Cellbxhealth S/Adr

Good morning everybody and welcome to Angle's preliminary presentation for 2024. I'm pleased to see a very good turnout considering it's half term in the FTI offices and a warm welcome to those of you who are participating virtually. It's been a year of substantial progress for Angle in a market that is moving towards us and I'm looking forward to telling you about the progress that has been made. Our large pharma strategy is now in place. We announced that in the middle of last year. It's firmly in place and it's moving forward well. This is all about using Parsortix to select and monitor patients in trials for pharmaceutical drug development. And that can progress all the way through to companion diagnostics where the Parsortix system could be used to select patients for each drug. This approach is critical to the new way that drugs are being developed for precision medicine. The new cancer drugs only work for some patients and it's critical to work out which patients. These kinds of new drugs, such as antibody drug conjugates, DDR inhibitors and immunotherapies, fundamentally require an understanding of what's happening in the patient's cancer. However, the cancer changes over time with clonal evolution. So the current standard of care, which is to examine the tissue biopsy to guide these drug selections, is insufficient, especially in later stage cancer. It does take time to educate the markets and the pharmaceutical companies about the opportunity that comes with the parasitic CTCs. But we're now making a lot of progress with that. And the pipeline is steadily growing in the right direction. In terms of the year of 2024, we had two major areas of development, which were the large pharma strategy and the DNA dual analysis and then four other significant achievements. In terms of the large pharma, we established and secured three large pharma contracts and one large biopharma contract. And I'm pleased to say that the three large pharma contracts, which I'll discuss in more detail later in the presentation, have all progressed very well indeed and successfully concluded. We also have a variety of other large pharma names under discussion to bring in Parsortix into their trials. And we have discussions with the existing large pharma in relation to the next stage of development. The second major area is the DNA dual analysis. Now, from a standing start, we've developed a new way to measure DNA mutations in cancer. And that new way involves looking at the living cancer cells, the circulating tumor cells that can be obtained with our past sort of system. in addition to looking at the fragments of dead cells, which is the circulating tumor DNA. So it's dual analysis, and we're the only company that's able to offer that potential to evaluate both aspects. We'll explain in more detail how that works and what the impact of it is. But suffice it to say, we had breakthrough results during 2024 showing the importance of analyzing the intact living cells, in addition to what the industry already is beginning to do, the fragments of dead cells. We move swiftly to position ourselves strongly with that new market opportunity by securing an exclusive deal for the next generation sequencing DNA panel that we'd used for that work, covering 6,500 mutations in 61 clinically relevant genes. And post-year end in this space, we were pleased to complete some similar work with an end-to-end Illumina solution, which was developed by Angle and was showcased at Illumina's EACR conference webinar. EACR is a very large European cancer research conference, and Illumina had a webinar there which they allocated entirely to Angle to present the results of our DNA dual analysis. In terms of the other areas where we've made progress during the year, we have developed a new approach to getting cancer cells or indeed any cells of small numbers down onto a microscope slide without cell loss. We developed a new It's actually more than a technique. It's a physical structure called the CellKeep slide, which reduces that endemic cell loss to virtually zero. This is really important when you're working with rare cells. And there are a number of uses outside of our own internal use for the CellKeep slide, which is now being offered and sold to our customers. And we have European and US patents now granted on the CellKeep. So another aspect where ANGLE is proactively innovating to address key issues in the marketplace to improve the adoption of liquid biopsy. We've also reached a milestone during the year of the 100th peer-reviewed publication by independent cancer centers showing how well the parsortic system works. We also completed a placing in adverse markets, raising £9.3 million gross in June 2024. Beyond that, we've opened up a new line of attack, which is to engage with the large medtech companies as well as large pharma. We're now working with large medtech companies with a view to giving them the opportunity for repeat testing of their existing tests. And again, I will say a bit more about that shortly. In terms of the financial results for the year, despite there being a very adverse market with FDA regulation of laboratory developed tests and actually problems with research grants post-COVID funding, we have achieved a 31% growth in revenues, 2024 compared to 2023. We also secured an ongoing gross margin of around 62%. And that was even after we had given a number of introductory offers to new customers to get them started with our technology. We've been bearing down on costs, and we've reduced our operating expenditure by a further 21%, and we continue to bear down on costs. And that, in conjunction with the increase in revenues, led to a reduction in our loss by 29%. The business is now streamlined. We have an improved cash runway of 11.6 million, including R&D tax credits at the year end. And that lasts through into Q1 of 2026, even on very conservative assumptions in terms of growth rates. And we're actively now driving our milestones and projects forward. In terms of our pharma services revenues, the initial contracts that we've had, the three large pharma, one with ESI and two with AstraZeneca, are actually the starting point for a pipeline of opportunities with