Avacta Group Plc

Good afternoon, good morning, ladies and gentlemen, and welcome to the Evato PLC preliminary results investor presentation. Throughout this recorded presentation, investors will be in listen-only mode. Questions are encouraged and can be submitted at any time using the Q&A tab situated on the right-hand corner of your screen. Please simply type in your questions at any time and press send. The company may not be in a position to answer every question it receives during the meeting itself. However, the company will review all questions submitted today and publish responses where it's appropriate to do so. These will be available via your investor meeting company dashboard. Before we begin, we would like to submit the following poll. And if you'd give that your kind attention, I'm sure the company would be most grateful. And I'd now like to hand over to Alistair Smith, CEO. Good morning.

Morning. Thanks very much, Mark. Morning, everyone. Welcome to our results for 2021. Thank you very much for sparing the time to attend. So you've got myself and Tony on the line this morning. I think most of you are familiar with us. I'm Chief Executive, Tony's Chief Financial Officer. We're just going to turn our cameras off actually to make those slides a little bit bigger as we move forward. Just do that. Great. Okay, so a few of you may not be familiar with the company, so a brief little bit of background. The Vactor Group is formed of two divisions, the therapeutics division and the diagnostics division. Therapeutics division, now a clinical stage oncology drug company. We have actually some exciting news that we are co-locating our research team that's been based in Cambridge for a number of years with the clinical development team in London. We'll talk a little bit more about that as we go through the presentation. The Diagnostics Division based in Weatherby in Yorkshire. Okay, Tony, could I hand over to you to go through the results for 2021, please?

Thanks. Good morning, everybody. Just to take you through the results. So these are the results for the year end in December 2021. And just to point out from the offset, these results are based on our continuing operations. As you may well have seen, our animal health division was sold in March 2022. And from a financial reporting point of view, that's treated as a discontinued operation, even though the sale took place after the year end. So the results that you can see in front of you reflect the diagnostics and therapeutics divisions with the revenue for the year just shy of 3 million up from 2.1 the previous year. And as we just walk away down through the profit loss account, you'll see the research costs is the big area of development spend where we've got obviously the clinical and preclinical development costs for the therapeutics business together with all the product development costs of the diagnostics division and in particular the SARS-CoV-2 lateral flow test. the manufacturing costs are reflected there and those costs which is a new cost during 2021 was the costs of the technical transfer and production batches of the lateral flow tests which were made with our partners Mologic and Abingdon Health the cost of those was taken through pause the tests which we will pick up and cover later. Carrying on down the income statement, admin costs have increased during the year as we have scaled up both the diagnostics and therapeutics business with the diagnostics building up its regulatory and quality functions as it's now a fully ISED 13485 IBD company and also the therapeutics is transitioning to a clinical stage. The taxation line there is a credit of 2.8 million and as some of you have heard me talk about previously we reclaim R&D tax credits and that helps us continue with the development costs so that 2.8 million will come back as cash into the business later on this year. The retained loss for the year is just over 26 million compared to 19 million in the prior year and that gives a loss per share of just under attempt move on just in terms of the um segmental analysis in terms of the different businesses to give you a bit of a flavor around the the revenues of these teams so the diagnostics revenue um includes license fees from our partner australia by separations uh there are some custom um after reagent projects there and some revenues from the uh anti-natural flow tests whereas the therapeutics revenues come from our collaborations and milestones with LG Chem, some licensing fees from Point Biopharma and some FTE income from the collaborations that we've got with LG Chem. and AFI Excel, and we'll update you on progress on those later on. The research costs, as you can see, centre primarily around the therapeutics business as the developments there scale up. Just a brief note just to pick up on the animal health side. Obviously that was sold in March. We receive an upfront payment of just shy of £900,000 and then there is contingent deferred consideration of up to a further £1.4 million and that'll be based on the sales of that division as it combines with NextMeans UK business over the coming 12 months. Moving on to the cash flows. The cash flows during 2021 was basically an outflow of 21 million covering all the development activities of the group. There was no fundraising that took place during the course of the year. So from a cash perspective, the cash position at the end of the year was 26 million. moved on from the 48 million that was there at the end of 2020. We have net assets of 41 million and that cash flow there takes us through well into 2023 to continue to develop the programmes that we have and we do appreciate there is a significant amount of discretionary and committed and non-committed spend on the different development projects as we move through those. So there's a good opportunity to manage that cash flow very carefully as we always have done. I will now hand you back over to Alistair to pick up on the therapeutics division.

