Good afternoon, ladies and gentlemen. Welcome to the Poolbeg Pharma PLC investor presentation. Throughout today's recorded presentation, investors will be in listen-only mode. Questions are encouraged, they can be submitted at any time using the Q&A tab situated on the right-hand corner of the 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 can review your questions submitted today and will publish those responses where it's appropriate to do so. Before we begin, we'd like to submit the following poll. I'm sure the company would be most grateful for your participation. I'd now like to hand over to the presenting team from Poolbeg, Jeremy, Liam. Good afternoon. Good afternoon, and thank you for that introduction. Good afternoon, everybody, and thank you for joining us for this presentation today. The plan of action is Liam and I will go through a set of slides, probably taking about 25-30 minutes or so to give you background and context to our kind of recent activities, recent news, and obviously future planning. We'll have 10 or 15 minutes or so for Q&A at the end. As stated, if you want to ask questions, please drop them in. We'll start off with the usual legal disclaimer, and then I just want to ground everybody, maybe new attendees, to Poolbeg, who we are, and I think why it's an exciting company to invest in and our plans for the future. We are a clinical-stage biopharmaceutical company with a core focus on transforming the cancer immunotherapy field. We'll talk about that in depth and detail later on with our POLB 001 clinical trial that's upcoming. We're also developing an oral patient-friendly obesity treatment. We're tackling two very large markets with significant unmet medical needs. The investment case in the middle of this slide here, we have a very experienced team with a proven track record of both clinical development and then transactions at the end. As you see, there'll be a trend coming through where we'll be partnering as a very core focus for Poolbeg right now. As mentioned, we've got high-value programs targeting these significant critical unmet needs in the oncology and the metabolic disease settings. As I said, we've teed this up that these programs are attractive for pharma partnering. We've always kind of said from a Poolbeg standpoint, we were capitalized. We want to generate this proof-of-concept clinical data proving that the science is verified and valid, and then partner with pharma who takes it forward from there in the longer and more lengthy clinical trials and ultimately on the market. Obviously, we want to get these drugs into patients at the end of the day. I'd say pharma are always looking to fill their pipeline of products. We want to tee that up with our clinical trials. We've announced our unaltered interim results today. We've got a cash runway into 2027, which then funds these near-term clinical value reflection points in this oncology and obesity setting. I think we're well positioned from a financial standpoint, and as I said, to move forward with our two attractive and exciting programs. As mentioned, partnering is a key focus to Poolbeg. We've had a lot of experience in this space. We generate high-value programs with strong intellectual property. We spend a lot of time generating and filing our intellectual properties, and announced several this year. We've gotten grants in various territories. As I said, running these proof-of-concept clinical trials, this is an ask. It's always an ask from pharma companies when you bring some exciting science to them. These are very busy people, and they're looking for clear and compelling and exciting human data that they can then take to their senior management to get deals and transactions approved. That's exactly what we're doing with our phase II A POLB 001 CRS prevention trial and then the oral GLP-1 study. Again, the high-quality and compelling human data is really what moves the needle for these companies. As I said, partnering then flows and follows on that. That's our strategy. I'd say we're going to detail on these particular clinical trials shortly. This is the pipeline as it stands today. Again, high value is a key takeaway from here. As I said, in some multiple near-term clinical value reflection points, that not only drives shareholder value, we believe, but also drives that interest in partnering. As I said, data is really what moves the needle from these partnering standpoints. We'll spend quite a bit of time tonight, and I'm happy to say Liam will spend quite a bit of time tonight talking about POLB 001. Our p38 MAP kinase inhibitors are already delivered, and we're positioning this as a preventative, as a prophylactic for cancer immunotherapy-induced cytokine release syndrome. As mentioned in the announcement late last week and reiterated this morning, we're commencing phase II here, and we put a lot of pieces in place to achieve this. Importantly and happily, we got FDA orphan drug designation for this back in May, which we've mentioned in the past, and I'll talk about it later on, multiple significant benefits to getting that designation. On the right-hand side, the key milestones here are the trials at the advanced stage of preparation. Those in the industry know that there's a lot of work going on in the background with regards to various regulations, manufacturing formulations, etc. A lot of work going on to get this clinical study up and running. We did, and again, announced last week, we've received or we approved bispecific antibody. We've secured this for the clinical trial. That's at no cost to Poolbeg, which is quite important because these drugs are quite expensive. I think that shows the kind of commitment and interest from pharma that they too want to see this solution for CRS, and they're willing to give us their drug to test POLB 001, as I say, to reduce or eliminate CRS from these studies, from these drugs. The plan then from a timeline is relatively short-term. Phase II A interim data is expected summer of 2023, and that'll give us a good read into the efficacy of the drug. Safety, yes, we'll check as well, but a good read into the efficacy. That then will accelerate the partnering discussions. We've been on oral GLP-1. We mentioned we'll discuss this briefly today, but this is clinical trial preparation as well. We're progressing towards trial commencement. A lot of activities caused this morning around the manufacturing front, etc. We're looking, this is a very short study. Top line proof-of-concept data is expected in the first half of next year. Rapid study that'll be