Good afternoon, and welcome to Alligator Bioscience Capital Markets Day. Welcome to you here at the Posthuset in central Stockholm, and also welcome to you who are following this event live, both in Europe and also in the U.S. A brief disclaimer before we get into today's material. Today's program is as you see here. I will introduce you to Alligator Bioscience, what we do, and our strategic outlook. Then we will spend some time on our lead asset, mitazalimab. Initially, our Chief Medical Officer, Sumeet, will take you through recent data, and then we have one of our U.S.-based key opinion leaders addressing us online from Pennsylvania. After that, we will go into a brief Q&A focused on mitazalimab. Then we will shift focus a little bit, focusing on the next wave of innovation coming out of Alligator, both our technology platforms and also the latest data on 4066, our third-generation conditional CD40 agonists. Then we will briefly talk about the other part of our pipeline, namely the 4-1BB assets, 1017, our fully owned molecule, but also 527 that we co-own and co-develop with U.S.-based Aptevo. And then finally, I will sum up, recount a little bit of the day, and start pointing towards the future for Alligator Bioscience. And after that, around four, we hope that you have time to stay this Friday afternoon for a glass of wine and a snack, and the opportunity to interact with my colleagues in Alligator's executive management team. These are the people that you will meet today. I'm here on the stage. You will hear from Sumeet, our Chief Medical Officer. You will hear from Laura von Schantz, our Chief Technology Officer. You will also hear from Peter Ellmark, our Chief Scientific Officer. It's always nice when you're doing sessions like this, that you have the main inventor of our lead asset, mitazalimab, in the room, and you have the main inventors of mitazalimab, of ATOR-4066, Neo-X-Prime, and also our RUBY platform also in the room. So you're going to hear the story from those people that really have been driving this. And finally, we also have Marie, our Chief Financial Officer, with us in the room today. So what is it really that we are trying to achieve with the science in Alligator? You're probably all aware that cancer therapy has come to new frontiers, broken new ground over the last 10, 15 years with immuno-oncology treatments, making a significant difference for a lot of patients in a number of indications. And I think today, we approximately 45% of cancer indications and cancer patients will have the opportunity to have one or another form of immuno-oncology treatments like Opdivo, Keytruda, and what they are all called. There's still issues with these treatments, as you can see from this slide. First of all, there's still more than 50% of patients that don't have access to immuno-oncology drugs because they are not approved and efficacious in their disease. As you can see on the slide here, you also have a large majority of patients where IO drugs is actually available, who don't have a significant benefit or a sufficient benefit from these treatments, either because they respond poorly or because that they get resistance to the treatment over time. And basically, what we are trying to do or what we are doing in Alligator Bioscience, is to develop drugs that can, on one hand, make those patients that have some benefit from Keytruda and other IO drugs, getting even more benefit, hopefully deeper responses, longer responses, leading to a better and longer life with their disease. As we'll see, especially with mitazalimab today, we're also working on making IO immune stimulatory drugs available in indications like pancreatic cancer, where there is no availability of approved drugs, immuno- oncology drugs today. So how are we doing this? We're doing this through our technology platforms and bringing them into fruition in our proprietary pipeline. Those of you who follow the company are very well aware that mitazalimab is our lead asset. It is in phase II clinical trials in first-line metastatic pancreatic cancer. We'll talk much more about that. We expect the top-line data from that trial in the first in early parts of the first quarter. We have ATOR-4066. We'll hear more about that. I already told you that that is the next generation of these, very interesting molecules. And then we have the clinical pipeline of, of the 4-1BB assets, ATOR-1017, and ALG.APV-527. And importantly, as you can see on, on, on this slide, we also have a number of, of partnerships. We don't talk much about that, but these partnerships are really, really important. And let me just give you a couple of examples of, of how these, partnerships actually play a central role in how we, how we run Alligator, how we, build value, for the future. So on the top here, you can see our partnership with Aptevo, which is a co-owned and co-developed molecule. Very interesting, currently in phase I clinical trials. We have worked with Aptevo over the last, five, six years. A partnership like this gives us the opportunity to bring new and breakthrough science into patients without Alligator taking the full risk, both in terms of FTEs, of full-time employees, but definitely also on financial risk. So that's one way of really boosting our ability to bring science to patients. And if you look at the bottom, you have another example earlier in the value chain. That's our collaboration with Orion, a Finnish, a Finland-based biotech company with an aspiration to develop immuno-oncology drugs. And here we are using our technologies to develop novel molecules that Orion can eventually develop. Laura will tell you more about that later. But from a strategic point of view, that is very important. It gives us an opportunity to continue to develop, adjust, fine-tune our technology platforms while we are actually not burning any of Alligator's cash on that, and at the same time, providing optionality in the pipeline and giving us both near-term, mid-term, and potentially also long-term income. So what is Alligator's journey about? What is it that we have achieved over the last couple of years? You know, Alligator has been around for a couple of decades, and we really believe that we have the opportunity to build a skyscraper like the Empire State Building here. If you look, especially on, on the last couple of years, we've done a lot of, a lot of work to ensure that we have the right organization, both on a executive level, on a mid-management level, and, and across the organization, to be able to deliver on our promise. I think we have shown that in a number of, of projects over the year. We have delivered on mitazalimab as promised, and actually a little bit faster than we initially communicated. We've been delivering on our Orion projects, for instance, faster, and we believe at a higher quality than we initially had expected. We have spent a lot of time on mitazalimab, needless to say, and then, as I said, we have used our, our proprietary platforms to develop both internal programs and also partner programs. So what's ahead for Alligator Bioscience? We believe that mitazalimab has a potential beyond pancreatic cancer, and our strategic imperative here is to find a partner that can develop mitazalimab in pancreatic cancer, but definitely also beyond, so that we maximize the commercial opportunity