Thanks very much Tony. So as Tony said we'll focus initially on the The main driver of value in the group, the therapeutics division, and obviously focus on ABA 6000, the precision platform. So to begin with, I will, for those of you not familiar with the precision platform, let me just take a few minutes to introduce it. So the precision technology is a method of targeting therapies to the tumour. ABA 6000, as we'll talk about in a moment, is a targeted, a tumor-targeted chemotherapy. There are other opportunities which we'll mention, but ABA 6000 is a tumor-targeted chemotherapy using the Precision platform. Precision is what's called a substrate. So this is a chemical moiety that is specific to an enzyme called fibroblast activation protein alpha. That enzyme is upregulated in most solid tumors. You see on the right hand side of this slide a range of different solid tumors and the amount of FAP alpha in those tumors. So you can see, for example, at the bottom cancer of unknown primary, sarcoma, salivary, very high levels of FAP in those tumors and so on. So FAP is very specific to tumor tissue and is in much lower concentration in healthy tissues in the body. The key point about the precision chemistry is when a chemotherapy is modified, we'll see in a moment on the next slide, when a chemotherapy is modified using the precision chemistry, it prevents it from entering cells. So that effectively renders it inert because it can't get into cells to kill them. But the precision chemistry, because it's a substrate for FAP, is removed by FAP. And as you see on the right hand side, that will happen predominantly in the solid tumor mass because that's where FAP resides. So precision is a way of rendering a chemotherapy much less cytotoxic because it can't get into cells and then activating that within the tumor mass when it encounters FAP. Now, that gives us an opportunity to play in a very, very large market chemotherapy market. worth around $60 billion in a solid growth rate. And all chemotherapies are limited in their efficacy and therefore their commercial opportunity because of tolerability for patients. So these are effective drugs. but they have significant toxicities and side effects, making them difficult to tolerate. So the precision chemistry allows us to improve that tolerability and open up some huge opportunities, not just with ABA6000, but with a pipeline of other chemotherapies that we can modify. I'll take you through that in a moment. As I mentioned, the precision chemistry can also be used in other ways, and although we won't dip into this today, we can use the precision chemistry in the linker of what's called a drug conjugate. to allow the warhead to be released in the tumor microenvironment. On another occasion, we can talk more about Avactor's TMAC program and the use of the linker in that format. And the final point on this slide, I'm sure you're aware that the precision platform is exclusively licensed to Avactor. from Tufts University Medical School in Boston in the US. So that's the precision platform itself, which can be used to modify chemotherapies. And then if we look at ABA 6000 as an example, specifically, On the left-hand side of this slide, you see doxorubicin circled in blue. So that's the chemical structure of doxorubicin, which is a generic chemotherapy that's been around for many years and first, second, third line for a number of different indications. We'll talk about that a little bit more in a moment too. And they're attached to it, modifying doxorubicin is the precision chemistry circled in red. So that's a small chemical that we attach to doxorubicin to make that in a form ABA6000. Now, when that is in the circulation, it will get into the tumor microenvironment through the circulation. And there it will encounter FAP alpha, fibroblast activation protein alpha, as we talked about, primarily on cells that are called fibroblasts in the stromal tissue. But it is present in other cancer cells, but primarily in the fibroblasts. And when it encounters FAP, FAP will do what it does, which is it will cut the precision chemistry off doxorubicin, releasing active doxorubicin. And as we saw on the previous slide, because the FAP is predominantly in the tumor mass and not in healthy tissue, that release of doxorubicin will be predominantly in the tumor and not in healthy tissue. So through that mechanism, ABA 6000 and other precision drugs are designed to improve the safety and tolerability by reducing the systemic exposure of these powerful drugs. So we'll have the opportunity next week actually to present a lot more of the preclinical data for ABA 6000 and I will take the opportunity to present the poster that is being presented by our team at the American Association of Cancer Research next week in New Orleans I'll take the opportunity to present that in a simplified form for non specialists so that that poster will be available online once it's been presented and I will take the opportunity to to try and talk through that in a way to get the broader audience to understand the data and the conclusions. But just one piece of that preclinical data that I think really illustrates very well why we are so excited about the precision platform and its potential to produce data. safer chemotherapies and really drive shareholder value over the coming years. So what you see in this figure on the left-hand side, so this is a mouse model of cancer. What you see on the left-hand side is the amount of doxorubicin appearing in the heart and the tumor when the mouse is dosed with doxorubicin. So as you would expect, you see exactly the same amount of doxorubicin appear in the tumour and the heart because the animal's being dosed systemically with doxorubicin. And that, of course, is the issue. As we'll see in a moment, doxorubicin has particularly severe cardiotoxicity, hence the focus on the heart tissue. So when the animal's dosed, With doxorubicin, you see effectively the same amount of doxorubicin appear in the heart and in the tumour, and that's the toxicity that we want to avoid. On the right-hand side, the animals are being dosed with AVA6000, and you'll see at the bottom there actually being given six times the dose that the animals are being given on the left, so a higher concentration of AVA6000 than is possible with doxorubicin. And because doxorubicin itself is being released in the tumor, we see a nearly 20 times increase in the amount of doxorubicin in the tumor compared to the heart. And that difference is what we call the therapeutic window or the therapeutic index. And obviously it's dramatically improved in this model using AVA6000. So that's one illustration. As I say, next week, the team will be presenting a lot of preclinical data at the Very prestigious meeting in the US, sort