Circio Holding ASA (CRNA) Earnings Call Transcript & Summary

Ladies and gentlemen, welcome to Targovax in our second quarter presentation. I'm the CEO. My name is Øystein Soug. And with me today in our office studio, I have Chief Business Officer, Erik Digman Wiklund; and Chief Financial Officer, Torbjørn Furuseth. If you have questions during the presentation, there is a button on the lower right-hand corner in the player. So you can push that and you can ask questions. But let's start with the glance at who we are. To remind you, our lead product candidate is an oncolytic virus called ONCOS-102. We're about to complete an early development program, where we have shown clear clinical activity of ONCOS-102 in several indications, in monotherapy, in combination with chemotherapy and in combination with checkpoint inhibitor. And importantly, we also see clear supporting mechanistic biomarker data, establishing ONCOS-102 as a superbly powerful immune activator. In addition to ONCOS-102, we also have a pipeline, which includes novel viruses and the mutant RAS cancer vaccine called TG, which we've taken through a single arm Phase I/II trial. And we aim to develop further through cost-effective collaborations and partnerships. Now much has happened in the last 2 quarters. In our mesothelioma trial, patients are still live, and we have not yet reached the final median overall survival. In our latest readout, however, we see that the survival is going to land between 22 and 25 months in the ONCOS arm, which is a clear improvement over the 13.5 months that we see in the chemo-only arm. In the colorectal trial, we completed patient recruitment. We are now waiting for the data, which we expect will take in, in the first half of next year. And in our quest to develop novel viruses with innovative modes of action, we entered into a preclinical collaboration with a biotech company, Papyrus Therapeutics. They possess a novel kinase inhibitor technology. And to get there with them, we are going to explore the possibilities of integrating that technology into a new virus. In July, we hired Lone Ottesen to the new post of Chief Development Officer. Lone comes from senior immuno-oncology positions in big pharma companies like AstraZeneca, the latest and before then GSK. And when we now continue to develop our product candidates, she will play a key role in the company going forward. Before then, the shareholders elected Sonia Quaratino to the Board, and she is the CMO in Kymab. We had much interaction with the FDA during the period. We had a scientific advice meeting regarding melanoma development and more about that later. And we received fast track for both mesothelioma and melanoma. But what exactly does Fast Track mean? Well, it means that the FDA regards the indication as important and that they encourage the development of new treatments in this indication. And it also means that the FDA regards our data as potentially valuable or beneficial for these patients, to the extent that they want to help us. And they help us by giving us priority when we interact with them along the way. And when we get closer to submission, we will face shorter time lines. But primarily for us now, it means that the FDA likes what they're seeing and they consider what we do as important. Now I'll give the word to Erik, who will take you on a tour through the ONCOS-102 data and how that data is guiding our next steps in melanoma development. Erik?

Thank you, Øystein. Melanoma is our most important indication, and we also recently reported data there. We have a plethora of immune data coming in, and we're starting to really understand what's going on, and I'll tell you a little bit more about that now. So in melanoma, this is in PD-1 refractory melanoma, so treatment refractory patients. And here, you don't really expect much. ONCOS-102 has shown 35% of ORR, and this is great in this indication. You can see here that it is highly competitive to other companies that have published data in this population. On the top panel, the first companies here are all doing essentially the same thing we are doing. They're taking their drug, combining with anti-PD-1 in the same type of patients. And as you see on the list, the 35% ORR for ONCOS-102 is really highly competitive. So why is ONCOS-102 doing so well in this patient group and more broadly? Well, that's because ONCOS-102 is a great immune activator. Now why do we say that? Let me first explain a little bit what we mean by being a great immune activator. So what characterizes powerful immune activation in the context of immunotherapy? Well, first of all, you need to activate an inflammatory response. You need to alert the immune system that there is a danger going on, and you do this by triggering alarm signals. In the case of ONCOS-102, it's done through what's called TLR9 activation. Secondly, you need to get infiltration of immune cells into the tumor. Many tumors have no or few immune cells present. And if there are no immune cells in the tumor, you can't get an immune response. So you need an immune activator that facilitates infiltration of -- we often talk about T cells, but you also need other cell types, such as NK cells, macrophages, dendritic cells, they all act in concert to drive an immune response against the cancer. Thirdly, you need to facilitate an immune reaction that is specific to the tumor, not just to the immune activator. And this is done by a release of tumor antigens and then support in stimulating antigen-presenting cells such as macrophages, dendritic cells to process these antigens and then stimulate