Q2 2026 Circio Holding ASA Earnings Call

Speaker #1: Welcome to Cirqueo and our first half-year report and R&D update webcast. My name is Eric Digman Wycland. I'm reporting from our new labs in Stockholm, and together we meet today.

Speaker #1: I have CTO Dr. Tomas Hansen, as well as CFO Dr. Lubergall. Important disclaimer: today we'll go through a little bit of a highlights. First, by myself and a market update.

Speaker #1: It's been a big year for circular RNA as well as in vivo CAR field, so that's exciting because it relates directly to what we're doing.

Speaker #1: Then Tomas will provide you with an R&D update, then the latest progress on the circuit platform and our gene therapy and cell therapy programs.

Speaker #1: We've been very active on business development this year. Luborg will summarize that, as well as financials. And then we wrap up at the end.

Speaker #1: So to start, this has been a highly consequential year from for Cirqueo in many aspects. Most importantly, we made major progress on our circuit platform.

Speaker #1: We have now demonstrated that we can achieve up to 60-fold improved gene expression from AAVs using circuit in 3 different tissues in vivo. Heart, eye, and now for the first time also in CNS.

Speaker #1: We're also continuously optimizing and enhancing our platform. We're testing various novel genetic components inserted into our circuit backbone, and we've identified several new features that, when combined together, we believe has the potential to improve on circuit further, achieving at least 200 times more benefit versus MVEC compared to the 60x we've shown today.

Speaker #1: 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 circuit DNA vectors using T-cell tropic LNPs.

Speaker #1: 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.

Speaker #1: So another important milestone and new data. And we're being recognized broadly in the industry. We had an oral presentation at the American Society of Gene and Cell Therapy in Boston in May.

Speaker #1: This is the largest, the most prestigious gene therapy conference in the world in the year. And we're also following that up with a presentation and 2 posters to be presented at the European Equivalent ESGCT in Hamburg in October.

Speaker #1: We're starting to get recognized in the industry. We're getting a larger volume of incoming requests for collaborations and Luborg will summarize this, but we've now have 23 ongoing research collaborations, including one with the top 5 pharmaceutical companies.

Speaker #1: 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.

Speaker #1: With this success in circuit R&D, as well as in business development, we've been able to garner positive market momentum, that allowed us to raise approximately $620 million or $65 million in 3 financing rounds during the first half of the year.

Speaker #1: 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.

Speaker #1: At the conference in the world in the year, and we're also following that up with the presentation and two posters to be presented at the European equivalent, ESGCT in Hamburg, in October.

Speaker #1: Part of the momentum for Cirqueo 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 US have all been acquired in the past 9 months.

Speaker #1: We're starting to get recognized in the industry. We're getting a larger volume of incoming requests for collaborations, and Luber will summarize this, but we now have 23 ongoing research collaborations, including one with the top five pharmaceutical companies.

Speaker #1: 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.

Speaker #1: 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.

Speaker #1: 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.

Speaker #1: With this success in Dirkvec R&D, as well as in business development, we've been able to garner positive market momentum that allowed us to raise approximately 620 million kroner, or $65 million, in three financing rounds during the first half of the year.

Speaker #1: And we're working on circular RNA, and we haven't in vivo CAR program. So I think Cirqueo is in a good position. And we're actually the only listed circular RNA biotech around.

Speaker #1: So if you're a normal investor and can't access VC rounds in these American companies, Cirqueo is the company you can potentially take a position in, and that maybe is part of the reason why there has been momentum.

Speaker #1: 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.

Speaker #1: For Cirqueo. So with that, I hand you over to Tomas for an R&D update. Thank you, Eric. There we go. Thank you, everyone, for tuning in this morning for our half-year webcast report.

Speaker #1: Part of the momentum for Circio is driven by general industry momentum for circular RNA, and as I summarized here on the right-hand side, you can see three of the—I’d say the three major circular RNA players in the US—have all been acquired in the past nine months.

Speaker #1: 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.

Speaker #1: 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 will be able to show today.

Speaker #1: 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 Cirqueo, and we are expanding and building on that.

Speaker #1: 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.

Speaker #1: And we're working on circular RNA, and we have in vivo CAR programs, so I think Circio is in a good position. We're 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 a company you can potentially take a position in, and maybe that's part of the reason why there has been momentum.

Speaker #1: So a lot of stuff in the making as well. But just to remind you, in contrast to the companies that Eric was just explaining about with Orna, Orbital, and Sail, they have in common that they're focusing on the circular RNA itself.

Speaker #1: We are taking a different approach at Cirqueo. We're working on the DNA cassette that encodes the circular RNA that then in turn makes protein in the cell.

Speaker #1: For Circio, so with that, I hand you over to Thomas for an R&D update. Thank you, Eric. There we go. Thank you, everyone, for tuning in this morning for our half-year webcast report.

Speaker #1: 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.

Speaker #1: 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.

Speaker #1: I will try to guide you through our most recent R&D update. There's a lot of data, and this is just basically the tip of the iceberg that we'll be able to show today. Otherwise, this would be a very, very long webcast. But I think this is just a testament to the very active and great R&D group that we have here at Circio, and we are expanding and building on that.

Speaker #1: 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.

Speaker #1: 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.

Speaker #1: 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—Orna, Orbital, and Sail—they have in common that they're focusing on the circular RNA itself. We're taking a different approach at Circio.

Speaker #1: So we have these 2 different legs. One is in gene therapy, basically an approach where we put our cassette in an AV that is a way that you can relatively easy go to your tissue of interest.

Speaker #1: We're working on the DNA cassette that encodes the circular RNA, which then, in turn, makes protein in the cell. So, we are engineering DNA elements and 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.

Speaker #1: 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 AV that's so effective that you can put it in at a much lower dose while still having a clinical meaningful effect from the AV.

Speaker #1: We have now shown, and we will show, the benefit of this approach. Basically, the secret sauce for us, and also for all the other circular RNA companies, is the stability of the circular RNA.

Speaker #1: And that's basically the main issue with AVs these days, is the high dose and the associated toxicity. So this is what we believe Cirqueo can actually overcome and solve which will make AV a much better and much safer therapeutic approach going forward.

Speaker #1: 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.

Speaker #1: 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.

Speaker #1: And this—I'll come into why that seems to be a benefit over conventional linear RNA-based expression profiles, which are inherently unstable and will not accumulate to the same extent.

Speaker #1: Durable and extended compared to normal. Approaches. So the way we normally approach this is that we use a reported gene. So we've presented a lot of data based on a Firefly luciferase reporter.

Speaker #1: So we have these two 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 easily go to your tissue of interest.

Speaker #1: So, we have a focus on heart, eye, and CNS. It may be expanded in the future, but these are our current focus areas where we try to make an AEV that's so effective that you can put it in at a much lower dose while still having a clinically meaningful effect from the AEV.

Speaker #1: 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.

Speaker #1: We can see the expression of the protein. Basically, by measuring light being emitted from the animal. So that is extremely handy. It's a very informative and it's easy to work with.

Speaker #1: And that's basically the main issue with AEVs these days: the high dose and the associated toxicity. So, this is what we believe CircVec can actually overcome and solve, which will make AEV a much better and much safer therapeutic approach going forward.

Speaker #1: 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.

Speaker #1: So if you compare here the Cirqueo 3.2, the top line compared to the yellow one, MVEC, you can see there's a clear difference in expression.

Speaker #1: 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.

Speaker #1: 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 non-viral-based approach to get expression in T cells.

Speaker #1: So we've been working on setting up Cirqueo for different therapeutic payloads. One being LAMP2B, which is basically the mutated protein in Danan disease. So here the treatment strategy would basically, if you have Danan disease, you're missing functional LAMP2B expression.

