Morning to those of you in the United States. My Name is Søren Bregenholt. I'm the CEO of Alligator Bioscience, and welcome to this key opinion leader webcast following the release of top-line phase II data from OPTIMIZE-1, our study with mitazalimab in first-line metastatic pancreatic cancer in combination with FOLFIRINOX. If I could have the next slide, please. A forward-looking statement. The next slide, please. With me today, I have our Chief Medical Officer, Sumeet Ambarkhane, and Zev Wainberg, who is Professor of Medicine at the UCLA and Co-Director of the UCLA Gastrointestinal Oncology Program. Zev has served as primary investigator and co-investigator on a number of phase I, II, and III trials in gastrointestinal oncology, including pancreatic cancer studies. If I can have the next slide, please. So today's agenda is an introduction, an overview of the treatment landscape in pancreatic cancer, and how mitazalimab is positioned as an emergent treatment in this disease, as Professor Wainberg will introduce us to. And then next steps in the development of mitazalimab will be taken care of by our CMO, Sumeet. And finally, we will open up for a Q&A to the audience via the streaming here. So if I could have the next slide. As you may be aware, mitazalimab is a best-in-class CD40 agonist. CD40 is highly expressed on the so-called dendritic cells, macrophages, and B cells in the immune system. CD40 acts as a switch to activate dendritic cells for robust priming of tumor-specific T cells, and also induces macrophage activation, leading to tumor stromal degradation and improved chemotherapy and immune cell penetration into the tumor, a mechanism that we will touch upon during today's talk. We have developed mitazalimab in a way to give the optimal efficacy within the tumor while balancing the systemic immune activation to develop a drug with a significantly improved efficacy and tolerability balance. We have obtained orphan drug designation both at the FDA and for EMA, for mitazalimab in pancreatic cancer, and the molecule also have an IND accepted for an advanced bladder c ancer. OPTIMIZE-1, the study that we're going to discuss today, is a phase II study in first-line metastatic pancreatic cancer. The study is conducted in Europe, and mitazalimab is tested in combination with the standard of care chemotherapy, modified FOLFIRINOX. Earlier, we have released data from the study in January last year. We presented fertility data. Further interim data were analyzed in June last year. And then finally, today, we have released the primary analysis from the OPTIMIZE-1 study that Dr. Wainberg will now discuss. So Professor Wainberg, over to you. And next slide. Thank you, Søren, and it's a pleasure to be here, really, to go over some exciting data. So we'll begin over some of the background, of course, of pancreatic cancer, and in particular, the role of mitazalimab, which we think has a role in the future treatment of this disease. And next slide. So just as context, I think we all know that we're dealing with one of the most difficult cancers. There's no screening strategies that have been proven. The symptoms are often nonspecific. The majority of the patients are diagnosed in advanced disease. There's very few patients who are found when they're surgical, and the majority are found when they've already had metastatic disease, leaving systemic therapy as the main option. Simultaneously with that, we are seeing a change in the incidence of the disease, which is rising every year. The 5-year survival of pancreatic cancer remains 10%, and it's even lower in those patients who present with advanced disease. Next slide. We can see here that in the, y ou know, these estimates are, are of the United States, but we're talking about a cancer which occurs in up to 35,000 cases annually and causes nearly the same amount of deaths annually in both women and men. Next slide. This is the mortality, which has been increasing steadily year after year, such that by the end of this decade, by 2030, the expectation, based on these projections, is that pancreatic cancer will replace colorectal cancer, when you look at combined men and women, as the second leading cause of cancer death. Next slide. As we know, we've seen dramatic improvements in lung cancer with respect to therapy and with respect to options as it relates to targeted immunotherapies. As the improvements in that disease have been clear and consistent based on current phase III trials, we haven't seen the same extent in metastatic pancreatic cancer, where in any large phase III trial, the median survival is still under one year. Next slide. When we talk about pancreatic cancer, we're talking about a very sinister disease, which is, most of which is called pancreatic ductal adenocarcinoma. These cells arise from the exocrine component, not from the endocrine component of the pancreas, and are very aggressive, progress very locally, very quickly, often cause pain, and sometimes back pain, and very often spread and metastasize to the liver. Next slide. The risk factors are not well understood for this disease, but certainly some of them include smoking history, a history of chronic pancreatitis, and a bunch of other random things which are poorly understood. There's thought to be a genetic component to this disease in up to about 10% of patients, and there's also thought to be a dietary link to this disease, which is poorly understood. Next