Circio Holding ASA (CRNA) Earnings Call Transcript & Summary

Ladies and gentlemen, welcome to the Targovax First Quarter 2021 Presentation. My name is Øystein Soug, and I'm the CEO of the company. For you today, we have a program, where we will delve into the melanoma data a bit further than we have done before. And to do that, we have our Chief Business Officer, Erik Digman Wiklund with us, and he will take us through the new data in melanoma. Also, we have Torbjørn Furuseth, our Chief Financial Officer, with us today, and he will go through the finances. You can ask questions as we go along, and we will answer them at the end. But first, let me give you a reminder about who we are and what we're doing. Our lead product candidate is an oncolytic virus called ONCOS-102. And with ONCOS-102, we have stellar efficacy data. We have really solid powerful immune activation data, and we are committed to take this compound further towards the market in combination with a checkpoint inhibitor. We also have an emerging pipeline where we explore novel viruses with new transgenes, new modalities but also mutant RAS cancer vaccine concepts and also the combination of the 2. What Targovax today is at a crossroads. We are going from being an early-stage development company into being a late-stage development company. And in this early-stage development program, we have taken ONCOS-102 through several Phase I and Phase I/II clinical trials in monotherapy, in combination with checkpoint inhibitors and in combination with chemotherapy. And we have seen some really good clinical efficacy data from those trials. But also, we have seen supporting mechanistic biomarker data, which positions ONCOS-102 as a really powerful immune activator. And based on these data, we will now go forward in checkpoint inhibitor refractory melanoma. So we'll set up a trial with ONCOS-102 in this indication with the aim of creating data that will take us through a registration eventually. But based on the strength and the breadth of the data that we've seen with ONCOS-102 so far, we are also quite enthusiastic about the expansion possibilities that are offered to us in addition to melanoma. And that is, first and foremost, mesothelioma, but also colorectal cancer, potentially other indications, other immuno-oncology combinations as well as platform development with new viruses. So there's an exciting time in front of us. Taking a quick peek at the pipeline, you will see here, there are 3 trials that we will concentrate on mostly. It's melanoma in combination with checkpoint inhibitors, colorectal cancer in combination with checkpoint inhibitors and mesothelioma in combination with chemo. Now the melanoma trial is finished. We are, as I mentioned, about to plan a Phase II, which will have the properties of creating registrational data. We'll hopefully start that trial soon, and we're guiding on the first half of 2022. The mesothelioma trial, we'll also touch upon today. That trial is not recruiting. It's fully recruited, but we have not been able to read out the final data yet, waiting for oral survival. And talking about mesothelioma. In the quarter, we received Fast Track from the U.S. FDA. Now what it means is that's an expedited development path and review. In essence, that means that the FDA like what they have seen. It means that there's an intention with them to help us take this forward, and we get more access to FDA processes and people along the way. We also did a 21-month survival sweep, and I'll present the data later. On the emerging pipeline, we entered a collaboration with a company called Papyrus Therapeutics. They have a kinase inhibitor. And together with them, we will create a new virus with a kinase inhibitor payload. That's quite novel. Nobody has done that before, so that's a very exciting collaboration we have entered into. Torbjørn will say more about IP in his section, but the highlight is that we got a new patent for ONCOS-102 in the U.S. in combination with checkpoint inhibitors, and we fought off in a position against TG -- the TG patents in Europe. And last but not least, we got a new board member, Sonia Quaratino. She's the Chief Medical Officer at Kymab, a company that was recently acquired by Sanofi. Taking a quick look at mesothelioma data. Now just to remind you, this was a small randomized trial in first, second and later lines of mesothelioma. And we are concentrating primarily on the first line. So these are the patients that have not been subjected to chemotherapy yet. And what we see in this data set is a good separation on PFS. Meaning that it took longer time for the ONCOS patients to progress than the patients who only got chemo. When we count up the patients alive after 21 months, we see that half of the ONCOS patients are still alive, while only 17% of the control patients, the chemo patients, are alive. And that means that the ONCOS patients have not reached a median overall survival yet. So the clock is still ticking. The last time we counted, it would be 20.5 months or longer. And for the chemo only patients, the median overall survival is 13.5 months. Now when we compare the ONCOS patients with other trials that have been done in this indication with chemotherapy and checkpoint inhibitors, we see this actually quite intriguing result here, where the other trials, they have reported survival between 8.5 months and 20.5 months. Perhaps the most important one here is the one ipi/nivo at 18 months. That's the one where BMS got an approval in this indication in October last year. And up in the right-hand corner, you see the arrow, which represents the ONCOS patients. That is an arrow because we do not have the final result yet. As I said, the clock is still ticking. And there will be a survival sweep later, which will determine what the real result is going to be. But as of now, obviously, this is a good result. It's a small trial, but the survival result is very good. Now going forward, we will continue to follow the patients to determine the median overall survival. In the meantime, we are working on the next steps. That is working on what patient population within mesothelioma we should go after and what sort of treatment these patients should get. And as soon as we made a decision about the next steps in mesothelioma, we will make an announcement about that. Good. Then we go over to melanoma, where Erik will show you the clinical data we have shown so far as well as some new immune activation data.