and reach as many patients to benefit from the molecule as possible. We will reinvest those proceeds in our pipeline. We believe that the Neo-X-Prime platform and the other proprietary assets have great potential, and we will see a number of these entering the clinic within the next five, six years. And then finally, we believe that our partner programs also have a potential to make a difference in the clinic. We already have two in phase I and phase II, and we see that the rest of the partner pipeline and potential future partnership will definitely also have a chance in the clinic. So we are building a skyscraper. The fundament is solid, the workforce is engaged, and we are really trying to lift up what we are doing. So let's just take a look at the key value drivers in Alligator. Of course, we have to start with mitazalimab. And if you look at a molecule like mitazalimab and the data we have, our current projections, you can say we can definitely launch this molecule before 2030, and probably sometime before that. But let's for the, for the matter of, of argument, just say we have a launch, before, before 2030. We modulate this molecule, at least in the first-line setting, with a peak sales of, more than $1.5 billion a year. I think that's a conservative estimate. We definitely can, can, defend a 10-year exclusivity period. And if you then sort of overlay that business case with your standard WACC or, and other, and other industry standards for how you make your, your financial case, the NPV of, of, mitazalimab is approximately $1.5 billion, and that is in a conservative setting. You will probably never hear a, a biotech CEO saying that his or her company is, is overvalued. Probably quite the contrary, and this is the case here. If you take the current market cap of Alligator, this NPV implies that the market actually only allocate a 2% success rate for the molecule to make it to the market. And I think with the data that you'll see today and the data that we hopefully will provide in early Q1, this is pretty low. And in this case, of course, you get the rest of the pipeline for absolutely free. If we look beyond mitazalimab, we have our CD40 bispecific antibody platform, which we call Neo-X-Prime, and you will see data on this both from Laura and Peter in the second half of today's program. We believe that this is the next best thing after sliced bread. It is a technology that allows us to take CD40 biology to potentially a new place, potentially developing a single-agent treatment for a number of diseases. And some of the data that we'll show you today underpins that very well. Here, ATOR-4066, our lead program in this technology is in R&D enabling activities, and we have the opportunity to make a number of new molecules using this technology. 4-1BB is also agonistic antibodies, directly activating the T cells. This is an area where there is a lot of pharma interest. We believe that this provides us a lot of optionality in going forward. For CD40 is our key focus, but these molecules definitely have merit. We are definitely believe that they can make a difference in the clinic, and we will pursue these to provide additional optionality in our pipeline going forward. And finally, we have a number of partnerships, as I just alluded to. These partnerships allow us to share risk. They allow us to generate revenue, short, mid, and long term. And again, these provide us an opportunity to branch out in new areas, should that be the case, or in the years to come. So all in all, for the current valuation, you get a lot of exciting science. You get a number of clinical programs, and also a number of partnerships showing that Alligator can develop great molecules, molecules with great safety-efficacy ratio, and we also have the machinery to deliver on these molecules throughout the value chain. So with these words, I would like to introduce to you our Chief Medical Officer, Sumeet Ambarkhane. Sumeet has a great experience from developing immuno-oncology drugs from a big biotech in Germany. And we have been tremendously lucky to have Sumeet on our team, driving our medical science, our clinical execution over the last couple of years. And Sumeet will take you through the latest data on mitazalimab. So, Sumeet, the stage is yours. Thank you. Thanks, Søren. It's a great pleasure for me to be in front of a distinguished audience this afternoon and to take you through our mitazalimab program, which we believe has a best-in-class potential as far as the CD40 monoclonal antibody is concerned. This, we believe, comes from basically the way mitazalimab is engineered. First of all, it binds to a distal epitope on the CD40 molecule on the immune cells, and the way it gets activated is dependent only upon binding to Fc gamma receptors. So basically, these two properties substantially help in improving the safety profile of the molecule compared to the first-generation, so-called super agonistic CD40 antibodies. Because of that, in our clinical program, we are able to dose mitazalimab to much higher dose levels, as high as 1.2 milligrams per kilo. So what we saw in our phase I program is not only an excellent and dose-dependent pharmacokinetic profile, but also proven biology and mode of action, in the form of activation of the T cells and macrophages that is expected for a CD40 antibody. And importantly, there was also evidence of single-agent clinical activity, in the form of objective response and many patients benefiting from the therapy over a long period of time. Importantly, the drug has received an orphan drug designation by both U.S. FDA as well as the European Medicines Agency. This is very important because it underlines the potential this drug has on top of the standard of care in terms of bringing additional therapeutic benefit to patients, and that's clearly going to help as far as the development and commercialization of the drug is concerned. Today, again, we are going to focus on our pancreatic cancer program and the data that are available in the form of the interim analysis. Before we go to the data, let's quickly see how the antibody works. Essentially, there are two main components of the mode of action. One is mitazalimab, by binding to CD40, activates dendritic cells, which in turn result into a better presentation of the tumor antigen to the T cells and increase the influx of activated T cells into the tumor. The second component is activation of macrophages and basically converting macrophages from an immune suppressive phenotype into an immune-activated phenotype, and that results into stromal degradation. Basically, we see the mode of action also confirmed by evaluating the tumor tissue that we see on the right side panel on this slide, that mitazalimab acts in synergy with FOLFIRINOX chemotherapy. Basically, the whole spectrum of cytotoxic activity, as well as immune activation, is covered by combining mitazalimab with FOLFIRINOX. This is exactly the same combination that we are also evaluating in our OPTIMIZE-1 clinical program that we will see. So coming to the design of our pancreatic cancer program, OPTIMIZE-1, the trial is conducted in patients who have a newly diagnosed metastatic pancreatic cancer, no prior therapies. The first part of the trial was a dose-escalation approach, where the higher dose of mitazalimab was declared to be