Poolbeg Pharma PLC

Good afternoon, and thank you for the introduction. I appreciate everybody joining us this late afternoon.

Finally, a bit of a sunny Dublin. It's -- bleak winter is over.

And we're delighted here to be able to present on the back of our full year results announced this morning, company update, company presentation and let you know where we are with particularly POLB 001 clinical trials. So again, appreciate you joining us this evening.

And I'll be sharing presentation duties tonight with Liam Tremble, our Principal Scientist, who will talk more of the POLB 001 clinical trial attributes. So just to give a setting, just a grounding, a reminder, Poolbeg, we're a clinical-stage company developing POLB 001 that we believe has the potential to transform the lives of cancer patients by delivering these cancer immunotherapies in particular safely and locally.

There's a big unmet need. There's a lot of issues around Cytokine Release Syndrome associated with cancer immunotherapies, and we believe we have a solution for that.

We'll talk a little bit more about the scientific and medical rationale for that later on. We're also developing an oral medication for obesity treatment, we'll touch upon later on as an oral GLP-1.

Again, very exciting space to be in. We are an AIM listed company, listed in London.

And we believe we've got a strong investment case. We've got a terrific team here behind us, both on the, as I said, the clinical business development, which will be critical, and I'll talk a lot about that and, of course, on the corporate and finance side as well.

The clinical -- stage programs we're developing, getting into the clinic, these are clear large unmet medical needs and large, growing markets. We've done an in-depth analysis, particularly on POLB 001, again, we'll touch upon later on.

So very excited about to get these moving forward. We have financial runway into 2027.

So we've got several key clinical inflection points coming up. So we're funded through these clinical inflection points and into 2027.

And that gives us scope then for partnering, for collaboration and licensing discussions. So again, we have had many discussions with potential partners over the last several months.

Again, I'll touch upon those later on. So there's a strong interest in what we're doing.

So a strong potential to secure partnerships. Of course, what comes with that is financial revenue, and we'll touch upon that later on.

So right now, we're certainly in clinical development execution mode, particularly with POLB 001. But over the last 6, 9, 12 months, we've been gearing up on the partnering aspects, talking to a lot of big pharma companies, midsized pharma companies, and again, pitching and promoting Poolbeg.

We've got high-value programs with strong IP. Those of us -- those of you who have kind of followed Poolbeg have seen the RNS that's talking about IP grants, very important in this industry.

The proof-of-concept clinical trials we touched upon are ready to be done, touch upon the timing on that later on. And what we've built thus far with regard to the programs, we've got very high-quality and compelling human data in the POLB 001 setting.

Again, touch upon that, Liam will cover. So again, our discussion with partners have gone exceptionally well.

They're very keen, obviously. They see the value inflection point, and the derisking episode will be the clinical data that will read out in the summer of this year.

A summary of what we announced this morning in our annual results. So we believe 2025 was a transformative year for Poolbeg.

We really got ourselves kind of focused and driven and aligned with not just the market, but the clinical community as well, the Cytokine Release Syndrome community in the cancer immunotherapy space. We finished the year with GBP 7.7 million in cash, again, a healthy cash position.

That allows us, as mentioned, to execute on our clinical development programs. The first bullet here, we have the TOPICAL trial, is fully prepared.

And with that, that's the POLB 001 CRS prevention trial. We've appointed ACT as the clinical trial executor, the CRO that will run the trial.

We've had fantastic discussions with Johnson & Johnson, and they have agreed to supply us with their approved bispecific antibody teclistamab. And they've given that to us at no cost because, obviously, they're keen to see the reduction in Cytokine Release Syndrome or CRS with teclistamab.

And we've enrolled now -- we've lined up 6 U.K. cancer centers to be part of this clinical trial, and we've finished the protocol and we've gotten MHRA approval, which is very important to allow us to start dosing patients.

Importantly, during 2025, we've got Orphan Drug designation from the U.S. FDA.

So again, they recognize the scientific validity of what we are doing, what we are trying and reducing CRS. It is linked to patients who will receive these T cell engagers.

And these are wonder drugs that are now demonstrating cures in these blood cancer patients such as multiple myeloma. So again, they're very good to get that.

There's a lot of additional bonuses that comes with that, we'll touch upon later on. But certainly, from a partnering standpoint, that actually adds a lot of value to the program when it comes to talking with a big pharma company.

So intellectual property is very important for this industry. It protects the programs as we get to the market.

It doesn't allow any competitors to invade our space. We did get multiple patents granted last year.

Many of you know, in the hypercytokinemia or the severe influenza space, we've been progressing down those roads for many years. But importantly, we got our first patent grants earlier this year in Australia when it comes to the cancer immunotherapy and CRS aspect.

So very happy with that. And again, that helps bolster the discussions with pharma companies when they know that the program is protected.

We also generated last year positive in vivo data, again, demonstrating that we can impact Cytokine Release Syndrome in an in vivo model. Liam will talk later on about a very exciting program we have in collaboration with Johnson & Johnson with the University of Manchester, that's looking into broader research into the immunology around Cytokine Release Syndrome.

