CRISM Therapeutics Corporation (CRSP) Q2 FY2025 Earnings Call Transcript & Summary

Good afternoon, and welcome to the CRISM Therapeutics Corporation Interim Results Investor Presentation. [Operator Instructions] Before we begin, I'd like to submit the following poll. I'd now like to hand to CEO, Andrew Webb. Good afternoon to you, sir.

Thanks, Alessandro. Good afternoon. Thank you for taking the time to join today's presentation. My name is Andrew Webb. I'm Chief Executive of CRISM Therapeutics. And today's presentation, we'll be looking to really reflect on the highlights for the interim results that we posted yesterday. And following that, I really want to take some time to look at the important development for the company, and that's our movement now into commence our clinical trials. So in order to take that forward, and I'm looking -- I'm joined today by Professor Garth Cruickshank. Professor Cruickshank is Professor of Neurosurgery at the University Hospital in Birmingham. And Professor Cruickshank, if you just take perhaps a couple of minutes to introduce yourself, that would be helpful.

Hi, Andrew, thanks very much, and welcome to everybody. Yes. So I'm Emeritus Professor of Neurosurgery in Birmingham. I've been involved with the treatment of glioblastoma for well over 30 years or so and have been heavily involved in the development of trials, which have really focused in on the very difficult ways of treating these tumors, bearing in mind that they sit within the brain. Also working with Chris McConville and with CRISM, I've been quite instrumental in helping design the current trial that's now been approved by the MHRA and also in particular, how we might actually progress this in terms of sort of practical solution for surgeons to use in the trial.

Okay. Thank you. So if I may start, firstly, I'll run through the highlights from our interim results. As those of you that have heard me talk before and give you more of an insight into the company, everything we do is around ChemoSeed. ChemoSeed is our key asset. It's the platform drug delivery technology, which we're developing. And we're developing it as a platform technology and the brain tumor work we're doing at the moment is our primary indication. There are other solid tumors, which we're looking to address and some of those programs have started, which I'll highlight shortly. As I mentioned briefly in our introduction, we've had an absolute focus on delivering our first treatments in the brain tumor indication. And the highlight really is over the last few months is that the -- our application to the MHRA, the U.K. regulator to commence our clinical trial has now been given approval. And so we are on track for H1 to make the submission and I'm delighted the MHRA at the end of August approved us to go into trial. That removes any regulatory hurdles now, and we're free now to set up commence the trial itself. Professor Cruickshank has highlighted, we are starting with the most challenging of the brain tumor indications of grade 4, which is glioblastoma, which we'll talk about in a little bit more detail. It's important just to note as part of the set of an approval for the clinical trial, we also had to see ethics approval and where we've got a very positive feedback on the approach we're taking to the trial. Clearly, given the unmet clinical need, this is a sensitive area. Clearly, ahead of the trial, we need to have a clinical batch of products of the ChemoSeeds and where our manufacturing partner has initiated the clinical batch. And so that manufacturing process is under GMP, which is the regulatory standard for human trials and human medical purposes. We talked about -- we announced that we've established the Scientific Advisory Board. And clearly, Cruickshank is our lead medical adviser here on the design and setup of the trial, which we'll hear more about shortly. I did mention just briefly that we worked on as a platform technology, and I know there's interest to think, we know where else can we be using the technology for. We have building up our portfolio now to extending into prostate cancer. And clearly, this is quite a bit of airtime sadly for some high-profile individuals that have been diagnosed. This is now the prevalent cancer in men, and we have a strategy and the ChemoSeed we believe is suitable. So with support from Innovate the Launchpad grants, we have actually already initiated that program earlier this year. So it's an early stage, but initial progress has been good. In order to move things along, we did pause and raise some money just in the end of June, July. I'm pleased to say that we raised some GBP 874,000 to take us through to the commencement of the clinical trials. And so we brought in quite a number of new investors, which was very pleasing. But I'm also grateful to very grateful to our incumbent shareholders who have been with us through this early part of our journey, which was raised GBP 74,000 as part of that offering. So thank you very much for that. Final comment is our net cash at the end of September was just over GBP 900,000. So just quickly in terms of ChemoSeed itself, I think many of you have heard me talk this, so I'll just be very brief. This technology is the -- really the brainchild of our Chief Scientist, Professor Chris McConville, Garth Cruickshank has an early influence as well on this program, as you'll hear when we talk about the early clinical journey that the technology has taken. But first McConville has had this vision to basically improve. We have a lot of good cancer drugs are out there. But often the way they're delivered and particular indications like the brain tumor where the blood-brain barrier really does a very too good job of actually keeping the therapies out from the brain. Local delivery, this is something that Professor Cruickshank has championed personally, really we believe is a significant opportunity to progress and for the company. So without further ado, I think it's fully appropriate now. I'll hand over to Garth. Garth will set the scene for the glioblastoma and walk through then the plans and the strategy for the clinical development of ChemoSeed treatment.

