Good afternoon. Thanks for joining us for another session at the 42nd JP Morgan Healthcare Conference. I'm Brian Cheng, I'm one of the senior biotech analysts here. On stage, we have iTeos' team. I'll pass the mic to iTeos for a short presentation, followed by a live audience Q&A. If you're joining us live, you can submit a question for the team through our conference portal. iTeos, the stage is yours, Michel. Thank you very much. Good afternoon, everyone, and welcome. I would like to thank you, JP Morgan, for hosting the conference and Brian for inviting us. Before to start, I would like to spend a few minutes to describe what is iTeos. For the last decade, we have built an incredible expertise in tumor immunology that allow us to go above and beyond to understand how to create differentiated therapies to help people living with cancer. Today, we are very excited to start 2024 because we are into an incredible position with most milestone-driven year in the company history. Let's move to the next exciting slide. I will make some forward-looking statement in this presentation. There are three things that I want you to know upfront in order to understand why we believe that 2024 will be defining year for iTeos. First, we are going to get two TIGIT readouts that will set the stage of how our PD-1 TIGIT doublet compares to the rest of the field. Second, we are going to get two data readouts on adenosine that will allow us to demonstrate that iTeos has been the only company able to unlock the adenosine-mediated immunosuppression. And finally, we have a $645 million cash position that gives us a cash runway through 2026 and the generation of multiple inflection points. Oh, sorry. Now, let's focus our attention on the pipeline. We are going to show this year progress and data across every program. First, for our belrestotug program, a TIGIT antibody. In blue, we are going to launch our first phase III later in the year in frontline lung, where we will combine belrestotug, our antibody, with dostarlimab, the PD-1 from GSK. In addition, we are going to release data on two phase II/I, GALAXIES Lung-201 in frontline non-small cell cancer in combination with dostarlimab. The second in head and neck cancer in combination with dostarlimab TIG-006. In addition to these two releases, we have four ongoing clinical studies evaluating original triplets in different indications. For the adenosine pathway, we have two programs, inupadenant, a best-in-class small molecule targeting A2A receptor in oncology, where we'll get the first data coming out of our ongoing phase II in second-line non-small cell lung cancer. And I'm very excited today to share a new target in our pipeline, which is an original discovery from our R&D team with ENT1, as a new mechanism to modulate adenosine-mediated immunosuppression and the ongoing dose escalation with EOS-984 that we'll present at the end of the year. Now, if we focus on belrestotug and why we believe we have the potential to be a best-in-class TIGIT PD-1 doublet. I would like to start with the summary, the recap of 2023. It could not have been a better year for us. First, there are several studies which has shown that TIGIT provides significant efficacy over a PD-1 or PD-L1 in different indication. Second, belrestotug continue to look like the highest quality TIGIT antibody, and we believe that this differentiation will be super important in order to demonstrate our clinical benefit. And we have also the combination with dostarlimab from GSK, which is shown to be one of the best PD-1 in current development. Third, we have learned that it's important to focus on specific indication where the biology of TIGIT will be highly impactful in terms of clinical outcome. And finally, we've also learned that the right study design and a high-quality doublet comparing to the standard of care will be important in order to generate robust data. We believe that our TIGIT program is set up for success and put us as a distinct advantage. Let's turn our attention to our first readout this year. GALAXIES Lung-201 is the largest study ever performed for a TIGIT antibody in frontline non-small cell lung cancer, and the most important readout that we are going to generate this year from our pipeline. This study is very robust. It will include 300 patients with a direct comparison with pembrolizumab, which is the standard of care. This is something which has been missing in other clinical trials. And because this study is so robust, it is allowing us and GSK to make near-term decision in our clinical development. We are going to get additional information about the dose justification that will be important for Optimus project. We are going to get information about the contribution of component. We are going to evaluate another triplet, combining dostarlimab, belrestotug, and an anti-CD96 antibody, another immune checkpoint of the TIGIT pathway. And we have also significant effort in the biomarker analysis.... Coming back to why we believe that it's important to get a highly