BioInvent International AB (publ) ($BINV)

Good morning, and welcome to the BioInvent KOL Event. [Operator Instructions] 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, [indiscernible], and welcome, everybody, to our BioInvent ovarian cancer KOL Event. And we're very happy to have with us today Dimitri [indiscernible], MD and 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 you see on the agenda, as you can see now. So I will start with some introductory remarks. Then I will hand over to Dimitri, and he will talk about the ovarian cancer treatment landscape, the medical need, future treatment of ovarian cancer. So really looking forward to that. Then we will hand over to Björn Frendéus, our CSO, and he will really talk about the differentiated mechanism of action that we have for 1808, which I think will be also very interesting and we just recently uploaded actually a manuscript that describes that in detail. Then that will follow by Andres McAllister, our Chief Medical Officer, and he will talk about the clinical data that we have to date, and that also will present it, obviously, will be presented at ASCO. And then he will hand over back again to Andres McAllister who will then have some more translational data, specifically highlighting the dynamics of responses, which is also very interesting. And then towards the end, Sylvia Rogers, our Chief Business Officer, and she will talk about the market opportunity as we see it for 1808 and then we have some final remarks and Q&A. So I was already introduced, but anyway, so my name is Martin Welschof. I'm the CEO of the company now for almost 8 years and indeed looking forward to very, very exciting times. So as I said, a quick and more detailed introduction for Dmitry. So Dimitri is MD, PhD and he is Professor of Oncology Section Head of Gynecologic Medical Oncology and [indiscernible] Director of the Center Of Excellence For Gynecologic Cancers at the Tisch Cancer Center at Icon School of Medicine at Mount Sinai and has served as a principal investigator and a translational share on multiple institutional and corporate group clinical trials, exploring novel immunotherapy combinations in oncologic cancers and other solid tumors actually. And so it's also at the translation of research [indiscernible] share 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 [indiscernible] therapy. So Dimitri welcome, and I'm really looking forward to your presentation. Then as already mentioned on the scheduled slide, the agenda slide. So we will have Björn Frendéus, our CSO, as you can see on the left-hand side in the middle, you see Andres McAllister, Chief Medical Officer. And then last but not least, [indiscernible], our Chief Business Officer. So before we start with Dimitri, so what we been trying to do is to develop a new standard of care for recurring ovarian cancer, as we will show you later in more detail. And that is actually also commercially very interesting since it addresses a very high unmet need. And based on our initial commercial analysis that we have done, we expect the [indiscernible] 1.5 billion in estimated peak sales. So 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. And as you will know, checkpoint inhibitors have created a major oncology markets, but there's still a lot of patients that will not really benefit of that. And also, as you know, large pharma is really looking for the next level new modulator since there's the IO combinations that are used at the moment are ahead of patent life, as I will show you also later in a little bit more detail. We have 2 first-in-class compounds. [indiscernible] BI-1206. They obviously will talk about BI-1808. We're targeting new resistance beyond current therapies, as we will show you before 1808 at least today. We have very strong antitumor activity with a very favorable safety profile, which is very important, especially when you want to treat advanced cancers. And beyond this, we have the potential to enhance on the efficacy and durability of existing new therapies, and I will discuss that today as well. We are quite integrated company, as you might remember. So we have a very proprietary human first platform, which is the worst [indiscernible] screening that allows us actually to identify new mode of actions as 1808 targeting [indiscernible] 2. 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 health care investors. Just very briefly. So this is actually a slide that covers all the IO markets, not only the new modulators, but also something like ABCs and bispecifics. And you can see it's a huge opportunity still growing. And on the right-hand side, you see the bottlenecks, right? So there are quite a number of bottlenecks, and we are actually focusing on the #1 bottleneck, which the immunosuppressive tumor microenvironment. So with 1808, we have something that modulates that from a tumor-friendly microbiome into a more hostile make environment, and we'll come back to that in more detail later. So this is basically showing you a couple of programs with the handful of large pharma, so anti-PD-1 as well as anti-PDL1 that are over 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. So we feel that we can really help to unlock the full potential of IO and why do we think we can do that. We can increase response rates, and we have shown that already, and 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 delivered deeper and longer-lasting responses, that would be something that Anders 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. And then 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. So before I hand over to Dimitri, just very briefly to a quick look on to our portfolio. And I will start from the bottom. So there you see our FcgammaRIIB platform, the lead compound that we have that is BI-1206, which is a subcutaneous formulated antibody [indiscernible] injection. And this antibody we currently develop in non-Hodgkin's lymphoma as well as in non-small cell lung cancer [indiscernible] melanoma and the [indiscernible] lymphoma actually will be presented at AHA and also highlighted KOL events ahead of AHA. Then, of course, the main topic today, BI-1808, we are at targeting kinase receptor 2. And I'll leave all the biology and mode of action to be earned, but it's really [indiscernible] very interesting amount of action. And today, obviously, you will 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 AHA and also in the conjunction of a KOL event. So I think this is the introduction that I wanted to do. So Dimitri, I will hand over to you, and please take it away. Thank you.

