Excellent. Welcome, everyone, to Jefferies Linton Healthcare Conference 2025. My name is Roger Song, one of the senior analysts medical biotech in the U. S. It is my pleasure to introduce our next presenting company, IO Biotech, CEO Mai-Britt. Welcome, Mai-Britt. Thank you. Thank you. It's always a pleasure to be here at Jefferies in London at this time of the year, and I'm happy to give an update on where we are. First of all, the forward-looking statements, and then into what I'm going to center my presentation around. Cylembio is the U.S. brand name for our lead product candidate, IO-102, IO-103, which is the product that is based on the T-win platform that we are using and developing all our candidates based on. Let me just go through the recent highlights of the company that have come out from all the developments we have done here during 2025. First and foremost, we had our readout from our phase III trial where we tested Cylembio in combination with anti-PD-1 pembrolizumab in first-line metastatic melanoma. The trial was set out to read out on PFS, and what we had was a narrow miss on statistical significance. I want to share that right away. What we really saw was a clear clinical improvement across virtually all subgroups in the trial. Let me just walk through the data as they came out from the trial. We had 19.4 month median PFS in the experimental arm versus expected 11 month in the control arm, anti-PD-1 alone. The hazard ratio was 0.77. I want to just reiterate that the p-value came out at 0.056. We needed to hit on a p-value of 0.045, so a very narrow miss. We were excited to see that the PFS improvement came virtually across all subgroups and also all stratification markers. We saw this effect without any systemic toxicity versus pembro alone. Of course, we took the data and tried our luck with the FDA to open up an opportunity to file based on these data, despite they miss on the statistical significance. They were not as open towards this as we were. Instead, we have been discussing now with the FDA, and we are planning on a new phase three trial. While we are doing this, we are in the process of discussing the data that came out from our phase III trial with the authorities here in Europe. There might be other guidelines that we can use in order to move forward and submit here in Europe based on the data that we had coming out of our phase III trial. We know that there is still a huge unmet need in this indication, 15,000 patients alone in the U.S. with advanced melanoma, and only 50% of those benefiting from today's treatment. Still a really good opportunity and a commercial opportunity that actually fits perfect with the opportunity we have with Cylembio. We see Cylembio as an ideal combination partner, and we mean that not only in combination with anti-PD-1, but also potentially other combinations and also across other indications, so going beyond melanoma as well. I'm going to share with you some of the background for these statements that we have made here. I just touched on the need that we have in melanoma. There is maybe no need for me to share that when patients come in and they are diagnosed, they get nervous, they are uncertain about the journey that they need to take to go through the treatments that they are in need of. We have focused our developments around bullet point number four here when patients come in and they have unresectable metastatic melanoma. We are also developing Cylembio around resectable melanoma. This means that when a patient comes in, they still have the opportunity to be cured or be having their tumor removed by surgery. Today, I will focus my talk around bullet point number four here, patients with first-line advanced melanoma. The trial we conducted, IOB-013, is the trial where we see the design right here. We enrolled 407 patients across more than 100 sites in Europe, Australia, South Africa, and also Israel and the U.S. We did that with the expected timeline. We really had a very successful execution of this phase III trial. The stratification was towards disease stage and also BRAF. We randomized, as you can see here, Cylembio in combination with pembrolizumab against pembrolizumab alone. PFS was the primary endpoint. We had multiple secondary endpoints as well. Here are the top-line results that we announced here in the fall of this year, released August 2025. The intent to treat analysis revealed what I shared in my introduction, 19.4 months of median PFS in the experimental arm versus 11 months for patients treated with pembrolizumab alone. Hazard ratio 0.77 and a p-value slightly missed what we needed to hit on 0.056. We went on and looked at the data, and we were really excited to see some of the subgroup analysis, what they showed us. If we, for example, look and we look at excluding patients that had prior treatment with anti-PD-1, these are patients that come in, and they come in in the neoadjuvant-adjuvant phase where surgery is beneficial for them, but where we already now today start treating with anti-PD-1. When we excluded those 36 patients, we actually saw a PFS value coming out at 24.8 months versus, again, the 