Speaker #1: Durable and extended compared to normal. So, the way we normally approach this is that we use a reporter gene. We’ve presented a lot of data based on 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.

Speaker #1: And that is what current sort of the current gene therapy approach would be trying to solve by expressing the functional LAMP2B in these patients.

Speaker #1: 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.

Speaker #1: Albeit with some toxicity that has been seen by rugged pharmaceuticals in a clinical trial. So we thought that this could potentially be a good fit for Cirqueo.

Speaker #1: 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 see in the heart a 40x enhanced expression compared to MVEC.

Speaker #1: 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 Cirqueo.

Speaker #1: So, if you compare here the CircVec 3.2, the top line, to the yellow one, MVEC, you can see there's a clear difference in expression.

Speaker #1: But of course, the question then begs, how does this translate to a therapeutically relevant protein? Because unfortunately, no patient will benefit from Firefly expression.

Speaker #1: 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.

Speaker #1: 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.

Speaker #1: We've been working on setting up CircVec for different therapeutic payloads, one being LAMP2B, which is basically the mutated protein in analyses. So here, the treatment strategy would basically be, if you have Danon disease, you're missing functional LAMP2B expression, and that is what the current gene therapy approach would be trying to solve, by expressing the functional LAMP2B in these patients.

Speaker #1: 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 Cirqueo vector system compared to MVEC.

Speaker #1: 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 into Firefly luciferase into a therapeutic protein.

Speaker #1: Albeit with some toxicity that has been seen by Rugged Pharmaceuticals in a clinical trial. So, we thought that this could potentially be a good fit for CircVec.

Speaker #1: We also now have a vector system that we could potentially put in a mouse model and see the clinical benefit of LAMP2B expression in a mouse lacking LAMP2B expression as such.

Speaker #1: We can lower the dose and get high expression from our vector system. And here you can basically see the expression profile at 57, comparing MVEC and CircVec.

Speaker #1: 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.

Speaker #1: OK. 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.

Speaker #1: 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 AV in the neck area of the mice.

Speaker #1: And hopefully, you can appreciate that on the right-hand side—I'm going to point to it here—you see much more staining on the gel, which basically shows that we have much higher expression, or substantially higher expression, from our CircVec vector system compared to MVEC.

Speaker #1: 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 Cirqueo compared to MVEC.

Speaker #1: 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 with 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 LAMP2B expression in a mouse lacking LAMP2B expression, as such.

Speaker #1: 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 AV directly into the brain.

Speaker #1: Here referred to as intracerebroventricular injection. A difficult word to pronounce. But here we see actually an even more pronounced hole change between Cirqueo and MVEC.

Speaker #1: 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-five pharma company, and we're also doing some work in-house.

Speaker #1: 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.

Speaker #1: There are different ways you can address CNS expression by local delivery. One being, as shown here, intracisternal magna injection, where you basically inject your AAV in the neck area near the eyes, and you monitor again using luciferase luminescence.

Speaker #1: And interestingly, we actually see a similar profile between Cirqueo and MVEC in the earlier time points. But the good thing about these reporter assays, we can monitor expression over time.

Speaker #1: And we can actually see that the MVEC has a temporal expression profile. It wears off over time. Cirqueo is persistent. And it may actually increase slightly over the course of this experiment here.

Speaker #1: You monitor expression and biodistribution in the mouse, and we can basically see that by that approach, we get roughly one order of magnitude higher expression from CircVec compared to MVEC.

Speaker #1: 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 AEV directly into the brain.

Speaker #1: So this is where we are with the CNS. We are gearing up to do an experiment together with a big pharma, Luba. We'll come back to that in the BD part.

Speaker #1: But we're very excited about this CNS data. And of course, CNS is also the sort of the natural habitat where you see natural circular nases being mostly expressed in humans.

Speaker #1: Here referred to as intracerebroventricular injection—a difficult word to pronounce. But here we see actually an even more pronounced whole change between CircVec and MVEC.

Speaker #1: In this case, it's roughly a 30x improvement in expression, again measured with luminescence. Finally, we've been doing intrathecal injections, where you inject into the spine in the lower back here. Interestingly, we actually see a similar profile between CircVec and mVec in the earlier time points, but the good thing about these reporter assays is that we can monitor expression over time, and we can actually see that the mVec has a temporal expression profile.

Speaker #1: So we believe that may be a huge potential for the Cirqueo platform in CNS specifically. But of course, being the CF or not the CEO, the CTO in Cirqueo, we are working a lot and this is something that's very close to my heart.

Speaker #1: The platform development. How can we perfect? How can we enhance? How can we make Cirqueo even better a better performing platform? So there's basically or essentially two approaches that we focus on.

Speaker #1: 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.

Speaker #1: We are gearing up to do an experiment together with a big pharma. Luba will come back to that in the PD part. But we are very excited about this CNS data, and of course CNS is also the sort of natural habitat where you see natural circular RNases being mostly expressed in humans.

Speaker #1: 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.

Speaker #1: 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 Cirqueo 3.2, which is probably our most characterized Cirqueo design, we can achieve a 3x sort of a tripling of the luminescence in this case from that one, which also translates to a 90 around a 90x improvement over MVEC.

Speaker #1: So we believe that there may be a huge potential for the CircVec platform in CNS specifically. But of course, being the CFO, not the CEO or the CTO, and Sergio, we are working a lot, and this is something that's very close to my heart.

Speaker #1: 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 Cirqueo.

Speaker #1: The platform development , how can we perfect . How can we enhance , how can we make sure even better a better performing platform So that's basically or essentially two approaches that we , we , we focus on .

Speaker #1: Still much better than MVEC. But this is at least a design system that are design aspect that we believe is much better in terms of producing the circular RNA inside the cell nucleus where this takes place.

Speaker #1: 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.

Speaker #1: 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.

Speaker #1: So we tested a few different things in vivo . So this is actually data from from mouse . And we can see here that we compared to our 3.2 , which is probably our most characterized Cirkovic design .

Speaker #1: 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.

Speaker #1: We can achieve a three x sort of a a tripling of the luminescence . In this case from that one , which also translates to a 90 around a 90 x improvement over Mbec .

Speaker #1: 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 Cirqueo, 170x improvement over MVEC in this case.

Speaker #1: But as you can also see , it's not all the designs that that that improve . So we have another design here , which was actually slightly inferior to , to still a still much better than Mbec .

Speaker #1: And as mentioned, these are two different aspects. We believe these are independent. So we of course, the next step is combining these two features.

Speaker #1: But this is at least a design system, or design aspect, that we believe is much better in terms of producing the circular RNA inside the cell nucleus, where this takes place.

Speaker #1: 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.

Speaker #1: 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 the protein production from the circular RNA itself .

Speaker #1: 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.

Speaker #1: And here, there are different tricks as well that you can do to try to optimize that. And we also worked on that. Again, this is data in vivo.

Speaker #1: But this is what the data suggest right now. And we will of course characterize and work forward to elucidate these different potential Cirqueo 5.0 candidates in more detail.

Speaker #1: And here we get an even better fold change with our best performing candidate of five X improvement over Mvac 170 x improvement over sorry , a five x improvement over 170 x improvement over M in this case , and as mentioned , these are two different aspects .

Speaker #1: 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 triggers us to pursue a heart program.

Speaker #1: We believe these are independent . So we of course the next step is combining these two features . And we believe this would at least give us a 200 X improvement over likely a much larger fold change .

Speaker #1: 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.

Speaker #1: 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 , you know , this is science .

Speaker #1: 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 Cirqueo platform.

Speaker #1: The data here is our current best estimates . But of course , there's always a level of uncertainty with all the all the specific numerical data that we present .