those companies. And as you can see from this slide, the moment we get into phase two, trials we could be looking at between one and four million pounds of revenue for each one of those trials and phase three is a major step up more like 15 to 45 million so if just one of these particular projects progresses all the way through there's a very substantial revenue opportunity for angle we've got currently three such areas and we are in discussions about multiple others Obviously, the ultimate aim is to get to the bottom of that box, which is a companion diagnostic. And the idea of a companion diagnostic is that the doctors will do a blood test on the patient, will use parasortics to look for a particular target. And that target is linked to the drug. And then the patient would be prescribed the drug if that target is present. That means that the farmer is likely to become a very, very large global customer for angle, and it plays directly from our services business into our products business, where we can sell the Parasortix instruments and consumables worldwide to support a companion diagnostic program. And as shown in that slide, a conservative level of revenue on an annualized basis would be in the 20 million pound range for a particular companion diagnostic. And it could be very much larger than that. So the reason that pharma is keen to do all this stuff is that their trials cost a lot of money. So a pharma. Phase 2 trial might cost $180,000, so spending a bit of money on angle to make sure you select the right patients and you monitor them properly is not very much, and hence we can charge up to £3,000 for each sample that we process in our laboratory. But overall, the cost of developing a cancer medicine is as much as $4.4 billion. So it is critical with these new precision drugs that they have a way of identifying which patients can be given the drug in order to get good clinical study results and get regulatory clearance and have doctors want to actually prescribe the drug. So this is not a nice to have for pharma. In the future, this is going to be absolutely essential to their future success. So a bit more detail on each of the contracts. The first contract with Isai, the large Japanese pharmaceutical company, is in relation to the measurement of HER2 in breast cancer because they have an antibody drug conjugate. So the way an antibody drug conjugate works is is the drug attaches to the cancer cell via a protein on the cancer cell, and then it puts its treatment into that particular cancer cell. So the idea of antibody drug conjugates is that they're much more specific. Instead of causing toxic side effects all around the patient, it's much more targeted to the individual cancer. However, the antibody drug conjugate will only work if the protein that is targeting is present on the cancer cell. And in this case, the protein is HER2, which is a very, very important target in breast cancer. There are... HER2-targeted therapies in first-line treatments, so trastuzumab, for example, and then there are HER2 treatments in later-stage cancer, such as in HER2. So as an example, in HER2, which is an AstraZeneca and Daiichi Sanko drug, has a current revenue line of circa $5 billion per year. Now remember, this only works if HER2 is present. HER2 is only present in a minority of patients, and it changes over time. So at the present moment, all those decisions are made on the tissue biopsy, which is cut out at the time of primary diagnosis. And yet, HER2 is often prescribed three, five, or even longer years later. So by that time, the patient's condition may have changed. And if it's changed, that means that the drug will be not effective for that patient or the other way of looking at it is as up to 60% of patients are HER2 negative at tissue biopsy and they never get offered that particular drug. So what I'm pleased about to report is that our HER2 study, which was a subset of E-size phase two trial, was very successful. We successfully managed to get consistent results between two blood tubes taken at the same time point. but in terms of the numbers of circulating tumour cells present and in terms of their expression of HER2. So we got a good, reliable, consistent test based on blood tests to tell you what is the status of the patient's HER2. We also showed, and this is the key point, that in the two time points, which were before and after the patient had the therapy, there were significant changes. So consistency between two tubes at the same time, but very significant differences between two time points. So in some patients, the number of CTCs reduced significantly, HER2 expression reduced. In others, it was unchanged. And in a few cases, it increased. So this is likely to be a guide as to whether or not the patient is responding to the drug. Very importantly, what it shows is that our assay is fit for purpose to measure on a longitudinal basis changes in HER2 status in the patient condition, which is critical to the prescription of this drug in the future. Now, ESAI have actually decided not to progress BB1701 and have turned it back to Bliss Bio. They've made a $2 billion commitment to this, and I guess in some of their internal financing structures, they decided that they didn't want to go down that route. But the good news is that ANGL is now in discussions with BlissBio about the next stages of this, and we're looking forward to presenting to them the results that we have in relation to the first trials. So that was very successful, and bear in mind that HER2 targeted therapies, there are many companies interested in that with products. I've already mentioned AstraZeneca's product which is already on the market. If AstraZeneca used our assay on the HER2 negative by tissue patients, And they've done the necessary clinical studies and secured an extension of the label to cover HER2 positive patients by CTCs. They could add at least $2 billion per year in revenue to their drug. So it means a lot. Antibody drug conjugates, by the way, there's many different antibody drug conjugates being developed for other areas, not just HER2. And our technology works well for all of those. So the next one is AstraZeneca's first contract, the DNA damage response. contract, which