Circio Holding ASA (CRNA) Earnings Call Transcript

Start, this has been a highly consequential year for Circio in many aspects. Most importantly, we made major progress on our circVec platform. We have now demonstrated that we can achieve up to 60-fold improved gene expression from AAVs using circVec in 3 different tissues in vivo, heart, eye and now for the first time, also in CNS. We're also continuously optimizing and enhancing our platform. We're testing various novel genetic components inserted into our circVec backbone. And we've identified several new features that when combined together, we believe, has the potential to improve on circVec further, achieving at least 200x more benefit versus mVec compared to the 60x we have shown today. So a novel generation 5 is in the making. We have also progressed on our cell therapy project. Now we've shown for the first time in vivo that we can deliver circVec DNA vectors using T-cell tropic LNPs and that we can do it at a substantially reduced dose compared to what we've done before and get a continuous signal that vastly prolongs over either RNA-based in vivo CAR or DNA-based in vivo CAR using mRNA expression. So another important milestone and new data. And we are being recognized broadly in the industry. We had an oral presentation at the American Society of Gene & Cell Therapy in Boston in May. This is the largest and most prestigious gene therapy conference in the world in the year. And we're also following that up with the presentation and 2 posters to be presented at the European equivalent, ESGCT, in Hamburg in October. We're starting to get recognized in the industry. We're getting a larger volume of incoming requests for collaborations, and Lubor will summarize this, but we now have 23 ongoing research collaborations, including one with the top 5 pharmaceutical companies. And this may sound like a lot, but it's actually quite strategic. They're split roughly evenly between the gene and the cell therapy projects, and they're also designed to address specific needs of each of those programs. With this success in circVec R&D as well as in business development, we've been able to garner positive market momentum. That allowed us to raise approximately NOK 620 million or $65 million in 3 financing rounds during the first half of the year. This now provides us with a solid capital base that funds the company into 2030, and we can execute at full speed on all of our programs. Part of the momentum for Circio is driven by general industry momentum for circular RNA. And I summarize here on the right-hand side, you can see 3 of the, I'd say, the 3 major circular RNA players in the U.S. have all been acquired in the past 9 months. Orbital by BMS, Orna by Lilly and Sail by J&J, all for several billion dollar deals. So this just illustrates the potential the industry is seeing in this format. All of these companies were mainly acquired for their in vivo CAR programs. So in vivo CAR utilizing circular RNA, that's sort of where it's converging. And we're working on circular RNA, and we have an in vivo CAR program. So I think Circio is in a good position. And we are actually the only listed circular RNA biotech around. So if you're a normal investor and can't access VC rounds in these American companies, Circio is the company you can potentially take a position, and that maybe is part of the reason why there has been momentum for Circio. So with that, I hand you over to Thomas for an R&D update.

Thank you, Erik. Thank you, everyone, for tuning in this morning for our half year webcast report. I will try to guide you through our most recent R&D update. There's a lot of data. I mean, and this is just basically the tip of the iceberg that we'll be able to show today. Otherwise, this will be a very, very long webcast. But I think this is just a testament of a very active and a great R&D group that we have here at Circio, and we are expanding and building on that. So a lot of stuff in the making as well. But just to remind you, in contrast to the companies that Erik was just explaining about with Orna, Orbital and Sail, they have in common that they're focusing on the circular RNA itself. We are taking a different approach at Circio, we're working on the DNA cassette that encodes the circular RNA that then in turn makes protein in the cell. So we want -- we are engineering DNA elements, putting them together in a way so you get circular RNA expressed inside cells. And this is what we've been developing over the past couple of years, and we now have shown and we will show the benefit of this approach. And basically, the secret sauce for us and also for all the other circular RNA companies is the stability of the circular RNA. So we are also leveraging that stability. But in contrast to the other companies, we keep supplying the circular RNA via the DNA template. So you get an accumulation of signal over time as well as a durable signal profile. And this I'll come into why that seems to be a benefit over conventional linear RNA-based expression profile that is inherently unstable and will not accumulate to the same extent. So we have these 2 different legs. One is in gene therapy, basically an approach where we put our cassette in an AAV that is a way that you can relatively easy go to your tissue of interest. So we have a focus on heart, eye and CNS. This may be expanded in the future, but this is our current focus areas where we try to make an AAV that's so effective that you can put it in at a much lower dose while still having a clinical meaningful effect