Speaker #1: But but this is what the data suggest right now . And we will of course characterize and work forward to , to , to elucidate these , these different potential .

Speaker #1: And we are now we have now shown LAMP2B proof of concept expression in the heart where we can actually express a therapeutically relevant gene.

Speaker #1: In the pipeline, of course, Cirqueo 5, this will be tested in heart as soon as possible. We are generating Cirqueo for other therapeutic proteins, other indications.

Speaker #1: 5.05.0 candidates , more detail . So to summarize a little bit , the gene therapy track , we have a focus on heart , at least earlier .

Speaker #1: And we're setting up a mouse disease model that actually has a conditional knockout of a therapeutic protein. So we can bring in Cirqueo, show that at a very low dose, we can hopefully show a clinical or preclinical benefit in such a mouse model.

Speaker #1: We've seen 40 X enhanced expression which which triggers triggered us to pursue a hard program . As you've just seen this , this is likely an underestimate 5.0 will , will will perform much better than that .

Speaker #1: 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 here struggling with a genetic disease in the heart.

Speaker #1: 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 circular platform .

Speaker #1: 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.

Speaker #1: And we are now we have now shown lamp to be proof of concept expression in the heart , where we can actually express a therapeutically relevant gene in the pipeline .

Speaker #1: I 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 capsid 5.

Speaker #1: Of course, five, this will be tested, tested in heart as soon as possible. We are generating search for other therapeutic proteins.

Speaker #1: 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 the circuit and show that at a very low dose, we can hopefully show a clinical or pre-clinical benefit in such a mouse model.

Speaker #1: 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.

Speaker #1: And , 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 who are struggling with with a genetic disease in the heart .

Speaker #1: 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.

Speaker #1: What cell types in the eye are actually being targeted and what cell types are expressing Cirqueo to the high extent that we've seen in the past using intravitreal injection.

Speaker #1: So, something we are very keen on trying to solve is to make AAV safe for those patients that basically have no other treatment option currently.

Speaker #1: I as well am still working hard on doing more work in the I. We are setting up a study very shortly where we are testing new capsules.

Speaker #1: 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 Cirqueo in a large animal model.

Speaker #1: We've been in dialogue with partners and pharma companies, and they requested us to test more specific capsids. So, this is ongoing now.

Speaker #1: So this seems to be more easily addressable with a local injection in the eye. So this is something that we work hard on establishing shortly.

Speaker #1: So we are hoping to actually start this experiment in the next couple of weeks, and then we will see how that goes.

Speaker #1: 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.

Speaker #1: And as you've seen, CNS exciting data. Between 10 and 60x enhanced expression for Cirqueo. Across these different routes of administration. Again, we believe Cirqueo 5 would be would add to that fold change.

Speaker #1: What what cell types in the eye are actually being targeted and what , what cell types are expressing . So to , to high extent that we've seen in the past using intravitreal injection here , actually therapeutic models in animals are more easy to establish .

Speaker #1: 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.

Speaker #1: Particular models for wet AMD. So, we hope to be able to set up a wet AMD model in the near future, as well as trialing in a large animal model.

Speaker #1: 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.

Speaker #1: So this seems to be more easily addressable with a local injection eye . So this is something that is that that we work hard on , on , on establishing shortly .

Speaker #1: So that sort of concludes the gene therapy leg. Cell therapy where we try to do a non-viral approach, package our Cirqueo cassette in a lipid nanoparticles systemic delivery.

Speaker #1: And as you see in CNS , exciting data between 10 and 60 in expression for vec across these different routes of administration . Again , we believe five would be a would add to that fold change .

Speaker #1: And then obtain durable expression in the spleen. Here, it's a little bit there's more moving part. Of course, Cirqueo, we are developing the expression system.

Speaker #1: Looking into also therapeutic genes that we could potentially express in the CNS . And of course we have we have the big pharma collaboration that that that we are proceeding with here .

Speaker #1: As you can see on the left, it has increased expression, extended durability. Enabling dose bearing or reduced dosing. So this is what we develop to make a functional CAR-T.

Speaker #1: I think most of the future work would be part of a partnership or an outlicensing deal, whereas in Heart and I, we believe that we can potentially bring a candidate to the clinic ourselves.

Speaker #1: 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.

Speaker #1: So that sort of concludes the gene therapy leg, cell therapy, where we try to do a non-viral approach, package our cassette in lipid nanoparticles for systemic delivery, and then obtain durable expression in the spleen.

Speaker #1: 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're called immune-coADNA.

Speaker #1: Here it's a little bit there's more more moving parts . Of course , we are developing the expression system , as you can see on the left , it has increased expression , extended durability , enabling dose bearing , reduced dosing .

Speaker #1: So there 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.

Speaker #1: And this is something we are and Lubo will come back to that. We are very active in identifying and finding partners that could provide these two puzzles that combined with our expression system would be the ideal.

Speaker #1: So this is what we develop to to make a functional car T . You also need delivery . As you can see to the to the right hand side .

Speaker #1: 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.

Speaker #1: 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 Cirqueo using LNPs, in a mouse, we basically see for a normal MVAC.

Speaker #1: And then on top of that, there are these different DNA formats that we're currently testing that may actually allow for better gene expression.

Speaker #1: They call them immune DNA, so they may also be a little safer for treatment and may allow us to actually dose at different levels without impacting any pathways in the target organism.

Speaker #1: 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.

Speaker #1: So this was mainly expected. And with this particular LNP that we use, it was supposed to target mostly the liver, a little bit liver, a little bit lung and a little bit of spleen.

Speaker #1: And this is something we are and will come back to that . We are very active in , in identifying and finding partners that could provide these two puzzles that combined with our expression system , would be the ideal .

Speaker #1: But for the mRNA, you only see that liver expression and it drops off as you can see. In contrast to Cirqueo, and we showed 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 three weeks into the experiment.

Speaker #1: We believe in the CAR-T therapy approach. So, as you've seen in the past, this is basically what initially triggered our CAR-T interest.

Speaker #1: When we deliver CVAC using LNPs in a mouse, we basically look for a normal MVEC. So this is what you normally see with LNP.

Speaker #1: 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.

Speaker #1: You get expression in the liver. It wears off quite rapidly. So, after a couple of weeks, you don't see signal any longer.

Speaker #1: 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.

Speaker #1: If we went to, in this case, five time reduction, we actually didn't see any signal back then in that experiment. So there the mice were blank.

Speaker #1: But for the for the mRNA you only see that liver expression and it it drops off as you can see , in contrast to .

Speaker #1: 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.

Speaker #1: And we showed that this , 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 three weeks into the experiment , which was extremely exciting , a very unique profile specific for a surgery based expression vector .

Speaker #1: So we've been partnering up with other companies that developed 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.

Speaker #1: This is passive targeting to T cells. And you can actually see with you look at the MVAC here to the left, you see a short expression in the T cell.

Speaker #1: So we're working on reducing the dose here because this is a very high dose. If we went to, in this case, a five-time reduction, we actually didn't see any signal back then in that experiment.

Speaker #1: If you look at this high dose. But just bear in mind that this is a dose level that's five to 20 times lower compared to the one we showed on the previous slide.

Speaker #1: So there the mice were blank. So we had to dose at a fairly high dose to get the signal. So of course, we're working on a more targeted approach so we can lower the dose and get more specific expression to T cells.

Speaker #1: So at a much lower dose, you see expression in the spleen. At a very short period of time with MVAC, and then in contrast to Cirqueo.

Speaker #1: As before, you need to wait three to four weeks and then the signal appears. In the spleen, even at this very, very low dose.

Speaker #1: So we've been partnering up with other companies that develop T cell tropic LNPs. In this case, it's an LNP that goes specifically, or mostly, to T cells.

