Poolbeg Pharma (LSE:POLB) — Company Presentation

0:00 Afternoon, and welcome to the POLBEG PHARMA PLC investor presentation. Throughout this recorded meeting, investors will be in listen only mode. Questions are encouraged, can be submitted at any time via the Q and A tab situated on the right hand corner of your screen. Just click Q and A, type in your question and press send. The company may not be in a position to answer every question received during the meeting itself. However, the company can review questions submitted today and publish responses where it's appropriate to do so. Before we begin, we'd like to submit the following poll. I'd now like to hand you over to Jeremy Skillington, CEO. Good afternoon, sir. Good afternoon. Good evening, almost a minute past

0:31 evening. Thank you, Paul. And thank you everybody for joining us this evening for this POOLBEG presentation, I think, the last day of of April. A very fast start for the years that were. You probably saw today we had a few announcements today. Obviously, our end of year results, 2023 results, that we announced. So we announced an option agreement with, Silk Road Therapeutics. We'll talk about that later on. And then an update on our brokers, joint brokers. So busy busy day, busy week, busy few months for POOLBEG, but, delighted to, to be joined, somewhat virtually on stage tonight by, my chief business officer, David Almond, and also doctor Tim Cote, who's a cofounder and CEO of our our collaborator, Silk Road Therapeutics. And what I'll do for the program of events, I'll go to give a general update on POOLBEG and our activities, pass it across to to Dave who'll talk through POLB zero zero one, the lead program, and the role for cytokine release syndrome following a immunotherapy administration.

1:34 And then Tim will talk about Syncro Therapeutics and their novel and interesting therapeutic for Behcet's disease. And then we do a wrap up and have some questions after. So I'm thinking maybe twenty five, thirty minutes or so for presentations that gives us ten, fifteen minutes or so for for questions at the end. Again, appreciate you for for joining us this evening. So as a kickoff, just to, you know, to to ground us all at POOLBEG, we've had a a terrific year take a terrific few years, I should say. But now we've built a fantastic team around the company. And, you know, the team that's around us here have been successful in the past, and that's always a good ingredient for success in the future. So, towards the end of last year, beginning of this year, bringing on three former average pharma, colleagues, to drive, the legal aspects, business aspects, and clinical development. So, again, fantastic to have them on board fully integrated right now and driving forward our strategy as we, you know, as we focus some more on the orphan and rare diseases, which we'll touch upon later on.

2:33 We are, as I following this kinda AMRIT pharma model. Some of you would have known the company cofounded by by our chairman, Carl Friedel, founded in 2016. And they're required last year for 1,480,000,000 by KAZ PHARMA PLC. So I get a very interesting model in the rare orphan disease space. So we're putting pieces together to to achieve that. And we talk about it later on. But partnering is very much of of key focus for POOLBEG with our existing programs. We're also looking externally to for other programs. I think Silk Road summarizes that very well. We'll talk about that later on. So the programs internally, touch upon later on, zero zero one, we think it's high value in the cancer immunotherapy space treating cytokine release syndrome. We've got an oral encapsulation technology. We have an oral GLP one receptor agonist program going into the clinic this year. But, again, moving forward on that, a big space, a big market. And, of course, we've been leveraging, very novel data in the infectious disease space and using artificial intelligence to identify new drug targets and new drugs for that. So we have finished last year with a very robust cash position, $12.1212200000 pounds at the end of the year. So now that gives us a nice long run which we achieve our near and medium term goals.

3:48 And as I say, we're focused now on looking for programs to bring in to generate near near near medium term revenue as well, the direction we'll take. Our pipeline, as again, those who are familiar with this in the past, we have added at the bottom here this exclusive option agreement with our with our friends and colleagues at at Silk Road. So we'll talk about that in detail later on. You know, Tim will give us a good run through there. But, again, very excited about the potential of POLB zero zero one for this cytokine release syndrome. So, again, we've been busy. We've been active moving these programs forward. We've always said from a POOLBEG standpoint for these programs, we'll get early clinical data and partnered programs. And I think the you're getting data in multiple myeloma patients is now our goal for POLB zero zero one and obviously looking at getting human data later this year for the oral GLP one program as well. So, again, a lot of progress, a lot of activity, but very excited about what the future holds. And we have been busy on the, you know, strategic collaborations front as well, partnering with a Nasdaq company, and obviously bringing in some non dilutive funding to move forward our oral vaccine, program as well. So, you know, fantastic to push that forward. I do wanna give an updates again since today was, results day. Just key achievements, that we had from last year that was expanding zero zero one into this immuno oncology space.

