Poolbeg Pharma (LSE:POLB) — Company Presentation

0:04 Good afternoon, and welcome to the POLBEG PHARMA PLC Company presentation. Throughout this recorded presentation, investors will be in listen only mode. Questions are encouraged and they can be submitted at any time using the Q and A tab situated on the right hand corner of your screen. Simply type in your questions 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 today on published responses, which is appropriate to do so. Before we begin, I would like to submit the following poll. And I would now like to hand you

0:35 over to Co Founder, Executive Chairman, Carl Friel. Good afternoon to you. Good afternoon. Thank you very much. I'd like to thank everybody for joining our call this evening. I see we've got nearly 200 people online, which is well, fabulous turnout. What we want to tell you tonight is about two hugely excited trials that we're kicking off momentarily over the summer, our GLP one obesity trial, and really importantly, our one oncology treatment trial, which is utterly transformational for us. Earlier today, just to let you know, in case you didn't see, we did complete our oversubscribed fundraise of over 4.8, almost 4,900,000. And that will fully fund those trials and fully fund the company right in the 2027.

1:24 I personally invested a 100,000 in that placing. That's on top of 100,000 I invested last year. And at the IPO, I also spent over £500,000 starting at full IPO price. I know the price is not where we want it, but I've now £700,000 real personal cash invested in POLBEG. Therefore, I think my goals are pretty clearly aligned with all of you shareholders. And I'm very, very excited and thrilled to be in the position POLBEG is where it is today with this treatment that is potentially transform cancer treatments. On that note, we are in discussions. Jeremy and Lame is gonna bring you to everything now, which is very high level. So we're in discussions with two of the top 10 pharma companies, we're very confident that we they will supply, and when that happens with a non site contract, bispecific trials for the zero zero one trial. This trial is an open label trial.

2:19 As such, the cost is quite low. The biggest cost is the drug supply and as such with those two big pharma table, we expect the biggest cost to be provided free of charge, that of the drug. We feel the drug being a bispecific cancer treatment. We feel our one has potential to utterly transform the treatment of cancer. With many of the new highly effective cancer treatments, the major bottleneck today is not getting the product, but is getting a bed in one of the specialist cancer treatment centers. This is because these new medical treatments have quite severe adverse reactions, primarily the CRS response. Many as maybe recall, the CRS is basically a cytokine storm, which we all heard about during the COVID times. And this is your own body attacking your own your own body's immune system attacking the body.

3:08 Our one trial is designed, and we believe it will substantially reduce the CRS response while not affecting the efficacy of the cancer treatment. As such, one could help, move cancer treatments from these specialist cancer centers where the beds are extremely limited into the local community hospital and even into the family home where the treatment can be applied. We're not trying to cure cancer and what we're trying to do is reduce the adverse reaction from the trans cancer treatments. As such, our trial will be very quick. This is an open label trial and as such, there is no placebo and each patient will get the drug and will know pretty quickly if this has been working basically if there's an adverse reaction or not. Therefore, we expect interim data by early next year. What are two trials underway? We no longer see the need to be at NASDAQ because I think you've got what I just said, if zero zero one trial is remotely successful as we think it is, it'll transform the treatment of cancer. But even more importantly, the zero zero one trial will ultimately transform the prospects for POOLBEG going forward.

4:18 This is why I invest in biotechs, and this is where I think we'll all invest in. Many people are chasing crypto these days for that five or 10 x. So hopefully, POOLBEG is as good as any crypto bet as Iran. That's a personal opinion. But you might say, I'd be biased because I'm the biggest, largest single investor and I'm following my money.

4:38 As such, our plan is to firmly stay on the AIM market in the weeks ahead. You will you may see some announcement. We'll be reducing our over overheads and rightsizing our cost base as being appropriate as no longer focusing on Nasdaq. And Jeremy will be very much driving the company going forward. Can I now hand over to Jeremy and Liam, who'll take you through these two exciting trials that are, I might believe, could transform the company, but also transform the treatment of cancer patients? Great stuff. Thank you, Kaho, for that introduction. Great to have everybody here tonight. Yeah. Jeremy Skillington, my name is CEO of POLBEG PHARMA. What Liam and I plan to do over the next twenty five minutes or so, we'll take you through our state of play right now where we are as a company, focusing in on the two main clinical stage programs, POLBEG zero one and the oral GLP one program.

5:29 We'll take you through those. I do wanna leave time for some q and a at the end. It's a very exciting day for us here. We had our general meeting in AGM here in London earlier on today, so all is good with that. We've got a lineup of, you know, several investor meeting over the next few days. So as I said, we're kinda looking forward to move forward with that. So what I'll do is I'll go through the slides here and say I'll hand off to Liam to go talk more about the science. But I think, you know, for for most of you aware of the POOLBEG, I think we're in a very exciting place right now. Certainly, with the the fundraising, now completed, we've got, as Carl said, that run into 2027. But what's more important, I think we've got a highly experienced team to execute on our on our focused strategy as it stands right now. Two highly valuable programs that certainly big pharma are looking towards to to look to bolster their own pipelines and POLB zero zero one for treating CRS or cytokine release syndrome associated with t cell engaging cancer immunotherapies.