of the key meeting of the year. And I will take an opportunity to go through that with a wider audience next week sometime. Okay, a quick word on doxorubicin. As I mentioned, it is a standard of care for advanced soft tissue sarcoma, second and third line for other cancers. It's generic. It's been around for many years. And as I mentioned, it has very serious dose-limiting toxicities, in particular cardiotoxicity, but also myelosuppression. And despite that, it's a billion-dollar drug, even as a generic drug. So ABA 6000 presents the opportunity to bring a proprietary of actors, proprietary, safer form of doxorubicin into this market. And we've done quite an extensive piece of work with external consultants, global life sciences, to try and understand what that market potentially is. And just in the UK and the US, so not even including the rest of the world, and just looking at three cancer types, advanced soft tissue, sarcoma, breast and ovarian, the peak sales should be around $1.5 billion for that proprietary drug. So it is a significant commercial opportunity on its own. But as I mentioned earlier, one of the really exciting things about the precision platform is that it can be widely applied to a range of other chemotherapies. And of course, the drug conjugates that we spoke about. But just focusing here entirely on chemotherapies, there are numerous other forms of chemotherapy that are appropriate for precision to be used to modify it and improve the safety and tolerability. One that we spoke about earlier in the year is we call it AVA-3996. That's the next most advanced in our pipeline, and that is a precision form of a proteasome inhibitor. The main proteasome inhibitor in the market is a drug called bortezomib or Velcade, which is a taqueda drug that has annual sales of around $1.2 billion. But as I mentioned, as with all chemotherapies, it has significant toxicities that limit its tolerability for patients. And in the case of Velcade, it is only approved in multiple myeloma because of peripheral neuropathy and other side effects. So AVA-3996 is a precision form of a proteasome inhibitor, which is an analogue of Velcade, so very similar to Velcade, but not precisely Velcade. Just to step back, in ABA 6000, you will have seen that ABA 6000 releases doxorubicin, actual doxorubicin. In the case of 3996, it's a very similar analogue to Velcade. We've now selected ABA3996 for preclinical development and that will carry on through this year and we expect to file CTA or IND in the first half of next year and hopefully dosing first patient later in 2023. So, as I said, on the right-hand side, there is a significant future pipeline, and that's not exhaustive by any means. We have made some very early progress with some of the other assets listed there, but Velcade is the precision form of Velcade. AVA3996 is by far and away our most advanced in the preclinical pipeline. So ABA 6000 is in the clinic. As you are aware, we are in the middle of the dose escalation phase, the phase 1A. I'll talk about the objectives, the primary and secondary objectives of that in a moment, so I won't dwell on them here. We are dosing a patient population that is a broad range of different advanced and metastatic cancers. So not specifically choosing any particular cancer type other than FAP positive. So we are in the second cohort. I'll give you a little bit more detail on that in a moment. The first cohort, because of COVID, the back end of last year was a little bit slow, just because of clinical sites having trouble keeping going. uh but we are now as i said in the middle of the second cohort we'll talk about that in a moment so so i um expect we will finish by uh the phase 1a by the end of q2 or possibly creeping into q3 that's how i've illustrated it there just because of those earlier delays but the middle of the year we will see the uh the output of the dose escalation study which i will go through in a moment That will be followed after a review of those data by the Safety Data Monitoring Committee. We will progress into the Phase 1B dose expansion phase, which will focus on two or three particular tumour types with around 20 or so patients in each of those different tumour types. So that we can talk about more later in the year as we head into the Phase 1B. So the progress with the phase 1A dose escalation study, we have up to six clinical trial sites in the UK. St. James is in Leeds, the Royal Marsden in London and the Christie in Manchester are all active and dosing patients. The Beets in Glasgow is now open and screening patients and we expect the Freeman in Newcastle and Weston Park in Sheffield to be open in the second quarter as well and contributing to the dose escalation phase. So the starting dose, as you saw on the previous slide, was 80 milligrams per meter squared of ABA6000, which is delivered just below the normal dose of doxorubicin. It's about 90% of the normal dose of doxorubicin, around 54 milligrams per meter squared. And that first patient was dosed in August last year at the Royal Marsden. Since then, in February, we reported dose escalation. So that follows a review of the data from the first cohort by the Safety Data Monitoring Committee. And we dose escalated by 50%, so 120 milligrams per meter squared. And we're in the middle of that second cohort now. We filed an IND and that was approved by the FDA in November of 2021. And we have two US clinical trial sites that are being initiated now and should contribute to the dose escalation phase in Q2. So just to focus on the objectives of the Phase 1A dose escalation study, so what we will learn as we get into the middle of the year this year. So the primary objectives, of course, are around safety and tolerability. That's the primary objective of Phase 1 study, the Phase 1A study. And to determine what's called the maximum tolerated dose and then the recommended phase two dose or the recommended dose for the phase 1B expansion phase. So those are the two primary objectives for the phase 1A study. But then the secondary objectives are also, well, certainly the first bullet point there is very important. And the study has been designed to be very data rich because we are going to get an opportunity here to see how the precision platform behaves in human for the first time. So the study has been designed to deliver a lot of information, which I've really just summarized here. And that's around what are called the pharmacokinetics. So, effectively, where is the drug and for how long in the plasma, in the urine, in the tumor. And what we'll be analyzing will be the presence of AVA6000, the drug that's delivered to the patient, the presence of the precision leaving group, so the bit that's removed by FAP. and of the active metabolites of ABA 6000, which of course