5:07 Dave and the team have done an in-depth analysis that we talked about later on, but now we're targeting a market to the value of $10,000,000,000. So the next generation of cancer treatments will be these immuno oncology treatments. CRS, cytokine release is a side effect that needs to be managed. So we see this as a whole market in itself that they will touch upon later on. We did garner a lot of interest, from, our pharma colleagues at the, the ASH meeting in San Diego in December. Again, when they see that we have a potential small molecule orally administered prophylactic treatment for CRS. So that raised a lot of eyebrows for

5:42 for the potential there. I I mentioned robust cash balance at the end of the year, 12,200,000 long runway. And, again, integrating our AMRED PHARMA team, it's has been, you know, terrific, and they've been up to speed really, really quickly as we push things forward. I won't touch upon the other milestones. I think they're they're well understood, but I think that as I said, we've we've had a very productive, a very active year, and again, driving value for shareholders in the the pipeline products and programs we have. As I said, we're four months or so into 2024, and we've achieved a lot thus far. So we're we're we appreciate the momentum that we have. I wanna continue that for the rest of the year. Again, announced today, we signed an options agreement with Tim and his team around the rare disease treatments. This is a topical PTX we've touched upon. Earlier this year too, we got positive in vivo data, I guess, validating to a certain degree the direction that we're taking in cytokine release syndrome and the fact that POLB zero zero one could play a significant role in in that disease.

6:40 Copperfield stepped up to be executive chairman, and we've gotten, you know, made good progress on our intellectual property portfolio. So, you know, keen to see these move forward as well because that protects the the directions we we take. So, you know, the the EPO in Europe and the USPTO reviewing our patent filings and looking upon them favorably, thankfully. So other key highlights is other new patent patent application has been filed and couple of myself responsible for buying shares of the company, you know, directly ourselves. So, again, lots to lots done, but a lot to do, lots to look forward with in the future. So we're well positioned to drive growth and value for POOLBEG PHARMA. So what I'll do now, I'll pass it across to Dave to talk us through POLBEG PHARMA. I'll step back again afterwards, to talk about Behcet's and and introduce Tim in in greater detail, and, and then we'll have a wrap up at the end. So, Dave, over to you.

7:33 Thanks, Jeremy. So let me just start by framing, the opportunity here. So, many of you recall we've covered cytokine release syndrome, but what the way to think about this really, it's an unwanted, side effect of the cancer immunotherapy. You do see it in infectious diseases where we we still have an interest in influenza. But in the burgeoning space of of of cancer immunotherapy, CRS is actually the primary rate limiter when it comes to the broad safe delivery of these, amazing therapeutics that Jeremy's described that will be the future of cancer care. And it's as high as over seventy percent of patients actually will show CRS of of grade one, two, three, or or above. It can be much higher than that in in certain settings, and therefore, it's very common.

8:23 And and and the way to think about it, if you look at the right hand side on the impact, even if you have grade one or two, which is the lower grades of CRS, you will be hospitalized, and that's a very costly business in a in a transplant bed in a in a cancer center. So there's a practical issue there. And with CAR T, it can be grade three and four, so it'd be be more serious, and actually that runs a a severe sort of morbidity mortality risk. We've estimated that just by 2030, just by managing CRS alone with the explosive growth of these therapeutics would cost directly 5,500,000,000 in The EU five and the and The US. So there's a huge direct cost implication of managing CRS as it stands today, which is why we're excited about really trying to prevent this problem and enable these therapeutics to be more broadly safely delivered.

9:14 There is a significant unmet medical need in this regard, both at a at a patient and center level, but at a health system level. And we're really excited about POLB zero zero one with the data we've generated thus far into normal volunteers. I'll recap on that in a second and also some some more recent in in vivo mouse models in a CRS model. Again, clearly demonstrating, that we're on a good track here. The one thing I'll add before we move off this slide is sometimes molecules take a while to find the right home, where the risks and the benefits are in in the right place. We believe an orally delivered p thirty eight MAP kinase inhibitor is really is really gonna take a place, in the prophylaxis or prevention of CRS in cancer immunotherapy.

10:07 It's a it's a it's a, I think, a strategic maneuver we've we've made where we're now the front runner in that regard. There is very limited, development going on out there to address this this issue. So POLBEG is really excited for for the future here.

10:23 Let me recap really quickly. For ASH, we we showed the phase one b, LPS human challenge study. The LPS is lipopolysaccharide. That's where you create an immune inflammatory response, And then we dose the the the dual volunteers with POLB zero zero one. Excellent safety, tolerability, very significant reductions in all the key inflammatory markers you would expect, I l six, TNF alpha, I l 10, etcetera. We confirmed the target inhibition, and we showed a dose dependent reduction in those inflammatory cytokines. And the way to think about that is we're not we're not ablating the immune system. We're just stopping the overreaction of the immune system with this with this asset.