Martin, thanks so much. So 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. So just as an introduction, the ovarian cancer is a cancer that typically not actually at the over, but more commonly started the origin of the fallopian tube. Its a little bit of a misnomer, but 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 0 screening strategies for this cancer. So even though the cancer progresses through the stages that are indicated on this slide, meaning Stage 1 is just ovary compliance. Stage 2 is the cancer that's combined to pelvis. This Stage 3 is the cancer that now metastasize to peritoneal cavity. And Stage 4 is the cancer that has spread beyond the peritoneal cavity to other organs. Essentially, the majority of the patients present for 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 and most cases of cancer is not curable. So 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 maturity of the patients present with this widely advanced disease, what they make in [indiscernible] these big symptoms of loading and then eventually develop more [indiscernible] as shown in the picture on the right. And then -- and 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 partial carcinomatosis. This is a visa cancer module that has spread through the peritoneal cavity and as you can imagine, this disease is difficult to resect. So what happens for these patients is that either they undergo initial cytoreduction surgery followed by adjuvant chemotherapy or more commonly now they start with the neoadjuvant chemotherapy followed again by surgical cytoreduction and then more adjuvant chemotherapy. And 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. And if they relapse after the initial chemotherapy is after 6 months, we'll call it the platinum-sensitive recurrence, meaning we can treat these patients with a platinum-based chemotherapies again. If the relapse is less than 6 months after the initial chemotherapy, we would call it a platinum-resistant disease. So unfortunately, the majority of the patients will eventually develop these platinum-resistant disease because even those who get treated with the platinum-sensitive recurrence with more platinum agents eventually do become resistant. And this is the one -- the highest area of therapeutic need because from the moment of development of platinum resistance, we used to estimate the survival of the patients on the order of about 12 months. [indiscernible] has some newer agents there that I'll highlight in a few slides, but probably extends that survival to maybe 1.5 to 2 years. But again, nevertheless, most of the patients will progress on these therapies and certainly need other new agents. So this is the summary of how we treat ovarian cancer. So as I mentioned before, the newly diagnosed patients will get carboplatin with paclitaxel chemotherapy. Some of them will also get avastin. And if the patients have evidence of [indiscernible] mutations or what we call homologous recombination deficiency, they may also get a park inhibitor [indiscernible]. As I mentioned before, most of these therapies are not cured. So over the past 25 years, while we have extended this arrival of these patients, unfortunately, the number of patients that we are curing has not changed. So 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 but maintenance with bevacizumab. We don't really use PARP inhibitors in the second line summing because even though they initially had an approval here, subsequent data have demonstrated that they do not improve overall survival. And in fact, our data to suggest that use of PARP inhibitors in this study may actually decrease survival possibly due to development of cross-resistance mechanisms that make them less sensitive to subsequent chemotherapies. And then once the patient event 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 antibody-drug conjugate called mirvetuximab, serotonin or [indiscernible]. This is an agent approved for [indiscernible] receptor 1 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. We do about [indiscernible] for cancers that are expressing PD-L1. We also have a new approval now with a drug called relacorilant, which is a gluco-portigoid receptor antagonist in combination with [indiscernible] paclitaxel or [indiscernible] outstanding therapies include single-agent chemotherapies, whether or not bevacizumab and also for patients that have HER2 positive cancers, we could use trustees to go to the account. And again, I want to highlight here that the respective of these therapies, virtually all patients will eventually experience disease progression. So here, just over the next few slides, I just want to highlight what is the evidence of efficacy that we see from these trials. So this is probably the first drug that was approved in the platform resistant setting that has demonstrated overall survival benefit. And this is margetuximab, Sorensen. It was appropriate a few years ago. based on both improvement in progression-free survival and overall survival in patients with the platinum-resistant ovarian cancer. And here, you can see the curves, the curves do separate nicely, suggesting that is antibody drug conjugate is certainly benefiting these patients. But yes, uniformly, you can see that these patients are accurate, right? And virtually all of them will eventually experience disease progression and the play other factories. This is sort of the standard kind of chemotherapies that we use. This is on the basis of AURELIA trial that was not reported in 2014, which is where we have the standard treatments that we have had fictions were chemotherapy, single agents, either paclitaxel, gemcitabine, [indiscernible] doxorubicin or [indiscernible]. And this was a trial that essentially put bevacizumab on the market for the patients were being treated with the single agent chemos whether without bevacizumab. And here are the drugs that are listed here. So what I wanted to highlight from this study is essentially out of these 3 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 combination with immunotherapy and relacorilant. So this is a newer data. This is the data that were just presented earlier this year. Well, actually, they were presented initially in ASCO last year, but the publication came out this year, and we just had an FDA approval. So this was a Phase III trial of nab-paclitaxel with legacies antagonists relacorilant. Essentially, the idea here is that the glucocortic receptor signaling, ovarian cancer cells mediate chemo resistance and and blockade of the receptor can actually be sensitized depends cells to the effect of paclitaxel. It's an oral agent by itself. It has essentially 0 activity, but when combined with chemotherapy, it did demonstrate prolongation of progression-free survival shown here on the left. But more importantly, the overall survival, there was approximately a 4-month improvement in overall survival, which is what led to the approval of the drug, again, in combination with [indiscernible] paclitaxel applications for platinum-resistant ovarian cancer. So this is now an option for our patients. And another key therapy that I want to talk about today is, of course, immune checkpoint inhibitors and this is the class of drugs that unfortunately has not seen to date as much success in ovarian cancer. So I'm not going to go through all of these trials here, but you can -- if you look at the column #3, you can see the maturity 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 chemotherapy and 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 and essentially this was a trial that there was a trial that was deemed positive and resulted in approval of pembrolizumab for patients with platinum-resistant ovarian cancer. And here are the data from the trial. And you can see that despite the statistically significant improvement both in progression-free survival and overall survival data are still not great, right? So if you look at the progression-free survival [indiscernible] on the left, both in the PD-L1 positive tumors and in the overall population, we saw progression-free survival improvement of approximately 1 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 curve on the right and specifically in the PD-L1 positive population, there was approximately 3 months improvement in OS. And so again, for these patients, the [indiscernible] tumors express PD-L1. This is certainly a treatment option. But again, I want to highlight that all of these curves coming down. These patients are not secured. We know that a good portion of them can drive a very durable benefit, which is typical of a media therapy trials. But unfortunately, still many of them are resistant to these agents. So 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 sensors can improve both response rate and progression-free survival. This is an example of a study that we have actually done for NRG Oncology, which was a randomized trial of nivolumab and anti-PD-1 onurolumab and ipilimumab, which is [indiscernible] and 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 and 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 new generation of against PLA in PD-1 inhibitors from [indiscernible] demonstrating similar data, a combination of anti-PD-1 and CTLA-4 in platinum-resistant ovarian cancer does exhibit a higher response rate. the response rates were also similar to the ones we have observed with the nivo. Again, I'm not necessarily highlighting CTLA-4 agent as an agent to use because it is associated with significant toxicities. But the key point to show this slide is he's demonstrated that these are immunogenic cancer. We just need to learn how to harness that immunogenicity. Other classes of immunotherapies are also being investigated in ovarian cancer. I mean, there is a lot of interest in T cell engagers at the moment and one of the hottest targets that we have is an [indiscernible]. There are several companies that are developing cloud bispecific engagers. These are the publicly reported data from Biotec here is a closing bispecific engagement was actually delivered by their liposomal preparation of a nanoparticle encoding and mRNA expressing the bispecific engager, not necessarily in need of this technology to deliver these class of agents, but nevertheless, what this slide does highlight specifically in patients with ovarian cancer is that these kinds of agents can have some activity, lot response rate in this study was relatively modest. But nevertheless, these patients can respond because they do have T cells in their tumors. And here, other therapies that we currently have on the horizon, just like in any other cancer type, there has been an explosion of ADCs against the targets that I have listed here, such as here [indiscernible] 6, [indiscernible] receptor 1, [indiscernible] 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 2 main payload classes, which are either TROP-1 targeted or tubulin targeted and emerging data seem to demonstrate that there is cross resistance between the different ADCs that have the same payroll, meaning the resistant series disease is likely not driven by the loss of the actual target, but rather by development of resistance through the chemotherapy. And 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, people have a patient who has received a HER2-targeted agent such as AMPR2, 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 would think of as targeted therapies, the toxicity profiles are actually quite similar to chemotherapy for many of these agents. And in fact, patients who are receiving weekly paclitaxel tolerated better than the majority of these ADCs are not all they are set out to be. They have a lot of toxicities. I mentioned the T cell engagers on the previous slide. I think there's some promising signals of activity in some studies, but be a still pretty early. Same goes for the adaptive cell therapies. We have seen some early promising signals of activities in some studies, but these have been difficult to stay also. So most of these are sort of slowly moving along, but again, major data are yet to be presented. And then targeted therapies, of course, where we saw a lot of excitement with the initial development of [indiscernible] inhibitors. There have been other agents targeting the DNA damage repair pathway in ovarian cancer, such as [indiscernible], ATR and [indiscernible]. Again, there have been signals of activity for these drugs either alone or sometimes in combination with PARP inhibitors. These have been difficult to be implemented 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 and some of these studies being conducted currently specifically by selection of the patients with specific mutations such as, for example, [indiscernible] amplifications automate combination deficiencies. I think this may be my last slide, yes, and I can stop here and then we can take questions later.

