Cantargia AB (publ)

Many thanks and welcome everybody to today's interim report of our first quarter 2025. On this next slide, you see our safe harbour statement, which of course its main effect is to make everybody aware that any forward-looking statements that we make should be taken with great care and not relied on or taken as guarantees of future performance. So as we've just introduced, I'm Damian Marron. I'm the interim chief executive officer. I'll be taking the first few slides for you and then handing over to Maureen Lynn Jensen, our chief medical officer. And we also have Patrick Remblad, our chief financial officer, who will take us through the financial section of today's presentation. So it's been a busy first quarter and actually a busy few weeks since the end of that quarter as well. So just quickly, here are the significant events that occurred in the first quarter of 2025. I was appointed as the interim CEO following the resignation of Joram Furstberg, our longstanding prior CEO. We then presented promising phase one data from our CAN10 first multi-dose cohort, as well as feedback from the FDA and the clinical experts. We finished recruitment in the randomized phase two TRIAD4 study in triple negative breast cancer with Nadionolimab, and we enrolled the first patient in a new investigator-initiated study of nadionolamab in leukemia that is taking place in the US. And we published two abstracts on IL-1 RAP-ADC and on nadionolamab's potential to reduce chemotherapy-induced neuropathy. We announced they will be presented at AACR, which has just taken place. Significant results since the reporting period are obviously the appointment of Morton Lindjensen as Chief Medical Officer, and he will be speaking with you today. We selected treatment-resistant atopic dermatitis as our second indication for CAN10, for CAN10's phase two program, and Morton will talk to you more about that. And we've also just announced that pharmacokinetic modeling, which used data from both the single ascending dose groups, but also the full data from the first multiple dose cohort in our CAN10 phase one study, has confirmed our choice of every four-week dosing in phase two, which we can see as a potentially quite a significant competitive advantage. And we'll show you some of that data in a few minutes. So moving to focus, first of all, on CAN10 and on the data we've been announcing since the start of the year. So just to quickly remind people, this is the design of our phase one first in human study our single ascending dose multiple ascending dose study so we started with cohorts 10 cohorts of healthy volunteers who received single doses of canten and at each cohort we increased the dose and each cohort had six subjects who received canten and two who received placebo that has been completed and finalized as we've already reported We then moved into the multiple ascending dose healthy subject cohorts. And here we have two dose cohorts, again, 6CAN10 to 2 placebo. These dose cohorts will allow us to move into phase two. So we anticipate finishing this study in Q2, being able to start phase two towards the end of Q4 of this year. We also have some psoriasis subjects that we are studying separately, which will enable us to undertake some exploratory mechanistic studies. And what we've shown to date is full receptor occupancy on immune cells. I'll show you that in a second. Full blocking of IL-1 family cytokines. And very importantly, we have seen no safety concerns in either the single ascending dose or the completed first multiple ascending dose cohort. So what have we seen as results? As I mentioned there, we have documented full receptor occupancy in the study. And you can see on the bottom left here for two different immune cell types, classical monocytes and neutrophils. As we increase the dose in the single ascending dose part of the study, we reached full receptor occupancy on both of those cell types. And you can see right on the right hand side that we also achieved this full receptor occupancy with the multiple ascending dose 14 days after the last dose was taken. So this is very encouraging data for us. On the right, you see an inhibition assay in whole blood taken from the subjects. And here on the right, you were looking at the ability of IL-36, one of the IL-1 superfamily that we block, to induce IL-6 release. And this is either at day one with the SAD or day 40 in the multiple ascending dose. And on the right-hand side, day eight, on the single ascending dose, so eight days after that single dose, or again, towards the end of the multiple ascending dose treatment. And again, what you see here is that we get, as we've got full receptor occupancy, we also get full inhibition. of IL-36. As we increase the SAD or we look at the multiple ascending dose of 300 milligrams, you can see that we completely block IL-36. There is no more IL-6 release induced by applying IL-36 here. And if we go to the next slide, we also looked at the ability of IL-1 beta to induce IL-6 release. And again, we see a similar pattern. that we can completely block the ability of IL-1 beta to induce IL-6 release, either after single doses or with the multiple ascending dose at 300 milligrams. This data is very important because it highlights the unique functions of CAN10 that we can block all of the IL-1 superfamily. So IL-1, IL-33, and IL-36. This is a unique function of an IL-1 RAP antibody like CANTEN and differentiates us from both approved treatments, but also treatments that are in development at the moment, such as the IL-1 alpha-beta blocker lutecizumab, the IL-36 blocker spasolimab, or indeed the IL-1 beta blocker that is in development by the U.S. Biotech Avalo. And the importance of this is that we then made the immune cells non-responsive to IL-1 and IL-36. And these are the immune cells that migrate into the tissues and actually cause the damage that we see with NHS patients, hydrodentis suppurativa. Finally, I spoke just before about the fact that our data now supports that we can use every four-week dosing, or Q4W, as it is shortened to. We have seen excellent PK results. We have a linear PK profile. We have a higher bioavailability of CAN10. And this model that we're showing here is being developed by Sitara using the data from all the subjects in the study, both single ascending dose and multiple ascending dose. And the results from these simulations, as you can see, support the feasibility of Q4 weekly dosing. Along the bottom of the slide, you can see at each four-week interval that we have 95% confidence. We do not have the drug level in the patient's blood. Dropping below what we call the CTROF level, which is the lowest estimated level that we need for efficacy, which has been set based on the results I just showed you of the inhibition of the cytokines and the receptor occupancy. So our combined results so far suggest we have great potential for efficacy. We have good safety. We have certainly great convenience for the use in HS and other future applications. And with this, I'll pass you over to Morton to take you through the next few slides.