from the AAV. And that's basically the main issue with AAVs these days is the high dose and the associated toxicity. So this is what we believe circVec can actually overcome and solve, which will make AAV a much better and much safer therapeutic approach going forward. We also have the other leg. I'll come back to that with cell therapy that is the CAR-T program where we do a nonviral-based approach to get expression in T-cells durable and extended compared to normal approaches. So the way we normally approach this is that we use a reporter gene. So we've presented a lot of data based on a firefly luciferase reporter. It is an amazing research tool because it allows us to monitor gene expression over time in a mouse. In real time, we can see the biodistribution. We can see the expression of the protein basically by measuring light being emitted from the animal. So that is extremely handy. It's very informative and it's easy to work with. So here, you see data that we presented in the past where we could basically in the heart see a 40x enhanced expression compared to mVec. So if you compare here the circVec 3.2, the top line compared to the yellow one mVec, you can see there's a clear difference in expression. But of course, the question begs then how does this then translate to a therapeutically relevant protein because unfortunately, no patient will benefit from firefly expression. So we've been working on setting up circVec for different therapeutic payloads, one being LAMP-2B, which is basically the mutated protein in Danon disease. So here, the treatment strategy would basically, if you have Danon disease, you're missing functional LAMP-2B expression, and that is what the current -- sort of the current gene therapy approach would be trying to solve by expressing the functional LAMP-2B in these patients, albeit with some toxicity that has been seen by Rocket Pharmaceuticals in a clinical trial. So we thought that this could potentially be a good fit for circVec. We can lower the dose and get high expression from our vector system. And here, you can basically see expression profile at day 57 comparing mVec and circVec. It's a little more tedious to work on a therapeutic protein because here you have to basically take the tissue of interest. You have to extract the proteins and run it on a gel and then stain it with an antibody, and this is what's been done here with a process termed Western blotting. And you can -- hopefully, you can appreciate that on the right-hand side, I'm trying to point to it here, you have much more staining on the gel, which basically says that we have a much substantially higher expression from our circVec vector system compared to mVec, exactly as we've seen for firefly expression to the left. So basically, this not only informs us that we can translate all the work we've done to firefly luciferase into a therapeutic protein, we also now have a vector system that we could potentially put in a mouse model and see the clinical benefit of LAMP-2B expression in a mouse lacking LAMP-2B expression as such. Okay, but we're also working on other avenues. CNS is one of the very interesting avenues we've been exploring. We have a collaboration with a top 5 pharma company. And we're also doing some work in-house. There's different ways you can address CNS expression by local delivery, one being, as shown here, intracisterna magna injection where you basically inject your AAV in the neck area of the mice and you monitor again using luciferase luminescence, you monitor expression and biodistribution in the mouse. And we can basically see by that approach, we get roughly one order of magnitude higher expression from circVec compared to mVec, so a 10x improvement with that route of administration. You can also access the CNS by basically drilling a small hole in the skull and injecting the AAV directly into the brain, here referred to as intracerebroventricular injection, a difficult word to pronounce. But here, we see actually an even more pronounced fold change between circVec and mVec, in this case, roughly a 30x improved expression again, measured with luminescence. And finally, we've been doing intrathecal injection where you inject into the spine in the lower back here. And interestingly, we actually see a similar profile between circVec and mVec in the earlier time points. But the good thing about these reporter assays, we can monitor expression over time, and we can actually see that the mVec has a temporal expression profile. It wears off over time. CircVec is persistent, and it may actually increase slightly over the course of this experiment here. So this is where we are with the CNS. We are gearing up to do an experiment with -- together with a big pharma. Lubor will come back to that in the BD part. But we are very excited about this CNS data. And of course, CNS is also the sort of the natural habitat where you see natural circular RNAs being mostly expressed in humans. So we believe that may be a huge potential for the circVec platform in CNS specifically. But of course, being the CFO, -- not the CFO, the CTO in Circio, we are working a lot, and this is something that's very close to my heart, the platform development, how can we perfect, how can we enhance, how can we make circVec even a better performing platform? So there's basically essentially 2 approaches that we focus on. One would be the biogenesis, basically how effective can we generate the circular RNA from our DNA template. This is what we refer to as the biogenesis. So we tested a few different