Thank you, Øystein. So over to melanoma. Let me remind you first what this trial is. So we are testing ONCOS-102 in what we call PD-1 refractory melanoma. So these are late-stage advanced melanoma patients that are not eligible for surgery. And normally, what these patients would be treated with is an anti-PD-1 checkpoint inhibitor, which is very helpful and gives deep responses in many patients. But unfortunately, the majority of patients will still progress. What we're trying to do with ONCOS-102 is take those progressing patients, give them ONCOS-102 and then put them back on an anti-PD-1 checkpoint inhibitor to see whether we can reinstate the response to the treatment. So that's the hypothesis we are testing. These patients have a very poor prognosis, few treatment alternatives. There really isn't anything approved for this population. What they have is clinical trials and experimental therapies. In our trial, we enrolled 20 of these patients. They were advanced with a roughly 50-50 split between Stage III and Stage IV, Stage IV being defined as patients with metastatic disease. So that's the patient population. We tried 2 different treatment regimes in this trial. In the first part, we only gave the patients a priming treatment of 3 ONCOS-102 injections. And then we put them on 6 months of the anti-PD-1 checkpoint inhibitor, KEYTRUDA or pembrolizumab, which is the generic name. In the second part, we tried to expand the dosing of ONCOS-102. We gave the first 3 injections, the same as in part 1. But we kept giving the oncolytic virus, ONCOS-102, each time the patient came in to get their pembrolizumab infusion for up to 6 months. The response data in the trial were very good. 35% ORR, that means 7 out of the 20 patients had a tumor response. And here, you're really expecting 0. These patients were progressing on the anti-PD-1. We were able to get 7 out of those 20 to get a response to the tumor or the tumor responded to the treatment, which only can really be explained by an effect of ONCOS-102. So this, we are very pleased with. Out of these 7, 1 patient had a complete response and 6 had a partial response. A complete response means 95% or more of the cancer has disappeared. Importantly, we also saw, as we reported before, several examples of systemic effect. So we are giving the oncolytic virus intratumorally into one lesion or maybe a couple. But in metastatic setting, the patient will have more lesions. So when we say systemic effect, it means we see a response in a tumor lesion that was not injected. That means we generated an immune response in the injected site that then was able to enable a regression in a distant lesion. And this is, of course, very important to show that ONCOS-102 can drive a systemic antitumor response. We saw this in several patients. And in fact, in 2 patients, there were examples of a non-injected lesion that completely regressed. It means we didn't inject it and it completely disappeared, can only be explained by a systemic immune response to ONCOS-102. We have now been busy analyzing immune data that came in from the trial, and I will show you much more of that in the coming slides. Otherwise, we can also comment on the safety, which has been excellent. We have no problems with the regimen. It's well tolerated, either as just a priming in part 1 or concomitant dosing as we did in part 2 of the trial. So really, no safety concerns beyond what you expect from just the anti-PD-1 monotherapy alone. Here is a graph that shows you how the patients progressed over time. So let me explain. What we do is we measure at baseline the size of the patient's tumor, and then we index to 100. So then what we're looking at is the difference from baseline for each patient in relative terms. And we have measurements done at week 9, week 18 and then the end of study, which is after 6 months. And the line would indicate how the tumor has developed over the time. And in the dark blue, the example of the complete response. You can see that already at the week 9 measurement, we're down to 0. There is no detectable tumor left, and this lasted throughout the duration of the trial. The other light blue lines are for the partial responders, so patients with regression but not a complete regression. And you can see here that most of them actually already by week 9 have a very clear drop in the tumor volume that then keeps going. The light gray and the dark gray are patients with stable disease and progressive disease, so these are the nonresponders. But one thing to note is that even though they are progressors on nonresponders, it's not a dramatic shift in the tumor. The tumor is not growing very quickly. We also see one example, and you may note that there is this one line that first increases and then drops, and this is what you can refer to as a pseudo-progression. That means it seems like the tumor is growing and the disease is getting worse, but then it comes down later. And this is something that happens at times in -- with immunotherapy. And probably the reason is you're triggering a local inflammation influx of immune cells. And this gives you an impression that tumor is growing when, in fact, what's happening is there is an immune response, and then later you may actually see the tumor reducing. And that's what we believe is happening in this case as the patient clearly had a drop from week 9 to 18 and week 27. And I will come back to this patient in the next couple of slides. So that's how the patients were doing clinically. We also have some pictures to just give you a flavor of what this looks like for the tumor of a natural patient, and here is the patient with a complete response. On the very left side of the graph or of the slide, you see the tumor the patient presented with. So this is after the patient is progressing on the anti-PD-1 therapy. Then the first 3 weeks, we give ONCOS only. So there is no pembrolizumab given in the first 3 weeks. And you clearly see on the photograph that there is a dramatic reduction already at week 3 in the tumor, which shows you