Yes, hello, my name is Morten Lind Jensen and I'm CMO in Cantagia. First of all, what we have been looking at is how do we best utilize the very broad mode of action of this molecule. We know that the IL-1 family is broadly associated with both acute and chronic inflammation. And we know that there is a strong involvement of the multiple inflammatory cascades that we impact. And therefore, it also impacts multiple inflammatory diseases. So this broader mechanism where we both target inflammation and fibrotic elements is really something that can be used in many different indications. So we contracted with Lumenity and explored where could such a molecule have a relevance and identified both respiratory indication indications with the bones and joints, indications in the gastrointestinal tract, and other systemic indication. And we did identify skin as one of the first indications for us to move into with the Hydradenitis superativa as the primary indication. But also, atopic dermatitis, since it has such a broad involvement of both GH1 and GH2 inflammatory pathways, has been identified as something that is highly relevant. And in particular, since we now know that dupilumab is very broadly prescribed when there is a need for in biologic treatment but but but there are people who don't benefit from topilumab and of course they should have an adequate treatment that's one um but in hs our primary term indication the treatment landscape really looks like there is Adalimumab and there are the IL-17, Logaspin, Kizumab and Secoquinumab. And those medicines are reasonably effective. They're administered every week or every second week. But what we believe we can really obtain with this broader mode of vaccine is a higher efficacy and a less frequent dosing for the convenience of the patients and also for the adherence to treatment. So we do want to look at the harder to achieve endpoints. We want to use high score 75 because it's more relevant for the patients compared to high score 50 it's really about looking at abscesses and inflammatory nodules and and tunnels in this disease and it's super painful for them so the pain those lesions this is what we want to go for and we believe that we can get high efficacy with a um with a less frequent dosing so we really target the every second week dosing regimen in hs And similar to ATS, when we looked at atopic dermatitis, it's clear that there is this very broad activation of the inflammatory pathways. And in particular, when AD becomes more chronic, then there seems to be a shift from the Th2 driven pathways towards Th1, Th22, and Th17. where it's also clear that dupilumab is not relevant, it's IL-4 and IL-13, right? So, our exploration of this indication really also looked at the indicators from other single cytokine monoclonus, where it looks like there is an effect, but it also looks like there is a requirement for broader target of the inflammatory cascades. So the green boxes here are where where there have been relevant individual cytokine studies and where we think there's potential if we target broader. And targeting broader is exactly what we do. So if we look at the non-clinical data we have and also the ex vivo human data from the phase one study and from biopsies, It's clear that we do target multiple pathways. We have both data from animal peritonitis, animal cardiac inflammation, animal skin inflammation, lung and skin fibrosis models and we have the ex vivo human human whole blood study and the biopsies and if we look at it cumulatively all these pieces of information it's it's clear that we do target much broader and we also target at different levels in the inflammatory cascade so We have CANTEN that blocks 33 and 36 as we have talked about and also IL-1 alpha and beta as we have already talked about. But we also have in our heat maps clear indicators that we reduce IL-17 we reduce IL-5, we reduce the infiltration of monocytes, neutrophils, neosinophils and T-cells, we also reduce activation and permeability of the endothelial cells, and we reduce the activation of mast cells. So really all these things with a broad inflammatory involvement in the disease, which gives rise to the itch and the scratching and all the skin lesions, this molecule will really be good for that, even in patients who do not respond to topilumab. So this is one of the other indications where this molecule has a great promise. I think this was my last slide. Should I advance it?

