Poolbeg Pharma PLC

Good afternoon and welcome to the Paul Begg Pharma PLC full year results investor presentation. Perhaps recording meeting investors will be in listen only mode. Questions are encouraged. You can be submitted at any time by the Q&A tab situated on the right hand corner of your screen to simply type in your question and press send. The company may not be in a position to answer every question received during the meeting itself. However, the company can review all questions submitted and publish responses where appropriate to do so. Before we begin, we'd like to submit the following poll. I'd now like to hand you over to Jeremy Skillington, CEO. Good afternoon, sir.

Good afternoon, and thank you for the introduction. I appreciate everybody joining us this late afternoon. Finally, a bit of a sunny Dublin. It's, you know, the bleak winter is over, and we're delighted here to be able to present on the back of our full year results announced this morning, a company update, a company presentation, and let you know where we are with, particularly, POD001, so again, appreciate you joining us this evening. And I'll be sharing presentation duties tonight with Liam Trimble, our principal scientist, who will talk more of the policy or zero-one clinical trial attributes. So just to give a setting, just a grounding, a reminder, Poolveg, we're a clinical stage company developing POG-001 that we believe has the potential to transform the lives of cancer patients by delivering these cancer immunotherapies, in particular, safely and locally. There's a lot of issues around cytokine release syndrome associated with cancer immunotherapies, and we believe we have a solution for that. We'll talk a little bit more about the scientific and medical rationale for that later on. We're also developing an oral patient-friendly obesity treatment, which we'll touch upon later on. There's an oral GLP-1, again, very exciting space to be in. We are an AIM-listed company, listed in London, and we believe we've got a strong investment case. We've got a terrific team here behind us, both on the clinical business developments, which will be critical, and I talk a lot about that, and, of course, on the corporate and finance side as well. The clinical stage programs we're developing, getting into the clinic, these are three-year large unmet medical needs and large growing markets. And we've done an in-depth analysis, particularly on POG001, again, we'll touch upon later on. So very excited to get these moving forward. We have financial runway into 2027. So we've got several key clinical infection points coming up. So we're funded through these clinical infection points and into 2027. And that gives us scope then for partnering for collaboration and licensing discussions. So, again, we have had many discussions with potential partners over the last several months. Again, I'll touch upon that later on. So, there's a strong interest in what we're doing. So, strong potential to secure partnerships. Of course, what comes with that is, you know, financial revenue, and we'll touch upon that later on. So, right now, we're certainly in clinical development execution modes, particularly with POG001. But over the last six, nine, 12 months, we've been gearing up on the partnering aspects, talking to a lot of big pharma companies, mid-sized pharma companies, and again, pitching and promoting PoolBank. We've got high-value programs with strong IP. Those of you who have kind of followed PoolBank have seen the ORNS is talking about IP grants and very important in this industry. The proof of concept clinical trials we touched upon are ready to be done. We'll touch upon the timing of that later on. At the end, what we've built thus far with regard to the programs, we've got very high quality, compelling human data in the POG001 setting. Again, first of all, that we will cover. So again, our discussion with partners have gone exceptionally well. They're very keen, obviously. They've seen the value reflection points. And the de-risking episode will be the clinical data that we'll read out in the summer of this year. A summary of what we announced this morning in our annual results. So we believe 2025 was a transformative year for Kuhnbeck. We really got ourselves kind of focused and driven and aligned with not just the market, but the clinical community as well, the cytokine release syndrome community in the cancer immunotherapy space. We finished the year with 7.7 million sterling in cash. Again, a healthy cash position. That allows us as mentioned, to execute on our clinical development programs. The first bullet here, we have the topical trial is fully prepared. And with that, that's the POG001 CRS prevention trial. We've appointed ACT as the clinical trial executioner, the CRO that will run the trial. We've had fantastic discussions with Johnson & Johnson. And they have agreed to supply us with their approved bispecific antibody teclistamab. And they've given that to us at no cost because, obviously, they're keen to see the reduction in cytokine release