differentiated doublet. Last year, I was standing here claiming that not all antibodies are created equal. Today, I'm telling you that we are seeing that play out. What we have learned is that in order to, for TIGIT PD-1 doublet to be succeed, you need a great PD-1, and this is what we have with the TIGIT dostarlimab, I will show you. But we need also a great TIGIT, and I will never stress that enough. You need to show that your antibody has quality target engagement, not only with TIGIT on one side, but also with Fc gamma receptor, which is a key regulator of immune response, in order to trigger a multifaceted mechanism for the tumor, antitumor response that will increase antitumor efficacy. We have also in a situation with GSK, where GSK is the only company which has compared their PD-1 dostarlimab with pembrolizumab, the reference PD-1. That make us very confident that we have a high quality doublet. Turning our attention to our TIGIT antibody, belrestotug. When we designed drugs at iTeos, we spend a lot of time determining that the best molecule we can obtain in order to give to patients. Here, we believe that we have selected an antibody with a unique epitope. It is translating into high affinity and a unique potency compared to the other antibodies in clinical development. We have also an antibody that has shown the best data so far in the phase I, compared to all TIGIT antibodies in clinical development. And finally, I want to attract your attention on the fact that we are the first and only TIGIT which has shown a TIGIT depletion at all doses. Why is it important? It is important because TIGIT depletion is going to reflect how effectively our antibody is activating Fc gamma receptor for the multifaceted mechanism. What you see here on the right panel is that our antibody, at a dose as low as 20 mg, in blue, is giving an 80% TIGIT depletion. Whereas when we compare to the competitors, BeiGene has reported a 20%-30% TIGIT depletion at a dose of 1,800 mg, almost 100-fold higher than the dose where we have seen a very important effect. Roche claimed they would have loved to see some TIGIT depletion, but were unable to report such data. We don't know for Merck, and Arcus Biosciences cannot see anything because they've decided to develop a silent isotype, we will have limited antitumor efficacy. This data are the reason why GSK decided to collaborate with us. Now, let's turn our attention to the second component, dostarlimab. This trial, which has been reported last year at the ESMO, it's important because this is the largest comparative study of two PD-1 inhibitor ever. What we see here is that in frontline non-small cell lung cancer, dostarlimab, in pink, compare, combined to chemotherapy, is giving a median overall survival of 19.4 months, which is four months better than pembrolizumab in blue. That illustrate how we have-- we are lucky to get access to a quality PD-1 backbone that will be integral to the success of our combination. Moving forward, if we go back to 2023 and the different data which has been released, by the competitor, the most critical one is this setup of data, the SKY-01, the Roche data released in last August, and this reveal a number of key insight. First, TIGIT is a validated target. You see that in red, the combination of TIGIT plus atezolizumab, or the tiragolumab antibody from Roche, TIGIT plus atezolizumab, is giving an increase of six months in the median overall survival compared to atezolizumab alone in blue. This is a data, this is validating TIGIT, and this is not any more any dispute about this clinical validation of TIGIT. What is also important is that this data are giving a baseline that we believe we can improve. First, with our high quality TIGIT PD-1 doublet, we believe that we can get better data after what I have shown you about our differentiated TIGIT and the excellent PD-1 provided by GSK. On top of that, we believe that the design of this trial can be improved, not only by using pembrolizumab as the control arm, that will allow to make a direct comparison between the standard of care and our doublet, but also by adapting the statistical design that will generate a more robust result. All of this learning here has been integrated in our coming phase III trial design. Moving to the next steps, where are we today? We are starting this first phase III in frontline non-small cell lung cancer. It's a competitive arena, but we believe that we could be in the top two in this indication. What is important next, is to consider that there are multiple other tumors that could be important for a combination of TIGIT with other standard of care, and we are currently working on this validation.... In addition, in collaboration with GSK and beyond this collaboration, we are evaluating other doublets beyond PD-1, but also triplets and unique triplets with the GSK pipeline. And finally, I'm very excited today because we've been able to identify a novel biomarker that we are currently validating in our study. And we believe that this biomarker is very