That's great. No, thanks, Morten. Thank you for that very clear run-through of our approach to HS and our newly chosen second indication there of AD. So I hope everybody has seen that, you know, the first quarter of this year and the subsequent few weeks have been really rich in data, strongly supporting the development of CAN10 and the serious skin conditions, as Morten has just explained there with the rationale. for both HS and AD. And obviously that our phase one single ascending, multiple ascending dose study has really produced all the data that we could have hoped for that absolutely back up why we have gone into these indications and demonstrate that we can block these cytokines, we can block these immune cells, and we do have great hope of delivering new levels of efficacy, safety, and convenience to patients with these inflammatory immune skin conditions. And then later, as Morton showed, on into other conditions as well. So that's where we will finish the focus on CAN10. And we will now move to talk to Nadjun Olimab, of course, or CAN04, our one RAP antibody that we've been developing in oncology for quite a long time now, but for which we have now developed quite some substantial data and we continue to move forward. So in terms of the Naginolimab clinical development, we have announced obviously that we have the diagnostic test in development. This is a diagnostic test to be able to identify patients who have different levels of IL-1 RAP in their tumors at the start of treatment. What that will enable us to do is to select as we go forward or enrich, if you like, the studies that we are going to do, certainly in PDAC, pancreatic cancer, select those patients who have a high IL-1 RAP level so we can treat that subgroup, and that is the subgroup, as I'm sure you will recall, that showed very, very encouraging overall survival data in our previous clinical studies. We'll move that forward, and we're planning for regulatory interactions during 2025. The development of this test does take some time, and so that will be the major activity in the PDAC program for 2025. Of course, PDAC is not the only indication that we have looked at with Naginolimab. And indeed, we were very pleased to announce in March that we have completed the recruitment in what is our first randomized controlled phase two study with Naginolimab, the TRIFOR study in triple negative breast cancer. The patients are now, the last patients are now under treatment. And we estimate to be able to release the initial results, which will be on the overall response of the patients after three months of treatment. We expect to be able to release that in mid 2025. So that's obviously going to be exciting news for the company at that point. And of course, separately, we have announced that we have recruited the first patient. in a leukemia study, in acute myeloid leukemia and in early myelodysplastic syndromes. This is a study that is taking place at the University of Texas MD Anderson Cancer Center and is sponsored by the US Department of Defense. This is a very interesting study in a lot of ways because IL-1RAP itself was first identified actually here at the University of Lund. as being present on leukemic precursor cells. So this is, in a way, a little bit of a full circle for the IL-1 rap story and the development of Nadionolimab. Of course, we're not full circle because we still have a way to go before we can bring this treatment to patients. But this is a very exciting point in the development of Nadionolimab. Now, we have treated overall over 300 patients and we have as you can see here different oncology indications and opportunities for nadinolamab to become a new treatment for patients who need these new oncology treatments and to become a multi-million dollar product and develop value for our shareholders We also have been presenting posters and having publications published around our Nagin Olimab work and IL-1 RAP work. So we presented a very interesting poster just recently at the American Association of Cancer Research Conference of linking clinical data with higher doses of Naginolimab to a reduced instance and a delayed onset of chemotherapy-induced neuropathy, which is an exceedingly troublesome side effect of a number of chemotherapy regimes, which leads to patients discontinuing treatment or leads to patients having to reduce their dose or prolong the interval between treatments and all in all means that patients are very poorly and are also not receiving their optimal anti-cancer treatment. So this data is very interesting and we back this up with supporting preclinical data from mouse models looking at the mechanism of action which indicate together that targeting IL-1 RAP with nigenonimab not only has good anti-tumor activity, as we've shown, but also can significantly reduce this chemotherapy-induced neuropathy. And actually, we've also shown that can do that in the context of antibody drug conjugates as well, which are also known to significantly induce these neuropathies. So this is another very interesting set of data to support the development of Maginolimab as we go forward. We also had a publication in Cancer Discovery by Hanahan et al., followed up actually by a presentation by Professor Hanahan at AACR, where he highlighted the data, our preclinical and translational data, identifying the IL-1 family and its signaling as a key driver of cancer-related systemic immune suppression. These findings really do provide strong support for us in our development of nadionolamab and its potential to counteract tumor-driven immune suppression and therefore enhance its own activity, but also that of immunotherapy and potentially cancer vaccines also. So all in all, some very, very interesting and strong data around nadionolamab as well since the start of this year. Finally, I want to say a few words to you about our CANXX program. This is based on our library of over 200 IL-1RAP antibodies, which we can tune to have different properties and which offer us a number of pathways to value creation as we go forward. And in particular, we have actually published data, a poster at the AACR also, about an anti-IL-1 wrap ADC. So IL-1 wrap is overexpressed in many tumors and also in the tumor in microenvironment and in the stroma around the supporting tissue, if you like, around the tumor and through the tumor. And what we were able to show was our anti IL-1 wrap ADC. So an anti IL-1 wrap antibody conjugated through a linker to a tumor killing toxin, but a toxin which you normally cannot deliver because it is too toxic for the body. But if you can make it locate in the tumor through a targeting mechanism, in this case, IL-1 wrap, then you have very strong potential for treating the cancer. And what we were able to demonstrate was very strong tumor growth inhibition in tumor models expressing both high and relatively low levels of IL-1 RAP in their tumors. The ADC was also well tolerated in preclinical models, and we showed that adding the ADC function did not reduce the IL-1 RAP binding that we would look to see. So very exciting data in and of itself. but also illustrating the strength of this platform. So we have, as I said, numerous antibodies with different properties that we can develop into new IL-1 rat-based therapies. So not just ADC, but we could look at bispecifics in oncology, but also in immunology along where we have CANTEN. And we can look just to develop other of our antibodies targeting different indications. You saw the very large number of indications that the IL-1 RAP and the IL-1 superfamily are implicated in immunology and autoimmune inflammatory diseases. And we could develop antibodies which are more suited for certain of those diseases than others, for instance. So not only do we have CANTEN and Nijunolimab, but now we have also in early stages, admittedly, but anti-IL-1 RAP ADC. and the possibility to continue to develop other very interesting molecules as we go forward. Finally, from me, before handing over to Patrick to talk you through the financial figures, are our milestones for this year. So we have already, in Q1, been able to publish the very exciting initial phase one. Data with CANTEM, SAD and MAD. We have completed the recruitment of the Naginonimab triforce study, and we've started the investigator initiated trial at MD Anderson in AML and MDS. As we move through the year for CANTEM, we will fully complete the phase one study. And later in the year, we will look to file our IND and subject to financing, start our study. For PDAC, we will provide a regulatory update later in the year. And obviously, as I said, in around mid-year, we will have to try for initial results. And then for Can10, around the end of the year, we'll have the phase two start in HS and AD, as I just mentioned. So we have an extensive news flow expected during 2025, and this can also be backed up with additional new preclinical and translational results as well of the type that I've just shown you. So with that, I will hand over to Patrick to take you through our financial results. Thank you, Patrick.