11:09 And then on the right hand side of this chart, two points I'll make. This is the most recent data where we've we've in a in vivo a mouse model, we've we've shown in a CRS model the same, type of effects on, pro inflammatory cytokines, dosing POLB zero zero one at different levels. Actually, the important point about this more recent data is we we put prophetic filings in for patents over a year ago, and now we've, we've we've now, filed the data, to protect the asset potentially out to twenty forty three

11:46 leveraging these datasets. So, again, great progress on the on the clinical preclinical side. ASH, Jeremy mentioned it. I won't dwell here other than to say it's a premier conference for hematology. The data was accepted and and presented in a poster presentation. We attended. We had great industry interest, and, we also had scientific, and vet investigator interest in in the asset. And when we scoured the landscape at ASH, we saw very limited alternatives, to proactively address this problem, which will only get more prominent, as these therapeutics grow in in breadth and and depth across the cancer space.

12:32 If we think about market opportunity here, Jeremy already alluded to this, we we we recollect, you know, the monoclonal antibody space, was explosive growth in its day, really bringing value to patients in a number of settings. And this is not going to be dissimilar. Predictions vary, but here we we we're estimating a $120,000,000,000 market by 2030, and that's on the current trajectory. That that doesn't account for if there was a a better enablement of the broader applications of these, therapeutics outside of the cancer centers alone where they're currently delivered. So that could be a thin end of the wedge in terms of the opportunity here that that that's out there as these therapeutics become the next driving force in cancer care.

13:20 What I did from a market opportunity perspective was was to take a conservative view. Let me describe, what I mean. So I took two tumors alone. Why did I do that? It was because multiple myeloma and diffuse large B cell lymphoma, which is a high grade lymphoma, are the most prominent to hematological malignancies where where, in cancer immunotherapies have made the most progress in terms of approvals. We then estimated that if all of those patients in those in those two indications were, first, second, and third line, were were accessible. So and that and what you'll see actually in this space is that these therapies are indeed moving up the lines from third line plus into second, and I have no doubt they will get to first line because when you have that type of survival data, that's very typical in cancer to to move up the lines of therapy.

14:14 We took no account of the potential expansion of the opportunity if we enabled these therapeutics to be delivered outside of a cancer center, in a smaller hospital, or as an outpatient. And, therefore, we also took into account the, you know, the the if if the therapeutics were were were much broadly used in ALL, uveal melanomas into solid tumors such as lung cancer and beyond, we did not calculate these into the into the numbers. I took a very, modest view on an analog for price in this analysis, and it's it it it immediately gets us to an estimate of a 10,000,000,000 market opportunity in The EU five and US alone. So I think this is this is the thin end of the wedge, as I said earlier.

15:02 The other way we think about this strategically is is this is not a simple supportive care strategy that you see in cancer. We believe this is a true enabler strategy. So if you envisage the five hundred thousand patients I described coming into the funnel at the top with myeloma and lymphoma alone, that doesn't account for the other indications, And you're trying to deliver these therapies only in cancer centers, are limited in number and throughput, and there's an inefficiency in the system because they end up in hospital for one, two, sometimes three weeks if they get CRS, which is common. Therefore, you end up with a potential bottleneck, for delivering those seamlessly to the patients, who need them depending on their on their accessibility to the center and the efficiency of the center.

15:52 What we also modeled was we know CRS happens. It happens over seventy percent of cases, and we know from a a published source roughly what it costs just direct costs only, not the indirect costs, just direct costs only. Grade one, two, and three CRS has a very significant direct cost burden on the health system. So we modeled that out. That that's where we derive the 5,500,000,000 potential, budget impact on the health systems if there is no, suitable prophylaxis to prevent this problem in the future. That is not how we price drugs, but that certainly helps us to demonstrate value, to payers if we can help to offset some of these incumbent, costs that come with the burgeoning, explosive growth of cancer immunotherapies.

16:40 The other thing we've done, and we've been busy, doing this because we we we prefer not just to think internally that we know, the answers. We've really gone outside to the outside world and pressure tested our hypotheses both in The UK, in France, in Canada,

16:58 and in The US with some of the top key opinion leaders. We've taken a selection of some of their comments here in the boxes in the middle of this slide, but what I'm gonna focus on is just the three points on the right hand side. So access to CAR T and bispecific antibody is restricted to specialist centers and limited by inpatient capacity. That that is confirmed. That's what the key opinion has told us across the globe. Prevention of CRS would allow for outpatient administration to enable safer, broader delivery of these. So this would be an an an enabler or expansive opportunity for the therapeutics to be used more broadly. And when we presented the POLBEGPHERON profile to these, top experts, actually, in lymphoma and myeloma, these experts were, Then, they said that if you hit that profile in your clinical program, that would be highly attractive, to our clinical practice to increase efficiency and have these patients out of these transplant beds.