6:23 That really is, as Carl said, a company maker. I think it's gonna be very exciting as we progress that into the clinic. As such, we've got multiple near term value inflection points. We've got clinical trials start at the end of this year for zero zero one and the same actually for the oral GLP one as the plan, and then getting data readouts in the first half of next year for both programs, and then full top line data readout for zero zero one in h two next year. So, again, we've been engaging over the last several years with pharma companies. One of the key requests for us, they they see the CRS approach. They see the value of POLB zero zero one, but they're kinda regular or recurrent or frequent request is can we see this in patients? Can we see the data? We we've have it in humans and healthy volunteers, but they're asking, can we see this in in patients?

7:09 So that's why we'll be starting this trial in multiple myeloma patients, and we go through that in greater detail later on. As mentioned, delighted to to complete the oversubscribed fundraise, 4,865,000, which, again, along with our existing cash balance, takes us into 2027. So, again, that gives us a nice long runway to kinda conclude or con you know, complete these clinical trials and, again, it's runway to get us a completion for the the partnering with PHARMA that we've got planned. The pipeline as it stands today, as I mentioned, POLBEG zero zero one. It's a a small molecule already available, p thirty eight MAP kinase inhibitor. And MAP p 38 MAP kinase is a master regulator of that immune response. So, again, we see this as a you know, you know, an exciting target to pursue for this cancer immunotherapy induced CRS. So a lot of work has been done in the background by the by the team. So, essentially, we are phase two ready. And by phase two, we wanna put this in patients. And so we're working hard to to achieve that with all the various work streams going on the background around, you know, the the the kind of preclinical, completing that regulatory aspects, you know, getting the drug supplies. We talked about big pharmas and, you know, talking to the clinical trial sites and clinicians, etcetera. We will speak about it. We're very excited in the last few weeks. We received FDA orphan drug designation.

8:26 We'll talk about that later on, but they see the value of this program and the potential to help patients in the future. And on the right hand side of this POLB zero zero one, just highlighting that we have several near term clinical milestones that are coming up. That gives us a nice cadence of news flow when it comes to, keeping the market updated of our activities. So first patient dose is planned by the end of this year, so h two twenty twenty five. As Carlos said, it's a open label trial, so we'll have access to the data as it rolls out. So we'll have the interim analysis expected in the first half of next year for the first, let's say, subset of of patients on on drug. And then by the end of next year, we'll have the the top line data for all of the patients. We've got 30 patients planned for this clinical trial. So, again, nice cadence there. And, you can layer on top of that the oral GLP one program. As you know, the the world is pivoting towards looking at these treatments for obesity, the majority of which are injectables.

9:20 So they're looking for these, you know, better deliveries, more convenient drugs, and certainly giving this, orally delivery oral delivery is something that the market is looking for. I'd say we are starting our proof of concept clinical trial plan by the end of the year, and, again, top line data reading out early next year. And, again, this is a very short focused clinical study. And, again, if the data is positive positive of that, there'll be lots of interest in pharma. And we won't touch upon today, but two other programs in the background, novel drug discovery, AI programs, worked with Cyrese and m one three using our human viral challenge study database that we we acquired or we licensed from Hvivo when we demerged. And we got some really interesting data, really interesting targets from both of these AI studies. But in the interest of time, I will we won't cover that today.

10:08 We will focus quite a bit on POLB zero zero one, but I do wanna ground this in the background, just talk about CRS as a as an issue, as Colin said. So I think it raised people you know, came into people's minds during the pandemic with these cytokine storms that were causing a severe disease. And, obviously, as a company, you know, spinning out of h v v o initially, we focused on severe influenza. But recently, we saw that there was a, you know, significant unmet need in this cancer immunotherapy space where there's still that same cytokine storm concern, cytokine issue. The sick patients can get very sick after receiving these, these bispecific and CAR T cell treatments. And, you know, so a solution is needed to help these patients, and that's where POLB zero zero one comes in. On the top right here, you'll see greater than seventy percent of these patients receiving bispecific antibodies or CAR Ts develop CRS.

10:59 And, of course, that's a challenge, and that's an issue for the patients. But even on top of that, it's a challenge and an issue for the health care system where they need a lot more patient care in these dedicated cancer clinics. So our goal, if our clinical trial is successful, is to take these cancer patients out of these dedicated cancer clinical trials. They can receive their treatments. There's POLB zero zero one treatment from home because it's already delivered. I would say preventing CRS is something that the market and the clinicians and health care system is looking for. Right now, treatments are actually in a in a reactive manner where if CRS is developed, they have to be in the clinic to receive their drugs, one of which is a drug called tocilizumab. It's an antibody, so it has to be given by injection or infusion. We feel that, we can have a better solution by preventing CRS from happening in the first place. So say we've got our clinical trial design. One of the key endpoints is the prevention of grade two CRS. And Liam will go through that in greater detail later on. Now, again, we looked at this last year from a market standpoint, you know, what what size marketplace we're moving into. And we see that there's a large uptake of these cancer immunotherapies. And as such, if you can solve the CRS issue with these cancer immunotherapies, there's a potential $10,000,000,000 US dollar market here, and I'll go through some of the logic of this later on.