Speaker #1: 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 this T cell tropic these T cell tropic properties.

Speaker #1: Although this is not with active targets, this is passive targeting to T cells. And you can actually see, when you look at the back here to the left, you see a short expression in the T cell.

Speaker #1: If you look at this high dose. But just bear in mind that this is a dose level that's 5 to 20 times lower compared to the one we showed on the previous slide.

Speaker #1: 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 or the DNA formats combining different things with our Cirqueo cassette to see if we can make this technology even more potent compared to what it is already.

Speaker #1: So at a much lower dose , you see present in the spleen at a very short period of time with mvec . And in contrast to vec , as before , you need to wait 3 or 4 weeks and then the signal appears in spleen , even at this very , very low dose .

Speaker #1: And it's very specific in the spleen . And again , this this is using a T cell tropic MP . So the status there is that now confirming what we've seen in the past are completely different .

Speaker #1: So yeah, as you can see with the temporal profile of Cirqueo, I think this we believe this is sort of a sweet spot in CAR-T.

Speaker #1: You have the permanent lentivial 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 in hot these days, the very temporal short term RNA based in vivo CAR approaches.

Speaker #1: LNP with this T cell Tropic these T cell tropic properties ongoing is to characterize what cell types in the spleen are actually emit the signal .

Speaker #1: This is still a work in progress. And we are now screening multiple MPs. The DNA formats are combining different things with our vector cassette to see if we can make this technology even more potent compared to what it is already.

Speaker #1: But with Cirqueo, we believe that we can do a non-integrating approach. But with a very long expression profile, as we just showed, months of expression.

Speaker #1: And it will be re-dosable in case that's needed. So we think that actually opens up CAR-T for multiple indication, 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 lentivial approach.

Speaker #1: So yeah , as you can see with the temporal profile of , 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 .

Speaker #1: But this is a costly, costly affair. It's not without risk. And then you have what's very in hot these days.

Speaker #1: 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.

Speaker #1: The very temporal short term RNA based in vivo car approaches . But with that , we believe that we can do a non-integrating approach , but with a .

Speaker #1: 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 AV gene therapy.

Speaker #1: Very long expression profile , as we just showed . Month of expression . And it will be reversible in case that's needed . So we think that actually opens up Car-T for multiple indication , not only our community , but also in many more tricky to treat cancers without the risk of some of the secondary malignancies that you get from the viral approach .

Speaker #1: And of course, you can it's just mind boggling how that may affect AV gene therapy in general and of course Cirqueo in particular. The potential for that as a therapeutic modality.

Speaker #1: 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 in the nearby future .

Speaker #1: AV specifically, we now have a therapeutic payload with LAMP2B. We are working on others as well. And setting up our mouse model that is so we can evaluate actually the pre-clinical effect of expressing Cirqueo at a very low dose in these animals.

Speaker #1: 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.

Speaker #1: We believe we can go maybe 200 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 .

Speaker #1: Hopefully seeing a correction of the phenotype. And we see in CNS, I tend to 60x expression enhancement over conventional AV gene therapy. Also opening up dose pairing and potentially much safer gene therapy for some of these neurological unmet needs out there.

Speaker #1: And of course , in particular , the potential for that as a therapeutic modality , AAV . Specifically , when our payload will need to be .

Speaker #1: We are working on others as well and setting up our mouse model. That is so we can actually evaluate the theory of preclinical effect of expressing at a very low dose in these animals.

Speaker #1: And finally, with the in vivo cell therapy, T cell tropic LNPs, confirming the long-term Cirqueo 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.

Speaker #1: Hopefully seeing seeing a correction of the of the phenotype . And we see in CNS , I tend to 60 x expression in enhancement over conventional AAV gene therapy .

Speaker #1: So with that, I would like to conclude the R&D update. And I'll introduce Dr. Luba Gao for the business development update. Thanks, Thomas. I have the pleasure to present a business development activities for this first half of the year.

Speaker #1: Also, opening up dose and potentially much safer gene therapy for some of these neurological unmet needs out there. And finally, with the in vivo cell therapy T cell, tropical LNPs confirming the long-term expression in the spleen.

Speaker #1: And I think 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 an R&D group has done tremendous success in R&D.

Speaker #1: And we now do in vitro and in vivo characterization of of the expression profile and the specific cell types that are that are involved in this in this signal .

Speaker #1: So with that, I would like to conclude the R&D update, and I'll introduce Dr. Lubergal for the business development update. Thanks, Tomas.

Speaker #1: And our business development activities fall into two major categories. Here, the first one we are doing business development to strengthen expand Cirqueo technology as Thomas was saying.

Speaker #2: 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. Business development has been a phenomenal year.

Speaker #1: 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.

Speaker #1: We also of course do partnership with other companies to test our Cirqueo platform in pre-clinical models to generate more data. And just explore novel Cirqueo application, especially in area which are non-core to us.

Speaker #2: This year , partly or because Tomas has done a group has done tremendous success in R&D and our business development activities fall into two major categories here .

Speaker #1: So that we can really leverage the full potential of the Cirqueo technology in areas that we don't pursue ourselves. So you will see more of those technology collaborations and they may lead to in or out licensing in the future.

Speaker #2: The first one we are doing business development , to strength and expenses . Technology . As some are saying , always trying to improve the technology , make it better , make it applicable in different areas .

Speaker #1: On the other hand, of course, we're 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.

Speaker #2: And as you can see , these are collaborations to access complementary technologies . We also , of course , the partnership with other companies to test our software platform in preclinical models to generate more data and just explore novel applications , especially in an which are non-core to us so that we can really leverage the full potential of the technology in areas that we don't pursue ourselves .

Speaker #2: So you will see more of those technology collaborations , and they may lead to , outlicensing in the future . On the other hand , of course , we're also will focusing , especially in the future , in 27 on doing forming more strategic platform .

Speaker #1: So this is our future applications of Cirqueo 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.

Speaker #2: This is when we take our technology and we talk to gene therapy company and big pharma company about trying our technology to , to collaborations , ideally strategic platform partnerships , but also just outlicensing gene by gene or some kind of corporate or corporate co-development capabilities .

Speaker #1: So look out for more in 2027. So let me show you a little bit what that means for gene therapy as Thomas already said.

Speaker #1: Cirqueo in order for Cirqueo to become a gene therapy that we can be given to patients, it needs certain parts. And we have for gene therapy, we have most of these parts in-house.

Speaker #2: So, this is our future application to generate better therapies. And when these companies use our technology, this will generate revenues for the company in terms of upfront, milestone, and royalties.

Speaker #1: But there are other companies who claim to have better parts that we are testing. And this is for instance the AV 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.

Speaker #2: So if you look out for more in 2027—so let me show you a little bit how, what that means for gene therapy.

Speaker #2: As Thomas already said , you know , in order for to become a gene therapy that can be given to patients , it needs certain parts .

Speaker #1: And here you can see what are these therapy collaboration we have in gene therapy. So as we said, we have a Science 3 collaboration of which two are undisclosed in the AV capsid space.

Speaker #2: 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 .

Speaker #1: These are companies like Genasyst who said we have a capsid that goes specifically to muscle cells and it could be leveraged in the heart or also they are specific in T cells and going to T cells.

Speaker #2: And this is , for instance , the AAV capsid area where we , as Thomas said , we're testing targeted tax capsules to go to tissues and improve the expression of the protein in a specific tissue .

Speaker #1: 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.

Speaker #2: And here you can see what these therapy collaborations we have in gene therapy are. So, as we said, we have three collaborations, of which two are undisclosed in the AAV capsid space.

Speaker #1: And these companies claim that with their using their capsids, it will only go to that tissue that we want. And it will not be entering cells in other areas of their body.

