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.