Thank you very much, Damian. And we announced this morning our financial report, which is actually topic of why we are here today for the first quarter of 2025. And we started out with R&D expenses at about 41 million Swedish, which is slightly higher than we have been trending in the previous quarters, and it's 6% higher than Q1 last year. And that increase is driving and reflecting a somewhat higher activity in the clinical programs, both CANTEN as well as TRIFOR in adenoma, but also that we have decided to produce more of CANTEN antibodies in order to have that for the phase two programs. We have already finished the drug products so that we can start the studies according to plan, but we are proactively looking at making sure that we have a buffer of stocks there. On the GNA side, we saw costs for plus a million in the quarter. We have implemented relatively tight cost control, but we saw an increase compared to the same period last year, mainly due to organizational changes. So all in all, our operating loss was at 45 million and the reporting loss at 47. And the difference there is reflecting impact on currency fluctuations, which has a negative effect on our currency hedging currency accounts. All in all, we also ended the quarter with a cash position of 104 million. We started at 33 million by the turn of the year. We received 107 million in net proceeds from the rights issue that we conducted back in the end of 2024. And we had a net outflow of 36 million, which consisted of 34 million in operating cash flow and 2 million in currency adjustments. And that sort of took us to 104 million. Now, we estimate that this will take us into Q4 this year in terms of our financial position, but we have flagged that it's not sufficient to fund operations throughout the entire year. And we are actively together with the board working on various various tracks and various transactions, potential transactions, aiming at strengthening our financial position and making sure that we are stronger funded. And those activities include, but not limited to BD discussions, potential equity raises and other financial alternatives. And with that, I hand over to you, Damian, for closing remarks.