syndrome, CRS, with teclistamab. And we've enrolled now. We've lined up six UK cancer centers to be part of this clinical trial. And we've finished the protocol. And we've gotten MHRA approval, which is very important to allow us to start dosing patients. Importantly, too, in 2025, we've got orphan drug designation from the U.S. FDA. So, again, they recognize the scientific validity of what we are doing, what we are trying and reducing CRS. It is linked to patients who will receive these T-saline gators, and these are wonder drugs that are now demonstrating cures in these blood cancer patients, such as multiple myeloma. So, again, they're very good to get that. There's a lot of additional bonuses that comes with that. We'll touch upon that later on. But certainly from a partnering standpoint, that actually adds a lot of value to the program when it comes to talking to big pharma companies. So intellectual property is very important for this industry. It protects the programs as we get to the market. It doesn't allow any competitors to invade our space. We did get multiple patents granted last year. Many of you know in the hypercytic anemia or the severe influenza space, we've been progressing down those roads for many years. But importantly, we got our first patent grant earlier this year in Australia when it comes to the cancer unit therapy and CRS aspects. So very happy with that. And again, that helps bolster the discussions with pharma companies when they know that the program is protected. We also generated last year positive in vivo data, again, demonstrating that we can impact cytokine release syndrome in an in vivo model. Liam will talk later on about a very exciting program we have in collaboration with Johnson & Johnson with the University of Manchester. That's the broader research into the immunology around cytokine release syndrome. And then lastly, making progress on our Oral GLP-1 program, which is now expected to start in the second half of this year. used to revise the manufacturing lead time. I will highlight that last year we were again very utilized to fundraise 4.865 million from the market, tough conditions in the market, but I think the investors saw the potential of what Poolveg is doing, what we can bring to the market. And speaking of this market, we've done some independent analysis where we see that preventing CRS in these cancer immunotherapies is a markup of over 10 billion. And we'll talk about the details around that later on. When it comes to 2026, this year, again, we are at full pace right now. It's a full steam ahead situation. As I said, the first four months or so of this year has been, again, very productive from a pool-based standpoint. I mentioned, again, the patent grant, and again, that's in the cancer immunotherapy space, which, again, adds validity to the program that we're doing. And again, we're hopeful that there will be many other opportunities to announce patent grants in other territories as we're going forward. We have a wide patent application in various territories, and they're moving through the process. It can be kind of a long process, but I think we're encouraged by the responses we're receiving from the various PTO organizations and the EPA organizations going through. Again, exciting this year, we've got our LPS challenge study. This is our phase 1B study that, again, was a very successful study run in the Netherlands. We were able to get peer-reviewed data published in that. And, again, this peer-reviewed is important because if people looked at the data, looked at the paper itself, and they saw a worthy publication, we've gotten some very good feedback from that. And that springboards us then. into the CRS prevention study we're talking about. When we see prevention of that inflammatory response in the LVS challenge, we're hopeful that we'll see the similar prevention of the inflammatory response when it comes to cytokine release syndrome that's caused by these cancer immunotherapies. We were very excited. We had several discussions last year. with Dr. Adrian Kilcoyne. He's an expert in the cytokine release syndrome space. He's had many, many interactions with the US FDA around developing clinical trial programs around CRS. He came on board to join our scientific advisory board and is now a very active member of our development team when it comes to planning what the future holds for CRS clinical trials. I mentioned we got MHRA approvals this year as well. Very exciting. Again, it's a rigorous process where they take and review all of our data, clinical and preclinical. As I say, it's a very high bar for any drug to get into human-tensible trials. So the MHRA gave us that approval in the past few weeks. Again, we've announced that the ORNS. And that gives us the green light to progress and move into the clinical studies that Liam will talk about. Again, we want to make sure, when we're talking to partners, We want to make sure that they're aware that this is a significant market opportunity. So to achieve that end, we've had independent analysis done where we look at