Good morning, welcome to the BioInvent KOL event. At this time, all attendees are in a listen-only mode. A live question and answer session will follow the formal presentations. If you'd like to submit a question, please use the Q&A text box below the webcast player. As a reminder, this call is being recorded, and a replay will be available on the BioInvent website following the conclusion of the event. I will now turn the call over to Martin Welschof, CEO of BioInvent. Please go ahead, Martin. Thank you very much, Wilson, welcome everybody to our BI-1808 Ovarian Cancer KOL event. We're very happy to have with us today Dmitriy Zamarin, MD, PhD, and I will do later a more detailed introduction. Before I do that, I will briefly highlight what we're trying to cover today, which is here on the agenda, as you can see now. I will start with some introductory remarks. I will hand over to Dmitriy, and he will talk about the ovarian cancer treatment landscape, the medical need, future treatment of ovarian cancer. Really looking forward to that. We will hand over to Björn Frendéus, our CSO, and he will really talk about the differentiated mechanism of action that we have for BI-1808, which I think will be also very interesting, and we just recently uploaded, actually, a manuscript that describes that in detail. That will foll ow by Andres McAllister, our Chief Medical Officer, and he will talk about the clinical data that we have to date, and that also will be presented at ASCO. He will hand over back again to Björn, who will then have some more translational data, specifically highlighting the dynamics of responses, which is also very interesting. Towards the end, Sylvie Ryckebusch, our Chief Business Officer, and she will talk about the market opportunity as we s ee it for 1808, and then we have some final remarks and Q&A. I was already introduced, but anyway, so my name is Martin Welschof. I'm the CEO of the company now for almost eight years, and indeed looking forward to very, very exciting times. As I said, a quick and more detailed introduction to Dmitriy. Dmitriy is an MD, PhD, and he is Professor of Oncology, Section Head of Gynecologic Medical Oncology, and Co-director of the Center of Excellence for Gynecologic Cancers at the Tisch Cancer Center at Icahn School of Medicine at Mount Sinai, and has served as a principal investigator and a translational chair on multiple institutional and cooperative group clinical trials, exploring novel immunotherapy combinations in gynecologic cancers and other solid tumors, actually. Serves also as the translational research co-chair on the NRG Oncology Cervical Cancer Committee. His research is very much focused on understanding of mechanism by which gynecologic cancers are recognized by the immune system and on the identification of biomarkers that could be predictive of response and resistance to immunotherapy. Dmitriy, welcome, and I'm really looking forward to your presentation. As already mentioned on the schedule slide, the agenda slide, we will have Björn Frendéus, our CSO, that you can see on the left-hand side. In the middle, you see Andres McAllister, Chief Medical Officer. Last but not least, Sylvie Ryckebusch, our Chief Business Officer. Before we start with Dmitriy, what we are really trying to do is to develop a new standard of care for recurring ovarian cancer, as we will show you later in more detail. That is actually also commercially very interesting since it addresses a very high unmet need. Based on our initial commercial analysis that we have done, we expect a $1.5 billion in estimated peak sales. At BioInvent, we are developing the next-generation IO therapies that are really designed to address one of the biggest remaining unmet needs in cancer treatment, which is the tumor microenvironment. That's our main focus. As you will know, checkpoint inhibitors have created a major oncology market, but there's still a lot of patients that do not really benefit of that. Also, as you know, large pharma is really looking for the next-level immune modulators since the IO combinations that are used at the moment are ahead of patent cliff, as I will show you also later a little bit more in detail. We have two first-in-class compounds, BI-1808 and BI-1206. Today, obviously, we'll talk about BI-1808, that target immune resistance beyond current therapies, as we will show you for BI-1808, at least today. We have very strong anti-tumor activity with a very favorable safety profile, which is very important, especially when you want to treat advanced cancers. Beyond this, we have the potential to enhance on the efficacy and durability of existing immunotherapies, and I will discuss that today as well. We are quite integrated company, as you might remember. We have a very proprietary human-first platform, which is a reverse phenotypic screening that allows us actually to identify new mode of actions, as BI-1808 targeting TNFR2. We have multiple phase II studies with upcoming readouts, and I will come back to that later a little bit more in detail, and proven strategic partnerships backed by leading global healthcare investors. Just very briefly, this is actually a slide that covers all the IO market, not only the immune modulators, but also something like ADCs and bispecifics. You can see it's a huge opportunity, still growing. On the right-hand side, you see the bottlenecks, right? There are quite a number of bottlenecks, and we are actually focusing on the number one bottleneck, which is the immunosuppressive tumor microenvironment. So with 1808, we have something that modulates that from a tumor-friendly microenvironment into a tumor-hostile microenvironment, and we'll come back to that in more detail later. This is basically showing you a couple of programs with a handful of large pharmas for anti-PD-1 as well as anti-PD-L1 that are all facing patent cliffs and obviously have generated a huge income for those companies, but of course also help patients, and we need something new, and we think with 1808, we have that in hand. We feel that we can really help to unlock the full potential of IO. Why do we think we can do that? We can increase response rates, and we have shown that already. We'll discuss that in more detail later. We have a very favorable safety profile, which of course enables a much broader use and combination, which I think is very important, especially when you think about more advanced cancers. We deliver deeper and longer-lasting responses, and that would be something that Andres McAllister will address also in his presentation. The key word there is progression-free survival, where we already have quite interesting data, even at this early stage of the clinical development of 1808. Obviously, as I already mentioned, we target resistance in the tumor microenvironment. As such, we have many avenues to unlock the full potential of IO. Before I hand over to Dmitriy, just very briefly, a quick look onto our portfolio, and I will start from the bottom. There you see our FcγRIIB platform. The lead compound that we have there is BI-1206, which is a subcutaneous formulated antibody to a 2mL injection. This antibody we currently develop in non-Hodgkin lymphoma, as well as in non-small cell lung cancer and uveal melanoma. The non-Hodgkin lymphoma actually will be presented at EHA and also highlighted in the KOL event ahead of EHA. Of course, the main topic today, BI-1808, targeting TNFR2, and I leave all the biology and mode of action to Björn, but it's a really super cool, very interesting mode of action. Today, obviously, we'll discuss the ovarian cancer data that will be also presented at ASCO, but we also have very strong, compelling T-cell lymphoma data, and that will be presented also at EHA and also in the conjunction of the KOL event. I think this is the introduction that I wanted to do. Dmitriy, I will hand over to you, and please take it away. Thank you. Fantastic. Thanks so much. What I was hoping to do here today is really to just give you a brief overview of the current treatment landscape of ovarian cancer altogether, and then specifically, we'll focus on what we call platinum-resistant ovarian cancer, since this is probably the highest unmet need opportunity and probably the first point of entry for the majority of newly approved drugs at this point. Just as an introduction, the ovarian cancer is a cancer that typically starts not actually at the ovary, but more commonly starts at the origin of the fallopian tube. It's a little bit of a misnomer, this is something that we have come to recognize over the past decade or so. The problem with ovarian cancer is that we unfortunately still don't have good screening strategies. In fact, we have zero screening strategies for this cancer. Even though the cancer progresses through the stages that are indicated on this slide, meaning stage 1 is just ovary confined, stage 2 is the cancer that's confined to pelvis, stage 3 is the cancer that's now metastasized to peritoneal cavity, and stage 4 is the cancer that has spread beyond the peritoneal cavity or to organs. Essentially, the majority of the patients present with this stage 3 or stage 4 disease, which is a major therapeutic challenge for us because as you can imagine from many other cancers, once you present with the metastatic stage, and stage 3 is considered to be a metastatic stage, in most cases, the cancer is not curable. This is essentially probably the most important slide to cover the entire presentation, and this is how we treat ovarian cancer today. As I mentioned, the majority of the patients present with this widely advanced disease, where they may come in with these vague symptoms of bloating and then eventually develop marked ascites