promising, not only to select specific indication, but also relevant patient population. This is what we are going to do in the next future. If I want to summarize where we are today for TIGIT, on the left, I believe that we have the best quality TIGIT, with a very good PD-1 to combine with in order to have this best-in-class doublet. We have also the right partner, and with all what I've shown you in terms of design, the control arm, and what could be the power of the study, we believe that we have a strategic approach to select relevant indication in order to show a clinical benefit for the patient living with cancer. On the right, this is a summary of this fantastic deal with GSK. We have obtained a $635 million upfront payment for our phase I asset two years ago, and up to $1.45 billion in milestones. We have a co-commercialization deal in the U.S. and a 50/50 profit share. In addition, GSK is funding 60% of all the clinical costs. All this data together is allowing me to say that 2024 will be a year of significant momentum for this collaboration with GSK. Now, moving to adenosine pathway, which has been frustrating for many companies, I believe that iTeos stands on its own as a company that not only knows how to tackle adenosine-mediated immunosuppression, but also how to develop best-in-class compound to oppose it. Here on the left, I want to summarize how adenosine has been considered for decades as being important for T cell immunosuppression. In fact, adenosine has been described 20 years ago as being a key inhibitor of T cell function by binding to a receptor called A2A, adenosine A2A. And what we have done with our team, our R&D team, we have showed that indeed, this T cell activity is important, but we've also been able to show that adenosine A2A receptor in dark blue here, is playing a key role also on other immune cells like plasma cells and B cells. What we have done, we have developed the first A2A receptor antagonist, inupadenant, which is able to inhibit the receptor at any concentration of adenosine found in the tumor microenvironment. This is really unique today. On top of that, we have discovered a novel mechanism mediated by a transporter called ENT1, which is also expressed on T cells, B cells, and NK cells. And we have developed another inhibitor called EOS-984, that will allow us to modulate this mechanism of action, which is very important not only for immune cell activity, but also immune cell proliferation. And we believe that it will be a real breakthrough in the adenosine field. Moving to the main data set that you will see this year for adenosine, this is an ongoing randomized phase II, in second-line non-small cell lung cancer in patients who have been treated with immuno-oncology and who are chemo-naive. We believe it's a significant patient population with more than 15,000 patients in the U.S. The reason why we have selected this indication is because chemotherapy is known to increase adenosine at very high concentration and will inhibit the immune system to work with chemotherapy. We believe the combination of inupadenant with chemotherapy will restore the synergistic effect and will improve the chemotherapy response. In summary, you see here the key takeaway. As I told you, 2024 will be a defining year for iTeos. We are going to make progress on all the fronts. We are going to launch our first phase III in collaboration with GSK, and we are going to get two data readouts, one in the frontline non-small cell lung cancer, a second one in head and neck cancer, that will allow to compare our best-in-class TIGIT PD-1 doublet with the other competitor. For adenosine pathway, we are going to get a first read out in the second-line non-small cell lung cancer, and for ENT1, we are going to release at AACR later this year, the mechanism of action, and at the end of the year, the results of the dose escalation. And finally, I want to attract your attention that with $645 million, we have a cash runway that will allow us to go through 2026 and generate a significant amount of inflection points. I thank you for your attention. Great. Let's start with the Q&A session. For those of you who are in the audience, if you have any questions, you can raise your hand. We have runner on the floor. You can also submit questions on our portal as well. Hey, guys, it's good to have you all here. Maybe we'll start off with a couple questions on the TIGIT side, maybe before I turn it to the audience. What's the latest on your preparation work related to the phase III study in front line non-small cell? When could we expect a potential start for the phase III? And I guess, what are the gating factors to that start? Then, oh, should I push? No. Oh, no. You're good. Then, as I show you, we are at a stage where we are going to get, in the near future, a significant readout in the phase II GALAXIES Lung-201, and it's important for us to be data-driven. Then we have already seen some data, and we want to see more of this data set that will make us confident that investing into a