And then lastly, making progress on our oral GLP-1 program, which is now expected to start in the second half of this year due to the revised manufacturing lead time. I will highlight that last year, we were, again, very delighted to fund-raise GBP 4.865 million from the market.

Tough conditions in the market, but I think the investors saw the potential of what Poolbeg is doing and what we can bring to the market. And speaking of this market, we've done some independent analysis where we see that preventing CRS in these cancer immunotherapies is a market opportunity of over $10 billion.

And we'll talk about the details around that later on. When it comes to 2026, this year, again, we are at full pace right now.

It's a full-steam-ahead situation. As I said, the first 4 months or so of this year has been, again, very productive from a Poolbeg standpoint.

I mentioned the patent grant, and again, that's in the cancer immunotherapy space, which again adds validity to the program that we're doing. And again, we're hopeful that there will be many other opportunities to announce patent grants in other territories as we're going forward.

We are, as I said -- have a wide patent application in various territories and they're moving through the processes there. It can be kind of a long process, but I think we're encouraged by the responses we're receiving from the various PTO organizations and the EPO organizations going through.

Again, exciting this year, we've -- our LPS challenge study. This is our Phase Ib study that again was a very successful study run in the Netherlands.

We were able to get peer-reviewed data published in that. And again, this peer-reviewed is important because as people look at the data, they look at the paper itself and they saw worthy of publication.

We've gotten some very good feedback from that. And that springboards us then onto -- into the CRS prevention study we're talking about.

When we see prevention of that inflammatory response in the LPS challenge, we're hopeful that we'll see a similar prevention of the inflammatory response when it comes to Cytokine Release Syndrome that's caused by these cancer immunotherapies. We're very excited.

We had several discussions last year with Dr. Adrian Kilcoyne.

He's an expert in the Cytokine Release Syndrome space. He's had many, many interactions with the U.S.

FDA around developing clinical trial programs around CRS. He came onboard to join our Scientific Advisory Board and is now a very active member of our development team when it comes to planning what the future holds for CRS clinical trials.

I mentioned we got MHRA approval this year as well. Very exciting.

Again, it's a rigorous process where they take and review all of our data, clinical and preclinical. As I say, it's a very high bar for any drug to get into human clinical trials.

So the MHRA gave us that approval in the past few weeks and we've announced at the RNS. And that gives us the green light to progress and move into the clinical studies that Liam will talk about.

Again, we want to make sure, when we're talking to partners, we want to make sure -- or we make sure that they're aware that this is a significant market opportunity. So to achieve that end, we've had independent analysis done where we look at the market, the Cytokine Release Syndrome, the incidence that occurs in the various bispecific antibodies and CAR T cell therapies, these T cell engagers.

And the impact it has on the health care system, the impact it has on patients, what it costs for the health care systems. So again, we were able to do an in-depth analysis looking at -- it's a multibillion-dollar peak U.S.

sales potential stand-alone. So we spoke to 3 different payers talking about CRS and our program, and they're very enthused that this is a drug that they would happily reimburse if and when it gets onto the market because they see CRS is a cost drain for them as an insurance company.

So they'd like to get rid of that. And as you know, we're talking about prevention of CRS.

So I think it's a very important goal, a very important goal that we want to achieve here. And it's very well received by these insurance payers both in Medicare as well and Medicaid.

Again, momentum in partnering has accelerated. As we get closer to the clinic, it's becoming more kind of apparent.

What we have here is a very exciting program, as I mentioned, some of the large pharma companies and more midsized companies that maybe are in the more cancer supportive care area specifically. So they're all very excited to wait and see what this data hold, this clinical data hold as it reads out.

And as I said, we've got multiple upcoming milestones in the near future. So again, I talk about momentum, I talk about running at full speed.

So as I say, the POLB 001, the trial site initiation visits have been scheduled. So these are the 6 sites that we've -- are going to run this trial in the U.K.

It's going to be led by Dr. Emma Searle at The Christie in Manchester, and she's brought some of her hematology colleagues onboard to be part of this clinical trial.

So very excited to get that moving. As I say, the next step then is trial -- patient recruitment and dosing, so basically getting the patients onboard, these multiple -- these relapsed/refractory multiple myeloma patients, get them onboard and get them dosed, to get the clinical trial to -- the clinical trial up and running.

But we always comment that like 80%, 90% of the work is done in advance of dosing patients. So we've come down the road quite a long way.

So we're very excited to be at this stage right now. So again, we're looking to have this interim data, the POLB 001 CRS prevention data, in the summer.

So again, it's linked to the patient enrollment. These are very short clinical trials Liam will speak to, so we should have data relatively rapidly out here.

And then the second half of the year, we're looking for to commence our oral GLP-1 clinical trial. I'll talk a little bit about that later on.

So fantastic, exciting time for the company. Again, very productive 2025, very productive first 4 months of 2026.

So we're excited to be progressing this forward, and again, generating that key data, which will be the value inflection point, really derisking the program. And then transactions and collaborations, license agreements will follow from there.

So we're very excited to be in the space. And again, thank you for attending this evening.

Liam will present on the POLB 001 program. I'll return in the end and talk about the market opportunity and the oral GLP-1 program.

And then we will open up the floor for questions. So again, thanks for your time right now.