11 months in the control arm, and now with a nominal p-value significant at 0.037. What we were especially excited about was to see the effect in PD-1 negative group. Median PFS was here in the experimental arm, 16.6 months versus the expected three months for anti-PD-1 alone. This is a profound effect. The nominal p-value is at 0.006 and hazard ratio of 0.54. Very excited to see this. This is a group of these patients that are mostly in need of better treatments. What we are seeing as well is that overall survival is also trending favorable for the experimental arm. We are excited about this data set that clearly shows that we have a drug in hand. You will also share that with me when you see these Kaplan-Meier curves, where we are seeing a clear separation of the curves at three months and then widening over time as well. Also, when we look at the OS, and this is really impressive, we are seeing that the curves start separating at nine months and then widening over time. Of course, we are expecting that OS will mature as it's maturing more in 2026. I already mentioned the safety profile, which is clean, no added toxicity on top of pembro alone. This is what we are showing here. This is not a surprise to us. This is what we have seen in all the trials and all the patients we have treated with Cylembio. Where are we now? When you miss on the primary, you get back and you need to start then analyzing what's next, especially after the discussion we just had with the FDA. I want to say again and reiterate that the discussions with the EMA are still ongoing. We are still trying to push for an opportunity to file in Europe with the data set that we have right now. But, we are working towards a new plan, and this is based on what we know as of today for the U.S. market and based on what we have already been learning from the different studies we have conducted. We set out the 013 trial based on the phase I phase II trial MM1636, where we learned that we had the opportunity to really see an impactful effect in patients with metastatic melanoma, and we launched the phase III trial. While we have been executing on our 013 trial, we actually engaged with Memorial Sloan Kettering Cancer Center, who has been conducting an investigator-initiated trial at the institute together with two other sites, and they have enrolled more than 40 patients right now. What we know from the first 32 patients that were available for PFS readout is that we are already seeing effect also in combination with OPDIVO. This is very important because OPDIVO is really becoming the standard of care in the U.S. and being the most used treatment for patients that come in with metastatic melanoma. OPDIVO is having already 30%-35% of the market in the U.S., and it's expected to be growing. We were very excited to see these data coming out from the Memorial Sloan Kettering trial. After the discussions we have had with the FDA and based on these data, we are now proposing a next study where we will move ahead and we will combine Cylembio with OPDIVO. We will do that based on the learnings that we had from the phase III trial IOB-013, where now we will stratify the patients for PD-1 status, and we will also stratify according to prior treatment with anti-PD-1 or anti-PD-1 as well. We will take in patients that have more or less the same eligibility criteria as we had in our first trial, and then we will do a sample size re-estimation when we have gone through the first phase of the trial, which is to enroll around 400 patients. We will conduct the phase III part of the study where we will roll between 550 and all the way up to 800 patients. We expect we will have the PFS to be the primary readout or the primary endpoint. This is the design that we will be discussing with the FDA in the near future. We will share more when we learn more around this trial as our next step when we have had those discussions. I mentioned in my introduction that this is not only a drug that works in melanoma, and this is based on the other studies that we are conducting with Cylembio. As you can see here in the pipeline overview here, we have in the top here, we have IOB-013 and also the new trial we are presenting or proposing, the 023. In addition to that, we also have IOB-022. This is a study, a basket trial, where we have tested Cylembio in combination with anti-PD-1 pembrolizumab in first-line lung cancer and also in head and neck. We have already shared data at several conferences from these indications as well. We are seeing encouraging data in both indications showing that this is not a drug effect that we are seeing only in melanoma. We are also conducting a trial 032 in neoadjuvant-adjuvant settings in melanoma and in head and neck. We will be very excited to share data from that study during 2026. I shared in the beginning that the platform we are working on is also generating new targets, and we have IO-122 coming out. This is targeting arginase 1. It is also very exciting data that we are seeing from this target, where potentially we can go into a different type of indications compared to those we are working with already