as shown in the picture on the right. If you look in the abdominal cavity, which is the picture on the bottom right, is essentially this is what you see. You see this significant peritoneal carcinomatosis. These are the cancer nodules that have spread through the peritoneal cavity. As you can imagine, this disease is difficult to resect. What happens for these patients is that either they undergo initial cytoreduction surgery, followed by adjuvant chemotherapy, or more commonly now, they start with a neoadjuvant chemotherapy, followed again by surgical cytoreduction and then more adjuvant chemotherapy. While the majority of these patients will achieve what we call initial remission, most of them will have some minimal residual disease, and over 80% of these patients will eventually experience a relapse. If the relapse after the initial chemotherapy is after six months, we call it the platinum-sensitive recurrence, meaning we can treat these patients with the platinum-based chemotherapies again. If the relapse is less than six months after the initial chemotherapy, we would call it a platinum-resistant disease. Unfortunately, the majority of the patients will eventually develop this platinum-resistant disease because even those who get treated with a platinum-sensitive recurrence with more platinum agents eventually do become resistant. This is the one that the highest area of therapeutic need because from the moment of development of platinum resistance, we used to estimate the survival of these patients on the order of about 12 months. We have some newer agents there that I'll highlight in a few slides that probably extends that survival to maybe 1.5 to two years. Again, nevertheless, most of the patients will progress on these therapies and certainly need other new agents. This is the summary of how we treat ovarian cancer. As I mentioned before, the newly diagnosed patients will get carboplatin with paclitaxel chemotherapy. Some of them will also get Avastin. If the patients have evidence of BRCA mutations or what we call homologous recombination deficiency, they may also get a PARP inhibitor maintenance. As I mentioned before, most of these therapies are not curative. Over the past 25 years, while we have extended the survival of these patients, unfortunately, the number of patients that we are curing has not changed. Despite the receipt of the maintenance with the PARP inhibitors or bevacizumab, most of these patients will experience a relapse. Once they experience a relapse, if it's a platinum-sensitive recurrence, they will again receive a platinum doublet chemotherapy, possibly with maintenance with bevacizumab. We don't really use PARP inhibitors in the second-line setting because even though they initially had an approval here, subsequent data have demonstrated that they do not improve overall survival, and in fact, there are data to suggest that use of PARP inhibitors in this setting may actually decrease survival, possibly due to development of cross-resistance mechanisms that make them less sensitive to subsequent chemotherapies. Then once the patients eventually develop platinum-resistant recurrence, I have listed the drugs here that we can use, and I'll go over these studies in a moment. One is an antibody drug conjugate called mirvetuximab soravtansine or ELAHERE. This is an agent approved for folate receptor alpha positive cancers, which is approximately 35% of all cases based on the cutoff that they use. We have a new approval of pembrolizumab or KEYTRUDA in combination with paclitaxel, with or without bevacizumab for cancers that are expressing PD-L1. We also have a new approval now with a drug called relacorilant, which is a glucocorticoid receptor antagonist in combination with nab-paclitaxel. Our standard therapies include single-agent chemotherapies with or without bevacizumab, and also for patients that have HER2 positive cancers, we could use trastuzumab deruxtecan. Again, I want to highlight here that irrespective of these therapies, virtually all patients will eventually experience disease progression. Here, over the next few slides, I just want to highlight what is the evidence of efficacy that we see from these trials. This is probably the first drug that was approved in the platinum-resistant setting that has demonstrated overall survival benefit. This is mirvetuximab soravtansine. It was approved a few years ago based on both improvement in progression-free survival and overall survival in patients with the platinum-resistant ovarian cancer. Here you can see the curves. The curves do separate nicely, suggesting that this antibody drug conjugate is certainly benefiting these patients. Yeah, uniformly, you can see that these patients are not cured, right? Virtually all of them will eventually experience disease progression and require further therapies. This is the standard chemotherapies that we use. This is on the basis of AURELIA trial that was now reported in 2014, which is where we had the standard treatments that we have had for the patients were chemotherapy, single agents, either paclitaxel, gemcitabine or liposomal doxorubicin or topotecan. This was the trial that essentially put bevacizumab on the market where the patients were being treated with these single-agent chemos, with or without bevacizumab. Here are the drugs that are listed here. What I wanted to highlight from this study is essentially out of these three chemotherapies, combination with bevacizumab was shown to be beneficial with all of them, but paclitaxel clearly emerged as the winner. You can really see that the response rate in combination with bevacizumab and progression-free survival was significantly longer in the paclitaxel arm. I'm highlighting this slide because this is the drug that has been used as a potential base for further combinations, including the combinations with immunotherapy and relacorilant. This is a newer data. This is the data that were just presented earlier this year. Well, actually, they were presented initially at ASCO last year, but the publication came out this year and we just had an FDA approval. This was a phase III trial of nab-paclitaxel with glucocorticoid receptor antagonist relacorilant. Essentially, the idea here is that the glucocorticoid receptor signaling in ovarian cancer cells mediates chemoresistance and blockade of the receptor can actually resensitize the cancer cells to the effect of paclitaxel. It's an oral agent by itself. It has essentially zero activity, but when combined with chemotherapy, it did demonstrate prolongation of progression-free survival, shown here on the left. More importantly, overall survival. There was approximately a four-month improvement in overall survival, which is what led to the approval of this drug, again, in combination with nab-paclitaxel for patients with platinum-resistant ovarian cancer. This is now an option for our patients. Another key therapy that I want to talk about today is, of course, immune checkpoint inhibitors. This is the class of drugs that unfortunately has not seen to date as much success in ovarian cancer. I'm not going to go through all of these trials here, but if you look at the column number three, you can see the majority of those were phase III clinical trials, and they have used either single-agent immune checkpoint inhibitors, and here I'm really highlighting just PD-1 or PD-L1 inhibitors, either alone or in combination with chemotherapies, including platinum-based chemotherapies. Really only a single trial, which is all the way on the bottom. This is the KEYNOTE-B96, pembrolizumab with paclitaxel and with or without bevacizumab. Essentially, this was a trial that was deemed positive and resulted in approval of pembrolizumab for patients with platinum-resistant ovarian cancer. Here are the data from the trial. You can see that despite the statistically significant improvement, both in progression-free survival and overall survival, data is still not great. Right? If you look at the progression-free survival curves on the left, both in the PD-L1 positive tumors and in the overall population, you saw progression-free survival improvement of approximately one month. This is not the reason that the FDA approved it. The reason for the approval was for the improvement in the overall survival, which is seen in the curves on the right, and specifically in the PD-L1 positive population, there was approximately three-month improvement in OS. Again, for these patients whose tumors express PD-L1, this is certainly a treatment option. Again, I want to highlight that all of these curves coming down, these patients are not cured. We know that a good portion of them can derive a very durable benefit, which is typical of immunotherapy trials. Unfortunately, still many of them are resistant to these agents. What's in the future for checkpoint inhibitors in ovarian cancer? Well, we know that, again, these cancers are not completely immunologically cold. We know that combination therapies in these cancers can improve both response rate and progression-free survival. This is an example of a study that we have actually done through NRG Oncology, which was a randomized trial of nivolumab, an anti-PD-1, nivolumab, and ipilimumab, which is anti-CTLA4. We could double or even triple the response rate, and you can see there are a number of complete responses which are quite durable. Again, it highlights that ovarian cancers do have an ability to respond to immunotherapies. They're not fully immunologically cold. We can modulate the endogenous T cell immunity in these cancers. This was not the only trial that demonstrated it. Now, this is a newer generation of, again, CTLA-4 and PD-1 inhibitors from Agenus demonstrating