Liam, over to you.

Brilliant. Cheers, Jeremy.

So just I'm going to do a brief introduction to POLB 001. But before we jump into the asset itself, I want to give a little bit of context of where the field has come.

So obviously, over the last number of decades, a massive amount of progress has been made for cancers. It's not been symmetrical.

Some cancers have had significantly more progress than others. But if we look at something like multiple myeloma, it's really been a poster child for where significant progress has been seen.

So for somebody diagnosed 23 years ago, 2003, 5-year survival, 10-year survival really wasn't that great. 30%, 5 years; 10 years, about 20%.

And it's because the treatment options really weren't that effective. And a lot of these you might be a little bit familiar with: pomalidomide, chemotherapy, corticosteroids.

They didn't do a massive amount for all patients. Fast forward 20 years and the progress has been exponential.

If you're diagnosed now, 5-year survival rate is well over 80%, or estimated; 10 years, well over 60%. And I say estimated because the progress is so quick that the pace of clinical trials is faster than the survival data we have from those clinical trials.

So at the moment, in multiple myeloma, we've obviously -- we've had immunotherapies be approved in the last number of years, so CAR T cell therapies, bispecific antibodies, but also a number of other therapies like antibody drug conjugates, proteasome inhibitors. It's quite common now for multiple myeloma patients to actually get quadruplet therapies as first line or even quintuplet now because the therapies are so effective.

And a lot of the projections, so this is a disease with a median, so 50% of people get it age 69 or older. And some of these frontline therapies have median progression-free survival projected to be up around 15 years.

So really in myeloma, you're at a position where people are discussing functional cures where really patients will pass away from old age rather than their disease. And that's what we're ultimately trying to achieve for all cancers.

What's important about this is that when we get to this stage where multiple effective options exist, patient preference has a significant impact on market uptake of the drug. Patients don't always go for the drug with the best overall survival.

They also consider things like time at home, treatment time, having to travel to hospitals. Some of the tolerability issues can be quite significant for these drugs.

The immunotherapies, for instance, have a lot of severe infections that can happen for years afterwards. So they all have a very meaningful impact on what drugs patients actually decide to take.

So for these CAR T cell therapies and bispecific antibodies, they really are revolutionary. For the CAR T cell therapies, are potentially curative in some patients.

And it's really making sure that they are accessible to all patients. So if I zoom in on the bispecific antibodies, these are breakthrough immunotherapy as well.

And they're extending into early lines of therapy. As I'll show you on some of the later slides, at the moment, they have to give micro-step of doses.

And it's quite common for patients to be hospitalized for 5 to 10 days just for these initial doses because of the risk of CRS. So they have a significant amount of time in hospital just to get on to these therapies.

And then obviously, they have downstream infection risks as well. So a lot of these therapies as well are restricted to specialist cancer centers who have the expertise and the tools to manage these patients.

It depends on what country you're coming from, but in some countries, this is a very significant obstacle to accessing these therapies. Particularly in the U.S., people talk to things called treatment deserts.

It's where patients can live hundreds of kilometers and miles from their nearest hospital who can administer these therapies, and really is a significant issue for a lot of late-stage patients. So CRS, as I mentioned, is a major barrier for some of these immunotherapies to become more widely available, with over 70% of some patients being affected on the immunotherapies, and hospital stays due to the risk of CRS may negatively affect the uptake of these therapies themselves.

So the next slide. So just zooming in on that for 2 seconds.

So on the left-hand side of this slide as well, we've shown a simple diagram to have these therapies and how 001, POLB 001, could change the treatment paradigm. So the current standard of care, on the left here, is typically a patient will come into hospital, they will get their immunotherapy.

And the immunotherapy will actually activate their immune system. And what this induces is Cytokine Release Syndrome.

And the risk of Cytokine Release Syndrome or indeed CRS after the onset can result in significant hospitalization for these patients. So it can persist for days to weeks.

And in severe cases, it can mean that the patients have to discontinue the immunotherapy, so they have to opt for something else. And obviously, they lose time between these different choices.

So it's really important that when patients do opt to go on to a therapy, that they can continue with it. If we bring in 001, potentially, we have something where they can take orally before they have the immunotherapy.

They come into the hospital, they are administered it. And rather than the immunotherapy causing activation of the immune system, we still allow activation of the immune system, but it doesn't cause Cytokine Release Syndrome.

And if we're able to avoid Cytokine Release Syndrome, then we can potentially prevent this hospitalization and make this step onto the treatment a lot more manageable and feasible for the patients themselves and for the health care systems that have to deliver it. So just zooming in on POLB 001 a little bit deeper.

So it's a p38 MAP kinase inhibitor. What this means is that it selectively prevents excessive inflammation without immunosuppression.

So compared to some other drugs, they completely block a pathway. Actually, p38 is kind of like a master inflammation switch where if you activate p38, you can get global expression of a lot of pro-inflammatory cytokines, which are things that cause CRS.

If you don't p38, actually the production of these falls 80% to 90%. So the drug itself is an oral agent, again, particularly important where we positioned this as a prophylaxis.

It really needs to be easy for the patients and the hospitals to administrate. And we have a strong patent portfolio with potential coverage out to at least 2044.