12:15 So as I say, what what what that does will prevent CRS, but it also will enable a lot of these cancer patients to get access to these cancer immunotherapies in a in a a rapid manner. The molecule itself, as said, we've a lot of work's been put to this molecule. It's a terrific selective and potent p thirty eight MAP kinase inhibitor, and it's given orally. Again, it's got great bioavailability. And we know from all of our studies, it prevents this excessive inflammation, importantly, without immunosuppression. So it lowers that risk of patients developing infections that other immunomodulators might provide. And, again, rapidly, we've built out a a patent portfolio to protect our interest here, particularly in the cancer immunotherapy space we've touched upon. And as I say, importantly, we received recently this FDA orphan drug designation.

13:01 So that's, you know, again, a great milestone for the company. I think, again, it acknowledged the FDA with all of our dialogues back and forth. It acknowledges that, you know, we have a a potentially very exciting treatment here at the FDA's you know, would like to see us develop. And if we do so, it gives us certain benefits including market exclusivity. We'll talk about that later on.

13:22 On the right hand side here, it's a lots of work. We are phase two ready, so we are ready to go into patients. So the team is working hard to achieve that as mentioned before the end of the year. Very favorable safety and tolerability profile of the drug itself. And we've demonstrated that we can inhibit key cytokines such as TNF alpha. We've demonstrated this in two phase one trials in healthy volunteers and also potent inhibition of interleukin six and other key inflammatory markers. So we're not just hitting one target like tocilizumab. We're actually seeing the reduction of a lot of different targets, and Liam will touch upon this shortly. Again, I wanna talk about the speed of movement from POOLBEG. As a small biotech company, we're nimble. We we know that big pharma have been accused of, you know, moving a lot, you know, a lot more slowly through the drug development process. I think in 2023 where, you know, we were pursuing our our studies thinking about severe influenza, it happened upon the both Brendan Buckley and Liam had great discussions around the strategic expansion into immunotherapy, cancer immunotherapy, and that POLBEG zero zero one could play a significant role here. Again, we've had lots of discussions with big pharma companies, and we know that they're interested in seeing the data from our studies. We filed patents back in 2023.

14:31 And at the same year, we presented our phase one b LPS human challenge data at the American Society of Hematology Conference that was on San Diego as a keynote. So, again, this is something that the hematologists see as, this could be pretty exciting video in their space to prevent CRS in the first place. Then in 2024, we move rapidly. We did our deep market analysis, you know, convincing you know, with with a convincing $10,000,000,000 US market opportunity. We talked to a lot of key opinion leaders, some thought leaders, clinicians, payers. And, they validate the approach to where, you know, we're we're we're taking, which is very exciting for us. It gives us that great endorsement. And, again, similarly that year, we presented our preclinical CRS prevention data at the the ASH conference again in San Diego. And, again, that was very well received. So where we are today, as I said, ready to to begin our clinical trial later this year. As we said, we've got two big pharma companies willing to give us a bispecific antibody, likely more likely moving forward with one of them. They've shown strong indications that they'll provide this drug for free, which as Colin said costs a lot of money if he wants to pay for it on the market. But they wanna see this outcomes from this patient study. And I think that will obviously kinda garner a lot of interest, not just from the bispecific antibody provider, but other pharma companies as well in the same cancer immunotherapy space.

15:47 And, again, lastly, getting this orphan drug designation, again, fantastic from a POOLBEG standpoint. And I I, you know, I applaud and credit the team for the hard work, yeah, they did into getting that accomplishment across the line. So what I will do now, I'll pass across to Liam who'll go into more of the science behind the program and then talk a bit more about our our clinical trial that's that's planned. Liam, over to you. Cheers. Thank you so much, Jeremy, and, yeah, really excited to speak to all of you today at what is a very exciting time for the company. So I'm I'm just gonna mention some of the existing data that we have and then go into our clinical plans over the next year. And just to mention as well that POLB zero zero one was initially developed as a a treatment for chronic inflammatory diseases. So on top of the data not shown here is that this has extensive nonclinical data in a first in human study that shows that the the tolerability and safety of the molecule is excellent.

