of course, was not only on clinical trials directly, but as well on advancing the science, right? And I think this is where pharmaceutical industry, and then as well our partners that help us to get, let's say, get it on the road, we have to go away from pure academic research, but driving science into clinical development. And I think that is where I've seen IXICO very strong being academically driven.

1:33:07 Good understanding. And if you look at your website, have very nice publications. But then as we make sure we take this understanding into clinical trials. And I think this is what we need. We need to understand how the science is then as well moving forward. And I think meeting IXICO was as well in endeavors like IMI consortia, or where we are close. You had Mike Wiener just here before me, and there is a reason for it, right? ADNI is one of the big endeavors that has moved the needle in terms of understanding. Neuroimaging was one critical part in that. Just being part of that community and helping us to shape the clinical trials environment to be upfront and to use the best science and the best technology to bring that in a clinical trial is critical.

1:34:01 And this is not trivial in the sense that when we do clinical trials, we have to do it to a very high quality measure. We have to use standards that are reproducible. It's not just about publishing a paper. It's about developing results that we can rely on, and patients can rely on, and agencies can rely on. And I think bringing that together is critical for me. And that is where we have to partner strongly on. Well, thanks for bringing that up. I don't know if you were here when a question from the audience came up around publishing together or publishing the data, where clearly we made the comment that we don't publish the data of our clients because it's their trials, it's their data. But I think what you're alluding to as well is that it is sort of an across industry collaboration, right?

1:34:53 And that it goes above that commercial relationship, if you wish, that we have, of course, with our sponsors. And so thanks for bringing that up. Moving on. What's important here is we are, for instance, we are committed to make data publicly available. And I think this is a commitment that most pharma companies today share. So that meaning you can often look at baseline data. You can ask for data. You can work with the data. We work in consortia together. And this is was from or is and was for me a critical point that we do science together. And science has to be transparent and public. So why I fully understand that yeah, and I hope everybody understands we cannot be full transparent about our molecules early on. We have to understand it and that the data are primarily there then as well to support the development of the drug. We as well know that we are part of the scientific community and we make data available as much as possible.

1:35:54 So maybe bridging then a little bit more to Lundbeck, right? And obviously delighted to have you here as the head of R and D. What are you excited about? What's happening at Lundbeck? What is on the roadmap there? Again, I'm not sure if we have investors in Lundbeck here today, but why do our paths converge? First of all, important clarification. I'm head of global clinical development, not R and D. So clinical development is fantastic, and that's a great role. I'm super happy to be here. Now, what are we excited about? And I think you talked about the legacy in neuroscience. When we look at it today, we really believe that we want to build on our neuropsychiatry legacy. So this is still super important for us. And we are trying to move that forward.

1:36:53 We now then, as well, have two other pillars which we think are critical. That is neurospatiality and neurorare. What does that mean? We have a focused innovative strategy. So we really want to advance in the science. We wanted to use the science and advance in a focused way in these disease areas. When you look at our current ongoing phase three programs, we have mexicathrin and amlanituk in phase three programs, which are targeting very specific indications where we need to demonstrate superior efficacy. Now when we, for instance, look at biomarkers and understanding then a disease like MSA, neurodegeneration, we really have to bolster that with our biologic understanding.

1:37:47 And that continues into a lot of our early development and research. So translational medicine is a strong focus for us, meaning we want to understand what are the biomarkers in there. How can we early derisk? One of the credos of our head of R and D, Johan Lutmann, is early derisking. We know that neuroscience has been troubled with late stage failures. And this is something we cannot afford. So what we have to do is we have to de risk early, and then take these de risked molecules into late stage programs. And de risking early has to be via translational medicine. So the early program where we understand the mechanisms, disease, how does the mechanism in the disease interplay, that is super critical for us. Do that well, and then take a derisk acid into late stage development. And that is what we are committed to in Lundbeck. And in neuroscience, we need advanced biomarkers to be good at that.

1:38:52 Thank you. And also, thanks for that correction. Think it's actually useful for the audience indeed. IXICO, of course, is very much active in the development part of the R and D section, if you wish, which is also why Johannes, for us, is the important stakeholder, for example, with Lundbeck. There is actually a question which I think we will be answering separately around what is the role of imaging in discovery as well, right, preclinically. That is a whole other debate which we could open as well, which we chose not to. I think another part which I'm hearing, Johannes, is the importance of rare diseases, in CNS and how I think you're very excited about the growth that you're seeing there as well. Because obviously, to this audience as well, we are talking a lot about Alzheimer's and Parkinson's because we do believe the time is now for those big areas.