Thank you very much, Patrick. Yeah, so just in closing remarks, it has obviously been a very active and very exciting first quarter and subsequent few weeks for the company. All of this is taking place against a background, macroeconomic and geopolitical background. which is exceedingly disfavorable for the whole biotech industry. I think anybody who is invested in biotech companies would be aware of that right now. This doesn't make our job of creating value any easier, but nevertheless, we are working exceedingly hard. We have a number of different tracks ongoing. Business development has Patrick referenced there also corporate transactions that we are looking at and other ways to make sure that we can be in a position where we can finance the company and take the company forward. It's always a difficult area to talk about because we cannot give any detail for very obvious reasons of confidentiality with the parties with whom we're in discussion. But, you know, we continue to move forward. We remain as confident as we can be in the current circumstances. And, of course, with no guarantees that we will be able to close a value creating transaction for the company in the relatively near term. And so they are my final remarks for today other than to thank you and thank all of our shareholders. for their support. We don't take it lightly. And, you know, we're all working very hard to create value for you. But also, we're all driven by the desire to develop new medicines for patients in serious need. And I think you can see that we're making strong progress on that as well. And that is how we will develop value for everybody. So now we can move across to Q&A. Thank you.

If you wish to ask a question, please dial pound key 5 on your telephone keypad. To enter the queue, if you wish to withdraw your question, please dial pound key 6 on your telephone keypad.

The next question comes from Luisa Morgado from Van Lanchet Kempen.

Please go ahead.

Hi, team. Thank you for taking my questions. Maybe to start out with CAN10, I was wondering, since you're now starting the cohort in healthy volunteers, and the one with influenza is continuous with recruitment, I was wondering when will you share more data, if this will just happen throughout H1 of this year? And then also for CAN10, in terms of the pilot study in atopic dermatitis, Could you provide any more details here in terms of trial design, timelines, duration, that sort of thing?