Speaker #2: These are companies like Genesis 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.

Speaker #1: 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.

Speaker #2: And 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.

Speaker #1: Then we also partner for novel delivery or GIO means stands for gene of interest partnerships. And then we have five 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.

Speaker #2: And these companies claim that when they're using their capsids, it will only go to that tissue that we want, and it will not be entering cells in other areas of the body.

Speaker #1: And they have a technology to improve that. And traffic gene 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.

Speaker #2: 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 GIO means a gene of interest .

Speaker #1: Here we have of course our collaboration with the top five pharma which is going really well. As you may remember, these collaboration or all collaboration have different parts.

Speaker #2: Partnerships . And they have five collaborations . And for instance , like revenue Biosciences . One thing we want to do is like produce proteins that have to be secreted in order to work in the entire body .

Speaker #1: 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.

Speaker #2: And they have a technology to improve that . Traffic is a novel technology to just deliver DNA to cells . And then more importantly , like I said , on the other buckets we're doing , partnering , co-development collaborations with companies here .

Speaker #2: We have , of course , our collaboration with the top five Pharma , which is going really well , as you may remember , these collaborations or all collaborations have different parts .

Speaker #1: 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.

Speaker #2: So it goes out in different work packages . We have successfully completed the first part of the collaboration , which we announced earlier , and we 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 , the preparation and the collaboration is going really , really well .

Speaker #1: And we're not going to be able to disclose results from this anytime soon. Abogen is another exciting collaboration space. This is a German gene therapy company focused on heart diseases.

Speaker #2: And we will 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 .

Speaker #1: They have a proprietary gene that they want to deliver to the heart. And they also have a proprietary capside. And we are in a technology feasibility collaboration with them.

Speaker #1: And we're very excited to work with them. And we plan to have more such collaboration going forward.

Speaker #2: Abidjan is another exciting collaboration in 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 also have a proprietary capsule.

Speaker #2: So let me switch to cell therapy and cell therapy. Our B needs are a little bit different as Thomas was saying. We need more components in order to make it work.

Speaker #2: And on the one hand, one component is similar, the delivery technology. But in this case, it's not a virus it is a non-viral technology we call it.

Speaker #2: And we are in a technology feasibility collaboration with them, and we're very excited to work with them. We plan to have more of such collaborations going forward.

Speaker #2: We call it LNP. But we can also plot other non-viral delivery technology formulations. And then this is DNA vector format that Thomas explained that we need in order to make this better solution.

Speaker #2: So let me switch to cell therapy. And cell therapy needs are a little bit different. As Tomas was saying, we need more components in order to make it work.

Speaker #2: And there , on the one hand , one component is similar . The delivery technology . But in this case , it's not a virus .

Speaker #2: And so you can see we actually been very active in the DNA vector format. We signed five collaboration of them really recently. This is a testament to the interesting technology that we have.

Speaker #2: It is a non-viral technology. We call it— we call it LNP, but we can also explore other non-viral delivery technology for—.

Speaker #2: I mean, the reason why we have been so productive as a cell therapy space is that other companies consider our Cirqueo technology incredibly exciting and interesting.

Speaker #2: And then, this is a vector format that Thomas explained that we need in order to make this a better solution. And so, you can see we have actually been very active in the DNA vector format.

Speaker #2: And they want to try it with their own technology. So it's actually really interesting. It's really fun to do business development for Cirqueo because we really get a lot of really good receptions.

Speaker #2: We signed five collaborations 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 as a therapy space is that other companies consider our technology incredibly exciting and interesting , and they want to try it with their own technology .

Speaker #2: 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're also do have collaborations in T cell delivery systems.

Speaker #2: So it's actually really interesting. It's really fun to do business development for, because we really get a lot of really good receptions.

Speaker #2: Here, as he said, there's two different delivery system we call them active and passive. Passive is when it's more or less just the formulation.

Speaker #2: You know , we really have really good discussions . There's a lot of interest to try our technology . So it's been quite exciting .

Speaker #2: Where they claim that this formulation is taken up by T cells. This is something like for instance CERTES we're testing with CERTES here. And then there's what we call active where actually on that formulation you put a receptor.

Speaker #2: So I was saying, we also do have collaborations in T-cell delivery systems here. As I said, there are two different delivery systems.

Speaker #2: We call them active and passive. Passive is when it's more or less just the formulation where they claim that this formulation is taken up by T cells.

Speaker #2: Not necessarily you put a ligand. A ligand and that ligand binds to a T cells actively. And therefore should be taken up even stronger by T cells.

Speaker #2: That's something we have tested with Acuitas. That's something that they provide. So here is very exciting testing as well active as well as passive targeting.

Speaker #2: This is something like , for instance , we're testing with certain sera . And then there's what we call active , where actually on that formulation you put a a receptor .

Speaker #2: And seeing what works best for the collaboration with Cirqueo. And then we are plotting other collaborations, other applications. I mean, for instance, United Immunity, they actually did not target T cells.

Speaker #2: So you put a ligand, a ligand, and that ligand binds to T cells actively and therefore should be taken up even stronger by T cells.

Speaker #2: That's something we have tested with a few tests . 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 cigarette .

Speaker #2: They actually want to target macrophages and so we tested their technology with our Cirqueo technology. And then we have this collaboration with UTMB which stands for University Texas Medical Branch.

Speaker #2: And then we are following other collaborations , other applications . I mean , for instance , with United Immunity , they did not target T cells .

Speaker #2: And they are 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 Cirqueo.

Speaker #2: They actually want to target macrophages. And so we tested their technology with our chemical, with our technology. And then we have this collaboration with UTMB, which stands for University of Texas Medical Branch.

Speaker #2: And they all want to test antibodies for viral or anti-infective therapy. So again, it is in our interest to partner our technology with companies outside our core space in order to leverage our technology.

Speaker #2: So with that, I want to wrap up the BD activities. It's been super exciting to do BD. With Cirqueo in 2026 and of course we can expect to continue in 2027.

Speaker #2: And, of course, generate licensing transactions for future revenue. So with that, I want to wrap up. The media activities have been super exciting to do.

Speaker #2: We have done our first partnering deal with a major pharma company. And that's a goal for 2027 to do more of those. And also of course we want to enter into more collaboration with gene therapy companies.

Speaker #2: BT with 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 good goal for 27 to do more of those .

Speaker #2: On the cell therapy side, we're a little bit early stage. We're not as advanced as another mature stage as with gene therapy. So the focus here will be more on technology collaborations.

Speaker #2: And we're looking forward to testing more non-viral delivery either active or passive. And also other applications of course to expand the use of Cirqueo.

Speaker #2: 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.

Speaker #2: So again, it's been exciting so far. But I think I expected to continue like this and go into 2027 and be really a phenomenal year.

Speaker #2: We're not as advanced as in the mature stage as with gene therapy. So the focus here will be more on technology collaborations.

Speaker #2: And we're looking forward to testing more non-viral delivery, either active or passive, and also other applications, of course, to expand the use of it.

Speaker #2: With that, I would like now to switch and then start the financial presentation. And as Eric was saying, 2026 has been a transformational year in terms of finance.

Speaker #2: 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.

Speaker #2: We had several financing events, three finance events to raise $620 million in the first half of 2026. This has been started by a rights issue.

Speaker #2: With that , I would like to switch . And then start the financial presentation . And as Eric was saying , 2026 has been a transformational year in terms of finance .

Speaker #2: Which was announced and approved by a 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.

Speaker #2: We had several financing events , three financing events to raise 620 million kronor in the first half of 2026 . This has been started by a rights issue , which was announced and approved by shareholders in late 2025 , when financial situation was quite challenging .