1:39:42 We do think that is also a commercial opportunity for us as a company. But I think what we're witnessing here as well is a company that is very deep into this rare disease space and where I think there's a lot of progress made as well. I don't know if you want to comment on that at all. Yeah, I think that is critical, right? And when we talk about rare often, we do not say neurorare or the ultrarare. Neurorare, but not ultrarare. And then for a neurologist, a lot of these rare diseases are often coming into your office. So the neurologist sees diseases like PSP, MSA, in the day to day practice. But we have yet not developed sufficient clinical solutions for these patients.

1:40:30 You're working on Huntington's disease, spinocerebellar ataxias. These are diseases that are very important, high unmet need, well described, but no solution yet there to really help these patients forward in the treatment. Or solutions at the breakpoint, something where we really need to move forward. And I think this is why we are committed to this space, because we feel we see high unmet medical need. And we see well defined patient populations. It is not that we say we only want to do something for selected few. That is absolutely not the case. What we say is we want to have a well defined population. That is then going into the neuro rare sometimes. It doesn't have to be neuro rare, right? We as well do neurosppecialty when you look, for instance, into our migraine prevention.

1:41:22 But the key thing, it has to be well defined. So we have to understand the mechanism, and that then puts us into these groups for diseases. Where again, I still remember in my neurology education, I always loved to be in the neuroradiology. Because the neuroradiology were the ones that, in a wizard like way, could tell me what this could be or could not be. So when we look in a diagnostic way, you do not have that many tools. You have a patient you can examine up and down. A neurologist loves to do that for hours. An MRI gives you a relatively quick, very thorough look on that brain to tell you what it can be and what it cannot be. And that is very important for us, specifically as well the cannot be. So we want to treat the right patients. We don't want to treat patients that potentially have something completely different, but just by symptoms look very similar.

1:42:19 Thank you for bringing that to life. I hope that actually does bring it to life also for the audience, because we often show pie charts with the disease areas. We did that again today, granted that. But I think we pride ourselves very much in having actually that dominance in rare CNS as well. And I think as you hear, we actually believe there's a lot of growth there as well. And so maybe that is a segue to my last question. I invite you, of course, Johannes, to make your own comments. What does excite you in the space, in the neurodegenerative space in general? And I don't know if you want to sort of sprinkle in there the comment that was made earlier around AI and digital as well, right? So in truth, I would like to answer that in twofold.

1:43:05 Maybe start on the digital and AI. Clinical development has a fantastic opportunity in AI because we are digital enabled. And that has certain reasons. So quality in clinical development has been super high. I still remember when I was an investigator, we had paper CRFs. We moved away from that for a long time. Patient data at the site is all digital. Everything we do is digital. Every outcome measure is collected digital. MRI has been digital from the get go, right? You said digital native. There is no MRI with a digital analysis. But that means that our data lends themselves to all sorts of AI applications. And we have a visualization pathway. So I have to say, coming here to Lundbeck, I'm super excited how the team had already built that super strong foundation.

1:44:02 Now we have a very strong commitment, as well, from our leadership team to make sure we use AI where it is used for us. We really see it as an enabler a lot. There are areas where it is breaking out completely new ground. But it's as well in those areas where it will be a productivity measure. It will make us faster, more efficient. It will improve quality. And these things we as well have to use. And there are tiny things like writing a report to us, bigger things like getting a file together. Or then in research where you as well might have seen our colleagues in research are using AI now as well. And we have strong collaborations where it might go to a territory where we never could have been. So I think this whole digital AI is super exciting.

1:44:52 And we have to do it. I don't think there is any choice. This is just the way forward. What excites me in neuro rare and I think I started to talk about that I did my neurology training in the '90s. And at that time, we still were very phenomenology driven. We had neuropathology, but in the clinic, a lot of phenomena. We have electrophysiology, and then imaging came. But now these better diagnostic measures have been coupled with a better biologic understanding. So the understanding of these diseases has moved fantastically. We now can differentiate them on the neuropathology, on the biology. And that leads us now to the point where we can develop treatments. So we come from an area that is phenomenology, we added diagnostics, diagnostics like neuroimaging.

1:45:43 And now we use neuroimaging as well for readouts and pharmacology, clinical pharmacology. And this is a fantastic era. I think the era of neuroscience, as Alton said, is just here, because we can do things today that we were not able to do earlier. That's why I think neuroscience development hopefully will have a very strong goal, because there is a huge unmet medical need. If you look at the morbidity disability by neuro diseases at all, it's a huge factor for patients and a huge factor in the life science area. So lots of tasks, but fantastic opportunity. Yeah. Well, we'll end on that. I think you really bring to life very well also our understanding underlying biology is really what biomarkers is about. I think that's what Robin was describing, who unfortunately had to leave as he had to catch a plane. But I think Johannes is very much sort of bringing that to life. Johannes, is there anything else you wanted to share today?