Thanks, Louisa, for your questions. I'll take the first one, and then I'll hand you over to Morten to talk about our first ideas about what our AD study could look like. But yes, our second multiple ascending dose cohort is fully recruited. and is on the study right now and running forward. So we'll expect to be able to announce the data from that before the end of this quarter or around the end of this quarter. Psoriasis is a little more difficult to predict. The enrollment of patients has been stop-go, or subjects, I should say, but these subjects with psoriasis, it's been stop-go, and I'll be quite honest, it's not been that easy. It's asking a lot of a person with psoriasis to take part in a study where they need to be staying in a clinic overnight, where they're having skin biopsies taken and so on. But we continue to move that forward, and hopefully that we may get another subject or two into that shortly. So I can't give you a time at this point when we can talk about the psoriasis data, but I would just remind that that is not on our path to being able to file an IND and move to phase two. It really is exploratory for mechanistic purposes. So that's the content phase one. So Morten, over to you about the AD study.

Yes. On the question to the AD pilot study, I think it's... The question was about timing and trial design and so on. So what is really important for us is to understand if this non-clinical, you could say, clearly mode of action fit to AD translates into clinical effect. And therefore, our first step at it is a small pilot study. So what we really aim to do is to expose around 30 patients with ad for around 16 weeks and then enrich the study with them with a inadequate to pilliomap responder so that we clearly understand whether um whether this translation holds true and also the the place we are at right now is that we have engaged with a handful of different cro's which are highly experienced within both hs and atopic dermatitis and we do right now interact with them on the right study design because the recent Yes, atopic dermatitis has become increasingly hard to recruit in and conduct good studies where we don't get too impacted by the placebo response. So it's critical to understand how we can collaborate with the CROs to make sure that we actually deliver on this small pilot study while we at the same time execute on the bigger HS study. So what we really hope to be able to do is to start the recruitment or start the study at the end of this year both in terms of the ad study the small pilot study in 80 and the hs study thanks martin i hope that answered your question louisa thank you

Yes, very clear. Thank you. And nice to meet you, Martin. And maybe just one final question from my side then. And in terms, so you mentioned the regulatory interactions that you will, that you are planning for this year for not generally maps. And could you just elaborate in terms of what do you expect to gather in terms of conclusions here? And this is not only relative to just a diagnostic test, right? This is also just for the trial design of CDAC.

Yeah, initially we are looking at discussions around the path to being able to get the diagnostic to a position where it is able to support, you know, advanced phase two stroke phase three. you know, registrational type studies. That's very important and make sure that we advance that in a way that will be acceptable to the regulatory agencies at the end of the year. And then, yes, of course, as we go further on, we would expect to have some further discussions with the agency around design. We've already had some in the past. Some, of course, which came back with answers relevant to Project Optimus. which has made us have to change our plans more than once as we've gone along. And so, yes, we'll be having those very important discussions as well in due course.

Okay, thank you so much. That's all from my side.

Thanks, Louisa. The next question comes from Richard Romanius from Red Eye. Please go ahead. Good afternoon.

I had some questions relating to the clinical study, phase 2 study of CAN-10. So I guess that's for Morten. Could you say something more about the design of this study? What line of patients do we use respectively or patients who haven't undergone treatment before? And you mentioned in your presentation that you would use the high score 75. Is there something about your expectations in this? Since I know from Moonlight, they made a lot about their, I think it was high score 75, if I remember correctly, which was superior in their study. So what relative performance would you expect? And also, I may ask it straight away, really. There have been issues with phase two studies not translating perfectly into phase three in ages, and I think in psoriasis as well. Are you taking that into account in the design of the phase two study?

Um, can i should i start answering yes and so richard what this thing about the high score it's it's sort of an artificial construct because the regulatory requirement in particular from the fda is to use high score 50 in phase 3 studies but what it really is is that it's a reduction in inflammatory nodules and abscesses of more than 50% if it's high score 50 or more than 75% if it's high score 75 without an increase in either abscesses or fistulas. And the thing is that when we explore the efficacy is the delta between the placebo and the active that is important and it is so in the different trials that it's harder to get a high placebo response in high score 75 because if you improve with to a higher degree then it really requires efficient treatment. So that's the rationale for selecting high score 75. It's really to see less of a placebo response. But in terms of interpretation, it's the delta between the placebo and the active arm we would be looking for. And in terms of moving forward in phase three at a later stage, we would maybe have to change to high score 50 but for phase two the fda has accepted high score 75 because it is essentially the same construct um then about the translatability i think yeah it really You would always be concerned about whether it translates into the right effect when you expose the right patients. But I think the best thing we can do in this situation is to understand the disease and HS is... is something that really broadly involves inflammatory cascades. And then in the more progressed disease stages where you get a lot of tissue destruction, it gets even worse. So in my opinion, I think the broad mode of action is really what makes it super suitable for ATS. So I wouldn't be particularly concerned. that we don't translate. And in particular, if we can administer the drug every four weeks, then I think we have, then we are at a good place with this molecule. And then Richard, you had a third element, I think, but I forgot what that was.