that ONCOS-102 is having a monotherapeutic activity here. And then by week 9, after 2 infusions of pembrolizumab, it was a complete response, which then lasted throughout the trial. There is still some coloring on the skin, but this is mainly hematoma or bruising and biopsy marks. This was a confirmed complete responder. The patient was a late-stage patient that had 3 time surgery before, have been treated with several different types of immunotherapy as well as BRAF and MEK inhibitors. So it's a very late-stage heavily pretreated patient where we're actually able to drive a complete response, which I think is remarkable. And we can also look inside the tumor of this patient. So the previous picture shows you just the visual tumor, how it changes. Here, we're looking at the inside of the tumor, how that changes. So let me explain. On the left-hand side, baseline and then middle, week 3. So this is after ONCOS only, and then week 9 is after 2 infusions of pembrolizumab. And then we are doing immunohistochemistry on tumor biopsies. And what you're seeing is the blue indicating living cells, so just any living cell. And then the red is indicative of T-cells in this case. In the top panel, it's CD8+ T-cells, so your cytotoxic T-cells. And in the bottom panel, it's CD4+ T-cells, so the helper T-cells. And if we start on the left-hand side at the baseline, we see for the CD8, there is maybe the occasional CD8 cell present, but it's very little -- a few more CD4s. But by week 3, very clearly, you see now the red starting to come up. That means the T-cells are infiltrating into the tumor, which is exactly what we're hoping to see. And importantly, it's happening before we start treatment with pembrolizumab. So it means this is driven by ONCOS-102 injection. And then by week 9, you can see here that the picture has completely changed. You're no longer seeing the small blue circles that are indicating live cells, but it's more diffused. What this is really illustrating is dying cells, necrosis inside the tumor. There are still a few T-cells present, but overall, we're just confirming what we saw on the photographs that the tumor is disintegrating also at a cellular level. On the right-hand side now here, we have done a quantification of the amount of T-cells present in -- on the total slide of the biopsy. And you see from baseline up to week 3 massive increase in the T-cell population, both the CD8 and the CD4. By week 9, it goes down a little, but this is explained by the fact that it's now a complete response and you mainly have a necrotic tissue. This is not a fluke. We see this routinely. We see it again and again. Every single patient we look at basically fit this picture. Here's another case example, which we think is particularly interesting. In this case, the patient had actually been treated with TVEC before, and TVEC is another oncolytic virus that is approved and on the market. So this patient that had TVEC and anti-PD-1. So it's refractory to oncolytic virus and refractory to also the anti-PD-1 checkpoint inhibitor. And in this case, we were able to get a partial response. The patient had 2 lesions, the first lesion on top and the other one on the bottom. And you see the first one is completely disappearing, and then the second one is more or less stable. So again, we see an example of one lesion that actually completely regresses. And I also like to highlight here. You see week 3, remember, monotherapy before pembrolizumab. And on the top picture, you see very clearly that something is happening when you inject ONCOS-102. The molecule is active. Now let me show you the same T-cell stains for this patient. We see the exact same thing. It's low infiltration at baseline, both of the CD8+ and the CD4+ T-cells on the left-hand side. By week 3, this increases. In this case, it's about threefold increase from baseline in both of these cell types, and then further increase by week 9. So again, we're confirming the mode of action. We're getting T-cells into the tumor. The patient is responding. ONCOS-102 is behaving and doing exactly what we wanted to do. And here, you can see it progressively -- the T-cell count is increasing. Baseline, threefold increase to week 3 and further increase at week 9. And in this case, we're looking at a partial responder. So it makes sense, in the other case, the tumor was gone at week 9, which explains why there was somewhat lower T-cell count at that stage. So here -- that's case examples, some individual patients. We also can look at all the patients at once, and that's what we're doing on this graph, and let me explain what you're looking at. So again, these are CD8+ T-cells. And now we've sorted the graph. So it shows the complete responder on the left, then the partial responses, PR, in blue -- in light blue. In gray, stable disease and then progressors in red. And then the first line, the gray is baseline. Number 2, with the thick dark line is week 3 and then at week 9. So what does this show us? Again, looking at TILs, CD8 inside the tumor. What's very clear is that there are much more CD8+ T-cells in the tumor of the responders. There is this one example here of one of a progressor that has a strong increase in the CD8+ T-cells. But this, interestingly enough, and maybe not unexpectedly, is the patient with a pseudo-progression. So this single PD patient with a strong increase is, in fact, the one with pseudo-progression, and I think this explains why the tumor first grew and then later comes back down. So a very reassuring case. If we quantify this to make it a little bit easier to look at than the individual patient graph, you see here averages. So this is the average T-cell level per group, complete response, partial response, stable disease and so forth. And you see here, the increase is very clear in the CR and the PR case. It goes up. The T-cell count goes up. It's less so in stable disease. There is a small increase in partial disease -- in the progressive disease patients. But when we remove -- as indicated by the asterisk, when we remove the