similar data. A combination of anti-PD-1 and an CTLA-4 in platinum-resistant ovarian cancer does exhibit a higher response rate here. The response rates were also similar to the ones we have observed with the ipi and nivo. I'm not necessarily highlighting CTLA-4 agent as the agent to use because it is associated with significant toxicities. The key point to show these slides is to demonstrate that these are immunogenic cancers. We just need to learn how to harness that immunogenicity. Other classes of immunotherapies are also being investigated in ovarian cancer. There's a lot of interest in T cell engagers at the moment, and one of the hottest targets that we have is claudin-6. There are several companies that are developing claudin-6 bispecific engagers. These are the publicly reported data from BioNTech. Here is a claudin-6 bispecific engager that was actually delivered by their liposomal preparation of a nanoparticle encoding an mRNA expressing the bispecific engager. Not necessarily in need of this technology to deliver this class of agents. Nevertheless, what this slide does highlight specifically in the patients with ovarian cancer is that these kinds of agents can have some activity, although the response rate in this study was relatively modest. Nevertheless, these patients can respond because they do have T cells in their tumors. Here are other therapies that we currently have on the horizon. Just like in any other cancer type, there ha s been an explosion of ADCs against the targets that I have listed here, such as cadherin-6, folate receptor alpha, TROP2, claudin-6, NaPi2b, and some others. These have demonstrated very impressive response rate. Some of the newer agents have response rate over 50%. Some of these can be durable. The key disadvantages that we have with the antibody-drug conjugates is that currently they really just utilize two main payload classes, which are either Topo1 targeted or tubulin targeted. The emerging data seem to demonstrate that there is cross-resistance between the different ADCs that have the same payload, meaning the resistance to ADCs is likely not driven by the loss of the actual target, but rather by development of resistance to the chemotherapy. In fact, most of these clinical trials at the moment will exclude patients who have received prior ADC that have the same payload, which makes it very difficult to enroll patients to these clinical trials. As you can imagine, if we have a patient who has received a HER2-targeted agent such as ENHERTU, which is FDA-approved, they can no longer go on these studies. The second major disadvantage actually is that despite being antibody drug conjugates, which we think of as targeted therapies, the toxicity profiles are actually quite similar to chemotherapy for many of these agents. In fact, patients who are receiving weekly paclitaxel tolerated better than the majority of these ADCs. The ADCs are not all they are set up to be. They have a lot of toxicities. I mentioned the T-cell engagers on the previous slide. I think there are some promising signals of activity in some studies, but these are still pretty early. Same goes for the adoptive cell therapies. We have seen some early promising signals of activities in some studies, but these have been difficult to scale. Most of these are sort of slowly moving along. Again, major data are yet to be presented. Targeted therapies, of course, where we saw a lot of excitement with initial development of PARP inhibitors. There have been other agents targeting the DNA damage repair pathway in ovarian cancer, such as WEE1, ATR and CHK2. Again, there have been signals of activity for these drugs, either alone or sometimes in combination with PARP inhibitors. These have been difficult to implement just because of significant hematologic toxicities that many of these drugs carry, particularly when used in combination with PARP inhibitors. I think the future for these therapies will really be in a biomarker-driven fashion. Some of these studies are being conducted currently, specifically by selection of the patients with specific mutations such as, for example, cyclin E amplifications or homologous recombination deficiencies. I think this may be my last slide. Yep. I can stop here, and then we can take questions later. Yeah. Exactly. Thank you very much, Dmitriy. I think we switch over now to Björn, and Björn will highlight, as I already mentioned, the mechanism of action. Please, Björn. Thanks, Martin, for that introduction, and thanks Dmitriy for a great introduction to ovarian cancer and the current treatment landscape. At BioInvent, we're dedicated to discovering and developing antibody-based drugs for cancer immunotherapy. My background is, of course, that these types of drugs have transformed cancer survival, and they're continuing to do so. This is reflected by sort of the T-cell-infiltrated hot tumors where immune checkpoint blockers shown in the left graph are inducing long-term survival and even cure in patients that previously had no hopes of surviving. This long-term survival and curative potential of these drugs is indicated by a flattening of the survival curve from three years and onwards. Has been shown to correlate with these drugs' ability to actually clonally activate CD8+ T-cells of the immune system to seek out and destroy different cancer cells that are differently mutated. Accordingly, these drugs are approved for treatment of more than 30 different types of cancer. As has been introduced by Professor Zamarin, it has been difficult to use these drugs in so-called cold types of tumors that are not robustly infiltrated by CD8+ T-cells. I think certainly by that definition, ovarian cancer fulfills this cold tumor type. Until recently, so a few weeks, you would say even months back, three months back, for the first time, an IO regimen was approved for treatment of ovarian cancer. Not only did this show increased survival activity compared to other tested modalities, including the ADCs that Professor Zamarin mentioned, but also bispecific antibodies, but it came with that flattening of the survival curve, indicating potential for long-term survival and even cure when combined with other things. As great as these drugs are, we do need to improve. Let's see. What we need to come up with is, again, on the note of safety, drugs that are really safe that can be added to the existing state-of-the-art. When they're added, they need to be powerful, of course, both alone and such that they enhance the overall survival activity in these new combinations. This is not a trivial task. Many companies have pursued multiple different targets and few things, admittedly, have come out of it. Why are we so interested and excited at BioInvent in developing immune modulatory antibodies? Well, of course, it comes down to data. What we've found in using BI-1808, our antibody, is that TNFR2 seems to be a particularly promising new type of immunoreceptor that can be safely targeted by our BI-1808 compound to induce tumor regression in various types of cancers, including those of cold type, in a manner that correlates with activation of this critical CD8+ T-cell anti-tumor immunity. Our data suggests that these powerful effects derived from the antibody's highly differentiated mechanism of action. Not only does it delete the most immunosuppressive CCR8 positive T regulatory cells, but it also activates and reprograms the myeloid cells to call for CD8 positive T cells to come into the cold tumor setting, and actually also in other types of settings, to combat and kill off the cancer cells. You can appreciate from this graphic that our mechanism acts indirectly to activate the CD8 positive T cells, and this in contrast to anti-PD-1, which acts directly on the CD8 positive T cells. This means, of course, if we combine the two drugs, we may expect to get even better activity. This is exactly what we find. If we look in the most resistant preclinical models, this is a B16-F10 model, which is poorly infiltrated by CD8 positive T cells and accordingly does not respond to anti-PD-1 or anti-CTLA-4. We find that when you combine anti-PD-1 with our drug, we actually induce curative responses in a significant fraction of the animals. Not only have we seen combinatorial activity with anti-PD-1, but also with paclitaxel, the other component of that recently approved IO immunotherapy approved for treatment of ovarian cancer. Very importantly, our drug is also active in patients. This is steaming fresh data from the lab showing that in ovarian cancer patients that are being treated with single agent BI-1808, shown in red lines in this graph, our antibody does induce T regulatory cell deletion. It induces serum cytokines that are associated with effector T cell activation, such as interferon-gamma, CXCL10, also macrophage activation, compellingly IL-12, and even cytokines that are associated with tertiary lymphoid structures that are known to predict survival in response to immunotherapy. Further consistent with our mechanistic characterizations, when we combine our drug with anti-PD-1, we're seeing these interesting effector responses being enhanced. With that, I'll leave it to Andres to take you to our really exciting clinical development piece. Super. Thank you. Thank you. Right on. Yep. Thank you, Björn. We'll be describing what we have been doing from the clinical standpoint and show you where we stand. We are very happy about these results and happy to describe them to you. This is the study schematic. We started dosing BI-1808 as monotherapy, and we are able to go up to 1,000 milligrams. That was already very good news because, as you have understood from the previous speakers, safety here is a key issue for