safe in combination with modified FOLFIRINOX as a chemotherapy combination partner. With that recommended Phase II dose, the rest of the enrollment of the trial has been completed. The trial passed a pre-planned futility analysis in the form of an encouraging response rate, and the results are maturing as we move along. Importantly, the primary analysis of the trial is coming up in the early part of the first quarter of the new year, and those results are going to be quite important in order to fully interpret the results of the program and realize basically what potential this combination can have for the patients. So how is the treatment administered? In the trial, basically the very first treatment that the patients get is mitazalimab, the CD40 antibody. And here, this is leveraging the mode of action that we just saw. One week later, the FOLFIRINOX chemotherapy is administered, which goes on for a couple of days. And at the end of those two days of FOLFIRINOX, there's another infusion of mitazalimab that is given to patients. That is for the first cycle of treatment. Subsequently, it's simpler, the chemotherapy followed by the antibody infusion, and this treatment patients receive as long as they are benefiting from the treatment. So this is not a fixed length treatment. This is basically given to them as long as they benefit and until progression. So coming to the results of the trial, the baseline characteristics of this patient population that we have enrolled in the OPTIMIZE-1 trial essentially is very well representative of what one expects to see for patients with newly diagnosed metastatic pancreatic cancer. We believe that this forms a good basis for our subsequent planning, because we can easily feel confident about the results that we have from this trial that can be extrapolated in a much larger set of patients when it comes to confirmatory development in the phase III part of the program. The highlight of our interim results that were published in June this year are basically in the form of the swimmer plot, where we see every single patient in the trial in the form of one bar, how long the patient has been in the trial, what is the benefit that the patient has received, that we see in the form of the stars or the diamonds on these bars. It is very encouraging to see that not only there is quick onset of response, but many patients keep benefiting from the treatment and stay much longer on the treatment, as much as 18 months. And typically, the duration of treatment with FOLFIRINOX only is 4-6 months. So compared to that, it appears to be much longer in terms of durability of response. And even if these data are not fully mature, it gives a trend of basically the long durability and what to expect from our primary analysis that is coming up. Basically, the benefit in terms of long durability comes from tumor shrinkage, and that we see in this waterfall plot, that indicates how much was the reduction in the tumor lesions for these individual patients. Important to see the last couple of patients on this slide, the last two or three green patients, where there was a 100% disappearance of their tumor lesions. Basically, that is a fantastic outcome for this very difficult-to-treat patient population and a very aggressive disease such as pancreatic cancer. Last but not least, in terms of data, is the safety profile of the combination that we see on this slide. If you look at the incidence and the severity of adverse events, the serious adverse events or events that led to permanent discontinuation of the treatment, it is essentially reflecting the safety profile of the chemotherapy regimen FOLFIRINOX. And mitazalimab, as a CD40 antibody, is not really adding any toxicity to the chemotherapy. And we hear from our investigators that the patients are happy and that the treatment is very well-tolerated, which is a very important feature for any treatment in pancreatic cancer. So how do we put these data and the very encouraging results into context? Here we have to sort of try and contextualize them with respect to the standard of care therapies in this patient population. So in the gray, in the shades of gray, the treatments are representing gemcitabine, either as monotherapy or in combination with nab-paclitaxel, whereas the light green bar is representing FOLFIRINOX on its own, and the dark green bar represents our OPTIMIZE-1 trial data, so FOLFIRINOX combined with mitazalimab. In terms of both objective response rate as well as the durability of response, mitazalimab clearly stands out, compared to these two important standard of care therapies. That, together with the very good tolerability profile, makes it a very appealing regimen for the development and to be administered eventually to a large number of patients suffering from pancreatic cancer. This is also seen in the form of this sort of broader benchmarking of the data, where we lay down the outcomes from the various chemotherapy regimens, as well as other CD40 antibodies that are being evaluated in the recent times, together with gemcitabine, paclitaxel as a chemotherapy. And again, the long duration of response that we see in the OPTIMIZE-1 trial is clearly differentiating our data from what has been reported so far with other therapies. So what does that mean in terms of overall development of the program and as far as regulatory activities are concerned? So important to note that we do have an active IND with the FDA for mitazalimab in various advanced solid malignancies. So basically, the development of the molecule can be broadened substantially. We also have an approved IND, particularly in the bladder cancer, where mitazalimab is combined with a PD-1 therapy, such as checkpoint inhibitors. And again, as I mentioned, we have orphan drug designation for mitazalimab, both by FDA and E.U. Importantly, from a manufacturing point of view, we are very much on track. We've confirmed basically our approach recently with FDA, taking their guidance into account, and the development of the manufacturing process for a timely start of a phase III trial is very much on track. What is there to look forward to is essentially a couple of important milestones that we are approaching. The first one is a guidance meeting with FDA, where we are going to discuss how the confirmatory study could look like and what would it mean potentially for even, even more accelerating the development pathway for mitazalimab and, and bringing it even quicker, to patients with pancreatic cancer. And thereafter, we will have a very formal end of phase II meeting, which is kind of a required milestone before getting an agreement with the authorities in terms of how the design of a phase III trial is gonna be, and then one can embark on the start of the phase III trial. So, I think what is important to note is, mitazalimab is not the only CD40 antibody that is in development. Here we see various bigger as well as smaller companies pursuing this target, in terms of the first generation as well as the second-generation antibodies. But quite important is to note that based on all the important features, such as the safety profile, the development stage, the data that we have been generating in our program, sort of clearly leaves mitazalimab in terms of the front runner as far as CD40 targeting treatments are concerned. And