Poolbeg Pharma PLC (POLB) Earnings Call Transcript

Good afternoon, and welcome to the Poolbeg Pharma plc Investor Presentation. [Operator Instructions]. Before we begin, I'd like to submit the following poll. I'd now like to hand you over to Jeremy Skillington, CEO. Good afternoon, sir.

Good afternoon, and thank you for the introduction. And thank you, everybody, for joining us this afternoon for the Poolbeg presentation, of course, on the back of our RNS this morning talking about the interim results. Again, we have a fantastic presentation to go through to kind of update you on that. I'm delighted to be joined by my colleagues, Liam Trumble and Ian O'Connell, and we kick off and let's go through this. So as I say, we're -- we've got the team with us today. I'll talk about the background, talk about the company to kind of set the scene. Liam will talk more about the clinical trial, the topical clinical trial I say we've kind of announced the positive interim data this morning. We're all delighted with that just as things are moving. We've got some terrific momentum now. So we're looking to kind of execute. And then I -- Ian will speak more about the commercial opportunity that we have here because ultimately, we're looking for partners and partner the program. So we'll talk a little bit about that. So again, to set the scene, Poolbeg Pharma, clinical stage company. We're developing POM001 to potentially transform the lives of cancer patients. to allow them to have their cancer immunotherapy treatment safe and locally. And by doing that, we're preventing CRS is the plan. That's our goal to prevent cytokine release syndrome, and that means then they can take their drugs from home in the community. And we also have an oral GLP-1 program that we may touch upon later on. But many of you know, we have a fantastic team here, a proven track record of deals and transactions, executing deals with big pharma companies, selling companies, et cetera. Very excited about the clinical trials we are pushing forward. And I'd say the focus today will be on POL-001 and the topical trial and these interim data. And again, clearly, the goal of the company is to partner this program. We have a very clear path forward what a Phase III looks like and ultimately getting on the market. We talked in recent times about meeting with the FDA earlier this year. So that kind of lays out that groundwork. And again, we have some terrific ongoing discussions with both big and midsized pharma companies about the program. and what it would take to move that forward. And I say we're building nice momentum in that setting as well. And importantly then, we had a fundraise earlier this summer. So we've got a financial runway into Q2 2028. So that gives us a nice solid foundation for those negotiations. As I say, PO-001, potentially the first approved preventative therapy for cancer immunotherapy-induced CRS. And we mentioned this in the past that cancer immunotherapy are essentially wonder drugs. They're driving cures of certain cancers that didn't exist 10 years ago. So in essence, cytokine release syndrome didn't exist in this context. So it's a large and growing issue for these cancer immunotherapies, and we believe that we have a drug that could potentially prevent CRS from occurring in these situations. And as I mentioned, ultimately getting these drugs into the community care, patients can take them at home. And there's a big unmet need there and a lot of interest in what we're doing. As a reminder, CRS or cytokine release syndrome, we see ourselves as having that potential solution. It's a systemic inflammatory side effect for these cancer immunotherapies. And again, in a nutshell, cancer immunotherapies are redirecting your own immune system to go after your tumors, but you have these nasty side effects, including CRS. What does that mean? Patients get fevers, they get increased heart rates, they get low blood oxygen, low blood pressure. And then that can escalate into severe issues around kidney injury, neurotoxicity, leaks, et cetera. So again, that's a severe issue that start. It's a bit like a runaway train. There's an issue where you want to put your foot on the brake of that train and kind of bring it back to normal. And I just say, with POG001, we believe we can stop that from happening in the first place. Now it is an oral agent given orally. It's an inhibitor of an important immune control system called p38 MAP kinase. It's a gatekeeper of that inflammatory response. we want to inhibit these cytokines that drive that kind of inflammatory response. And as a master regulator of that inflammatory response, p38 MAP kinase is an excellent target in that context. And again, this drug has been in humans previously, we've done our standard Phase I single ascending, multiple ascending dose. So it's been in many people, many humans. And as many of you know, we did an LPS challenge study a few years ago and saw excellent results there to prevent inflammation that's caused by a bacteria fragmented LPS. Now again, it's important to note that one of our significant advantages is we're given orally. Patients can take our drug from home. They don't have to come into the hospital and get an infusion or an injection of a protein-based drug, for example. But as I say, what we're happiest with here is that the coverage, and you can see here in the lower box, the red dots, admitted the fond is quite small. But what we're seeing here is PO001 can inhibit a whole host of cytokines and far more than other drugs in this section can as well. Tocilizumab is given as a standard of care once CRS develops. And you can see the red dots there. It's only a handful of these cytokines that inhibits and far less than PO001 can. So again, there's other drugs like dexamethasone, which docs don't like at all because that can have an immunosuppressant side effect. And then JAK inhibitor as well that's going to inhibit some, but not a lot of these cytokines. So we see advantages there for PO001 in that setting. And I mentioned about this large and growing market of cancer immunotherapies. The graph on the left shows the expected growth in revenue of these many approved T cell engagers they're called, and they come in 2 different classes of bispecific antibodies, which we are using in our clinical trial as well as CAR T cell therapies. And as I mentioned, the efficacy they're seeing, particularly in the blood cancers such as myeloma is very impressive. But as you can see in the table on the right-hand side, these approved drugs, you can see the big pharma companies, J&J, who we're collaborating with on this topical trial, other companies like AbbVie and Roche, they have these bispecific antibodies approved and on the market. As you can see on the right-hand side, they have significant issues around CRS. And these are noted that teclistamab or TEVEI is here in our clinical trial, 72% of patients develop cytokine release syndrome. And I said, for our topical trial, we're looking to kind of reduce that number. But it goes across the board. They know it's an issue. They know it's coming. They know patients have challenged with CRS. It's an added burden to the health care system who are there to look after the patients and their cancers, but now knowing that a large majority of them can and will develop cytokine release syndrome. So they're looking for solutions as well. And as you know, when we talk to particularly clinicians in the U.K. about our work, there's a lot of interest in participating in our clinical trial. I do want to -- there's a video here I want to show Bob Munroe is an actual myeloma patient. And Bob talks here about 1 minute, 1.5 minutes about his issues that he had in the past with CRS. So I want to bring our story to life and what the challenge and issues are for patients. [Presentation]