17:58 So let's just, listen to to the to the confirmatory words of of doctor Martin Kaiser at the, he's the head of the Royal Marston. He was like, how do I get that to play, Jeremy? Great. Thank you. So really an oral therapy that could prevent the CRS or even just treat the CRS for by the patient at home would be highly, highly beneficial to patients' health care systems and really, I think, have to have a big impact on reach and access to such treatments. Super. That's great. Thanks for that, Dave. Again, very insightful. I think we're very excited about the the path we're on with this. I think there's something kinda unique or discussions with pharma, the fact that I mentioned earlier on this is orally delivered, potentially prophylactic, you know, given before the the drug is given before the immunotherapy itself, and there's something they could do at home.

18:56 So as, you know, Dave was talking about to me, there's many advantages to this particular drug. So excited about the the potential for that. But what we'll do, we'll we'll transition. We'll the old expression switch gears, and we'll talk about the the option deal that we signed today with with Silk Road Therapeutics. So I'll start off just giving you a little bit of background into Behcet itself, but Dave or sorry. You know, Tim is gonna dig a lot deeper to this, but, you know, we see this a very exciting rare orphan disease opportunity. And just to set the scene, you know, Behcet's, I think, is quite interesting. There's a there's a there's a link, I think, you know, Tim Tim could talk about, you know, Silk Road Therapeutics that they you know, the the prevalence of this disease is quite mixed. I mean, it's rare and orphan, but across different countries, territories, it's quite mixed. But you can see a very high prevalence here in the likes of Turkey, and it does go along that kind of old silk roads where, you know, the Chinese are bringing their silk back back to Europe. But hi. And and Tim, he he'll talk about later on, run a phase two trial in Turkey. And I think recruitment there will be very straightforward, which again is one of the challenges of rare and often diseases finding patients. But I think having these, let's say, kind of high prevalence regions, you know, aids and assist the execution of of clinical trials. Again, Tim will talk to that. But from a best shot standpoint, let's say it's a debilitating disease with no cure. It causes inflammation of blood vessels and tissue. These are lifelong symptoms, so it's actually quite debilitating for the patients. It causes these oral ulcers, which, you know, you can imagine have an impact on essential functions just like simply eating,

20:27 drinking, and even speaking. So the current standard of care is, you know, is inadequate, and they're looking for for better, you know, options, better solutions. And I think when Tim will share it, the phase two data is quite compelling that Tim has generated, obviously, you know, taking that forward. So I I say quite an interesting disease, rare and often, that's the direction we're taking. I think on the next slide, we will look at we we'll play the patient testimonials just to give you a taste or a context of the of the issues that the disease caused. So, Paul, if you could roll that.

21:05 About six months after I graduated, I started to notice that I was getting recurrent mouth ulcers, so I was having severe ulceration in my mouth to the point where I couldn't eat. And I went to the GP and he said I was run down to drink plenty of water, try and exercise, eat plenty of fruit and vegetables. I think at one point I had up to a 100 mouth ulcers covering a whole of my mouth, the back of my throat, my palate. And then it just sort of progressed from there so I became chronically fatigued. So by chronically fatigued I mean you can't get out of bed, you can't walk a flight of stairs without sitting down.

21:47 And obviously solutions needed. And, again, to provide more context, what what Tim has developed thus far is a topical mucoadherent formulation of pentoxifilene. This topical PTX is the PTX itself has been used in the past as a kind of an oral, you know, IV delivery, but, you know, for various other diseases. But Tim has identified just getting the higher doses of drug directly to the point the pain point, you know, part of the pawn of the the models is is the way to go. And, you know, again, Tim, you know, we'll see the next slide, has lots of experience with with rare and orphan diseases. His phase three trial is, you know, deemed a success. He secured orphan drug designation and indeed fast track designation for the US FDA. And he's positioning the drug as a potential for this five zero five b two, approval path, which is somewhat fast tracked as using as leveraging data already generated. So we've signed this twelve month option agreements. We wanna complete our due diligence. You understand the the clinical regulatory route that will get us as quickly as possible, as affordably as possible to the market. So a bit of work to do there, but I get excited to see what we've done thus far. As I say, Tim now I'll I'll pass off to Tim in a second, but Tim has done tremendous work.

23:00 And I think it's one of these things I will comment on. It's it's always great to have a collaborator who's maybe smarter than you are. Tim has a vast amount of experience in in the space. And you can see here just a a few bullet bullet points. You know, he's lived and breathe its orphan drug development for for many, many years, twenty three years at the US Federal Service, at the FDA, the NIH, and the Centers Disease Control. And indeed, he was the director of the FDA office of orphan products development. So implemented the orphan drugs act. So you couldn't ask for a better collaborator and, again, presided over decisions of 1,400 orphan drug designation applications. So, you know, fantastic to have, you know, have have Tim on board to join us in in this journey. But, Tim, I'll pass across to you now to talk a little bit more about the the product and the program and the and the future.