very large phase III will be relevant. And this is where we are today. We are ready to launch this global study. We have some data coming in the near future, and that will be an important catalyst in order to move forward with a high confidence that we have the best-in-class TIGIT PD-1 doublet. So with GALAXIES Lung-201 and TIG-006 coming in later this year, first of all, what is the cadence? You know, which one will come first in terms of data flow? Do you want to comment? Sure. So at this time, we're guiding just to at some point during this year. We have ongoing discussions with GSK right now in terms of what's the right forum to disclose. Do we save it up for a more robust package at a medical meeting? Do we have an event where we disclose it? Do we do a top-line PR, saving enough for a medical event? So, we met with them just this morning to go over cadence details around disclosures, and if the data comes in, we'll have more information. It is important as we launch into TIGIT, as Michel mentioned, you know, a target that's had some wins and failures in it, that we go out with data demonstrating the conviction that we have for the plan that we're announcing. It'd be a joint decision of, you know, we're launching, and here's the data that supports that decision. Any questions from the audience? Thank you for the presentation. I have a question around the adenosine. So in response to chemotherapy, adenosine is upregulated. You know, how do you square that with the fact that in most settings, the chemotherapy, together with a PD-1 inhibitor, leads to higher response rates in non-small cell lung cancer? And would you be looking to use adenosine and to... You know, with a triplet combination in that setting, to get more out of that? Or what are your long-term thoughts on that? Yes. Then indeed, you can see what we believe that we can reach with this combination is that we can increase the immune response. We don't say that there is a complete inhibition of the immune response, and indeed, in this setup, in the low PD-L1, you see a benefit of PD-1 with chemo compared to PD-1 or chemo alone. We believe that the data supporting the fact that chemotherapy treatment is increasing at a high level, the mechanism that produce adenosine, and that is increasing the immunosuppression that you can find in specific indication. Then, we believe that this combination could be highly relevant in second line. Doesn't mean that we don't discard the fact that in front line, in combination with PD-1 plus chemo, it could also add an added value. When we think about GALAXIES Lung-201 and, you know, TIG-006, you know, how should we think about just what to look for? I mean, it seems that, you know, especially, you know, that there could be some read-through to how you think about the phase III design as well, right? So how should we think about, you know, from an investor perspective, what aspect of the readout should we focus on to get a better sense of how you're thinking about the phase III design? As I said, the phase III design is completed. We are ready to launch this global study. And we have learned a lot from the SKY-01 intermediate analysis from 2022 last August, from Roche. Here, what we want to see from GALAXIES Lung-201 is the confirmation that dostarlimab performs similarly to pembrolizumab, and that TIGIT is adding a significant benefit over the PD-1 alone. What's your thought about SKY-01's delay? Is there any read-through to how you're thinking about phase III? Oh, it has been a very interesting week, and it's interesting also to see that we have two different sides. We have people who are drama llama, saying, "Oh, it's a disaster. It's postponed again." And this morning, we are discussing with an investor, which is very well informed about TIGIT, and say, "Oh, fantastic news!" It's showing that they are waiting, they are event-driven, and it will increase the quality to be successful. Again, we have learned all what we need to learn from SKY-01. The final readout will be important to confirm the clinical benefit of TIGIT for the street. On our side, it is not impacting anymore what we are planning to do next. Remind us again, what is the latest thought around the trial design? How big is it? And you know, what should we expect in terms of, you know, potential arms, and any color you can give would be super helpful. Then I would say... When you compare the other trials, you have size between 600-1,250, depending on the design. Here we are going for a design that will be, in terms of arms, very similar to SKY-01, except that, as I said, it's important to use pembrolizumab as the control arm. We are going to get a second arm with the combination of dostarlimab and belrestotug. And with the learnings from SKY-01, we have powered the trial in order to be sure that we are going to generate a very robust data set. And you will see all the detail when we start the study. Okay. Any questions from the audience? You mentioned that there's biomarker work that you're working on to- Yes. You