1:46:45 Then I don't know if we have time for questions as well or Okay. So we've got five more minutes. I don't know, Johannes, if you had anything else. Otherwise I I tried to give you all my wisdom. I don't know if there are questions in the room or online, but happy to answer. We've got a question here. Yeah, hi, thanks. So you talked about neuropsychiatry and obviously looking at the symptoms, now starting to more understand the biology and the underlying disease. So maybe I'm a bit behind on this, but I wonder whether there's any options for imaging of the brain in neuropsychiatry like there is in sort of the neurodegenerative area. Not that I am aware of immediately. Now, what we do understand, and just at ECNP, neuroinflammation was front and center. So we do understand that inflammation is a huge part in neuropsychiatric diseases. This is something obviously we can image.

1:47:45 We, unfortunately, still today, can not image as psychosis. We have functional MRI. Functional MRI has betrayed us a little bit in clinical development. So this is one part that we have been using on advanced MRI. And advanced MRI, I think that is good. But super good scientists can give you an image when you're speaking. And then they have the activation of the brain. We have not yet been able to translate that into clinical development, really. Try to do it, but it's super difficult. And I think this would be then the psychiatric part of it more. And this is tricky. So in the traditional psychiatric diseases, mood disorders, bipolar, schizophrenia, it's much more difficult than in neurodegeneration.

1:48:41 And I think there's lots of work ahead. And I promise Johannes I didn't tell Chris to ask that question because I actually had that discussion with Johannes briefly. And we said we were going to continue it over coffee because Robin spoke about neuromelanin, which obviously we're positioning in Parkinson's disease, if you follow. We did a webinar a few months ago on neuromelanin and did actually get some phone calls from pharma, which were more in that neuropsychiatric space, which excited me. But I think it's indeed something that requires further discussion and analysis. Yeah, and I agree with that, right? And it was kind of interesting, even in discussion with experts. Unfortunately, let's say neuropathology, molecular structural pathology of psychiatric diseases has not revealed much.

1:49:30 Autopsy studies don't give a specific view. You know the neurotransmitter changes, and that has been successful. But that is not the strength of MRI. Neuromelanin could be really interesting. But we have to understand that better. Very good. I think we're going to conclude it here then. Thank you so much Johannes, and we'll let you get back to Thanks important a lot. Have a good day. Bye. So we're coming towards the end and we're gonna conclude with a section which is a deeper dive on what the IXICO technology looks like and what the IXICO technology platform does. And I appreciate we've talked a lot about AI today it can be quite an ethereal concept and so hopefully what we're going to do now is demonstrate what this actually looks like and the utility it actually has when it comes to neurodegenerative diseases.

1:50:31 So great pleasure in introducing Mark Austin who's our CTO. Thank you James. So as James said I'm the CTO, I've been at IXICO for seventeen years and had the pleasure to work on this technology platform over those seventeen years. And I'm going to start today with some eye candy. So I've got the pleasure to show you what the platform looks like first and then I'll step back and take you through how we get here. So what you're seeing here on the screen is our integrated viewer. It allows us to see the output of these AI algorithms. So this is launched directly from the platform. And so these algorithms, as Robin has showed you, we can look at volumetrics. You can look here for example, this is a whole brain segmentation.

1:51:19 So when I say segmentation this is calculating the volume by saying what is brain and what isn't brain. And this can be done manually. We've got people at our company that can do this manually. But obviously what's a lot better is if you can do it automatically because that's then reproducible and it is faster and it is also more accurate. What you're seeing here is a multi region segmentation, so here we're able to define more than 140 regions of the brain, which I'll show you later is really useful, not only to look at specific areas for specific diseases, but also enable some of our advanced MRI and PET analysis. As I think was mentioned earlier today, what is really important is being able to measure changes over time of these regions.

1:52:06 So we can see here that we are able to look at a specific region but also see multiple sequences taken over different periods of time and you can see the changes there. We are able to measure those subtle changes and that is what is really measuring that neurodegeneration in, for example, Alzheimer's or Huntington's. What we're looking at here then is a four dimensional scan to this advanced MRI. I'm not going to go into lot of detail on how this works, just to show that we can visualise these four dimensional data sets with their time series. So you see in a moment we can overlay those segmentations that we have taken from the structural MRI on top of those advanced images. But we can also visualise the motion and the time series, which you will see in a moment as we scroll through that time series there. So what looks like a video is actually the time series looking at one specific slice of the brain.