Thanks, Andrew. So I thought it would be useful for those who are perhaps not up to speed with the complications of patients with glioblastoma to give you a good feel for what the problem is and how we've gone about attacking it. So this slide shows you a montage of MRI scans using contrast enhancing substances to show up a tumor in a patient over time. Now there are unusual set in the sense that the very first scan actually occurred in this gentleman 9 months before he presented with his brain tumor. So we have what you might call a normal scan right at the top. And we can then see the focal development of his glioblastoma when he first presents on that second -- second montage with a tumor in the brain, which enhances. You see it's very focal nature. And you can see what happens over time over those scans. So at the beginning, when he first presented, he actually presented with mild headache, and we actually thought he might have had problems related to his previous head injury. But when we did the scan, we found this tumor in the right side of his head here. Now the appearances on the MRI scan were fairly diagnostic of that. But it was important to try and understand also whether we've missed anything before. So we checked on the previous scans and so on. Now patients who present with glioblastoma don't always present with headache. That's a relatively unusual way to present. Most of them usually present with what we call focal symptoms related to the part of the brain in which they actually have their tumor. A few will present with seizures. And later on, if the tumor gets larger and starts causing swelling, so they will develop headaches and a very particular type of headache that's persistent. But going back to the presentation, which is sort of what you might call focal symptoms, these can often be very difficult to pick up and GPs and doctors have real problems trying to understand whether a slight discomfort in the hand or a little bit of memory loss or whatever it happens to be, is really a symptom or not. So unfortunately, a number of these patients will present quite late. And that means that the tumor is already of the kind of size that you can see there. And that makes it more of a challenge to deal with. Glioblastoma is universally unifocal. You do occasionally get patients who've got multiple sites at the time of presentation. But more often than not, it's really focal. And this means that as a sort of surgical target, it becomes quite possible to think about trying to remove as much of this tumor as possible. So you can see on that third scan down that we've managed to get quite a lot of the -- if not all of the enhancing tumor out. But unfortunately, these tumors are not discrete. They have a diffuse component and a focal component. And that means that there's an amount of tissue -- tumor tissue still left in the walls of the area where we've actually operated. It doesn't enhance, but it's definitely there. And if you were to do further biopsies in that area, you would probably be able to demonstrate it. Now the current treatment for these patients is good surgery, followed then about 4 weeks later by radiation treatment and chemotherapy running together. And although that can have an effect, and I'll show you some of the results of that, by and large, these patients will recur and then go on to get progression of the tumor. Once you've had recurrence, there's virtually no treatment available for these patients. And perhaps one of the more solitary things to pick up here is that the picture on the right there shows you a postmortem specimen of a patient who had a glioblastoma. And although you can see there that sort of darker brown patch, and you can see the brain being distorted there. And this a coronal section highlights the damage that these tumors cause to both function, which can obviously impact on something like physical behavior or physical performance, but much more frightening and awful to patients and families is the erosion of mental function and personality, making this type of cancer truly awful. So down the bottom right there on the slide, I've shown you that the median survival is on/or around 15 months or something like that for these patients, but they all go on and progress and less than 5% of patients live 5 years. So it's a truly dreadful cancer in many different ways. If we have the next slide, please, Andrew. Now this is an important slide, and many of you who look at the literature will see this slide. This goes back to 2005. It's from a European ERTZ study and the publication was by Roger Stupp. It is probably -- and this is sad to say as someone in the business as it were, the last time we saw any real benefit from any particular agent in this disease. It's a survival curve. So on the y-axis there, you can see the percentage of patients surviving. On the x-axis, you can see time in -- I think it's in months there. It's in months. And you