Cantargia AB (publ)

Thank you. It's a pleasure to present Kantariga's half-year report of what I think has been a very exciting period in the company. So to take you into the highlights, we've had a very good news flow regarding both our clinical programs. But what I really like to point out here is that Kantariga has taken a major step forward that we now have two clinical programmes of significance. So the CanTen programme passed a number of important milestones during the period. We are almost completed with the initial SAD part of the phase one trial. And SAD means then single dosing. And we've had the independent safety review on unblinded data that has not picked up any safety concerns. So the safety is obviously very good on CAM-10. But we also start to generate biomarker data, which shows that we have a very potent drug. So for instance, we've documented receptor binding on to the target I1 wrap on immune cells at a relatively early and predictive dose level. And we also generated strong biomarker data. So we'll present more about that when we go through the slides later on. And there's also been several scientific publications with new data. So obviously, that's also creating additional interest. In the oncology program, nadinilumab, we have presented data at several conferences. So we presented new data in pancreatic cancer, showing additional features on antifibrotic effects. We have new clinical results on prevention of neuropathy. And we also looked into that there is actually a link between K-RAS mutations, which are a major problem of pancreatic cancer, and how it fits very nicely with our mechanism of action. And finally, we are making progress in the upcoming leukemia trial, and we're also starting to see the end of recruitment in our triple negative breast cancer trial. And finally, we also have a much cleaner sheet now when it comes to our patents where the latest appeal against one-hour granted patents were withdrawn ahead of proceedings. So a good period for sure. So then just to remind you then on our pipeline, so to basically make it simple, we have two clinical programs. where we have most data in pancreatic cancer, triple negative breast cancer, non-small cell lung cancer. And then we have our second program, CAN10, which is in phase one. Plan is to enter phase two, second half of next year, once we're through the MAD part. And the lead indications, and here we have a small update, is that we're generating more and more support to go into a serious dermatological disease called hydrodinitis suppurativa. So that's clearly on our radar. And the second indication we're targeting is systemic sclerosis, which is also a very serious fibrotic disease affecting skin and lungs and internal organs. So very excited about these opportunities. And we also have the potential to broaden our pipeline as we have our CanXX program with new opportunities, both as ADCs as well as by specific antibodies. So very quickly then, we have had a good 24. We have high expectations for the rest of the year and next year as well. So obviously to continue to generate data in our two clinical programs, we have several milestones ahead of us. And I think as an investor, you should also expect that we are visible when it comes to publications and conference presentations of new data. Starting out with Canten, and Canten is really where we have made significant progress lately. So to just take you through biology first, Canten is targeting what's called the I1 family of cytokines. And the VIL-1 family of cytokines are driving several inflammatory diseases. So the potential in CAN-10 is enormous. And we're really having much more opportunities in front of us than we can handle. And as I said, we've decided to look into HS and systemic sclerosis lead indications. But the really key feature here is that, if you look at the bottom of the slide, is that CANTEN is, through its interaction with IL-1 RAP, is blocking the activity of three different cytokine systems. So you have IL-1 system consisting of IL-1-alpha and IL-1-beta. You have the IL-33 system as well as the IL-36 system. And they are all responsible to drive several diseases, but very often they work together. And that's been very clear when you try to block them individually, but in most cases, it's been very difficult to get strong, meaningful clinical signals. And it's just because you're just blocking one out of several compounds driving the disease. And if you look to the bottom and to the right, we're trying to illustrate this in a in vitro experiment where we are basically looking at the signal induced by a mix of IL-1, IL-33, and IL-36. And if you then try to block them individually, like all these black lines, you can see that there is very little potency in blocking IL-1, IL-33, or IL-36 individually. But if you use CANTEN like the blue line here, suddenly you have a super potent molecule which is active at the sub-nanomolar levels. So clearly a major step forward here. So going then into the next slide, the phase one has progressed very well and very timely. So if you, the trial is designed as in intravenous administration in the first part in healthy volunteers so that's the sad part we have really seen a very good safety we've seen receptor occupancy and that's illustrated on the top here to the right where we where we can look at The binding of or content to either monocytes or neutrophils, the two different types of immune cells in the blood. And if you look at what's called SAD1 and SAD2 to the left, that's the very low dose levels of contents. Obviously, the dose levels are too low to document anything. We increase the dose levels in SAD3 and upwards. You can start to see that we are saturating IL-1 rep on these immune cells. So, and this is very much in line with our predictions. But the next step, which has made increased enthusiasm even more, is that we have collected blood from these individuals, and you can see it in the bottom here. And we stimulated the blood with IL-36 before and after CAN-10, a single shot. And then we analyzed the ability for IL-36 to stimulate the cells eight days after they got CAN-10. And you can see that there is a nice dose response here as well. So at SAD-5, it's clearly that already here. we have a very potent inhibitory effect, which is then getting stronger and stronger. And at SADD7, we blocked the IL-46 signal. So it shows that CANTEN is doing its work, and it gives extended effect at least during a week afterwards. So we are very excited about this, and we are now very excited as we are starting the MAD part, which is carried out in participants