1:53:03 As I said, all launched from our platform. So to get to those insights, we have an end to end platform that really enables this. So I'm going take you through this workflow step by step at a high level. We're taking data from hospital sites, the MRI and PET images, as well as some clinical data. That's uploaded to our platform. We perform quality control. We have our radiology readers who can look at the data visually. We have our analysis pipelines. This is where our AI algorithms and other image processing algorithms are analysing the data and then we get report outcomes that can go to our pharma biotech clients. So the really key to this whole process is making sure we get the right data in. So first of all that's about getting the data uploaded from the sites, the hospital sites. So we have teams that train the sites in collecting the data with the right protocol, and then we have a no installation platform, web based platform, that these sites can use to upload the data. So we make it as easy as possible for them to get the data to us, and we can do so remotely. The training can be done remotely and the sites can upload the data without any installation.

1:54:18 And at the site, it will anonymise the data so we deal with patient privacy and we can also make sure that they are selecting the right data and help them get the right data in. Once the data gets to us, it's that quality control step. We then have teams that look visually at the data using those viewers that I showed you earlier, and also another view I'll show you later. What we're trying to do is make sure that we've got the right data and it is of the right quality for us to be able to run our AI algorithms and image processing pipelines, but also so it's the right data of the right quality for our radiology readers to be able to look at the data and provide those other insights that Robin mentioned. This allows us to guarantee that high accuracy and reproducibility.

1:55:04 We also have a data query mechanism that means that if the data isn't right we can get back to the site, communicate with them, potentially get a re scan if that's possible, which means we can guarantee more patients get onto the study. But if not, at least we can feed back the issues so that future images are of suitable quality. So not everything we do is fully automated, so we have our pool of expert readers led by Professor Fredrik Barkhoff from UCL and BUMC. So we provide a web based platform for them to perform these radiology reads. And here, this is the medical grade medical device certified viewer that we provide. Again, web based on the platform.

1:55:51 It has to be medical device certified because they're making supporting clinical decisions here. And it needs to have the tools that our radiologists expect to see on their imaging platforms available to them so that they can look at the images correctly, can look at images across time points and they can identify those clinical safety findings, possible drug side effects, but also support that eligibility process to make sure we're getting the right subjects onto these studies. This allows the radiologists to perform these reads also anywhere, anytime, because they can access the platform directly online. This is critical as these radiologists we work with are often thought leaders, they'll often be at conferences or they'll be working in multiple hospitals, they can access it from anywhere.

1:56:39 So as well as those manual reads we obviously have our automated and AI pipelines. And this is obviously perhaps the most exciting thing that we do. Those images that I showed you earlier all come through various analysis pipelines that are integrated directly into our platform. So we have a very flexible workflow engine which allows us to integrate these pipelines, integrate endpoint QC visual review of the data, What it allows us to do is really turn that innovation from Robin's team, the science team, into products that we can deploy in clinical trials, as Johannes was saying. That's really what the platform does really well. Obviously these results will come out and be transferred in reports to the sponsors, to our pharma sponsors, and that's really why they're paying us the millions of dollars to produce these results.

1:57:33 So just to look at a high level at some of these different types of imaging endpoints. Robin obviously touched on some of the exciting new technologies as well as a little bit on what we've done in the past as well. As I mentioned, volumetric MRI is about measuring neurodegeneration. By able to segment these regions in the brain we can help the pharma sponsors really track those disease modifying drug effects. But also these segmentations, as I said, will help us to drive our advanced MRI and PET pipelines by creating a patient specific atlas so we can see for each subject where the individual regions of the brain are, which means when we're assessing, for example, white matter integrity or brain network activity with advanced MRI to detect these subtle changes, can do so in a regional sense. And again for PET, we're able to visualize those amyloid and tau proteins that Mike was talking about so that we can monitor disease biology but also monitor the effects of the drug. Is it clearing out those proteins in Alzheimer's for example.

1:58:35 And so this platform has been built and engineered for scale. So by building this flexible architecture we've been able to integrate those bespoke workflows that we need to deliver at our endpoints. We can integrate those AI analysis, those automated analysis tools, but it also allows us to integrate third party pipelines as well. We have done that and we will be able to continue to do that. But this gives us a great platform then to be able to extend. And across the board we have regulatory compliance as a key component in this system. This whole process ensures that regulatory compliance and also most security. Here I've put in my cheesy AI image for the day. So this is representing the fact that this flexible platform and the agility that we have through our agile development processes and the extensibility of that platform, powered by both the AI that we use as a business, but also the new advances in AI enabling our accelerated development, we are able to, as a small UK innovator, play a big part in a global scale in precision healthcare.