Yeah, what line of the patient treatment naive or if they're refractory?

Yes, so we want to include both and we have proposed around 30% who is treated with prior biologics, either TNF-alpha or IL-17, and then 70% who are naive, to make sure that we, in the phase two study, get data indicating effect on both, whether they have been treated with prior biologics or whether they are biologics naive. And then your last question was to the expected level of effect in the high score 75 of this drug. I would say that at least 40%, if we look at an expected placebo of 20, so we would have at least the double the number of responders.

All right.

And if I could just add there, Richard, you know, our ambition, sorry, I could say our ambition, you know, clearly is to get high school 75s that are higher than the existing treatments. And we think the mechanism of action that we have, this broader mechanism of action gives us every chance because we hit more of the pathological processes of HS than the single pathway blockers do. So yeah, you know, that is the minimum that we expect to see, as Morten has just said, but our ambition is to be, you know, certainly better than existing treatments.

So let's see, if you achieve these results, how would that translate into the product placement I guess it would be difficult to get it in the second line in that case. Or if you get a really great score, would that be possible?

That's a really good question, Richard. It crosses over into a whole number of subjects, such as reimbursement, which is different in different countries. pharmacy benefit management and hospital formularies and so on. But the general expectation is that a lot of patients, unless your data is absolutely incredible, a lot of patients will, first of all, get generic biologics, so TNFs, before they move on to the newer biologic afterwards, and that is just simply a case of cost control. But the indication that we would go for, obviously, depending on the data, but given the population that we plan to use in phase two, if we use that in phase three, the indication would be to be able to treat both biologic, naive, and refractory patients down the line.

Interesting. Let's see, I had some more questions pertaining to nadinolamab. What Phase II activities remain before you can, or let's say, preparatory activities remain before you can start a Phase II study? You mentioned you had produced enough substance. Are you doing long-term toxicology studies or other activities?

Yeah, there is a toxicology study which needs to be completed and reported out, and that's on the same timeframe as the phase one study. So that is the other key activity. And then as we continue to move forward, there will be continued drug product and drug substance and drug product uh manufacturing but in terms of the actual activities to get to the trial it is getting the you know the relative amount the relevant amount of drug product in place to get underway and to ensure we can have continued continuity of supply and for the ind it's to complete the phase one study and wrap up and report the toxicology study and that is a prerequisite yeah Sorry, and as for Can10, did you actually ask about Nadir Nollimav? Sorry.

No, no, sorry. No, you're right. This was about, yeah, this was about Can10. My mistake, but you gave the right answer. No, my question in Nadir Nollimav was, I misplaced my notes. My question about Nadir Nollimav was, when you expect the results from the leukemia study?

Well, you know, that's an investigator-initiated trial, so it is not under our direct control. But we are expecting it is going to take around about two years for that study to produce results.

Okay, thanks.

all my questions okay thank you Richard appreciate it the next question comes from Stan Westerberg from analysis guide in please go ahead big congratulations to a very productive quarter to questions on can 10 first you can break up the expansion of the phase one trial a little bit more if originally estimated at enrolling 80 patients and now enrolling up to 116 it's a quite a big expansion for phase one study in my mind is this entirely related to the sad group or have you made changes in the other groups as well That's my first one, and also on the pharmacokinetics of the molecule, will you have to give a loading dose of CAN10 in phase two, or will you directly move into a four-week dosing schedule? These are my two questions.