slide. So what it boils down to for pancreatic cancer is, unfortunately, we do not yet have any approved targeted therapies outside of a very niche indication for olaparib with in the maintenance setting. But when we look, generally speaking, at pancreatic cancer, we're talking about systemic therapy and in particular cytotoxic chemotherapy, which has been the only mainstay of proven therapy, which include gemcitabine-based regimens, FOLFIRINOX-based regimens, NALIRIFOX emerged recently. Then the other targeted therapies and immunotherapies have affected very, very few individuals, and really, for immunotherapy, only the MSI-High patients, and for targeted therapy, only the maintenance setting, in which olaparib is utilized in people with BRCA germline. Next slide. We've known for about a little more than a decade that the standard of care is, in frontline therapy, either one of two regimens. Either FOLFIRINOX, which showed an improvement over gemcitabine, or Gem/Nab- Pac, otherwise known as Abraxane, Gemzar and Abraxane, which also showed an improvement over gemcitabine. These two became the mainstay phase III regimens about a decade ago, in which they showed improvements in survival over gemcitabine. Next slide. Last year, we published a study, one of the largest studies done in pancreatic cancer, which compared Gem/Nab to NALIRIFOX, which is a derivative of FOLFIRINOX using liposomal irinotecan, in which the study did meet its primary endpoint with a statistically significant p-value, improving overall survival by about 2 months, from about 9 months to about eleven months with the NALIRIFOX regimen. Next slide. So as we try to move on beyond chemotherapy, because I think we've all realized that chemotherapy, we've hit the wall in this disease with respect to what we can add, drugs-wise, to these chemotherapy cocktails. We have continued to remain interested in immunotherapy, generally speaking, as a field, but we're a lot less interested in checkpoint inhibitors right now, because checkpoint inhibitors, such as PD-1 inhibitors and CTLA-4 inhibitors, have been extensively studied in pancreatic cancer and have never shown any improvements beyond small, phase I trials. What I think people are excited about is now moving beyond checkpoint inhibitors, and obviously, CD40 has always represented a key rationale in pancreatic cancer. The reason for that is that it activates not just checkpoints, such as T cells, which may have trouble penetrating into the dense stroma, but also activates tumor-associated macrophages, can enhance chemotherapy sensitivity by releasing dendritic cells. Also, somehow affects enhanced T cell infiltration, which is a critical element to pancreatic cancer through a dense stroma. I think what we'll show you today is very provocative and exciting with respect to the role of the best-in-class CD40 agonistic antibody, mitazalimab. Next slide. So OPTIMIZE-1 launched a couple of years ago, as you just heard. It is a phase II trial in which patients were enrolled in combination with modified FOLFIRINOX and mitazalimab. Modified FOLFIRINOX is the most classical chemotherapy regimen we use in frontline patients now with metastatic pancreatic cancer. The study design enrolled patients with newly diagnosed disease who were metastatic. The primary endpoint was overall response rates, with secondary endpoints, including duration of response, PFS, overall survival, and safety, and PK, and PD. What's unique about this study is that it had a few features which are unique, you don't see often in clinical trials in pancreatic cancer. One of them is it had a priming dose of mitazalimab prior to chemotherapy. The purpose of that is to engage CD40 before the onset of cytotoxic chemotherapy, and this is based on preclinical data that have been done by several groups that have suggested that's the optimal time to prime CD40, is not after T cell suppression may occur from chemotherapy, but rather before. The second thing is that it combined with modified FOLFIRINOX, which for many people, we feel it's a superior regimen to Gem/Nab- Pac. And while not exclusive, the idea of combining it with a more active chemotherapy regimen, which has a higher response rate and overall survival, was felt to be a superior approach in this particular disease. Patients were treated until disease progression, or because of toxicity, were taken off. This study, as you heard, enrolled pretty quickly in Europe. Next slide. So the baseline characteristics of the patient population are listed here. This had a split, of course, of 65 or older, and a split of female and male patients. The ECOG performance status was also well-balanced in this cohort. Keep in mind that this was a fairly large cohort for a phase II study. Usually, our phase I combination studies include about 30 patients, and here what we've seen is a total of 57 patients, which included the first batch of patients and now the second batch of patients. And so what that really is is much more robust than a typical phase I study expansion cohort. What's of interest here, I think, is that very, very few patients had prior surgery, and that's unusual in academic sites where this study was done in Europe, insofar as the majority of patients who are enrolled in academic sites, as opposed to the community, in fact, have had no surgery, but about 20% often do. And here we only saw about 3.5% of patients had prior surgery, which may reflect