So we do have a strong preclinical and clinical data package to date. So favorable safety and tolerability profile, which again we think is really important as we move into this indication.

And we have potential inhibition of IL-6, TNF and other key inflammatory markers. IL-6 and TNF we mentioned because we know these are the main drivers or significant drivers of the Cytokine Release Syndrome itself.

So as well, Jeremy will go into later in the presentation that there is a very significant market opportunity behind this drug. So over USD 10 billion market opportunity.

There isn't anything approved in the preventative setting and there's a growing number of these drugs that induce CRS and they're going into earlier lines of therapy. So this problem is only becoming much, much more significant for hospitals across the world.

So at the moment, these bispecific antibodies will only be delivered in specialist cancer centers until there's a way to make them safer and easier to deliver. And POLB could make that treatment safe enough to extend bispecifics to a much wider treatment population.

Just there in the bottom of this slide, so we have engaged a lot of key opinion leaders on this who also believe in the program. And that's Gareth Morgan from the U.S.

Just to show you some of the data that we've presented before. So the last clinical trial that POLB 001 was in was an LPS human challenge trial.

So this is essentially where you use a pro-inflammatory stimulus, LPS. It's a component of the bacterial cell wall that induces a mild inflammatory response in patients.

So we can give this to healthy volunteers. It stimulates the immune system very similar to the way the immunotherapy would.

And they get something that approximate Cytokine Release Syndrome. So it's an incredibly strong model for us to test the efficacy of POLB 001 in.

What we also saw in that trial was that POLB actually had an excellent safety and tolerability profile, as we expected. We were able to confirm potent target inhibition, that's the p38 MAP kinase.

And we had a clear dose response relationship observed, which is really important from a drug development perspective. And then we also, from a CRS perspective, had a major reduction of key inflammatory cytokines.

On this slide, we're showing IL-6 and IL-8. So just briefly, this LPS challenge trial was placebo-controlled and had 3 different doses of POLB 001.

So the gray line, as indicated underneath, is the placebo. The green line is 30 mg of POLB 001 given twice daily.

The blue line, again, twice daily 70 mg, and the red line is the highest dose of 150 mg POLB 001 given twice daily. And what we can see in the graph is that actually, if you just give placebo with the LPS challenge, you see this spike of IL-6 and as well, on the right-hand side, IL-8.

But actually, as we introduce increasing concentrations of POLB 001, we see a suppression of these increases, which is exactly what we hypothesize it will do in Cytokine Release Syndrome. So the lowest dose produced a small decrease, but the 2 upper doses, actually you can see, they almost overlap, and this is probably the maximal inhibition through p38, where the inhibition is in the region of 85% to 95%, which is really promising as we move forward into further trials.

So we have the potential to effectively prevent Cytokine Release Syndrome while preserving key immune system functionality. I think that's a key element that we always have from clinicians in that a lot of the existing drugs and that completely blocked pathway, they have their downsides.

They often induce cytopenias or other adverse events, which really isn't preferable in an indication like this. So as Jeremy mentioned, we are really excited at the moment.

We recently announced that we have all the approvals in place to start dosing patients, and the trial is moving forward at speed. So POLB 001 first-in-patients TOPICAL trial, and it's being conducted in the U.K.

So it's a trial of prevention of immune cytokine adverse events in myeloma. It's being led by Dr.

Emma Searle, who's a leading hematologist based in The Christie Hospital in Manchester. And it's being run by Accelerating Clinical Trials.

Again, we've previously spoken about this to the market, that this is a specialist blood cancer organization who are equipped to run trials in the U.K., in these clinical trial centers that we're tapping into to recruit these patients. It's a really strong team who know the sites, who know the investigators, who are equipped to really accelerate this trial the way we need to.

And the objective of the trial is to investigate the safety of POLB 001 and also the efficacy, in particular, its ability to reduce the incidence of CRS in patients receiving an approved bispecific antibody, teclistamab. Teclistamab being an immunotherapy that induces Cytokine Release Syndrome.

So we'll have approximately 30 patients, and we will be recruiting a patient population of relapsed/refractory multiple myeloma patients and receiving this antibody. So we are really excited.

All of the leading sites in the U.K. are really participating on this trial.

So it's been led by Dr. Emma Searle, as I mentioned, at The Christie.

But also we have UCH, we have The Royal Marsden, Birmingham, NHS North Midlands, Royal Stoke and Edinburgh. And so we have an exceptionally strong team that we're really optimistic that we can complete this trial quickly.

Just a little bit more detail about the actual trial itself. So this is the design of the trial.

On the top left, this schematic is showing the trial design. So I mentioned with the bispecific antibodies earlier in the presentation that they're getting step-up of micro-doses.

So if you were to give a full dose of these bispecific antibodies, what would happen is you'll activate your T cells, you get other immune cells activated, you get overwhelming Cytokine Release Syndrome, which could potentially kill patients. The only way at the moment to deliver them safely is to give these micro-doses.

And the micro-doses are there to give the body a small exposure to cytokines. And the body needs to get used to seeing these cytokines without inducing severe CRS.

