Okay, good morning, everyone. I'm Brian Abrahams, Senior Biotech Analyst, at RBC Capital Markets. Our next presenting company this morning is HOOKIPA Pharma, represented by their CFO, Reinhard Kandera, and their Chief Development Officer, Mark Winderlich. So Reinhard and Mark, thank you guys so much for joining us today. Thanks for having us here at the conference. My pleasure. So maybe just to kick things off, you guys recently provided an important update with a plan for the pivotal study of HB-200. Can you elaborate a little bit more on how you guys thought about the design for the pivotal plan? And I'm particularly interested to learn about how you thought about selecting the optimal patient population with regards to oropharyngeal, you know, patients specifically and those with high CPS scores. Bigger picture, how did you think about the plan going forward? Yeah, so, I mean, obviously, let's, let's start with the bigger picture. Yep. As you know, we've done a lot of work in monotherapy. We've shown independent contribution of HB-200. We've moved on in combining in first line with pembrolizumab. A year ago, we've published first results, 15 patients, very nice improvement over pembro alone, doubling of response rates. We've confirmed that with more patients, at ESMO and at ASCO. In an oral presentation, we will again show a bigger number of patients. So looking at all of the data and already seeing the good results from the initial data, we started thinking about the design of a pivotal Phase 3 trial. What we came up with and presented to investors last month is a result of a data analysis and our desire to bring this product to market as fast as possible, with a doable patient population, while still capturing the most significant part of the market. And I will let Mark comment on what this means specifically. What I want to point out is, as you know, we are going after the high CPS patients, above 20, which usually is 50% of the patient population. However, it's also important to note this from a strategic commercial perspective. When you look at the market potential, it's a lot more than the 50%, because the market is not just the addressable population, of course, but also the duration of treatment for those patients. We've seen in our data, but even in the pembro standalone case, it's very clear that the high CPS patients have a better outcome, more responders, more stable disease, which means a longer treatment duration. So I think with our strategy, we are capturing a very good portion of the market, well above the 50%. Got it. Maybe Mark, a few words on the specifics of data and design. Yeah, I mean, first of all, we were very pleased to see that we consistently over several cutoffs and more patients in the cohort saw the benefit of the combination versus pembrolizumab monotherapy, and also consistently seeing a more pronounced effect in CPS 20 and above. So there's also a biological plausibility for this, because these are the tumors where T cells better infiltrate, and the tumor fights back by upregulating PD-L1. But usually when pembrolizumab monotherapy, these T cells are not very functional. They are exhausted, or not very active. This is why we only see 20%-25% response rate in pembrolizumab monotherapy. Yep. So, and here HB-200 comes and delivers the polyfunctional high number of T cells very active. So this is why CPS 20 and above. Oropharyngeal, this is the subgroup or subtype of HPV positive head and neck cancer, which is most prevalent. And of course, going into such a population gives us also homogeneity in our trial design and again, a higher probability of success. Got it. And what are the assumptions that went in with regards to the magnitude of benefit that you hope to see, the powering of the study? And, and I guess how are you thinking about conduct? Like, how long will this take to get up and running and to ultimately conduct? Yeah. Yeah, it is a seamless Phase 2, Phase 3 study. The Phase 2 part, the primary endpoint is overall response rate, and the Phase 3 part is overall survival, the primary endpoint. It's 250 patients and the Phase 2 part in total and the Phase 2 part for ORR is approximately 50% of the patients. The readout we expect to be in 2026. Then, a potential filing for accelerated approval. This was agreed and discussed with the FDA just a couple of weeks ago. The assumptions are basically what we have seen with pembrolizumab monotherapy in multiple historical trials, KEYNOTE-048, KEYNOTE-012, in different subgroups, HPV positive, CPS 20 and above, always a rate in the range of 14%-25% overall response rate. A clinically meaningful difference would be everything 15%-20% above this threshold. This is what the trial is powered for, always with a little bit of a statistical safety margin, I would say, so that we can demonstrate statistically significant ORR difference in this Phase 2 part and then go for accelerated approval. Okay. That makes a lot of sense. Do you plan to pursue the trial, independently or in a partnership? So we plan to do this trial independently. We are preparing; we are ramping up the sites. We expect to dose the first patient in Q4. As we move along, as we get closer to commercialization, this is, of course, an asset where a partnership can be discussed. And we've seen interest from pharmaceutical partners to get engaged in this project. Okay. Great. I know we're coming up on some additional data for the HB-200 plus pembro combo at ASCO. As you've noted, it's going to be an oral presentation. So can you maybe talk a little bit about what we should be expecting at the meeting in terms of I know we've seen data from about 20 patients so far. How many more patients are we expecting to see? What's the additional follow-up? What are some of the key metrics that we should be looking out for? Yeah, sure. So as you said, the last data set we have presented was with about 20 patients. So now it's the number double the number of patients, approximately, 40 patients. We will give an update on overall response rate. We will also give an update on CR rate. This is important because of the depth of the response