know, try to, you know, improve, also, you know, get another bump in terms of overall response with the TIGIT that you have. Mm-hmm. What does that, what does that entail? And given the number of trials that you have ongoing, how would you integrate that into your current strategy? Yes, and this is one of the big added value to work with, pharma partner, with some experience in that. iTeos, since I started this company 11 years ago, has invested a lot in conceptual medicine. As I told you, the data that we generated on Treg is the reason why GSK invested or collaborate with us. We have identified potential biomarker for adenosine pathway that we are currently validating. For TIGIT, we are in the same situation, and we are currently evaluating our best option to get a seamless integration of this biomarker when we have the relevant validation in order to be able to expand outcome of our phase III. Having said that, we are not going to wait to delay our start of phase III because we want to get the biomarker in. This is a parallel effort, and we are currently brainstorming what would be the best way to integrate the two together. How does the path look like for head and neck, head and neck SCC? You know, once we see the phase II update later this year, how should we think about the next step, you know, as you get closer to potential pivotal stage? Sorry, for head and neck? For head and neck, yeah. Yes. Then for head and neck, we believe that the biology is highly relevant for TIGIT. There's also this is also an indication where you have a very high concentration of Treg that would fit very well with our antibody. There are other indication where we have interest, but we decided to have additional characterization of this one. For the moment, we are testing different hypothesis where we have both the high and the low PD-L1 population, but we are also evaluating the doublet versus the triplets. When we start to get this data, and we could get some external data also from Roche with SKY-01, we'll be able to define what would be the most relevant strategy for phase III. I believe that we have to learn from the recent past. I mean, some companies decided to go blind in multiple phase III or big phase II without a very strong rationale, and now they are paying the price of that. We want to be disciplined in our investment and be data driven. Is there a question on the floor? Can you talk about the relative contribution of the Treg depletion over other therapies, and especially in light of kind of, you know, the Treg depleting activity of CCR8 or other Treg depleting therapies that have advanced into therapies? I, I guess, you know, how much of the additional activity you expect compared to other TIGIT therapies from the Treg depletion? Yes. Then what I want to make clear is that Treg depletion, as we have measured it, is more a PD biomarker for Fc gamma receptor engagement. Fc gamma receptor engagement will have multiple mechanism to trigger immune response, including cytokine release on top of Treg depletion. We have shown data where we have not only Treg depletion, but also exhausted T cell depletion. And interestingly, over the last few years, the different players have joined our rationale, saying that Fc gamma receptor activation is super important to have this multifaceted mechanism for TIGIT. What we want to see in the future is that this multifaceted mechanism will give the best possible response in patients. Some indication could be more relevant. Can we compare to what happened to ipilimumab? No, we are in a different situation. But recently, I heard this week that Gilead was super excited about their CCR8 program, which is the perfect example of a Treg targeting agent. Then we believe that Treg depletion has been undercover or underwhelmed by the initial data, especially the one related to ipilimumab. And there is more to come by understanding what Treg depletion can get as a clinical benefit relationship. Does it make sense? It does, yes. Thank you. Can you speak to the toxicity and the... Thank you. Can you speak to anticipated toxicities or what you've seen in the phase I for the adenosine pathway? Oh, yes. Then well, we have released data, and for adenosine pathway, well, we have two different mechanisms here. Independently, we have completed the phase I, dose more than 100 patients with a very clear safety profile. All the incidents that we have observed were unrelated to the drug by itself. Okay? Now we are moving to this combination with chemotherapy. We are currently completing the dose escalation part, which is important for Optimus, and we have a very clear and clean safety profile. For ENT1, we've been super excited because already at the first dose we have reached a very high target coverage, and we have a very nice safety window. Then we are very confident that we'll be able to move these two programs in combination with different standard of care. For TIGIT, coming back to the safety profile, I know that there's another company which claimed that the silent isotype