Speaker #2: And was a very successful event. We was oversubscribed. Then following positive momentum in the first quarter of this year, we were able to do a private placement.

Speaker #2: But through a lot of work, we were able to go out with a research that was almost 90% secured, and it was a very successful event, which was oversubscribed.

Speaker #2: Which raised $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.

Speaker #2: Then, following positive momentum in the first quarter of this year, we were able to do a private placement, which raised 250 million kroner.

Speaker #2: 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.

Speaker #2: This was really a transformational event for the company, because now the runway of the company is secured until 2030. That provides incredible security for our R&D activities.

Speaker #2: And through the positive momentum at the market, we were able to raise another $300 million and now to really develop our first clinical program.

Speaker #2: And this was very , very important to achieve . And then in June , we closed the Warrens exercise , which was , of course , part of the rights issue .

Speaker #2: 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.

Speaker #2: And through the positive momentum at the at the market , we were able to raise another 300 million kroners . And now to really develop our first clinical program .

Speaker #2: 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.

Speaker #2: So, this is 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.

Speaker #2: And this is partially due to more in view studies in R&D of course. We need to invest more into R&D. It's exciting time to need to show different potential, different applications.

Speaker #2: As you can see, the total operating expenses went up, and this is partially due to more in vivo studies in R&D.

Speaker #2: 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.

Speaker #2: Of course , we need to invest more into R&D . It's an exciting time . We need to show different potential , different applications .

Speaker #2: 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.

Speaker #2: Also , of course , the collaborations , as Thomas was saying , we have so many different interesting avenues that we can pursue .

Speaker #2: 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.

Speaker #2: 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 .

Speaker #2: 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 of items.

Speaker #2: 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.

Speaker #2: And there were deferred incentive pay which was paid in the first half of 2026. And very importantly, there's also a non-cash effect on options because of the option that was awarded in 2026.

Speaker #2: 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 of items you know so and they were different incentive pay which was paid in the first half of 2026 .

Speaker #2: 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.

Speaker #2: And very importantly , there's also a non-cash effect on options because of the the option was awarded in 2026 . This will have to be recognized with National Insurance Contribution , but did not affect the cash flow .

Speaker #2: But because of the one of 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.

Speaker #2: 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 expenses .

Speaker #2: What is good for us to now report is we had some currency gain and also some return on our cash investments. We of course investing in the cash that we don't need in very secure cash accounts or money market funds.

Speaker #2: We expect the second half of the 2026 to have lower expenses , lower operating expenses than in the first half . What is what is good for us to now report is we had some currency gain and also some return on our cash investments .

Speaker #2: 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.

Speaker #2: We, of course, are 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 a positive.

Speaker #2: And so this will be a very positive development. So from the money that we raised, $620, we now have $533 in the left in the bank.

Speaker #2: And of course, expect this to go up by the end of the year. And so, this will be a very positive development.

Speaker #2: 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.

Speaker #2: So from the money that we raised , 620 we now have 533 in the left in the bank . So they this is partly due to a lot of expenses .

Speaker #2: With that, then I would like to conclude on the finance. We had a phenomenal run in 2026. And this really had put us in a totally different situation as a company.

Speaker #2: Fundraising , unfortunately , isn't free . There is , of course , expenses involved . And this is recognized here in lower amount That then I would like to conclude on on the finance .

Speaker #2: Before or until April 2026, the limited funding that we had at Cirqueo 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?

Speaker #2: 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 .

Speaker #2: The limited funding that we had at the school 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 good science that Thomas and his team are doing in the lab? And now, since that—

Speaker #2: And now since that now this has been removed. So I would say over the runway until 2030, the financial risk has been made significantly reduced.

Speaker #2: 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.

Speaker #2: Now this has been removed . So I would say , you know , with the with the runway until 2030 , the financial risk has been very , significantly reduced .

Speaker #2: 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.

Speaker #2: And we can now really focus on R&D execution, on doing things well in the lab, and on doing things in parallel that we used to do sequentially.

Speaker #2: 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 the what brought us here .

Speaker #2: But because we raised money, it doesn't mean we're going to change the what brought us here. So we're going to continue to be prudent with our money.

Speaker #2: 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.

Speaker #2: 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.

Speaker #2: One of the things by advancing the program into towards the clinic unfortunately studies cost more money. These are more complex studies. We have to use CROs.

Speaker #2: We'll do more studies . We'll do more advanced . One of the things by advancing the program into towards the clinic . Unfortunately , studies cost more money .

Speaker #2: So these things 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.

Speaker #2: These are more complex studies. We have to use CROs, so these expenses will go up. But this will be gradual.

Speaker #2: 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?

Speaker #2: And then we'd be very prudent . And of course be very careful to really leverage your money to the best value possible . But do , still expect the the team size to grow .

Speaker #2: So expect the budget or the expenses for all of 2026 to be about 50% higher versus 2025. Don't take 2025 as a reference point.

Speaker #2: 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 .

Speaker #2: That was a time when Cirqueo had very few resources where we kept the team to as minimum and as small. I would think that we reset the base in 2026.

Speaker #2: Don't take 2025 as a reference point. That was a time when we had very few resources, and we kept the team to a minimum and small.

Speaker #2: So and that sort of it's not fair to compare 2026 to 2025. But now in a much stronger position to really take advantage of a lot of things.

Speaker #2: I would think that we set the base in 2026 . So and that sort of , you know , 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 .

Speaker #2: We are going to hire a larger team. A larger team needs more facilities. So we have a lot of badge. You can already see we are broadcasting from our new lab in Stockholm.

Speaker #2: We are going to hire a larger team , a larger team needs more facilities . So we're going to allow that . And you can already see we are broadcasting from our new lab in Stockholm means larger team means also , of course , higher productivity .

Speaker #2: 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.

Speaker #2: That will be, of course, very important on our business development side. So, we see a gradual increase of expenses until we have our first clinical candidate selection.

Speaker #2: 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 over and back over to Eric.

Speaker #2: And that will, of course, change the company. But it will be in the future. So with that, thank you very much for your attention.

Speaker #2: And I'll hand back over to Eric.

Speaker #1: So let's summarize. It's been a strong year on R&D. What I wanted to remember is we have a circuit generation pipe in the making.

Speaker #1: So, let's summarize: it's been a strong year on R&D. What I want you to remember is we have a Generation Five in the making.

Speaker #1: This looks like it should achieve 200 times 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.

Speaker #1: This looks like it should achieve 200 times or more better expression than conventional Aavs . This is this is big . If you can get the dose down for a vision therapy by 200 fold , this can be a game changer for all AAV field , and you may need to use expression to have a relevant AV in the future .

Speaker #1: And you may need to use circuit expression to have a relevant AAV in the future. We're not there yet. But we're making important progress.

Speaker #1: On the hard gene therapy, importantly we shown that we can express etheric putic gene. Until now we've mainly expressed reported genes. Luciferase that we can use as an experimental validation.

Speaker #1: 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 .

Speaker #1: Until now , we've mainly expressed reporter genes luciferase that we can use as a as an experimental validation . But now we've shown that the increased expression also applies to a disease relevant gene .

Speaker #1: 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. Circuit AAVs also work in the CNS.

Speaker #1: Very important validation . And we expanded now into CNS . The Aavs also work in the CNS . Same order of magnitude as we see in the heart and the eye .

Speaker #1: Same order of magnitude as we see in the heart and the eye. And we've shown it for three delivery routes. And the fact that it worked for three different delivery routes suggests that this is consistent data.

Speaker #1: And we've shown it for three delivery the fact that it worked for three different delivery routes suggests that this is consistent data . And this is , of course , where we also have the collaboration with the big Pharma .