is assessing, again, proteins on the cancer cells. You can't look at proteins, by the way, with ctDNA. And the time frame is not when the tissue biopsy is there. So this is the only way you can get an update on what's happening with DNA damage response in the cancer cells. And there are specific DDR inhibitor drugs which target that, try and stop the cancer cells repairing themselves after they've been dosed with chemotherapy is example use. So AstraZeneca paid angle to develop the ability to look at phosphocat one, a key protein, and to measure micronuclei, CTC micronuclei. We've done that development work and we've had sign off from AstraZeneca that we meet their requirements. So now we're waiting for AstraZeneca to tell us which clinical trials they want to use it in and how large those trials are and when they want to start. The second AstraZeneca contract is in relation to prostate cancer. A bit like HER2 is the leading protein for breast cancer, a leading protein for prostate cancer is androgen receptor. And there are drugs that target androgen receptor, androgen receptor inhibitors. So, we were initially contracted by AstraZeneca to develop a means of looking at androgen receptor on the cancer cells. We didn't have that, so they agreed a contract to pay us to develop that for them. The initial contract was 550,000. During the year, they extended that and increased it to 670,000. Now, we've successfully completed that. We've been able to demonstrate our ability to measure androgen receptor reliably and meeting their requirements. And actually, AstraZeneca have put us through our paces, testing our quality control system and the way that our clinical labs operate in order that they can be certain that we meet their requirements for large scale clinical trials. So we're currently waiting on the next steps in relation to that. We expect that they will want to deploy it in time on multiple different programs. And we're looking forward to hearing how we can help them with those programs. We got during the year a large biopharma customer called Recursion. Recursion is involved in using next-generation sequencing and artificial intelligence to identify drug targets. At the moment, it's an initial pilot study to show how CTCs might be of assistance to them. It's very interesting, actually, because the costs of next-generation sequencing and also the sensitivity are going faster than Moore's law in terms of their reduction. So Moore's law is that one where computers get cheaper and more powerful progressively. Well, this is even faster. data fast and look for patterns, etc. Again, the costs are coming down from artificial intelligence and the performance is going up. However, there is a limiting factor, and the limiting factor is the sample. if you're looking at the wrong sample it doesn't matter how deeply you sequence or how hard you look with artificial intelligence you won't find the right answer it's a standard garbage in equals garbage out so it's critical to have a good sample and we believe that and so does the industry now that the circulating tumor cells intact living cancer cells gives you the best possible window what is happening in the patient development and you can't just do it with fragments of dead cells so again the market is coming towards us CTC's do make a big difference We've got other biopharma customers which are developing nicely, particularly Ematics is moving forward, has got Parsortix in their laboratories and these other ones are also making progress. Arteos helped us a lot in the early days for the development of our DNA damage response assays. By the way, our strategy for developing new assays is despite customer paying for it, we own it at the end and it goes on our menu and we can offer it to all our other customers. And that's a key part of our development strategy. So onto the second major development area during the year, which is the DNA dual analysis. Now, this has been developed by ANGLE and proven by ANGLE. It's a very interesting area because the industry felt that they had DNA mutations analysis sorted with circulating tumor DNA. But ANGLE felt, well, we're going to investigate, actually, is there any difference between the living cancer cells and the dead cancer cells. Now, we already know that the advantage of the living cells is that you can do RNA analysis, and you can do protein analysis, you can do cell morphology, you can look at clusters. And none of those things can be touched with ctDNA. But the industry felt that the DNA part, at least, was covered by ctDNA. And that's why the American companies have had multiple billions of dollars invested in them to develop assays. For the first time, we've been able to show from the same tube of blood the analysis of living cancer cells recovered with Parasortix with a specific DNA sequencing panel compared directly with the ctDNA coming from the same tube of blood using identical sequencing. And the answer is that we find a lot of extra information from the living cancer cells. So this is critical information. This is information about how the cancer is changing over time. This is what is evading the immune system. This is what the drug is not killing. It's not dead. Therefore, it is not being killed by the immune system and it's not being killed by the drugs. Whereas the CT DNA is a different different analyte from that perspective because it is dead. So we now have evidence that shows that you can get extra information from looking at CTCs, and critically, which is part of our commercial positioning, you can combine it with ctDNA to get the maximum amount of information. That's the pitch to all of the large companies who've already established methods of analyzing ctDNA. Those are all good. You can add to that an analysis with the same approach of the circulating tumor cells. So following success with that, we moved quickly to secure a deal over the panel that we used for that analysis. This is a very high sensitivity panel. It's very good for looking at DNA mutations in amongst a lot of background. And it covers, it's a pan-cancer panel. It covers 6,500 DNA mutations in 61 clinically relevant genes. And Angle has now signed, whoops, what's happened to the