Good morning, everybody, and thank you once again for joining us for the 6th Annual Virtual Oncology Summit. I'm Yaron Werber from the TD Cowen Biotech Team, and it's a great pleasure to moderate the next session with IO Biotech. IO has very important data coming up in Q3 for their cancer vaccine, and we'll talk about that in a minute. With us today is Mai-Britt Zocca, who's the CEO, Amy Sullivan, Chief Financial Officer, and Qasim Ahmad, who's the Chief Medical Officer. Ladies and gentlemen, thanks so much for joining us. We appreciate it. Thank you, Yaron. It's always a pleasure, and thank you for hosting us today. Yeah, it's already the end of May, and sitting here today, we are excited about the prospects for Cylembio, which is, as you know, the U.S. brand name for our lead asset, IO-102, IO-103, which is a part of what we are going to discuss today. We have the readout from our pivotal phase III trial in advanced melanoma patients, which is expected next quarter, Q3, as we know. Our entire team, Qasim's team, and all the rest of our group is laser-focused on execution as we await the results of this study. All the preparations, as we have planned, are well underway to ensure that we are on track both for the BLA submission later this year and also, of course, very importantly, for the potential commercial launch in 2026. Altogether, this is very exciting times for all of us here at IO Biotech, and I would say for the entire field of immuno-oncology as well. With that, I will hand over to Qasim and Amy. Thank you, everyone. Terrific. We'll have a lot of questions. For the audience, if you have any questions, feel free to email us directly at yaron.werber@tdsecurities.com. The old Cowen email still works as well. I am plugged into the webpage, the Wall Street, you know, webcasting chat, so you can actually put the questions on there, and I'll be happy to take them for you. Maybe, Qasim, for you, the phase III is fully enrolled, 407 patients. It was fully enrolled in December 2023, randomized one-to-one, Cylembio, Pembro versus Pembro alone. You passed the interim analysis back in August last year, which was based on response rate with a high bar. The guidance change for PFS events from first half to Q3. What was the reason for that push-out? Was it slightly slower event rates, and what can you share with us? Was it in one arm and both arms? Sort of, what do you know? Thank you very much. I think, as you just alluded to, 407 patients were recruited in the trial back in December. Our study is basically blinded to us internally, though it is an open-label trial, but the IO Biotech team remains blinded to the individual patient assignment as well as across the arms. However, we do track events for the overall program right now, and we wanted to be a bit more specific in our guidance rather than just saying a particular half of the year. Based on where the events were being driven, we wanted to be specific, and hence the change or update in the guidance to Q3 of 2025. As of now, we believe that we are on track for that and confident that we will have the primary readout in Q3 of this year. The primary analysis is based on 226 events, right? That's true. PFS events. How close are you to that? I cannot tell you exactly how close, but as I said, we are pretty much getting there. Events had slowed down. That was one of the reasons we had updated the guidance, and we are almost close to the finish line. Got it. It takes you two months to clean up the data, so to speak? True. Is it faster than two months, or is it really two months? You can speed up between six and eight weeks. That's usually the time it takes, and that's exactly what we are calculating in our estimates. Got it. Okay. What can you share with us? It's a question, actually, from the audience. What can you share with us about the baseline characteristics in the phase III? Yeah. So, the study, if you go back, how we designed this trial, this was based off our data from MM1636, the study from Ingemar Swann, which led to the higher response rate of 80%, 50% CRs in almost 20, close to 26 months of PFS. We designed this trial keeping the standard of care at that time, as well as the MM1636 study. We assume that because the study has been run consistently without any significant changes in the external landscape, that it should be close to what you expect in this patient population across board. Is it similar to the RELATIVITY-047 baseline enrollment characteristics? The enrollment characteristics were pretty much the same, which are, I think, standard. RELATIVITY-047 actually recruited patients with a high proportion of PD-L1 negative population, which is, I would say, not what you see in real life. We will see as we get closer to cleaning and getting to the final sort of data cleaning process. That is a bit odd in RELATIVITY-047 compared to all other studies that have been reported in this setting. Can you just remind us, in this phase III, what was the enrollment criteria? Obviously, first. We are stratifying this study based off of disease state and BRAF status. That is our sort of enrollment randomization stratification. Other than that, we were recruiting patients just like other routine clinical trials in first-line advanced