will be beneficial in terms of safety profile. Well, dozens of patients have been dosed with an active isotype with no safety issue, and we don't believe there is any downside to use an active isotype. If inupadenant and EOS-984, you know, mechanistically, are they, do you see them both going into the same set of indications? Just how should we think about, you know, as you think about the phase I data, is this a program that you're gonna go into overlapping indications together so that, you know, you're gonna start putting these two assets in combination? We want to be very mindful about what we can do with these two program. The challenge of, of combining two investigational drugs is quite high in terms of clinical operations. For the moment, we are following two different rationale. A2A receptor could play a very important role by stimulating plasma cells, and that could be a different set of indication compared to ENT1, that will be more involved in immune cell proliferation. Yes, we are currently evaluating, and we have worked on that for several years. We are currently evaluating what would be the relevance of combining both of them, but for the moment, we are moving forward in parallel, and we will continue to evaluate if there is some rationale to combine both of them at some stage. Related to the phase I design for 984, you know, once you pick the RP2D, you're gonna get start doing pembrolizumab, pembrolizumab combination, right? Yes, and well, it's even a parallel track, in fact, and I know that in our deck, it's not well illustrated, but we have a design of the dose escalation. When we have clear dose, we can dose, we can test the dose below with the PD-1 combination. And what are the potential indications that you think would be great for, you know, the 984 approach in combination with PD-1? As I said, we are working a lot on the biomarker validation. We have a biomarker for A2A, which is, MUM1, marker of plasma cells. We've also obtained very nice data for biomarker on ENT1, and we will continue to evaluate if we should go for similar patient population or complementary patient population. What is important is that this pathway has been described more than 20 years ago, and it took 20 years, and finally, a few years for iTeos R&D team, to find this new mechanism that could be a breakthrough in the way that adenosine modulates the immune response. What's the latest on the expression assay for inupadenant? You mean the diagnostic tool that we are developing? Yeah. Then we are working. We have identified two potential biomarker, A2A receptor. We've been the first one to be able to validate an immunohistochemistry assay, to test in clinical samples, and with this data on MUM1. MUM1 is already being used as a biomarker in hematological cancer, will be easier to develop. We are integrating this MUM1 validation in the ongoing, phase II, A2A-005. How much of that work there reads through to 984? Does that set you on an easier path if you have to end up enriching for ENT-1 expression? Is there a... How much additional work do you anticipate? As I said, there are two different mechanisms which are currently pursuing. The MUM1 one is really specific for plasma cell and the role of inupadenant. Mm-hmm. And overall, I guess, how should we think about the next 24 months for, you know, the adenosine program, and the TIGIT program? I guess, in terms of data flow, what would be the key drivers in terms of news flow from our perspective? Well, we've laid out, you know, several times in the presentation, the next 12 months. As we look beyond that, the GALAXIES-201, that's, as Michel said, the largest phase II being run in TIGIT, 350 patients, so that data will just continue to mature and grow over time. With adenosine inupadenant, the data we're planning to disclose before the end of this year is from the dose escalation. So as we move into 24 months, you start to see the randomized portion of that data, and then 984 would move into the pembrolizumab combination if we continue to see success there. So it's really just a maturing of all the programs that we have ongoing. As Michel said, we're phase III ready. We wouldn't expect phase III data within that timeframe, but some really mature, really robust data across the portfolio. Would you partner off adenosine? And if so, what would be, you know, the ideal stage to begin that kind of conversation? Well, we have the ambition to develop a company with a commercialization strategy, and this is what we are doing in our collaboration with GSK. For adenosine, if at some stage we feel that a strategic partnership with a pharma will help us to accelerate, expand, and differentiate our clinical strategy, we will consider this option. But we believe that this pathway has been so frustrating for so many companies that we need to reach a clinical proof of concept before considering any strategic partnership. Great. I think that's it for us. If there's any question, the management team is on stage. Thank you so much for your time today. Thank you.