one of them is doxorubicin. That's one of the products of the reaction is doxorubicin. And there are others, several others actually, such as doxorubicinol and so on. And we'll be analysing those in plasma, urine and tumour tissue when the drug is given as a monotherapy as we've described. Now the point here I think is worth making is the information around the tumor tissue as well as the plasma and urine pharmacokinetics because it's very important that we also understand that doxorubicin is being released in the tumor tissue and that we will get from biopsies which are not mandatory in the phase one. But I'm confident we will get that data and be able to say something about the release of doxorubicin as well as the PK of the other components that we just discussed there. In certain tumour types where doxorubicin is an appropriate treatment, we may also get an initial look at anti-tumour activity. Of course, the phase 1b is more designed to do that and the phase 2, but we may get some early initial anti-tumour activity. against some very standard criteria in those cancer types where doxorubicin is an appropriate treatment. We're taking quite a broad range of cancer types, and doxorubicin is specific to certain tumors. So those are the primary and secondary objectives of the study, and we will have that data in the middle of the year, which is a really significant pivotal point for precision and for the company, of course. OK, so to move on to our partner programmes and really focusing on the two key programmes where we are actively involved, Tony mentioned Point Therapeutics, which is a licensing deal. We're not practically involved in that activity with Point. They have a licence to use the precision platform in their own radiopharmaceutical setting. But the two partner programmes where we are very actively involved are with LG Chem and Daeyong through the joint venture we have in South Korea called AFI Excel. So let me just give you a quick run through those. I won't read through all the prehistory, but LG Chem is a multi-target deal. They are focused primarily on what's called a PD-L1 inhibitor, PD-L1 antagonist, which is a checkpoint inhibitor. It is an AFIMA checkpoint inhibitor, an AFIMA PD-L1 inhibitor formed as a bispecific with an AFIMA half-life extension, which we call XT. So this is a true AFIMA-AFIMA bispecific molecule. which last year LG Chem took the decision based on preclinical data to take that asset through into full preclinical development and that triggered a milestone payment to a vector. in autumn of last year. So really, really good progress with LG Chem. You know, now in preclinical development and hopefully heading towards IND filing and the clinic. So successful preclinical development through this year will trigger further development milestones and obviously, hopefully, one of the first, if not the first, into the clinic, as we've said a number of times. So very, very good progress with LG Chem, a great partnership. Dayung and AFI Excel, similarly, actually, really good progress. So the AFI Excel partnership is different. It is about harnessing the AFIMA platform to really enhance the therapeutic benefits of cell and gene therapies. So very briefly, what we have demonstrated with Daeyoung is the ability to get stem cells in this case, to express, to make and secrete immunotherapies. So to be able to produce immunotherapies in the surroundings around the stem cell to really augment the therapeutic benefits of the stem cell. Now, this gives us, through AFI Excel, the joint venture AFI Excel, this gives us access into a very significant cell and gene therapy market, which is growing very, very rapidly. I can't talk about a huge amount of detail, I'm afraid, at this point. Hopefully, there'll be some significant events this calendar year, which will give us an opportunity to talk about these programs in more detail. But just to say that we, AVACTA, has successfully produced and characterized and handed over to AFI Excel the first affirmers against the first two targets of interest. And Affiexcel's team, where obviously the stem cell expertise lies, is currently focused on characterizing in vitro and in vivo the stem cells and the athema molecules to support the next stage in Affiexcel's development. So equally, both of those partnerships are going really well. I'm very pleased with how they're progressing. So I mentioned, well, for us an exciting bit of news, a move into London. So it's a fantastic opportunity for us to co-locate the research team and the clinical development organisation into a single facility in Scalespace in White City in West London. Part of Imperial College's campus gives us an opportunity to mix with a whole bunch of really exciting companies, investors, potential partners. It's a really vibrant environment in West London. Potentially, we could run a an event perhaps around the science to give people an opportunity to see it at first hand sometime in the future. But it's a great environment for us to be in. You see a few of the companies and organisations that are in the space. We have about Same space actually as we had in Cambridge, about 5,000 square feet of lab and office. And we are literally moving right now. So we should have completed that on schedule by the end of April. And yes, a very, very exciting transition for us as we bring the whole company together within one facility. I certainly won't read through the text here on the slide, but just to, I mean, certainly another very important highlight for us during the year, appointments of two very eminent biotech executives to the board, Mark Goldberg and Christina Coughlin. You can read their bios in detail on the website, but a significant addition to the board for us as we move forward as a clinical stage biotech. Okay, so let me move on to the diagnostics division. And I wanted to start by just giving you a little sort of run through of the key trends in the diagnostic market and certainly what drive our decision making. And I think there's three key points that I want to bring out. So the first one is the most important by a long way, which is the um the very strong trend to decentralize testing so by that i mean testing outside of laboratory pathology hospital pathology laboratories have centralized testing so it can include gp clinics and other forms of satellite healthcare providing as well as consumer home testing And within the things that are driving that move are a significant increase in chronic disease, primarily, I'm sorry to say, due to a poor lifestyle, but a significant need to monitor chronic disease, a real desire to do health screening, to get early indications of disease to drive early intervention, which obviously improves outcomes, but also improves the healthcare economics. There's