I appreciate Bob's comment on there because, again, I think it highlights the issue of CRS and the fact that in a real-world setting. And I would say our goal here is to allow patients to get their drugs and then as I say, go home and then not have to kind of stop or start their treatments or say, develop CRS, these nasty side effects. So that's kind of me in an intro. I'll be back in Ryan, but I'll pass across to Liam Trem to talk more about the clinical trial, as I said, from the RNS this morning. So Liam, I'll step to the left.

Thank you, Jeremy. Really excited to speak to you all today with this really exciting news for the company. So I guess just as background for those of you that maybe aren't so familiar with the story of the company, but this is really the transformation that POL001 is really going to make for these cancer patients. So these bispecific antibodies, if you look on the left-hand side of this slide, typically, this is done in hospital. They have to be hospitalized for up to a week. And what happens is you give this immunotherapy and it activates T cells. This drives the production of cytokines results in cytokine release syndrome. And this happens through p38 MAP kinase signaling. And this is a potentially life-threatening side effect that needs to be managed quickly so that it doesn't progress where if it progresses, it can affect virtually any organ system in the body. In addition to this, if cytokine release syndrome does happen, that week of hospitalization can be extended. So if they have cytokine release syndrome, they can't get the next dose and what they're in for a week because they have to get 2 or 3 doses, and these are small doses before they get a full dose. And this is purely to get the body used to it so that we don't have overwhelming cytokine release syndrome in these patients. So if cytokine release syndrome does occur, then they need to delay the step-up doses. That week can turn into a much longer period. And obviously, this is a challenge not just in the existing centers to administer, but also making it more widely accessible to centers that don't have that resource utilization to have beds for these bispecific antibodies. Alternatively, the hypothesis with POL001 and the solution that it will offer is that we can actually give this orally at home. They can take it before their cancer immunotherapy happens. It doesn't affect the cancer immunotherapy. They still get the benefit of the therapy. They don't get this cytokine release. They can get this in an outpatient or at-home setting. p38 blocks the CRS. And by preventing CRS, then we actually reduce the hospital stay. We enable administration, particularly in community hospitals and improve patient quality of life. And that community hospital piece is so, so important because as I'll talk to in a moment, particularly in the U.S., a lot of patients actually can't access treatment in what we refer to as high-tech or centralized hospitals. In America, 75% of late-stage relapsed myeloma patients only get treated in the community care, which is very different to what we're used to. So getting into this community setting, critically important that we get this treatment out of the hospital setting. So just a little bit more on the topical trial itself. Obviously, we're excited to share really good news on this. Just before we go into some of that, what is the trial? So it's a first in-patient trial, as I mentioned, in multiple myeloma patients, relapsed/refractory, so quite ill patients who are receiving the bispecific antibody teclistamab. It's been led by Dr. Emma Searl, who is a consultant hematologist at the Christie Hospital in Manchester, -- it's been conducted by a blood cancer specialist organization accelerating clinical trials who are really equipped to deliver this as quickly. And we've made a lot of effort to design this trial in a way where it can be delivered quickly and equipped with teams that are able to make that happen as well. So the trial is planning to recruit about 30 patients. And down the bottom here is, as Bob just spoke to, Emma, the Chief Investigator, experiences this day-to-day and the challenge that it presents to patients, obviously, on their quality of life, but also from her perspective to get these treatments to more patients, you really need something that removes CRS, removes this bottleneck, and that's how you will access a broader population and get these life-saving immunotherapies to the patients who need them. So the trial, this on the left-hand side is the design of what's happening in the trial, designed to be conducted quickly. So cytokine release syndrome, as I mentioned, happens when these patients are getting step-up doses. So we have it here as TEC dose 1, TECT dose 2, that's teclistamab dose 1 and 2. After these first 2 small doses, they get what we call a full dose. And it's during this period where we step up the level of the dosing the cytokine release syndrome occurs. So what we do is we give the patients PO001 to take twice daily orally at home during this period. And then they can get the bispecific antibodies without cytokine release syndrome happening. So the trial itself is single arm, which means that everybody in the trial is getting our study drug PO001, and it's open label. So the data is available to the investigators to read as it goes along. And as I mentioned, it's going to recruit approximately 30 patients -- there is a partnership with J&J there for the provision of tculizumab, which we think is a really important endorsement to the program, that they see the promise of this cytokine release preventative strategy as well. So endpoints in the study, what are we looking at? Obviously, the safety of POL-001 is critically important. We're going into a late-stage cancer population who are severely unwell. That's the first time the drug is going into that population. So safety is a key focus. And related to that, we're obviously looking at the incidence and the severity of cytokine release syndrome. And then we're also looking at other things from a drug development perspective, like confirming the safety and the pharmacokinetics of the drug itself. And that pharmacokinetics refers to the level of blood level of drug in the body before it's metabolized and it's eliminated from the body. This