that it's a poorer prognostic group of patients than your a typical patient population. Also, about a full half of the patients had an elevated CA 19-9 over 1,000, which is also a poorer prognostic group. Next slide. Here are the top-line results. The confirmed response rate was 40%, which met the primary endpoint of what was set out to be achieved. There were 38.6% partial responders, with a disease control rate of 79%. The duration of response is what I think is one of the most exciting things here, 12.5 months. That's not been shown before in metastatic pancreatic cancer with a durable response like that, as we'll describe in a minute. A median PFS of 7.7 months, with an overall survival of 14.3 months, with a mature follow-up time of 12.7 months. So really, a very nice package of efficacy that's presented here, with a well manageable safety profile, as we'll discuss, with the toxicities largely consistent with modified FOLFIRINOX toxicities. Next slide, please. Here you can see on the swimmer plot that really shows just how long many of these patients remained on study. So a response duration of 12.5 months is, as I mentioned, highly unusual for pancreatic cancer. Usually, the response rates in some of these trials are in the range of 35%-40%, but the duration of response is quite a bit shorter, sometimes half this. So the fact that there are still 51% of the patients still ongoing in the study at data cut, with 32% of patients ongoing on treatment at the time of data cut, would suggest that, in fact, we're gonna end up seeing quite a bit longer duration of response in PFS as the data matures. The longest treatment duration of a patient is 23 months, which is ongoing at this time. Obviously, now down on reduced doses of chemotherapy, but remains on mitazalimab. So when you see this, you start to really, you know, start to inquire as to the role of the experimental agent beyond chemotherapy, when you see durations of response like this, and many, many patients on the study, for over a year. Next slide. So some preliminary PD biomarker work was done in collaboration with Alligator, to look particularly at what the mitazalimab PD biomarker could look like. And based on some pre- and post- whole blood analysis, one can see that there is an increase in CD4 effector cells being generated by CD40, which is in line with the mechanism of action of this agonistic antibody. That did correlate with some degree of clinical benefit, in such that responders seem to have a higher rate of CD40 production, consistent with the impact of CD40 agonistic antibody. Next slide. So when we compare how this OPTIMIZE-1 cohort did relative to some of the other published literature, which include primarily phase III trials, you can see here that the response rates, in fact, compared about the same, I would say, as some of the larger trials. A little better than some, obviously, that use Gem/Nab-P ac, but with respect to FOLFIRINOX, there has been a higher response rate with that regimen. However, when one looks at duration of response, one certainly sees that OPTIMIZE-1 is an outlier here, with a far greater duration of response than any other chemotherapy regimen ever reported in the literature. And the overall survival, of course, albeit this is a 57-patient cohort, also compares very favorably. Keep in mind, these numbers may improve as the data continues to mature, particularly insofar as overall survival, as many of these patients are on study for quite a while now. So the fact that a 57-patient cohort can demonstrate these promising signs of efficacy, to me, is an encouraging sign. Next slide. When we benchmark this in a table, which is a busy table, but you can sort of see on the right the OPTIMIZE-1 data, we are struck by a couple things. Number one, there is no prior chemotherapy regimen, and only 3.5% of patients who had surgery. As you can see, in some of the other phase I studies that have been done, phase I and II studies, in which I've participated in many of these, the imbalance is there. Here we have a group of patients in the OPTIMIZE-1 who did not have chemotherapy before, as opposed to the PRINCE trial, which was another CD40 agonistic antibody with Apexigen, and 22% of patients had prior chemotherapy. If one looks at some of the other literature with respect to Seagen trial, also their CD40 agonistic antibody, 26%. So what we're starting to see here is that this OPTIMIZE-1 regimen, perhaps because it was done in Europe, where there were less of these clinical trials ongoing at the time, just simply had a different group of patients, which was poor prognostic. No chemotherapy in the past, no adjuvant chemo, no neoadjuvant chemo, and almost no patients had prior surgery. Those represent two definite positive prognostic markers. And so with the lack of those patients in OPTIMIZE-1 suggests a poorer prognostic group of patients enrolled in OPTIMIZE-1. And of course, landmarking the duration of response relative to these other studies, as well as median overall survival and 12-month overall survival rate of 59.3%. All of these compare very favorably, in my opinion. Next slide. So the summary of this primary analysis reveals that OPTIMIZE-1 represents a previously untreated patient population that would, combined with FOLFIRINOX, met its primary endpoint for response rate and was safe and well-tolerated. Highly durable responses were observed, providing an overall survival of about 