run at the University of Ulster. That's in partnership with partners at Innobio who have this terrific encapsulation technology. On the bottom, we won't discuss today, but we are exploring partnerships around novel drug discovery aspects that we did using two AI collaborations previously around pretty impressive influenza clinical challenge data with a group, Cytoreason, and then RSV with OneTree. It's a potential drug, potential drug targets that we're discussing for potential partnerships, not something we'll drive forward ourselves. That's where Poolbeg is today. They're very excited about POLB 001, which we'll discuss. I just want to talk briefly about the reasons why we're doing this. The potential to make cancer immunotherapy safer and more accessible. We've talked recently about progress that the industry has made for cancer therapies, cancer treatments. We've mentioned on various panels that not too long ago, you had the 50s and 60s, 1950s, 1960s, where they were discovering chemotherapies, and that was like a blunt approach for many, many years. The cancer biologists understanding the disease progression came up with more targeted treatments where they're able to inhibit pathways, for example, that tell the cells to replicate. Again, more recently, now we're moving into the realm where we're using the body's own immune system to go after the tumor. That's where these cancer immunotherapies have been quite impressive when it comes to efficacy data over the last 10 years or so. As I say, we have an issue with regard to these when you're activating the immune system against the tumors. You're getting this cytokine release syndrome as a nasty and unwanted side effect. These are severe and potentially life-threatening. Approximately 70% of patients undergoing CAR-T or bispecific treatments can be affected by this. This puts a lot of strain on the healthcare system. Obviously, on the patient, that goes without saying. Because of that, the treatment is restricted to these specialist cancer centers. We always give the example that somebody rural has to come up to the city to get their cancer treatments, have to stay there for maybe a week or two, highly inconvenient for themselves and the families, but obviously adds burden to the healthcare system as well. Extended hospitalization, high consumption of healthcare resources, that's an issue with cytokine release syndrome. There is an unmet need, and it's been recognized by the industry. They're looking for solutions. Right now, it's more in a reactive setting in that if the CRS develops, they come in with drugs that are trying to quash it, calm down the immune system, calm down that inflammatory response. There's nothing approved for the prevention of it. We believe this POLB 001 can play a role here. I'd say right now they're using drugs like t ocilizumab, which is an antibody against the target called interleukin-6, which they use to kind of block that immune or cytokine response. Your data for prevention is pretty scattered and unimpressive. Now we're looking for something that's oral. As I said, we look at POLB 001 as an oral drug. Patients can take this from home. It doesn't have to be given in a hospital like these IV infusions of antibodies like tocilizumab. As I said, we feel it can selectively prevent excessive inflammation and, importantly, without causing immunosuppression. You're not blunting the immune response. You're just blocking that inflammatory response and ideally blocking that cytokine release syndrome. The drug itself, POLB 001, we have an extensive data set on that. We've demonstrated favorable safety and tolerability. We've got patent coverage out to at least 2043 from filings that we did back in 2023. As mentioned earlier on, I'll talk about later on FDA orphan drug designation, which again makes this a very attractive approach for our pharma partner. That's setting the scene of cancer immunotherapies and CRS and why the industry and the market indeed is looking for a solution here. I'll pass you across to Liam now to dive into the science aspects and our clinical trial and our partners. I'll be back later on to talk more around the market and the strategy. Liam, over to you. Thank you, Jeremy. As Jeremy mentioned, I will speak you through some of the existing data that we have and then also some of our upcoming clinical plans and the trial that we announced just last week. I guess first thing off, you know, we're going to prevent cytokine release syndrome. It's quite important from a development perspective that we're differentiated and, you know, we have a reason to believe that this is going to be very successful in the clinic. POLB 001 is a p38 MAP kinase inhibitor. Just very briefly, what does p38 MAP kinase generally do in the body? It's an inflammatory protein. It's a gatekeeper to inflammatory responses. Generally, it's perceived as a gatekeeper to hyperinflammatory responses, when the body needs to amplify immune responses to have a really potent, quick response. Importantly, what we've seen, not just through our molecule, but with the inhibition of p38 in general, is that we can have a potent decrease in the wide range of pro-inflammatory cytokines without ablating the immune system. What this is doing is preventing the hyperinflammation without preventing the inflammation altogether. This is very important in the use case of cytokine release syndrome because obviously these patients have tumors, have blood cancers, and a lot of those cancers carry risks of things like infections that can really impact not just their quality of life, but actually their outcomes as well. What we importantly see as well is that we can actually inhibit P38, inhibit these hyperinflammatory responses without having any impact on T cell responses, T cells being a core component of the immune system. The hope is with these immunotherapies that you're harnessing the immune system. It's really important for us that we are not actually preventing those effective breakthrough immunotherapies from having their full potential. We also see some evidence that we can potentially enhance tumor clearance with p38 inhibition. Just briefly on the bottom, I have four rows shown, and tocilizumab and dexamethasone are existing treatments for cytokine release syndrome, not used preventively, only reactively. Tocilizumab is only approved for the treatment of CAR-T cell-induced cytokine release syndrome. What you can really see here is that there's a wider range of cytokines inhibited by p38 inhibition compared to these other effects. Steroids notoriously