these patients. When we dosed BI-1808 as monotherapy, we did not see any grade 3 or grade 4 adverse events related to BI-1808 treatments. Even at the highest dose, we saw no serious adverse events related to the drug. We decided to move forward, treat a few more patients to make that certain, which we did. We're here also using BI-1808 every three weeks, so very much aligned with what pembrolizumab does. We then moved on to three different expansion cohorts. One little bit of a basket study where we try the agent in different indications and different tumor types. Our monotherapy expansion cohort in ovarian cancer and one monotherapy cohort in T-cell lymphoma, and more specifically about CTCL, cutaneous T-cell lymphoma, which we have actually moved forward into dose optimization part of the study. As Martin mentioned, we will be communicating a little bit about where we stand on that respect in a couple of weeks from now. When we first determined that the drug was safe, well-tolerated, then we were able to start the combination with pembrolizumab, depicted here in part B. Pembro, we started dosing at 225 milligrams, but we're able to dose up to 1,000 milligrams, knowing that dose provides full receptor occupancy for definitely for the three weeks, but probably much longer. Given the safety profile, we decided to move that same dose, so 1,000 milligrams, into the same type of expansion cohorts. The one, of course, that we will be discussing here is our results in ovarian cancer, which will be a matter of excitement for us. Basically, what we have seen in these heavily pretreated patient populations. I'd like to stress that point because these are patients, as opposed to many of the patients, for instance, in the KEYNOTE-B96 study, these are phase I patients, so patients who have been through just about every possibility and exhausted every therapeutic possibility. These are the patients that you get in your study. In that patient population with no chemotherapy here, just please note that as well, we saw an objective response rate of 24% out of 25 evaluable patients. The patient with a complete response, five patients with a partial response, and several disease stabilizations that have lasted for a good amount of time. It's important to know that platinum, the previous lines of therapy are important in our study. This has been shown already for ovarian cancer, how each line actually decreases the PFS, et cetera, for each particular line. In our study, we had one to 10 prior lines. The median was five prior lines of treatment, we still saw responses in those patients. Very, very exciting data. Here is the waterfall plot of our study. You see the magnitude of the responses there. By the way, something that we, in this study, we are aiming to recruit 40 patients, which have actually pretty much already been recruited. By the end of the year, we should have the dataset for the 40 patients that we aim to recruit in this particular phase. That's already pretty much ongoing, and that will be a good readout by the end of the year. In the meantime, with these 25 patients, we took a stab at trying to understand the duration of responses or characterize somehow the duration of those responses, understanding that we are not yet, that this is not finished, that several of these patients, actually nine patients, are still on treatment. We took a first look at how the PFS would look like, and that is actually at 10.3 months right now. Very exciting for this patient population and with two agents and no chemotherapy. We are very excited about that. Just a word about safety, because as mentioned before by Professor Zamarin and also Björn, safety is of the essence here, and it's actually what contributes to the quality of life of these patients. When you use BI-1808 in monotherapy, this is basically what you see. Basically, grade 1 and grade 2 adverse events. This is out of 62 patients, it's quite a good dataset. Basically what you see, of course, is pyrexia, pruritus, fatigue, chills, et cetera. Things that can be managed medically without very much concern. Importantly, we didn't see any tissue-specific toxicity. This is a perfect agent for combination purposes. Here again, just basically summarizes what I just said, but I wanted to point your attention to the discontinuation rate, which, for instance, in the studies that Professor Zamarin showed, usually it's quite high when you combine anti-CTLA-4, anti-PD-1s, et cetera. Here, the rate of discontinuation is less than 5% so far. We're also very happy about that, and this allows us to envisage a good treatment for ovarian cancer. Right. Here's what we saw in monotherapy. This is a patient who had ovarian cancer. They entered the study after receiving, of course, all the standard of care, as I mentioned, several lines of platinum, PARP inhibitor, bevacizumab, and topotecan. The patient had one target lesion and then two non-target lesions. To our huge surprise, when the patient came in for the first scan, we saw complete disappearance of the lesions, which was, of course, a matter of excitement. I'd like to just pause here for one minute because this, as has been mentioned by Björn as well, is something that many other IO agents have not, aside anti-CTLA-4 or PD-1, PD-L1 targeting agents, this is not something that you often see. This is quite amazing and very impressive, I think. Just in the middle panel in the bottom, you see the tracking of the Tregs, and you see how those Tregs go down. Here is another patient you might have seen already in our presentations, but this is also a very instructive situation because the patient here had a GIST, so it's a sarcoma of the intestinal tract. This patient entered the study. At the first scan at nine weeks, we saw what seemed to be disease progression. Fortunately, we use iRECIST. We took another scan four weeks later and saw that some of the lesions were starting to decrease in size. We met with the investigator. We decided that the patient should be kept on treatment. That patient went on to develop a very nice partial response that lasted for the two-year treatment. The patient went on, and actually, those lesions that we're still seeing were biopsied for a couple of times, and no tumor tissue was found there. Very much indicative of a potential complete response. Interestingly, if you look in the middle bottom panel, you see how the Tregs actually go down very steeply at the beginning. It was thought that the patient had progressive disease. The patient missed two infusions. The patient was being prepared for something different. You see that the Tregs go back up, when treatment was restored, Tregs will actually go way down. This is, of course, one thing that is important, perhaps not all, as Björn mentioned, but at least part of the activity is based on this Treg deletion. Perhaps more importantly, to the right, you see that the tumor, before dosing, it was a very dark and pooled tumor. By week five, you see all those red, yellow dots. Infiltration of CD8+ T cells and indicating a release of granzyme B, things that is exactly what you want to get into a tumor after treatment. By the way, that patient had received several, 12 previous lines of TKI inhibitors. Very impressive as well that patient went off to the end of the study after two years. Here is the data that has us so excited so far. This, I think, is impressive and meaningful. On the right-hand side, you see the spider plot of our patients. These are 25 patients, and the first thing that you see is two colors. You see orange and blue, and the orange is clear cell ovarian cancer. The blue is high-grade serous. The first thing that is important to note here is that it works on the two types of malignancies. The other thing that I want to point out here is that you see that at the beginning, at week nine, several of those patients, the tumors actually grow very much like what we saw in that GIST patient. This is something that we have to deal with because we could be losing some patients to pseudoprogression. Basically, Björn Frendéus will show you a good amount of preclinical data, where we have been studying these questions. Also, importantly for us, there came the approval of the KEYNOTE, the pembrolizumab plus paclitaxel, as Professor Zamarin mentioned. This is probably going to become a new standard of care, even though those curves are still deficient and our target is definitely to improve them. Something that I want to point out to you is that if you look at the objective response rate of pembrolizumab plus paclitaxel compared to paclitaxel alone, and that is what drives a lot of the response rates at the beginning is paclitaxel. You obtain with that agent alone 46.6% response rate. That's already very good, and that's why we think that adding paclitaxel to our combination treatment will induce a much better objective response rate. I'll take you back to the spider plot. If you look at this early phase of the disease after treatment, then you see that we will definitely get a number of those patients below the line of progression due to paclitaxel. That we hope will give for the immune system to kick in and get on with those long-lasting responses that we are observing in this study. Great. Of course, what we want to do, as Björn mentioned, and it's obvious from the immunotherapeutic approach, is that, of course, one thing is to drive that blue line higher in terms of responses of patients. Then also try to get that flattened curve because it actually means DVT on survival. That's what pembrolizumab with paclitaxel achieved, and that's definitely our aim and what we already think that we're after. Right. This is just a summary of what I just said. In this very