14 months. This will continue to mature. This combination, in my opinion, deserves to be evaluated now in a frontline phase III trial. These encouraging data also warrant evaluation of mitazalimab across the board, to see if we can understand where the impact in other cancers may be as well. Next slide. Hopefully, in the next steps, we'll pass it off to Sumeet to discuss these. Yeah. Thank you. Thank you, Professor Wainberg. This was very helpful to hear your expert opinion and very valuable perspective on the primary analysis data of the OPTIMIZE-1 trial. And of course, with such compelling and exciting data, comes the question: What are gonna be the next steps? Just before the end of last year, we had a very valuable scientific guidance and interaction with FDA, wherein they also endorsed the value of these emerging data and mentioned that the next step from a development point of view for mitazalimab will be, or would need to be a randomized phase III trial to be performed head-to-head against modified FOLFIRINOX as a standard of care. So, following that guidance from FDA, as well as the results of the primary analysis that we just saw, the plan is to continue the dialogue and the discussions with FDA, as well as European authorities, so that we get additional guidance on what the patient population should be, the detailed inclusion/exclusion criteria, the statistical approach, and importantly, the endpoints for the randomized phase III trial from a confirmatory point of view. So we are fully committed to continue these interactions, and also from an operational point of view, do everything that is necessary to be ready as soon as possible to start the phase III trial, and with the hope that mitazalimab can be brought to the patients as soon as possible. So I think that's that these are gonna be the key next steps, and maybe I pass it back to Søren for a concluding remark. Yes. Thank you, Sumeet. Thank you, Dr. Wainberg. Very exciting data indeed, and interesting to see the data put in context in today's and potentially the future's treatment landscape in pancreatic cancer. We should now move to a number of questions that we have received on the chat. The chat is now open. And I think the first one is to you, Professor Wainberg, and it goes like this: Looking at the NAPOLI-3 trial with the NALIRIFOX, which you know well since you had a key role in the trial, what is your feeling when the data came out on, and how do you think the NAPOLI-3 data is going to change the treatment landscape in pancreatic cancer? So, so as many know, we're hoping to hear from the FDA in the next four weeks about that particular regimen, the NAPOLI-3 regimen. The expectation is that hopefully it'll be approved. But I don't think the impact will be that dramatic, and, and by that I mean, I think there will be a segment of patients who utilize this regimen. But I don't think it'll absolutely replace modified FOLFIRINOX, or do I think it'll absolutely replace Gem/Nab- Pac. I think it's, it's gonna be a choice for patients. There will be some people who will switch to that regimen, but many certainly in the context of what the regimen represents, will stick with the modified FOLFIRINOX. However, I do think that that regimen needs to be exploited a little better, and additions to it beyond just NALIRIFOX are gonna be necessary if the regimen is gonna have a larger presence. Thank you. And this one is also to you, Professor Wainberg, and I think you touched on it a little bit already. But looking at the patient baseline between NAPOLI-3 and OPTIMIZE-1, we know that the patient OPTIMIZE-1 had, on average, an ECOG score better than the NAPOLI-3 trial. But how would you compare the patient population between the two trials on the ECOG score? I actually think the characteristics of this group of OPTIMIZE-1 compare to the NAPOLI-3 group of patients quite well. ECOG performance status, to me, is always a tricky thing to measure because most people try to get their patients on the study between 0-1. And so there is a lot of interchangeability there. But what I do think, which is quite unique here, is that the characteristics of three things always strike us when we do small studies, that we're careful we're not, you know, dealing with a better prognostic group, and those include, the lack of prior chemotherapy, the fact that they've had surgery in the past and an elevated CA 19-9. The Alligator cohorts in OPTIMIZE-1 really did represent the poorer prognostic group, which I think is actually similar to the NAPOLI-3, insofar as that was mostly a community study that did not have these patients who had prior surgery or prior adjuvant chemo. When I look internally at our studies that are being done now in academic centers, we see a lot of those patients. As I mentioned earlier, it could be up to 20%. And if you have a group of patients who are prognostically favorable, that high a cohort in that high a in that small a cohort of that high a percentage, it does make us puzzled sometimes as to whether we can read this truthfully. So that's why I think actually, the OPTIMIZE-1 cohort is more similar to a community oncology cohorts, which represents a poorer prognostic group of patients, which to me, makes the efficacy a little more favorable. Thank you. Then we have a couple of questions here about response rate and patients on study. And Sumeet, please feel free to chime in here. One question from Richard Raminius