can see that these curves coming down, and you can see them separating. And this was actually at the time, quite a remarkable slide in the sense that for the first time, someone had actually shown that something worked in terms of separating out a control group who are having standard therapy with radiotherapy and those who had radiotherapy and a drug called temozolomide. And although they are separating -- those curves are separating, the downward trajectory of those cures is still fairly disappointing. And indeed, this is an important trial for us to understand because it was a trial which never achieved its intended statistical outcome. That is to demonstrate that you could get a 3-month improvement in survival. However, this treatment then went on to become the gold standard treatment and still is for this drug in conjunction with radiotherapy for patients with glioblastoma. And if you look at the figures, the reason why it actually went into and became the standard drug was because the 2-year figures, 24 months there showed that there was a rough doubling in terms of patients surviving from about 8% or 10% up to over 20%. Not remarkable, not fantastic in terms of the living 5 years, where I say less than 5% live about 5 years. But nonetheless, it did show an improvement. Now look, that date there is 2005. And if I'm right in saying that's 20 years ago, and we've hardly seen any real improvement since that. Also, less than 50% of patients with glioblastoma get any real benefit from this additional drug, temozolomide. And subsequent research has failed to advance even on this limited benefit despite many trials. So many have failed, I think, because we've not been able to ensure that the tumor is adequately dosed or that with the new drug, all because of poor penetration, as Andrew was saying, into the brain. And also one of the more problematic areas, of course, is that some of these drugs is a limitation on the dose you can give systemically before you get more side effects, making a limitation on the total amount that you can actually give. So this led me to think about what other ways could we overcome these problems and particularly to start thinking about whether we could put drugs in proximity with the tumor and also whether we could do it as early as possible as, for example, during surgery. Go to the next slide, please, Andrew. So this rather wordy slide describes some information around a Phase I trial that I did probably 8 to 10 years ago. So we know that irinotecan is a topoisomerase inhibitor. It works in a completely different way to temozolomide and carmustine. And it's been shown in -- had been shown in clinical trials at the time to have an effect on patients with glioblastoma that you almost always had to discontinue the therapy because they had too many side effects. However, those that were able to stay on it seem to get benefit from it and quite clearly were showing imaging changes as well, which was helpful. We know also that the substrate for irinotecan, the topoisomerase enzyme is upregulated in glioblastoma and is more potent and that the product of the enzyme creates a substance called SN38, which is about 1,000x more toxic than irinotecan. So there were some good biomechanical chemical reasons why exploring irinotecan seemed a good idea. Not only that, but it seemed to have in terms of tissue status relatively little toxicity. So in a Phase I study, I had access to some microbeads, about 100 micron microbeads that we were able to inject in a gel, an allogeneic gel directly into the tumor margin, in this case, recurrent patients, patients with recurrent disease. And we were able to demonstrate not only that it was safe in the sense that we didn't have anything like the inflammation and wound problems that we had with carmustine wafers, but also that these patients felt well after it. They were not having to have further chemotherapy because they had their chemotherapy put in. And not only that is that there was some evidence from the 9 patients that we treated that there was an improvement in survival somewhat unexpectedly, bearing in mind that we understood that one of the problems with what we were doing and what we hadn't realized was that there was very rapid offloading of the drug from these seeds. But it had a sort of silver lining effect in the sense that we were able to work out what dose was released from those seeds at the time. And this gave us a starting point for considering where we might want to go if we could improve the treatment. So that is the time that I started to talk to Chris McConville about the idea of, well, now isn't it possible for us to put in a much bigger dose of irinotecan and control the dosing in a way in which we could get prolonged release in a format formulation that would fit for a surgeon to be able to put into a tumor. And I think, Andrew, you're going to summarize briefly what some of the work that Chris has done.