heavily pretreated patient population, and without chemotherapy, we see an objective response rate of 24% with a 56% disease control rate, an early look at PFS of 10.3 months, and probably will get better. Because, of course, there are, as I said, nine patients of those 25 are still on treatment. The others have not yet gotten to the point where they are assessed, but we'll be there very soon. I mentioned before, the final doublet data will be available by the second half of this year. Importantly, I think what we want to do now is what is depicted here and in the green oval there is we have put already into our protocol the combination of pembrolizumab plus paclitaxel and 1808. We will be testing two different doses of 1808. We know that both doses provide really good receptor occupancy for the entire three-week period, so this is likely to be very encouraging. We're looking forward to that, and our idea is that we will beginning recruitment of this in this part of the study by Q4 of this year. We're basically getting ready as we speak. Regarding the timelines, as I mentioned before, the idea is to complete here in 2026 our study of those 40 patients. We have requested fast track designation, and we're basically waiting for the response. In the meantime, we were preparing for the triplets, recruiting of patients in the triplet combination. At the end of that exercise, we will be hopefully requesting breakthrough therapy designation and requesting a meeting with FDA and, hopefully, be able to launch a pivotal study with this triplet, which we are pretty much convinced that will benefit patients on safety-wise on the one hand, but also in terms of responses and more importantly, on overall survival. I think those were the slides that I wanted to present. Yes, we'll get back to the questions, and I'll hand over to Björn to provide some very exciting preclinical data as well. Thank you. Thanks very much, Andres. I will switch gears a bit then to talk about the nature of the BI-1808 response, specifically pharmacodynamics of the BI-1808 response. One of the things we noted early in the program, besides BI-1808's compelling antitumor activity, which is also reflected by the surrogate of 1808 in the lower graph in this particular slide, showing enhanced survival of 1808-treated animals compared to anti-PD-1-treated animals. This is the triple-negative mouse EMT6 breast cancer model. Despite that enhanced antitumor activity, we found that it seemed to take longer for the 1808 response to kick in. This was really by assessing individual tumor growth curves from the animals. From this upper graph, you can see that some of the lines point up towards the sky. Those would be the animals that have not responded to treatment. There are some lines that initially grow a bit, and then they come down and flatten at the Y-axis. Those are the animals that have responded and are in fact cured by PD-1 and 1808 treatment. If we take away the non-responding animals, the picture becomes a bit clearer. I think you can all appreciate that the tumor growth curves in blue of the 1808-treated animals, they seem to grow to larger apparent tumor volumes before they then quite dramatically regress and are eliminated compared with the anti-PD-1-treated animals, indicating that it actually may take a bit longer for 1808's responses to kick in, which certainly makes sense from a mechanistic perspective, by the way. To quantify this a bit more, we simply pooled data from eight individual experiments, we assessed the time to respond, as defined by the first time point when tumors started regressing for either of the two treatments, indicated by the dotted lines in this middle graph. Ultimately, what this resulted in was us able to then calculate the mean times to response. Dramatically, we found that actually there is a doubling of time to response in BI-1808-treated animals compared with anti-PD-1. We, of course, then also did the experiment where we combined the two drugs. Interestingly, we found that response times were intermediate to single-agent treatment with either of the two compounds. You may say, "Oh, this is all really nice, but how is this relevant to clinical development and to a patient that is being treated with a drug? Certainly, it doesn't matter how long it takes. All that matters is that it's active and the depth of the response." Well, ultimately, this may be true when the drug is approved, but now we're in an exploratory phase, and when we judge whether a patient has responded or not is defined to a certain time point. You have already heard from Andres about the GIST patient that at the time of first response assessment actually had tumor volume increases of 40%, and yet just some time later, actually developed a very significant and robust response that spanned all of the target lesions that were identified. We also know now from what Andres told us that this had resulted from a pseudoprogression. There was a massive influx of inflammatory cells, including activated CD8 positive T cells already at week five, four weeks before this first tumor volume assessment was made. A second case study is provided in the right graph. This is from the ongoing ovarian cancer study, where similarly, at the nine-week time point, there's a mean 30% increase in tumor volumes. To a clinician, this would certainly indicate the potential for a progressive disease. Whereas a few weeks later, and then owing to RECIST criteria, this patient was kept on, and we're seeing a dramatic decrease in tumor volumes of this patient. It does beg the question that Andres had already posed. Maybe in some patients, if our response is taking longer, we risk missing them if we don't add other ways to assess whether response is ongoing or not. What might some types of assessments be? Well, for example, circulating tumor DNA is a measure that can predict or happen before the apparent tumor volume decrease that is provided by radiography. That was actually shown to be the case in this ovarian cancer patient. You see in the blue line that ctDNA decreases already by the first time point of assessment of response. ctDNA analysis would have the potential to early identify 1808 responders. What we can then also do, of course, which has been alluded to and which we've already communicated in the prior slides from Andres, is to develop even more powerful combination therapies that are based on BI-1808. Perhaps it's not rocket science to think that how about adding 1808 to PD-1 and paclitaxel combination therapy, which we've already shown preclinically makes a lot of sense from our drug enhancing both of those. To the far left in this slide, you're seeing that when we add 1808 to the combination of PD-1 and paclitaxel, we are in fact improving the survival of the treated animals. Very interestingly, if we treat the animals with such a triplet, we're also further decreasing the time to response, meaning that we're maximizing chances of patients staying on the therapy. All in all, this upcoming triplet is expected to enhance from a number of different perspectives, the efficacy of our drug. Firstly, by providing increased efficacy, secondly, also by making patients respond quicker and staying on therapy and benefiting from treatment. With that, I'll hand over to Sylvie, who will take us through the commercial opportunities and what we're going to be considering moving forward there. Thank you very much, Björn. This slide illustrates asset herding, which is an increasing problem in our industry. It's particularly prevalent in oncology, with numerous similar assets being developed against a restricted set of targets. This is shown in this bar chart of the most popular targets in oncology, and each bar representing the number of assets being developed against that particular target. The risk of this approach is that when there are high-profile failures, such as happened with TIGIT and CD47, to just name a few, there are significant value destruction as numerous programs are stopped. Just in the case of TIGIT and CD47, there were collectively 121 such programs in 2024. In addition, companies with poorly differentiated me-too drugs that do reach the market, such as PARP inhibitors, struggle to capture market share. This makes TNFR2, the target of BI-1808, particularly attractive and valuable, as this is a new first-in-class target with so far very little competition. Today we're talking about ovarian cancer and the potential of BI-1808 in this indication. As Dr. Zamarin has already described, it's clear that ovarian cancer is a deadly disease with a high unmet medical need. Just two numbers on this slide to remember. It's the 11th most common cancer in women, but the fifth leading cause of cancer death in women. Indeed, when we look at the evolution of five-year survival rates for ovarian cancer versus all tumor types in the last 50 years, we see that while new treatments have increased overall survival, the increase in survival for ovarian patients is modest, and five-year rates are still well below the average for all cancer patients. We've already heard about the treatments for ovarian cancer from Dr. Zamarin, and he showed a similar table, in fact, more detailed. How do they stack up? In brief, and as is obvious from the previous slide, all the major classes, chemo, anti-VEGF, PARP inhibitors, and ADCs only confirm modest PFS gains and will not fundamentally shift the five-year survival curve I showed in the previous slide. While ADCs are an exciting new modality, they're no exception. ADCs are not likely to lead to long-term remission. They have other shortcomings as well, such as restriction to biomarker-positive populations. Interestingly, immunotherapy, the last row in this