have wide effects, but somewhat unknown in an immune context. They have both inflammatory and anti-inflammatory effects. Tocilizumab is really affecting downstream. It's an IL-6 receptor antagonist. It's very specific. When we go to p38, what we actually see is that there's a whole raft of cytokines that we can prevent from going into this hyperinflammatory state. This is important because cytokine release syndrome is a systemic condition. It involves multiple immune cells within the body. We believe that, you know, having this systemic effect and a broader effect is a reason why we could see superior effects in the clinic. It's very important that we have a novel and differentiated mechanism of action. Let's go to the next slide. Briefly, just to mention some of the preclinical data that we have, and I'm showing some of the important data on this slide. As Jeremy mentioned, the molecule itself has a very extensive non-clinical and preclinical package of pharmacology and safety pharmacology. POLB 001 was initially developed for chronic autoimmune diseases. The safety package supports use in a low morbidity disease, which generally means it has to have a much cleaner profile than something that would be used in the acute condition and potentially something in the setting of oncology where a lot of existing drugs are somewhat harsh compared to other indications. We're going in a really strong position with a molecule with an excellent safety profile. What's been shown here on this slide is actually an animal experiment that we did of cytokine release syndrome. These are quite difficult to do. We need to use humanized mice, and humanized mice essentially have the full human immune system. The mice are bred without a functional immune system. There is a residual immune system that's taken out, and actually human cells are inserted. These really have the full range of the human immune system that we want to look at. This model can also recapitulate cytokine release syndrome when we induce something like LPS challenge or in this case a CD28 challenge. This allows us to investigate POLB 001 in a model really closely aligned to what we're trying to tackle in the clinic, which is really important. On the top is the design. In short, there's a lot of detail there, but we humanize the mice, just meaning we give the human immune system, and then we actually give them a tumor again to mimic what we're trying to do in the clinic. We induce cytokine release syndrome. In this case, we use a CD28 super agonist. What does that mean? It's just a really potent way of activating a lot of immune cells in the body at the same time. On the bottom left, what we can see is actually the blue is background. These mice will have a level of graft versus host disease. It's a technical artifact. Importantly, in the red, you can see that when we introduce CD28, you get this increase in the CRS score. The CD28 is driving cytokine release syndrome. As we introduce POLB 001 in increasing doses, from light blue to dark blue to green, what we see is almost all of the doses we gave are highly effective in mice. We also compared this against an anti-TNF antibody as a really robust comparison. Robust because antibodies in mice will have a half-life of days or weeks. They stay in the system for a long time. A small molecule like POLB 001 that's not designed for animals actually only lasts for a couple of hours. It's quite difficult even to get the exposure in the mice to the same level. Even with all of these technical challenges in the experiment, what we can see is that POLB 001 was as effective as the gold standard prevention in this model. Really enthused by these responses. On the right-hand side, we validated that that is actually part of the prevention of cytokine release syndrome, what we were seeing. IL-6 and TNF alpha are highly responsible for driving cytokine release syndrome. Here we can see that we were able to reduce them in a dose-dependent effect with our drugs. The green being lower than blue in the IL-6, even lower than with the anti-TNF antibody. You will notice on the right-hand side, anti-TNF was lower, but there is a technical artifact that because we're comparing against the anti-TNF antibody, TNF levels will be lower because it's quenched in the body. Really enthused by these results pre-clinically with POLB 001 and a really strong position as we move forward into the clinic. Moving into the clinic, just to recap some of the existing phase I data we have. Here I'm showing the phase 1B LPS human challenge study that we did. There was also a first-in-human trial done. In both studies, the molecule had an excellent safety and tolerability profile. What I'm showing here is the LPS human challenge study and more of the pharmacological effects. Why we think it's going to be effective as we move towards the phase II A in cytokine release syndrome. Again, on the left-hand side, we use LPS, which is a component of the bacterial cell wall. From a science perspective, it's really potent at activating the immune system. It binds to toll-like receptor agonist 4 and drives hyperpotent responses and is a really effective way for us to measure p38 inhibition and the effects of it. What we did was we pre-dosed the volunteers for six days. On the left-hand side, you can see day one, two, three, four, five. They were pre-dosed with POLB 001 twice daily. On day six, we introduced this intravenous dose. There is day four, which is blue there as well. That's because we also did a skin challenge to see how effective the molecule is in preventing tissue inflammation, which is quite important. We're not going to go into that today. In the middle and right-hand side, I'm showing a selection of this data. We presented it more extensively previously, but what we could see is across a range of markers that are quite important in cytokine release syndrome, including IL-8 and TNF not shown here, what we saw was a dose-dependent reduction. What we didn't see was complete ablation, as Jeremy mentioned, which was very important to us. We're not completely knocking out the immune system here. What we're doing is bringing it down to a safe level so we get a normal immune response, not a pathogenic immune response, not an immune response that's going to threaten a patient's life. On the right-hand side, we're showing heart rate. The reason I'm showing heart rate here is because it's one thing to show an effect in cytokines, but what we really want to show is that effect in cytokines can actually have an impact on clinically meaningful variables. Something