Exactly. Thank you very much, Dimitri. I think we switch over now to Björn and Björn will highlight, as I already mentioned, the mechanism of action, please.

Thanks, Martin, for that introduction and thanks Dimitri for a great introduction to ovarian cancer and the current treatment landscape. So in final net, we're dedicated to discovering and developing antibody-based drugs for cancer and immunotherapy. And the background is, of course, these types of drugs have not transformed cancer survival, and they're continuing to do so. So this is reflected by sort of the T-cell infiltrated hot tumors for a new checking shown in the left graph, indeed long-term survival and even pure in patients previously had no hopes of surviving. So this long-term survival and curative potential of these drugs is indicated by a plating of the survival curve from 3 years and onwards and has been shown to correlate with these drugs ability to actually [indiscernible] activate CA positive T cells or immune cystine to CCAP and destroy different cancer cells that are differently mutated. Accordingly, these drugs are approved for treatment of more than 30 different types of cancer. Now as has been introduced by provinces Mary. It's been difficult to use these drugs in so-called cold types of tumors that are not robustly infiltrated by [indiscernible] T-cells. And I think certainly by that definition, ovarian cancer fulfills this cold tumor type now until recently. So if we say the months back, 3 months back after the first time. 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 is a mentioned, but also by specific antibodies. But it came that flattening of the survival curve indicating potential for long-term survival and he's been when combined with other things. Now that's great as these drugs are, we do need to improve. And let's see -- slides what we need to come up with [indiscernible] is, again, on a lot of safety drugs that are really safe that can be added to the existing state-of-the-art -- and 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 a few things and we have come out with it. So why are we so interested in an excited environment in developing a neuromodulating antibodies. Well, of course, it comes down to data and what we found using 1808 antibody, is that TNFR2 seems to be a particularly promising type of immune receptor that can be safely targeted by IV generic compounds to induce tumor regression in various types of cancers, including those of cold type in a manner that correlates with activation of this critical CD positive T cell antitumor immunity. Our data suggests that these powerful effects derived from the antibodies highly differentiated mechanism of action, not only that we believe the most immunosuppressive CR-positive 2 regulatory cells, but it also activates and reprograms the minor itself. To call for CDA positive T cells to come into the cooler tumor setting and actually also in other type of receptor [indiscernible] to come back and kill off the country cells. You can appreciate from this graphic that our mechanism acts indirectly to activate the CD8+ T cells. And this in contrast to anti-T1, which acts directly on the CDA positive T cells. This means, of course, if we combine the 2 products, we may expect to get even better activity. It is exactly what we find. If we look at the most resistant preclinical models, this is a B16-F10 model, which is poorly infiltrated by CD8+ T cells. And accordingly, [indiscernible] response to anti-PD-1 or CTLA-4. We find that we will combine anti-PD-1 with our drug. We actually induce curative responses and a significant fraction of the analysts. Not only are we seeing combinatorial activity with anti-PD-1, but also with paclitaxel, the other component of that recently improved approved IO therapy approved for treatment ovarian cancer. Very importantly, our drug is also active in patients. So this is steaming trustee from the lab showing that in ovarian cancer patients that are being treated with single agent PI showing red lines in the graph, our antibody does induce regulatory cell deletion and it induces [indiscernible] cytokines that are associated with effective T cell activation, such as industrial gamma [indiscernible] also macrophage activation, compelling the IL-12 and even cytokines that are associated with [indiscernible] structures, structures that are known to predict survival in response to immunotherapy. Further, consistent with our mechanistic characterizations. And when we combine our drug with anti PD-1, we've seen these interesting effector responses being enhanced. So with that, I'll leave it to Andres to take you through our really exciting chemical development piece.