table, which is in orange, comprehensively failed to show efficacy in this indication until very recently with the approval of a pembrolizumab-paclitaxel combo in February of this year. This is an exciting new development in the field. As my colleagues have already stated, on which we would like to build. Indeed, for the first time, a regimen containing a checkpoint inhibitor was able to show an overall survival benefit and a potential flattening of their survival curve. I think this particular graph has been shown already three times, I'll show it again because it's a nice supportive graph for our story. Back to BI-1808. As you all have seen from previous presentations, we have both preclinical and clinical evidence to support the addition of BI-1808 to this doublet to create a formidable new standard of care in ovarian cancer and perhaps achieve the long-term remission or even cures that have eluded this field. This graph is a representation of key competitors in platinum-resistant ovarian cancer. It's not comprehensive, or it would have been too busy, but includes the most important late-stage and approved treatments. It plots overall survival on the x-axis versus objective response rates on the y-axis. The newly approved pembrolizumab plus paclitaxel doublet is the bright pink circle in the top right quadrant. Basically, the best in class so far. You can also see on this graph certain of the high-profile ADCs in development, as well as ELAHERE, the folate receptor alpha targeting ADC, which is the lighter pink circle in the middle with the dark outline. The dark outline, by the way, on this gra ph signifies a black box warning. Our hypothesis is that adding BI-1808 to the pembrolizumab doublet will both increase ORR and increase overall survival based on data we are seeing in our phase II trial. We expect that no ADC will be able to exceed the efficacy of this treatment, which by virtue of its good tolerability, should be very well received by both patients and clinicians. Now some market research results of our initial study have yielded an estimated peak revenue for BI-1808 of $1.5 billion in the seven major market countries as a base case for platinum-resistant ovarian cancer. This estimate is based on conservative assumptions and an initial approval restricted to PD-L1 positive patients. One of the attractive features of this regimen is that other than the PD-L1 status of the patients, no other biomarker is required, which leaves a large eligible population. There's an upside potential to achieve even higher revenues with an all-comers label without the PD-L1 positive restriction. In addition, this BI-1808 regimen could be sequenced either before or after an ADC, though we believe that the good safety profile will make it an attractive option for early lines. In brief, BI-1808 is the most exciting new immunotherapy to be developed since anti-PD-1. It has a powerful effect on the remodeling of the tumor microenvironment, both deleting Tregs and expanding effector T cells. Early efficacy in combination with pem brolizumab in ovarian cancer is impressive, with a 24% objective response rate. BI-1808 has no serious additive toxicity, so is perfect for combination therapies. As might be expected from an immunotherapy, we also anticipate long-lasting responses, which we're starting to see in our trial. Finally, this is a first-in-class antibody against a new target with the potential to be developed as a platform in many additional solid tumor indications. That's my last slide, I think. Thank you very much for your time. Thank you very much, Sylvie. Before I thank everybody for the excellent presentations, just the last point that I wanted to make, progression-free survival, which I think is already, as you have here on your slide, better than what we see for the combination of pembrolizumab paclitaxel. I think what is also important to note here, and I think that's interesting for the audience potentially, is that our progression-free survival that we show with the doublet is in a much more heavily pretreated patient population compared to the 8.3 months that has been shown for the pembrolizumab paclitaxel. I think I just want to make that point, and maybe that's something that we can also discuss later in our Q&A. I think that's what we should do now. Let's move into Q&A, and then at the end, I have a couple of concluding remarks. Wilson? Thank you, Martin, and to all of our speakers. At this time, we'll be conducting a live Q&A session. As a reminder to the webcast audience, if you'd like to submit a question, please use the Q&A text box below the webcast player. To our covering analysts, please raise your hand to be added to the queue. We'll now hold for a brief moment to pull for questions. Our first question comes from Arvid Necander from DNB Carnegie. Please go ahead, Arvid. Arvid, you may be on mute. Yeah, sorry about that. I was on mute. First of all, thanks everyone for a great update. Data looks very directionally encouraging, I think. The first part of the question, I guess, is for management. Have you stratified the responses by PD-L1 expression, or do you plan to? If Dr. Zamarin is still on the call, how important would you consider PD-L1 expression when interpreting data in this very heavily pretreated population? If it turns out that the responders were ultimately enriched for a high PD-L1 expression, does that materially weaken the argument for added benefit beyond the pembrolizumab monotherapy in your view? I'll start there. Thanks. Thank you, Arvid. Maybe we start with Dmitriy, because I don't know what time he has. Dmitriy, maybe you can address the second question from Arvid, and then I think we hand over to Andres. Yeah, absolutely. PD-L1 is a horrible biomarker in ovarian cancer. If you look at the progression-free survival curves in the Merck study, the B-96, there was absolutely no difference in progression-free survival in that population, whether you enriched for PD-L1 or did not. The only enrichment that came was in the overall survival, and we think just because PD-L1 is really a prognostic marker. There's some interaction that's happening there. Prior studies that have used PD-L1 as a biomarker in ovarian cancer have not been conclusive at all. In some studies, in fact, low PD-L1 seemed to suggest benefit from immunotherapy. Overall, I don't think that it's a good biomarker. At the cutoff that Merck has used, it was essentially such a low cutoff that 75% of the patients with ovarian cancer are expected to be PD-L1 positive. Just like you have asked, I would be curious to see the data from the BioInvent study to see whether there was a PD-L1 enrichment, although I wouldn't be surprised that it didn't really make a difference. Yep. Thank you, Dmitriy. Andres, do you also want to comment quickly on the first part? Yes. Yeah, absolutely. We haven't looked at PD-L1 expression, and the reason for that is because PD-L1 expression has not been traditionally used in ovarian cancer. That was that. I would expect our patients to reflect the overall population without any bias. I would reiterate what Dr. Zamarin said, which is PD-L1 expression didn't really indicate very much enhanced activity in the KEYNOTE-B96. What will we do? We will test for PD-L1 expression in the future. We will look at it. We pretty much are convinced that we don't need to select patients based on PD-L1 expression, but we will capture the data in the upcoming studies, look at it and see if there is a difference and if there is something that we should be paying attention to. It's not something that we think will determine what we do. Thank you, Andres. Thank you for your questions. Our next question comes from Richard Ramanius from Redeye. Please go ahead, Richard. Rich? Yes. Hello, good evening. I'd like to hear from Dr. Zamarin, if he has any comments on the BI-1808 results in ovarian cancer. How promising are they? Yeah. I think if I weren't interested, I probably wouldn't be here. The response rate, of course, is great, but as has been highlighted that we can get good responses with chemotherapy alone. I think what's quite curious about the findings so far is this really durable response or even really a long progression-free survival. The data that they're showing, demonstrating progression-free survival of nine to 10 months, this is better than the ADCs that we're seeing, right? Some of the ADC studies that I have shown you have progression-free survival of about six months, seven months, even though they have a pretty good response rate. I think this is certainly more reflective of the activity that we're seeing with immunotherapies in other cancer types where we see a higher response rates. And again, this is without chemo right now. I think what has really caught my attention is the potential durability of the clinical benefit that we can get in these patients. And I can imagine that you can enhance the response rate and maybe even improve it for the patients by starting it with the chemotherapy and then potentially drop the chemotherapy and just continue immunotherapy as well for the prolonged clinical benefit. Yeah. Thank you, Dmitriy. Just another final question. I was wondering about the safety profile, whether there's any difference at all, you're seeing any difference at all compared with pembrolizumab monotherapy. Should I address that? Yeah, or Dmitriy. Yeah. Either one of us can address it. Far, I think the data look quite similar to what we would get with pembrolizumab monotherapy. We don't get pyrexia with pembrolizumab here. It's interesting. I forgot whether Björn showed it or maybe, Andres, you showed it. I think there was some initial pyrexia. I think it was just in the very beginning, right? With