pseudo-progressor, there is no change. So the whole change we saw in the PDs is just driven by this one pseudo-progression case. And taking that out, all the progressors, there is no average change. Now you're looking at the same thing for the CD4+ T-cells. So it's different T-cell population, and the pattern is exactly the same. The level is clearly highest in partial response patients. And the one progressor with this pattern is the pseudo-progressioning in patients. The same goes for looking at the averages. There is an increase in the responders. The stable disease and PDs don't have this. And again, you see the difference here on the asterisk progressing population that there is no difference when we take out the patient with the suspected pseudo-progression. So these are the overall T-cell populations. Now there is a lot of dynamics going on in the tumor, and you have different cell types performing different tasks. So we like to go in and look at the subpopulations of these T-cells. And let me explain what you're looking at here. So in this graph here, we're showing now CD8 T-cells but CD8 T-cells expressing granzyme B. We can refer to these as activated or effector T-cells. What they are doing is that this shows -- when a T-cell is expressed in granzyme B, it means this T-cell is actively killing something. It's an ongoing immune attack. And in this case, that would be on the tumor. So you really want these cells to be high. You want them to go up. That means there is an active immune response. And like before and even more pronounced in the partial responders, it's a much higher level of these granzyme B expressing T-cells, exactly what we want to see. When we average it out, like we did before, you're looking at the same thing again, just the total for each group of patients. And here you see in the PRs, it's high. It's increasing. Whereas in the stable disease and PDs, it's, if anything, going down a little. One thing to note here is that this is extremely high level of granzyme B expressing T-cells. So the right-hand panel now is the percentage of the total T-cells. So close to 40% of all the T-cells in the tumor are granzyme B expressing T-cells. This means most of the T-cells are actively attacking the tumor, and I think this is a remarkably high level. We don't see it going up so much in the PRs, in the partial responders, but we believe the reason for this is that there are just plenty. There is more than enough available already, and there is a very potent immune response ongoing, it seems, in the patients here. Somewhat interesting, it's low in the complete responder. But I will come back to that, and we have an explanation for why that's happening. Now on the bottom panel here, I'm going to show you a different type of T-cells, and these are what we call regulatory T-cells, CD4+ and FOXP3+ T-cells. And regulatory T-cells have a function in the immune response to shut it down when it's ended. You don't want an immune response to disease to go on for too long. And therefore, you have a very tight regulation of the immune response shutting it down when it's time to do so. And these Tregs are responsible for shutting down a T-cell attack. In the context of an antitumor response that we want with ONCOS-102, we want the Tregs low. If you have high Tregs, it means the immune system is actually fighting the immune response and trying to stop it. And the first immediate thing that strikes you here is that the regulatory T-cells are much lower than the cytotoxic T-cells on top, which is what we want, less Tregs than cytotoxic T-cells. And looking at the percentage, and here you care about the ratio of the cells, how many are there relative to each other. And I mentioned before the CR, and you can see the complete responder actually had close to 50% of the T-cells present being Tregs at baseline. This is probably why the patient was no longer responding to the anti-PD-1 therapy. We give it ONCOS, boom. The Tregs go down to less than 10%, and the immune response or the tumor response is reinstated to the anti-PD-1. And we believe this may be -- might be sufficient. Just this reversal of the Tregs is making this patient again responding. Same for the PRs. In average, they had a much lower level of Tregs at baseline than the complete responder. But it is reduced, and it comes down to less than 10%. And it's, in fact, only in the responding patients, we see the regulatory T-cell population being under 10% after treatment. In the SDs and the PDs, it's higher. It's above 20%. So it may mean that this is a threshold you kind of need to get under, have a low enough level of Tregs to enable an effective antitumor immune response. So overall, data is pointing in the right direction. The T-cells are going up and the favorable T-cells are increasing. The unfavorable T-cells are decreasing. So we are very pleased with this data, and we try to compare to our peers who are also active in this indication. And here with -- we have scored on various parameters, how we think we stack up. And the top line is Targovax, and then the other companies that are active in the anti-PD-1 refractory melanoma space. In the first column, you can see the ORR, as reported in the data so far. Our 35% is stacking up very well. It's equivalent to the other best alternatives out there and better than most others. So these data hold up really nicely when you look at the other molecules in development. And remember, nothing is approved in this patient population yet. Looking at the next check marks there, clinical benefit. We show, of course, the ORR. That's important. Two, we show the abscopal effect or systemic effect that's demonstrated in this trial. We've done previously a monotherapy trial. We know ONCOS is active by itself. We also see it in the melanoma trial. In those first 3 weeks, remember, already there, we see tumors regressing, and we see the clear immune responses. So ONCOS-102 is working by itself. It's not just working in concert with the other -- with the anti-PD-1 therapy. Fourth, we have the combination