So those of you that listened to our presentations before maybe be familiar with this slide. This slide was actually pivotal in the proposal to the MHRA to take this proposed treatment forward. So what we show here is that the differences we're comparing -- this is the first work with the ChemoSeed. This is the small cylindrical implants loaded with the drug, irinotecan. What it means is here, we've compared this to the standard of care, which is temozolomide and also irinotecan itself when given intravenously. And as you can see that we had an exceptional survival on the ChemoSeed. So just to put it in context, this was a study conducted in mice, -- they've been administered well in the brain was actually a human cell line, which is very aggressive. It's called a patient-derived xenograft. So it's actual human brain tumor that was administered. And then we put in a ChemoSeed to treat it. And you can see that from those images on the right-hand side, at the end of the study, this is 148-days was the ethical limit of the study. Those mice that hadn't died through the brain tumor as has happened in most cases were then euthanized, we imaged the brains afterwards. So what was remarkable here is that those mice which had the ChemoSeed showed no sign of recurrence at all. We did lose one mouse early on, and that was really felt that it didn't recover fully from the surgery. But with temozolomide, you see on the right-hand side, as you'd expect and as Professor Cruickshank just described, inevitably sadly the tumor that does return, it does really, really quite aggressively. So -- but to have no recurrence of ChemoSeed really gives us a reason to be optimistic about the opportunities for the program. So with that, I'll hand back to Professor Cruickshank, and he'll talk about now the plans and how we're going to take the ChemoSeed technology through into clinical trials.

So when Chris and I discussed this, we were trying to think of a formulation that would enable us to give perhaps a higher concentration of irinotecan in such a way that it's released at a dose rate, which would be satisfactory. So Chris then went on and did a number of in vitro studies looking at what kind of dose we had to achieve to kill tumor cells, and he did a lot of studies during that. And also to look at the way and the kinetic behavior of his formulation to enable that dose to be released under the conditions that exist within the tumor bed margin here. And also in a form in which we could actually use this as surgeons to put into the tissue to allow us to carry out the dosing. There has been around for a number of years, a drug called calmustine, which is in a wafer form, which you tend to -- which is approved by NICE for use in this particular situation. And the problem with that is that it looks a bit like sort of peppermint tablets, sort of like little seed tablets you just place within the cavity. And the trouble with this is that it just releases drug into the cerebral spinal fluid that bathes this area and virtually none of it goes into brain. So built on what I had done on the Phase I study, we felt that implantation that is actually putting the drug into tissue and allowing that to, as it were, temporarily heal over it would allow diffusion of the drug within parenchymal tissue, brain tissue directly. And that proved to be the case even from some of the seeds we used in the Phase I study. But this form of it as little rods. So these rods are 6 millimeters by 2 millimeters and they contain about 7 to 8 milligrams of irinotecan. And the matrix that they're in certainly breaks down over time, giving us -- we estimate somewhere between 30 to 60 days release of the drug, which is an important time period to understand because that's from the time of surgery to well into the time of radiation for these patients -- and not only that is that you're getting dose into these patients from the moment of their surgery from the moment you've got the pathological diagnosis, you're getting treatment running. The other problem that we had to think about here was dosing. Well, we had information from the Phase I study, which gave us an understanding about what sudden high doses might happen because of the offloading effect. And we were then able to calculate how we might do the dosing up to about 30 seeds to generate a reasonable dose for treating these patients. You can see there in that left-hand picture, you can see how the seeds are rained into the resection cavity. And then on the right on the cartoon, where you do this is to make a small 6-millimeter hole, a little bit bigger there with a standard brain cannula and then you put the next seed in. How do you work out the distance between them? Well, we use the sort of raster pattern as I've demonstrated there on the right. And that enables you to cover the area that you want to cover. And indeed, because of the imaging and because of what you know is the surgeon when