Yes. Thank you, Björn. So yes, happy to be describing our -- what we have been doing from a clinical standpoint to show you where we stand and of course, we are very, very happy about these results and happy to describe them see you. So basically, this is the study schematic. So 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, a year is a key issue for these patients. when we dose BI-1808 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 series of percent related to the drug. So we decided to move forward to seasons to make that certain which we did. We're here also using BI-1808 every 3 weeks, so very vice aligned with what memos. And we then moved to 3 different expansion cohorts, 1 a little bit of a basket study where we try the agent in different indications, different tumor types. Our monotherapy expansion cohort in ovarian cancer, the monotherapy cohort in [indiscernible] more specifically about [indiscernible] T cell lymphoma, which we have absolutely moved forward into the dose optimization part of the study. And as Martin mentioned, we will be communicating a little bit about where we stand on that percent 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 pembro, the picture in Part B. We started doing at 225 milligrams, but we're able to dose up to 1,000 milligrams, knowing that, that those provides full receptor occupancy or definitely for the 3 weeks, but probably much longer. So -- and given the safety profile, we decided to move that same dose of 1,000 milligrams into the same type of action cohorts. And the one of cost 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 the family retreated patient population. So I'd like to stress that on that point. because these are patients, I suppose many of the patients in increases in the ONT study. These are 1 unit patients. So patients who have been through just about every possibility and a cost delivery possibility -- therapeutic possibility. So these are the patients that you get to in the study. In that patient population, with no chemotherapy here here please note that as well. We saw an objective response rate of 24% or 25 of our [indiscernible] patients, the patient with a complete response, 5 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. And so in our study, we had prior 1, 2, 10 prior lines the median with 5 prior lines of treatment. We still saw responses in those patients, so very, very exciting data. Here's the waterfall plot that study, you see the magnitude of the response there. When -- and the way, something that we study, we are aiming to recruit 40 patients, which have actually pretty much already been recruited. So by the end of the year, we should have the data set for the 40 patients that we aim to recruit in this particular phase. So that's already pretty much ongoing, and that will be a good read out by the end of the year. In the meantime, with these 25 patients, we took this data trying to understand the duration of responses or characterized on how the duration of those responses understanding that we are not yet that this is not finish that they made several of these patients between 9 patients or no treatments. We took a first look at how the PFS would look like and that is actually at 10.3 months right now. Again, very exciting for this patient population in and with 2 ages and no chemotherapy. So we are very excited about that. Just a word about safety because as I mentioned before, by [indiscernible] and also Bjorn, safety of the study is actually what contributes to the quality of life of these patients. When you use BI-1808 monotherapy, this is basically what you see so basically grade 1 and grade 2 adverse events, 60 out of 62 patients. So it's quite a good number of 2 good data sets. And basically, what you see, of course, is pyrexia pruritus, fatigue or things that can be managed many without very much concern. And importantly, we didn't see any tissue specific toxicity. This is a perfect agent or combination purposes. So here again, just basically summarizes what I just said, but I wanted to your attention to the discontinuation rate, which, for instance, in the studies that [indiscernible] showed usually is quite high when you combine it CTLA-4 and anti PD-1, et cetera. Here, the rate of discontinuation is less than 5% so far. So we're also very happy about that. And this allows us to who we envisage a good treatment for ovarian cancer. Right. So here's what we saw in monotherapy. So this is the patient with who had ovarian cancer center, the study after being, of course, all the standard of care, as I mentioned, several lines of platinum PARP inhibitor, bevacizumab and topotecan. The patient had 1 target lesion and then 2 nontarget patients to our huge surprise when the patient gaming for the first 10, we saw complete disappearance of the lesions, which was of course, a matter of excitement and I'd like to [indiscernible] here for a minute because these stocks have been mentioned by Bjorn as well, is something that many other value agents have that aside or PD-1, PD-1 targeting agents. This is not something that you often see. This is quite a amazing and very impressive thing. So we -- and just in the middle panel in the bottom, you see the tracking of the rates, and you see how those rigs go down, on other patients, you might have seen already in our presentation, but this very also very constructive situation because the patient here has reduced so it's sarcoma of the intestinal tract. These patients entered the study at the first time at 9 weeks, we saw what into the disease progression. Fortunately, we use [indiscernible]. So we took another stand 4 weeks later. We saw that some divisions were starting -- we're 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 2-year treatment the patient were not actually, said that those lesions that we're still seeing were obvious for a couple of times and no tumor tissue was found there. So very much indicative of potential complete results. Interestingly, if you look in the middle bottom panel, you see how the T [indiscernible] actually go down very steeply at the beginning because if we start with the patient had progressive disease the patient needs 2 infusions. It is the patient is being prepared for something different. Then you see that the [indiscernible] go back up -- and then when treatment was restored, [indiscernible] will actually go way down. And this is, of course, 1 thing that is important, perhaps not all, as John mentioned. But at least part of the activity is based on the [indiscernible] division. But perhaps more importantly to the right, you see that the tumor before dosing, it was a very dark and cold tumor than [indiscernible] week 5, you see all those red yellow dots so infiltration of [indiscernible] plus T-cells Class 3 cells and indicating maybe [indiscernible] things that is exactly where you want to get into the tumor after treatment. And by the way, that patient had received several -- 12 previous sizes of TKI inhibitors so very impressive as well that patients is went off to -- of the study after 2 years. And here the data that has been 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 then the first thing that you see is to commerce. So you see orange blue and the orange is clear cell ovarian cancer. The blue is 0. So the first thing that is important to note here is that it works on the 2 types of malignancies. And the other thing that I wanted to point out here is that you see that at the beginning of week 9, several of those patients, the tumors actually grow. But most like what we saw in that [indiscernible] station. So this is something that we have to deal with because we could be losing some patients to pseudoprogression. And basically, what Bjorn will show you good amount of preclinical data, where we have been studying these questions, but also importantly for us, there came the approval of of the keynote of pembrolizumab plus paclitaxel, as [indiscernible] mentioned, these species probably going to become a new standard of care, even though those curves are still deficient and our target is definitely to improve them. But something that I want to point out to you is that if you look at the objective response rate of the [indiscernible] plus paclitaxel compared to paclitaxel alone. And that is what drives a lot of the response rates at the beginning is paclitaxel. So you obtain with that agent alone, 46.6% response rate. So that's already very good. And that's why we think that happening paclitaxel to our paid to our combination treatment will induce a much better objective response rates because if you take you back to this fire plot, if you look at this early [indiscernible] of the disease of the after treatment, then you see that we will definitely get A number of those patients below the line of progression to paclitaxel. And we -- 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. And of course, what we want to do, as Bjorn mentioned, and so views from the immunotherapeutic approach is that -- of course, 1 thing is to drive the blue line higher in terms of responses of patients and then also try to get that flatten curve so that because it actually means on survival. That's what pembrolizumab with paclitaxel and that's definitely with our aim and what we already think that year after. All right. So this is just a summary of what I just said. So 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, 9 patients of those 25 are still in treatment. The others have not yet gotten to the point where they are assessed, but we'll be there very soon. So as I mentioned before, they find no double data will be available by the second half of this year. And importantly, I think what we want to do now is [indiscernible] here and in the green oval there is we have [indiscernible] already into a protocol, the combination of MRO plus paclitaxel and 1808. We will be testing 2 different doses of 1808. We know that both doses provide really good receptor occupancy for the entire period. So this is at to be very encouraging and we're looking forward to that. And our idea is that we will begin recruitment of this -- in this part of the study by Q4 of this year. We're basically getting ready as we speak. And regarding the time lines, as I mentioned before, so the idea is to complete it in 2026, our study of those 40 patients. We have requested [indiscernible] designation, and we're basically waiting for the response. And in the meantime, we were preparing for that [indiscernible] recruiting of patients in the triplet combination. And at the end of that exercise, we will be hopefully, requesting breakthrough therapy designation and requesting and meeting with FDA and hopefully be able to balance a pivotal setting with this triplet which we are pretty much convinced that we'll benefit patients on safety wise on the 1 hand, but also in terms of responses and more importantly, on overall survivor. I think those were the sites that I wanted to present, and yes, we'll get back to the questions, and I'll hand over to Bjorn to provide some very exciting preclinical data as well.