16:40 And the data I'm showing you here today is really how we're positioning it towards cytokine release syndrome or cancer immunotherapy induced cytokine release syndrome. So the graph I'm I'm showing today here is a humanized mouse model that we did. Humanized meaning that it's a severely immunocompromised mouse that is essentially given a human immune system. So we ablate the the mouse model immune system, and we actually inject a human immune system. So on the top of the slide, the graph is showing that day zero humanization, that's actually the the radiation treatment to destroy the existing immune system and to inject in a human immune system, and then on day five to give it a a tumor. So the very same case as what we would have in the clinic for somebody getting a bispecific antibody to the human immune system, and then we give them an immunotherapy that induces cytokine release syndrome on on day six. And during that, then we're also dosing with POLB zero zero one twice daily.

17:36 And in this model, we used, obviously, gold standard of cytokine release syndrome and a c d 28 super agonist to induce cytokine release syndrome, and we also compared POLB zero zero one against the TNF alpha antibody. And the reason we did that is because while tocilizumab and IL six receptor antibodies used in the clinic, in in the mouse model, empirically, a TNF antibody actually works much better. So this is a stronger standard to use against. On the graph on the left, the CRS scores, what we're looking at it actually is the cytokine release syndrome score induced in the mouse model. So the the navy blue on the left hand side is essentially no cytokine release syndrome. And then when we introduce the c d 28 super antibody, then actually we get cytokine release syndrome plus that elevation. And as we introduce POLB zero zero one, the light blue, the blue, and the green, what we see is that all three doses of POLB zero zero one that we gave were actually very effective in reducing cytokine release syndrome scores, down to the background level of no CRS similar to how the anti TNF antibody worked in this model.

18:41 On the right hand side, I'm showing a selection of cytokines. We did publish this data at ASH last year, and it went down very well. We we showed a wider level of cytokines, including IL eight and IL 10. But here you see IL six, which obviously very important in cytokine release syndrome and also TNF alpha across all the cytokines that we

19:00 looked at. We actually saw that POLB zero zero one was very effective at reducing the levels of these cytokines. And with the exception of TNF alpha, and POLB was actually superior to the TNF antibody across all of these cytokines that we tested. So these are extremely promising results and are a good omen as we move forward towards clinical studies. This is a previous clinical study that we did to the LPS human challenge study that some of you may be familiar with. So in this model, human subjects, healthy subjects are given an LPS stimulus. LPS is a component of the bacterial cell wall. And what it does is it induces an acute inflammatory response similar to what we would expect in cytokine release syndrome. So in the left hand side of the slide, and what we're looking at is the trial design.

19:45 So the healthy subjects were brought into a clinic, and they were dosed with POLB zero zero one from day zero to day seven. And what happened was on day four, we gave them four intradermal doses of LPS. And then on day six, we gave them an IV dose of LPS. And what this model is on on the intradermal doses allows us to see the local effects of POLB zero zero one, so how it behaves in the tissues. This is actually in the forearm of the subject, so it gives a real good idea that the drug can perfuse into tissues and also exerts anti inflammatory effects there. And, obviously, with a slight more focus on it today, the IV dose was the one that is particularly pertinent in terms of cytokine release syndrome because it's this systemic inflammatory response. And, again, I'm only showing you a subset of the data, IL six here. We've previously presented the TNF alpha data and also the IL eight data.

20:38 But what we're seeing here is the gray line is essentially after we give the LPS challenge, you see a spike in IL six. Again, this mimics what we would see in cytokine release syndrome. And as we introduce POLB zero zero one, so the low dose is green line, what we see is the levels of I l six coming down, and the middle and upper dose actually are both very effective at reducing I l six to the point where they're equally effective, and that's just because with bidaily dosing, we we get effective coverage and bioavailability of this drug. So really promising in terms of moving forward into a patient population. On the right hand side, we also looked importantly at a a number of clinically meaningful variables. So what I mean about that is that clinical manifestations that anybody would notice on a on a patient, so things like heart rate, body temperature, that we can measure and that have an impact on patient welfare. So, again, with the LPS challenge, it doesn't just introduce molecular inflammation.

21:33 You actually see that in terms of the temperature. And what you're looking at here, you see an elevation in the heart rate after giving LPS to the subjects, very similar to what we're seeing with I l six. Actually, when we pre dose subjects with POLB zero zero one, you don't see the same level of heart rate rise. So, again, these are very promising results that we can actually exert a biological effect in the endpoints of modern cytokine release syndrome. So what we're looking forward to do, a really exciting time for the company, obviously, we've been working on this project for a while now, and, you know, we've built up the relationships and really excited to move into the clinic and get these results. So what we are looking at is a phase two clinical study in multiple myeloma patients, relapsed refractory, being treated with an approved bispecific antibody.

22:25 We're expecting to start the trial later this year, importantly, with interim analysis in the first half of next year and top line data in the second half of next year with potential for partnering and positive data. And as Jeremy mentioned, we do have very strong indications that big pharma will be willing to provide the bispecific antibody free of charge for use in the trial, and that's, you know, only a symbolic testament of the the level of interest, not just from pharma, but also from academia and across the medical landscape that we've seen in in this molecule being developed. And a number of leading myeloma clinicians are re enthusiastic to participate on this trial and to get it moving as soon as possible. So what is the trial? We're keeping it very simple. You know, looking at cytokine release syndrome. We want to keep this as easy to recruit and as quick to execute as possible.