is really important information as we go forward to make sure that these patients have an adequate amount of drug in the body. And then we're also looking at things like how is CRS managed and how is tocilizumab used because this tocilizumab is an IL-6 receptor quite often given by IV. There's a lot of pieces that go into CRS management that's quite burdensome from the hospital. This is reported in a lot of the biggest trials that happen across the world with these bispecific antibodies that revolutionize cytokine release -- well, sorry, multiple myeloma treatment. So seeing all of that fall away is quite an important aspect of what we're doing. So we're not just looking at the cytokine release. We're also looking at a lot of that administrative burden and burden to the patient falling away as well. So just to quickly mention, this is not a typical oncology trial. So obviously, we're looking at multiple myeloma patients. And typically, when you're doing a trial in this population, you're given a disease-modifying drug. You're trying to prevent their cancer growing. You have to follow them for a long time. So while cytokine release syndrome would happen at the start of their therapy, you have to wait months or years to see how these patients respond. And as long as they continue responding, they stay on protocol. So that's why trials in this setting can typically take many, many years to complete. What we're looking at with the topical trial is actually we're only looking at that first section of the patient journey of cytokine release syndrome and when it occurs. So basically, that's going to happen in the first couple of weeks. The patients will only stay on protocol for a month or 2. And after that, they'll come off. So as soon as we can get the patients through this process, that is the trial done. So as I mentioned, short-term monitoring 1 to 2 months. Open label, as I previously mentioned, really important. That's rapid visibility for the investigators that they know whether or not this drug is working. And as I mentioned, single arm. So every one of those 30 patients is receiving PAS -001. So not like a typical trial where only half of your patients will get the drug. So just to give you a background of what we've done to date. Obviously, a lot of effort went into designing this trial so that we could deliver it rapidly. We announced earlier this year, MHRA approval. That was a long time ago. It feels at this stage, a lot of work has gone in since. And so we -- after that, we made sure we had the right sites on board that they have the right volume of patients and also they have the right quality systems to conduct this trial and collect the data in a high-quality manner. That was validated by going to site initiation visits where we went and checked really these sites are fully equipped to deliver everything to do and to hold them to delivering a certain amount of patients if they want to partake in the trial. There's an obligation there where they're meant to try to recruit has gone. And as we've seen, as we're announcing today, that designing the trial to recruit quickly has been validated now. We're seeing certain sites really able to deliver patients quickly, which we're really excited about. So site activation occurs after all of that. Once site activation happens, that this is all CRO that accelerating clinical trials led activities with the chief investigator. We really move into site level pieces. And this is patient identification. So typically, what happens is you'll have a multidisciplinary team of specialists who sit once every couple of weeks in every hospital. And they'll go through all of their patients and they'll identify patients who need to go on to a new line of treatment and also who's suitable for a clinical trial. After that, you go to the patients and see if they want to actually participate on the trial. So we've got really good feedback that a lot of patients are really happy to partake in this trial that it's attractive to them as well, which is a really important part of the trial design. And then if they're willing to take part, the patients are screened to make sure that they align with the formal eligibility criteria of the trial. And then they can be recruited and dosed into the trial. And this is really where the substance of the trial happens. It's where we're at now. It's where we're rapidly gaining momentum as more and more sites come on board, and we're continuing to hopefully get that momentum. And then obviously, as we're announcing today that recruitment, dosing results in interim data. And so we're really enthused with what we've received. So the clinical trial interim data, we're super excited. This is a major milestone for the company. Obviously, these are seriously unwell patients and the safety review committee have reviewed the data. They have announced that the study can continue, no modifications to the protocol. So obviously, they have a lot of faith that this is safe to continue and that they have a lot of optimism that the study can go forward as it is. For us, obviously, cytokine release syndrome is itself a safety endpoint. So these are all really positive milestones. And the fact that the study drug can be administered as we expected in this really sick population is a really encouraging signal for us at this stage, and we're enthused by this. So as I mentioned, this is a really positive sign for the program as we position it that it can be scaled up quickly, that it's attractive for partners and that it can get, as we mentioned earlier this year after the pre-IND feedback from the FDA that there is a clear path to market here that can happen quite quickly. And this is a key derisking point in the program that gives us a lot of confidence in the program and also instill a lot of confidence in potential partners to really move forward with it. So we have a lot of momentum. The recruitment is continuing. Even since having this news, we've already got news that there's another patient being dosed which is just fantastic. So we really are thankful to accelerating clinical trials and all the sites involved in the trial to date. And the feedback so far has been really good. So we're super excited. Obviously, we'll be sharing this with partners, but I'll let Jeremy speak more about that.