Thank you very much, Andres. I'll switch gears a bit then to talk about the nature of the BI-1808 response, specifically pharmacodynamics of the BI-1808 response. So one of the things we noted earlier in the program besides BI-1808 compelling at the tumor activity, which is also reflected by the surrogate of in the lower graph in this particular slide, showing enhanced survival of BI-1808 [indiscernible] compared to anti-PD-1 treated animals. This is the triple negative mouse EMT-6 breast cancer model. Despite that enhanced tumor activity, we found that it seemed to take longer for the BI-1808 response to kick in. And this is really by assessing individual tumor growth curves from the animals. And 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. And then there are some lines that initially grow a bit, and then they come down and flatten at the Y axis. So those are the animals that have responded and are in fact cured by PD-1 and 1808 treatment. So if you take away the non-responding animals, the picture becomes a bit clearer. I think you can all appreciate that the tumor growth curves are 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 responses to kick in, which certainly makes sense from a mechanistic perspective, by the way. So to quantify this a bit more, we simply pulled data from 8 individual experiments. And we assessed the time to response as defined by the first time point when tumors started regressing for either of the 2 treatments indicated by the dusted lines in this middle graph. And ultimately, what this resulted in was us able to calculate the mean time to response. And dramatically, we found that actually, there's a doubling of time to response in 1808 treated animals compared with anti-PD-1. We, of course, then also did the experiment where we combined the 2 drugs and then interestingly, we found that response times were engined to single-agent treatment with IV compounds. So you may say this is already and, but so how is this relevant to clinical development and to a patient that's being treated with the drug. Certainly, it doesn't matter how long it takes. All that matters is that is active and the depth of the response. Well, ultimately, this may be true when the drug is approved, but now in an explorative phase. And when we judge whether a patient that's responded or not is defined to a certain time point. As you have already heard from Andreas about the just patients that at the time of first response assessment actually had tumor volume increases of 40% and yet just sometime later, actually developed a very, very significant and robust response that span all the target lesions that were identified. We also know now from what Andres told us that this has resulted from a pseudoprogression. There was a massive influx of inflammatory sul,including activated CD8 positive cells over at least 5, 4 weeks before this first tumor volume assessment was made. The second case study is provided in the right graph. This is from the ongoing ovarian cancer study. or some revenue at the 9 weeks standpoint, there is a mean 30% increase in tumor volumes. So to a clinician, this would certainly indicate the and so for a progressive disease, whereas a few weeks later and then owing to ISS criteria, this patient was kept on and we're seeing a dramatic decrease in tumor volumes of this patient. Just very good question that Andres had already posed. Maybe in some patients, therefore response is taking longer, we relisting them if we don't add other ways to assess where the response is ongoing or not. And what might some types of investments be? Well, for example, circulating to DNA is a measure that can sort of predict or happen before the apparent tumor volume decrease that is provided by a geography. And that was actually going to be the case in this ovarian cancer patients, you see in the blue line that CDNA decreases already by the first time point and assessment of response. So ctDNA analysis without the potential to earlier identify 1808 responders. What we can then also do, of course, which has been alluded to and which we've already communicated in the product side from Andres is to develop even more powerful combination therapies that are based on 1808. And perhaps it's not look at 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. So to the far left in the slide, you're seeing that when we add 1808 to the combination of PD-1 and paclitaxel, we are, in fact, improving survival of the [indiscernible]. Very interestingly then, if we treat the animals we set a triplet, we're also further decreasing the time to response, meaning that we're maximizing chances of patients staying on the therapy. So all in all, this upcoming triplet is expected to enhance from a number of different perspectives, the efficacy of our drug. First is by providing increased efficacy. But secondly, also by making patients respond quicker and staying on about benefiting from treatment. So with that, I'll hand over to [indiscernible], who will take us through the commercial opportunities and what we're going to be considering moving forward there.