23:46 Well, thank you, Jeremy. That's a laudatory introduction. I'm really grateful for that. It's a pleasure to be here with POLBEG. It's, it's nice to be with professionals who are are familiar with the specialness of drug repurposing and, finding ways that meet both the the scientific, the regulatory, and the and the commercial value of of bringing a new product forward for for a rare disease. Silk Road Therapeutics is kinda what I did between my two consultancies. In addition to what, Jeremy mentioned, I've also written more orphan designations than anybody in the world, probably about 800 at this point. But I had a noncompete after I sold the first one to IQVIA, a very large company.

24:33 And, that's when I spent this time working on Silk Road. So, this is an accelerated five zero five b two regulatory pathway because it takes a product that's already approved, references all the work that's already been done that's in the FDA files, and leapfrogs over and moves it straight into this question of getting a new indication and a new formulation. So here's the here's the high, 30,000 foot perspective of it. Pentoxifiline, it's already known it's derisked. We know that it's not poison. We know that it's, it's been well used in in hundreds of thousands of patients, and it's got proven safety. And it was proven to have efficacy. And intermittent claudication is what it's approved for in an oral format.

25:18 Now we didn't wanna use an oral format because that means you take a pill, you chew it up in your stomach, your liver chews it up some more, and then you dilute it by the volume of the human body. We wanted the actual strength of the therapeutic value directly on those ulcers, those nasty lesions you saw in this woman's mouth, because we had word that there were a few cases that might actually respond to this, from the medical literature. So we conducted a a and I'm gonna tell you a little bit about the clinical trial that we did in Turkey. So we, got FDA to agree that this five zero five b two pathway can go forward. We're pretty confident that it can be developed in a very capital efficient manner in part because FDA said that eighty percent of the cases can come from Turkey.

26:04 So, wow, we are really able to save a lot of cost because it's about 10% of the cost of The US drug development. And, as I mentioned, I I I'm no shirk when it comes to, regulatory affairs. That's where the fun is if you ask me for this. So let's talk a little bit about Behcet's disease. Nobody knows what caused this. Of course, it was discovered by doctor Behcet. It's, it might be genetic. It might be environmental. It might be infectious, some people have said, but nobody really knows what it is. But it's found along the ancient Silk Road. In fact, I don't know any other disease that's found on a particular road, but but Behcet's is. It's really common in Turkey. That road runs from Istanbul all the way out to Tokyo, and Kusili Behcet back in, like, the late eighteen hundreds discovered that, jeez, all these people are wrong on this road.

26:51 By the way, it's not just oral ulcers. It's also genital ulcers. If it couldn't be bad enough, it hurts so bad. They come in crops. These people cannot eat right. They can't, speak right. They can't have sex. These are all things that human beings want to do. And, accordingly, people with Behcet's have very high suicide rates. It's quite quite awful, frankly, as a disease. Also eye effects they can have as well. So nobody knows what really causes it. Rheumatologists, dermatologists have been treating it. So, we took it upon ourselves during that period of my noncompete to reformulate the product, just taking the active pharmaceutical ingredient and making it into a mucoadherent, product that could be directly applied directly to the lesions in the mouth is where we did the study.

27:41 We took pictures of people as they came in, their index ulcer, their largest single ulcer, and we followed it over time, and we were able to digitalize that, using computer imaging, to see exactly how large those ulcers were. And I'm gonna show you some data on that in just a moment. We also took pain scores and things like that along the way. Here is the money shot. This is what shows you what where we really were. The picture on the left is the ulcer area. You can see that they pretty much all started at the same, level at about six square millimeters. This this is the index ulcer, the single largest ulcer at the time of entry into the into the trial. And over the course of fourteen days, the red line, dropped in size much, much faster than the black line. Remember, these are ulcers that by their natural history are gonna come and they're gonna go. They're gonna come and they're gonna go. This is a product which makes a substantial impact on these ulcers.

28:38 Now, over on the right hand side, you can see that we also took pain scores. That's a lot more subjective, and these people, you know, you might say that, bias could introduce them to that because people knew that they were on drug or not on drug. It was not a blinded study. It was a phase two trial, but it was not blinded study. But the one on the one on the left, with ulcer area, which was digitalized in a blinded fashion, you can't disagree with that. We really had a dramatic effect on these cases. This is forty one patients that we're testing. Okay. Moving along. We have been to the agency a few times. I've had several meetings with them, had open INDs both for the oral, trial, which I just showed you the data from, and for a genital trial, which I haven't showed you data from because we haven't enrolled it, but we got orphan designation, as you would expect. It's a guy who used to sign off on them. Fast track designation, and we've agreed to multiple different things. We have concurrence on a clinical endpoint. That's the holy grail in drug development. If you can agree what it means for a drug to work and you can define it and come to concurrence with the review division, then you're golden because you both have a shared understanding of it.