th e first cycle. I remember seeing pyrexia in some of the older studies that we have done either with the CD40 agonists, essentially just highlighting that there's probably a modulatory effect that's happening in the macrophages, which is probably what's leading to this. The pyrexia seems to be quite manageable, overall, just if you're looking at the long-term toxicities, it appears to be quite similar. For full disclosure, I have not treated any of these patients. I haven't spoken with them. The fact that the discontinuation rate also is quite low for the toxicities really highlights that the discontinuation rate is similar to what we would expect with a single-agent immune checkpoint inhibitor. It highlights that it's quite reasonable. It's certainly lower than what we saw with the CTLA-4 combinations. Yeah. Thank you for your questions, Richard. Our next question comes from Sebastiaan van der Schoot from Kempen. Please go ahead, Sebastiaan. Hi. Hi guys. Hi team. Thank you so much for the insightful presentation today. I first wanted to ask a few questions to Dr. Zamarin, if I could. I want to dig in into the ipi nivo combination that you evaluated in ovarian cancer that showed a pretty strong OR level but was not further pursued. I'm just wondering whether that was because of the level of toxicity or is that because the OR did not translate in further progression-free survival benefit or OS? Yeah. There was progression-free survival benefit on that study, and in fact, some of these patients are cured now. Now, more than 10 years later since we have started, these patients had complete responses, and it's done. I think the decision was really from company-driven. The ipi patent was running out. We have actually approached BMS and said, "Can we do a randomized phase III trial and move this further?" They were not quite interested in pursuing it at the time. This was already past 2020, and that seemed to be the reason. Again, this was also the first time that the CTLA-4 was used in patients with ovarian cancer. The majority of patients that get treated with gynecologic cancers are, at least in the U.S., get treated by gynecologic oncologists who are surgeons who might not be familiar with these drugs and the toxicity management. Again, it has changed since then. I think it was probably a wrong time, wrong place. There is clearly an interest. I believe that Agenus is planning to pursue their combination going forward. They're obviously moving it in a colorectal cancer. Based on the ovarian data, from what I hear, they're planning to move it forward. I think they should. Yeah. That's super interesting. Regarding the available treatment options that you now have available, where would you slot in the 1808 combination with pembrolizumab? If I understand you correctly, would you also see an opportunity to first start with chemo and the immune checkpoint combination and then get patients off chemo as soon as possible just to get them into response? Is that kind of how I should see it or how? Yep. No. I think the most natural combination would be to build on that B96 kind of a study. The question still comes up, as was asked earlier, is can we benefit more patients than just the ones that have PD-L1 positivity? I can certainly see that there's a rationale for doing the study in both PD-L1 positive and negative patients. Just in terms of the chemotherapy component, the problem with paclitaxel drug is that it's actually reasonably well-tolerated, but the long-term toxicities are not good. These patients all lose their hair. That's fine. Hair is not dangerous, but neuropathy is a big problem. We cannot keep patients on paclitaxel long term because of neuropathy, because then they start dropping things. They have difficulty maintaining balance. You cannot keep that drug going for a very long time. Clinically, essentially, the way that we like to do these things is, we achieve potential maximal response, then we drop the chemotherapy, and we continue with immunotherapy alone, or this is what we used to do when we had, let's say, just the bevacizumab as a partner. We can add back the chemotherapy should the patient develop progression. I think it becomes more of managing on the basis of the toxicities. We can't treat these patients until progression, because then they end up in the wheelchair. Here I can imagine that one could design a trial where you start with a chemotherapy, and then the investigators could be allowed to drop the chemotherapy part if the patient achieves a durable response or even durable stable disease. Yeah. Got it. That is super helpful. Maybe for the BioInvent team. Thanks so much for all the color today also on the baseline characteristics. That's super helpful. I'm wondering regarding the preclinical and the clinical observation on pseudoprogression. I'm wondering for the remaining patients that you want to slot into this expansion cohort, I think there are still 20 remaining. How do you make sure that if there is pseudoprogression, that these patients will continue on treatment and maybe still show a response? Andres? Sure. Thanks, Sebastiaan. Yeah, it's a tough question because obviously, and we have discussed it with our investigators, they of course, feel that they want to do the best for their patients, and it's not always obvious when you have a patient who has a larger tumor per scan to continue on treatment. What we have been doing is making them conscious of the possibility that this may be happening. There is also, and maybe Dr. Zamarin can tell us about that. There is also a notion of this is not a scan, it's a patient, so you can assess whether clinically their patient seems to be progressing or not. That assessment can be made and discussed, and if they feel that they want to continue with the patient on treatment, that is definitely a possibility. Other than that, we can't do very much because obviously, this is what the protocol calls for and we have to respect that. To the point that you were asking before, that's exactly what Dr. Zamarin said. That's exactly what we want to do, is we want to put paclitaxel up front during the first three months and then allow the clinicians to, depending on the patient that they have in front of them, allow them to use chemotherapy as they feel it has to be used. Allowing vacations of chemotherapy, perhaps stopping the chemotherapy. We certainly have cases in this data set where chemotherapy has been stopped and patients have continued on the two other drugs and the response has continued on. It's definitely an approach that makes sense to us also. It should also impact the rate of discontinuation, because obviously, if you keep patients on chemotherapy, there will come a point where they cannot tolerate it and they have to walk away from the therapy, and that would be a shame if the two other agents are working well. Got it. A final question, then we'll jump back in the queue. I am just wondering regarding the populations with, sorry, with high-grade serous carcinoma and the clear cell carcinoma patients. I'm wondering, is there a difference in how these subpopulations respond to treatments? Are you asking me, I guess, or the? Both. Whoever wants to take it. I guess I can tell you just, so traditionally, the clear cell carcinomas respond less to chemotherapy than the high-grade serous ovarian cancers. The clear cell carcinomas tend to be more chemo-resistant. There is some evidence that they may be a little bit more immunosuppensitive, not that much more. For example, if you estimate the pembrolizumab response rate being, let's say, 8% in this population as a single agent. In clear cell carcinoma, it would be 12%. It's not significantly more immunogenic. Just in terms of chemotherapy response, it's usually lower. Yeah. Andres, additional comments? No. No more comments. I think that was the answer that I would give to that question. Thank you, Dmitriy. Great. Thank you, guys. I will hop back into queue. Thank you for your question, Sebastiaan. Our next question comes from Oscar Haffen Lamm from Stifel. Please go ahead, Oscar. Yes, good afternoon, and thank you all for organizing this event. I actually have a question for Dr. Zamarin. Since the KEYNOTE-B96 data came out, how has been the perception in the medical field for this combination with pacs and pembrolizumab? Do you ultimately think this therapy will become the new standard of care for PROC patients? Well, it is a standard of care right now. Basically, it is FDA approved. We have a lot of confusion in the field right now. Just because we've got two approvals essentially at the same time. We have the nab-paclitaxel with relacorilant, and paclitaxel with pembrolizumab. The question is, if you fail one, then technically you become resistant to paclitaxel. What do you do next? Will the paclitaxel with pembrolizumab still work or not? We still haven't resolved that in the field. The decision to use one versus the other, which one do we use first, is also not very well established. I think this is just going to be a matter of preference. Personally, I will probably use the B96 regimen as a first as opposed to the relacorilant, just because the relacorilant study had more toxicities. Just as a conscientious physician, it's much more expensive. I think both from the point of view of nab-paclitaxel being more expensive, but also relacorilant drug being more expensive and puts more onus on the patient that have to take these pills three days before every nab-paclitaxel infusion. To your point, yes, the B96 is a standard. We will use it just as much as we will use the ADCs that are also a standard. The order is not very well established, but the order probably doesn't make a difference