23:14 So, essentially, a bispecific antibody, we're using approved bispecific antibody, and we'll be giving twice daily dosing of POLB zero zero one the same way we did in in the previous study. There'll be approximately 30 subjects, and it's gonna be an open label single arm study. This is really important because it means that we will actually see a lot of the results in real time feed in next year. So a bispecific antibody at the moment is given to what's called step up doses before you get the full dose. And the reason they do step up doses, these are essentially micro doses because if they were to give a full dose to a subject, there'd be overwhelming cytokine release syndrome. So they give small doses to get the subject used to it and then work up towards a full dose. And as Jeremy mentioned at the moment, this is predominantly done in a hospital setting where they're they're an inpatient for approximately a week while these doses mainly just for the risk of cytokine release syndrome. So our intent will be to study the subjects during this time. And, again, this is an endpoint where it happens within the first one to two weeks. Ninety nine percent of all cytokine release syndrome of bispecific antibodies occurs in the first two weeks.

24:20 So we'd be doing a very short trial focused on this period and seeing how effective the drug is at preventing cytokine release syndrome. Our priorities was to really make this trial simple, neat, and straightforward for subjects, that's reflecting the endpoints that we're gonna be looking at. So what are we looking at? We're not following subjects to things like overall survival or progression free survival that you might see in other typical oncology studies. What we're looking at is something that happens very quickly during the step up dosing, and the results of this trial will be evident quite quickly as well. So we're looking at the instance of grade two plus cytokine release syndrome. Grade two just means it's slightly more severe. I mean, that's one of the indications that the regulators finds the there's more importance, I guess, behind grade two plus cytokine release syndrome. We also want to confirm the safety and pharmacokinetics of POLB zero zero one itself. First time going into patient population, exceptionally important to do. And then we'll also be looking at other endpoints, such as the instance of all grade CRS and how much tocilizumab is used. Tocilizumab is the standard of care essentially for cytokine release syndrome, but importantly, reactively, not prophylactically.

25:27 We're just gonna dose POLB zero zero one, and the hope is that there won't be any cytokine release syndrome in these subjects. On that, I am gonna hand back over to Jeremy to go through a couple of slides in the market opportunity. Super. Thank you, Liam, for that. Yes. One second there. Yeah. Sorry. I just had a bit of a glitch there. Sorry. Thanks for that. So, yeah, so I wanna talk through again the value that we're gonna bring here. I think we we talk a lot about the, you know, the signs and the, you know, patient benefit, etcetera, health care benefit. But what yeah. What's the what's the financial, you know, benefit here, I think, overall to share, you know, to shareholders of POOLBEG, etcetera. So I just wanna share, on the left hand side here, the growth in these bispecific and CAR T cell therapies. These cancer immunotherapies are growing exponentially.

26:13 They're being approved, very regularly, and, you know, the, you know, the data coming out of them is is quite impressive. You know, there's a lot of, you know, success. There's a lot of indeed talks about cancer cures, you know, for these hem hematological cancers. What's interesting right now is that they're moving more into solid tumors and even into all immune diseases, so there's a scope for expansion there. But right now in 2030, they expect that these, you know, T cell engaging therapies

26:38 can have a revenue generation of 120,000,000,000 on their own. But as I said that I mentioned earlier on, seventy percent or so develop CRS. So we're looking to be alongside these for all of these drugs when they're given. There's a potential POLB zero zero one will be given as well. And, obviously, we can, you know, kind of market that and and commercialize that independently. I didn't mention about the FDA orphan drug designation. Again, fantastic achievement for the team. But what this does, and I think importantly for us and and our potential partners, this gives us seven years of US marketing exclusivity from the date of approval. So, again, you're cornering your market there. You can prevent CRS. You're using these p 38 map kind of delivers. And, as I say, so we've gotta jump on the field that way. All the benefits include, you know, cost savings with regard to, drug application fees, upwards of a $4,000,000 value there and early access to these, special protocol assessments. That's like you gotta it's like your red telephone line into the FDA to get, you know, to to help in the assistance of the application also potential benefit for tax credits for qualified clinical trials. Again, all of these will be of interest to our pharma partners. So, again, POLB zero zero

27:41 one potential to be the first approved preventative therapy for cancer immunotherapy induced CRS. So when we looked at the numbers, we picked two different patient types here who received these CAR Ts or bispecifics. We looked at multiple myeloma patients and diffuse large B cell lymphoma patients in both The US and The European Union, and we estimate that's about five hundred thousand patients. You can see on the right hand side there the breakdown of, of these two patient types, say diffuse large b cell lymphoma and multiple myeloma. And as I say, you know, preventing CRS really opens up the market here where many more of these patients can get access to the drugs Because right now, there's a delay in getting access to drugs because they're sitting in these cancer clinics, these, you know, cancer beds waiting for CRS to even develop, and then they're treated on-site.