a big consumer push towards general health and well-being monitoring. So that pushes the home testing market. And that's being driven by the big tech companies as well through wearables that provide some of the more physiological information to go alongside actual test results. There's the increasing availability of immunodiagnostic and also molecular, so PCR-like molecular testing platforms to be able to do these types of measurements outside of big laboratories. The lateral flow test is one that's been around for many years and in the immunodiagnostic space. And obviously another big driver is the fact that pretty much everyone in the world now is aware of lateral flow testing and has become very familiar with that. So that has opened up a market and a desire to test for a lot more things. The other two points around digital connectivity have touched on very quickly. So there's an increase in use of AI. These are not things of actually directly involved in But using AI to combine the wearable information with diagnostics to really produce actionable medical intervention. That's a very hot area. And companion diagnostics, which is about identifying patients that will benefit from certain drugs. It's a big focus in oncology because of the cost of the drugs, but it is heavily driven by the pharmaceutical companies who obviously own the drugs. So it's a slightly challenging market. And again, not something we are specifically looking at at the moment. But those are the key drivers, decentralized testing being absolutely fundamental to our thinking going forwards. And we are, I believe, uniquely positioned as a UK diagnostics company because of the AFMA platform, which allows us to develop, as we've seen numerous times in the past, high performance, high quality proprietary tests that give us competitive advantage and obviously therefore drive commercial and shareholder value. So our strategy is to maintain focus on that decent point of care testing as well as in future build the consumer home test market. and to continue that primary focus on developing our own products as well as looking at partnerships. So very straightforward strategy to exploit the AFIMA immunodiagnostic platform. So briefly mention, as Tony did earlier on, one example of an extremely sensitive and excellent performing test, the AFID-X SARS-CoV-2 antigen lateral flow test, As I'm sure you're all aware, we had just achieved with our partners, Medusa 19, the consumer self-testing CE mark in December as the Omicron variant was emerging. And again, this is old ground, but you'll be aware that more than 30 mutations in Omicron compared to Delta. And for information, more than 30 mutations difference between BA1 and BA2, the newly emerging Omicron variant. Now, this challenge of constant mutation, as we've said many times, will be here for a long time, as long as the virus is with us. So we took the decision to close sales in January, as you're aware, because of the reduction in the performance of the test from really good to only satisfactory in our view, and not really good enough to provide the detection of infectious individuals, which is what's needed. We are redeveloping the test to restore that performance and we're doing it in a manner to be as robust as we can to those future variants because it will continue. So we'll perhaps talk about that a little bit more in a moment. The timescale, we've been asked many times about the timescale, and I'm not being evasive at all. The timescale depends on the development process, which depends on us producing a robust and high-performance test. It's difficult to put a precise timeline on that, but it also depends on regulatory requirements. The introduction of the new IVDR regulations in Europe has an impact and so on. You know, when we have a clear timeline so that I can update the market, we will. But I can tell you we are very actively redeveloping that test. We are making good progress, actually, in detecting BA1 and BA2. So as soon as I can give a material update to the market, I will. Now, that broader diagnostics vision, driven by primarily that decentralised testing trend that I talked about, has driven us to focus in four key areas. So infectious disease and infectious respiratory, of which COVID, of course, is one. I'm not going to read through all of these, but infectious disease, uh chronic disease as we as we mentioned a big big increase in chronic disease as well as a big increase in infectious disease globally so these are good market opportunities for decentralized testing and then those two markets around health screening and fitness and well-being driven both both from a healthcare perspective but also a consumer interest perspective so these are the markets that we're focusing on and we are developing products in-house in these areas. We'll talk about that more later in the year, as well as looking at opportunities to partner. So that brings me to the summary. So, I mean, I've said this several times. We've said it in the prelim presentation. It has been a transformational 18 months for Avactor with the move from a preclinical research therapeutics business to a clinical stage biotech and the dosing of first patients with ABA6000, that first precision chemotherapy and the launch of the first ever AFIMA driven in vitro diagnostic product. So looking forwards, you know, therapeutics is without doubt the key value driver for the group and has been. ABA 6000 were in the middle of that phase one, a dose escalation study in the UK. And we'll get US sites on board in Q2. And we fully expect to see the readout in Q3. And as I said earlier on, very pleased with progress and very encouraged by what we're seeing so far. That readout from phase 1a will be pivotal for all the reasons that we've mentioned, pivotal for the precision platform because we'll learn a huge amount about the PK of that in human and therefore pivotal for the group. So really exciting a few months ahead of us. I'm very pleased that we have a a rich pipeline of preclinical precision and AFIMA assets as well as the ABA 6000 clinical development to drive milestones through this year and next year. From a diagnostics perspective, We now have a fully ISO 13485 certified IVD product business, and that is developing IVDs, as I've mentioned, with a focus around decentralized testing as well as redeveloping the antigen test as part of that much broader diagnostics pipeline. As Tony mentioned, we're in a strong balance sheet position, so that's great. And obviously, with the progress in ABA 6000, the potential for partnering and licensed deals, we have opportunities for non-diluted funding as well. But we have a strong balance sheet that takes us well through 2023. Okay, I will leave it there. And Mark, if we can take some questions.