Speaker #1: And this is of course where we also have the collaboration with the big pharma. These data are our own and independent. But obviously to suggest that circuit works well in this tissue.

Speaker #1: These data are our own and independent, but obviously, it suggests that that circ works well in this tissue. These data led to a substantial body of activities.

Speaker #1: 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.

Speaker #1: I mentioned the pharma collaboration. This may lead to a licensing transaction next year. And we have numerous R&D collaborations ongoing.

Speaker #1: 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.

Speaker #1: 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.

Speaker #1: It's not advanced 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.

Speaker #1: 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.

Speaker #1: 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 circuit in vivo car concept.

Speaker #1: 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 circuit in vivo CAR concept.

Speaker #1: We need a safe and efficient vector. These are being screened. And we need a targeted delivery system. To get safe, low dose therapeutic concept.

Speaker #1: We need a safe and efficient vector . These are being screened and we need a targeted delivery system to get safe . Low dose therapeutic concept and these these were now screening .

Speaker #1: And these we're 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 circuit in vivo car construct.

Speaker #1: 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 circuit in vivo CAR construct.

Speaker #1: And we have the capital now to execute on these plans. We have 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.

Speaker #1: And we have the capital now to execute on these plans. We have 550 million in the bank. This finances the company until 2030.

Speaker #1: And and we're in a solid position to deliver on , on all these plans . And expand as we go along I'll leave you with the pipeline here .

Speaker #1: I'll leave you with the pipeline here. These are our three programs in gene therapy, heart, eye, and CNS as well as the in vivo car.

Speaker #1: These are our three programs in gene therapy , heart eye and CNS , as well as the in vivo car and major upcoming milestones on the right hand side that you can look forward to in in the next month and into 2027 .

Speaker #1: And 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.

Speaker #1: Now, again, I'd like to stress that you shouldn't get too hung up on every single readout. This is what we're currently doing.

Speaker #1: This is what we're currently doing. These are the plans we have. But experiments are unpredictable. You never know exactly what works and what doesn't work.

Speaker #1: These are the plans we have, but experiments are unpredictable. You never know exactly what works and what doesn't work. You may need to repeat certain things.

Speaker #1: 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.

Speaker #1: 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.

Speaker #1: 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 substantial amount of data coming out.

Speaker #1: At the moment, it looks strong, and we need to select what works the best and what partnerships work the best.

Speaker #1: And what I can assure you is that there will be substantial amount of , of data coming out . And we expect to have our next update towards the second half of , of November , when we usually have R&D updates .

Speaker #1: 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 three months.

Speaker #1: Remember, we do these updates every three months. In addition, we'll be publishing data at the European Society of Gene Therapy Conference at the end of October.

Speaker #1: In addition, we will be publishing data at European Society of Gene Therapy Conference and the end of October. So there will be both an oral presentation and posters presented there.

Speaker #1: So there will be both oral presentations and posters, and with that, we wrap up and can move to a Q&A section.

Speaker #1: So with that, we wrap up. And we can move to Q&A section. So do you want to join me again Thomas and Lubor? You did not mention eye, AAV today.

Speaker #1: So, do you want to join me again, Thomas? And Libor, you did not mention what I have today. Could you comment on what the status is there?

Speaker #1: Could you comment on what the status is there?

Speaker #2: Yeah. 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.

Speaker #3: Yeah. So the current status is we continue to work on it. We are still very excited about ophthalmology in general. We are now setting up our larger study.

Speaker #3: So that has taken a while to , 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 .

Speaker #2: 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'll be a lot of exciting partnerships going forward.

Speaker #3: 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.

Speaker #2: On top of that, this study is also powered in a way so we can do these 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.

Speaker #3: On top of that , this study is also powered in a in a way . So we can do the single cell type of analysis .

Speaker #3: So we actually get a very granular readout on what cells are being targeted, what cells express circular RNA, and to what extent.

Speaker #2: So that would 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.

Speaker #3: So so that would be the extremely interesting data set that will come later this year . I expect . So the study will is planned to commence later this month .

Speaker #1: So just because we didn't update specifically on the eye gene therapy today does not mean we're not very active.

Speaker #1: So just because we didn't update specifically on the iodine therapy today does not mean we're not very, very active.

Speaker #2: Very active. And we're setting as we speak working on wet AMD payload and other payloads that could potentially go into a transgenic mouse model also quite soon.

Speaker #3: Very active. And we are, as we speak, working on wet AMD payloads and other payloads that could potentially go into a transgenic mouse model.

Speaker #3: Also, quite soon. But this is still a little bit timeless, a little more unclear there.

Speaker #2: But this is still a little bit timelines a little more unclear there.

Speaker #1: We've received several questions around the safety of circuit and generally it relates to the fact that we produce protein for a very long time and at very high levels with circuit.

Speaker #1: We've received several questions around the safety of Cirkovic, and generally it relates to the fact that we produce proteins for a very long time and at very high levels with Cirkovic.

Speaker #1: Does that lead to any safety concerns or toxicity problems? And is there an off switch in circuit?

Speaker #1: Does that lead to any safety concerns or toxicity problems? And is there an off switch in the circuit?

Speaker #2: Yeah. 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.

Speaker #3: Yeah , of course , that's a that's a great question . I think , you know , at least for gene therapy , I guess you want lifelong expression because this is a expressing a protein that you're not able to express yourself .

Speaker #2: So that would 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 circuit cassette now we have circuit 5.0.

Speaker #3: So , so that would be needed . But whether you can overexpress and get a toxicity readout is something that we will , of course , carefully evaluate .

Speaker #3: Of course , with the cassette . Now we have Cirkovic 5.0 , but in case that basically overshoots the therapeutic relevant gene expression , we can just settle back with the 3.2 and then use that one so that that gives us some flexibility to actually adjust the gene expression profile to the indication of , of interest here .

Speaker #2: But in case that basically overshoots the therapeutic relevant gene expression we can just settle back with the circuit 3.2 and then use that one.

Speaker #2: 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.

Speaker #3: And off switch , something that we've also been considering is not something that's built in for the time being , but it's something that's definitely on the table .

Speaker #2: So there's 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 circuit cassette.

Speaker #3: 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 cassette.

Speaker #2: 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.

Speaker #3: 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.

Speaker #1: So we received also several CAR-T questions and important one again for you Thomas is has circuit confirmed that the durable circuit signal following LNP delivery in vivo originates specifically from T cells?

Speaker #1: So we received also several CAR questions. An important one again for you, Thomas, is: Has Sergio confirmed that the durable signal following LNP delivery in vivo originates specifically from T cells?

Speaker #2: Short answer here would be no. This is a top on our to-do list. So this is ongoing work. There's been some logistic challenging with how you get the spleen sample.

Speaker #3: A short answer here would be no. This is at the top of our to-do list, so this is ongoing work. There have been some logistical challenges with, you know, how you get the spleen sample.

Speaker #2: You have to get that analysis done. But we get an in-house machine later this month that will actually allow us to do that work.

Speaker #3: You have to get that analysis done. But we get an in-house A machine later this month that will actually allow us to do that work.

Speaker #2: We can say that we see it in the spleen. It is still confirmed in the spleen with the T cell tropic LNPs. And we've also done in vitro study in T cells also showing a circuit benefit.

Speaker #3: We can say that we see it in the spleen. It is still confirmed in the spleen with the T cell tropic LNPs. And we've also done in vitro study in T cells.

Speaker #3: Also showing a benefit . So I think those data combined suggests that , I mean we believe we have T cell expression . But of course , you know , we need to get that data data point .

Speaker #2: So I think those data combined suggests that I mean we believe we have T cell expression. But of course we need to get that data point.

Speaker #2: And this is definitely something that we're working hard to achieve.

Speaker #3: And this is definitely something that we're working hard to achieve.