1:59:44 I've ahead. Here we go. So we've mentioned AI a lot today, so I just want to stop on this slide for a little bit and talk a little bit about the history of AI and then how IXICOV used that AI and the development of AI over time in the best way for our business. So artificial intelligence has been around for a long time. There's been a lot of buzz about it recently, but it's been around since the fifties. Machine learning, which is a critical type of AI for IXICO, is about being able to learn from data, and that's really where IXICO came as a foundation. So we built our technology around that ability to learn from data and develop predictions or calculate volumes. But more recently from around 2012 onwards, that machine learning developed into deep learning, so much larger neural networks, which really drove huge accelerations in improving the way that you can recognise patterns in data and analyse images. So that really drove the development of our more accurate IXIQ AI segmentations, able to create extremely accurate and very fast segmentations, as well as driving some of our other pipelines. So we took that on board almost immediately and made that part of our platform.

2:01:02 And more recently with the onset of generative AI, large language models, OpenAI and their competitors, This is starting to make a difference for us as well, initially a little bit like Yohanna said, in really just scaling and being able to make the business more efficient. But with the onset of Agenetic AI as well, we're seeing huge advances in the development pace that we're able to achieve with these advanced tools. So AgenTik AI is about taking those large language models and the intelligence that comes from that, but then allowing access to tools and giving it goal directed targets. So with the ability that it has to generate code, that can hugely speed up your development capabilities and allow us as a relatively small business to develop huge advances in our technology platform.

2:01:54 So the future for us looks like taking our existing foundation and thinking about how that allows us to integrate and partner, but then continuing to work with both deep learning algorithms where sometimes that's the right technology to advance our AI imaging, but also making the best use of generative AI and agentic AI to increase our development efficiency and be able to deliver these new opportunities around trial automation, new analysis endpoints and clinical decision support. To finish, I just want to sort of visualise that for you by looking at this report that we generated that could be launched from our platform. This is a report that takes in blood based biomarker data, imaging data, both PET and MRI, and uses AI to generate differential diagnostics.

2:02:43 So this shows how by partnering and using our AI platform we can just let it load again we can provide insights, precision insights, through our platform. That's it, thank you. Thank you Mark. So that concludes sort of the formal presentations for today. I would invite anyone else that has any questions please to go ahead and ask them. Do have a couple of online ones too that I'd like to get to but does anyone in the audience have any further questions? Thank you for all the very interesting presentations.

2:03:35 I think one thing that'd be helpful to touch on from my point of view is where IXICO sits within its competitive landscape. I'd like to understand a little bit about of the all of the benefits you discussed today, which are particularly USPs for your company over competition? And also, I'm sure you're not alone in driving innovation. And are there any kind of innovations that are on your radar that you're looking to make sure you have in order to keep up with competitors or you see competitors taking a lead on potentially within your core areas of business or in adjacencies that may prove to be complementary? That would be, I think, very interesting. Thank you. Let me maybe start. And, obviously, I invite my, my colleagues to chime in, Grant and and Mark.

2:04:29 It depends a little bit on what you consider competition. I think until a few years ago, and as you know, I've been with the company since a year, people might have said, IXICO is an MRI company. They're very specialized in analyzing MRI images. And so you there were others, such as in vitro, which is now perceptive, which are very well known for PET analyses, but also PET tracer management for, clinical trials. We've caught up to that. I think today, one is saying that we're an MRI company. We are an imaging a CNS imaging analytics company. And so I think that sort of basic catch up has happened. And I think I can truly say that today as a company, as an ICRO, we're very much at par, if not better, with some of these big competitors, which would be in our world mainly Perceptive and Clario, which are massive companies. Right? I mean, Clario, we've talked about it already. Clario does more than imaging. Otherwise, they would not be doing 1,200,000,000 in in top line, which brings me, I think, to the second point, which is AI and how do we utilize data and AI, And are we at the forefront there with our platform?