with anti-PD-1. It's safe. It's effective. And from our mesothelioma trial, we also have combination with chemo. So we know ONCOS works in monotherapy, and it combines well with other treatment options. On the right-hand side, we sorted biomarker data, and these are important to confirm that ONCOS-102 works as we expect. And we show TLR9 signaling goes up. This is the alarm signal that is triggered when the virus infects into the body. This happens when we infect -- we treat with ONCOS-102 in the tumors, exactly as expected. We have an inflammatory response. T-cells go up. We also see cytokines in the periphery. Everything points towards the patient having a local or a systemic inflammation happening with a local treatment. This is also confirmed by clinical parameters, such as the patient developing fever. We see T-cell infiltration into the tumor and also PD-L1 upregulation. So you can see we're actually coming to a stage where ONCOS-102 is very well validated. It works in multiple contexts. It drives the clinical benefit. Tumors are aggressing the mechanism lineup. So we're very comfortable that we're in shape to move forward here. So we get confidence from the biomarker data. It shows us mechanistically, ONCOS-102 works as it's supposed to. It gives us confidence that we're driving clinical benefit. Tumors are aggressing. Patients are getting a good outcome. And third, it gives us confidence that we're in good shape compared to the competitors. We are a competitive player in this space. And when we compare, you see below here, there is no other modality in development that ticks the boxes on all these axes like ONCOS-102 does. So to summarize, I think we've shown that ONCOS-102 activates an immune response and counteracts multiple mechanism of immunosuppression that are active in the tumor of these refractory patients. The microenvironment is shifting. We're getting infiltration of T-cells, and we're getting a favorable shift to the T-cells you want and reduction of those you don't want. And we see the synergy with the anti-PD-1. So we think ONCOS-102 is a perfect combination partner to checkpoint inhibitors. Now we took this data and have shown them to top international KOLs to ask for their advice and consult on what we should be doing next. And in the left box, you can see we spoke to. It's really well done here by our R&D team who was able to discuss this with the top international people like Jedd Wolchok from Memorial Sloan Kettering, Mario Sznol. This is really a list of who's who in the melanoma space today. The feedback overall is, one, the 30% -- ORR of 30% or higher is viewed as very interesting for the clinicians. We have 35%. So they think this is a meaningful data that can help their patients. Two, they say the systemic effect is really important, and they consider what we have shown better than what they would have expected to see. They also advise us that we must continue development. This really warrants the test in a bigger trial, whether the data will hold up. And the feedback is that a single-arm Phase II trial should be sufficient to reach an accelerated approval if the 35% ORR or close to that holds up in a larger trial. Interestingly, we're also advised to consider a double checkpoint combination, so that would be ONCOS-102 plus anti-PD-1 and CTLA-4 double checkpoints. So this is another option we're actively exploring at the moment. I'm also pleased to confirm that all the KOLs we spoke to were interested in participating in the next trial we do, and Douglas Johnson from Vanderbilt has confirmed that he will be the PI of the Phase II to follow. So that means we have a very strong KOL willing to take on this trial and drive it. Shortly in the next steps here, we're working on the design at the moment. Our plan is to run ONCOS-102 plus anti-PD-1 trial, just exactly as we did in the Phase I and gear it so that we can get to an accelerated approval from the FDA based on such a trial. At the moment, we think around 100 patients in a single-arm setting should be sufficient. Remember, there is no standard of care. So there really isn't anything to compare to, and that's why we may not have to do a randomized trial in such a setting. Primary endpoint will be ORR. What we're seeing in the industry is that here, ORR really should be sufficient as an endpoint to get you to this accelerated approval. And the dosing we're going to go with is the part 2 regimen. That is the dosing regimen where we keep injecting every time the patient comes in for their pembrolizumab infusion. So we're now going back to KOLs. We're testing study design ideas. We're subsequently going to ask the FDA if they agree with our design and endorse this path to an accelerated approval with such a trial, assuming the data holds up. And we're also discussing with anti PD-1 companies for collaborations. We haven't yet selected who we're going to go with, but it will be ONCOS-102 plus an anti-PD-1 checkpoint inhibitor. And the aim is to start enrolling the trial at some point during the first half of 2022. So this is, of course, now a very important work going on in Targovax designing this trial and making all the necessary preparations, finding the relevant collaboration partners there to get this off the ground, and, hopefully, take ONCOS-102 all the way to data that can enable us to go to the FDA and ask for an accelerated approval. I might add that even if you get accelerated approval, you still need to do a more standard confirmatory, large trial, but that's typically something you agree at the time or just before you submit your application for accelerated approval. You agree what the confirmatory trial should look like. That needs to be done. It needs to be confirmed to give you a full license. But with the accelerated pathway, you're then allowed to start marketing your product before or at that time when you start the confirmatory trial. So that's how we're thinking about the development here. So that concludes the melanoma part of the presentation. Let me hand over to Torbjørn on the finances.