computer? Looks like we've lost our power, maybe. I don't know why that is. I'll keep talking on the basis that we've got. That's the first time that's ever happened in quite a number of these. Hopefully, that's back up now. I think that's all right. So we move quickly to get exclusive rights over this panel. So we're the only ones who are allowed to use it for circulating tumor cells. And we're the only ones allowed to use it for a combination dual analysis of circulating tumor cells and CT DNA. It's now being made available to our pharma customers for use in our lab. And soon, eventually, we'll be selling kits as a product to others as well. All of this information needs to be backed up by solid third-party evidence. In this industry, nobody takes much notice of what a company says. They want to see what independent cancer researchers have published under peer-reviewed processes. We now have over 100 peer-reviewed publications from over 40 independent cancer centres, and they all say exactly the same thing. that we can get information from the living cancer cells harvested by the parasitic system that we can't otherwise access. And that information is absolutely critical to the future decisions about the patient management. And they've published now in 24 cancer types. So this system works without modification right across the piece. And again, the market is moving towards us. So, in terms of our revenue build, going forward, Angle is extremely well positioned with both... Something funny is going on with the computer. Angle is extremely well positioned with... We've got a system update going on. Cancel. Right, I'm being helped with the computer. I don't know why it's been problematic today. So, in terms of our revenue build, we have a products and a service business. So, under the service business, our research laboratory is able to develop tests that can be run on CTCs for our paying customers, which is the assay development, and then they get added to our menu. Our clinical laboratory is staffed up with experts who have parasitic systems and a variety of downstream analysis techniques so that we can run blood samples for patients in the pharma customers, pharma trials. The key thing is we also have a products business, currently selling products to research use customers who are generating the evidence that I was just describing. But we are extremely well-placed to help our pharma with the companion diagnostic rollout. For that, you need products. Most other companies in this industry have a service-based clinical lab, but they have no product. We have the product which can be used worldwide across all the different cancer types. And then here's our last side. In terms of the outlook, we have multiple large opportunities under discussion. They are binary in nature. We either get them or we don't get them. And their timing is uncertain. So as a consequence of that, we're confident of modest growth in revenues. So we expect revenues to increase in 25 compared to 24. But dependent on the large opportunities under discussion, this may be exceeded. So following the successful completion of the existing large pharma contracts, we're awaiting follow-on contracts which are expected to be substantially larger in revenue levels. And we're also in discussions with prospective additional new large pharma customers. We decided to move that same approach into the large medtech companies, and those companies are now looking at how they could work with parasitic CTCs to extend repeat testing of their existing tests. We had a very successful webinar on the Illumina EACR slot, progressing our DNA dual analysis, and that is gaining traction and a lot of interest. There's also been, as was announced, there were two announcements in January of this year, there's also been some very significant therapeutic developments using parsortics with the potential for drugs which could block the spread of cancer in the future, so to contain cancer. And the pipeline is very encouraging. And I just give you a couple of examples about why I think the market is moving towards us. I mean, a very, very interesting and poignant one. is the development of the HER2 testing. So I explained we've had a contract with ESAI, that went very well. There are multiple HER2 targeted therapies out there which could benefit by increasing their revenues if they also tested patients who were HER2 negative by tissue biopsy and become HER2 positive by their CTCs. But a poignant comment is that In our informed study, which is targeting the recruitment of 1,000 patients from six NHS trusts, and we're making very good progress with that, we have already had three breast cancer patients who were put onto palliative care, told there was nothing more that could be done for them, who were HER2 negative, according to their tissue biopsy, and therefore were not given HER2-targeted therapy. Those three patients, we proved beyond a shadow of a doubt that they were HER2-positive in their circulating tumor cells. And you need to do a clinical trial to prove this, but you could expect that they might respond to a HER2-targeted therapy if they've got HER2-positive cancer cells. And what happened? Nothing at all. And all three patients died within six months. That is what we're addressing here. An opportunity to radically improve cancer treatment. And that message is what we're getting out to the market. We're beginning to educate the market. There's lots of elements to it. I've just stressed, obviously, they're the benefit to patients. There is opportunity for patients to have a much better outcome than they currently have. But on top of that, there's an opportunity for the farmer to make a lot more money, because if they extend their label to these patients who are HER2 negative, then they will get paid for those drugs. And The final leg to the stool is that the healthcare systems are spending enormous amount of money on drugs which are ineffective because they keep prescribing based on historic information, which may be three to five years out of date, when right in front of them is a solution which can give them the information they need to do that properly. Thank you very much. We're happy to take some questions from the floor.