2:05:35 I'm hoping that today we've shown that that is the case. Very specifically in CNS, of course, we've we've picked a few battles. And in addition, we've picked battles of application, which is, for example, vascular. That's why we've you've heard us talk about that. Because if we try to make a difference in too many areas, then we do actually become like a Clario just at subscale. And so the choice has been to go deep into certain areas, use a platform, I think, as Mark hopefully eloquently said, that can really do big things for a small company that we are to be very competitive, especially in that CNS and in that neurodegenerative space. I don't know, Mark or Grant, if you wanted to add in, and if that answers your question. Maybe, I think possibly what I would say to that is because of the fact that we specialize so much in CNS and because we've really made this effort and I think if Robin was here, he would definitely send this to really identify what are those really key areas that differentiate us potentially from our competitors in these key therapeutic indications for us. We've really focused our investment on that.

2:06:49 We are making sure that we are leading, as we say, in that scientific field. So I think whilst we have some competitors who are much bigger than us in scale, their focus is much more broad brush and not as focused as as SARS is. I think that's what gives us that that edge. Maybe to bring that to life, sorry if we're belaboring it a lot, but you may have, you may remember actually when when I came to your offices also for the for the capital raise that we said we're making some choices, and we're also not choosing to go into other other areas. MS is a big area where today we're not necessarily positioning ourselves deeply, even if we have MS trials that we're supporting and our platform is being utilized.

2:07:36 There was a specialized MS company. It has been acquired over the past year by Clario, NeuroRx, Canadian company acquired by Clario. There's another smaller company, unfortunately, which has announced publicly that it is going to stop business in Switzerland. Again, these are opportunities that present new business to us. But I think it sort of reinforces how if we had tried to be good in MS and Alzheimer's and Parkinson's in addition to that entire rare disease space, then I think we would sort of start to spread ourselves too thin. Obviously, the question that I will be asking the group in addition to partnering the technology with some of these big data groups with some CROs is what are some of the imaging areas that we do wanna continue to invest in?

2:08:25 Because, obviously, the road map that I presented for the capital raise was a twelve to twenty four month road map, and we don't wanna fall off a cliff. And so I do think that we need to have a discussion, for example, around how can we go deeper into MS. But, obviously, that does then come off the basis of traction that we have generated first in Alzheimer's and Parkinson's. So sorry, that was a long winded answer. I was just curious in terms of other instances where there are different reads from, say, the human analysis and the AI analysis? And especially as AI becomes more advanced, what would be done to resolve these issues if there was differences? It's probably best for Robin to answer. I'm happy to take it for now. I think at the moment we don't tend to if we are running both human and AI analysis on a study, one of them will be that primary endpoint and then the analysis of any differences between them would then come afterwards as a secondary analysis to review either improve the quality of the automated analysis or investigate why those differences are happening. There are cases where we have actually used image analysis pipelines as part of a read, so supporting the read, providing data, but that's usually supplementary so it's giving that additional information to the reader to help them make their decision.

2:09:49 So they don't tend to compete with each other. That's not how studies would be set up. Maybe I can answer that as well. We've also seen for a long period of time that one manual read might differ from someone else's manual read. In fact, that same manual read might be different in the morning to the afternoon with the same person. And that's why AI really comes in, because AI standardizes and gives that consistency. So actually, it's the complementing of the two, which is really what IXICO can do, and obviously others as well, that really benefits the clinical trials or even indeed the clinic itself. Speak slightly cheeky, ask two questions. One, just developing the Clario news and your initial reaction to that news beyond perhaps the seven times revenue multiple that's been paid.

2:10:40 What was your immediate reaction as to what you think it means for IXICO? Is it an opportunity or is it potentially more of a threat? My second question, a slightly different one, which is in the first section of your presentation, Ram, you talked about going beyond potentially the fee for service type revenue opportunities. When do you think the sort of timing of those in terms of partnerships and so on will be most likely? The questions are actually linked, would say, so it's a nice segue. My first reaction was an email to my colleague saying seven times multiple. It's just so you know. But, if you look at Clario, as I mentioned, it is much more than an imaging company. So we do encounter them on the market the whole time because they are an excellent imaging company, it needs to be said. But they obviously are not specialized in CNS, and their biggest business is on oncology.

2:11:27 But they do good CNS work as well. What Clario has been doing rapidly is, consolidating not only imaging, but also ECOA, so cognitive data, digitalization. We've got a sister company that you're well aware of, here in Cambridge that is doing a similar type of business. They do a lot of other biomarker and clinical trial work. And now, of course, PPD, which is really that part of Thermo Fisher that is mainly interested in clario. So it's it's about consolidation. So I think it's good news. I think it's good news for you guys because I do believe all eyes have been on IXICO since a while, but will be even more on IXICO. But, obviously, as I've always said, I feel like we're in a business now of creating value before we have further discussions there.