Speaker #1: And can you comment on who delivered the LNPs used this we're not doing yet. We're screening multiple LNPs here. And we will select one to move forward with.

Speaker #1: And can you comment on who delivered the LNPs used in this? We're not doing that yet. We're screening multiple LNPs here.

Speaker #1: And we will select one to move forward with. And we're not going to disclose here which specifically we used in this case.

Speaker #1: And we're not going to disclose here which specifically we used in this case. We showed today. Have any of the delivery collaboration so again on the LNP produced data that made them fall away or be more prioritized this.

Speaker #1: We showed today . Have any of the delivery collaborations . So again , on , on the LNP produced data that made them fall away or be more prioritized .

Speaker #1: I think this probably also then relates to some of these alternative applications. Do you want to comment on that Lubor?

Speaker #1: This, I think, probably also then relates to some of these alternative applications. We want to comment on that later.

Speaker #2: I mean I think it's too early to talk about that. I think we are still testing these different technologies ongoing studies. And we'll make that assessment at a later point in time.

Speaker #2: I think it's too early to talk about that. You know, I think we are still testing these different technologies, and there are ongoing studies.

Speaker #2: And we'll we'll make that assessment at a later point in time . So right now , I would say no . But this , of course , people should say we will definitely compare technologies .

Speaker #2: So right now I would say no. But this of course people should say we will definitely compare technologies. So we don't expect to go forward with all of them.

Speaker #2: So we don't expect to go forward with all of them . I mean , it is to , to , to select the best for that purpose .

Speaker #2: I mean it is to select the best for that purpose. So we will look at the data and then identify only one of them to go forward and then do more testing.

Speaker #2: So we will look at the data and then identify only one of them to go forward with, and then do more testing.

Speaker #1: And following up on that we get questions on this vector types. So what is the difference between the vector types and do you have a preferred format?

Speaker #1: And following up on that, we get questions on these vector types. So, what is the difference between the vector types?

Speaker #1: And do you have a preferred format?

Speaker #2: Yeah. So I think there's a few different things you can consider when you look at vector types. One would be the manufacturing of the vector type whether it's done synthetically or in a bacteria or in a bacteriophage.

Speaker #3: Yeah . So I think there's a few different things you can consider when you when you look at vector types , one would be the manufacturing of the vector type , whether it's done synthetically or in a bacteria or in a , in a , in a bacteriophage , the other thing would be whether it's double stranded or single stranded and the size of the vector .

Speaker #2: The other thing would be whether it's double stranded or single stranded. And the size of the vector. So there's a few different aspects that we are considering.

Speaker #3: So, there are a few different aspects that we are considering. I think right now it is well established that if you bring in a double-stranded DNA, which is sort of the typical vector format, it may elicit some DNA sensing.

Speaker #2: I think right now it is well established that if you bring in a double stranded DNA which is sort of the typical vector format it may elicit some DNA sensing part of our immune system to and that may trigger some unwanted effects.

Speaker #3: Part of our immune system to , to , to . And that may trigger some unwanted effects . So you have to be careful with your dose level .

Speaker #2: So you have to be careful with your dose level if you go in with a double stranded DNA. So we believe with the single stranded DNA that we're currently testing that this is and that's why it's being termed immune quiet will not have that adversive effect.

Speaker #3: If you go in with a double-stranded DNA, so we believe with single currently that this is, and that's why it's being termed immune-acquired, it will not have that adverse effect.

Speaker #2: And we plan that this would be much more effective in terms of the non-viral gene expression and I think here in particular we believe circuit could be an added benefit to that technology.

Speaker #3: And we we plan that this would be much more effective in terms of the Non-viral gene . Gene expression . And I think here in particular , we believe it could be an added benefit to that technology .

Speaker #2: So that combination is very a very interesting combination going forward. So very excited how that will how that will read out.

Speaker #3: So so that combination is very a very interesting combination going forward . So very excited how that will how that will read out .

Speaker #1: We can add that this area of DNA vector technology and maybe in particular single stranded DNA is a very hot field. At the moment we're seeing numerous companies launching with big financing and high profile investors.

Speaker #1: We can add that this area of DNA vector technology, and maybe in particular single-stranded DNA, is a very hot field at the moment.

Speaker #1: We're seeing numerous companies launching with big financing and high profile investors . It's a it's a bit like circular RNA was three years ago .

Speaker #1: It's a bit like circular RNA was three years ago. So we follow this closely and we believe the fit with circuit is great. And this will be important to make the most potent and safe circuit in vivo car product possible.

Speaker #1: So we follow this closely, and we believe the fit with Cirkovic is great. And this will be important to make the most potent and safe Cirkovic in vivo CAR product possible.

Speaker #2: Yeah. And I would like to stress that the interest is mutual. It's not just we only think that is really a good combination of technology but also those circular DNA company think that.

Speaker #2: And I would like to stress that , you know , the interest is mutual . It's not just we not we only think that it's a really good combination of technology , but also those circular DNA companies think that .

Speaker #2: And it was to run it from a business ball in front of you it was very easy and quick to sign this collaborations because they're equally interested because they understand the potential of the circuit technology.

Speaker #2: And it was really, from a business point of view, very easy and quick to sign this collaboration because they're equally interested, as they understand the potential of this technology.

Speaker #2: So both parties believe that the combination should make a lot of sense and should be very interesting.

Speaker #2: So both parties believe that the combination should make a lot of sense and should be very interesting.

Speaker #1: So I think that wraps up the technical questions. I can deal with a last one here which is asking if we can comment on our expansion plans and how many employees we are now.

Speaker #1: So, I think that wraps up the technical questions. I can deal with a last one here, which is asking if we can comment on our expansion plans and how many employees we are now.

Speaker #1: So we are not planning to go overboard. We are an organization of tight resource and cost control. We plan to continue with that. But we grow as it makes sense to be able to increase our capacity and get more capacity in house like Thomas pointed out before being able to do this immune cell characterizations ourselves.

Speaker #1: So we are not planning to go overboard . We are an organization of tight resource and cost control . We plan to continue with that , but we we grow as it makes sense to be able to increase our capacity and get more capacity in house like Thomas pointed out before being able to do this , immune cell characterization ourselves .

Speaker #1: So we're recruiting people and internalizing equipment that allows us to , to , to do these things . We're growing the lab . We've expanded roughly 50% .

Speaker #1: So we're recruiting people and internalizing equipment that allows us to do these things. We're growing the lab. We've expanded roughly 50% the lab footprint since our fundraising.

Speaker #1: The lab footprint since our fundraising, and we are now 16 employees. So costs will go up, but they're not going to explode.

Speaker #1: And we are now 16 employees. So cost will go up but they're not going to explode. We expect something like a 50% increase as the peer compared to our previous cost base.

Speaker #1: We expect something like a 50% increase as compared to our previous cost base . Looking ahead in 2027 , I think we we aim to expand the team to 20 to 25 people and that's where we're going to stay for for a while So that concludes the webcast .

Speaker #1: Looking ahead 2027 I think we aim to expand the team to 20 to 25 people. And that's probably where we're going to stay for a while.

Speaker #1: So that concludes the webcast. I think we dealt with most of the questions. But we got quite a high volume of incoming requests today.

Speaker #1: I think we dealt with most of the questions, but we got quite a high volume of incoming requests today. So feel free to contact us afterwards.

Speaker #1: So feel free to contact us afterwards also. And we are happy to follow up on email or on the phone if you have specific areas of interest or questions.

Speaker #1: Also . And we are happy to , to follow up on email or on the phone . If , if you have specific areas of interest or questions .

Speaker #1: Thank you all for tuning in, and I wish you a nice day.

Speaker #2: Thank you .

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