And once the body has seen the cytokines once or twice, actually then they can go forward with normal dosing. But these step-up doses are critical purely to mitigate the risk of Cytokine Release Syndrome.

These typically happen over a 5 to 8-day period. During this period, patients are typically hospitalized, depending on the cancer center that they're in.

And so what we're trying to do in the trial is we are going to pre-dose POLB 001 for prevention from before that first step-up dose until after the first dose. So here in the schematic, that would be indicated on day 1, 4, 7.

So we'd be dosing. Actually 96% to 100% of all the Cytokine Release Syndrome happens in that period.

And that's the period that's really hard for clinicians actually managing these patients at the moment and is mandating the hospitalization. So twice daily oral dosing of POLB 001.

It's a single-arm trial, meaning no placebo. But we're really trying to get the evidence of efficacy as quickly as possible, so we want to give everybody our drug.

30 patients, as I mentioned. Teclistamab, really promisingly, is being provided by J&J.

And it's an open-label trial in that all the patients know that they're getting POLB 001. So we're really excited that we have fantastic investigators.

We have the collaboration with J&J. And we have the right team to really deliver this trial quickly.

And the protocol has been finalized. All the regulatory approvals are in place and site initiation deals are scheduled, and patient recruitment and dosing to commence shortly.

And we hope to be able to give further updates as we go. The key endpoints, as I mentioned: incidence of CRS, severity of CRS, confirmation of the safety and pharmacokinetics.

That's more just to make sure that the drug, as I mentioned, is exposed to patients at the right level. And then obviously, CRS management and tocilizumab usage.

CRS management, what we mean is the duration of hospitalization. So everything to do with the current challenges of managing CRS to be managed or measured in this trial.

We have a great team of investigators. We have J&J.

That's because there is a massive amount of excitement about this program. If we can find a drug that really solves the CRS problem, I think a lot of people realize the potential of it.

So there's also been a GBP 3.4 million grant to the University of Manchester and The Christie. The program is called RISE.

So RISE is about reducing immune stress from excessive cytokine release with advanced therapies. And it's being led by the University of Manchester and NHS Christie Trust, where we're the lead site on the TOPICAL trial, is the clinical lead.

We are the lead business partner because we are experts in Cytokine Release Syndrome at this stage. And J&J are an industry partner providing teclistamab for it as well.

So it's being led by a fantastic cell therapist who delivers solid cancer cell therapies to patients, Dr. Jonathan Lim.

He's a Clinical Senior Lecturer and Honorary Consultant Medical Oncologist at The Christie and the University of Manchester. So we really have a multidisciplinary team.

And the whole idea of this grant is actually to research things of this is an on-target effect of immunotherapy. So there's nothing surprising that these immunotherapies induce Cytokine Release Syndrome.

It's predictable. We know the mechanism, we know the triggers.

We know how to potentially prevent it. But that's a great opportunity to learn more, to really research this in the clinic.

So POLB 001 is going to be a key element of the overall research grant for preclinical and clinical, but the TOPICAL trial itself will be a central focus of it. So we'll be generating additional clinical evidence as part of this on CRS from bispecific antibodies and CAR T cell therapies.

Because as Jeremy will have mentioned before, there is a major commercial opportunity for the prevention of CRS related to CAR T cell therapies as well, not just bispecific antibodies. And so this is real significant recognition of the unmet need in CRS, and it's something that we're really excited for.

We do expect if there's positive results from this trial, that the interest in the program is only going to grow. So we're really excited moving forward.

And with that, I will hand back to Jeremy.

That's wonderful, Liam. Thank you for that.

I think it's a very nice segue as we do talk about the market opportunities. So as I mentioned at the outset, we've done a lot of work trying to assess what the global CRS market looks like.

We've taken on board some consultants to get that independent perspective. And I'd say it's a very important acknowledgement when it comes to the partnering and partnerships, kind of what the value we're bringing to the table is here.

So as I say, we're looking, from our analysis, about a $10 billion market opportunity. And I'd break that down as to how we came to that number briefly.

But I just want to flag that for both bispecifics and CAR T, these are quite expensive drugs in their own right. But as Liam mentioned, we believe that these are life-saving drugs.

Sometimes there's cures observed. But for CAR T, now it's more of a laborious approach where you take a patient's T cells out, you re-engineer them, and you introduce them back in, and they're bringing the immune system closer to the tumor.

And these are quite expensive. But as I said, these are reimbursed in the U.S.

by the American insurance companies. When you look at bispecific antibodies, it's slightly less, but it's still a significant cost to the insurance companies.

Now what we did with this analysis is that we narrowed in on 2 different tumor types, 2 different blood tumor types: diffuse large B cell lymphoma and multiple myeloma. And if you look at the markets in the U.S.

and the European 5, the incidence of these diseases, they total to about 500,000 patients between now and -- between 2023 and 2030. So the market is kind of large.

Market is growing. But what we did when we looked at what would we charge, what would we charge the insurance companies for POLB 001, we looked at a very interesting and probably very appropriate comparator.

This is a drug, Neulasta, which is used to treat neutropenia. So when patients get chemotherapy as an example, then they get -- they're obviously trying to reduce their tumor burden, but it also reduces a lot of their kind of white blood cells.