2:12:19 And that brings me to that second question, which is we can do the same from a technology perspective. I think you heard Mark say that we can maybe even do more, especially in CNS. But we can't, with who we are and where we are, put armies of people to sort of commercially scale that up. So we need to partner. And those discussions are ongoing. You haven't seen much of James, but you will see more of James in the future. We are having these discussions as we speak. I don't think they're ready for prime time, but it's clear that commercial scaling of our platform and being part of that multimodality, cognition, imaging, blood based, has to come through bigger partners where we think we can sort of almost plug in our platform into their ecosystem. And that will not be fee for service.

2:13:06 That will be that other revenue model, I think. Possibly one for Mark. Obviously, IXICO is dependent on the images that are supplied from the MRI machines and the PET scans. So are you seeing any innovation in that sort of pre use of systems in terms of the imaging that's coming through and development of the techniques for actually getting scans and is there anything there that's coming through that might be of interest for IXICO? I'm not aware of anything myself. Again it would probably be Robin that would be better to answer that. But at the moment I think the advances are not in the scanner technology so much as those techniques like neuromelanin and those other more advanced techniques that are coming through that we are obviously taking a lead in developing.

2:14:01 Just going back to the point about the competition, as I understand it within HD there were very few trials and new guys that really captured that market. Are sort of in the mid teens, thirteen, eighteen trials going on globally. Whereas in Parkinson's and Alzheimer's, there's two sixty eight we heard today. So I mean, if you get even a small part of that market, that's a huge opportunity, let alone worrying about MS or any other type of imagery. Absolutely. We actually have 17 on our radar, and it's growing because obviously as soon as you see that FDA is now starting to talk about Fast Track, and I think someone asked the question, oh, maybe you might miss out on Phase three because they may get approval after phase two, but that still will create a lot of excitement in the industry.

2:14:48 I think what I've learned over the past year, myself personally, is we should not rest on our laurels. We do need to keep investing in Huntington's disease as well. We do need to make sure that we, Robin said it, we are managing a consortium together with the Huntington's Association based in New York. We need to make sure that we stay at the forefront, that we make sure that any Huntington company becomes part of that consortium, because as soon as they're part of that consortium, they're going to find their way to IXICO as well. Right? So, hopefully I I think your question was a bit of a comment more than a question, but, my message clearly is we we can't rest on our laurels, and we do need to continue also to innovate in the Huntington space, because indeed today, we believe we've got 80% of that market. So we have one other question we probably we did have quite a few online questions, but actually the audience in the room has posed quite a few of those questions. So the last one I just wanted to address probably with you, Graham and Grant, is how do you see the pipeline of revenue and new contract momentum building, And what options do you have to accelerate this through your sales strategy? I think we had slides on this, and I'm happy to go back to them. But do you wanna answer or should I go back on this slide? No. No. No. I'll I'll try to answer it without slides and then you can chime in.

2:16:14 How do I see the momentum? The momentum is there very much in terms of the discussions we're having with new partners and the RFPs that are coming in and the proposals that we can prepare. Sales cycles are long, so I would have wanted to have a bigger order book by now. I came on board twelve months, ago, but we clearly now have a pipeline. I think Grant has actually has showed that funnel. Right? So when he says in Alzheimer's disease, we think there's 40,000,000 in business to be accessed, of which then sort of 80% is readily available for us to go into. We know which programs they are. We've done really when you set an analysis, we know which sponsors that are. We know which programs that are. And we now have an active commercial team together with the medical and the innovation team that approaches those companies and that actually now tries to get in, especially in those phase one and phase two trials.

2:17:08 So I think we've done the pipeline building. You've seen that we've also got the platform now to make a difference. You've heard one client at least that is very excited. You've heard a key opinion leader that is also clearly saying you've probably made the right bet by going into vascular. So that is something that excites me a lot now. Obviously, what I want now is that I can come with that order book and with some of these deals in next coming quarters. Yes. I think the only thing I'd perhaps add to that is 's two elements to this, which is, one, investments that we've made over the last twelve months. Have they been the right investments? And are they going to put us in a better position to win trials? And the other is the market itself. And Is the market warming up and are we seeing more trials coming through? There was an interesting report and webinar given by Global Data recently which seemed to indicate that there are now more trials starting in the market. We're seeing that as well, after what has been a bit of a challenging time for the market over the last couple of years. We are seeing that start come through. And then it's these investments that we are making, are they really going deliver? And we are very confident that they are. An example that I have very much in my mind is that we announced a contract win alongside our trading update just after the end of our financial year.