we hear that more often from the different pancreatic cancer experts that we are talking worldwide, which is very reassuring. So I mean, these are good data and encouraging. Obviously, what does it mean eventually from a commercial standpoint? And here we have tried to estimate the sort of commercial case when mitazalimab will be coming to market. That leaves, I mean, even when we just looked at the major markets in U.S. and the European countries, that leaves us with a very sizable number of patients with pancreatic cancer that can be treated with mitazalimab as an immunotherapeutic approach, combined with chemotherapy. Even the conservative estimate leaves a very substantial market size, almost close to $2 billion. Of course, that comes from the fact that mitazalimab will be combined with the chemotherapy, and importantly, our development program focuses on FOLFIRINOX as the partner of choice. What sort of adds a booster to our program is the results from a recently published NAPOLI-3 trial in pancreatic cancer, which was one of the first positive phase III trials in many, many years as far as pancreatic cancer is concerned. Their regimen, called as NALIRIFOX, which is very similar to FOLFIRINOX that we are implementing in OPTIMIZE-1 trial, that was proven to be statistically significantly better than the gemcitabine/Abraxane chemotherapy combination. And that only means a very likely upside potential, because NALIRIFOX has outcomes exactly the same as FOLFIRINOX. And these data mean that FOLFIRINOX will be becoming very much the choice of treatment and the standard of care above and beyond gemcitabine-based treatment. And that basically, I mean, that has to be taken together with the fact that we have a very long durability of response in our program with mitazalimab, and we believe that this is going to even further improve the overall survival of the patients with pancreatic cancer. So it does have a significant upside potential with the positive results of the NAPOLI-3 trial. And we believe that this, this will, this will be a, an important factor, for the overall commercial case of, of mitazalimab. So I think that, that's—I mean, this is, this is what we, at Alligator believe in. I think what is also important to, to, to, to take into account is how do experts look at mitazalimab, and, how do they interpret the data as well as the potential of, of a CD40-targeted antibody in pancreatic cancer? And for that, we have today with us, online, Dr. Gregory Beatty, who's a distinguished, physician, in the Department of Hematology Oncology from University of Pennsylvania. He has led several first-in-human clinical trials in pancreatic cancer, covering different immunotherapeutic modes of action. I mean, his area of expertise includes not only CD40, but also other modes, such as CAR-T therapies. And he's been a recipient of several grants and awards to foster breakthrough research in cancer. So, Gregory, if you hear us well, happy to hand over to you, and the audience is eager to hear from you. Thank you, Sumeet, and thank you for inviting me to be able to speak to you about some of the experiences that we've had in the community regarding pancreas cancer and the use of immunotherapy as well as CD40 immunotherapy. Are the slides up? I can't see them. Yep, there we go. So, you know, pancreas cancer has become very well-recognized as one of the most difficult and lethal diseases of cancers that we can experience. It's certainly the 12th most common cancer worldwide. It's expected to become the second leading cancer of death in the next 10 years. Across the United States and Europe, there's over 200,000 annual cases that are expected, and unfortunately, most patients who are diagnosed with pancreas cancer present with metastatic disease. From the graph that's shown here, you can see that there has been a significant amount of progress that's been made for patients who are diagnosed with disease that is resectable, that can go to surgery. But as you move to the setting of distant metastatic disease, our efforts to improve long-term overall survival have been quite disappointing. Some of that relies on the fact that the approaches that we've continued to use for treating pancreatic cancer have relied on drugs that are merely cytotoxic to the cancer and don't maintain durable responses. Chemotherapy is the standard of care. It offers minimal benefits, unfortunately, to most patients. Some patients will respond, and they will have a sustained response, but for most, the norm is recurrence of their disease. There are two major chemotherapy regimens that are employed mainly in the clinic at this point. One is the FOLFIRINOX regimen, which is a four-drug regimen, and the other is gemcitabine and nab-paclitaxel. These are the most widely used, and I would say that FOLFIRINOX is becoming the preferred regimen now, particularly within the United States, for most patients. Immunotherapy, on the other hand, has not yet really demonstrated reproducible responses for most patients with pancreatic cancer, with the exception of a small subset. There's about one population of less than 1% that have microsatellite un stable disease. These pancreatic cancers have a high level of mutations, which makes them much more easily recognized by the immune system, and I do think that that's the mere fact that immunotherapy works for some patients with pancreatic cancer opens the doors for the possibility that it could work for more. There are other therapies that have recently become available for other subsets of patients with pancreatic cancer, in particular, inhibitors called PARP inhibitors, which are approved for patients who have BRCA mutations. But even here, acquired resistance is usually the norm. So, you know, pancreatic cancer has garnered this label as being remarkably treatment-resistant. So, this raises the question of, you know, why immunotherapy for cancer? And I think there are a couple of key attributes that immunotherapy seeks to bring that are important for treating cancer. The first is that the immune system has this remarkable diversity and specificity to be able to recognize the difference between what's self and what's non-self in the body. Usually, this is for recognizing pathogens like bacteria and viruses, but the immune system's also capable of recognizing cancer cells, which are normal cells that have gone awry in the body. And because the immune system is constantly present within the body, and it has this ability to expand to enormous amounts, it makes it a living drug. The concept of the immune system and medicine has long been because of vaccines, and that's the ability of the immune system to remember to rapidly respond to previous encounters. As one thinks about engineering or educating the immune system to fight cancer, this becomes important because it harnesses a key attribute, which is the ability of the immune system to constantly survey. There's this continuous monitoring for non-self in the body, and not only is the immune system capable of recognizing cells that are cancerous, but it has the ability to essentially poke holes in those cells and mediate effector activity such that it can eliminate those cancer cells. Next slide, please. So in terms of immunotherapy and pancreas cancer, the standard forms of immunotherapy that have been