the market, the cytokine release syndrome, the incidence that occurs in the various bispecific antibodies in CAR T-cell therapies, these T-cell engagers, and the impact it has on the healthcare system, the impact it has on patients, what it costs for the healthcare systems. So again, we were able to do an in-depth analysis looking at, it's a multi-billion dollar peak. US sales potential standalone. So we spoke to three different payers talking about CRS and our program, and they were very enthused that this is a drug that they would happily reimburse if and when it gets onto the market. Because they see CRS as a cost trade to them as an insurance company. So they'd like to get rid of that. And as you know, we're talking about prevention of CRS. So I think it's a very important goal, a very important goal that we want to achieve here. And it was very well received by these insurance payers, both in, you know, Medicare as well and Medicaid. Again, momentum and partnering has accelerated as we get closer to clinic. It's becoming more kind of apparent what we have here is a very exciting program. As I mentioned before, the large pharma companies and midsize companies that maybe are in the more cancer supportive care area specifically. So they're all very excited to wait and see what this clinical data holds as it reads out. And as I said, we've got multiple upcoming milestones in the near future. So again, I talk about momentum, I talk about running at full speed. So as I say, the Apollo 001, the trial site initiation business have been scheduled. So these are the six sites that are gonna run this trial in the UK. It's going to be led by Dr. Emma Searle at Christie in Manchester, and she's brought some of her hematology colleagues on board to be part of this clinical trial. So I'm very excited to get that moving. As I say, the next step then is patient recruitment and dosing. So basically getting the patients on board, these relapsed refractory multiple myeloma patients, get them on board and get them dosed and get the clinical trial up and running. But we always comment that like 80, 90% of the work is done in advance of dosing patients. So we've come down the road quite a long way. So we're very excited to be at this stage right now. So again, we're looking to have this interim data, the POS-001 CRS prevention data in this summer. So again, it's linked to the patient enrollment. These are very short clinical trials they must speak to. So we should have data relatively rapidly out here. And then the second half of the year, we're looking to commence our ORS GLP-1 clinical trial. I'll talk a little bit about that later on. So fantastic, exciting time for the company. Again, very productive 2025, very productive first four months of 2026. So we're excited to be progressing this forward. Again, generating that key data, which would be the value inflection point. It would be de-risking the program and then transactions and collaborations, license agreements will follow from there. So very excited to be in this space. And again, thank you for attending this evening. Liam will present on the POG001 program. I'll return in the end and talk about the market opportunity and the Oral GLP-1 program, and then we will open up the floor for questions. So again, thanks for your time right now. Liam, over to you.

Brilliant. Cheers, Jeremy. So, I'm going to do a brief introduction to OLD001. But before we jump into the acid itself, I want to give a little bit of context of where the field has come. So obviously, over the last number of decades, a massive amount of progress has been made for cancers. It's not been symmetrical. Some cancers have had significantly more progress than others. But if we look at something like multiple myeloma, it's really been a poster child for where significant progress has been seen. So for somebody diagnosed 23 years ago, 2003, 5 years survival, 10 years survival, really wasn't that great. 30% 5 years, 10 years about 20%. And that's because the treatment options really weren't that effective. A lot of these you might be a little bit familiar with, thalidomide, chemotherapy, corticosteroids. they didn't do a massive amount for all patients. Fast forward 20 years and the progress has been exponential. If you're diagnosed now, five-year survival rates well over 80% are estimated, 10 years, well over 60. And I say estimated because the progress is so quick that the pace of clinical trials is faster than the survival data we have from those clinical trials. So at the moment, in multiple myeloma, we've obviously had immunotherapies be approved in the last number of years, so CAR T-cell therapies, bispecific antibodies, but also a number of other therapies like the anti- antibody drug conjugates, proteasome inhibitors. It's quite common now for multiple myeloma patients to actually get quadruplet therapies as first line or even quintuplet now because the therapies are so effective. And a lot of the projections, so this is a disease with a median, so 50% of people get it at age 69 or older. And some of these frontline