T cells that are reactive to the tumor. And then thirdly -- or lastly, you need to counteract negative pathways. So the immune system is really finely tuned to activate and then deactivate the immune response in a timely manner. You don't, in a normal setting, want too powerful immune response and you don't want it to go on for too long. Now the tumor actively uses this as a strategy to abate the immune response by triggering these inhibitory pathways. So inside the tumor, you really want immune response to keep on going and not be blocked. And the way to deal with this is to counteract the inhibitor in molecular pathways and also try and push the dynamics of the cells that are present in favor of the immune reactive cells and then diminish the immune suppressive cell subsets. Now I'm going to go through the immune data that we have and show you how ONCOS-102 deals with each of these 4 issues. First of all, T cells. This is what you always look for and you want to see the T cells in the tumor because they are the ones that are actively destroying and killing the cancer cells. So on this page, we're showing you a case example from melanoma. This is a patient that had a complete response. And then we have pictures taken by microscopy first at baseline, then at week 3 and at week 9. And by week 9, this patient had a complete response, meaning there is no tumor left so to speak. And clearly, you see here at baseline that there are -- the green dots here represent cancer cells and the red RT cells. Top panel is CD8+ T cells, and the lower panel is the helper T cells, CD4+ T cells. And at baseline, you can see some sporadic T cells present, but typically very few. By week 3, the picture has clearly changed. You have much more infiltration of T cells now, both the CD8s and the CD4s between 12 to 15 fold increase. And then by week 9, there is a complete response. And now you can see the tumor, the cancer cells are dying, the structures you see in baseline and week 3 are disintegrating. And there are very few living cells left and the occasional T cells are still there. Now you may argue that we're just showing you some cherry-picked photos here. So that's why we have the graph on the right-hand side, which is a quantification of the whole biopsy we've taken. And again, you see the same picture, baseline low level of T cells goes up by week 3. So exactly what we want to see, and it's very consistent across patients and that I'm showing you on this page now. So what you're looking at here is the aggregated T cell data for all the patients grouped by response. So the average level of T cells by response, and then if we start from the left, CR is the complete response patient I just showed, and then PR, partial response. So these 2 form together your responders with the ORR and then stable disease and to the right in red are progressive patients. The left graph are CD8s and the right are the helper CD4+ T cells. Now what we learn here is, one, ONCOS-102 leads to an increase in T cells in general in the tumor, and this happens across the board. After you treat with ONCOS-102, there is more T cells than before you treated with ONCOS-102. But what's also important is that this increase is higher in the responding patients. So this tells us that not only do we drive an increase of T cells, but it matters. The more T cells you get in, the likelihood of the patient is to actually have a positive impact of the treatment. We also have little asterisks here in the red. And there was one patient that had, what we called, a pseudo progression. And this typically happens with immunotherapy. You get a massive infiltration of immune cells into the tumor. So initially, it looks like the tumor grows, it becomes bigger, but it's becoming bigger because there are immune cells present. And in fact, there is one patient in the group of progressors that is classified as PD, but it turned out later, it was actually a pseudo progression. If you take this patient out from the PD group here, you see that there is no difference in the T cells actually in the progressors. So a very interesting case example of this one. Now I mentioned before that you have certain cell types that are favoring the immune response against the tumor and then you have others that are negative to the immune response. So let me first show an example of a favorable immune type. When it comes to the T cells, you have a variety of active and nonactive T cells. And what we want is the high proportion of the active ones, what we call effector T cells. So the way we measure this is by looking for expression of Granzyme B. So Granzyme B is one of the key molecules expressed by T cells when they're engaged in combat. So if a T cell is Granzyme B positive, it means that it's an actively engaged T cell that is killing a tumor cell. So you want these, of course, to be high and to be increasing. And indeed, it's what we see. Overall, in the melanoma data, the proportion of Granzyme B expressing T cells is very high. You see on the graph here from 30% to 40% of all the CD8s and the tumor are actually expressing Granzyme B. This just as a general observation is very, very high. In other tumor types, we look, it tends to be more like 10%. So we're dealing here with an immune -- with a tumor type that is already very favorable to immunotherapy. Now what we observe is in the progressing patients, this remains high and it goes up, whereas in the stable disease and progressors, it's either flat or it goes down. And again, removing this pseudo progression from the PD patients, you see actually the group of