you go into these, you can avoid risky areas and you can make sure you try and put it in areas where we think it's more likely that the tumor is going to be so you can get the most effective dosing that you can hope to achieve. And this is obviously based on the idea, most important idea that a very high proportion of these glioblastomas will recur locally, implying that that's the area to hit when you're going to retreat these patients. So if we go to the next slide, Andrew. So in terms of designing our study, we have to build -- we are obliged to build on the work that we've done already. We're not allowed to just jump off into unknown territory. We have to build on what we've done on the Phase I study, take it that bit further, prove safety and go on from there. So in this study, what we've got -- we've done is broken into 2 parts. In part 1, we're going to use the same kind of patients that I used in the Phase I study. And what we're going to do is to dose escalate. Because we know the kind of dose that was released quickly in the Phase I study that I did, we know that we're unlikely to get to what you might call dose-limiting toxicity in the early phase. So the last thing we want to do is to disadvantage these early patients by giving them suboptimal therapy. So the idea is to try and get the dose up as quickly as possible. So what we've designed is a novel Bayesian approach based on the probabilities of toxicity arising from the first study to rapidly increase the dose so that as many patients get as good a dose as we can give them early on. And it's probably more useful in terms of toxicity to have more patients at the higher dose than to have a lot of patients who are on suboptimal doses. The MHRA were concerned about the rate of dosing versus the numbers of seeds, and we explained in detail that, of course, this will be dependent very much on what the surgeon thinks they can do. I'm very grateful to Victoria Witt, who is our lead investigator for a lot of discussions on how we might achieve the kind of high doses that we actually want to achieve and the sheer practicalities of actually doing this towards the end of a period of surgery on these patients. So we plan to treat in the first quarter of this part 1, 12 patients. And from that, we will confirm the dosing, and we will also get a much better idea of any issues and complications to do with the technical procedure and also how patients respond to this. Now the most important thing for us is to optimize the chances of getting a result from this kind of therapy. We need to get ourselves in a position where we can get the best chance of getting these patients to respond. So by selecting patients who are newly diagnosed, who have the smallest amount of tumor left because they just had maximal surgery and to treat them at the earliest instance, i.e., the moment we've got that diagnosis at least for glioblastoma offers a unique opportunity, I have to say, because I've not seen any studies which have tried to do this in quite this way and quite so early is to get a high dose of chemotherapy in very early on with the idea of building on the surgery that you've done to get as big a cytoreductive effect as you can. And that will also see patients through the 4-week period whilst they're recovering from their surgery and then before they start their radiation therapy later. So this is the plan, and we hope to recruit in the initial phase, 60-odd patients and be looking at progression-free survival. This is a very common parameter to measure in these sorts of patients. And what we've opted for is to look for a slightly better threshold to obtain this kind of data statistically with the idea that we will get an answer quicker as to whether these patients are getting any kind of response. Not only that, but we've set up the statistics so that if we do get an answer, if we are able to demonstrate statistically significant progression-free survival, automatically, we can then consider overall survival, median overall survival as another critical endpoint, the kind of endpoint that NICE and the NHS will need to hear about to be able to take this further. So that's where we stand at the moment. We've had a lot of discussions with MHRA about the trial, and they're extremely enthusiastic to see how we get on. And this is really breakthrough from the point of view of this kind of cancer in these patients. And I'm very optimistic, me as a surgeon I know I've been heavily involved with this, but to be able to offer surgeons something that they can do over and above just surgery alone here and accelerate the therapeutic armamentarium that they've got for these patients is just -- is it very exciting, but it's also very needed and given, as I said, for the outcome for these patients, absolutely needed to try and progress this field further. So I think that's more or less all I've got to say, Andrew. I think you've got some other slides there, yes.