So this Neulasta brings those back up. When that was launched many years ago, it was introduced in at about $18,000 per cycle.

So we kind of took that realm, that POLB 001 could be in that. If you take roughly $20,000 by the 500,000 patients, then you're looking at a $10 billion market opportunity just for these 2 tumor types and for these 2 markets, the U.S.

and the EU 5. And obviously, we could go broader than that.

We've mentioned a few times that CAR T cell therapies, bispecifics are now moving more into solid tumors, so there's an opportunity there where CRS is also observed. And interestingly, looking into autoimmune diseases.

But that's a story for another night. But as I say, we're looking to prevent CRS from happening in the first place.

And I think that if we -- this is where we got J&J's attention, for example. And I'll talk a little bit later on about our partnering initiatives.

But they got the attention. To prevent is obviously better than cure.

It's an old statement that's well worn. But they see that if we can prevent CRS, then they can get their drug, their bispecific antibody, as an example, into community hospitals, getting it away from these dedicated cancer centers.

Because you need people on hand to manage the CRS, but if the CRS isn't there, then we're in a fantastic situation. So as I say, it is a cost to insurance companies, cost to the health care system.

We talk about Grade 3 CRS actually costing greater than $70,000 as a management, as treatment. But of course, let's not forget the patients who have to go through this issue.

So there's many things at play here. But more recently, this is the most recent piece of work that we did that was very enlightening, where it's one thing about understanding the patient population, these multiple myeloma, diffuse large B cell lymphoma, but we needed to talk to ultimately the payers.

These are insurance company. We looked at the U.S.

because that's the large and major market. And we partnered with Acumetis Global.

So they held 3 different payers that cover 75 million lives in the U.S. They introduced them to POLB 001, the target product profile, what it is, what it does, what it's intended to do, and asked about payments.

"What would you be willing to pay for these drugs?" And I think there's a -- it's quite a long quote here.

I won't go through it all. But it was very clear that there's a willingness to pay for a commercially meaningful price for POLB 001.

Because they know the offset. They know that they can -- patients will spend less time in hospitals, so overall their insurance burden is less.

It's obviously beneficial for the patients. But it takes the pressure off the health care system as well.

And maybe it spreads a little bit thinner. Instead of these patients being in these dedicated cancer clinics, they can go kind of outside to their community hospitals.

And that's really where people are attempting to go, have the treatments on your doorstep. And I think from a psychological standpoint, these patients are already going through cancer treatment, but if they can get it closer, their treatments closer to home, all the better off because they'll have family support networks around.

So as they say, they see that POLB 001 is a compelling CRS solution with significant market potential. So that was obviously music to our ears when we -- we kind of believed in the program, but to see it in black and white that the payers would be willing to pay was very exciting and very gratifying, I must say.

But again, from the market opportunity, and I've outlined this already, so 500,000 patients. There is that bottleneck where they can't get access to the drug rapidly because beds are being taken up in the CAR T setting.

As I say, if you can remove CRS, then you can open up this. And we've talked, as Liam said, many key opinion leaders, thought leaders in the space, multiple myeloma docs.

And they're all echoing the fact that if you can reduce or eliminate CRS, then a whole load of infrastructure falls away. Their lives are easier, the patients' lives are easier.

And as I say, we now, we're confident that the insurance companies are willing to pay for the drug as it goes forward. So again, very exciting time for the company.

Again, there is -- I see a question coming in about partnering, so maybe I'll address that right now. With my background, I'm a scientist by training, but in the industry, I spent a lot of time on business development in the partnering setting.

So we spent the last, in particular, the last 9, 12 months really focusing, ramping up the partnering, as we're getting closer to the clinic, that laying the groundwork, talking to the big pharma companies, as I said, the midsize companies, about 001, what we do. We've caught a lot of attention.

And I think that happens, and it's not by coincidence, that it's closer to the clinic, because then there'll be a data readout, and as I mentioned, a derisking readout. So again, people appreciate that there are more and more cancer immunotherapies coming to the market, and CRS is still an issue with them.

Pharma companies are looking to fill their own pipeline as well with new programs coming through. And that's all linked to the patent cliff.

I mean it's been shared that GBP 300 billion in annual prescription drug revenue will fall off because of patent cliffs. They'll be substituted by generics.

So pharma need to kind of boost their bottom lines, so they get more drugs into their pipeline. But I think when we talk to the smaller companies and show that we can have POLB 001 in combination with any and all CAR T or any and all bispecific, they see this as a significant market opportunity.

So over the last, as I mentioned, 9, 12 months, we've attended a lot of conferences. JPMorgan in San Francisco this year was particularly productive.

Again, face-to-face meetings with decision-makers at pharma companies. We attended BIO in Europe, LSX as well.

And these are, again, lots of partnering meetings talking about POLB 001. Just last weekend, Liam and our clinical colleague, Mina, attended the British Society of Hematology, meeting directly with our investigators, again, building momentum on that front.

And then in the near-term future, we're attending the European Hematology Association meeting in Stockholm and then BIO Convention in San Diego. And again, that's where all the pharma kind of descend on a city.