because unfortunately, most of these patients will have a progression. We tend to reserve the paclitaxel-based regimens until later, just because, again, of the substantial neuropathy that's associated with chronic paclitaxel use. Great. Thank you very much. Thank you for your questions, Oscar. We have one more question from Arvid Necander from DNB Carnegie. Please go ahead, Arvid. Thank you so much. I was cut a bit short there. I had another question on the baseline characteristics, and it's sort of similar to what was asked previously on the histology split and the implications. As noted before, I guess this readout included a relatively high share of patients with clear cell histology, both in relation to real-world prevalence and also what's been reported in previous studies. I think that was noted. It was breaking up a little bit to me when you guys talked about it. In clear cell ovarian cancer, it seems like there's a higher sensitivity to pembrolizumab, as seen in KEYNOTE-100, if you compare it to the broader ovarian cancer population. How should this subtype mix influence how we interpret the signal here, both considering chemo, which I think you guys discussed more about, but also the expected response to pembrolizumab, essentially? Dmitriy, you want to address that? Sure. Absolutely. Again, just with regards to response in clear cell carcinomas, the response rate, and you have mentioned KEYNOTE-100, Arvid, very rightfully so. Like I said, the response rate to clear cell carcinomas appears to be a little bit higher than it is to the high-grade serous. Like I said, it's not that much higher. At least to the single-agent immune checkpoint inhibitors. With the pembrolizumab alone, I think you get about 8% with the high-grade serous, maybe on the order of 12%, slightly higher than in the clear cell carcinoma. I think the highest that I have seen would have been like a 15% in a smaller study. The response is higher with combination with CTLA-4 and PD-1. There was a study that was conducted specifically in clear cell carcinomas with the CTLA-4 and PD-1. Overall, just even looking at the data in here with the BioInvent combination, we see it in both. The responses do appear to be deeper in the clear cell carcinoma patients. Again, I think the numbers are a little bit too small, and I think the overall response rate is still pretty similar between the two. Again, I don't want to necessarily talk about responses as much as about the durability. I think the durability was quite similar between the two. The other question you had was more about the baseline characteristics of patients. Was that specifically just focusing on the histology, or you had something else in mind? That was specifically on the histology. If you have more insight than we do, I'm happy to take your view on that. The other key thing to highlight, I guess, and I think Andres has already mentioned that the KEYNOTE-B96 trial allowed up to two prior lines of therapy. I think this one had a much heavier pretreated population. The KEYNOTE-B96 is not a population that we enroll to these kinds of studies. Certainly, it's not a population that we treat in clinic, because in clinic, normally by the time the patients get to it, they will have had a few more prior lines of therapy. I think making cross trial comparisons is also not necessarily fair in here. Even with that kind of a comparison, I think the data so far look fairly compelling. Yep. Great. Thanks for that comprehensive answer and thanks everyone for this well-organized event. Thank you, Arvid. I will now turn it over to Björn to read any written questions we have received on the webcast. Please go ahead, Björn. Right. I guess we're already a bit late. I think 12 minutes past the intended time of closing. Is that right? Yeah, roughly. Nevertheless, we can have a couple of questions maybe. I think some of them have been addressed already, so I'll skip those. One question relates to potentially other combinations including targeted therapies and certainly with this safety profile. If I can start addressing this and then the other guys can chime in. I think potentially makes a lot of sense. We do see that based on the preclinical modeling, that the paclitaxel combination amongst the different chemos we have tried seems to be speaking the best with our drug, which is perhaps not a surprise, because paclitaxel is immunomodulatory beyond being just a pure chemo. We'll do whatever we can to sort of identify the most beneficial types of partners for a drug from that perspective, I think. Another question perhaps for you, Andres, relates to if we have an estimate of the size of what a pivotal study could look like in ovarian cancer with pembrolizumab and paclitaxel. We don't know exactly what that would look like. What we can estimate is something of when we're thinking about this, we're thinking about the size of KEYNOTE-B96, that was in 650 patients roughly. Yeah, that's basically what I can cite as an appropriate benchmark. This being said, of course, we're doing the exercise right now. We will have a good understanding of the delta at the end of the next part of the study, that will allow us roughly to get to a better calculation of those patient numbers, et cetera. Okay, great. Right. I think we have commented on the potential utility of our drug in other combinations without paclitaxel. We touched on different types of tumors where you want to see better responses and our antibody synergizes with anti-PD-1. There's a question that relates to myeloid reprogramming. What evidence do we see of this in patients? I think that's a good one, because we do believe this biology is important, and we've already touched on a few different parameters, where we're seeing this being activated. I see Andres waving, and you can take on from me when I'm done. Just to mention that we are seeing modulations of myeloid cells following administration of our antibody in the patients. For example, the FcγRIII-positive population is increased, and this is known to be a population that supports to have inflammatory responses, ADCP and that sort of thing, which is included in our MOA. We're also seeing that IL-12 that I showed you being increased in patient serum and preclinically, we find that it's only the myeloid cells that actually produce this, and this is consistent with other people's findings. We need to do more, and it's early days and analysis of tumors is always lagging a bit behind because there's a number of different things we need to do first. We'll get back to you on that. Certainly, this biology is being reflected in the patients. Okay, Björn, I think Andres was waving because Dmitriy has left. He had to sign off. That's why Andres was waving. Okay. I think what we should do is, anyway, maybe we can collect all those other questions that we didn't address yet, but we are actually already quite beyond the time that we have planned. Maybe we stop here because you mentioned also that a lot of those questions that are there online have been covered already during the Q&A session with the analysts and addressing Dmitriy as well as the team. What I would suggest is that I just finish the presentation with a couple of concluding remarks. In order to do that, I'm trying to control the slides, but I can't do it at the moment. Now I can do it, perfect. F F irst of all, I think, before I briefly summarize the key expected milestones for this year and maybe some highlights also for next year. Thanks to everybody. Unfortunately, Dmitriy has left, but I think everybody, Dmitriy, Björn, Andres, and Sylvie, very good presentations. Thank you very much, for the attending audience, plus the good question that we heard from there. As I said, I think with the data set that we will present at ASCO 1808 and ovarian cancer, we feel it's very compelling and exceptional. Just to highlight again that it's already three times more than KEYTRUDA alone in this patient population. I think even more exciting, the progression-free survival, which is already at this early stage, higher than the most recent keynote study. Also keep in mind that the patient populations are different as highlighted by Dmitriy. The next step there would be then really to start the triplet, and then basically comparing the standard of care with the standard of care plus 1808. That readout would be available during the second half of next year. Obviously today we were focusing ovarian cancer, but we also have very compelling data in CTCL, and that will be presented at EHA, which is I think in two weeks from now roughly. Plus also, we'll have a KOL event around that and also to mention it here. If everything goes according to plan, we will be ready for pivotal study in CTCL already during 2027. Obviously no topic today, FcγRIIB, our lead compound targeting FcγRIIB, which is a very interesting target. Just to mention it also here again, BI-1206 is sub-Q, so very convenient. There the next data release will be also at EHA. We're developing BI-1206 in non-Hodgkin lymphoma, as you can see here. That data set will be discussed and presented at EHA and also will be presented in the KOL event. We'll have two KOL events in one go, one for T-cell lymphoma, the other one for non-Hodgkin lymphoma just ahead of EHA. Last but not least, we will have the first readout for the first-line non-small cell lung cancer and melanoma during the second half of this year. The BI-1206 non-Hodgkin lymphoma study would be potentially also ready for pivotal study during 2027. Since we're already quite ahead in time, I will stop here. Thank you again for everybody, to the presenters for the presentations and of course the attendants as well as the good questions. Thank you very much