Just a final slide. But thanks very much for what is an exceptional account of the story, the back story really to where we are today. And we certainly -- I certainly share your enthusiasm for the potential that we have within our grasp here. So just on a final summary slide. One that we haven't mentioned, we talked about the drug irinotecan. This is a well-known, it's a well-understood drug. We can only derisk these programs to a certain extent. The MHRA they're welcoming irinotecan as a choice. It's a well understood, well used drug. It's still used in first-line in bowel cancer and also as part of the drug combination in pancreatic. So it's well-known, it's well understood. And as being described, it is a mechanism of action, which we feel will be complementary to the other treatments out there at this point. Clearly, the securing access to the trial with the MHRA has been a most significant tipping point. It's been a significant amount of work. And Cruickshank and colleagues as well as our COO, actually put in -- this has been months of work to get this. And we've had a great engagement and a very positive engagement, I'm pleased to say with MHRA. So we're looking forward, everything now is to focus on the clinical trial setup and treating our first patient hopefully early into 2026. The commercial opportunity clearly is significant, and we've highlighted that before. We would hope that with our innovation passport, you may remember, we were awarded as of last year. We are under regulatory fast track, as I've indicated, we are getting very, very good support on this journey. We do have some service contract work. It isn't the primary focus. We're reactive, but it does certainly brings in some additional revenues to help mitigate the cash burn. And clearly, that is key. We need to make sure that we manage our cash runway as best we can at this point. But we know the journey, this is really this -- what we're doing here in brain tumor, I do believe is open the door to other opportunities. I'm pleased that Innovate saw that in us when they've helped to agree to fund the initiation of our prostate program. So that's started a little earlier than planned, but with the funding that was available, it gave us the opportunity to get a head start there. But plans are also commencing for commercialization as well. And again, the regulatory environment is supportive of that. So this has really been quite a remarkable journey. I've been through this with this lived this for some 8 years now, 6, 5, 7 years. But clearly, for professor Cruickshank, this has been a long and exciting journey, and we're actually really quite an inflection point. But -- so that really ends the formalities of the presentation. And Professor Cruickshank, thank you again for your input there. There will be 1 or 2 questions, which I'd like to pick up on before we close. One which I think I partly covered beyond glioblastoma, how do you see ChemoSeed developing as a platform for other cancers? And I think we touched on the fact that it is suitable really for any solid tumor. And we believe we can formulate most drugs into this -- into ChemoSeed, and that gives us a great opportunity. They just put some parallels. So with pancreatic cancer -- sorry, with prostate cancer, which we started on, we're using it again, a well-known well understood drug, docetaxel. Docetaxel has similar challenges. It's delivered systemically, but it does have some challenges how its uptake into the prostate. So working with the lead hematologist, we've got some guidance now about implanting these seeds into the prostate directly. And that's a program we're running at this point. Pancreatic is something we really, really would like to be doing. It's more global complex, will require more development because we're looking at doing cover today standard of care is a 4-drug combination. And we believe we can formulate this, but it will take a little more in terms of development. Somebody asked, can you please give an approximate cost for treating the first 12 patients in the Phase II trial and expand on how you intend to raise the cash? Clearly, this is key. The cost of the trial will start in this month. So it was about GBP 250,000 for the setup. It's going to take probably to get to a reportable data point, probably around GBP 700,000. Total Part 1 costs will be -- we're thinking somewhere around GBP 1 million in totality. That is -- I hesitate a little on that. And the reason being is that the rate of recruitment is going to be key here. And -- but as you can understand from Professor Cruickshank's network, we're working with to on board numerous clinical trial sites that will help to speed up that recruitment. This is really all about -- it's a rare disease, so there's only so many patients, but we believe there's a level of interest in order we can cover this very quickly. How the question is, how do you plan to balance advancing clinical pipeline whilst creating value for shareholders in the near term? All I can say is we believe that the commercial opportunity is significant. There is -- the standard of care has been adequately described here has not changed for 20 years. There's a real appetite for this. We have the proposed costing, which has been -- came from an independent health economic report done by patient consulting a couple of years ago. That gives us a good figure, somewhere it was around GBP 13,000 per patient. This sits nicely within the NICE guidelines as we currently understand them. There's always going to be pressure on the drugs. But one thing the company is very clear on we do not want to fuel this health and quality we see with such expensive cancer therapies coming forward. So we're trying to find -- we obviously find a pathway through that. And we will likely partner at some point. But this is something we're working on. So the -- in terms of the approval, just to be clear on the question, in terms of approval, we will have these inflection points as Professor Cruickshank described, where we can issue data through to the MHRA and we could get an early approval on the basis of the data, and it's all about the data. And I think that has been adequately described, we have a very good preclinical data set and some early clinical experience with irinotecan, which gives us reason to be optimistic. But our primary market will be with NHS in the first instance and then we've rolled out through Europe and then leveraging the ILAP program for other markets. And U.S. is very much on our radar. There's a question here for...