we want and hope to see. We will also show first durability data. So it's an approximately 6-month longer follow-up now and also preliminary data on progression-free survival and on overall survival. We will zoom in, of course, into the patient population with CPS 20 and above, because this is the patient population we are carrying first into a registration path. That's about half the patients? Exactly half of the patients, yeah. Great. Maybe to note this at ASCO, so this is one oral we will have in the main session of head and neck cancer. Then we have a second one. This is our IIT. Maybe you come to this later. No, no, but yeah, go ahead. I know. I think the oral is the main presentation of your data is on Tuesday, but then I know you'll have another, I guess, a brief. A rapid. This is a new category at ASCO, this rapid oral session, six or seven minutes or so. Yeah, tell us more about that. Yeah. Yeah, yeah, yeah. This is also interesting. This is our IIT with the University of Chicago with Dr. Rosenberg. And it's in the neoadjuvant setting, so not the metastatic setting, which we just talked about a few minutes ago. And it is the neoadjuvant setting in locoregional head and neck cancer. And here the University of Chicago will present first data on the safety, feasibility of HB-200 in combination with chemotherapy, neoadjuvant, curative intent, and to see do we get deeper responses in the combination to get to a higher cure rate and a lower relapse rate. Got it. Maybe going back to the presentation then in the non-neoadjuvant setting at ASCO. Will we also see updated information on intratumoral T cell infiltration and some of the other immune metrics that you guys have provided in the past? Yeah, we will have. What do we look out for there? Exactly. We will have new data, first of all, on the T cell response in peripheral blood, but also some data not in this presentation on biopsies because it's very difficult to get paired biopsies. You know, this is always the problem. I assume in the randomized trial we will have a few more just because of the higher number of patients. But what we will present is very nice data on T cell response on more patients. Again, the magnitude, also the functionality, meaning which cytokines are released by these T cells and which then fits nicely again to what we see clinically in terms of tumor shrinkage. You mentioned in terms of benchmarking for this population, a CPS high population, that from a response rate standpoint, it's in the range of about 20% for PD-1 alone. How should we be thinking about the benchmark for PFS as we kind of look towards seeing some of the longer duration data that we'll get at ASCO? What would we expect historically patients on a checkpoint alone to get to? Yeah, unfortunately, I mean, median PFS never has reached more than 2, 3, 4 months or so. This is because of the low response rate. So 20, 25%, that means a very high progression rate. So disease control rate also below 50% or at 50%, that means the progression rate is very high and the median of PFS is reached within the first cycles, so to say. And this is unfortunately true for CPS 1-19, but also for CPS 20 and above, also in oropharyngeal HPV-positive cancer. If you look at real-world data or the subgroup analyses, this is the benchmark. In some publication it goes a little bit higher, like 5-6 months. But this would be, so to say, the benchmark. Got it. Okay. And do you think that the vaccine works, the therapeutic vaccine will work in CPS low patients as well, or just not as well as the CPS high, or is the efficacy really concentrated in the CPS high population? No, we see benefit in CPS 1-19 as well. Just as a reminder, KEYNOTE-048, CPS 1-19 had a response rate of 15% or 14.5% and a CR rate of 3%. We see benefit of the combination in this combination in this CPS subgroup as well. It is not as pronounced. So we think the synergy is also there, but not as high as in CPS 20 and above, which again, biologically, makes a lot of sense if you think about the defense mechanisms. And I would also like to add that this is early data. So the 1-19 group in our patient cohort requires some further investigation. We continue to enroll patients in the trial. By coincidence, our 1-19 happens to be a 1-10. So essentially all of the patients are at the CPS score below 10 coincidentally. So it's a bit difficult to assess, at this stage of the trial, the true benefits. And we're sure we can provide further updates. But yes, we do see benefit. How, how tough was it to get an oral presentation at ASCO for a relatively, you know, early to mid-stage study without that benefit? I think the data speaks for itself. It's strong data. I think ASCO is also recognizing the modality as a whole. There are other companies showing similar approaches or in one session, which is actually a separate session from a general head and neck session. So, I think the modality of targeting HPV positive head and neck cancer is in the meantime well recognized. There is a clear benefit. We think we have very nice competitive data. We think we have a well-defined FDA agreed path to licensure, so hopefully being the first in that cohort. But the oral session, I think, is an evidence that the benefits of those treatments and ours in particular is recognized by the medical community. Good. Yeah. It's, I mean, as Reinhard said, separate sessions. So EGF receptor, for example, targeting next generation compounds are in a separate session, general head and neck cancer. And the field is differentiating and clearly acknowledge the fact that HPV positive versus HPV negative head and neck cancer are two different disease entities with biologically distinct features. And this is how we see the development will continue in the next couple of years. And here, HB-200, yeah, is at the forefront. One of the questions we get frequently is how reliable, how reliably matched the historical data is. So I guess what's your level of confidence that there aren't any sort of major changes in the patient characteristics or the way treatment is practiced today versus when some of the checkpoint studies were done, such