shown benefits across many other malignancies, well, melanoma, lung cancer, kidney cancer, and more, these therapies have also been tried in pancreas cancer. And those therapies represent some that are on this slide, which are drugs that target molecules that are designed to take the brakes off of the immune system. These are drugs against CTLA-4, PD-L1, PD-1. And the use of those drugs in pancreas cancer has largely shown limited to no benefits for most patients, even when combined with chemotherapy and even when combined with other vaccines designed to try to get an immune response going. So overall, there's really minimal responses that have been received, seen thus far with immunotherapy in pancreas cancer. And so this raises the question of why is it so resistant? And if we understood this, could we reverse and overcome this resistance and make immunotherapy an opportunity? Well, there's a number of potential immune escape mechanisms that cancer can use, and pancreas cancer tends to use each one of these. First, the immune system has to be able to recognize the cancer cells, and that means that those cells must be perceived as non-self. And there are very few mutations that are seen in pancreas cancer overall, which makes it in some ways potentially invisible initially to the immune system. Cancer cells can also set up this kind of propaganda, where it establishes itself as being harmless to the immune system by reducing its immunogenicity. In doing so, it creates this neighborhood, which has long been a hallmark of pancreas cancer, which is this fibrotic surrounding tissue that can weaken the immune system when it gets close to cancer cells. So this neighborhood or environment can suppress the immune system. And finally, as cancer develops within the body, and we know this is particularly true for pancreas cancer, it can weaken the immune system, and its overall health and fitness can be impaired. And so strategies to improve upon that are important. Next slide, please. So, you know, I think CD40 has long been perceived as a potential opportunity for the treatment of cancer. This goes back to the late 1990s. It's because of its ability to really step on the gas in the immune system to push the generation of tumor-specific immunity. CD40 is well-recognized to be a primer of the immune system against cancer. Its use in patients has been found to be safe and tolerable. In other words, antibodies that will activate CD40 and its downstream pathways are safe to do in patients. But we've noticed over the years that CD40 monotherapy by itself really has limited activity, and it's become very clear that combinations will be necessary. One such combination involves the use of chemotherapy. Here, chemotherapy has the opportunity to alert the immune system because it kills cancer cells. And that process can then allow for the immune system to be activated, with the CD40 activation boosting that immune response and generating a productive anti-tumor immune response. And this has been tested with some promising results in studies that are shown here, and really forms the basis for the clinical trial, OPTIMIZE-1. Next slide, please. There's also another reason for using CD40 in cancer, which has gone somewhat unappreciated for many years, which is the fact that CD40 can also modulate or alter the tumor microenvironments in cancer. It has this potential to remodel the fibrosis that's present there, that has been shown to be one determinant of the activity of chemotherapy. By delivering CD40 first, an antibody against CD40 that can actually enhance the efficacy of chemotherapy, thereby sensitizing the tumor to chemotherapy. Next slide, please. It's these scientific observations that's really formed the basis and the rationale behind the OPTIMIZE-1 trial that was just presented. I think this trial leverages two key aspects here: both the ability of the immune system... or both the ability of CD40 to boost the immune system and generate an effective anti-tumor immune response, but also the ability of a CD40 antibody to remodel the tumor microenvironments in cancer to enhance the activity of chemotherapy. This is due to the unique aspects of this particular trial, which are based on the sequencing of, in this case, mitazalimab with chemotherapy. In this trial, mitazalimab is given first, which is not what has been done historically in other clinical trials. And that's designed to cause stromal degradation, to allow chemotherapy to be more effective, and then chemotherapy is delivered. And at that point, that allows for an alert of the immune system, and then CD40 is again delivered after mitazalimab, to then boost that immune response. I think there's one other unique aspect here, which is the choice of the chemotherapy in this trial. Historically, gemcitabine and nab-paclitaxel has been the choice of chemotherapy to combine with CD40. Here, FOLFIRINOX is being used, and I think this is quite clever, given the fact that FOLFIRINOX is really becoming the preferred first-line regimen for pancreas cancer. So if we then take a look at some of the results from this interim analysis, here showing the spider plots that were generated for this trial, I think there's a couple key things to note. So if you click once, the first is the response rate. You see these early responses that are triggered in patients. In fact, almost the majority of the patients here are having an early response, which is very important in pancreas cancer, which is an aggressive, very progressive disease, and needs to be controlled quickly. The second, if you click again, is the response durability. Once these patients are having the response, that response appears to be maintained, and that's very important as well. It allows the patient to recover, and it shows that the treatment has durability. If you click one more time, I think this is the survival outcomes, and this is the place where we want to watch. I think these data are quite promising. Patients are having durable responses out past nine months, which is quite impressive. These are interim data, and we'll look forward to seeing more of this data as we go forward. But these are promising and compelling, and I think that the next step here needs to be a randomized phase III trial, and that would be my recommendation. So if we go to the next slide, you know, I think the prospects for CD40 and cancer remain strong. Drugs have been around for a long time, and I think the information that we've learned during that period has been quite important. We've learned that CD40 agonists are safe to deliver to patients, and we've learned that common combination strategies are going to be necessary in cancer. And so where we are is at a new place where I think the opportunities are quite enormous. There's an opportunity here now to learn how to combine CD40 agonists with other therapies, whether they be checkpoint inhibitors, new checkpoint inhibitors that are coming out, other agonists that are being developed, or targeted therapies that are in the development. And the role here is really to improve the response durability here. The other place is thinking outside of pancreas cancer, to non-inflamed or cold tumors, things like colon cancer, brain cancer, that are fraught with these myeloid cell populations that CD40 agonists aim to target and