That's brilliant, Alistair. Tony, thank you very much indeed for updating investors this morning. Ladies and gentlemen, please do continue to submit your questions using the Q&A tab situated on the right-hand corner of your screen. Just while I ask Tony to take a few moments to review those questions submitted already, I'd like to remind you that the recording of this presentation, along with a copy of the slides and the published Q&A, can be accessed via your investment company dashboard. Alistair, Tony, as you know, we received quite a considerable amount of questions ahead of today's event, and they did kind of form into different kind of categories or themes, and just given the attendance on today's call, I guess to make best use of the time, you've very kindly given me some of those that do cover a number of those topics. So if I may start with the first question, An actor spoke of the need for biopsies in the last presentation, appreciating that this is a very sensitive topic. Has there been any progress in this regard?

Thank you. Yeah, so we've touched on that a little bit, but I mean, just to sort of point out that we can't sort of answer this fully, i.e. we can't talk about the number of biopsies taken and we can't give a running commentary on the clinical study for obvious ethical reasons. But I think it's worth Just reiterating that point about the importance of the biopsies, because the PK data will tell us about the serum and urine levels of ABA6000, doxorubicin, and the Levin group, but it doesn't tell you about whether doxorubicin is being released in the tumour. So biopsies are not mandatory in phase one, but I'm confident we will obtain some tumour material for analysis. And we've worked with partners It's a UK based on a world leading pathology laboratory in the UK, and we have put in place the validated assays to properly analyze those very precious biopsy samples. So there has been lots of progress, but I can't sort of go into more detail than that. We will be able to, of course, when we talk about the full results from the phase 1a study.