things in vivo. So this is actually data from mouse. And we can see here that we -- compared to our circVec 3.2, which is probably our most characterized circVec design, we can achieve a 3x sort of tripling of the luminescence in this case from that one, which also translates to a 90 -- around a 90x improvement over mVec. But as you can also see, it's not all the designs that improve. So we have another design here, which was actually slightly inferior to circVec, still much better than mVec. But this is at least a design system that a design aspect that we believe is much better in terms of producing the circular RNA inside the cell nucleus where this takes place. Then the circular RNA traffics to the cell cytoplasm. That's where translation goes on. So I think this is a completely independent aspect, namely the protein production from the circular RNA itself. And here, there's different tricks as well you can do to try to optimize that. And we also worked on that. Again, this is data in vivo. And here, we get an even better fold change with our best-performing candidate, a 5x improvement over mVec, 170x improvement over -- sorry, a 5x improvement over circVec, 170x improvement over mVec in this case. And as mentioned, these are 2 different aspects. We believe these are independent. So we, of course, the next step is combining these 2 features, and we believe this would at least give us a 200x improvement over mVec, likely a much larger fold change. But of course, we need to do the experiment before we can say anything with certainty. And of course, also be mindful that this is science. The data here is our current best estimates, but of course, there's always a level of uncertainty with all the specific numerical data that we present. But this is what the data suggests right now, and we will, of course, characterize and work forward to elucidate these different potential circVec 5.0 candidates in more detail. So to summarize a little bit the gene therapy track, we have a focus on heart. At least earlier, we've seen 40x enhanced expression, which triggered us to pursue a heart program. As you've just seen, this is likely an underestimate. 5.0 will perform much better than that, we believe. We have better tissue specificity. We didn't show that today, but we've shown that previously that we get much less expression in the liver, much more on-target heart expression, which is an added benefit for the circVec platform. And we have now shown LAMP-2B proof-of-concept expression in the heart where we can actually express a therapeutically relevant gene. In the pipeline, of course, circVec 5, this will be tested in heart as soon as possible. We are generating circVecs for other therapeutic proteins, other indications, and we're setting up a mouse disease model that actually has a conditional knockout of a therapeutic protein, so we can bring in circVec show that at a very low dose, we can hopefully show clinical or preclinical benefit in such a mouse model. And in general, we are working on identifying the best path forward in cardiomyopathy. It's a huge unmet need. There's a lot of patients struggling with a genetic disease in the heart. So something we are very keen on trying to solve and make AAV safe for that population of patients that basically have no other treatment option currently. Eye as well, still working hard on doing more work in the eye. We are setting up a study very shortly where we are testing new capsids for eye. We've been in dialogue with partners and pharma companies, and they requested us to test more eye-specific capsids. So this is ongoing now. So we are hoping to actually start this experiment in the next couple of weeks, and then we will see how that goes, but that is going to be very exciting. And as part of that experiment, we hope to also characterize a more cell-specific distribution within the eye, what cell types in the eye are actually being targeted and what cell types are expressing circVec to the high extent that we've seen in the past using intravitreal injection. Here, actually therapeutic models in animals are more easy to establish, particular models for wet AMD. So we hope to be able to set up a wet AMD model in the nearby future as well as trialing circVec in a large animal model. So this seems to be more easily addressable with a local injection in eye. So this is something that we work hard on establishing shortly. And as you've seen, CNS, exciting data between 10x and 60x enhanced expression for circVec across these different routes of administration. Again, we believe circVec 5 would be -- would add to that fold change looking into also therapeutic genes that we could potentially express in the CNS. And of course, we have the big pharma collaboration that we are proceeding with. Here, I think most of the future work would be part of a partnership or an out-licensing deal, whereas in heart and eye, we believe that we can potentially bring a candidate to the clinic ourselves. So that sort of concludes the gene therapy leg. Cell therapy, where we try to do a nonviral approach, package our circVec cassette in lipid nanoparticles, systemic delivery and then obtain durable expression in the spleen. Here, it's a little bit -- there's more moving parts. Of course, circVec, we are developing the expression system, as you can see on the left. It has increased expression, extended durability, enabling dose sparing or reduced dosing. So this is what we develop. To make a functional CAR-T, you also need delivery, as you can see to the right-hand side. This is not our