manipulate. Here, there's an opportunity to overcome primary resistance to immune therapy and improve outcomes. And I do think that there's an opportunity here in the right space for inflamed tumors, that those tumors that are considered to be immunologically hot, and those would be tumors like lung cancer and skin cancer. You know, not all patients have a complete response, and can CD40 agonists be used to help push patients into that complete response by enhancing the depth of the response? Of course, not all patients have long, durable, responses to immunotherapy, and can CD40 agonists improve the durability of those responses? So I think this, overall, I would say that this is an exciting era to be in, for drug development with CD40, and I'm very optimistic and, and hopeful to see that, to hopefully see that CD40 will make its way into, a standard of care, for patients, with cancer in the future. Thank you for inviting me. Dr. Beatty, this was excellent, and I think the floor is now open for questions. It's all my guess. And one question is that since we see that there is both different response rate and also different GPS scores for the patients in this study, is there a risk when you sort of reveal the data, there will be outliers and the number of patient is not enough to get a good response? And how do you look at that? Yeah, I think that's an important point. However, overall, we believe that the patient population that we have enrolled in the OPTIMIZE-1 trial is very well representative of frontline untreated metastatic pancreatic cancer patients. And the small or the minor variations, if we may call them, in terms of the distribution of the age or the performance status and so on, still result into similar outcomes with the standard therapies. And from that point of view, the additional benefit that we are observing, or at least a very strong trend towards that is very meaningful. Sumeet, may I add to that question, just for a moment? Please, yeah. I do think that, it's an important point, and there's some of the other data with other CD40 agonists that have been published in Nature Medicine in the past. A third of the patients in those trials have had surgically resected disease that were then enrolled because they became metastatic. My review of the data from the OPTIMIZE-1 is that there's very few of those, that patient population in this trial. It's less than 10%, I think even less than 5%. So that sets this apart because those patients actually historically do better overall, and so I do think it's an important question, but I think this trial has uniquely enrolled the right population of patients to be able to look at. Thank you. That's helpful. Can I have a follow-on question? And that's, more sort of if the data is really, really strong, could you have applied for accelerated approval in the US? We have been thinking of that, and that's certainly going to be one of the things that we would like to cover with the agency during the upcoming interactions. This being a field where many, even large phase III trials have failed to demonstrate a positive result, it's not going to be easy, but we haven't given up. We will be—I think this is all going to be data driven, and that's why we have to look up to the results that are coming up. If they are even more encouraging and impressive, we will also try to put them in context, basically with what has been reported so far with FOLFIRINOX or even other therapies, and certainly encourage the authorities to consider an accelerated development pathway. Yeah. Thank you. I have several questions, but I can start with a simple one. Could you say something more about the patients who had 100% tumor shrinking? Why, why, why are they not registered as complete responses? Yeah, that's an important question, and that comes from the fact that the graph that we saw represents the tumor lesions that could be measured on a CT scan, and those were the lesions that sort of completely disappeared in these patients. However, they had disease, which was sort of non-measurable because we followed the RECIST criteria, and those patients had, like, lesions in their peritoneum or ascitic fluid. You cannot really measure from a radiological point of view, how big they are. However, these lesions were still persistent, and that's why formally they were not classified as complete responders. Whereas it is equally encouraging because some of these patients had, like, really big... I think one patient had 6-7-centimeter mass that completely disappeared, although the little fluid or the little lesion in the peritoneum that was non-measurable, that was still there. So formally, these are not complete responders, but again, excellent outcome and benefit that they have achieved with the treatment. A more general question. CD40 has been around for, I think, at least 15 years, at least in clinical trials. So why, why do you think it's going to succeed now? Yeah, I think obviously from our point of view, we believe that our data distinguish mitazalimab with respect to the other CD40 approaches so far, and we believe that we are on a good track here. But probably here, I would also appreciate, Gregory, if you could comment with all your expertise in this field. Yeah, I think, there's a, there's a couple of key points here. The first is that, early studies looked at CD40 as monotherapy, and I think I made the point that that's not sufficient. The second is that, many studies have always relied on a sequencing of chemotherapy and CD40, which... wherein chemotherapy is given first and CD40 is given second. The idea there had always been that chemo will alert the immune system, CD40 will boost the immune system. And, you know, even some of the early data that I led, with the Pfizer compounds, we had taken note that, CD40 seemed to be making chemotherapy work a little bit better. And so this trial is different than any other trial that's ever been really run, and wherein CD40 is given first, and then chemotherapy is delivered. And I think the other piece is that, you know, the chemotherapies that have been tried, at least in pancreas cancer, have been, you know, gemcitabine, gemcitabine Abraxane. This is a different drug. I think overall, it's about how you use CD40, and that's what I'm getting at. When, how you sequence it, how do you put it together? What are the right patients to actually go after? I think all of those are key determinants to making CD40 work, 'cause there are probably, in melanoma and lung cancer patients, for which CD40 activation is not needed, it's already in place. And so, you're not gonna boost anything there. But there are a select group of patients there too, that I think if you understand the patient selection, CD40 can provide that benefit to those patients. So I think it's all about patient selection, and it's about how you put CD40 into the treatment mix that will allow it to become one, a promising therapy moving forward. And the other piece is the right combinations. And I think there's more combinations that can be explored, but having a good CD40 agonist in place is really important. And I think this drug is doing what we would expect it to do based on all the preclinical data that we have available to us. Thank you. One more question. Have you followed these two or three more or less complete responders? What