now. Arginase is overexpressed in liver, colorectal, prostate, and multiple other difficult-to-treat cancer indications. We are also working with TGF-β IO-170, where we have found a way to actually drug TGF-β, which has been attempted multiple times. What we are seeing is that we are able to target TGF-β in a way where we are not having any tox effect. This is also very exciting data as well. We have shared from both these two targets at multiple different scientific conferences updates from them as well. Let me just share the data that we have from head and neck and lung, as I have listed it here. We have in the top melanoma and the totality of the data. I'm sure will excite you all as it is exciting us here at IO Biotech. Head and neck met the primary endpoint with a readout of overall response rate of 44.4% and a median PFS of 6.6 months. This is almost doubling up compared to what we see when patients are treated alone with anti-PD-1. We have benchmarked it here, 23% ORR and also median PFS 3.4 months. With lung, we had overall response rate coming out at 55% unconfirmed, 48% confirmed, and median PFS of 8.1 months. This is also an improvement compared to the benchmark we have with anti-PD-1 alone, where ORR sits at 39% and median PFS at 6.5 months. This is really encouraging and is adding to the excitement that we have around Cylembio. But of course, what we are focusing on and what we are addressing right now is to hit home on first-line advanced melanoma. This is what we are working on right now. I just want to share with you how we are viewing the market opportunity in all the indications that we are working on. So not only the 15,000 patients in melanoma, but also 40 patients in the two other indications and more than 100,000 patients in the earlier indications. It is really giving a great opportunity alone just for Cylembio, and we have more to add in the pipeline, as I already have shared with you. This is how we see the potential for the future. I'm sorry about this noise. It is really annoying, but I hope you can hear what I'm sharing. So 2022 - 2025, we have validated the platform with really compelling data. As we move forward, we are intending to really reach the point where we can submit applications not only in Europe, but also in the U.S. based on data readout from our trials. Of course, as I've shown with you already now, is to expand in three dimensions into other indications and also into other targets coming out of the T-win platform. Just to mention the data that we have both from arginase and TGF-β. We have shared with the community both scientifically and also some early data from safety studies run at academic institute from arginase that it's really validating what we are intending to see, that we are not only targeting tumor cells, but indeed also the immune suppressive cells in the tumor microenvironment. We have an IND that could be ready for filing or planned for 2026. Similar for TGF-β, we are seeing a clear tumor growth inhibition in several of the animal models that we have tested. We are also seeing that we have an opportunity to go into fibrotic diseases with this target. Really exciting data that we have here from both of them. Just to give a little bit more details on the T-win platform in itself, because it's really novel biology that we are pioneering here at IO Biotech and now being taken on by other companies as well. We are still front leading the field. The way that we have approached a therapeutic cancer vaccine field is to understand how immune suppression is actually limiting the activity of the T cells. Therefore, it was very important for us to target not only the tumor cells with our T cells, but also the immune suppressive cells. This is exactly what we are doing. The T cells that are being activated and introduced after subcutaneous injection of peptides from the proteins we are working with are generating T cells that will target both tumor cells and immune suppressive cells. In the case of Cylembio, it will be with cells that are expressing both IDO and PD-1. By doing that, we are actually lowering the immune suppression and allowing a better hit on the tumor cells themselves. We also know that this will modulate and inflame the tumor microenvironment, enabling further tumor cell killing. Not only have we thought about how to approach the tumor cells and the killing of those, we have also thought about how patients feel when they come into the clinic and they need treatment. They want to have it fast, and they want to spend as limited time as possible while they are at the hospital. We have developed an off-the-shelf therapy that is accessible very fast, and it is ready for the patients when they need treatment. We think the patient convenience is also a huge part of what we need to think about as drug developers. How does the future look? This is my last slide that I want to share with you here. Of course, going into 2026, we will potentially initiate a new phase three trial and also potentially submit an MAA in the EU based on the data that I have shared with you coming out of the 013 trial. We will continue to develop