Thank you for that, Liam. Yes, I appreciate that. So listen, we're kind of nice momentum on a lot of fronts. So on the business development front, I mentioned this previously, we've had some really productive discussions with several different companies. They're interested, obviously, to see the outcomes of this interim analysis and as the clinical trial develops. But I think what's important here is that we see this and they see this as a derisking issue. So interim data we have now, the safety review committee has reviewed that, told us to kind of go forward, keep the same dose. Everything is going according to plan. As Liam said, recruitment is going exceptionally well across the sites. So we're excited with that. And as I said, we're building that data package from a business development standpoint. I think what's interesting in that front is that we -- in the background, we've looked at the commercial opportunity that it provides as well. That's one of the key questions I asked. Now Liam is going to talk us through that aspect, and then I'll be back later on just to wrap up. Liam or Ian, over to you.

Thanks, Jeremy. So following on from Liam on the clinical side, as Jeremy said, we want to spend just a few moments to run through the recent commercial work, which we've done, again, which is strongly supportive of the program. So earlier this year, we commissioned Acumedis to run independent payer research in the U.S. So this was conducted by means of structured interviews with current commercial payers covering around 75 million lives in the U.S. So pretty broad cross-section of the market right the way across commercial insurance, Medicare, Medicaid. And this was again complemented by cost offset modeling, whereby Acumedis were able to quantify the cost savings from avoiding the CRS-related costs such as hospitalization that Liam already spoke to. And the first thing that came back loud and clear from the payers was that CRS for them is an expensive problem and one that they recognize. Hospitalization, ICU use, length of stay and acuity are key drivers of this cost. Secondly, the research found that an effective preventative therapy could support the broader outpatient delivery of these cancer immunotherapies. And again, there would be meaningful access and cost implications for the payers if this was able to be affected. And on P001 specifically, they think that is positioned as a commercially meaningful CRS prophylactic or as what we say, preventative therapy, driven by reduced hospital burden and broader outpatient use. So I think most significantly, the key insight was really that on the payer side, because of all these issues, there was a clear willingness to pay at commercially meaningful price points. So on that then, we'll click on to the next slide, and you can see the conclusion of Chris Grimes Compton, who led the research at Acumedis. And I think it's there pretty direct. PAL001 is positioned as a compelling CRS solution with significant market potential. And because payers are able -- are willing to pay a commercially meaningful price points because of all the factors that we've talked about, such as hospitalization, they concluded that taking into account the patient flows and the epidemiology of the condition that there is multibillion-dollar peak sales potential in the U.S. alone for POD001. So again, really significant commercial product and one piece that really resonates with potential partners. So now that we've covered the validation of the commercial opportunity, I'll hand you back to Jeremy to talk about the partnering in a little more detail.

Great. Ian, thank you so much for that because I think it's an important component. And for those of you -- some of you might have been at the Investor Summit last Friday, we had a terrific panel there that included Michel Broker at UBS. And he talked about what pharma look for, what pharma looks for in the deals that they send their scouts out to scout the world essentially to look for. And let's just kind of summarize here quite accurately, scientific rationale and we put this in the context of PO001, like are we checking these boxes? Do we meet the needs that pharma look for when it comes to partner. And I think from our standpoint, scientific rationale, absolutely. Poolbeg is a great target. There's nothing out there to prevent CRS right now, and we've got a terrific preclinical and clinical data set. And again, the clinical data is obviously a very important component. And obviously, that's where the topical trial is moving forward. And again, happily today, as I