with the plaque psoriasis, mild or moderate plaque psoriasis. And so it gives us another opportunity to learn even more as we can get skin biopsies from these patients in addition to what we already can measure in the blood. And we expect the first individual to start treatment any day now. So very good progress in this phase one trial. And as I said, we are already planning for phase two to make sure that it can start as quickly as possible once the phase one has finished and sometime during H2. So then just a comment on hydrogenated suppuritiva, because I'm sure everyone are not extremely familiar with it. But it is a very complex disease which starts out as inflammation, which is then getting worse and worse on the inside of the skin. And what's interesting is that there is documentation that all the components were addressing. So IL-1, IL-43, and IL-46 are all upregulated in the skin from these patients. And recently, there was clinical data being presented on IL-1 blockade using ludicizumab from AbbVie that reached a primary endpoint in a controlled phase two trial. And the results were strong enough for AbbVisa to start phase three, which started earlier this summer. And in parallel, Boehringer Ingenheim is developing an antibody against IL-36, which also showed positive results in a phase two randomized trial. Boehringer Ingenheim is also continuing the development. So our anticipation here is that the very positive data from the tachysomab especially on some parts of a disease combined with what you're burning in our soul with specialimab can be added together and that can can combine all these features into one product so we are super excited about this and also hs it is a very common disease It's estimated that around one percent of the European and the US population suffers from it right now and it's increasing. So so if we summarize a little bit, It has been shown that the IL-1 blockade can counteract the inflammation. And it's also been shown that the IL-36 blockade from Bering-Ingelheim is affecting something called the draining tunnels, which is an important part of the disease development. And more speculatively, IL-33 is involved. We know that from other diseases that it's contributing to serious itch. Even though there is no data, we have a strong belief that blocking IL-33 through CANTEN will also have an effect on that, which means that CANTEN actually can attack three different parts of this serious disease. So then moving over to nadunilumab, we have previously presented data in pancreatic cancer, which shows that what clearly indicates a treatment effect and with nice survival data in first-line patients where we combine with chemocytopenia braxen, which is part of the standard therapy. And we've also shown that the more IL-1 rep the patients have in their tumor, the stronger efficacy we can observe from this combination. And this is exciting as the high IL-1 RAP is associated with the worst prognosis from KRAS mutations. So if you look to the left here, you can see that the survival is about 14.2 months in the high IL-1 RAP group versus 10.6 months in the low IL-1 RAP group. And also, if you look at these spider plots to the right, you can see that here in the middle where you have IL-1 wrapped high patients. that they respond to the therapy in a stronger way, but also that the responses are much more durable. So you can see that you have patients that have been in response for almost one and a half or two years, while the high IL-1 RAP group, they typically deteriorate after six months. very positive results in pancreatic cancer, which is obviously very, very difficult to treat disease. And we are planning to take these findings forward into phase 2B trial. But another interesting observation from this trial, which was presented during the period, is that not only do we have an interesting anti-tumor effect, but we also seem to alleviate a serious side effect from the chemotherapy combination partner, which is neuropathy. So if you look to the left, that's data from the clinical trial. You can see that the patients that were treated with 1 mg of nadonidumab, which is the gray bar here, developed much more neuropathy. also got the onset of neuropathy earlier than patients that received all the higher dose levels of 2.5 or above. And to remember, 2.5 is the dose level we are targeting in future clinical trials. And to the right, we also have a collaboration with a group in Brisbane, Australia. who have been investigating mouse models of chemotherapy-induced neuropathy. And again, we can see that nadonimumab seem to counteract this neuropathy. It could be sensitivity to mechanical pressure, or it could be grip strength. Nadonimumab seem to do a very good job here to counteract this very unpleasant side effect. And then to remind everyone that besides pancreatic cancer, we're also working in triple negative breast cancer. The initial part of the trial has been presented as it was non-controlled. It was more dose finding. And here we can see a 60% response rate, which is about twice as high as expected from chemotherapy alone. And again, this is chemotherapy combination of first and second line patients. And the survival was also longer, and the progression-free survival was longer than expected from historical controls. So we're very excited to start to deliver those results, and we're looking to do that first half next year. So to quickly summarize the biology here, and I apologize because this is a slide which It may be a bit difficult to read, but the point is here that if you look to the left and into this biological mass, which illustrates what's happening in the tumor, nadunarumab can block signals at all these different red crosses here, which is leading to different type of tumor-promoting signals. Then if you look very carefully, you can see that there are some yellow parts here, which indicates IL-1 rep overexpression. And here, this antibody has been designed to stimulate immune cells to attack these tumor-promoting cells. So the drug is active at a large number of different places to really block the tumor progression. And at the same time, it's interesting that the same signals can then be used to counteract the neuropathy as illustrated down here at the lower part of the leg, where you can see red crosses blocking some inflammatory mechanisms that will lead to this unbearable pain of neuropathy. So that, I think, reflects the progress, but also reflects a little bit of what's going to come here during the next part of the year. So for that, I would like to hand over to Patrick, who can go through the finance part.