further data with the other studies that we are running and, of course, also share with them as they are coming out. And also we will potentially also submit an ID for the 0112 target. With that, I would like to thank you all for your attention, and we have five minutes left. Yeah. All right. Thank you. Thank you. Thank you. I think that OPDIVO as the comparator for the phase three makes sense. Is that coming from the FDA recommendation, or that's in your. So we had the luck of not only having the meeting with the FDA in that period, but also to have an ad board meeting where we had 20 of the KOLs from the Melanoma Society that you really want to speak with. Based on the recommendation, both from the FDA and also from the discussions we had at that ad board meeting, this is why we have developed this trial design. This will be U.S. focused, or it will be global? I mean, it will be a global trial. This will be a trial where we need to enroll many patients, and we cannot only enroll patients in the U.S. It will be a global trial, but with the focus on, of course, a submission at the FDA. Yeah, but OPDIVO, you say 30%-35% people are using in the first-line metastatic melanoma using OPDIVO. How about ex-U.S.? I know that there is a different profile or label for OPDIVO in Europe, where only PD-1 negative patients are approved. We have done a feasibility study for how we can actually also conduct the trial in Europe, and it should be feasible. Got it. What will be the statistical assumption? You say you start with the 400, and then maybe adapt. What's the 400? Yeah, so I think we can share that later on when we are further on with the developments. Yeah. Maybe since you are talking with the FDA for the next stage, how do you think about you may potentially kind of find a partner to do the phase III if you can align with OPDIVO on the design? Yeah. With partner, you mean about the comparator, or? Yeah, I mean maybe pharma or any company interested in this. Yeah. As biotech is used to, we are exploring all the opportunities we can to set up the trial as best possible for success. Yeah. Maybe just can you tell us a little bit on the feedback you've been getting on the phase III? Just like you said, it's narrowly missed, but also hitting almost all the secondary endpoints that's approved. The feedback from your investigator, physician, and then also the potential partner pharma side, and then how do you think about the data? I think everybody is excited. I mean, we clearly have a drug, right? First of all, all the investigators that have participated in the trial were very excited to see the readout. Disappointed, of course, to see the miss on the p- value. It has been a big work for everybody to conduct this trial. It is not every day that you have such a clear effect and then miss so narrowly. It happens. I think that everybody we speak with are very excited to see what we have seen in this trial. I think most other of these types of modalities have failed in phase three. You can call this a failure, but I do see that we have a drug, and this is what is driving the excitement and the enthusiasm for us that I think it's the first time that a cancer vaccine strategy actually has shown such a clear separation of the curves when you measure PFS as an outcome. For that, we are very proud together with the investigators that have been a part of the study. Got it. In your phase three, you have very clear, even the p- value also statistical significant for certain subpopulation, particularly for the PD-1 negative pure NIE patient and not even a neoadjuvant. Why do you not design that population for your new phase III? Yeah. We are still working on the design, and we will have the design fully locked down in the Q1 of next year. Yeah. Maybe on the LAG-3, any biology reason IO Biotech is working better or worse with adding the LAG-3, just adding additional? I see it adding more of the same, right? Anti-PD-1, LAG-3 is really checkpoint inhibitors in the same class. One works at the earlier stage of T cells and the other one at the more exhausted stage. It is more really of the same type of treatment where we come in and we are completely different. We really just flush the tumor microenvironment and the tumor with T cells and give that spark and that kick. In that sense, I do expect that everything is working very well together. This is also what the early data are showing us. Yeah. Maybe can you just speak to the pushing for the approval in Europe, how you see them looking at this differently than in Europe? Yeah. Even though the FDA and the EMA might seem similar, there is some difference in some of their guidelines, and this is what we are reading through. That is what also we are basing our push in Europe for compared to the discussions we had with the FDA. It is some of the guidelines that you can find here in Europe that is giving us an ability to at least open up, hopefully, the door. Do you have any timelines on this? We are pushing as much as we can, and we are hopeful to have some indication before the end of this year, but it might slip into the beginning of 2026. No further questions.