Morning, it's Sam England from Berenberg. I've got three questions, but I'll maybe do them in turn. So firstly, can you just give us a sense for how the early discussions with the potential MedTech partners that you're speaking to are going and how big you see the opportunity in MedTech being relative to the opportunity you have in pharma? And then how do you see those deals with MedTech partners developing, particularly in terms of the financial structure of the partnerships? And I'll do the other two afterwards.

Okay, I'll dive into that one. So the difference between Medtech and Pharma is that the Pharma have a defined process for clinical trials, which they spend a lot of money on. So I was indicated in the presentation, they spend up to $180,000 for each patient who is enrolled. So it is more straightforward for them to have a biomarker input into those trials. We've got the right clinical lab to be able to process the samples. So that fits into a sort of understood process. In addition, there are... thousands of potential trials that we could be in. So that's an existing market that we're breaking into. And obviously, we're having to educate the market. They don't all necessarily believe this stuff until they see data. But it is fitting into an existing structure. The medtech, there are smaller numbers of opportunities, but they can be very, very large. And the reason that the medtech can be interested is that at the moment, their tests can only be used once. So if you're a large med tech company that has a diagnostic test for breast cancer, let's say, that would be deployed when the patient has a biopsy and you've got a source material. But that's a one-time revenue opportunity for that company. If they're willing to engage and run the same test on cancer cells that come from blood and run the necessary clinical trials to show that the patient responds in the expected way, Then they could measure the patient every six months or even every three months. Well, certainly on progression. So that's what we're seeing with our NHS informed study is the massive gap is that doctors are trying to make decisions on late stage patients who are progressing without any new information. And if you've got the same old information, how do you make a different decision? And the truth of the matter is it's done by, to an extent, guesswork and seeing whether the patient does or doesn't respond. So the way we can engage with the large medtech, and we've started doing this, is um provide them with some of our past sort examples and look to see whether they can actually analyze those samples with their existing approach and if they can then we could engage with them in similar way to the farmer to help them do clinical trials to prove it out and then ultimately they would then want to sell the past sortic system or you could use it themselves in their in their business and we would make money out of every single test So if you look at the cost of tissue biopsy in metastatic breast cancer, it's averaging at $16,000. So if a solution came through at $2,000 or $3,000 for the sample prep using parsotis, it's much, much cheaper, but it obviously makes a lot of money.

I think what I'd probably add to that as well is that key thing is that, you know, the tissue biopsy is the standard of care. We'll take time to change that. You add in the CTC analysis at time point one at the same time. So that's the key thing here is that you can do the repeat testing and the longitudinal monitoring. That's going to pick up the status change in patients and so forth. And that is the immediate time expander because they've already got the tissue biopsy diagnostic test. It's now expanding it to tissue plus liquid and that's the TAM expander for them.