at Redeye is, should we compare the confirmed ORR of 41% or the unconfirmed at 51% with the FOLFIRINOX benchmark at 32%? And maybe a comment about the overall response rate in these trials in general. Yeah, I think that's an important question. I think the comparison should be made with the confirmed response rate, because that is also how the original study performed with FOLFIRINOX reported their data. At the same time, the unconfirmed response rate gives an indication of how many patients actually benefited from the treatment, such that there's substantial reduction in their tumor burden. So that is also helpful in understanding even if not, you know, lasting long enough, but the extent of patient that had a benefit from the experimental treatment. Okay. Thank you. Zev, any additional comments to that? No, I mean, I think that's the fair way to compare it, as Sumeet says. I mean, it's a little tricky when you're dealing with a smaller phase II study than with a large phase III trial. Mm. But I think, you know, I think we're getting to the point where, you know, the response rate is not gonna be that much more than it is in this disease. I mean, I've never been particularly in pancreatic cancer, I've never been particularly exclusively dependent on response rate. For me, response rate is tricky to measure sometimes in this disease, cause the patients have large pancreas masses, which are poorly measured. But generally speaking, I don't think we're gonna achieve more than a 40%-50% response rate in this disease in most large studies. That's not where we're gonna improve outcomes. We're gonna improve outcomes in this disease, I believe, by improving duration of response, and that will translate into overall survival, and that's why I've been encouraged by this OPTIMIZE-1 data set when I've seen it now a few times. Thank you. Then, another question that might be hard to answer, and it goes like this. Although it may be too early to answer, but did you notice a significant difference in the median overall survival between the responders and the non-responders, and in particular, w ould you know what the median overall survival of the partial responders is versus that of stable disease? I think that's to you, Sumeet. Yeah, that, that is indeed an interesting but a not so easy to answer question. I mean, what I can say is that we are in the process of looking further into the data and identifying if there are, like, any important differences in the characteristics between the responders versus the non-responders, as well as the pattern and durability of the response, again, between the responders versus non-responders, particularly the time to progression. I think what is worth noting, although from the Swimmer's plot that Professor Wainberg showed, is the fact that many patients stayed long in the treatment, and a lot of patients continued to experience only disease control, so only stable disease, but for a rather long duration of time. That indicates the immunotherapeutic contribution of mitazalimab. So yes, there may be differences in the pattern and time to progression between responders and non-responders, but the long stable disease is also a treatment effect and a benefit to patients that comes particularly from mitazalimab and this combination with FOLFIRINOX. Thank you, Sumeet. And now that I'm trying to group the questions a little bit here. And now that we have you, there's another question here that says, "You disclosed that, uh, 32% of the patients are still on active treatment versus 51% still on the study. What were the reason for the discontinuation of treatment of those 19%? Yeah, so majority of the patients discontinued because of the progression of their pancreatic cancer. That has been the case for almost or more than 90% of the patients. And a very small minority of the patients discontinued for various other reasons, and a couple also because they did not tolerate the treatment combination that well. So, but again, majority discontinued because of the progression of the underlying malignancy. Okay, thank you. And then, one for you, Professor Wainberg, and I think you touched on it a little bit in your presentation as well. The role of PD-1 in pancreatic cancer, could we get an answer on that, yes or no? Is the question here from the audience. Yeah. I mean, I'm not convinced at all that PD-1 inhibitors have a role in this cancer. In fact, in the PRINCE trial that we did with CD40, if you recall, with their CD40, with chemotherapy, with Gem/Nab-P ac, the patients that performed the best on that three-arm study were the group of patients who got the CD40 plus chemotherapy, or CD40 with checkpoint inhibitor, not the combination of these things. So I don't personally think that the checkpoint inhibitors play a role in this disease. I think there's rationale scientifically why they may, but there's many studies that have been done in pancreatic cancer, some of which have been not published, but many phase II, phase III trials which have shown no signal of efficacy with the checkpoint inhibitor. Now, some of these may still be done, cause scientifically, we all feel that engagement of T cells may help your partner work better, but we have not demonstrated that in the clinic. And so, I am personally in favor of not mandating a PD-1 inhibitor in any large trials. And I don't see a role personally. Thank you. And then quickly back to some of the readouts here. We