happened to them afterwards? Right. I think we are following all the patients, and I think that's a very important point you bring because, because these, these patients have been on the treatment for a rather long time and are doing well. I think as of now, we have almost two-thirds of the patients in the trial that are either in the treatment or in the survival follow-up. So we are really looking forward to our primary analysis data. I think, maybe instead of commenting on the individual patients, so what I can say that, yes, they are doing well, and we are following them up for their ongoing treatment and survival. But even more important are going to be the outcomes at the cohort level, where we see a large majority of the patients either in treatment or in the survival follow-up, and that is going to contribute to the results of the overall survival from this trial. Second question is the stromal degradation effect. Is that of such importance that it can be used as a separate mode of action, meaning that mitazalimab can be used with combinations of more or less every solid cancer there is? I think that that's a very important point as far as the mode of action of mitazalimab is concerned, and we are undertaking translational experiments on our tumor tissue, I mean, the tumor tissue that we are collecting from patients in the trial. And we are hopeful that we will be able to demonstrate the result in the tumor with the stromal degradation. But again, I would appreciate, Gregory, if you could comment on the question whether stromal degradation, what does it mean in the context of a therapeutic effect. Yeah, I think, you know, stromal degradation is something that we've looked at in pancreas cancer. It's been looked at clinically in patients who have received a CD40 agonist and then gone to surgery, and stromal microenvironment that surrounds pancreas cancer is clearly altered. In other malignancies, the fibrotic, anti-fibrotic effects has been less studied. But we do know that in those other malignancies, there's been recent results with gastroesophageal cancer showing that CD40 will remodel the immune response within those tumors, and so we do expect that to happen. We don't know the effects of how that really translates into changes in the fibrosis in gastroesophageal cancer, to my knowledge. I think this is an open area of investigation, though, and I think, you know, these determinants should be looked at as CD40 agonists apply to other cancers, whether it's bladder cancer, lung cancer, melanoma, and so forth. 'Cause you're right, that this could be a very important mode of action of a CD40 agonist that has gone unappreciated for many, many years. Okay. I think we have to move on. Very exciting introduction, very exciting discussion here. So I want to thank you, Dr. Beatty, for your insightful inputs to today's discussion. Thank you, Sumeet, for presenting data, and thank you to you, as audience, for the engaging discussion. So now we will move on in today's program and talk more about Alligator's technology platforms and how we put them in play in our collaborations, and definitely also in our own internal projects. First, you will hear from Laura von Schantz, our Chief Technology Officer, telling you a little bit about our technology platforms. Laura, the stage is yours. Thank you so much. All right, can I have some slides, please? Oh, thanks. All right, so I'll take this opportunity to present to you three of our, key proprietary technologies. And these are technologies, as Søren says, gives us several advantages, and I am particularly proud of them. I'll start with the libraries. We have ALLIGATOR-GOLD, ALLIGATOR-FAB. With these technologies, we are able to generate our own binders in-house, and that gives a lot of flexibility, not only in the fact that we can generate binders against any target, but more important, that we can tailor which binders we want to work with and want to isolate. That, in, you know, in terms of affinity, in terms of how they bind and how they cross-react, and so on. We use phage display to isolate the binders. We have now complemented that with a more advanced platform using next-generation sequencing and digitized and automated processes. We also have RUBY. This is a bispecific format that just keeps impressing us. It is a format that solves several of the limitations that have been seen with other formats out there. I mean, as I'm sure you know, that bispecifics are like the next wave of drugs in cancer development and in other areas as well, but there are some challenges associated with them. And we have invented a format that I will go through it, but takes into the advantages that you can get from a monoclonal specific monoclonal antibody, both in terms of affinities and biology, and most important, stability, and you still can bind two targets at the same time. And last but not least, I will talk about Neo-X-Prime, which is, you know, the next generation of CD40 bispecifics. This is a unique way of targeting CD40 bispecific antibodies and provides several advantages on how to get a broad T cell response that will kill and eradicate the tumor. All right. On the libraries, we have single-chain libraries. That's ALLIGATOR-GOLD. We also have FAB libraries, Alligator -FAB. These are very large libraries with huge diversity. We have tested them and validated them, selected antigens or antibodies against so many different antigens, protein, peptides, haptens, whatever. We know we can generate binders against any different target, and importantly, as I said, with any property. And one example is, for example, the CEA antibody that we have in ATOR-4066. This is an antibody that binds to CEA in a particular way, and I know for a fact that when we present this, other companies that work with CEA, they are really impressed. This is not something you can get from these quick and dirty selections that people perform, you know, at CROs and so on. You really have to tailor the whole process, to be able to generate something like this. So the libraries and our process provides us with advantage to be able to select whatever we want to. We have used the libraries to generate ATOR-4066, ATOR-1017, ALG.APV-527, and so on, and we continue to use them, of course, both internally and externally. All right, on RUBY. So I call this a tetravalent IgG-like bispecific format. What that means is that it binds. It has four binding arms, two against each target, and that provides one of the biological benefits that you don't see with other bispecific formats. Having two arms allows for the use of binders that have natural affinities and not these super high unnatural affinities that you can't, you know, get the antibodies to penetrate the tumor, or you get antibodies that really don't behave as they should. And the other part of the title here, IgG-like bispecific format. As you can see, the other parts of the monoclonal structure are retained. So we have an Fc, and we use FAB domains. That gives something that is stable. Formats that, for example, use single-chain fragments, though those unfortunately are not stable. Those moieties are just not stable in the same way as a FAB. I have some summary here of things that we have tested. We have generated hundreds and hundreds of RUBYs by now, and this is what we see. We see an inherent and