Obviously, the EHA is hematology-specific, so we'll be talking directly to the decision-makers in the hematology or myeloma spaces. And then BIO is on the business development front.

And we've got meetings set up there as well. And again, they're very excited to see the clinical data as it comes through.

So I think, obviously, from our past successes, you could say, great discussions with Johnson & Johnson providing their bispecific antibody free of charge. They want to see CRS reduced, and we're hopeful we'll be able to do that with this TOPICAL trial we've discussed.

And as I say, the midsize pharmas are interesting because they've got smaller pipelines, but they see this cancer supportive care element that they could obviously get this drug to market relatively quickly. We can talk separately on that, but these are very short-term trials because we're only looking at that initial immune or inflammatory response.

And as I say, lots of really productive discussions there. We have a virtual data room that's populated and open.

And we've got people in the data room kind of exploring the, as I say, the preclinical and clinical data we have. And it's all a case of once we have that clinical data in hand, then we kind of trigger those negotiations around, a deal and a transaction, to generate revenue from there.

So again, I'll reiterate from a POLB 001 standpoint, we're very excited with the progress we've made. And obviously, in the not-too-distant future, there'll be very exciting milestones to report.

I think we've gone over a little bit on time, so I will just kind of go briefly through the GLP-1 program. People are very familiar with GLP-1, initially diabetes drugs, but now very applicable to obesity.

These are primarily given by injection, and there's a big need or an unmet need to have an oral option for that. We've partnered with AnaBio here down in Cork.

They've got drugs that -- sorry. They've got products on the market that use this encapsulation technology.

And it's more in the food science space. But we're using this technology to encapsulate GLP-1, protect it from the stomach acids.

And when there's a change in pH, that is released in the small intestine, which is the site of action here. So a huge market, huge opportunity.

In our partnering discussions we've had at the partnering conferences, people have reached out to discuss this program. And as we're standing now, we've got a clinical trial that's designed, ready to execute.

We are moving into that kind of manufacturing phase, the timelines for manufacturing, that's going on. Again, it's -- the manufacturing has been demonstrated before.

We've done a lot of the validation studies on acids, et cetera. So now it's just to get that GLP-1 material ready for the clinical trial.

It'll be run by a Professor Carel le Roux up in University of Ulster. He's very well recognized in the metabolic disease space.

Again, it's a very straightforward clinical trial in that it's 20 volunteers. We're looking at safety and tolerability and pharmacokinetics, getting the drug onboard.

And we'll test that from glucose tolerance test. Very simple study where we want to see the drug having effect on metabolism essentially in these volunteers.

So it's designed to get the rapid readout and so very excited to see this program move forward as well. Again, there's a good deal of interest in that from a business development standpoint.

I'll wrap up with this slide. I certainly want to leave time for questions and I see there are a few coming in.

But again, a reminder, a very experienced team. We are executing right now.

And I think we've done a very -- I'm very proud of the team. We've done a terrific job the last 12 months to move 001 to be here.

We are on the precipice of dosing patients, so that's very exciting. These are very high-value programs.

I think we've found the right disease for POLB 001 to go after, this acute inflammatory condition. Importantly, with the fundraise last year, we've got our financial runway into 2027.

So that gives us time and scope to negotiate the best deal for Poolbeg once we have the data in hand. But as I said, the partnering discussions have been on many levels, as I say, large and small companies.

We've got many discussions going on in parallel, data room open, reviewing the preexisting data. But as I say, people are waiting for this clinical data to read out.

Because that's the value inflection point. That's the derisking episode where you're having data in this TOPICAL clinical trial in multiple myeloma patients -- relapsed/refractory multiple myeloma patients.

This will be the key trigger for Poolbeg. So again, thank you all for your time again this afternoon, this late afternoon.

And what we'll do now is that we'll switch to some of the questions that came in, and again, appreciate your time on that.

All right, so we'll jump straight in. Oliver has a question.

When are the CRS trials due to be completed? Summer '26.

Can you pin this down, June, July or August? Although summer in the U.K.

is virtually a 2-week period. Nice one.

Good bit of levity there. Also once completed, will it be go or no-go decision?

Or is there a potential for a phased decision tree solution if not the results you're looking for? I think, listen, that's a really good question.

We could spend a while kind of talking about that. I think we mentioned earlier on, like one of our ambitions was to get the data as quickly as possible.

That goes without question. And this is why with ACT, who are going to run the clinical trials with Emma, we're zoning in on 6 clinical trial sites.

Now we're exploring options for more. And what comes from that then is kind of rapid enrollment.

That's ultimately the goal here, get more patients onboard quickly, get more drug onboard quickly. Liam and Mina and the team have done a terrific job of kind of lining up that kind of analysis that comes after that.

It's well understood that teclistamab drives CRS in greater than 70% of patients. But we're going to analyze that immune and inflammatory response at a molecular level.

So these are looking at all of the cytokines that are there, signs and symptoms, but at the kind of blood and molecular level looking at that. So it depends is probably the answer.

But it is once we have that certain number of patients going through where we can kind of interpret the data. We've done statistics, et cetera, that up to 30 patients would be the full trial.

But as mentioned previously, this is an open-label trial, so we'll have access to the data pretty rapidly on that for each individual patient. So it's not blinded, so we know that each patient will get the drug.