that's causing a symptom in the clinic, a symptom to patients, and it's going to suggest that these patients will be better off taking 001. Right-hand side, we're showing heart rate. What we can see is in the gray line, which is LPS only, when we give an LPS challenge, they have a massive spike in heart rate, which is expected. As we introduce POLB 001, the green line is the lowest dose, the blue line is the middle dose, and the red line is the top dose. What we see is that the green line brings down heart rate, and the blue and the red almost completely overlap. What this means is that in this model, at least with the timing of the doses, the 70 mg and 150 mg for both are highly effective and probably as effective as we wanted them to be. This gives us great hope that we have the potential to potentially prevent cytokine release syndrome while also preserving key immune system functionality. Just to quickly mention before I go into the trial, we've been quite active in this space, and it's really important to us that we do make sure there's a strong unmet need, that this is something patients and clinicians really need, and we position this molecule correctly. A couple of weeks ago, I was over in Toronto at the International Myeloma Society, really enthused by not just clinicians interested in supporting POLB 001 and really supporting in any way they can so that we can get it through the clinic as quickly as possible and get access to them. From their perspective, myeloma in particular is in an incredible spot at the moment where for some patients they are discussing functional cures. Myeloma is typically considered non-curable, and it's very difficult to get rid of the clinical disease. Actually, they're now questioning whether or not they have functional cures because the overall survival is far exceeding the average age of onset. A lot of patients will have 50% of patients diagnosed with multiple myeloma at the age of 68 or onwards. Some of the emerging data for first-line therapy, so bear in mind in myeloma, there are three, four, or five effective lines of therapy. With first-line therapy, some of the latest results they're seeing is a progression-free survival in the range of potentially 17 years. First-line therapy can be really effective for a lot of people. I think a lot of the interest is changing from all patients to really categorizing those who get multiple myeloma younger or get a high-risk form of disease and how we can treat these differently, and also how we can bring immunotherapies into a front-line setting. To really benefit from the immunotherapies, the hypothesis is that you really want a fit immune system because as cancers progress, it generally breaks down your immune system. It makes it quite difficult to generate an immune response. Giving these immunotherapies to late-stage response refractory treatments is difficult. If you bring it back into front-line when you have a more immunocompetent body, you can actually get much more effect out of the immunotherapies. What they're trying to do at the moment is to broaden access and extend learnings, how they have the academic centers and how to deliver these immunotherapies and broaden access to them. Very challenging. As I mentioned, there are a lot of lines of therapy that are effective, and that means that patient preference plays a massive role in treatment selection. Things like staying close to home, reducing treatment-related toxicities, and staying with existing healthcare teams. One of the ways I always like to think of it is the actual definition of multiple myeloma is when you have symptomatic disease. There is a precursor condition known as smoldering myeloma, which is essentially the same thing, but when you don't have symptoms. These patients will commonly have bone disease, weak bones, a lot of pain. As this goes on, it really is important that you look at quality of life in addition to survival. Now with so many options, patient preference is playing a larger role than ever. Staying with existing healthcare teams who they trust, and also, as I mentioned, reducing those treatment-related toxicities because it's one thing to survive, but this is really about how we get the best for patients. On the bottom, I have here outpatient delivery of certain immunotherapies is not feasible. This is largely done in the U.S., and they're really investigating how to make these treatments more available. It's just so difficult with something like cytokine release syndrome. It can progress so rapidly, and even with massive philanthropic grants, the top centers are struggling. It's really only for the fitter patients, those who have a full-time caregiver that they're able to do it. A lot of major hurdles as they try to do that, even in a resource-rich environment. Being able to migrate this out to environments where they aren't as resource-rich is a massive challenge as we move forward, and it really needs novel solutions. Speaking about solutions, POLB 001 and the trial we're advancing, first-in-patient phase II A trial. Shown on the bottom here, I'll go straight into it. Dr. Emma Searle, a Consultant Hematologist at the Christie NHS Foundation Trust in the U.K. in Manchester. It's one of the largest cancer centers in Europe. It is actually the largest single-site cancer center in Europe. We're really excited to have Emma on board. Not just does she really believe in the molecule and the unmet need, but also she has so much fabulous experience with early-stage trials to really accelerate this trial, design it properly, and get the most out of it. We're using Accelerating Clinical Trials. They're a specialist blood cancer trials organization to support with Emma's leadership. We'll be using all U.K. sites to complete the trial, a handful of sites along with the Christie NHS Foundation Trust. The goal of the trial is we're looking at multiple myeloma patients, as I mentioned, the last trial over at the IMS conference in Toronto. Those patients will be receiving approved bispecific antibody. These bispecific antibodies typically induce cytokine release syndrome in up to 70% of patients. It's a really strong position for us to investigate POLB 001 and its ability to prevent this potentially life-threatening side effect in about 30 patients. It's going to be rapid. Our focus is getting proof-of-concept data out. I'll go into it in some more depth on the subsequent slides. We're really excited as we move forward into this trial. Just a little bit more on Accelerating Clinical Trials, or ACT for short. They are a specialist