Yes, thank you very much, Joran. And I'm going to take you quickly through the highlights of finance. And we do not mirror the same successes or progress with increases in cost. As you can see, it's quite the opposite. We have a 30% reduction in our operating expenses in the second quarter, where we went from 63 million in 2023 to 44 this year. And it's driven, as you can see, by R&D. So we dropped 17 million to 40 million SEK in the quarter. And our cost for administration, so we report in this graph, we combine it with other operating expenses, but our main administration costs were unchanged, but we had less other operating expenses, which then reduced the total by 2 million from six to four in the quarter. And then if you look at the results for the first half year, we had a 39% reduction in OPEX from 140 to 85. Again, obviously driven by R&D. And if I just take two seconds to explain what's behind that, and it's the fact that we are now running two clinical trials. As Joran has mentioned, we are running the triple negative breast cancer study with Nadenolimab Tri4, and we are actively recruiting the CAN10 first in human study. Whereas in the same period last year, we had a full program for Nadenolimab with studies that are still active. They are still active, but from a financial point of view, we are about to reconcile and eventually close them down. So the spend is much lower. We have been able to reduce our administration cost by one million in the first six months. So that's included in the reduction there that you see from 11 to 7. The rest is operating expenses that were lower. All in all we reported a Operating expenses of 85 as you can see there and all in all the net loss was 80 million because we have 5 million in financial Gains so net financial items were positive 5 million. So, um, We also report on the development of our available funds, which, of course, is important. And our available funds are important because that's what's funding all the activities that we do. And available funds, repeat, is the sum of what we report as cash and bank balances, as well as short-term investments. And those are mainly fixed-term interest rate funds. We ended the six months or end of June we had 105 million in available funds which represents a decrease of 38 million which was lower than the 52 that we saw in between the fourth and the first quarter of 2023 to the first quarter of this year. We expect that the 105 million that we have available now will suffice through to the first quarter next year or if we make prioritizations we can extend that to the first half of next year. With that I hand over back to you Joran.

Thank you. So I would just like to finish off here with showing some of the upcoming milestones. So the Venadunilumab program, there are lots of activities ongoing right now. So we have a pancreatic cancer trial, which is still pending financing, but we have a number of interesting discussions ongoing regarding our pipeline here. But the plan is to start a phase 2b trial, which will be a big trial in 150 to 200 patients as quickly as we can. We have a triple negative breast cancer data where recruitment is ongoing, but we expect randomized data to be released in June first half next year. And we're also very excited about the grant from the US Department of Defense to sponsor the upcoming trial in leukemia, AML and MDS. And as you may have seen from the communication, the IND was approved We expect the ethics approval to be done in the near future, which then means that the site can start to initiate for recruitment of patients during Q4. So exciting progress and much more to come. And the CanTen program obviously has generated lots of interesting data from the SAD part during 2024. And our intention is to continue to be transparent when we reach material progress. And what we now have in front of us is the start of the multiple dosing, the MAD part, where we believe that we will put another level of excitement around the data as we now can collect tissue from participants with psoriasis. And the plan is then to go ahead and file a USID and start phase two next year. And we also have a number of clinical trials where, as we continue, we will get long-term follow-up of patients. And in the near future, we're presenting new data in lung cancer, as well as on the Keytruda combination at the ESMA conference. And I'm sure it's going to be more data at upcoming conferences, both in 24 and 25 from this program. So by that, I'd like to thank you for your attention, and Patrick and I are extremely happy to make additional clarifications or take questions afterwards.