expertise. So there, we need to partner with companies that have developed ideally T-cell-targeted LNPs that allow effective delivery of our cargo to T-cells. And then on top of that, there's these different DNA formats that we're currently testing that may actually allow for better gene expression. They are called immune-quiet DNA. So they may also be a little safer for treatment and may allow to actually dose at different levels without impacting any pathways in the target organism. And this is something we are -- and Lubor will come back to that. We are very active in identifying and finding partners that could provide these 2 puzzles that combined with our expression system would be the ideal, we believe, CAR-T therapy approach. So you've seen in the past, and this is basically what triggered initially our CAR-T interest. When we deliver circVec using LNPs in a mouse, we basically see for a normal mVec, so this is what you normally see with an LNP, you get expression in the liver. It wears off quite rapidly. So after a couple of weeks, you don't see signal any longer. So this was mainly expected. And with this particular LNP that we used, it was supposed to target mostly the liver, a little bit liver, a little bit lung and a little bit of spleen. But for the mRNA, you only see that liver expression and it drops off, as you can see. In contrast to circVec and we've shown this before, we see the -- we don't see the accumulation in the liver, but we see the accumulation in the spleen starting here from roughly 3 weeks into the experiment, which was extremely exciting, a very unique profile specific for a circRNA-based expression vector. So we're working on reducing the dose here because this is a fairly high dose. If we went to, in this case, a 5x reduction, we actually didn't see any signal back then in that experiment. So the mice were blank. So we had to dose at a fairly high dose to get the signal. So of course, working on a more targeted approach, so we can lower the dose and get more specific expression to T-cells. So we've been partnering up with other companies that develop T-cell tropic LNPs. So in this case, it's an LNP that goes specifically or mostly to T-cells, although this is not with active target, this is passive targeting to T-cells. And you can actually see when you look at the mVec here to the left, you see a short expression in the T-cell if you look at this high dose. But just bear in mind that this is a dose level that's 5x to 20x lower compared to the one we showed on the previous slide. So at a much lower dose, you see expression in the spleen at a very short period of time with mVec and then in contrast to circVec. As before, you need to wait 3 to 4 weeks and then the signal appears in the spleen even at this very, very low dose, and it's very specific in the spleen. And again, this is using a T-cell tropic LNP. So the status there is that now confirming what we've seen in the past, a completely different LNP with these T-cell tropic properties. Ongoing is to characterize what cell types in the spleen are actually emitting the signal. This is still work in progress. And we are now screening multiple LNPs, other DNA formats, combining different things with our circVec cassette to see if we can make this technology even more potent compared to what it is already. So yes, as you can see with the temporal profile of circVec, I think this -- we believe this is sort of a sweet spot in CAR-T. You have the permanent lentiviral to the right that will give you lifelong expression, but this is a costly affair. It's not without risk. And then you have what's very hot these days, the very temporal short-term RNA-based in vivo CAR approaches. But with circVec, we believe that we can do a non-integrating approach but with a very long expression profile, as we just showed, months of expression, and it will be redoseable in case that's needed. So we think that actually opens up CAR-T for multiple indications, not only autoimmunity, but also in maybe more tricky to treat cancers without the risk of some of the secondary malignancies that you get from the lentiviral approach. So this is a very exciting avenue, and we are working hard and expanding the team to really explore this in more detail in the nearby future. So hopefully, we'll have more data soon to show. So in summary, A lot of excitement with the platform. 5.0 is in the making. We believe we can go maybe 200x or above compared to conventional AAV gene therapy. And of course, you can -- it's just mind-boggling how that may affect AAV gene therapy in general and of course, circVec in particular, the potential for that as a therapeutic modality. AAV specifically, we now have a therapeutic payload with LAMP-2B. We are working on others as well and setting up a mouse model that is -- so we can evaluate actually the preclinical effect of expressing circVec at a very low dose in these animals, hopefully seeing a correction of the phenotype. And we see in CNS a 10x to 60x expression enhancement over conventional AAV gene therapy, also opening up dose sparing and potentially a much safer gene therapy for some of these neurological unmet needs out there. And finally, with the in vivo cell therapy, T-cell tropic LNPs, confirming the long-term circVec expression in spleen, and we now do in vitro and in vivo characterization of the expression profile and the specific cell types that are involved in this signal. So with that, I would like to conclude the R&D update, and I'll introduce Dr. Lubor Gaal for the business development update.