Thank you very much. Bjorn. So this slide illustrates asset [indiscernible], 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. So 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 is significant value destruction as numerous programs are stocked. So just in the case of TIGIT and CD47, there were collectively 121 such programs in 2024. In addition, companies with poorly differentiated [indiscernible] 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. So 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 2 numbers on this slide, remember, it's the 11th most common cancer in women but the fifth leading cause of cancer death in women. So indeed, when we look at the evolution of 5-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 5-year rates are still well below the average for all cancer patients. So we've already heard about the treatment for ovarian cancer from Dr. Zamarin and he showed a similar table in fact, more details. So how do they stack up and 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 5-year survival curve I showed in the previous slide. While ADCs are an exciting new modality, there are no exception, ADCs are not likely to lead to long-term remission. They have other shortcomings as well such as restriction to biomarker positive population. 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 the pembrolizumab paclitaxel combo in February of this year. This is an exciting new development in the field. And as my colleagues have already stated on which we would like to build. So indeed, for the first time, a regimen containing A checkpoint inhibitor was able to show an overall survival benefit and a potential flattening of the survival curve. I think this particular graph has been shown already 3 times, but I'll show it again because it's a nice supportive graph for our story. So back to 1808. As you all have seen from previous presentations, we have both clinical 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 a long-term remission or even cure [indiscernible] alluded this field. So 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. So the newly approved pembro 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 [indiscernible], the folate receptor alpha targeting ADC, which is the lighter pink circle in the middle with a dark outline. So [indiscernible] outlined, by the way, on this graph signifies a black box warning. So our hypothesis is that adding BI-1808 to the pembro 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. So now some research, market research results of our initial study have yielded an estimated peak revenue for BI-1808 of USD 1.5 billion in the 7 major market countries as a base case for platinum-resistant ovarian cancer. So 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 biomarkers 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. So 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 the leading T-regs and expanding effector T cells. Early efficacy in combination with pembro in ovarian cancer is impressive with a 24% objective response rate. BI-1808 has no serious additive toxicity, so it's perfect for combination therapies. As Mike [indiscernible] expected from an immunotherapy, we also anticipate long-lasting responses, which we're starting to see in our trial. And 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. So that's my last slide. I think. Thank you very much for your time.

Thank you very much, Sylvie. And before I thank everybody for the excellent presentations. Just the last point that I want 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 pembro and 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 pembro paclitaxel. So I think I just want to make the point, and maybe there's something that we can also discuss later in our Q&A. So 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. [indiscernible].

[Operator Instructions] So our first question comes from Arvid Necander from DNB Carnegie.

So first of all, thanks, everyone, for a great update. Data looks very directionally encouraging, I think. So 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? And 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 enrich for high PDL1 expression but that materially weaken the argument for added benefits beyond the Pembro monotherapy in your view. I'll start there.

Thank you, Arvid. Maybe we start with Dimitri because I don't know how much more time you have. So Dimitri, maybe you can address the second question from Arvid and then I think we hand over to Andres.

Yes, absolutely. So PD-L1 is a horrible biomarker in ovarian cancer. And it's -- if you look at the progression-free survival curves in in the Merck study, the B96, there was absolutely no difference in progression-free survival in that population whether you enrich 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. So there's some interaction that's happening there. Prior studies that have used a PD-L1 as a biomarker in ovarian cancer have not been conclusive at all. And in some studies impact low PD-L1 seem to suggest benefit from immunotherapy. So overall, I don't think that this is -- it's a good biomarker. At the cutoff that Merck has used, it was essentially such a little cut off 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 that has been agreed to make a difference.

Thank you, Dimitri. Anders, do you also want to comment quickly on the first half.

Absolutely. So we haven't looked at PD-L1 expression in the region for that is because PD-L1 expression has not been traditionally used in ovarian cancer. So that was that. And so I would expect our basis to reflect the overall population without any bias. And I would reiterate what Dr. Zamarin said, which is PD-1 expression didn't really indicate very much enhanced activity in the B96. But 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 if there is something that we should be paying attention to, but it's not something that we think will determine what we do.

Our next question comes from Richard Ramanius from Redeye.

I'd like to hear from Dr. Zamarin if he has any comments on the BI-1808 [indiscernible] in ovarian cancer of promising body.

Yes. So I think it's -- I mean I think if I weren't interested that probably want to be here. So it's -- 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 finding so far is really durable response or even really long progression-free survival. I mean the data that they're showing, demonstrating a progressive [indiscernible] of 9 to 10 months. This is better than the ADGs that we're seeing, right? Like some of the ADC studies that I have shown you have progression-free survival of about 6 months, 7 months, even though they have a pretty good response rate. So I think this is certainly more reflective of the activity that we're seeing with immunotherapies in other cancer types or help where we see a higher response rates -- and again, this is what our chemo right now. So I think what has really caught my attention is the potential durability of the clinical benefit that we can get in the stations. And I can imagine that you can enhance the response rate and maybe even improve it for the patients by starting it with a chemotherapy and then potentially drop the chemotherapy and just continue immunotherapy as well the prolonged clinical benefit.

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 now.

Can you address that.

I don't want to can address it so 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 you get I think I forgot what is [indiscernible] showed it or maybe Andres, you showed I think there was some initial pyrexia, I think it was just in the very beginning, right, for the first cycle. So just sort of -- I remember seeing [indiscernible] in some of the older studies that we have done with either with the CD40 agonist that 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. But 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, but the fact that the discontinuation rate also is quite low for the toxicities that it really highlights that it's probably -- and then again, the discontinuation -- it's similar to what we would expect with a single agent in mean checkpoint inhibitors. So it's highlight that it's quite reasonable. It's certainly lower than what we saw with the CTLA-4 combinations.