have a question from Lars Harholt, an analyst from Denmark, and he writes, PFS is not that strong compared to the control group. How should we interpret that specific data point? So, I mean, it depends on what the reference to a control group. I don't know, is that just a general control from NAPOLI-3, or is that, so, if the reference is to NAPOLI-3, it's about, it's NAPOLI-3 was 7.2 months, so about the same. I do think that, you know, one of the things to consider here is that PFS, to me, is also challenging in this disease. I am always careful that with immunotherapy combinations, and here I do think there is some activation of the immune system that is critical. The impact of the therapy is not necessarily exclusive to when they're on frontline therapy. So by that, I mean, we do see in a number of studies in pancreatic cancer, where the impact of your, immunotherapy, and, and this has been shown with many drugs to some extent, that may continue beyond progression. And that's only gonna be realized in an overall survival readout. And so, to me, the PFS, similar PFS, let's say, to the NAPOLI-3 and nab-paclitaxel regimen, is not necessarily a big surprise either, because I also feel that it's very, very hard to continue patients on modified FOLFIRINOX for that long. But for a number of reasons, I actually don't think it's that important in this disease either. I think we need to retrain our, our minds a little to think about overall survival, which requires more patience. By that I mean more patience to let the maturity of the data read out. And so that's something I think it will become increasingly important if we're ever gonna read out a drug. Cause we're never gonna get drugs approved in this cancer off of progression-free survival anyways. That's not our accepted regulatory endpoint for now. It's only gonna be about overall survival. So unless we have an overall survival signal, which I think we do here, you know, I don't think it's going. The lack of a superior PFS, let's say of nine months here, wouldn't necessarily be more important than an overall survival that OPTIMIZE-1 showed. Sorry, it was a little long-winded answer, but. Yeah, I think we got the drift of it. Then I'm gonna sort of group two questions here into one from Luisa Morgado, who is an analyst with Kempen, and Roger Smith, one of our investors. So in your view, Professor Wainberg, what are the characteristics of PDAC that makes it such a hard-to-treat indication? And when you look at mitazalimab, is it the activation of dendritic cells or the stromal degradation that has the most impact? I mean, there's so many reasons why it's such a difficult cancer to treat. Those include everything from the majority of patients presenting with advanced disease, to the performance status of some patients being inadequate, to the fact that there's a group of patients in this disease, up to 20%, who will progress right away no matter what you give them. So unfortunately, the cancer moves that fast, so there's always in the first part of any curve, you'll notice that patients drop off quickly. It's up to 10% or 15% or 20%. And so, you know, it's such a tricky disease that way. And many, many companies and investigators have tried for so long, to try to improve outcomes here, and it's, it has been a struggle beyond chemotherapy. With respect to the stroma, I mean, there have been, I've been around long enough to know how many stromal drugs have been tested to see if we can reduce the stroma and break through, and allow more chemotherapy penetration, or in fact, allow T-cell penetration, and that's been a struggle. I do think that the tumor-stromal interaction is far more complex than we think, and there's so many different, probably proteins and prothrombotic activating proteins that get involved there that just make it extremely difficult to understand. I will say that in the studies that have been done with checkpoint inhibitors, there have been a few that have looked at pre and post biopsies of patients. What they've shown is that on the post-treatment biopsy, after a checkpoint inhibitor and chemotherapy, there simply is still too much stroma and inflammation, that there's no T-cell penetration into those primary tumors. So this, to me, is still remains such a massive task for the field to understand. Thank you. And maybe a little bit on the same, on the same, theme here before we move into some, forward-going questions to, to development of MITA. What does the two-year survival rate exist as an endpoint, and could it become relevant for approval of MITA, given the good, durability of response? It certainly is something they should look at. I mean, it's not a, it's not a classical endpoint because so many patients are not alive at two years. But, and we've used 12-month survival rate. But I think now, you know, there's a few studies out there that we can look at two-year survival rate. As the data matures, that is gonna absolutely be something that OPTIMIZE-1 should look at, too. If you are improving duration of response, let's say, and you're improving stable disease, and, the impact of your therapy exists beyond frontline therapy, which it may for a number of these patients, as I mentioned, 2-year survival point will be interesting to look at. Then, one last question. Beyond pancreatic cancer, what would be the obvious indications for mitazalimab, or for Alligator to explore mitazalimab? So is that question