So it's a really good question, but as I say, we're planning and what we've built so far is going to get rapid enrollment to say 6 clinical trial sites, maybe more. And then your question around decision trees.

I mean it's -- obviously, we got to wait to see what the data is. But I think if the data is strong, and the way we've built up the business development, partnership aspects, I think there'll be multiple suitors here.

I think there'll be strong interest if the data's positive. Because it can be applied to multiple pharma companies, and I mentioned the cancer supportive care area.

So as I say, we'll be running full steam on those negotiations when it comes to -- one of the interesting questions here is kind of the deal type. We feel that, on the one hand, with the big pharma may come in and just take over and run the trial themselves, there could be opportunity to partner with a smaller company where we would kind of help and assist, kind of run the clinical trial.

Because it is our baby in one sense, but it is our expertise in what we're doing. So you're right.

There'll be decision trees and discussion negotiations, multiple parties. We'll figure that out.

Oliver had a second question here. Is 30 people enough for a trial for a commercial outcome?

Again, maybe, Liam, you can talk to that just around the stats discussions that we've had around how we ended up with 30.

Yes. So really happy to, Jeremy.

Yes, so 30 patients is essentially more than enough for our purposes right now. About 70% of these patients are going to have CRS, so there's going to be a very strong indication of the level of efficacy.

The priority from a clinical development perspective is to really get into your placebo-controlled trials as early as possible once you have an idea of the effect size. So we're going to see the effects in Grade 1 and Grade 2 and also the other elements of CRS management, like hospitalization, that will give us a really good indication of how to design later-stage trials.

So 30 patients for this purpose is actually ample.

Cool. These are kind of numbers that are not plucked out of the air.

There's been kind of deep analysis into what are the right numbers. So again, credit to Liam and the team for their discussions with qualified statisticians to come up with those numbers.

All right. Another question here.

Could we see a deal after interim data? I mean again, it's a good question.

Maybe I've already answered it. But when it comes down to what that data looks like, and as I say, rapid enrollment, we'll get an early read into what the data look like, if it's -- if we're seeing an impressive suppression of that inflammatory response, that CRS, then I think for certain companies, that might be enough to transact.

For others maybe, and I've been through this in my past where there's always that next experiment or the next data point or the next dataset. Some companies are maybe a little more conservative when it comes to decision-making.

Maybe I'm alluding to the fact these are more the bigger guys who have to work the chain of command. But I do think that, as I say, having interim data will be a key point.

And if it's positive, I think there'll be strong interest. Richard had a question.

Your projected time scale towards commercialization. Again, commercialization is always tricky in this industry.

I mean getting on the market is one question. Again, that'll be done with a partner and we're driving that forward.

As I say, we're experts in CRS, we're experts in running these initial clinical trials. The larger clinical trials we can do ourselves.

But having a partner onboard to kind of fund that would be critical. But there are -- that'll be kind of a few years down the line.

But as I say, once it's launched on the market, then it'll be -- we feel it'll be broadly applied to any and all bispecific CAR T. So again timeline, that'll be driven by the partner and say that we don't see ourselves as obviously driving that forward ourselves in isolation.

Potentially through a partnership. Another question.

If data lands well this summer, what does success look like? That's a really good question.

I mean in my mind, and this goes back to my kind of business development training, I mean, we're looking at a nice, substantial transaction. We're looking at a partner to come onboard with capabilities, with funding, with funds.

What happens in the industry when it comes to these licensing transactions, whether, as I say, maybe people want to buy the program, buy the company, just license the program, that'll be for another time and other discussions. But I think that what we're seeing what success looks like is certainly a juicy upfront payment when it comes to the work that we've put in.

Because we've done a lot of work. We've derisked the program.

It's a large market, it's an attractive market. We've filed important intellectual property, so we'll be protected.

So we see significant value for our contributions there. And then, as I say, the structure after that is down to the individual company we'll speak with or decide to collaborate with, whether it's, as I say, just passing the baby across that a large pharma could develop, or co-develop ourselves.

But that's all -- we believe, with strong data, that Poolbeg will have the leverage for those negotiations because the interest is so high. Appreciate that.

I think we have time for one more question. How much interest are you seeing in the oral GLP-1 for potential partners?

Again, appreciate the question. Good question.

In our most recent partnering conference attendances at BIO-Europe, for example, we had companies reaching out to us. I was always pleasantly surprised, some of them are kind of in Asia, some of them in Europe.

Some of them already had existing metabolic disease programs, and they were looking to kind of branch out, add to their pipeline. I think -- I don't want to be flippant and talk about no-brainer.

But if you get GLP-1 that can be delivered orally, it opens up a whole host of markets and market opportunities. It's a huge and growing market.

And moving away from injectables, the industry wants to go there, the patients want to go there. So if we can demonstrate that clinical proof of concept in the trial that I outlined with Carel le Roux, I think there'll be strong interest then in partnering the program out.

And again, revenue from upfront payments, et cetera. So appreciate that.

I think we've ran slightly over time. Appreciate people's patience.

But yes, we can wrap up now. Just again, thank you again for attending.