trials delivery organization dedicated to blood cancers. Work solely in the U.K., and they've been embedded in the UK hematology community for some time. They actually have existing networks in 15 UK hospitals covering a massive number of cancer patients. Really strong position and relationship, not just with the investigators who are going to be on our trial, but also with the wider UK hematology community. They have extensive, as I mentioned, a positive relationship with those leading centers, which is really important for us to be able to recruit this trial rapidly. Equipped to provide registrational standard trials and an ideal profile to complete the topical trial. They're a really good balance of having that network, having the understanding of the molecule, being able to produce high-quality data that's going to be attractive to partners as well. Importantly, they are driven by a mission to improve outcomes for patients with blood cancers. They're a very specialist organization, purely there for blood cancers within the U.K., with a mission to drive outcomes and trials that they really believe in. It's a testament to the unmet need for cytokine release syndrome and the potential for POLB 001, really not just to prevent cytokine release syndrome, but as a net effect to actually broaden access to these immunotherapies and improve patient outcomes across the board. The trial itself, as I mentioned, is in multiple myeloma. It is a phase II A, open label, single arm trial, so no randomization. This means that everybody's going to be given the drug, and there's going to be no blinding. We're going to see data come out really quickly next year. The trial itself, on the left-hand side, I have a schematic here showing how it works. This is an artifact of cytokine release syndrome that bispecific antibodies actually have to be given in two step-up doses, they're called, in myeloma patients. These step-up doses are actually microdosing. If you gave a first dose of a bispecific antibody to a patient, what they will have is uncontrollable, potentially lethal cytokine release syndrome. To avoid this, what they give is a small dose, and then they give a bigger dose of about 3%, then about 30%, and then 100%. This process takes about a week to 10 days to actually dose a patient up to the level they need to get to. By giving these microdoses, they get the body used to it, and it mitigates the risk for cytokine release syndrome. Even with this step-up dosing, they still, as I mentioned, get about 70% of cytokine release syndrome. We're going to be giving POLB 001 twice daily. There's going to be about 30 patients, and we're going to be using an approved bispecific antibody, as Jeremy mentioned. The supply of approved bispecific antibody has been secured at no cost to Poolbeg. Very important to us. We're ready to proceed and pace into this. We have a supply of GMP-grade POLB 001 ready to go. We're in a really strong position. Everything's at an advanced stage of preparation, and we are expecting interim data in the summer of next year. The actual endpoints on the study, as I mentioned, the dosing will be given before the onset or before the administration of the first step-up dose of the bispecific antibody. We're dosing during that high-risk period for CRS, which typically lasts for about two to three days after the first three doses. 99% of cytokine release syndrome will actually happen either between day one and seven there on the slide or eight, nine, ten. After that high-risk period, the risk of CRS actually goes down massively. This is actually a really focused position where we can investigate POLB 001. We'll be able to really quickly get data from this trial after the first 14-28 days. We're going to know if the drug has been effective or not. The key endpoints that we're looking at are obviously the incidence of CRS, the severity of CRS, safety, because we're first in patients. We also want to confirm the safety and pharmacokinetics of the drug. Again, first time going into patients, we'll just confirm that the exposure of the drug itself is sufficient. We're also going to be examining CRS management and tocilizumab usage, again, to get a real idea of how effective our drug is, but also how effective our drug is at preventing the need for additional treatment for these patients. Typically, if they do have CRS, the hospitalization is longer. If they have CRS after the first step-up dose, they can't get the second step-up dose until it's resolved. That hospitalization period really gets pushed on. In nearly all centers, that step-up dosing is actually happening in an inpatient environment. What that means is that the patient has to come in, and they will come in for the full five, seven, eight, nine, ten days. If they have CRS, that kicks that out. This is incredibly challenging. Typically, oncology wards throughout the world are full. They try to reserve beds. Even in this sense where you can plan when the patients will come in, it's still very challenging because a lot of centers will actually have patients even in the emergency room waiting to come up to a bed in the oncology ward. This is really a bottleneck for the patients. The fact that we're able to do a trial potentially where we limit that inpatient duration is going to be really attractive to the hospitals. Again, just emphasizing that this is a trial that's going to be really attractive to investigators and to patients to participate in. Really light touch. We're not trying to cure cancer with this drug. We don't need to follow the patients out until survival. The only period of interest we have is in the first month or so, and the trial will be quite short after that. That's great, Liam. With that, I will pass back to Jeremy. Thank you. Thank you for that overview, Liam. Again, you can hopefully sense the excitement that we have. We're troubled a bit to ready to get going at this in the patients. Again, it's a nice milestone for anybody in your company, but obviously from a Poolbeg standpoint. I want to take a step kind of backwards and just talk about the, again, context here. You know, we talk about bispecifics and CAR-T cells, these engaged T cells to go after the tumor. As I mentioned earlier on, in the last 10 years or so, it really has exploded onto the scene and fantastic efficacy with these kind of side effect issues that we're trying to resolve. Because of their efficacy, their revenue generation is increasing somewhat exponentially. There's a forecast that by 2030, there'll be $120 billion roughly in revenue of these T cell