Thank you very much, Erik. Very interesting. Okay. So to the financials. And in first quarter, we saw the operating expenses to be very much in line with the previous 2 quarters and summing up to NOK 23 million. External R&D at NOK 9 million, including patents and other operating expenses rounding down to NOK 2 million. It was almost two point -- it was NOK 2.4 million, so rounding down to NOK 2 million, but glad to see that other operating expenses are down. In terms of cash, there was a burn of NOK 27 million in the quarter, taking us to a net cash position of NOK 95 million. So to the sort of key figures, the cash, as I said, NOK 95 million, cash burn of NOK 27 million for the quarter. Current market cap, around NOK 700 million, and we see that the liquidity in the share is still quite strong throughout the last 12 months. It's 150% of the shares being traded, almost 3.5 million per day. So that's quite strong, and we're happy with that. In terms of coverage, DNB, Carnegie and Wainwright are covering us. So I would like to draw your attention to the patent opposition case that Øystein also mentioned in the introduction. And we are, of course, very pleased to see that the TG plus chemo patent was maintained as granted after the opposition last week. So just to provide you some information or the background. There was an undisclosed party that filed an opposition, a very thoroughly developed and deep analysis of the patent and with a lot of documentation, where they claimed that the patent lack novelty. There was also a lack of inventive step. That the patent did not disclose in full -- the full invention and also that it extended beyond the application. So a very thorough attack, and they demanded the patent to be revoked in full. The proceedings were held last week. And we're very pleased, of course, to see that all the objections from the opponent were rejected by the opposition board. So this was a full victory on a very significant attack on the patent. So they now have been through the acid test and still remains. The opponent might decide to appeal, and we will see if they do that in the coming months. So to wrap things up. Targovax, with our lead compound, ONCOS-102, targeting the large checkpoint inhibitor market of $25 billion, where there is a high and growing need for immune activators that can enhance the efficacy of the checkpoint inhibitors. As you saw now, Erik quite thoroughly took you through our data set. And with the class-leading data on the clinical side and also with a broad and powerful immune activation, we are now entering late-stage development in refractory melanoma. Also, there are upsides to this platform, which now is validated what is our data and also the recent vaccinations, showing that the adenovirus platform is a very suitable vehicle to generate immune responses and the immune activation. We have a strong patent protection to our assets and also a robust and strong team to pull this off. Upcoming events. We're coming to the Radium podcast next week and also ABG (sic) [ ABGSC ] Life Science Summit towards the end of the month and also the Oncolytic Virus (sic) [ Viruses ] Symposium. Next data points will be a 24-month readout or follow-up in mesothelioma. And subsequently, also the data from the colorectal trial with metastasis to the peritoneum. So with that, we conclude our presentation, and we will move over to Q&A. And I will have Erik and Øystein come up here, and I will read the questions.