therapies have median progression-free survival projected to be up around 15 years. So really in myeloma, you're at a position where people are discussing functional cures where really patients will pass away from old age rather than their disease and that's what we're ultimately trying to achieve for all cancers. What's important about this is that when we get to this stage where multiple effective options exist, patient preference has a significant impact on market uptake of the drug. Patients don't always go for the drug with the best overall survival. They also consider things like time at home and treatment time, having to travel to hospitals. Some of the tolerability issues can be quite significant for these drugs. The immunotherapies, for instance, have a lot of severe infections that can happen for years afterwards. So they all have a very meaningful impact on what what drugs patients actually decide to take. So for these CAR T-cell therapies and bisodific antibodies, they really are revolutionary for the CAR T-cell therapies that are potentially cured up in some patients. And it's really making sure that they are accessible to all patients. If I zoom in on the bispecific antibodies, they are a breakthrough immunotherapy as well, and they're extended into early lines of therapy, as I'll show you on some of the later slides. At the moment, they have to give microcephalic doses, and it's quite common for patients to be hospitalized for five to 10 days just for these initial doses because of the risk of CRS. So they have a significant amount of time in hospital just to get onto these therapies. And then obviously they have downstream infection risks as well. A lot of these therapies as well are restricted to specialist cancer centres who have the expertise and the tools to manage these patients. It depends on what country you're coming from, but in some countries, this is a very significant obstacle to accessing these therapies. Particularly in the US, people talk about things called treatment deserts. It's where patients can live hundreds of kilometres and miles from their nearest hospital who can administer these therapies and really is a significant issue for a lot of late-stage patients. So CRS, as I mentioned, is a major barrier for some of these immunotherapies to become more widely available, with over 70% of some patients being affected on the immunotherapies. And hospitals say it's due to the risk of CRS, may negatively affect the uptake of these therapies themselves. Next slide. Just zooming in on that for a few seconds. So on the left-hand side of this slide as well, we've shown a simple diagram that to have these therapies and have 001, Pulse 001 could change the treatment paradigm. So the current standard of care on the left here is typically a patient will come into hospital. they will get their immunotherapy and the immunotherapy will actually activate their immune system. And what this induces is cytokine release syndrome. And the risk of cytokine release syndrome or indeed CRS after the onset can result in significant hospitalization for these patients. So it can persist for days to weeks. And in severe cases, it can mean that the patients have to discontinue the immunotherapy. So they have to opt for something else. And obviously, they lose time between these different choices. So it's really important that when patients do opt to go into a therapy that they can continue with it. If we bring in 001, potentially, we have something where they can take orally before they have the immunotherapy. They come into the hospital, they are administered it, and rather than the immunotherapy causing activation of the immune system, we still allow activation of the immune system, but it doesn't cause cytokine release syndrome. And if we're able to avoid cytokine release syndrome, then we can potentially prevent this hospitalization and make this step onto the treatments a lot more manageable and feasible for the patients themselves and for the healthcare system to have to deliver it. So just zooming in on POL001 a little bit deeper. So it's a P38 MAP kinase inhibitor. What this means is that it selectively prevents excessive inflammation without immunosuppression. So compared to some other drugs that completely block a pathway, actually P38 is kind of like a master inflammation switch where if you activate P38, you can get global expression of a lot of pro-inflammatory cytokines, which are things that cause CRS. If you've done a p38, actually the production of these falls 80 to 90%. So the drug itself is an oral agent, again, particularly important where we've positioned this as a prophylaxis that really needs to be easy for the patients and the hospitals to administrate. And we have a strong patent portfolio with potential coverage out to at least 2044. So we do have a strong preclinical and clinical data package to date. So favorable safety and tolerability profile, which again, we think is really important as we move into this indication. And we have potential inhibition of IL-6, TNF, and other key inflammatory