29:50 And we have open we've opened INDs both for the oral and the genital, activities, and I think I mentioned most of the rest of there. Okay. So we have a, industry team that's leading. In hummus. That's for me. For you. Let's go back to your side. Come on. Okay. Where is that slide? You're part of you're part of the team already, Tim. I love this. Alright. Thank you. Thank you, Jeremy. Thanks for that, Tim. Thanks for that overview. I'm sure there'll be there'll be plenty of questions to come, but I I'll wrap up. This is my last slide. As I say, this takes us to about thirty minutes or so. But just to remind people where we stand, you know, we've got an industry leading team. As you say, yeah, I mean, you've just met Tim there who will be, you know, our collaborator as we as we go through this kind of, you know, option evaluation. And, again, fantastic team to move the company forward, so very excited about that. Again, focusing on these kinda, like, late clinical kind of commercial stage. Again, Amrit like to bring revenue into the company from, from outside products and programs.

30:45 But, obviously, you know, not losing focus on our very exciting and attractive internal programs. Zero zero one, we talked about today. The, the oral GLP one, we haven't. But, for those who, know, who who see the news of late, GLP ones are exploding as a market standpoint. So an oral delivery of a GLP one agonist will be very exciting indeed. And as I said, that'll be in the clinic this year as a proof of concept clinical trial. And then with our AI discovers, we're we're talking to, you know, collaborators about driving that program forward. So we got a healthy cash balance and the focus is near term revenue generation and profitability. I would say, I think we're in a very strong position. We've worked, you know, as a team, you know, very hard, very focused over the last, you know, almost three years is now. But, you know, as I say, a lot a of the road is is traveled, but a long way to go, but a very exciting journey. Again, appreciate the the investors that have come along for for that journey. So what we'll do now, we we'll take we'll take a pause.

31:42 Maybe we'll get Tim and Dave back on, and then we'll have, you know, some questions have have come in, and I'll through these questions and, you know, delegate as best I can. As I say, it's nice to have, you know, Dave and and Tim to share the stage to to answer the the questions directly. So let me start. I'll take the I'll just stick this on. I'll take the first one from Nathan. Thank you, Nathan. Is there a cost for the option for the best assets, and how much will be required to allow commercialization of the assets? Short answer is yes. I think we we talked about together. It was a a modest, you know, payments to get, to lock in the option. And I think that then gives us the the time to spend, again, talking to Tim, talking to his team, talking to the FDA about what that, you know, clinical path, what that regulatory path looks like. And then, of course, we can kinda cost it up from there. But as Tim said, like, know, the option to run this, in Turkey for essentially what's, you know, 10% the cost of running clinical trials in The US is, of course, very attractive, and the FDA will recognize that. So I think that's, you know, there's many, you know, many points about this, asset, about this collaboration that are attractive, and certainly that's, something I think there's a a clear regulatory path ahead of us here. Again, as I say, with Tim as a collaborator, I think, you know, that that bodes well because, you know, he's seen and done this, you know, from an FDA standpoint, certainly the the orphan standpoint.

33:06 Second question, Nate Nathan's hogging all the questions. What kind of a deal are we looking to structure for POLB zero zero one, an outright sale, an upfront, and milestones? Maybe, Dave, if you wanna take a crack at that, I I can weigh in as well. Yeah. So, I mean, we're we're not fixated on on a certain deal structure, but I think the most likely scenario is where we would take some form of investment to accelerate the phase two a study. We we have designs. We have investigators. We're good to go. And if we get support to to accelerate that that investment, be potential optionality in a positive readout scenario from a licensing perspective. That that's a broad level description, Jeremy. I don't know if you'd add anything to that.

33:55 Yeah. No. I think the flexibility is the key point there. And and I I will say our our discussions with PHARMA, they're they're they're they're aligned as well. I mean, they see this as, you know, certainly for CRS. And I and I like to give the example of, you know, what the current standard of care, standard of treatment is an antibody against interleukin six receptor. This is a a Roche drug. But anybody who's in the, you know, the bispecific or CAR T space is using Roche's drug as, like, supportive care. So Roche initially got her indicated. She got her on the on the market for rheumatoid arthritis, but now it's been used for this. So I think our discussions with pharma, they see that, you know, it'll benefit, you know, the drugs that they have themselves in their pipeline, but it could be potentially used broader. So I think they will be looking for, you know, that kind of broader structure of a deal that, you know, they'll take control, they take ownership of. I think we're happy with that. Again, the POOLBEG, you know, development of business strategy has always been to, you know, to partner with PHARMA, and then they'll take it forward into the later stages, phase two, phase threes, and commercialization.