That's great. Thank you very much indeed. A couple of questions, more than a couple, around perhaps the next inflection point. What do you see as the next major shareholder value inflection point?

Yeah, well, I think without doubt it is that point in the middle of the year where we have the full readout from the dose escalation phase and, of course, the full review of that data. by the Safety Data Monitoring Committee. So, you know, a positive readout, which means good safety, good PK data, as well as an indication that Dr. Rubison is being released in the tumor tissue, that that not only adds value to ABA 6000, But opens up a broad pipeline, as we've discussed, and that creates all sorts of opportunity, obviously, for taking ABA 6000 forwards in the clinic, but taking other programs through preclinical development and potentially licensing some of those earlier programs as well. So genuinely exciting. pivotal for precision and for a factor.

That's great. Thank you. Moving on, if I may, to the next question. Can you elaborate on the use of human tissue or cells, the PDX model, in the preclinical mice studies and explain how this makes the preclinical trials much more relevant to the current phase one in human trials?

That's a really good question. And I think it speaks to that whole point about, you know, how translatable our mouse models. Yeah. So, you know, it's just it's just not true to say that, you know, if you get these results in a mouse model, you're going to get them in humans. So that's we never do that. But of course, the PX model, the patient derived xenograft model uses an actual patient tumor or cells from a patient tumor. implanted into the mouse that has a reduced immune system so the tumor cells are not rejected. So those patient derived cells are sort of more diverse, more heterogeneous than sort of, let's say, less realistic models. They've often got a tumor architecture and look from a molecular perspective more like the original tumor. So those cells in the mouse do look more like an actual human patient tumor. So the PDX models are, I think they're deemed to be the best models for translating, certainly in many cases, the data from PDX. from mice to human. But as I say, there's obviously clear differences between rodents and humans, right? So the, you know, for example, the circulating FAP levels in rodent blood, are higher than they are in humans. So there's a very relevant difference straight away. I mean, of course, that works in our favor because it's lower in serum in humans. But we can be guided by the data from those PDX models, which I think, as I said in the presentation, is why we're so excited. This is a very significant improvement in therapeutic index.

Thank you very much indeed. How will a vector determine the maximum tolerated dose in P1A? They go on to say theoretically each dose escalation shows minimal side effects and could get to the maximum lifetime dose in one cycle. How would a maximum tolerated dose be determined?

okay so this is very technical um but you know it's worth answering you know at some level so that the maximum tolerated dose uh is defined as the dose uh the dose just below that at which a third of the patients experience a um a dose limiting toxicity okay so so in other words two-thirds of patients don't a third of the patient do the mtd is defined just below that that level So, as the questioner points out, you know, it may well be that a maximum tolerated dose is not identified due to a lack of dose limiting toxicity. And then the recommended dose for phase 1B, that will be based on a combination of the safety data, the tolerability, the PK data and so on by the clinicians involved. so that it's not as simple as the MTD of ABA6000 being related to DOCS lifetime cumulative dose because ABA6000 is targeted to the tumor. But I think the question also asked about how many cohorts are likely to be needed. And the final number of cohorts and the dose in each cohort, again, will be determined by the clinicians and the Safety Data Monitoring Committee. We expect to go through three or probably four. And that's certainly the timeline that we've described, to go through four cohorts.

Thank you very much indeed. When do you expect the two US sites to join the AVA 6000 clinical trials and start recruiting and dosing their first cohorts?

Okay, so I touched on that in the presentation. So we expect those two sites to become active in Q2. But I think it's an important question because it's important to make clear, and judging by the way the question is asked, it's important to make clear that those US sites will not run in an independent fashion. They're not doing separate study. They're not running independent cohorts. So there could be two patients in the US and one in the UK for particular cohorts. So they are in the same study and the data is combined. So it's not independent and additional in any way.

Thank you very much indeed. If I may turn to the next question, all three LFTs approved for use by the NHS are based on the nucleocapsid antigen. It appears that the spike protein of COVID-19 is very susceptible to mutation. So why doesn't Avactor's LFT target the nucleocapsid antigen rather than the spike protein antigen?