PDs, the ratio or the percentage of the Granzyme B expressing T cells to total T cells is actually decreasing. So it shows how we are able to not only drive the infiltration of the T cells, but ensure that the T cells are in the state we want them to be. Now there is one interesting observation here, and that's the CR, which you probably see that the CR patent is much, much lower than all the others, and this is sort of counterintuitive. But this we can actually very nicely here explain with the regulatory T cells. So let me explain what regulatory T cells are. These are T cells that during an immune response over time increase and what they are responsible for is shutting down the other T cells. So these are inhibiting an active immune response. So you don't want to have a high proportion of Tregs that means you're actually shutting down your immune response. Now in the CR patients, you look here at baseline, we have a very high proportion of Tregs. Almost 50% of the CD4 T cells in the tumor were Tregs. And this is probably the reason why this patient was no longer responding. We treat with ONCOS-102, boom, drops down less than 10%. And immediately, there is a response in the tumor of these patients. Looking at the other patients here, you see the same, the PRs, it's going down. So it's actually only CR and PR where the Tregs dropped to below 10% of the total. In the SDs and PDs, it's more scattered or remains flat. And we think this probably is some sort of threshold that you need is to go below 10% to release an effective immune response inside of the tumor. So again, I showed you we increased the T cells, but the detail is important. You want the Granzyme B to go up, you want the Tregs to go down, and that's what we see here. Another point I want to make is, if you have just a one-trick pony-type immune activator that can push one button that may not be sufficient. In the case of the CR here, what we needed to do was reverse these Tregs and if your immune activator is dealing with something else, well, you probably wouldn't get any response in this case. So therefore, you want immune activators that are able to push multiple buttons at the same time. And what eventually leads to response in the patient might be highly individual. So what I showed you up until now is biopsy data, so pictures taken by microscope are actually tumor samples taken from the patient. Now here, we're showing you data that is new from gene expression. So here with the gene expression analysis, molecular analysis of patient samples. And importantly, these data confirmed the immunohistochemistries. With [indiscernible] method, we see exactly the same thing. But this also goes much deeper. So with this gene expression data, we can explore a lot of more things that are going on in the tumor. All sorts of different pathways we're now able to investigate. And the picture on the right here is just an illustration, this is fairly complicated, but it's to illustrate the breadth of the data that we are generating with this type of analysis. So here, on the graph, you're looking at the change from week 9 to baseline in the expression of important gene categories that drive immune response. And the black line is 0, that means no change. To the right, it's up regulation. To the left, is down regulation. And the simple message I want to give you is you can see how broadly across almost all of these pathways ONCOS-102 is driving an immune response. It's pushing or activating all these pathways that are generating the antitumor immunity. To pick a few examples. We talked about cytotoxic genes, Granzyme B. You can see in the middle here, that is one of the most up regulated classes of genes. We see chemokines and cytokines going up that shows that there is inflammatory response actively happening. We also see checkpoints and co-stimulatory receptors up regulated, which again is indicative of an active combat going on between the immune system and the tumor. So this tells us a few different important things that we try to list in the bullet points here. One, it's very clear that we have a broad pro-inflammatory or hot, if you will, remodeling of the tumor microenvironment. And also importantly, this persists until week 9. So a criticism against treatments like an oncolytic virus may be well, you drive this immune response, but it's really short lived, and it doesn't last long enough to give you a real benefit in the patient. Well, we are showing here that actually at week 9, you still have very profound immune response ongoing. And this biopsy is actually taken 3 weeks after the last ONCOS injection. So 3 weeks after the last injection, and this is injection number 6, we're still seeing broad, powerful up regulation of important immunomodulatory pathways. The other thing that this data allows us to do is understand in a little bit more detail what is happening. And this can inform us what do we or could we combine with in addition to the anti-PD-1 we're doing right now to further boost the immune responses. And that's what we want to do in the future to really take ONCOS-102 to the next level in terms of generating patient benefits. So far, we looked at melanoma. We also did the same analysis in mesothelioma, and I want to show you that the picture is identical in mesothelioma. And this is important because it confirms: one, it's not just a fluke we see in melanoma, it's consistent across all the tumor types. It also shows it works in melanoma, which is a hot or inflamed tumor type that is responsive to immunotherapeutics. It also works in mesothelioma, which is a much more