Thanks, Thomas. I have the pleasure to present the business development activities for this first half of the year. And I thank everyone for dialing in and showing interest in our presentation. And business development has been a phenomenal year this year, partly or only because Thomas has done and this R&D group has done tremendous success in R&D. And our business development activities fall into 2 major categories. Here, the first one, we are doing business development to strengthen and expand circVec technology. As Thomas was saying, we're always trying to improve the technology, make it better, make it applicable in different areas. And as you can see, these are our technology collaboration to access complementary technologies. We also, of course, the partnership with other companies to test our circVec platform in preclinical models to generate more data and just explore novel circVec application, especially in areas which are noncore to us so that we can really leverage the full potential of the circVec technology in areas that we don't pursue ourselves. So you will see more of those technology collaborations, and they may lead to out-licensing in the future. On the other hand, of course, we also focusing, especially in the future in '27 on doing -- forming more strategic platform partnerships. This is when we take our technology and we talk to gene therapy company and big pharma company about trying our technology to do collaborations, ideally strategic platform partnerships, but also just out-licensing gene by gene or some kind of corporate or co-development capabilities. So this is our future applications of circVec to generate better gene therapies. And when these companies then license our technology, this will generate revenues for the company in terms of upfront milestone and royalties. So look out for more in 2027. So let me show you a little bit how -- what that means for gene therapy. As Thomas already said, circVec -- in order for circVec to become a gene therapy that can be given to patients, it needs certain parts. And we have -- for gene therapy, we have most of these parts in-house. But there are other companies who claim to have better parts that we are testing. And this is, for instance, the AAV capsid area, where we -- as Thomas said, we're testing targeted capsids to go to tissues and improve the expression of the protein in a specific tissue. And here, you can see what are these therapy collaboration we have in gene therapy. So as we said, we have signed 3 collaborations of which 2 are undisclosed in the AAV capsid space. These are companies like GenAssist who said, "We have a capsid that goes specifically to muscle cells that could be leveraged in the heart or also they are specific in T-cells and go to T-cells." So this is very interesting to try because one of the important things in gene therapy is that you want to express the protein only in the place where it needs to be, but not in the entire body. And these companies claim that when they are using their capsids, it will only go to the tissue that we want, and it will not be entering cells in other areas of the body. So this is super exciting for us, and we are testing this, of course, if we can achieve very targeted high-level expression in the tissue. Then we also partner for novel delivery or GOI, which stands for gene of interest partnerships. And then we have 5 collaborations. And for instance, like with Avenue Biosciences, one thing we want to do is like produce proteins that have to be secreted in order to work in the entire body, and they have a technology to improve that. And TraffikGene is a novel technology to just deliver DNA to cells. And then more importantly, like I said, on the other bucket, we're doing partnering co-development collaboration with companies. Here, we have, of course, our collaboration with a top 5 pharma, which is going really well. As you may remember, these collaboration or all collaboration have different parts. So you go start in different work packages. We have successfully completed the first part of the collaboration, which we announced earlier, and we're now working in the second part of the collaboration, which will take some time because that's the most labor-intensive part of the collaboration. And the preparation and the collaboration is going really, really well. And we will update when we can, but you have to respect that the activities with this company are confidential, and we're not going to be able to disclose results from this anytime soon. AaviGen is another exciting collaboration in the space. This is a German gene therapy company focused on heart diseases. They have a proprietary gene that they want to deliver to the heart and they also have a proprietary capsid, and we are in a technology feasibility collaboration with them, and we're very excited