markers. IL-6 and TNF we mentioned because we know these are our main drivers, our significant drivers, the cytokine release syndrome itself. So, as well, Jeremy will go into later in the presentation that there is very significant market opportunity behind this drug. So, over a $10 billion market opportunity. There isn't anything approved in the preventative setting. And there's a growing number of these drugs that induce CRS, and they're going into earlier lines of therapy. So this problem is only becoming much, much more significant for hospitals across the world. So at the moment, these bispecific antibodies will only be delivered in specialist cancer centers until there's a way to make them safer and easier to deliver. And Paul could make that treatment safe enough to extend bispecifics to a much wider treatment population, just down the bottom of this slide. So we have engaged a lot of key opinion leaders on this, who also believes in the program, and that's Carrick Morgan from the US. Just to show you some of the data that we've presented before. So the last clinical trial that POLV001 was in was an LPS human challenge trial. So this is essentially where you use a pro-inflammatory stimulus, LPS. It's a component of the bacterial cell wall that induces a mild inflammatory response in patients. So we can give this to healthy volunteers. stimulates the immune system very similar to the way the immunotherapy would, and they get something that approximates cytokine release syndrome. So it's an incredibly strong model for us to test the efficacy of POLB001 in. What we also saw in that trial was that POLB actually had an excellent safety and tolerability profile, as we expected. We were able to confirm potent target inhibition, that's a P38 MAP kinase. And we had a clear dose-response relationship observed, which is really important from the drug development perspective. And then we also, from a CRF perspective, had a major reduction of key inflammatory cytokines. On this slide, we're showing IL-6 and IL-8. So just briefly, this LPS challenge trial was placebo-controlled and had three different doses of LPS. PALD001. So the grey line as indicated underneath is the placebo and the green line is 30 mg of PALD001 given twice daily. The blue line again twice daily 70 mg and the red line is the highest dose of 150 mg PALD001 given twice daily. And what we can see in the graph is that actually if you just get placebo with the LPS challenge you see this spike of IL-6 and as well on the right hand side IL-8 But actually, as we introduce increasing concentrations of POV001, we see a suppression of these increases, which is exactly what we hypothesise it will do in cytokine release syndrome. So the lowest dose produces a small decrease, but the two upper doses, actually, you can see they almost overlap, and this is probably the maximal inhibition through D38, where the inhibition is in the region of 85% to 95%, which is really... promising as we move forward into further trials. So we have the potential to effectively prevent cytokine release syndrome while preserving key immune system functionality. I think that's a key element that we always have from clinicians in that a lot of the existing drugs and the completely blocked pathway, they have their downsides. They often induce cytopenias or other adverse events, which really isn't preferable in an indication like this. So, as Jeremy mentioned, we are really excited at the moment. We recently announced that we have all the approvals in place to start dosing patients, and the trial is moving forward at speed. So, POLS001 First in Patient Topical Trial, it's been conducted in the UK. So, it's a trial of prevention of immunocytokine adverse events in myeloma It's been led by Dr. Anna Searle, who's a leading haematologist based in the Christie Hospital in Manchester. It's been run by Accelerating Clinical Trials. Again, we've previously spoken about this to the markets, that this is a specialist blood cancer organisation who are equipped to run trials in the UK in these clinical trial centres that we're tapping into to recruit these patients. It's a really strong team who know the sites, who know the investigators, who are equipped to really accelerate this trial the way we need to. And the objective of the trial is to investigate the safety of PULSERA-01 and also the efficacy, in particular its ability to reduce the incidence of CRS in patients receiving or approved by specific antibody teclistamab, teclistamab being the immunotherapy that induces cytokine release syndrome. So we'll have approximately 30 patients, and we will be recruiting a patient population of relapsed refractory multiple myeloma patients receiving this antibody. So we are really excited. All of the leading sites in the UK are really participating on this trial. So it's being led by Dr. Emma Searle, as I mentioned, at the Christie. But also we have UCH, we have the Royal Marsden, Birmingham, NHS North Midlands, Wells Stoke and Edinburgh. So we have an exceptionally strong team that we're really optimistic that we can