Great, thanks. And then the second one's just around the uncertainty that you're seeing. I suppose, have you actually seen evidence so far of projects getting cancelled or sort of major delays that have affected the business? And do you think these are really just temporary delays that are going to affect 25 and the longer term opportunity is pretty much unchanged? It will just maybe shift back a bit as a result of the research funding challenges and tariffs this year?

So one of the examples is the east side they found about their project to list by and we've seen a few others that are passing those assets back and obviously that creates a bit of inserting to an outside because we had a path. way through with Esai. Now we're back to sort of discussion with Bliss Bio. They appear interested in progressing, still progressing the asset. We've got good data as Andrew said, but the original path was with Esai. So, and what we're seeing is even with some of the larger companies such as Esai, we'd already seen it before with the smaller biopharma, because of the funding environment. So there is a bit of a tightening and that we think is sort of delaying some of the decisions. And we just have to sort of recognise that that's one of the indications in the market.

Yeah, I mean, the pipeline's building and what's happening is that some of the decisions have been slipping, which is disappointing, but it doesn't mean that there's not interest, there's just delays.

And in terms of some of the other on some of the product side of things directly in the US, the sort of uncertainty and cutbacks in NIH funding again is sort of pausing some of the buying decisions. So we're not seeing them go away, but we are seeing them sit on them and sort of waiting for some clarity for that to come through. And in Europe, to a lesser extent, we've seen a little bit of that as well, but also an increased emphasis on, you know, people trying to go for a procurement process. So, you know, they want to choose us, but they said for, you know, financial reasons, they have to go for a procurement process, even though we're the only ones who can effectively do this to the level that the researcher wants. It still then delays the process. So we are seeing a few more delays in that fashion.

Great. And thanks. And the last one is just around the cost piece. You called out that you've got sufficient cash through to Q126. Does that assume any further cost reductions to come this year or are you really where you need to be now on the cost side?

So we continue to try and take some of the costs out of the business. But there's a bit of a balance there because we have been investing in the clinical lab as well. And the reason for that is, of course, is that we've got to make sure we've got the capability and the capacity to deliver for the AstraZeneca and so forth. And they do, you know, they test our quality systems. They make sure that we've got everything in place to meet their criteria, that we're a selected vendor. So we've gone through that process with them. There's various initiatives such as SOC 2 and everything. We have to do a bit of investment to make sure we're fit for purpose. That has an upfront cost, but it's a one-off. But in general, we're trying to keep that cost base fairly tight and be as efficient as we can.

Great. Thanks.

Yeah, hi. It's Chris Cavendish. Just actually on your last bullet point there on the Outlook slide in terms of pipeline, I assume there's a bit of commercial pipeline in there, but also I was wondering in terms of product development, is there also a Palsortix pipeline that you're working on and bringing through? And if you can provide a bit of detail around what that might be and what that looks like going forward. Thanks.

Yeah, thanks Chris. I mean, we're primarily focused on development of the uses of the cancer cells rather than developing the actual instrumentation. So, the Parasortix instrument and the Parasortix cassette, they're stable. We're not developing them further because they're best in class already. We have done development work, as I mentioned, on the cell keep to get the slides down onto the microscope slide. But that's all completed and is also stable. So where we're doing development work is on methods to analyze the cancer cells. So we've done a lot of work on next generation sequencing of DNA. And we're also working on RNA. And we've done paid for by customers mainly. We've done a lot of work on proteins, like I mentioned to her too in the DDR. So that's where the product development is coming through. It's in the uses of the cells. And it's non-trivial to do that. You have to have a sort of lockdown process and then you have to test it and make sure it's analytically valid and you get consistent results and so forth. So that's what we're working on. But our focus on the large pharma strategy enables us to get that funded in the main by them.

Hi, Edward from Singers. So just two questions, if I may. So I think the first one, you might have touched upon this already, but just those large pharma opportunities under discussion, you say they're binary in nature. So I just want to kind of understand, is that more to do with reservations about the CTC technology, or is it more to do with competition in terms of CT DNA or CF DNA?