to work with them, and we plan to have more such collaboration going forward. So let me switch to cell therapy. In cell therapy, our BD needs are a little bit different. As Thomas was saying, we need more components in order to make it work. And there, on the one hand, one component is similar, the delivery technology. But in this case, it's not a virus. It is a nonviral technology we call it, we call it LNP, but we can also explore other nonviral delivery technology formulations. And then there's a DNA vector format that Thomas explained that we need in order to make this a better solution. And so you can see we've actually been very active in the DNA vector format. We signed 5 collaboration of them really recently. This is a testament to the interesting technology that we have. I mean the reason why we have been so productive in the cell therapy space is that other companies consider our circVec technology incredibly exciting. and interesting, and they want to try it with their own technology. So it's actually really -- it's really fun to do business development for circVec because we really get a lot of really good receptions. We really have really good discussion. There's a lot of interest to try our technology. So it's been quite exciting. As Thomas was saying, we also do have collaborations and T-cell delivery systems. Here, as I said, there are 2 different delivery systems. We call them active and passive. Passive is when it's more or less just a formulation where they claim that this formulation is taken up by T-cells. This is something like, for instance, Certest, we're testing with Certest here. And then there's what we call active, where actually on the formulation, you put a receptor, not necessarily put a ligand and that ligand binds to T-cells actively and therefore, should be taken up even stronger by T-cells. That's something we have tested with Acuitas. That's something that they provide. So here, very exciting testing as well active as well as passive targeting and seeing what works best for in collaboration with circVec. And then we are exploring other collaborations, other applications. I mean, for instance, with United Immunity, they actually did not target T-cells. They actually want to target macrophages. And so we tested their technology with our circVec technology. And then we have this collaboration with UTMB, which stands for University of Texas Medical Branch, and they want to test antibody for viral or anti-infective therapy. So again, it is in our interest to partner our technology with companies outside of our core space in order to leverage our technology and, of course, generate licensing transaction for future revenue for circVec. So with that, I want to wrap up. The BD activities has been super exciting to do BD with circVec in 2026. And of course, we can expect to continue in 2027. We have done our first partnering deal with a major pharma company, and that's a goal for '27 to do more of those. And also, of course, we want to enter into more collaboration with gene therapy companies. On the cell therapy side, we're a little bit earlier stage. We're not as advanced as not a mature stage as with gene therapy. So the focus here will be more on technology collaborations, and we're looking forward to testing more nonviral delivery, either active or passive and also other applications, of course, to expand the use of circVec. So again, it's been exciting so far, but I think I expect it to continue like this and go into '27 and be really a phenomenal year. With that, I would like now to switch and then start the financial presentation. And as Erik was saying, 2026 has been a transformational year in terms of finance. We had several financing events, 3 finance events to raise NOK 620 million in the first half of 2026. This has been started by a rights issue, which was announced and approved by our shareholders in late 2025 when financial situation was quite challenging. But through a lot of work, and we were able to go out with a rights issue that was 90% secured and was a very successful event. It was oversubscribed. Then following positive momentum in the first quarter of this year, we were able to do a private placement, which raised NOK 250 million. This was really a transformational event for the company because now the runway of the company was secured until 2030, and that provides incredible security for our R&D activities, and this was very, very important to achieve. And then in June, we closed the warrants exercise, which was, of course, part of the rights issue. And through the positive momentum at the market, we were able to raise another NOK 300 million and now to really develop our first clinical program. So this has really a transformational event, and this will really put us in a totally different league in terms of biotech companies in Europe. So