28:28 So we can potentially make this kind of a community treatment where the patients can go home, and we'll manage their CRS from home. So as I say, fantastic opportunity for for the patients, you know, to have you know, to not develop CRS in the first place. But I think what's intriguing and exciting to pharma companies is that they will get more of their drug, more of their bispecific antibody CAR Ts into patients because, as I say, they're not sitting around in the in these transplant beds, you know, preventing other patients from getting their drug. So we see this as a bottleneck that POOLBEG can open up. And as mentioned, we see this as a preventative therapy, remove the bottleneck of greater than $10,000,000,000. We've talked, as mentioned, all the key opinion leaders or many key opinion leaders, across in The US, in France, in The UK. I think Martin Kaiser sums it up well, so, you know, stating that if there was a therapy that was already delivered, a whole lot of the infrastructure requirements fall away. You So need less hospital beds, less doctors, less nurses, but they can be assigned elsewhere. So I think we're we're providing a very important service here across POLBEGPHER one. I do wanna spend just a brief minute on GLP one before wrapping up. Because I do wanna leave time for questions. Unfortunately, we gotta, you know, shut things down at 05:45 because I gotta run to get a train.

29:38 We're here in London right now. We're we're heading up to Manchester to meet with other investors later on tomorrow, etcetera. So I do have a hard stop at at 05:45. So talking about the GLP one program, let's say the world has kinda turned in that direction. The obesity epidemic as is, they realize that these what were once diabetes drugs have profound effects on, weight loss. And, the majorities are given by injection. You know, you have the likes of, you know, Wegavy. People are familiar with semaglutide, another the generic name, but a lot of these drugs are in the market sizable marketplace, a 150,000,000,000 by 2031. So we're looking to run a clinical trial for this oral encapsulated technology. So this is a validated technology itself. So we're encapsulating this oral, the GLP one receptor agonist, and then giving it orally to patients.

30:26 And, as I say, we're we're looking forward to getting that trial as you worked up as well. Getting that started before the end of the year is the plan. Lot of work going on the background around, your manufacturing, getting the clinical trials out ready, etcetera. And we're gonna run this with professor Carol Larue. He's, based in Dublin, but he runs out he work also works at the University of Ulster. And, basically, we're looking to to demonstrate the safety, tolerability, and pharmacokinetics of orally delivered GLP one to demonstrate its uptick. We're looking at 20 volunteers here. These are obese subjects. I said, yeah, working closely with and our technology collaborators, to move this forward rapidly to get it in the clinic. Again, importantly, to get that human proof of concept data that pharma so so crave. Again, the numbers on the left hand side, huge impact on obesity on the the the economic impact. Again, that's in The US only.

31:17 But the revenue generation, 150,000,000,000 by 2031, I

31:21 mentioned. As we know, The US population, about forty two percent are affected by obesity, so they're looking to reduce those numbers. And on the right hand side then, it won't dwell, but there's a lot of issues with the current drugs that we could potentially benefit. As I say, giving this orally, you can see you could potentially see a lot of these issues moving away, particularly with, you know, patient adherence to taking the drug. As mentioned, our colleagues, there in the bottom, they have a large manufacturing facility themselves, the FDA accredited. And, you know, they they have a number of commercialized products using their technologies about, you know, oral delivery of, say, probiotics and vitamins, etcetera. So it's a validated technology. So we're just looking forward to see that pharmaceutical benefit, let's say, in delivering GLP one orally. So, again, with the trial beginning before the end of the year with, again, very rapid trial, so we'll have top line data in the first half of next year if all progresses as expected.

32:13 So investment behind us, just to my wrap up slide before we get to the q and a, a reminder, fantastic team behind us. Very exciting pipeline with two very attractive and high value programs, zero zero one as well as the GLP one. We do believe with zero zero one, we can have the potential to transform this cancer treatment, this, you know, T cell engaging, this cancer immunotherapy so that people so it'd be more in the community that'll be in the hospitals, which, again, great benefits to everybody all around. Again, multiple near term value inflection points. Again, we'll update the markets as these are progressing. And, we see these are very partnerable that once we have the human data and pharma have told us this. Having human data is really what drives our interest. We'll be able to, you know, get these progress partnered and, again, driving value for POOLBEG at the same time. And, again, very excited. Obviously, today is important day where you get the approval for our oversubscribed for fundraise. So we have a combined cash to get us into 2027 to complete the trials and obviously complete the transactions, the the partnering transactions thereafter.