melanoma in stage three and four. Do you have a sense how much is stage three versus stage four? I cannot disclose it right now, but yes, we do have some idea as we're getting closer to cleaning the data. Right. So, you enrolled both low and high-risk disease, right? BRAF mutants and wild type, right? Yeah. You know, so it's basically head-to-head, Pembro alone, 200 Q3 weeks versus, you know, IO, you know, 102, 103, you know, Pembro. Every three weeks, yeah. Every three weeks. Do you have any sense what percentage of patients had Pembro in the adjuvant setting? As you can see, we started recruiting this trial back in 2022, and we finished recruitment in 2023. Adjuvant was becoming sort of, especially in academic setting, it was getting traction. We do not expect that there will be a lot of those patients. However, the protocol did allow patients to have had prior PD-1 therapy with a six-month gap from the previous therapy. It was allowed. Okay. With six-month gap. Yeah. It allowed both patients, well, it's adjuvant, right? So, you don't really know. Yeah. It allowed any prior therapy in adjuvant setting. Right. So, you don't really know if they were responding or not responding. And then what percentage of this is Europe, Australia, South America, Israel, you know, in the U.S.? What percentage was U.S. versus ex-U.S.? The majority of our sites are in Europe. We do have a considerable number of patients in the U.S., which would meet our criteria for FDA's requirement. Okay. Okay. Got it. Just looking to see. Yep. Okay. Just looking to see. I'm getting questions as we speak, but I've actually been asking some of them, and some of them I'll keep for later in the right time where it would fit just the order a little bit. One of the things when we looked at frontline melanoma studies in general, we've seen the BioNTech vaccine in the frontline setting. We know their vaccine with Libtayo and the two different vaccines, obviously, worked against historical controls in second line, but in frontline, they never actually released the data, but that ultimately did not work out. It looks like both arms had much fewer events, or at least the Pembro control was doing a lot better than historical. What would be the reason for that? I don't know if I can comment on their trial. There could be many reasons, whether it was like the sample size, the powering, and everything that was done on the statistical analysis. I cannot comment on their trial. I think for our study, we have considerable, like, we've revisited it a few times in the past. As you know, we increased our sample size from 300 to 380. We enrolled 407 patients. The study is appropriately powered with 89% power and with a 0.65 hazard ratio for the primary endpoint of PFS. I think we feel confident that the way we've designed the study, it should meet the criteria that we have set. What degree of a delta over KEYTRUDA can you hit on PFS? As I just mentioned, our assumptions on this trial design are with a 0.65 hazard ratio, so at least a 35% benefit in PFS over KEYTRUDA. Okay. Is it possible to hit it statistically with a 25% delta, let's say? Yes, it is. 0.65 is basically just the assumption. Okay. Can you hit it on 15, or it's not power enough for that? It is still better, but it is not really. I think you have to look at the totality of data, statistical significance, its clinical relevance, and clinically meaningful as well, and keeping in consideration other options that are available to the patients. We believe we still, I think, based off of the totality of information that we have, not just from our melanoma study, but from other trials, that the way we have designed the study, we should be able to show a considerable benefit, which is both statistical as well as clinically meaningful. What are you looking for? What would be, what's the lower end of what do you think is clinically meaningful? Is a 20% delta clinically meaningful? It's an interesting question. Clinically meaningful, obviously, has not just the statistical part of it. It's just like, what else do I have in my hand as a physician to treat my patients? And not only efficacy, safety, quality of life matters. So far, we've had a very, I would say, a favorable safety profile for our product with completely no significant added systemic toxicity on top of what you see with KEYTRUDA. When it comes to clinical meaningful and applicability, then other factors do also play a role there. We believe that the way we've designed the study, if we have a product, it will show both statistical and clinically meaningful difference in addition to the safety aspect. Okay. Got it. In terms of PFS for KEYTRUDA alone, did you use the 006 study of Pembro against Ipi as the control, you know, as the historical, or was it KEYNOTE-001? No, it's a KEYNOTE-006. As you can also see, Pembrolizumab across different studies has had, or even Pembro, or I would say anti-PD-1, Pembro and nivo included, the median PFS has ranged anything between 4.9 and 11, like, you can even say 12 months. We took that as a consideration, but KEYNOTE-006 is our main benchmark. Yeah, but so Pembro did 5.5 in that study, right? Ipi did 2.8? So pembrolizumab in KEYNOTE-006 is close to 11 months. Maybe what I'm looking at is the