So what I was trying to refer to is the need to educate the farmer. So when we engage with farmer, there may be people who don't know much about CTCs at all, in which case we need to explain what they are, how they work, etc. Or there may be some people that use the legacy system cell search in maybe 10 years before. and didn't get as good results as they want. So in that case, we need to explain what's different about Parasortix, the fact that it gets all the cancer cells, it doesn't damage them, it gets them easily out, etc. And the sort of education process is really driven by data. So for example, with one large pharma, we are engaging with them specifically in relation to glioblastoma, which is a brain cancer, It's a very major market need because 40% of brain cancer patients don't have a biopsy. They don't have surgery. They don't have biopsy. So we have recruited a number of patients ourselves in-house to get a base data that we can show to that pharma, listen. You may think that you can't get. So CT DNA does not work in glioblastoma. There's just not enough fragments of dead cells at all. So let alone being limited, it doesn't work at all. So there's an expectation that CTCs don't work. to the extent that some of the leading researchers in the world are working on trying to get cells out of the spinal column fluid instead of a simple blood test. So what we've done is some pilot studies ourselves. So we're soon going to be having that data that we can then take to these pharma and say, we told you about this and you've seen it in a publication and here's our data. So that's what we mean by education.

No, that's very helpful. And then just my second question, just more about the assays that have been added to AstraZeneca's many validated assays. I just want to kind of understand the visibility you have in terms of the potential contracts you might win or potentially be asked to kind of use your assays on. And are they primarily going to be sort of earlier stage, so phase one, phase two? Or do you think there's the prospect of even going on to phase three?

I don't think there's much prospect. It's not impossible. I don't think there's much prospect that we would go straight to a phase three. I think there's more likely there'll be a phase two and then a phase three. In terms of the two areas that we've done so far with AstraZeneca is the androgen receptor in prostate. And we know it's publicly available. You can look on their website. They've got multiple prostate cancer drugs being developed, which target androgen receptor. Or even if they don't target androgen receptor, it would still be an important thing to measure as the patients are progressing in their trials. So we know that there's Several different applications there. And in DNA damage responses, it's one of the six key areas of AstraZeneca's investment. There's a whole separate part of their website about that. Again, we're offering them an assay. They cannot get they requested it. paid for it we've developed it they can't get that assay from anybody else so and it makes sense to use it with all of their ddr inhibitor trials but in terms of the specifics of which trial when and how how big we don't we don't have visibility on that and that's not something they would discuss with us until they're ready unfortunately thanks

Can I go back to the commercial question that was asked right at the start? You're not the only company to face headwinds, but I'd like to get a feel for what your impact is. So can we start? Tariffs, are you affected directly or is it your clients who would be affected?

So with tariffs in the US, we're just passing the cost straight on. We have a unique offering. So we can't absorb those costs ourselves. And the customer base seems to accept that's just a consequence of dealing with us. So we just pass the tariffs straight on.

And Ian, the next one is going to be a bit more visibility. Obviously, we've got uncertainty on funding, on basic research. That's a very small individual order from each client, but a large number of clients. Do you have visibility on when that will open up again? Will it be like a floodgate that everything comes through or will it be more staggered? And roughly the timing on that?

No, we don't know what Trump's going to do, I'm afraid, and how the entities are going to respond. What we anticipate is that as they get... And the plan is obviously to slash back the budget significantly on the public research side. So if he follows through with that, they are going to have less funds available for their projects. So that would directly affect us. But we don't have the visibility, obviously, because we don't know whether he will fully throw through on that. And then the other thing is that many of the organizations will try and secure funds from other sources. So some of the ones that are funded from philanthropic resources will not be affected. And you'll see some of the bigger institutions will you know, they'll replace the funds from other areas. The government institutions, they will struggle and they'll have to focus on, you know, priority areas. So it'll be a bit of a mixed bag.

Thanks, Ian. So the next question then is on Big Pharma. Obviously, they're less susceptible to funding crises than the smaller ones. But following on from what Ed was saying about the binary outcomes, do you have any visibility when the likes of AstraZeneca will press the button and say yes?

No. And that's one of the challenges and sort of feedback. What we know is, as we said in the prelims, it's been a slower start. What we can see is some of the uncertainty in the environment and that we just have to reflect that and be more cautious in what we think is going to happen. But if we look at the pipeline of opportunities, there's quite a few big is in there and one of those comes through it starts to give us that visibility and certainty but until we've got that signed up and inked with the customer and we've agreed the work programs and the profiling and all of that there's challenges on assessing the timing there's getting the sale and then there's getting the revenue recognition and so even with the sale your revenue is going to be spread Thank you Ian

Okay, well, that concludes the questions. Thank you very much, everybody, for listening into the webcast. And we look forward to delivering another important year of progress in 2025. Thank you.