Yeah, good question. So both the nucleocapsid and the spike proteins are susceptible to mutations. But it is true to say that the spike protein, particularly in this virus, looks to be more highly mutated. There are reasons. So there's a clear reason there for saying target the nucleocapsid protein. There are also reasons to target the spike protein because it's a more stable, more soluble, more easily retrieved from clinical samples and so on. But what I will say is that it's clear that we need to produce a robust test that is robust to mutations going forward. So despite the fact that some nucleocapsid tests have had their performance affected by these mutations, Our redevelopment strategy is to look at, I can confirm, is to look at the nucleocapsid target as well as alternative binders to the spike protein with a view of delivering something that is robust going forward, certainly as robust as we can.

That's great. Thank you. Can a factor explain what advantages the precision platform has when compared to antibody drug conduits in targeting the chemotherapeutic agents?

Yeah, so there is some similarity in the approach, given that both the drug conjugate and the precision chemotherapies are trying to target the chemotherapy to the tumour. Antibody drug conjugates are a combination of using an antibody or of course an ephemera, using an antibody or an ephemera linked to the chemotherapy and ADC approaches are totally dependent on standard ADC approaches, are dependent on the target being expressed on the tumor cell, like HER2, for example, 5T4. And when the drug conjugate binds, it's internalized into the cell to let the cytotoxin kill the cell. As an aside, that is what is novel and unique about the TMAC program, that we use the precision chemistry in the linker. So the warhead is released extracellularly and doesn't need internalizing. But to go back to the point, a comparison of precision chemotherapies and ADCs ADCs are complex drugs, right? They're combinations of biologics, aphemers or antibodies with the cytotoxic. And tumors actually evolve over time to reduce the amount of the biomarker, which the ADC is targeting. So it's a really interesting area. It's a very hot area. But FAP is expressed both on tumor cells and in the tumor microenvironment in the fibroblasts and gives us an opportunity to be somewhat tumor agnostic so that you can target high fat expressing tissues. So it's different, but it's similar in many ways.

That's great. Question around funding, really, if I may. What funding options for further phases of the precision platform, both for AVA6000 and other pro drugs, are a factor considering? Will these be in the best interest of shareholders and create minimal dilutions?

Yeah, so we are, the company is very mindful of utilising non-diluted funding routes wherever that is possible. So there's clearly a number of potential funding options that include non-dilutive as well as dilutive. Right now, as we've said very clearly, we have a long cash runway, well through 2023. With good ABA 6000 data in the middle of this year, then that will create obviously huge value across the whole pipeline, the precision pipeline, and gives us an opportunity to think about commercial partnerships and licensing to provide that non-dilutive funding. um you know that that is obviously attractive to the company as well as shareholders so we're completely aligned in that uh in that way now licensing ava 6000 our lead clinical asset is unlikely because we can generate a lot more value for shareholders by taking that further forwards ourselves but really good data from 6000 obviously creates value throughout that whole pipeline and of course licensing the precision platform to let third parties modify their own chemotherapies. So yeah, we're very mindful of using those non-diluted funding routes. That's great. Thank you.

Thank you very much indeed, Alistair. Obviously, we're coming up to the hour and thank you to all the investors that have pre-submitted questions and indeed for all those that have been submitted throughout today's presentation, which of course all may be visible to the company and obviously we'll publish all those responses where it's appropriate to do so and notify you by email when they're ready for your review. Alistair, Tony, I know investor feedback is important to you both and I'll shortly redirect investors to give you their thoughts and expectations. But before doing so, I wondered if I may, Alistair, just ask you for a few closing comments to wrap up with. And then, as I say, I'll redirect investors to give you their thoughts.

Yes, thank you. Yeah, well, really, just to reiterate that the company has gone through a transformational growth period on both sides. Obviously, everyone is disappointed with the emergence of the Omicron variant, the effect that had. But we will soon turn that round. The diagnostic business is now much more advanced than it was and is in a position to deliver a pipeline of products as well as the COVID antigen test. The real value driver, as I said several times, is around the therapeutics and ABA 6000. And we have a very exciting summer ahead of us. So thank you, everyone, for your time. Look forward to catching up again soon.

That's great. Alistair, Tony, thank you once again for updating investors this morning. Ladies and gentlemen, please do not close this session as we'll now automatically redirect you for the opportunity to provide your feedback in order that the company can better understand your views and expectations. This will only take a few moments for you to complete, but I'm sure will be greatly valued by the company. On behalf of the management team of Evactor PLC, we'd like to thank you for attending today's presentation and may I wish you all a very good day.