interim then. What was the ORR? 38. Yeah. Yeah. I think what I was referring to is the initial data. You said it's close to 11 months? Yeah. And that's the best Pembro has done. You have to keep in mind that these are not apple-to-apple comparisons in different studies. KEYNOTE-006 had a very high percentage of population with PD-L1 positive patients. It was almost 80% of patients were PD-L1 positive. That was back in 2016, 2017. Things have evolved. The standard of care has sort of evolved a little bit from that. Different studies have had different proportions of PD-L1 positive patients. Depending on that, the outcome can be different as well. We do know that there are other Pembro studies which did not make it. In most of those cases, as you were just referring to, the Pembro median PFS is close to five months. Yeah. In your study, just remind us, these are PD-L1 positive, right? No, we are including patients across PD-L1 positive and negative. Okay. That is actually going to be one of the benefits that we will have over the emerging standard of care or the emerging treatment option like Opdualag, which mainly only works in PD-L1 negative patients. We believe that we will be able to demonstrate efficacy across positive as well as negative PD-L1 status. Okay. Can you share, do you have a sense of what percent are positive in your study? No, I cannot share that today, but yes, we will be sharing that information as we disclose the data. Okay. Yeah. We're getting questions here. What was the BioNTech control PFS? We don't know that yet. They did not release the data. Okay. In terms of manufacturing, I don't know if it's for you or for Mai-Britt, you know, just given the adjuvant that you're using as well, can you give us a sense where would manufacturing be? Would it be globally as manufacturing in sort of each territory? You're doing this centrally in Europe, or remind us where you're producing it? I can take that one, Yaron. Yeah. We have secured manufacturing onto a commercial scale now, and we have also secured the logistics in terms of securing that there is material or product in place for all the patients that we anticipate treating both in the U.S. and the rest of the world when we get there as well. Is that a single supplier? Is it out of Europe? We have several suppliers, both for drug substance, drug product, and then we also have an additional supplier for the adjuvant as well that goes into the product. Can you remind us where they are? Are they U.S.? Are they in Europe? They are in Europe. Sorry about that. They are in Europe, yes. Yeah. They also have global footprint. The ones that we are using right now, they are in Europe. Yeah. Were they used in the phase III, or were they? Yeah. We haven't changed supplier. We haven't. So, you don't need to do any tech transfer or biochemical? No, no. Remind us about which adjuvant you're using. Yeah. We are using the adjuvant Montanide, and I'm sure that Qasim can also chime in here, but it is an adjuvant that is securing a slow release of the antigens, the peptides up on subcutaneous injection of the patients. Yeah. Did you need to do a user, you know, kind of a phase I user study about how to mix the Montanide? Yeah. No, we haven't done that, but we have done very careful material instructions to all the sites, the clinical sites that have participated in our phase III. And what we have seen is actually a very, very low rate of, you know, failure to emulsify the product. So, we have been very happy with the success rate that we have seen in our phase III on how to provide the product. You don't think you need to do a user study, right? No. Yeah, yeah. Unless you are referring to human factor, we have done human factor, and we do not really see any concerns there. Yeah. Okay. And how the mixing, that's something the physicians will do. Is it six times that you need to move it back and forth? Not the physician, the pharmacist. Yeah, at the site. Yeah. The pharmacist will emulsify. Okay. Yeah. The vaccine gets delivered too. The doctor just needs to schedule it. Yeah. It's off the shelf. That's the other benefit with our vaccine. It's off the shelf. It's actually sitting there at the pharmacy as the physician orders pembrolizumab. They order it at the same time. It gets delivered to the site, like within the hospital or the clinic for patients to just get access to it immediately. If it's done in a community center, in a private practice? It's very simple. The emulsification process is very simple. Like, if you get trained on it for, like, doing it a few times, you can do it as well. That is something the nurse can do or the physician can do on-site. Yeah. Yeah. Okay. Just looking to see. How fast do you think you can file for approval? Our current aim is that based on the outcome of the study, which is Q3, when we have the primary endpoint results, we will be able to file before the end of the year. That is the plan, and we are on track for that. You're in CBER, right? Or are you in CBER? You're in CBER. Have you had any, you know, since Dr. Prasad took over, have you had any interactions with CBER yet? And the. Not in the last few weeks, but we are in constant touch. We've been having feedback and review meetings with FDA throughout