cold or less immune reactive phenotype. So in broadly different tumor types, we see the same type of thing. Also remember, in melanoma, we're combining with a checkpoint inhibitor. So you may argue well that you're seeing this because it's the checkpoint inhibitor that's doing it. Well, in mesothelioma, we're combining with chemotherapy. So here, there is no other immunotherapy, and we still see the same thing. It tells us it's ONCOS-102 is driving all these modulations. It's not a combination partner. So to sum it up. It's consistent across tumor types, and it's consistent no matter what you combine with. Here, I'm again showing you the graphs with the T cells. And as expected, the T cells exemplified here by CD8s, go up in the responders. It goes up, but a little bit less in the stable disease and it actually decreases in the progressors. On the left side here is individual patient effect. So you see that the pre and post treatment for each patient. And I want to highlight one example that there is only a single PD patient where there was a relatively high level of T cells at baseline. But in this case, the T cells actually dropped and the patient progressed quickly and unfortunately had a short survival. So again, it's important to push this in a favorable direction. And here below, we showed a case example of how deep we can go into these patients. So for this particular patient, the stable disease patients that had a particularly good outcome here that the patient is still alive after 24 months, they've never progressed. The tumor stayed stable. And as you see here from baseline to day 36 and the picture, we have a sixfold increase in the CD8 infiltration, but not just the CD8s. If we go down the bullets on the right-hand side, you see Granzyme B expressing CD8s, they're up 16-fold. Every single parameter we look at behave the way we want. We're pushing all these buttons. We're really showing how ONCOS-102 is a broad immune activator doing exactly what you want. Here is the radar plot where -- so in mesothelioma, we have a longer follow-up and now we're actually able to correlate these immune responses to the survival of the patients. And that in the end is what you want the patient, how does this translate into patient survival. It's the most important measure of patient outcomes in the end. And the blue lines here are patients treated with ONCOS-102 and the red are patients treated with only chemotherapy. And then the solid line represents the patients that were still alive at 18 months. 18 months is sort of the threshold in mesothelioma where the first-line therapy of ipi/nivo got approved. So therefore, we make the cutoff there longer and shorter survival than 18 months. Now what becomes evident when you look at it this way, these are all these parameters I talked about of great immune activation, you see how much more profound it is in the ONCOS-treated patients compared to the chemotherapy-only patients. And it's clearly better in the survivors. So this immune response matters. Now what you really want to do is can we push this even further? Can we -- what does it tell us in terms of how we can improve response rate, but also what is the ideal combination partner for ONCOS-102. And let me give you a few examples. So on this left-hand side, you can see the PD-L1 expression goes up. This tells you PD-L1 is sort of a don't-kill-me signal expressed by the tumor, which tells the T cells not to actively engage in combat against it. So by blocking that, you block the tumor's defense. And it's a very obvious combination partner. And that's what everyone is doing. Everyone is combining with anti-PD-1 checkpoint inhibitors because it makes such sense with these types of therapies. But you can do much more. We talked about Tregs. Well, anti-CTLA-4 actually reverses Treg. So maybe combined with an anti-CTLA-4, you can get your Tregs down even more, boost the response that way. You want antigen-presenting cells to be maturing, processing and presenting the tumor antigens, exemplified here by macrophages. What can you do? Well, you could combine with a vaccine to stimulate an antitumor immune response that way or again, anti-CTLA-4 is highly active in stimulating the maturation of these antigen-presenting cells. We have the Granzyme B cytotoxic T cells there actively killing T cells, right? Now many of these will probably be recognizing the virus and not the tumor. You can make these attack the tumor as well if you combine with something like a T-cell engager, which relies on tumor targets. So you redeploy the antiviral T cells and make them active against the tumor. So this is something we're exploring. T-cell engagers have been producing a very promising data in liquid cancers. And now they're emerging as a class that is becoming relevant in solid tumors as well. So this we're actively looking at. And then finally, here, we talked about generating an infiltration of CD4 and CD8 T cells. Well, you want to push them into the correct phenotype, right, and that you can do with something called co-stimulatory molecules. The examples of this is OX40, CD40. These are co-stims that push your CD4s and CD8s into the correct effector phenotype that you want. So now our scientific team is working very closely here and looking at what is the perfect combination partner, and we're also actively in dialogues with companies that have these types of molecules that we believe would be excellent for combination with ONCOS-102 and can enable us to further release the power here and drive the patient benefits. So with that, I hand over to Øystein again.