34:52 So, we're flexible, but I think there's there's a clear path there. For that, Dave. Question from Mark s. Could POLB zero zero one be useful for intermittently flaring, relapsing, autoimmune, and floundering relations like psoriasis? Again, a really good question. And there's a little bit of a, maybe, a history kinda lesson here with regard to p 38 MAP kinase. Pharma, you know, they always look for new and novel targets. So I think maybe twelve, fifteen years ago, p 38 MAP kinase, you know, popped up or cropped up as a key regulator of that immune inflammatory response. So a lot of pharma companies went after, yeah, p 38 map kinase, you know, developing inhibitors of this. But what they realized was that even though the drugs they had were, you know, successful in, you know, finally and blocking the target, what they realized was for these chronic indication or these chronic diseases that, you know, if you're on drug for six, nine, twelve months, that the the body or, in particular, the liver didn't like the drug being around. So a lot of pharma then, you know, when it wasn't gonna be their obvious, you know, blockbuster for, you know, rheumatoid arthritis or asthma, they kinda moved on to a new target. So Dave mentioned earlier on about, you know, here's a drug and it's kinda like it's searching or looking for its its, you know, ideal disease. And I think for us, we're we've kinda, I won't say, stumbled across across CRS, but CRS wasn't an issue, you know, ten, twelve years ago where these drugs have been developed. But now with these cancer immunotherapies, it's it's moving through. So, I mean, the the the bottom line there is that it could

36:22 potentially be effective, but we don't have that toxicology coverage for a long term chronic disease such as psoriasis. What we're looking at is these kind of short inflammatory, you know, these acute inflammatory conditions where you're on drug for maybe, you know, two weeks or three weeks, even four, but nothing more. It's just our tox coverage, goes out to three months. They're they're beyond us. So but it's a good question. It's one of these things that it could work in that that area, but not our drug given the, you know, the work that's been done thus far. But, Mark, really, really good question in that regard. Question here from, Martin, how involved will Tim be going forward? I think that As long as they can be. That that yeah. That that's a good way to answer, Tim, is, you know, because I think we kind of indicated this is, you know, this is Tim's baby as it were, and, obviously, he brought this forward a long way. Wants to see it, you know, get to the, you know, the finish line as it were. And I think, we know his, you know, his knowledge and and expertise can be a benefit to POOLBEG. So I think it's, you know, a nice kinda match up of his expertise and our desire to to move in that, rare and offer disease setting. So I like that answer, Tim. Very good.

37:33 Let's see here. Claire asked a question. Keen to understand how many such agreements and options on a setting progress for clinical unmet need that POOLBEG can identify and manage. Good question. Can you perhaps talk us through how you go through that process? Dave, do wanna do you wanna talk about that? Did did you get the question? How many such agreements and options on exciting products for clinical unmet needs that POOLBEG can identify and manage? I guess, our process or our our search and evaluation process for these rare and rare diseases? Yeah. So we we start with a in the funnel, we start with a lot of opportunities, and we have an in house capability with the team to to distill those because for one reason or another, they may or may not be attractive either strategically or for some other reason. And so what comes out the end of the funnel once we we we scour the landscape are are are fewer alternatives that really are a fit.

38:34 And in in in answer to your question is, I mean, there's always question around capacity in in these situations, but but don't forget, we run a very lean structure and we can manage multiple opportunities because we can outsource some of the clinical work as necessary with CRO support. We can use flexible resources if we have to. These are not as intensive as having, you know, fully blown commercial assets, which we will we'll we'll get to. So I I think we can manage a a good number of them on the lean basis that we've shown. We we you know, it was three years since IPO. We we've been burning through that cash very slowly because we we use it very judiciously on opportunities that really fit.

39:21 And and with the team, we have the bandwidth to manage several of these at a time. I will add though that we have prioritized within the we have a longer list of opportunities within the company. What you're seeing today are our top priorities and a new partnership. When we go commercial at some point, the other beauty of orphan disease is orphan diseases are not only serious, rare, debilitating diseases with high unmet medical need, they're also typically highly concentrated and reachable for a small company because they tend to be managed by major centers. So you don't you don't then have to deploy huge divisions than the old traditional pharma model. You can deploy very lean teams who can manage more, you know, a number of leveraged assets in that space, which is also highly attractive from a a a p p and l and contribution perspective.