Yes. So from your experience of clinical trials, Professor Cruickshank, do you think ChemoSeed will have making a significant difference to the life outcomes of patients of the trial has been completed. The answer is I don't know. But the reason why I think it might be work and some evidence to prove that it probably will work is the fact that in a number of patients where we were able to treat super early with temozolomide, for example, in 1 or 2 of the trials that I was involved in, there was no doubt that, that cohort did better. In other words, indicating that very early treatment of the tumor, whilst it's small, is actually beneficial as a general principle of treating this kind of cancer. So that's very clear. The other thing is that in a few of the patients that I've treated in the Phase I study, some of the results are quite remarkable. And it was as if, if we want to hit some kind of threshold, maybe you could get an effect. That's why I think that there's a very, very good chance because we're doing something that's not been done before, bearing in mind that previous trials have failed where you've done about conventional adjuvant type treatments. This is what you might call ultra early. And I think that this stands a really good chance of having an effect. So if one can not only treat early and get the tumor smaller, but you can also expect to see some enhanced effect of the radiation because of the presence of irinotecan there as well, which we know from our biological work is probably true, then I think that the outlook for this is good. So I would be -- what's the word? Probably about 75% certain that we're going to see some kind of a result here. Is that result going to be big enough to make a real difference in terms of patients now living -- going from 5% at 5 years to 25% at 5 years. I think that's a tall order. But I do think we might see something that's better than the impact of temozolomide was in terms of those curves for a larger number of patients. And this is really actually economically important because most of the current trials that are going on or most of the current attempts of treatment are involved in looking for molecular pathways and particular molecular signatures within tumors where you can target whatever it is with some kind of IB or AB type drug. Now the trouble with that, particularly in glioblastoma is that so variable is the tumor and so heterogeneous is it that you have a relatively few number of patients who are likely to respond. So for example, larotrectinib works extremely well on the NTK (sic) [ NTRK ] fusion, but only in 1% or 2% of cases of glioblastoma where the abnormality is demonstrated. And a lot of the current drug companies are worried that their molecular-based approaches are only going to yield relatively few patients who are going to be sensitive. Now our treatment here that we're proposing here seems to have a much more broad effect based on its particular effect on the universal mechanism to do with basic excision repair and the way in which repair mechanisms work, double-strand breaks and so on in tumors. So I think it's much more likely that, one, we'll get an effect; and two, we'll be able to do it in many more patients. So that's the best answer I can give you, I'm afraid.

That's great. So I think that concludes the questions. I don't think we've had any more come in. No. So I want to take this opportunity to thank everybody very much for taking your time and for your attention during this presentation. Thanks to Professor Cruickshank for that insightful information really about the setting the scene for glioblastoma and how we plan to address such a challenging disease and one where clearly, as we've seen, the unmet need is really there with some need to address with some urgency. So I look forward to keeping shareholders updated as we continue our journey. But thank you again for your commitment, your support is immensely important to us, and I look forward to updating you again in due course. Thank you very much.

That's great. Well, thank you both for updating investors today. Could I please ask investors not to close the session as you now be automatically redirected to provide your feedback in order the management team can better understand your views and expectations. On behalf of the management team of CRISM Therapeutics Corporation, we'd like to thank you for attending today's presentation, and good afternoon to you all.