Thank you, Erik. Now summing up in melanoma. We have an extremely attractive data set leading to best-in-class response rates, supported by a highly consistent biomarker data, which not only confirm and give support to the clinical efficacy that we see, but also points us in potential new directions. As Erik just explained, the way ONCOS-102 changes and optimizes the tumor microenvironment suggests which combinations beyond PD-1 blockade may boost response rates even further and above the 35%. But also, as I already mentioned, we've had several interactions with the FDA in the last periods. We received Fast Track in 2 indications, and we got scientific advice on the next steps in melanoma. We previously communicated that we plan to get scientific advice from the FDA on whether continuing with a single arm trial would support an accelerated approval. In the scientific advice meeting we had with the FDA, they advised us to adjust that plan into a 2-step approach, a randomized Phase II trial and then a registrational trial. As before PD-1 refractory melanoma remains our lead indication and in order to assess a contribution of components, which is important to the FDA, the next trial needs to have both an onco-mono arm and an ONCOS PD-1 combo arm. And data from this trial alone could then lead to a registrational trial. But moreover, part one of this defined will serve as the basis on which we may add 1, 2 or even more arms with novel IO combinations on top. But ONCOS-102 will actually be part of any and all of these arms, probably also a PD-1, then adding third components, like the ones indicated on the radar plot by Erik just now, like CTLA-4 or co-stimulatory agents. The intention being to push the efficacy even higher and thereby differentiate ourselves better and further from the competition. So we intend to do these arms with collaboration partners, and we are already in talks with several potential candidates with which we would like to work. And we believe this is going to be a great trial yielding highly competitive and differentiating data, early data, frequent data and not least interesting data for potential partners. Now in addition to this, the FDA noted that data from this trial will open up possibilities in the highly attractive first-line melanoma indication. Previously, we were just going after the PD-1 refractory. And based on these Phase II data and the FDA confirmed this, we can decide at a later point whether we will set up the registrational trial in first line or continue in the PD-1 refractory setting or maybe even do both. So we think this is going to be a great trial. Summing up our pipeline, it remains quite similar to what we have shown you before. We plan to recruit the next mesothelioma patient in the first half of next year. The final mesothelioma data will come towards the end of this year and colorectal data early in 2022. With that, I hand over to Torbjørn and the finances.

Thank you. Okay. So to the finances and the high-level view. We spent NOK 24 million in the second half -- second quarter. This is very much in line with previous spend. And that left us with NOK 71 million at the end of the quarter. Market cap currently around NOK 630 million. And while trading has been down a bit during the summer, it's still quite strong trading in the share with slightly above NOK 3 million traded daily on an average basis in the last 12 months. On the shareholder base, roughly 1/3 of the shares are held by private -- professional institutions like HealthCap, Nordea, AP4, Arctic Aurora and also 7% are held by nominee accounts, which typically also represent professional institutions. The largest shareholder is still HealthCap with a 14% shareholding. And the 20 largest shareholders holds 48% of the shares. And in total, we have 5,600 shareholders in the company. So a bit more details on the spending in the second quarter. And the OpEx is very much in line with previous quarters. We had somewhat higher spend on our OpEx on payroll and related expenses. That's related to -- half of the increase is related to option costs, the accounting of those, so no cash effect on that. And the second half is to recruitment. And as Øystein mentioned, we have recruited Lone to the lead clinical development, which is a very strong and a valuable addition to the team. Also, we are recruiting for head of manufacturing, and we have also recruited 2 people to clinical team. We have also expanded business development team with one person and also the science team. So really great additions to the Targovax team in the last few months. So total operating expenses of NOK 24.5 million running to NOK 25 million. In terms of cash burn, as you saw on the previous page, also NOK 24 million, leaving us with NOK 71 million cash at hand at the end of the quarter, and that will provide a cash runway into 2022. So to sum up, as you've just seen today and from our data, ONCOS-102 is the best clinically documented immune activator in refractory tumors. We have shown that across several aspects in different tumor types, in different settings, both monotherapy in combination with checkpoint inhibitors and in combination with chemo, so broadly documented. And important also, as Erik went a bit deep on today, the immune activation and the mechanism of action, we really see what we -- exactly what we want to see. The immune cells that should go up and the activated are increasing and the immune cells that should go down are also decreased. So