So first to the melanoma trial. Øystein, in which countries are you planning to conduct the melanoma trial? And also, are you planning for interim readouts in a trial? And if so, when could this take place?

So first, on the interim readout. So this is going to be an open-label trial, which means that it's going to be possible to do readouts along the way, and I think we'll try to time them to the important conferences, first and foremost. The first part of the question was -- remind me.

The countries.

The countries. So in -- this is a trial where we will -- we need to recruit in many different centers, and we will probably do that in -- on both sides of the Atlantic as well as maybe also in more distance geographies like in Australia. Clearly, it's going to be several centers across the world.

Okay. And question to Erik, also on the melanoma trial. So Replimune announced yesterday the outcome of the meeting with the FDA concerning their trial in anti-PD-1 refractory melanoma patients, and also CheckMate has provided some color. Could you please comment these important regulatory events? And also let us know a bit on your -- on the status of your current discussions with the agencies.

Yes. So this information from Replimune was just announced yesterday, and we haven't fully been able to analyze what's come out of that. But as far as we understand, the FDA endorsed the plans of Replimune to run, in their case, 125 patient single-arm trial. And assuming the data holds up and it's compelling, that should be sufficient to enter into the accelerated approval path with a parallel confirmatory trial. So it seems the FDA has endorsed the plan of Replimune. And of course, our plan is, I would say, highly similar to Replimune's plan. So I think it gives us comfort that this strategy is a viable strategy for the next step. Looking at the other companies like CheckMate that are active in the space and OncoSec, they're all doing trials that are roughly the same size and design, around 100 patients, single-arm, all aiming at the accelerated approval path. So of course, we need to go to the agencies and ask the question for Targovax and test our concrete proposal, which we are intending to do probably in August. That's the plan, and then we'll see, but we're reassured by the developments and what others are doing in the space.

Okay. Good. And last question to Øystein regarding the colorectal trial. Could you please give an update on the patient enrollment and estimated time line?

Yes. To remind you again, this is a trial, which is being sponsored by Ludwig Cancer Research, so we're not having both hands on the wheel here. But from what we understand, that trial is now reaching full enrollment, not quite yet, but we're getting there. When it comes to data from this trial, we are conservatively guiding next year, but we'll see. And there are no more questions?

No.

No. In that case, I'll just thank my colleagues and thank you who listened in, and we'll come back later. Thank you. Bye-bye.