complete this trial quickly. Just a little bit more detail about the actual trial itself. So this is the design of the trial. On the top left, this schematic is showing the trial design. So I mentioned with the bispecific antibodies earlier in the presentation that they get things called step-up or microdoses. So if you were to give a full dose of these bispecific antibodies, what would happen is you'd activate your T cells, you'd get other immune cells activated, you'd get overwhelming cytokine release syndrome, which could potentially kill patients. The only way at the moment to deliver them safely is to give these micro doses. And the micro doses are there to give the body a small exposure to cytokines. And the body needs to get used to seeing these cytokines without inducing severe CRS. And once the body has seen the cytokines once or twice, actually then they can go forward with normal dosing. But these step-up doses are critical purely to mitigate the risk of cytokine release syndrome. These typically happen over a five- to eight-day period. During this period, patients are typically hospitalised, depending on the cancer centre that they're in. So, what we're trying to do in the trial is we are going to pre-dose POL001 for prevention from before that first step-up dose until after the first dose. So, here in the schematic, that would be indicated on day 147. So we'd be dosing, and actually 96% to 100% of all the cytokine release syndrome happens in that period. And that's the period that's really hard for clinicians to actually manage in these patients at the moment, and is mandating the hospitalisation. So twice daily oral dosing with POD001. It's a single-arm trial, meaning no placebo, but we're really trying to get the evidence of efficacy as quickly as possible, so we want to give everybody our drug. 30 patients, as I mentioned. Ticlizumab, really promisingly, is being provided by J&J. and it's an open-label trial and that all the patients know that they're getting POD001. So we're really excited that we have fantastic investigators. We have the collaboration with J&J, and we have the right team with ACT to really deliver this trial quickly. The protocol has been finalised. All the regulatory approvals are in place, and site initiation deals with their schedules, and patient recruitment and dosing commence shortly, and we hope to be able to give further updates as we go. The key endpoints that I mentioned, incidence of CRS, severity of CRS, confirmation of the safety and pharmacokinetics. That's more just to make sure that the drug that I mentioned is exposed to patients at the right level. And then obviously CRS management and hospitalised and out of usage. CRS management, what we mean is the duration of hospitalisation. So everything to do with the current challenges of managing CRS to be managed and measured in this trial. We have a great team of investigators. We have J&J. That's because there is a massive amount of excitement about this programme. If we can find a drug that really solves the CRS problem, I think a lot of people realise the potential of it. So there's also been a 3.4 million sterling grant to the University of Manchester and the Christie. The programme is called Rise. So Rise is about reducing immune stress from excessive cytokine release with advanced therapies. And it's been led by the University of Manchester. The NHS Christie Trust, where we're the lead side on the top of the file, is the clinical lead. We are the lead business partner because we are experts in cytokine release syndrome at this stage. And J&J are an industry partner providing cyclistamide for it as well. So it's been led by a fantastic cell therapist who delivers solid cancer cell therapies to patients. Dr Jonathan Lim, he's a clinical senior lecturer and honorary consultant medical oncologist. at the Christie and the University of Manchester so we really have a multi-disciplinary team and the whole idea of this grant is actually to research things of this is an on-target effect of immunotherapy so there's nothing surprising that these immunotherapies induce cytokine release syndrome it's predictable we know the mechanism we know the triggers we know how to potentially prevent it and but that's a great opportunity to learn more to really research this in the clinic so PULB-001 is going to be a key element of the overall research grant for preclinical and clinical, but the topical trial itself will be a central focus of it. So we'll be generating additional clinical evidence as part of this on CRS from bispecific antibodies and CAR T-cell therapies because, as Jeremy will have mentioned before, there is a major commercial opportunity for the prevention of CRS related to CAR T-cell therapies as well, not just bispecific antibodies. significant recognition of the unmet need in CRS and it's something that we're really excited for and we do expect if there's positive results in this trial that the interest in the program is only going to grow and so we're really excited moving forward and with that I will hand back to Jeremy.