engagers. You can imagine the market we're playing in. I mean, if each one of these has a CRS issue, they're looking for something like POLB 001 to come in. Effective CRS management, you know, we could achieve that. That's, you know, the reason why we're driving forward with this. I mentioned earlier on about receiving orphan drug designation from the U.S. FDA. This was terrific for the company and fantastic, let's say, outcome from the hard work for the team to achieve this. It is kind of, I think, quite impressive validation that the FDA looks at this and sees the unmet need here. The benefits are seven years of U.S. market exclusivity following approval. You get a waiver of new drug application fees, typically in the range of $4 million. When you get this orphan drug designation, earlier access to these special protocol assessments. It's just, you know, speeding your way through the FDA is one way to look at it. Then tax credits for qualified clinical trials. Now we say, like, this is what's attractive to our partners. They see that we have this and, you know, the bispecific antibody supplier, you know, when they saw this news, you know, they kind of got back in touch with us. They're great to see because they can see down the road as a benefit to them or add value to the program. Very excited about that and a reminder of potential first approved preventative therapy for cancer immunotherapy-induced CRS. Now, again, we're not working in a vacuum here. We did a lot of external key opinion leader talks and talked to, you know, 10 or so different myeloma docs globally, U.S., France, U.K.. Talked to her about the unmet need is one thing, but we've done our own kind of in-depth analysis of where we would fit in here. The feedback generally was like this bottleneck we've talked about in the middle here, where, as Liam said, patients are kind of coming in, they're taking up beds. I don't mean that in a bad way. It's like they have to remain in hospitals for a week or two for fear that CRS develops. We're looking at 500,000 patients for diffuse large B-cell lymphoma and multiple myeloma only. That's, again, patient diagnosis estimates in the U.S. and the EU five. With this bottleneck area, not enough patients are getting the life-saving drugs. We think if you remove the CRS, you'll remove this bottleneck. We'd be able to kind of obviously charge for POLB 001. If you could do the analysis of the number of patients versus what you could charge for a drug like this, and there are comparables out there, we're looking at potential $10 billion market. I think that's kind of quite exciting. As I say, getting that proof-of-concept data now in this clinical trial is really what's exciting us. I think Martin Kaiser, we'll hear from Martin shortly in a video, but he sums it up well. Martin's a myeloma specialist at the Royal Marsden Institute. If there was a therapy that was already delivered, a whole lot of the infrastructure requirements fall away. We talk about getting it into the community, getting the drugs into the community setting away from the dedicated cancer trials or clinical units. If that can fall away, it makes life a whole lot better for many, many people. I said POLB 001 has the potential to transform cancer immunotherapy by expanding administration of the cancer immunotherapies themselves from these specialist cancer centers into the community. We're always going to refer, instead of coming down to London, for example, patients can stay in their hometown or their home village or their home cities and get their treatments. I think that we could have a significant impact on the space, on the fields, and on patients here. Obviously, it'll be a sizable, significant market. From that point, I let you, we, Martin Kaiser, as I mentioned, has a few words on a recent panel that we spoke of. That CRS plays into this, for example, because at the moment, it needs such specialized knowledge with the way how it is dealt with at the moment that it is limited to very specialized centers. In some economies like the U.S., for example, the treatment centers have to even apply for a license to be able to give these drugs because of CRS, so that they demonstrate and that they document beforehand that they can deal with it. CRS is a big problem. CRS is a big problem. Yeah. Potentially, it would enable immunotherapy to come into the more sort of local area hospitals as opposed to specialists. For the existing therapies at the moment, yes, that. As I say, Martin is a highly regarded, highly respected myeloma doc. We leave the last word for him. I do want to just kind of mention briefly, and I'm conscious of time, we have kind of run over a little bit. Just on one slide on the oral GLP-1 program that they're moving forward with, getting again another proof-of-concept clinical trial that'll be pretty rapid in generating data. We expect top-line data in the first half of next year. As mentioned earlier on, it's a proprietary delivery technology to encapsulate the GLP-1 peptide, which normally would be digested, so it protects it from the gut and gets it into the site of action. The trial investigator, Professor Carel Le Roux, he'll be running this at the University of Ulster. Just want to make sure that the GLP-1 gets into systemic circulation. Again, a very straightforward analysis of the pharmacokinetics and pharmacodynamics. We will look at glucose tolerance tests. We're looking at 20 obese subjects here, so a very focused clinical trial, but it gets us the data that we need to facilitate partnering. You saw Pfizer did a big deal during the week with Metsera around getting access to GLP-1 programs. There is RYBELSUS, only one orally delivered GLP-1 receptor agonist on the market, and that has its own issues with only about a 1% bioavailability. We believe we can improve on that. Very excited about seeing that moving forward as well. I'll just kind of wrap up and certainly leave a few minutes for questions. Again, reminder, partnering focused, an excellent team. I myself have been in the industry for 20+ years and have gotten more recently an exit back in 2020 with the last company, InfoZone. I know how the process works from deals and collaboration standpoint. As mentioned in our interims today, cash balance of GBP 10 million as of the 30th of June. That pushes us for giving us some runway to 2027. Multiple catalysts from an investor standpoint, this clinical data coming up. As I said, the POLB 001 here, one phase II initiation and interim analysis, and then top-line data, and then the oral GLP-1 as well. Well capitalized