say, we've kind of passed muster when it comes to that kind of first kind of interim safety analysis, which is terrific. And as we mentioned, recruitment is going and we're keeping at that same dose, the 150 mg twice a day dose that we have data generated from. So again, we were also encouraged to see that recruitment is pushing on. And we've been approached by other clinical trial sites in the U.K. that they want to kind of join this trial as well. So great enthusiasm from the field because there's such an unmet need. From a regulatory standpoint, how do you get this drug through the clinic and on to the market. And that's where the regulators come in, the FDA, the EMA. And we mentioned we sat down with the FDA back in May this year and talked about the program, talked about what a Phase III would look like, and they gave us fantastic feedback on guidance what a label would look like, where exactly you can sell it. and the endpoints in Phase III. That gave us great kind of clarity or confidence we're on the right track. And we share this with pharma all the time. This is where the FDA thinks we're going. And as Liam mentioned, particularly the topical trial, these are short clinical trials. So again, getting this to the market quite rapidly is very exciting to a lot of people. Intellectual property, key component in this industry. And again, we've had several announcements this year of patent grants across Canada, Europe, South Africa, Australia, notices in Israel. So there's great confidence that we have protection. We have exclusivity when it comes to -- once we get it on the market. And Ian spoke about the commercial validation. It's an unmet need. And I said earlier on, it's a relatively new space because cancer immunotherapy drugs are relatively new. So they're going and growing. And again, big market, large unmet need, multibillion dollars in the U.S. So as I say, we have a lot of kind of compelling discussions with big pharma and midsized pharma about the program and kind of moving that forward. And I think we're excited where we are right now, I'd say, from the clinical trial standpoint and building up that bit of competitive tension about getting the partners into our data room to do their diligence. And this is a slide, again, I borrowed from Nikhil from the conference last Friday, but pharma is under pressure. They have a patent cliff coming where a lot of their big selling -- largest selling drugs are going off patent. And there's a list here when they go off patent from 2026 to 2023. But about $400 billion in revenue, big pharma goes off patent, so they lose exclusivity. So they need to find other drugs to kind of fill those gaps, fill those holes. I would say, our discussions with partners is like POG001 can do that. We can generate revenues. We mentioned market is $10 billion in size and over $2 billion in revenue. So it will plug a little bit of that hole. So big unmet need for pharma. And as I mentioned, we have diligence ongoing. Pharma companies are in our data room. Again, the font size here is quite small, but we've got all of our documentation in these virtual data rooms online, they can access and review. So we call it -- they're doing diligence on the program to understand everything we've done so far. So I'd say we're going to build up that story, build up that competitive tension. And ultimately, the goal is to transact on POG001. So we'll wrap it up there, and we do -- I do want to leave some time for questions. Again, I appreciate those who've been sending questions in. So in summary, very experienced team here at Poolbeg executing. And I think that should come through in this presentation. There's been fantastic execution of the clinical trial in 2026. And again, with thanks to Liam, Ian and Paul and the team for driving that forward along with our collaborators such as ACT. And again, very exciting with the stage of the programs and moving those forward. Again, high value with large unmet needs, again, partnering focused. And again, a reminder, we have cash runway into Q2 2028, which again gives us that buffer period where we can negotiate strong deals, attractive deals for Poolbeg and our investors and looking forward to the next stage of the company. So again, I appreciate all of your time this afternoon. We'll wrap it up there from the presentation standpoint, but I do want to get to questions and again, appreciate those that have submitted. We'll go through as many as we can in the next 10 or 15 minutes or so. And again, appreciate the input in advance from Liam and Ian as I read out these questions.