Our next question comes from Sebastiaan van der Schoot from Kempen.

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 into the ipi/nivo combination that you evaluated in ovarian cancer. That showed a pretty strong ORR level. But what's 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.

Yes. So 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 have complete responses and it's done. I think the decision was really from company driven. The IP patent was running out, we have actually approached BMS and said, can we do a randomized Phase III trial and move this further and they were not quite interested in pursuing it at the time. This was already past 2020. And that seems to be the reason again, this was also the first time that the CTLA-4 was used in patients with ovarian cancer. And the majority of patients that get treated with gynecologic cancers are at least in the United States get treated by a gynecologic oncologist for surgeons who not maybe might not be familiar with these drugs and the toxicity management again, it has changed since then. So I think it was probably a rock time and place, but there's clearly an interest. And I believe that Agenus is planning to pursue their combination going forward. I mean they're obviously moving it in the colorectal cancer, but based on the ovarian data from what I hear, they are bigger, they're planning to move it forward. And I think they should.

That's super interesting. And then regarding the available treatment options that you now have available, where would you slot in the 1808 combination with pembrolizumab. And then if I understand you correctly, would you also see an opportunity to first start with chemo and immuno checkpoint combination and then get patients of chemo as soon as possible, just to get them into response, is that kind of how we should see it over how...

Yes. No, the -- so I think the most natural combination would be to build on the B96 kind of a study. The question still comes up as we last early as can we benefit more patients than just the ones that have PD-L1 positivity. So I can certainly see that there's a rationale for during the study in both PD-L1-positive and negative patients. Now 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. So we cannot keep patients on paclitaxel long term because of neuropathy because they have been -- they start dropping things that have difficulty maintaining balance. So you cannot give that drug going for a very long time. So clinically, essentially, the way that we like to do these things is we achieved a potential maximal response and we drop the chemotherapy. And we continue with immunotherapy of all this is what we used to do when we had, let's say, just with bevacizumab as a partner. And then we can add back the chemotherapy should the patient develop progression. So I think it becomes more of a like managing on the basis of the toxicities. But we can't like treat these patients until progression because they end up in the wheelchair. So here, I can't imagine that one could design a trial where historically the 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.

Got it. That is super helpful. And then maybe for the bio event. 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 do progression. I'm wondering for the remaining patients that you want to slot into the expansion cohort, I think there are still 20 remaining. How do you make sure that if there is so progression that these patients will keep -- continue on treatment and maybe still show a response.

Andres?

Sure. So thanks, Sebastien. So yes, it's a tough question because obviously, and then 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. So what we have been doing is making them conscious of the possibility that this may be happening. There is also and maybe talk Dr. Zamarin can tell us about that. There is also a notion of this is not a scan [indiscernible] a patient so you can assess whether clinically their patient seems to be progressing or not. And that assessment can be made and discussed and 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 quite the article calls for and we have to respect that. So -- and to the point that you were asking before, that's exactly what Dr. Zamarin said, that's exactly what we want to do is what we want to put paclitaxel out front during the first 3 months and then allow the clinicians to depending on the patients 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 where in these data set were chemotherapy has been stopped and patients have continued on on the 2 other drugs and for -- and the response has continued on. So it's definitely something that we -- it is an approach that makes sense to us also and it should also impact the rate of discontinuation because obviously, if you keep patients on chemotherapy, they will come a point where they cannot celebrate it and they have to walk away from the therapy and that would be a shame if the 2 other agents are working well.

Got it. And then a final question, and I'll jump back in the queue. I'm just wondering regarding the populations with -- sorry, with high-grade series carcinoma and clear cell carcinoma patients. I'm wondering, is there a difference in how these subpopulations respond to treatment?

Are you asking me, I guess, or the ...

Both whoever wants to take it.

I can tell you just so traditionally, the clear cell carcinoma has responding less chemotherapy than high-grade [indiscernible] ovarian cancer. The clearcell carcinoma tend to be more chemo resistant there's some evidence that they may be a little bit more immuno sensitive, not that much more. So for example, if you estimate the pembrolizumab response rate being, let's say, 8% in this calculation as a single agent, in clear cell carcinoma, it would be 12%. So it's not significantly more immunogenic. But just in terms of chemotherapy response, it is usually lower.

Andres, additional comments?

No more comments. I think that was the answer that I was going to -- that I would give to that question. So thank you.

Our next question comes from Oscar Haffen Lamm from Stifel.

Thank you for organizing this event. And I actually had a question for Dr. Zamarin. I mean, since the keynote B96 data came out, how has been the perception in the medical field for this combination with PAX and pembro? I mean, do you ultimately think this they will become the new center of care for PV patients?

So it is a standard of care right now. It is FDA approved. We have a lot of confusion in the field right now, right? Just because we've got 2 approvals essentially at the same time. We have the [indiscernible] paclitaxel with relacorilant and this paclitaxel with pembrolizumab. So the question is, if you fire one, then technically, you become resistant to paclitaxel, what do you do next? Will the paclitaxel with pembro still work or not. And we do haven't resolved that in the field. the decision to use one versus the other, which 1 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 the first as opposed to the relacorilant is because the relacorilant study had more toxicities. And then just as a conscientious position, it's much more expensive towards us. So I think both from the point of view of [indiscernible] paclitaxel will be more expensive, but also real [indiscernible] drug being more expensive and puts more ones on the patient that has to take these pills like 3 days before every [indiscernible] paclitaxel infusion. But to your point, yes, the B96 is a standard. It's we will use it. 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 will have a progression. But we tend to reserve the paclitaxel be regimen until later just because, again, of the substantial neuropathy that's associated with chronic paclitaxel.

We have one more question from Arvid Necander from DNB Carnegie.

I was 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 and implications. As noted before, I guess, this readouts 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. And I think that it was breaking up a little bit when you guys talked about it, but in [indiscernible] cell ovarian cancer, it seems like there's a higher sensitivity to pembro as I've seen in KEYNOTE 100 if you compare it to the broader ovarian cancer population. So how should this subtype mix influence how we interpret the signal year both considering chemo, which I think you guys discussed more, but also the response to expected response to pembro essentially?