let me now focus on the financial results of the first half of 2026. As you can see, the total operating expenses went up and this is partially due to more in vivo studies in R&D. Of course, we need to invest more into R&D. It's exciting times. We need to show different potential, different applications, also, of course, different collaborations. And as Thomas was saying, we have so many different interesting avenues that we can pursue. And of course, this is also why we raised the money, and we want to test them. So we're going to invest more into R&D as well because this is also, of course, where the value is generated, and this is where the data is created that allows us to do the licensing deals that will bring in future revenues to the company. So this is a very important area, and we'll continue to invest there. We also have higher payroll expenses. This is partly due to one-off items. So -- and there were deferred incentive pay, which was paid in the first half of 2026. And very importantly, there's also a noncash effect on options because of the option that was awarded in 2026. This will have to be recognized with national insurance contribution, but did not affect the cash flow. In addition, what you can see, so basically, we do have a higher first half of the year. But because of the one-off items, this means -- does not mean that for the full year, we see a duplication of these expenses. We expect the second half of the 2026 to have lower expenses -- lower operating expenses than in the first half. What is good for us to now report is we had some currency gain and also some return on our cash investments. We are, of course, investing the cash that we don't need in very secure cash accounts or money market funds. And this is only a few weeks of performance that lets us allow report positive and of course, expect this to go up by the end of the year. And so this will be a very positive development. So from the money that we raised NOK 620 million, we now have NOK 533 million left in the bank. So this is partly due to a lot of the expenses, fundraising, unfortunately, isn't free. There is, of course, expenses involved, and this is recognized here in the lower amount. With that, then I would like to conclude on the finance. We had a phenomenal run in 2026, and this really put us in a totally different situation as a company before or until the -- until April 2026. The limited funding that we had at Circio was probably one of the biggest risk factors for the company. Would the company be able to secure enough funding to continue with the good research and the good science that Thomas and his team is doing in the lab. And now since that, now this has been removed. So I would say with the run rate until 2030, the financial risk has been significantly reduced, and we can now focus really on R&D execution, on doing things well in the lab, on doing things in parallel that we used to do sequentially. So -- and this, of course, helps us to generate a data package that really shows the true value of the technology and will then enable or make business development transaction easier. But because we raised money, it doesn't mean we're going to change what brought us here. So we're going to continue to be prudent with our money. We're going to invest it where it really generates value. As I said, this will be primarily in R&D. We'll do more studies. We'll do more advanced studies. One of the things by advancing the program towards the clinic, unfortunately, studies cost more money. These are more complex studies. We have to use CROs. So the think expenses will go up. But this will be gradually. And we'll be very prudent and of course, be very careful to really leverage your money to the best value possible. But do expect the team size to grow and also, of course, the expenses to grow. So what does that mean for 2026 and beyond? So expect the budget or the expenses for all of '26 to be about 50% higher versus 2025. Don't take 2025 as a reference point. That was a time when Circio had very few resources where we kept the team to a minimum and small. I would think that we reset the base in 2026 or so and that sort of -- it's not fair to compare '26 to 2025, but we're now in a much stronger position to really take advantage of a lot of things. We are going to hire a larger team. A larger team needs more facilities. So we have a lot of batch you can already see. We are broadcasting from our new lab in Stockholm means larger team means also, of course, higher productivity. That will be, of course, very important on our business development side. So see a gradual increase of expenses until we have our first clinical candidate selection. And that will, of course, change the company, but that will be in the future. So with that, thanks very much for your attention, and I hand back over to Erik.