that we can pretty reliably use, you know, a 20%, 15%-20% response rate, low CR rates, two or three months PFS as applicable to this same HPV-positive population with a CPS-high population that you guys are comparing it to in an open-label basis? I mean, the answer is twofold. One is there were also more recent studies like the LEAP-010 study and there, pembro mono had a 25% overall response rate. Secondly, pembrolizumab is now around for many years. And physicians know very well how to manage side effects. The standard of care has not changed a lot, or not at all in terms how side effects are managed. So to keep the patients on treatment. Also, when we talk to physicians, that's what they confirm to us. Plus the new studies, also with, I mean, other checkpoint inhibitors targeting PD-L1 like Regeneron's, for example, which are not approved in head and neck cancer, but the same mode of action. And what do they see? 20%-25% overall response rate. So we feel very comfortable with the data, very consistent, and we feel very comfortable with the data we see. There are also recent Black et al. real-world data studied also in the subgroups or subentities of oropharyngeal squamous cell carcinoma. And their progression-free survival, overall survival, still very similar to what has been reported in KEYNOTE-048 and KEYNOTE-012. So there's not a lot of change. Okay. Good. And then, you know, you mentioned AEs. So just maybe speaking of side effects, what are you guys seeing overall with HB-200? I guess what's your what's been the safety profile on it repeated administrations? What's your level of confidence that this will continue to have a clean safety profile? Yeah. Yeah, we are very pleased with the safety profile. So what we see is no meaningful additional toxicity over pembrolizumab monotherapy. And what we see is in the first cycle, so 1-2 first doses, flu-like symptoms like fatigue, some pyrexia and muscle aching, but all mild, grade 1-2. And this is, I mean, actually good because it shows the immune system is activated, but patients can deal very well with it. And then, once the immune system has built their response in the next cycles, the flu-like symptoms are gone. And importantly, there is no added incidence of immune-related adverse events, which are pembrolizumab related. So therefore the safety profile is really good. As for a vaccination expected flu-like symptoms, we see the immune system is strongly activated. Got it. Good. Maybe in the last five minutes, we'd love to shift gears to some of the rest of your pipeline projects. Maybe can you give us an update on some of the collaborative projects, namely, HB-400 and with Gilead and HB-500, in HIV, and then maybe talk about your plans, with respect to HB-700 and 800, which were previously part of the Roche collaboration. So happy to do that. As you know, our strategy, in fact, this is progress on programs in partnership. Our partnership with Gilead is working very well, also evidenced by Gilead becoming now a 20% shareholder, invested at a significant premium to market price, in December. Both programs, the hepatitis B program and the HIV program, are progressing very well. The hepatitis B program has been handed over to Gilead for clinical development. So any timing updates and data releases are up to Gilead to decide. The study started in early 2023. So Phase 1 data should be available in the course of this year and expected decision from Gilead whether to move into Phase 2, which would represent the next milestone in our collaboration. As you know, we've shown excellent data at conferences on preclinical models. We've seen multiple times that our vector technology is able to stimulate significant T cells. And this is really what we want to see in this Phase 1 in healthy volunteers as well as chronically infected patients. We are confident and it's obviously up to Gilead to decide if the thresholds that they expect to see will be met. On HIV, we have agreed that HOOKIPA is running Phase 1 and Phase 1b study. We've received all clearance from the FDA. We are in the stage of activating the first sites. And we expect the first patient in this study to be dosed still in this second quarter of 2024. So both programs, I would say, progressing very nicely. Just to give the bigger picture, these are both programs within the Hepatitis B and HIV cure efforts of Gilead. The intent is to combine with other modalities to provide ultimately a cure to those devastating chronic infectious diseases. With today's drugs, we can keep viral loads under control. And Gilead is certainly the leader in the field. But the ambition is really to start curing patients permanently from those viral infections. And Gilead believes that T cell therapy with high numbers of specific T cells is a key to success for these cure efforts. Great. Other programs, of course, our technology is broadly applicable. We think with HB-700 we have a great asset in hand. We have strategically decided to take the company to the next step with HB-200, focusing our spending on HB-200 on the pivotal trial without increasing our burn rate, which in a still difficult funding environment in biotech, we think is the right thing to do. So HB-700 could be a program for partnership. We are in discussions, but we are also looking at ways to progress the program into maybe a smaller first clinical study, if an attractive partnership does not arise in the near future. Great. Yeah. Yeah. And I'm personally very excited about the HB-700 program. KRAS mutations are the driver of many tumor types. And there is a lot going on in KRAS inhibitors. And a KRAS mutation vaccine, cancer vaccine would be, I think, a great addition in this development. Great. Well, thank you guys so much. We're out of time, unfortunately, but looking forward to the data in just a couple of weeks. Will we see, should I ask, will we see anything new in the abstract next week or will most of the data be at the presentation? No, you will also see some new data with an interim cutoff, so to say, in the abstract as well. Great. Well, looking forward to that. Thanks again. Thank you. Thank you. Thanks.