40:14 Well well summarized, Dave. Thanks for that. Tim, a couple of questions, if you're well, a and b, from from John. Why is topical formulation better than oral formulation? And then the follow-up is what are the benefits of FDA orphan and fast track designation? This is right in your wheelhouse. Sure. So topical is better because it's more of it where you need it. The you can expect that at the ulcers, it would be logs and logs and logs higher concentration than if you're diluting it by the volume of the human body. That's the main reason. It's really a pharmacokinetic kind of exercise. You're getting exactly the drug right where you need it, where it's gonna affect the, underlying vasculature right there. Yeah. Orphan designation, there are four things in the law.

41:02 You get orphan exclusivity, means you get to choose your price, and you're the only one who's selling it. Intentionally, orphan drugs are eye poppingly expensive sometimes. I mean, a $100,000 per patient per year is not uncommon, and that's by design. It creates an incentive for the creation of new products for people with rare diseases, which people normally wouldn't wanna do. There's fee exemptions. You don't have to pay the FDA $3,500,000 to reevaluate your your product. There's tax credits if you're doing trials in The United States, and you're exempted from some onerous pediatric rules. Those are the things that are in the law. What was not in the law, but it's clear, it's part of the reality, is orphans are smaller. They are cheaper. They are faster, and there are fewer clinical trials as you go forward. So all of those things together has led to a situation today where 65% of everything FDA is approving is an orphan drug. Interesting stat. That's wonderful, Tim. Thanks for that summary. Appreciate that.

42:03 Question here again, the Nathan's coming in. You know, I I kind of answered this. How many total patients needs to be the FDA approved next study for silk roll asset? The best way to answer that is, like, that's what our diligence will tell us. So I think that's why we feel we're gonna take that time to nail that down because then that helps us, you know, identify clinical trial sites, what the cost will be, and moving out from that. And I think the following question from Nathan is expected time needed for due diligence. The option is a twelve month period. But, again, I mean, those those who know POOLBEG know that we move rapidly, we move quickly. I think that gives us, kind of sufficient time to get it done. So, you know, we we wanna move forward quickly with this because, again, excited about the data that's already been generated and obviously want to move it, you know, forward rapidly from here. The last, I was gonna say, question received more like a comment. Good to see COLBEG Couldn't resist being more involved.

42:52 What is he bringing into the position of POOLBEG's strategy? Those who know, Kyle knows he brings lots of different ideas, lots of different angles. I think he's you know, brings, obviously, a lot of his own kind of expertise and knowledge. But he's he's always been very much involved, and, you it's know, great to have been as you know, as you say, that's gonna form a kind of a, you know, executive championship role. You know, Carlos is in the office every day. So I I you know, it's not I don't think there'll be that dramatic change. He's he's always been very active and very much involved. And very good There was that last question about the the due diligence, and I think let me see if there's any more coming in. Last question, I think given our our timeline, does the announcements of a joint broker indicate we may need a capital raise, or is it more for corporate action like reversing into Nasdaq targets?

43:42 Yeah. We we've mentioned that before. I do think, Shore Capital, you know, we talked earlier on about, not not essentially replicating the Yammerich story, but sure, we're involved in in Amherich and, you know, the the team here at POOLBEG have worked with them before. So they're very familiar with them. But, you know, we have stated that kind of ultimate objective of, you know, getting on to Nasdaq. We gotta build a company appropriately with that. But I won't say it's direct, but it's as you say, they're very familiar with the average story. So it's again, a little bit of kinda symbiosis, I guess, between the our our understandings and their understandings. But you know? So so we'll wrap it up there. Again, I think we're we're bang on time. I do wanna again appreciate and and thank, you know, Dave and Tim for for joining us even. Thought it was very informative. Again, Tim, really appreciate going through the the Silk Road story and the background to Beshett's and, you know, awful disease. But, hopefully, we're we're in a position to bring some treatment and therapies to patients that need it most. And lastly, I just wanna thank all the attendees this evening. If there's any kind of questions I missed, obviously, we do do a follow-up as well. But I appreciate your time this evening. I know some of you are probably rushing off to see, your Champions League semifinals or indeed, top of the table clash in the the championship.

44:53 But, hope you have a good evening, and, we look forward to giving you, further updates, for POOLBEG in the not too distant future. Thank you all. Fantastic. Thanks, Jeremy. Jeremy, David, Tim, thank you indeed for updating investors today. And as Jeremy said, of course, any further questions, the team will be able to review those. Can I please ask investors not to close the session? You should now automatically be redirected to provide your feedback in order the team can better understand your views and expectations. This will only take a few moments to complete, and those are greatly valued by the company. On behalf of the management team, POLBEG PHARMA PLC, we would like to thank you for attending today's presentation, and good evening to you all. Thank you, Paul. Thank you. Thank you.