33:11 So, again, greatly appreciate your time, and let's take we've got ten or twelve minutes over for questions. So I know that some questions have been coming through. So what I will do is I will read these out,

33:22 and I'll assign whether myself or Liam will take the questions, maybe back to call. But we can we can take it from there and take our time on this. Alright. Let's see. First question, this one is for for Liam. If you could take this, Liam. Has POOLBEG made a request to the EMA for orphan drug designation for POLB zero zero one? Good question. We have the FDA. But, Liam, over to you. Yeah. Really good question and, obviously, one that a lot of people are gonna have interest in. So at the moment, we we we have, of course, engaged the EMA, but we've also prioritized the FDA engagement process. The US market is the biggest in the world. That's always where launch is gonna be first, and and there's other complications that EMA orphan applications have to be updated every year and once they're reward awarded.

34:07 But we will be providing further details of that in due course as soon as we can, really. Brilliant. Thanks for that, Liam. And question two, I think this yeah. This is probably best for you as well, Liam, just on the technical front and the patent front. For POLB zero zero one, in simple terms, what do your IP patents cover? CAR T bispecifics, influenza? Are other areas included such as sepsis, COVID, hard tumors? I I presume solid tumors related CRS. Thanks, Jeremy. And, again, another really good and important question. We've always been really open with what our our patent strategy is and that we do have very broad IP in the cancer immunotherapy space, and and we're always looking to expand and strengthen that as we go along. With the existing filings, we do expect protection out to at least 2043, which is, you know, excellent.

34:57 And we are focused on that seven years market exclusivity in The US as well from our orphan designation recently. But, of course, as we increase our filings, we'll definitely extend the updates to the markets. Brilliant, Liam. Brilliant. And question three. Just reading this now. Liam, I think, yeah, you can take a break for a minute. I I'll take this one. What is happening with regards to your AI studies of influenza and RSV? Have possible new treatments been identified or old drugs been identified that could be repurposed? Are we likely to hear solid news on progress within the next six months? Again, appreciate the interest. And this, I'd say, in the interest of time today, we didn't have, you know, the the necessary time to go through in detail. So, again, historically, this is kind of interesting from a POOLBEG standpoint to when we spun out of hVIVO.

35:42 We did have a lot of the data that came from hVIVO. They've they've you know, essentially, it's the world's largest database of infectious disease progression data. This is where you're giving, you know, healthy volunteers a virus in a quarantine setting to, you know, they become sick and they recover, and we've taken colored blood samples all the way through. So I think, you know, ideal ideal data for this AI analysis to understand what's going on, let's say, under the hood when it comes to infectious disease progression. So we did establish two very important partnerships. CytoReason, who you know, they're they're Pfizer's AI partner of choice. Pfizer, I think, are a main investor in CytoReason. They've, you know, invested in their collaboration. They used them for a lot of their, you know, disease area, disease biology work from an AI standpoint.

36:29 And the the second part of them was with one three Biotech. They're based in New York who did our RSV work. So I think it's kinda kinda, you know, quite in for us is, like, certainly, there were very successful collaborations. We did identify some novel drug targets that, again, heretofore, we don't believe anybody would have associated with infectious diseases. And with RSV and one three in particular, we did identify some repurposing drugs. Some drugs that are, say, have progressed in the clinic, not for infectious diseases, but potentially could be repurposed because we know from our AI studies that they can, know, remodulate the biology or help, you know, stop disease from aggression. So I said that there is always been a lot of interest in big pharma companies in AI. And, of course, you know, the infectious diseases are not going away. They've always been around.

37:14 So the plan now is to seek partners for this work. You know, we do wanna see this move forward and say we do think we have some nuggets that we we wanna develop. But starting from a company standpoint, you know, zero zero one and or the GP one, I think, is the real value drivers and, again, to use calls for company makers. So, again, we'll keep you updated on the progression. Next question. I I'm happy to take this as well, Liam. What is happening with respect to the oral vaccine delivery program for which free funding was received? Again, thanks for that. So this is yeah. We received the the know, a grant essentially from the Irish government, the disruptive disruptive technology innovation fund. We're partnered with Anabio who have this oral delivery technology we talked about for GLP one as well as infectious disease experts at University College Dublin and Trinity College Dublin. And, essentially, it's looking to encapsulate vaccines to make them orally deliverable.

38:12 I a of vaccines right now, as you know, are given by injection. So you're you're absolutely right. This is a low cost program to POOLBEG because of this grant funding. And, you know, we have been working on this in the background. As I say, there are academic partners and other bio have been doing quite a bit of work as well. So we have made some breakthroughs, which I think are quite interesting. Again, you know, not to say or inestible. Not announced, but yet, you can say, know, within the confines. But we're happy with the progress that were were made. We're happy with identifying, say, you know, know, what key adjuvants, what we ought to use, what key antigens to use that help stimulate the immune system. So we've got some interesting work in that area, and, of course, we'll update the market as we progress. So, again, very productive collaboration with our academic collaborators as well as our our colleagues at at.