to get to these catalyst-rich areas. I'll leave it there. You can take a read on that. That just reiterates. What we'll do now is just transition. I know some questions have been coming in. I can see them on the screen here. We'll get through as many as we can in the next five, six, or seven minutes or so. Again, apologies for running over with the presentation, but I do want to get to some of the questions. Liam, I'll read these out, Liam, and see what I'll assign from here to you. I'll try not to make things too challenging. First question here. During the POLB 001 trial, will any information on progress be released? I think you're on mute there, Liam. Thanks. I'm back. Sorry. Absolutely, it's the short answer. We will keep you guys as updated as we can. As I mentioned, we're in a really advanced state of preparation, and as we have all of the additional, there'll be some additional information on trial design that we'll be excited to announce. The other sites that we're going to use, we'll announce them in time. Also, when we have the trial starting, first patient in, data coming out next year, we intend to give as many updates as we can throughout that process. Stay tuned. Brilliant. Thanks, Liam. Next question. Will the bispecific provider have first mover advantage if the trial progresses successfully? That's a really good question because it gives kind of insight into, I guess, the fact that they have committed drug. We talked earlier on about the value being significant. The clinical trial, as Liam said, is open label. We will see the data first. They'll be involved. For first mover, we've deliberately kept the door open. We didn't want to close the door where we'll just only do a deal with this company and nobody else. We've been doing outreach with all of the large pharmas who have bispecifics or CAR-Ts, just engaging with them, telling them about 001. As I said, the announcement last week will certainly help and accelerate the discussions that we're on firm footing with the phase II A. We've kept the door open. Of course, the fact that they're providing drug, I think, gives strong indications that, number one, they want to resolve their CRS issue that they have. We know, as I said, what they have in their pipeline is other CAR-Ts and bispecifics and drugs where CRS is an issue. First mover is a good way to state this. I mean, they'll have an insight. They're obviously committed. We're working the door open where others could, I guess, essentially come in and overbid, if you want to put it that way. Again, appreciate the question. Next question. If POLB 001 trial is successful, what monetization options are on the table? Company buyout, partner agreement with one pharma, many pharmas, expansion into other diseases, going on. That's, again, that's a great question. We could spend quite a bit of time talking about that. What I will focus on is that, as I mentioned earlier on, about keeping the door open. This could potentially be a license agreement where they could take the drug from us and apply it in a, as I say, a much larger, let's say, phase II or phase III. We'd receive upfronts for the work that we've done, the de-risking that we've done for the program, and then generate downstream milestones and sales royalties on successful development. That's one structure you could do. You're right. They may come in and say, we just want to buy, whether it is the company or whether it is the program. You know, maybe they don't have an interest in GLP-1s as an example. They just want to buy the program, and then you negotiate an agreeable price for that, and maybe some downstream continued value rights, you know, CVRs, some milestones, et cetera. That option's on the table as well. Going it alone, that's a no. We always thought that we'd generate this proof-of-concept data, and then we look to big pharma companies to take it on board and bring it forward because it gets very expensive in these large phase III trials and ultimately getting on the market. Big pharma have that expertise. We acknowledge that. The goal alone would not be. The other disease, a good question. We've had questions before about CRS. We've had questions about sepsis, et cetera. I do think that with pharma companies, when you license a drug, they like to take control of everything. Essentially, it'll be up to them to decide what disease areas to progress at. Again, thank you. That's a terrific question. Appreciate that. Next question. When is the oral GLP-1 trial expected, and what does trial data do? I think we covered that earlier on. There's a lot of work going on right now. I was on a call this morning around the manufacturing of both the encapsulated GLP-1 and the placebo, and then getting all the documentation needed for that. There are studies and assays going on with that. As mentioned, the data in the first half of next year. As mentioned, it's a very straightforward clinical trial. 20 obese subjects, they get a placebo one day, they get the encapsulated drug the next day, and you're going to compare their glucose tolerance test. Very straightforward. We're looking forward to getting that data in hand as well. Question here. What is your opinion on the disappointing share price response to the excellent POLB 001 trial news? I won't say, I don't mean to be glib by telling you, but I think we're working really hard in the background and moving the programs forward, as I mentioned, de-risking the programs. I do think we had a fundraiser earlier this year. Maybe people are taking a bit of profit off the table from that. I still think we're kind of, you know, heads are down. We're fully focused. I mean, I'm a shareholder myself, but I want to see this kind of drive forward. Disappointing is a word, but I think when the markets see what we're doing, when they see the market size, when they see the progress we're making, hopefully there'll be a kind of a turnaround and an acknowledgement of what the team is doing here and the value that we're bringing to de-risking the program, bringing value to shareholders. We're hoping that is acknowledged. I appreciate that. Question. Liam, I'll pass this over to you. How hard? This is tricky. How confident are we that POLB 001 will deliver the POLB 001 results we all hope for? Can we put a% on this? I love that. You're putting it on a spot, but listen, you can give your opinion, Liam. Maybe I'll add it. Yeah, I would love to put a figure on it. Our results today are incredibly promising. You've seen them. All the experiments we do point in the same direction. There's also a lot of