Dimitri, you want to address that?

Sure, Absolutely. So again, just with regards to response in clear cell carcinomas, the response rate, and you have mentioned chemos rightfully so. 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 tiers. But like I said, it's not that much higher. It's at least to the single-agent immune checkpoint inhibitors. So with the pembro alone, I think you get above 8% with the high-grade tiers 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 the combination with CTLA-4 and PD-1. In fact, there was a study that was conducted specifically in clear cell carcinomas with the CTLA-4 and PD-1. But overall, just even looking at the data in here with the BioInvent combination. We see it in both. It does -- the responses do appear to be deeper in a clear cell carcinoma patients. But 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. And again, I think I want to necessarily talk about responses as much as about the durability. And I think the durability was quite similar between -- the other question you had was more about the big line [indiscernible] of patients. Was that specifically just focusing on the histology or you have something else in mind?

That was specifically on the histology, but if you have a sore insight that we do, I'm happy to take your view on that.

I mean the other key thing to highlight, I guess, and I think Andreas has already mentioned the B96 trial allowed after 2 prior lines of therapy. And I think this is -- this one had a much heavier pretreated population. So certainly not -- the B96 is not a population that we are enrolled to these kinds of studies. And certainly, it's not a population that we treat in clinic because in clinic normally by the time the patient gets [indiscernible] a few more prior lines of therapy. So I think making cross-trial comparisons is also not necessarily fair in year. But even with that kind of a comparison, I think the data so far looks fairly compelling. Great.

I will now turn it over to Bjorn to read any written questions we have received on the webcast.

Right. So I guess we're already a bit late. I think 12 minutes past the intended time of closing. Is that right?

Yes, roughly.

We do have a couple of questions maybe and some of them have been addressed already. So I'll skip those. One question relates to potentially other combinations including like targeted therapies. And certainly, with the safety profile, if I can start addressing this and then the [indiscernible] can chime with them. I think potentially makes a lot of sense. We do see that based on a preclinical modeling that the paclitaxel combination amongst 2 different chemos we have tried seems to be speaking the best with our drug, which is perhaps not a surprise because paclitaxel is immunomodulatory deal on being [indiscernible] pure chemo. So we'll do what ever we can to sort of identify the most beneficial types of partners for our drug from that perspective, I think. Another question perhaps for you, Andres, relates to we have an estimate of the size of what got study could look like in ovarian cancer with pembro and paclitaxel.

No, we don't know exactly what that would look like. We -- what we can estimate is something of when we're thinking about this, we're thinking about the size of keynote B96, so that we're seeing 650 patients roughly. And yes, so that's basically where 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 and that will allow us to roughly to get to a better calculation 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 you want to see better responses in our antibody synergizes with CPI. There's a question that relates to myeloid reprogramming what evidence do we see at this in patients. I think that's a good one because we do believe this biology is important. And we've already passed on 2 different parameters, where we're seeing this being activated. So as Andres is waving and you can take on from me when I'm done. Just to mention that we are seeing modulation by our cells following our [indiscernible] of all our antibody in the patients. So for example, the -- [indiscernible] our 3 positive populations increase and this is known to be a population that supports [indiscernible] responses, ACT and that sort of thing, which is included in our MOA. We're also seeing that IL-12 that I showed you, be an increase in patient [indiscernible]. And preclinically, we find that it's only in the mono cells that actually produces and is consistent with other people's findings. So we need to do more, and it's early days. And analysis of tumor is always lagging a bit behind because there's a number of different things we need to do first. So we'll get back to you on that. But certainly, this biology is being recycled in the patient.

Okay. Bjorn, I think Anders was waiting because Dimitri has left, you have to sign off in. So I think what we should do is, anyway, we -- maybe we can collect all those other questions that we didn't address that yet, but we are actually already quite beyond the time that we have planned. So 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 Dimitri as well as the team. So what I would suggest is that I just finished the presentation was couple of concluding remarks. And 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. So first of all, I think before I briefly summarize the key expected milestones for this year and maybe some highlights for next year. Thanks to everybody. So unfortunately, Dimitri has left, but I think everybody, Dimitri, Bjorn, Anders and Sylvie, very good presentation. Thank you very much. And also thank you very much for the attending audience plus the good question that we heard from there. So as I said, I think with the data set that we presented ASCO 1808 in ovarian cancer, we feel it's very compelling and exceptional. Just to highlight again that it's already 3x more than KEYTRUDA alone in this patient population. And then I think even more exciting, the progression-free survival, which is already at this early stage higher than the most recent NO study. And also keep in mind that the patient populations are different as highlighted by Dimitri. So the next step there would be then really to start the triple and then basically comparing the standard of care with the standard of care plus 1808. And that we out would be available towards during the second half of next year. And then obviously, today, we were focusing ovarian cancer, but we also have very compelling data and that will be presented at EHA, which is I think for in 2 weeks from now, roughly plus also we have a key element around that and also to mention here. So if everything goes according to plan, we will be ready for pivotal study in CTCL already during 2027. Then obviously, no topic today as team, our lead compound targeting BI-1206 only component targeting at [indiscernible], which is a very interesting target. And as we mentioned also here again, the [indiscernible] subcu are also very convenient. And there, the next data release will be also at. So we're developing BI-1206 in [indiscernible] lymphoma, as you can see here and that data set will be discussed and presented at EHA and also will be presented in the [indiscernible] events so we'll have two KOL events in one go, one for T-cell lymphoma, the other one for non-Hodgkin's lyphoma just ahead of here. And then last but not least, we will have the first readout for the first-line [indiscernible] non-small cell lung cancer and [indiscernible] during the second half of this year. And then the 1206 non-Hodgkin lymphoma study would be potentially also for -- ready for people to study during 2027. So since we're already quite ahead in time, so I will stop here. Thank you again for everybody for the -- to the presenters for the presentations and of course, the attendants as well as the good questions. Thank you very much.