So let's summarize. It's been a strong year on R&D. What I want you to remember is we have a circVec Generation 5 in the making. This looks like it should achieve 200x or more better expression than conventional AAVs. And this is big. If you can get the dose down for AAV gene therapy by 200 fold, this can be a game changer for the whole AAV field, and you may need to use circVec expression to have a relevant AAV in the future. We're not there yet, but we're making important progress. On the heart gene therapy, importantly, we've shown that we can express a therapeutic gene. Until now, we've mainly expressed reporter genes, luciferase that we can use as an experimental validation. But now we've shown that the increased expression also applies to a disease-relevant gene, very important validation. And we expanded now into CNS. CircVec AAVs also work in the CNS, same order of magnitude as we see in the heart and eye, and we've shown it for 3 delivery routes. And the fact that it worked for 3 different delivery routes suggests that this is consistent data. And this is, of course, where we also have the collaboration with the big pharma. These data are our own and independent, but obviously, it suggests that circVec works well in this tissue. These data led to substantial BD activities. I mentioned the pharma collaboration. This may lead to a licensing transaction next year, and we have numerous R&D collaborations ongoing. I'd like to stress that don't expect us to update on each of these. These depend on the data we generate, the interest of the partner. What we're aiming to do is not advance every single one. We're going to pick the best ones, the most promising ones and where we have the best fit with the partner and then progress those. So we'll update you when it makes sense and where it makes sense. And very importantly, we need to identify these other components to carve out a complete circVec in vivo CAR concept. We need a safe and efficient vector. These are being screened, and we need a targeted delivery system to get a safe, low-dose therapeutic concept. And these were now screening. And as we progress, we will select our favorites and combine them together, and it will be important to secure access to these technologies for a future complete circular RNA-based circVec in vivo CAR construct. And we have the capital now to execute on these plans. We have NOK 550 million in the bank. This finances the company until 2030, and we're in a solid position to deliver on all these plans and expand as we go along. I'll leave you with the pipeline here. These are our 3 programs in gene therapy, heart, eye and CNS as well as the in vivo CAR and the major upcoming milestones on the right-hand side that you can look forward to in the next month and into 2027. Now again, I'd like to stress that don't get too hung up in every single readout. This is what we're currently doing. These are the plans we have, but the experiments are unpredictable. You never know exactly what works and what doesn't work. You may need to repeat certain things. So we always report what is going on, what the actual plans are, but it may not be exactly what we end up reporting in the future because we follow the data and the data at the moment looks strong. And we need to select what works the best and what partnerships work the best. And what I can assure you is that there will be a substantial amount of data coming out, and we expect to have our next update towards the second half of November when we usually have R&D updates. Remember, we do these updates every 3 months. In addition, we will be publishing data at the European Society of Gene Therapy Conference (sic) [ European Society of Gene and Cell Therapy Conference ] at the end of October. So there will be both an oral presentation and posters presented there. So with that, we wrap up, and we can move to a Q&A section. So do you want to join me again, Thomas and Lubor?

You did not mention eye AAV today. Could you comment on what the status is there?

Yes. So the current status is we continue to work on eye. We are still very excited about ophthalmology in general. We are now setting up our larger study. So that has taken a while to get ready where we test more relevant capsid, more eye-specific capsids in ophthalmology actually by request from some of our partners that we discussed with. So I think if that data in any way mimics or improves on what we've seen in the past, I think there will be a lot of exciting partnerships going forward. On top of that, this study is also powered in a way so we can do the single cell type of analysis. So we actually get a very granular readout on what cells are being targeted, what cells express circular RNA and to what extent. So that will be an extremely interesting data set that will come later this year, I expect. So the study will -- is planned to commence later this month.

So just because we didn't update specifically on the eye gene therapy today, it does not mean we're not very active.

Very active. And we are setting, as we speak, working on wet AMD payloads and other payloads that could potentially go into a transgenic mouse model also quite soon, but this is still a little bit -- time line is a little more unclear there.

We've received several questions around the safety of circVec and generally, it relates to the fact that we produce proteins for a very long time and at very high levels with circVec. Does that lead to any safety concerns or toxicity problems? And is there an off switch in circVec?

Yes, of course, that's a great question. I think at least for gene therapy, I guess you want lifelong expression because this is expressing a protein that you're not able to express yourself. So that will be needed. But whether you can overexpress and get a toxicity readout is something that we will, of course, carefully evaluate. Of course, with the circVec cassette, now we have circVec 5.0. But in case that basically overshoots the therapeutic relevant gene expression, we can just settle back with the circVec 3.2 and then use that one. So that gives us some flexibility to actually adjust the gene expression profile to the indication of interest here. And off switch, something that we've also been considering. It's not something that's built in for the time being, but it's something that's definitely on the table. So there are some different avenues you could explore there. There's riboswitches and microRNA target sites and so forth. So this is something that is possible, but it's not currently in the circVec cassette, but it's definitely a future potential in case, but that would be more maybe in a CAR-T therapy setting that could be applicable.

So we have received also several CAR-T questions. And an important one, again, for you, Thomas, is has Circio confirmed that the durable circVec signal following LNP delivery in vivo originate specifically from T cells?