to me, Søren, or to? Yeah, I think from a medical point of view. Okay. So I mean, the CD40 has been implicated in a number of different cancers, as an important pathway to activate. And remember, it's an agonistic pathway, so you're trying to induce some degree of a combination of innate and other parts of the immune system. I think it's been looked at in lung cancer to some extent, in colorectal cancer as well. Apexigen, as many know, had an advanced program in pancreatic cancer and in gastroesophageal cancer, which has now been terminated. No, I think the company's been terminated. But Seagen had a CD40 agonistic antibody, which was far advanced as well in a number of cancers. So I think those are the primarily epithelial cancers where this may have a role. Okay. Thank you. Thank you, Professor Wainberg. Now, I think we will switch gear a little bit. So Sumeet, a couple of questions to you. We have mentioned in today's announcement and also during the call here, that we expect both overall survival of durability to improve with longer follow-up. Can you guide us on when the market could expect some additional follow-up data from the study? Yeah, that's an important point to take into account as far as the data are going to evolve. I think so typically the literature has reported survival rates at, like, six monthly intervals. And from OPTIMIZE-1, we have seen the emerging data and we are able to comment on what the survival rate is at 12 months. So potentially we could think of looking at an 18-month survival rate, so like six months approximately from the analysis that has been performed. But obviously, the important thing is that we continue to have the patients on treatment and have them also in the follow-up. So the follow-up will continue even beyond the 18 months. However, probably, the 18-month time point is also gonna be relevant for us to, to see how the data mature and, how they look compared to what we have, as of now with us. Okay. Thank you. Thank you, Sumeet. And a couple of questions here around the phase III design and although we have not shared any details from our interactions with the FDA, could you comment maybe, Sumeet, on the boundaries of number of patients, accelerated approval, endpoints, so on and so forth? Right. I mean, from an endpoint point of view, it was clear, as Professor Wainberg mentioned, that that overall survival remains the gold standard and has to be also the endpoint that the study, the confirmatory study needs to look at. So no surprise there. What is encouraging to keep in the perspective, the possibility of getting potential and accelerated approval, again, using overall survival as an endpoint. Of course, that depends a lot on the number of patients that the trial plans to enroll, the specifics of the statistical design, the analytical approach, and so on and so forth. These are exactly the things that the team at Alligator will continue to work upon, and of course, also together with regulatory authorities, FDA, as well as EMA, and try to get clarity on that in the coming months, so that there can be a timely start of the phase III program. The size of the trial will be somewhat similar to or would need to be somewhat similar to what the phase III trials have been so far. I think it wouldn't be too different from, for example, the NAPOLI-3 trial. But again, the numbers and the details will be dependent on the statistical designs and all the assumptions behind. Thank you, Sumeet. Then we will close the session with a couple of questions from from Patrik Ling, analyst at DNB, and those questions are addressed at me, and it goes like this: "Can you say anything about the coming development for mitazalimab? I think you have already covered that, Sumeet. And is the data strong enough to sign a partnership for the drug?" And, I think that, I'm fairly confident that the data that we presented today, the undisclosed data that we have on file, the FDA guidance that we have, that we have alluded to today, and also some of the things that we have not talked so much about, manufacturing, development, so on and so forth, I think all these things together make it very, very likely that we will make a partnership deal on mitazalimab. As always, I'm not going to speculate on timing. It's important for Alligator that we do the right deal with the right partner to the benefit of Alligator, but also allowing mitazalimab to be developed not only in pancreatic cancer, but potentially also in some of the indications that that Dr. Wainberg alluded to before. And then, the natural follow-up question from Patrick is: "Can you update us on how these partnering discussions are going?" And I can tell you that there is a number of interested companies already under CDA, both pharma and big biotech, and there is a significant amount of interest in mitazalimab, an interest that has only become greater during the day. So in summary, a strong data set for mitazalimab in first-line metastatic pancreatic cancer, a potential role for mitazalimab in the treatment of the disease going forward. We had a good review of the treatment landscape, the mechanisms, and the different data points from the OPTIMIZE-1 phase II top-line data. With that, I will thank all of you for your participation and your interest. Thank you, Sumeet, and thank you, Professor Wainberg, for your contribution. Have a lovely day wherever you are. Thank you. Bye-bye. Thank you. Thank you. Bye.