All right. So the first question came in, I like it short and to the point, is this what you expected? Well, personally, I'd say this, I mean, we're happy because things move forward. But again, maybe I'll point to Liam to kind of give in a bit more kind of detail to what the expectations were and what this kind of readout is.

Yes. So thanks, Jeremy. So at this stage of the trial, this is -- we're really excited by this news that we're going to the sick population and the trial can continue with the safety monitoring committee. So this is really positive. It's a major milestone for us. I think it's a major milestone for the program, and it gives us a lot of encouragement in pushing forward. So -- so yes, that has to be considered in the context of where we're at. This is the first time going into late-stage relapsed/refractory myeloma patients. These patients can be severely unwell and being able to deliver the drug in a way in which the committee feel is safe is a strong endorsement of the program. So we're really excited as the program move forward and it gives us a lot of encouragement.

Super. All right. I'm going around. I should say that Liam and I are in Glasgow right now, the International Myeloma Society meeting is on. So a lot of good discussions here as well. So I appreciate that. So the next question is quite lengthy, but I'll kind of read through it. Today's RNS describes the interim safety review is positive, correct? Without asking would like to disclose anything commercially sensitive, can you give investors more detail on what the interim cohort actually showed, particularly the number of patients treated, CRS incidence and severity and whether there are any early signs of P001, having the intended biological effect I'm aware this is focused on safety, but often there's additional clinical indications to share. Thank you so much for kind of writing out that question. Again, I'm going to look to Liam to address that. But obviously, the commercially sensitive aspect as well, we're very kind of deliberate in what we're allowed to disclose. But Liam, if you can kind of address some of that.

Yes, absolutely, Jeremy. So the investigators are, as Jeremy mentioned, we're actually at the International Myeloma Society meeting now and a lot of the investigators in the topical trial are here. They will be meeting tomorrow. They will be going through all of the data in detail at the same safety monitoring committee went through. So this is -- the patients gone in, we have really good momentum. We're going to give updates as that enrollment picks up. So we'll keep everybody up to date on what goes. But the fact there's no change to the protocol. Cytokine release syndrome is essentially a safety endpoint as well, which needs to be borne in mind. So that safe in this population is really positive. This is a major milestone, as I mentioned, I'm really encouraged to move forward.