positivity going to a pathway which is extremely well researched. Other molecules that might have failed in this or similar areas might have failed for things actually unrelated to how effective they are. It can be things like infections or something else which really isn't tolerable. A lot of people have faith in the P38 pathway. I'll say that. There's a lot of results that we're quite confident on. Really, as we move forward, we'd be very optimistic that this is not just differentiated. It's also building on things that we know are somewhat effective in the clinic, like anakinra and tocilizumab. There are overlaps in the pathways, which is very important for us. We know we're hitting all the right markers as we go into this trial. We know we have good exposure. Look, I guess watch this space. We've a lot of confidence on this side. We're very optimistic as we move forward, but clinical development. Brilliant. Liam, thanks for that. Maybe I just got to sit down here for a while because the next one I'll pass across to you as well. Are there any more preclinical studies that you need to do? No, absolutely not. We're in a really strong position as we move into this from a regulatory perspective and also from, you know, our own pharmacology perspective. We've used some of the best models available for cytokine release syndrome. Nothing else planned before this study. All right. Thank you for that. In order for you, Liam, I'll leave it to you. Why is the trial so short? The trial is so short because we're only focused on that cytokine release syndrome risk period. This is a really well-defined condition. Cytokine release syndrome only came out, you know, about 10, 15 years ago when all these immunotherapies started to get approved. There's a lot of, you know, CD3 engaging bispecific antibodies where not just high rates of cytokine release syndrome, but also very similar, very similar timings, very homogenous disease. Really promising as we move forward for looking at something like a broad label. That also means that it's really well-defined when these patients are going to have cytokine release syndrome. It's going to be at the start of treatment. We can do our study adequately powered all within the first month. We're not trying to cure the treatments here, especially in this phase II A. There's a lot of data out there on our molecule and p38 inhibition that that's all we're focused on. The first couple of weeks of treatment, do we prevent cytokine release syndrome? We don't need to follow them. They might continue to get the bispecific antibody for longer, but the trial will not continue any longer than the first cycle or two. Got it. Let's take a deep breath, Liam. Next one is yours as well. They're actually the next couple of questions. I'll give two more minutes, just, and again, apologies for running over time. We do want to address as many as possible. From Marcus, is this a double-blinded trial? I guess CRS is so significant. Placebo, nocebo effect may not damage the data. It's a phase II trial. We're in a really strong, so short answer, it is not double-blinded. It is not blinded at all. It's open labeled and single armed. We know because we're going into a condition where 70% of patients have it, it's really well-defined. It's going to be quite apparent how quickly these are getting it. Cytokine release syndrome in this setting is really all defined by the timing. If you have a fever within the first day or two after you're given a step-up dose, it's almost certainly cytokine release syndrome. We don't actually have too many concerns. If the drug is effective, it's going to be apparent in this trial. We don't expect a placebo effect to be preventing cytokine release syndrome. Yeah, great. I'll take the next one. Peter N, thank you. Is the cancer drugs you're using FDA or EMA approved? The short answer to that is yes. This is an approved bispecific antibody on the market for multiple myeloma. We'll be talking further about that. I think it's important. It's very difficult to do clinical trials where two unapproved drugs, obviously, POLB 001, is unapproved for now. We're trying to prove the validity of moving it through the clinic. Yes, the bispecific is already approved and on the market in both. Let's go with the last question here. Was it how many sites will be involved in the trial? Short answer is it's not going to be a lot. It's a handful of sites. The advantage of using ACT is that they are incredibly well set up in the U.K. already. They're already networking to the biggest sites. We know what sites are going to be using the bispecific antibody we're doing. That means that we can do this in a relatively small number led by the Christie, which is, again, the biggest, can't stress that, the biggest single site cancer center in Europe. We really are able to do this without expanding out to 20, 30 sites. It's going to be small. We will share the sites in due time. Brilliant. Listen, let's call it an hour. A few more questions. We can address those offline, perhaps. Really greatly appreciate everyone's time. It's, you know, Poolbeg, as we've been through just the last, you know, 40-50 minutes or so, we have nice momentum now. As I say, we have funding to take us through to our clinical milestones we spoke to into 2027. Very excited about to get this trial going. We talk about pieces in place, similarly with the oral GLP-1. There's a lot of, as I say, data points, you know, with these clinical milestones in the very near future. Team is working very hard to get us there and achieve that. Again, to the point, you're hoping that the SharePoint reacts to this thing. I think we're on a nice track. We've got a very good mission. As I say, we're trying to, you know, change cancer immunotherapy treatment, get it away from these dedicated cancer clinics into the community. It's a worthwhile venture. We're, you know, very proud to be doing it. As I say, looking forward to benefiting patients in the future and shareholders as well. Thank you all for your time. We look forward to giving you future updates. That's great, Jeremy, Liam. Thank you once again for updating investors. If I could please ask investors not to close this session, we're going to automatically redirect you for the opportunity to provide your feedback in order that the company can better understand your views and expectations. Take a couple of moments to complete, but I'm sure it'll be greatly valued by the company. On behalf of the management team of Poolbeg Pharma PLC, we'd like to thank you for attending today's presentation.