2:18:32 That was a contract that we went for and we regarded ourselves as perhaps being the third place company for that. And perhaps in previous days, we wouldn't have won it. We won that purely off the basis in I'm a little bit further away than Robin and Bram, but really from the basis of the discussion of what we've developed and the pipelines we've developed and the fact that those pipelines can be utilized in a way that that particular organization hadn't envisaged. And that took us from third place to winning that contract. That was a really big moment me, not necessarily because of the value of the contract, but because what that showed, these investments, these areas we decide to invest in, potentially are giving us an opportunity that we didn't previously have. Hopefully that helps answer that question.

2:19:24 Well, thank you all for coming. And thank you to the presentation team. It's been really fascinating to hear from those at the forefront of science in this important field, especially when so many neurological diseases still lack effective treatments. A special thanks to Johannes for showing us how IXICO is supporting Limbeg in their clinical programs. As shareholders and investors, it's invaluable to see how this great technology is being applied to advance development of life changing treatments that have the potential to benefit patients worldwide. Cavendish has been proud to work with IXICO since April 2019, helping to shape its story, support its growth and raise the capital needed to advance its technology and diversify its markets.

2:20:15 From the very beginning, it was clear that IXICO possessed world class technology, providing essential services to both big pharma and biotech companies and consistently punching well above its weight in the market. Working side by side, we've helped the company amplify its achievements and navigate the inevitable challenges that come with being a growth company. And there's been a great deal to celebrate. The development of exciting new biomarkers that will play a pivotal role in tackling some of the most serious neurological diseases, including Huntington's, Alzheimer's and Parkinson's, as well as the company's strategic partnerships with the Global Alzheimer's Platform Foundation, giving access to valuable data from the Biohermy studies.

2:21:01 It's also clear that IXICO's work is making a real difference. By providing imaging analysis for new Unicure, IXICO contributed in a small but very meaningful way to Unicure's recent breakthrough in the treatment of Huntington's disease, a devastating and previously untreatable condition. Of course, as with any growth companies, there have been setbacks along the way. It's a testament to Grant and Bram that they foster such a strong sense of integrity and trust in the company, ensuring investors' confidence that any challenges will be faced head on and that IXICO will emerge stronger each time. And finally, I'd like to send my congratulations to Bram on his first year as CEO.

2:21:47 Take it from me, stepping into the leadership of a small cap company is never easy, but Bram has done a superb job, supported by a talented and dedicated team in driving IXICO forward. Under his leadership, the company has advanced its world class platform, won new business in new markets and continue to unlock its full potential. Thank you. Well, thank you, Julian. And I still remember when I had my first week in the job, which I think I was already in this building then, talking to Giles. And Giles said, well, this is baptism by fire because we immediately hit the road. Right? And I think by the time I had come on board, I already knew the names of a few of the key shareholders, of whom some are here in the room. So I want to end on a personal note. I think we've done an excellent job staying on time, so we'll try to let you leave on time indeed.

2:22:43 First of all, thank you, James, for organizing today because I think I enjoyed it, I hope that it was valuable also for the audience also remotely. So thank you for everyone who's made this happen also from a technology perspective and, of course, for Cavendish for having us. And, of course, for my team. I think for my team, it has been a great way also to sort of solidify what we've been doing, which during what has been a very intense past year, which I think has been very successful. So I want to end on Hopefully today you have seen that we have turned the page of that company, of the company. We are an ICRO that is back to growth, that will get to double digit top line and profitability within the timelines that we have set out. And, of course, there's always the hope that we can do this even faster, and that is through science, through some of the choices which we've made.

2:23:37 They were bets only twelve months ago, I would say, at least vascular definitely, and they are realities now. And you've heard that confirmed by some of the people who who know better than than definitely me, I would say. But I think it's the vision of Robin which clearly has informed that as well. But then there is that next chapter. We alluded to it a little bit. We spoke about it a little bit, but you will hear more about it. That's why I joined the company. I joined the company for the platform that Mark has been building, that I think with the vision of Grant has been shaped because despite the fact that we had revenues going down, a company that was profitable no longer being profitable, investments, millions of investments were made with your support, of course, in that platform. If that hadn't happened, frankly, I wouldn't be standing here because I would be, okay. This is a a company that is not going to make it. So that investment happened. The platform is there. We equipped it with the right algorithms because otherwise, it would not have had that impact which we're seeing now.

2:24:36 My task with the team is now in the next twelve months to show you that indeed that pipeline and that order book is translating into the top line. And then I want to have that conversation again with you about what is next, if you remember that purple line, which I kind of cartoonist put on the slide. So with that, thanks for being with us for two and a half hours today, and I look forward to meeting you soon again.