the mechanism of action is also solidly documented and we have not seen any one being able to document their product as good as ONCOS-102. So with this solid basis, we are now preparing for the platform trial that Øystein introduced to you and providing a lot of opportunities and opportunities for data and a very interesting path forward. The product is also protected by patents. So we have a patent protection to 2037. And we have orphan drug designations. And with the fast track designations as well, we'll also provide additional and valuable input from the authorities to the development plan. And in addition, the pipeline assets, we have some novel assets in-house and also in collaboration with partners and also the TG02, which is ready for Phase II trials. And we hope to be able to land some of the collaborations, low-cost opportunities to bring the program forward during this year. So on the outlook, there are some interesting conferences upcoming. Victor will be presenting at the Next-Generation Cancer Summit. And then we will be at ESMO and presenting our melanoma data. And in October, the Oncolytic Virotherapy Summit is in Boston, and that's the first in-person conference, we are aware of, and we will go there, and Erik is invited to present. So hopefully, crossing fingers that the situation is stable and we can go. And then the fifth Annual Next-Generation IO Conference will be a presentation by Victor. Data outlook. We will have a survival update on the mesothelioma data. And also very interesting next year, we will see the colorectal data with the patients with the colorectal cancer with a spread to the peritoneum. Next quarterly presentation is the 4th of November. So thank you very much for following us today. And we will continue with a Q&A session, and I bring Erik and Øystein up here.

Okay. So thank you very much, everyone, for submitting questions. I think the first question goes to Erik. You're in discussions with partners in melanoma. How are potential partners expressing their thoughts around clinical data provided from ONCOS? Do they agree that you are best-in-class?

So the response data here clearly holds up as highly competitive against the other relevant treatment options in development in this indication. But what really sets us apart is the biomarker package. As far as we see what is publicly available from other companies, the ones on our list, they are nowhere near the breadth and impressive level of response that we see. And I mean, you see some examples here and there of T cells going up, et cetera. So it's not like there is no immune activation data, but not to the granularity and broadness that we demonstrate. Now you can speculate that they probably do these analysis themselves and the fact that they're not published may mean that they're not as good, but we simply don't know. What we do know is that many partners are contacting us because they see that our mechanistic data would benefit their drugs like -- our cycle that we showed a certain combination opportunities that are particularly relevant. So we are engaged in multiple dialogues at the moment for doing combinations with other companies' products that make sense in this context.

Okay. And a bit more on the melanoma trial. Could you please detail how you see the path to the registration in ONCOS-102 in PD-1 refractory melanoma. When do you expect to be able to initiate upcoming melanoma study? And when do you expect the first readout?

Well, as I mentioned, this is a trial, which is going to have several components. And we remain with the guiding that we had previously that we will be able to start that trial towards the middle of next year. We're guiding the first half of 2022. And that's where we think that we'll be able to recruit the first patient into the first arm of this trial. And then depending on when we get the data and depending on which cohorts we'll go on with, that will determine when we will be able to take the next steps. But possibly, this should not take very long. I mean after the 2 leading cohorts, we will -- there will be a possibility to take the next steps based on that data. And we're not guiding formally on when that is going to happen, but we don't expect the time lines to be very long.

Thank you. And to Øystein again. Some questions on the funds. What are the chances for raising necessary funds through either selling the RAS platform, license out next-gen ONCOS or make a strategic partnership with a partner and license for ONCOS with both melanoma and mesothelioma?

Yes. So essentially, in a company like ours, there are 3 possibilities of finding the path forward. One is through partnerships. They can be quite important when they happen, but it's very hard to guide when they will happen. As you know, we have an option to out-license TG in China. So that is something which is still ongoing. That option has not been taken. We have a standard a time line. They need more time in China to make that decision, and we've given the time to them. And we're still optimistic that, that is going to become the reality. So that's one type of financing form that we do in biotech. The other one is co-development. And as we mentioned in the platform trial, we're setting up, we're doing that with potential funding collaborators. So there is a possibility that the partners or the collaboration partners in this setup will pay for a part of the trial. And the third option is then, of course, to raise money in the capital markets.