Thank you, Stan, and thank you for your counterbox at the start. In terms of the phase one study and the enlargement of that study, that was undertaken mainly to add single ascending dose groups to the studies that we could go higher in concentration or higher in dosing, I should say. because eventually we want to have the highest therapeutic window we can and make sure that we can deliver fully effective doses to patients. So given how very good the tolerability was, we added more groups to the study. I might ask Patrick, as he has more corporate memory than both Morton and myself, who are recent arrivals, if he has any extra detail to add.

No, that's absolutely true, but we also added MAD cohorts to, exactly as Damien said, to explore higher doses. And that's particularly because we saw that, in general, other competitors were actually dosing higher in HS than in other diseases. So we wanted to have the freedom to give the right dose levels in phase two to patients in HS.

Thanks, Patrick. As you can hear, Stan, our chief financial officer has a much wider view on the company than many chief financial officers do. Absolutely. And sorry, Stan, if you could remind me of your second question.

Yes, it would be interesting if you will need a loading dose of Clantan in the future studies or if you can move directly into the four week dosing schedule.

Yeah, to ensure that we get as quickly as possible to the steady state pharmacokinetics and making sure that we're always above that CTROF level. that I referred to, we will use one loading dose at the start of treatment in phase two.

One loading dose, okay.

Yeah, so to be clear, that would mean patients who get an initial dose, a two-week dose, a four-week dose, and then afterwards, every dose would be every four weeks in a Q4W arm, yeah.

Okay, understood. Yes. So I understand there will be a loading phase in the study. Yes, exactly. One loading dose, yes. In the ADC field, where there appears to be a lot of activities from all parties involved in oncology drug development, Can you provide us with any more future plans or directions of your own preclinical programs? Will you be able to come up with a CD anytime soon? Which are your plans in this interesting field?

At the moment, we're in very early stages. done this early work that we've just published. So we're some time yet from designating a clinical candidate and then moving forward into pre-IND studies. But on the other hand, the program has attracted some attention. You may also be aware that Pfizer published an IL-1 RAP-ADC poster at the AACR at the same time as we did our paper. So you can see that You know, there is industry interest in this area, and we would be very happy, you know, to have a collaboration with somebody around this, for sure.

Okay, thank you. That concludes my questions.

Thank you, Stan.

No more phone questions at this time. So I hand the conference back to the speakers for any written questions or closing comments.

Yeah, the first written question is, how does the blocking of IL-1 beta relate to the blocking of IL-1 alpha?

Morten, do you want to take that one?

yes but maybe i don't know if we could show the slides again there is one which really explains it quite well slide number eight um no well anyway it's showing there more to now right yeah oh yeah it is okay cool yeah so Obviously, our non-clinical team and the CMC guys are much better at explaining the science of this. But if you look at the small yellow thing in the middle of the two parts of the IL-1 receptor complex, and also 33 and 36, then the thing is that that putting it there blocks both alpha and beta in terms of the IL-1. So you could say, how does it relate? It relates in this way that it blocks both IL-1 beta and IL-1 alpha.

Exactly, Morten. And also, as you said briefly there, it blocks IL-33 and it blocks all of the IL-36 isotypes as well. The only reason we don't have data is that there isn't a whole blood ex vivo inhibition assay for IL-1-alpha. And that's why we haven't actually got data that we can show you. But that is the way mechanistically that this works.

Thank you. And the last question is related to the Can10 programme. How will you finance the next phase for that programme?

As I hope I discussed about earlier, we are looking, Patrick discussed as well, we are looking at a whole range of ways of getting finance into the company principally through business development and corporate transactions but we are also looking at all other options as well it's quite clear at the moment that we can't finance it but we you know we are as confident as i've said as confident as we can be in the current circumstances and with no guarantees that we will be able to close a transaction that will allow us to move our programs forward

Thank you. And that were all questions coming in from the web.

Thank you, Jonas. So on behalf of Patrick, Morten and myself, I'd like to thank everybody who's dialed in and listened today. I hope we've given you a good update about where we are and where we're going. We thank you. very much indeed for your interest and your support and we hope to repay that to you as soon as we can. Thank you very much.