38:58 So, again, you know, as I say, it's moving along in the background with some interesting interesting data coming through. Next question. Yeah. I'm happy to take this as well, Liam. If the oral GLP one trial is successful, what advantage does the Nasdaq strategic partner have? How does this translate in potential terms of a partnership agreement? Not sure I fully understand. I know we had a collaboration with a with a Nasdaq group around the same technology, but I said we're very excited. You know, I say I say this repeated repeatedly. You're getting this into humans, getting this into you know, you would get human data from the study will certainly trigger a lot of interest, you know, not just from, you know, Nasdaq strategic partners. I think it's global that you'll have pharma, you know, those certainly in the GLP one space. We're interested to see the data is coming out. So, again, very, know, as I've gone through earlier on, a very interesting trial, very straightforward trial. We'll have top line data next year. And I said, if if we can deliver, you know, an oral GLP one, I think there'll be substantial demand, you know, across all different companies. And as you know, the likes of Ozempic, for example, these are given by injection.

40:01 So people are looking for a more convenient administration. But I think importantly with the license that we have from ANNOBIO around metabolic diseases, we think that we could secure, you know, very attractive deal terms with the human data at hand. And as I say, we you know, from a business development standpoint, we continue to, you know, engage in pharma companies who, again, are interested to see the clinical data as it comes out as as you would expect. Let me think. There's one here, Liam. I'll I'll give to you. Oncology are very long oncology trials, I presume, are very long and expensive. Why is yours different? Yeah. Thanks, Jeremy. And, again, it's a really good question and an important question as we move forward into next year. And it's one of the things I'm trying to emphasize is that cytokine release syndrome is something that happens very quickly after the commencement of therapy, so during this step up period. So and, again, this is also something which is clinically observable.

40:58 So other oncology trials might have things like expensive radiology scans that really drive up the cost of trials. We don't need any of that. This is simple clinical observation. It's gonna happen really quickly if it happens, you know, in the first two weeks really after the initiate initiation of treatment. It's open label and single arm, which means that there there isn't any placebo control and there's no unblinding. Of course, next year, there'll be a couple of database readouts, but, really, when we have a good relationship with the investigators, we're gonna have a really good indication of how this is progressing in in real time. We're working with people who are gonna be keen to update it as often as possible next year. Brilliant. Brilliant. And, Liam, on top of that, there's a kind of a you can say a corollary question has come through. How can we run a valid test without a placebo?

41:45 That's from TB. So thanks thanks for it's a a it's a continuum, you could say, but, you you know, it's a good question. So, again, this is a really important question. And, of course, later in in the clinical development, we we would be doing randomized controlled trials either against a placebo or against something else. For this trial, we don't need to. So we're we're going first into patients. Sodicone release syndrome is something that occurs in a large proportion of patients, so about seventy percent of this patient population. So even with thirty patients, we're gonna have a really strong indication of how effective the drug is, that's and what we really need before we move into large powered studies because we need data to power those studies off. So this is gonna give us a lot of indication about what that would look like. And also from a a partner and pharma perspective, it's gonna give them a really good indication of of how effective the drug will be. Obviously, there there'll be molecular readouts as well, like cytokine profiles.

42:38 And, this is gonna give us a really compelling profile of what POLB zero zero one is doing in this patient population. Brilliant. Thank you for that, Liam. And just in the interest of time, just the last question, and I'll take this. Why should an investor buy in now? Again, great great questions as always. But I I think from a pool deck standpoint, you know, we really, in the last several months, you know, Colin talked about kind of, you know, the work done last year looking towards Nasdaq. You know, we're putting that in the, you know, the you know, behind our focus on the the a market. I think as you've seen from today's presentation, we've got a number of very exciting clinical milestones coming through. So there's gonna be a lot of, your news flow. There's gonna be a lot of updates. As said, you know, the POLB zero zero one, we do think will be is groundbreaking, and we think it'd be company making. So, again, you know, the the milestones there, we're starting the trial before the end of the year, interim data in the first half of next year, and top line towards the end, and the GLP one as well. So a lot of news flow coming through. Obviously, we've got other aspects going on the background as well. We'll update as they come through. But I think importantly right now, we're we're focused on execution.

43:39 You know, getting happily with the fundraise. We've got a runway into 2027. We we see we have a fantastic team. We know what we're doing. We're gonna execute on this. So I think now is a great time that, you know, the the the only way for POOLBEG is up from here is my belief. So, again, excited for, you know, for investors to come and join us for the journey. So on that note, I'm looking at the clock here because I do got a dash in thirty seconds or so. But, again, just want to spend the last few minutes to thank you all for your time today. I hope you appreciate the update and say a lot of work goes on in the background of POOLBEG. Really like engaging with our investors and would be investors to to bring them along for the journey. I'm looking forward to giving you more further updates as we progress. And, again, appreciate your time today, and I look forward to updating you for other activities in the future. So thank you for that, and I'll wrap it up there.

44:25 That's fantastic. Jeremy, Carl, Liam, thank you very much indeed for updating investors today. Could I please ask investors not to close this session as you will now be automatically redirected to provide your feedback in order that the Board can better understand your views and expectations. This will only take a few moments to complete, and I'm sure will 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, and good afternoon to you all. Thank you.