the process, and our communication with them continues as such. Even since Mai-Britt took over as well, our interactions have been going as planned. Remind us, you have breakthrough status, right? Yes, we did. Did you have an SPA in place? I can't remember. Sorry, what was that? A special protocol assessment, right? You did not need a special protocol assessment. No. Yeah. Okay. Let me maybe ask, I think we have about three minutes left. Let's talk about head and neck and then lung cancer as well. At ESMO, you shared the phase II data. This is the fully enrolled basket cohort, 18 patients. You showed a 44% response rate. It's 8 out of 18 or so. It comes nicely with KEYTRUDA alone in the past was about 23% in small cell lung cancer. Again, PFS was encouraging as well. You're going to update the PFS and durability in the second half of the year. What should we expect from that data, and what would be the next step? Yeah. We are continuing to track the study. First of all, I think I would just reiterate that we are really encouraged with both of these, the head and neck and the lung cohort in this phase I to study. We are continuing to follow up the patients for further maturity of data. I think the PFS 12 months, 18 months would be coming next. Further on, depending on when the durability of response becomes mature, we will disclose further updates from these cohorts by the end of this year. Okay. And so, Amy, can we chat a little bit about the balance sheet? And you just did a debt financing from the European Investment Bank, the European, you know, sort of bank, up to a tranche of EUR 58 million financing. The first tranche was EUR 10 million. And I believe you just drew that down, and you're eligible for another. The second tranche was just EUR 12.5 million. The third tranche is EUR 15 million, and then you have an accordion of EUR 20 million. Can you maybe just talk about the balance sheet a little bit, cash and the tranche financing? Yeah. So, we ended the first quarter with just over EUR 37 million. We did take the EUR 10 million, as you mentioned, down in May, and we are eligible to take that next EUR 12.5 million. If we talk about the first three tranches that are committed, those will take us and fund us on top of our current cash position into the second quarter of 2026. You mentioned we also have an accordion tranche that we're eligible to finalize, and that would be based on approval. We did talk about the condition for that, and that would be an approval of the product, first commercial approval. We think we're sitting here in a pretty good position, you know. Okay. You drew down the 10, you could draw another EUR 12.5 million, and they'll lead you through first half 2026. Into the second quarter. Into Q2, specifically into Q2. Yeah. The third tranche, so that into the second quarter includes the first three tranches. Yeah. The third tranche, and I think I drew, was EUR 50 million, right? EUR 15 million, and that's based on the BLA submission. Okay. By year-end. Yes. You could do the accordion tranche once you get approval, sometime second half next year. We could. Yep. Yep. Okay. Let me see. I think we're just in time. Okay. There's one more question that I'll take. When is the neoadjuvant melanoma coming out? The primary endpoint is MPR at the point of surgery. That's a major pathological response. Why is it taking time to get that data out? Thank you for the question. I think this perioperative study is quite an interesting study for us, one that will provide us a lot of opportunity to see the feasibility of the study as well as the biomarker data that is going to come out from that trial because we have the option for pre and post-surgery samples collected and analysis to be done from that. MPR for sure is, from a signal detection perspective, our primary endpoint. These are small studies, small cohorts of especially cohort A and B, just 15, 16 patients each. We expanded the trial to cohort C, which is a randomized part. We finished recruitment in January of this year. Patients go through the cycles of treatment, then they go through a period of surgery. After the surgery is done, the analysis for the MPR is done. We are pretty much tracking that, and hence our guidance is that we will be providing or able to provide preliminary data from the study before the end of this year, so that second half of this year. Okay. And is that something that can come out potentially at ESMO, or it's going to be more in the sort of the head and neck meeting? Because there's head and neck cohort, there's melanoma cohort, we are obviously looking at the most appropriate meeting to present it. It's not just going to be the efficacy safety information we're working on. As I said, this is more like a feasibility biomarker-driven program for us to look at further opportunities of development. This landscape, both in head and neck and melanoma, is fast evolving, so we're keeping that into consideration as well. Hopefully, with the data from the 013 pivotal study, it will be the totality of information that will help us determine. Okay. Terrific. Team, thank you so much for joining us. I think we're over time now. Thanks, you know. Be in touch. Thank you. Yeah, we're excited. Thanks so much. Bye.