high developability. So we see that we can produce the antibodies. We can... if you produce a set of several hundreds, we can still have several hundreds to test in research studies. If we produce them from stable cell lines, we get yields similar to what we get from monoclonal antibodies, and we have physicochemical properties that resemble monoclonal antibodies, so we can use the same platforms that already exist for the production of mAbs. Moving on, we also study the PK/PD properties, and we see there that we have antibodies that have half-life, and serum concentration, serum stability, similar to monoclonal antibodies. I will show you some data on that. We have also studied the tumor penetration. Obviously, that is very important, so we will follow how the antibody behaves in a tumor, if we can detect it inside, and we can. And we have also generated this format in a way that the sequence-related immunogenicity risk has been decreased as much as is possible, generating a format that hopefully won't have the same issues that other bispecific formats encounter in the clinic. All right, on the functionality, as I said, we can have bivalent interaction against each target. That's important. That allows us to play around with affinity and avidity. That allows us the possibility to use different sets of, you know, different types of biology that you can't get with the format that only have one arm against each target. We also have an Fc, and we have the possibility to change the Fc to whatever we want, IgG1, IgG4, IgG2, and even mutated versions of those. We have tested, and we know it works well. And we have also, obviously also tested the functionality, both in vitro. I will show you some data. We've also tested in vivo. Peter will show you some on that. And overall, I hope that with this information, I am convincing you that, you know, this, this is a format with remarkable properties. We have, in addition, also validated the format in the collaboration with Orion. I'll talk on, a little bit on that soon. First, a little bit of data. I'm sure you are as excited as I am. So we have, on the left top, that is a chromatogram looking at the quality and the purity of the data. If you are, as me, into protein science, and you see a narrow single peak as that one you see up there, I hope you are as impressed as I am. You seldom see this with bispecific antibodies. In the bottom, I'm showing you data from pharmacokinetic studies. Here, we're studying how the presence of the molecules in serum after IV administration, and as you can see, we have studied both monoclonal and RUBY. They look practically identical, right? The curves. So the bispecific RUBY behaves as a monoclonal in vivo. We also tested functionality. Bispecifics are used to create many different new type of biology. One new biology is the conditional activation that we want to achieve, for example, in ATOR-4066. That means that we want to activate immune cells only in the presence of a TA, and that's what we can see here in vitro. So here we have immune cells that have been treated with RUBY, in the presence or in the absence of TA. So the green line is in the presence of TA. There we see a strong signal, in the absence, there is no signal at all. This means that this bispecific antibody has the potential to be active only in the tumor and not in the periphery, where it could may cause toxicities or safety issues. All right. So, as I said, we have used RUBY and the libraries, internally and externally. Orion is a company in Finland that we have collaborated with. This is a pharma company that has been around for some time, but they have also, in the last years, decided to enter a new field. They took a strategic decision to enter immuno-oncology biologics, and they chose Alligator to collaborate with. We entered in collaboration 2021. The collaboration states that we leverage our technologies, the libraries, RUBY, and we generate candidate drugs in different projects. We are eligible to quite a large milestone of $333 million, and also royalties on sales, if we get that. The first project started in 2021. It has, you know, progressed so well that even before the end of the project, Orion decided to take the licensing option, and in addition, they decided to expand the collaboration with one more project that started beginning this year. In that project, we have already passed what is called the technical milestone feasibility. All right. I think that the Orion collaboration really shows, well, several things, that first of all, we can deliver on what we promise. We have a platform that can be used to generate candidate drugs from idea to development, and also that we can, you know, use this collaboration both to generate value to Alligator, both knowledgeable value, but monetary value at the same time. All right, last but not least, Neo-X-Prime. All right, so you already know a little bit on the CD40 biology and what it does in the tumors. With Neo-X-Prime, we do something similar, but obviously, better. So in the top left, you will see what happens with dendritic cells when you add the Neo-X-Prime. So you will get an activation only in the presence of the TA. That activation, dendritic cells, would lead to cross-priming and T cell activation. The T cells then go and kill the tumor. In addition, we also get the, the stromal modification, macrophage activation. That, too, will be in a conditional manner, so in the tumor, when the TA is present. What is unique with Neo-X-Prime, and what you don't get with monoclonal CD40 antibodies, is what we call the Neo-X-Prime mode of action. So that is depicted here below. So tumors and tumor cells would constantly release tumor debris. That is, you know, parts of the tumor, not, not whole cells, but just parts of vesicles and parts of the tumor. And that material will also carry mutations that are called neoantigens. What we can do with Neo-X-Prime is ensure that those antigens or those debris are taken up by the antigen-presenting cells. They are engulfed, taken up, cross-presented on the cell surface, and then activate and prime new T cells. That response will be broader than what you will get otherwise. So, and now you also understand the name, Neo-X-Prime, neoantigens cross-presented and priming the T cells. And what the great advantage with this, I can show here, is that when you get a broad response, you will target more parts of the tumor. So that you don't get with direct tumor cell killing therapies, for example, ADCs, where you target, you know, you have toxins bound to antibodies. Those antibodies will kill cells that have the TA expressed on the surface, but will not kill the surrounding tumor cells that for one or other reasons don't have the TA on the surface. That's the same for CD3 bispecifics. They will directly kill some tumor cells, but not all. So some cells will survive. You will get tumor escape, and unfortunately, that will lead to not a complete response, right? But with Neo-X-Prime, the response is not only against the TA; it's a broad response against the other mutations, the other new antigens that were present in the vesicles and debris. So the T cells are against several different cells. All cells can die. So what we are seeing now then is that we don't need to have CEA expressed on all cells to get a full eradication of the tumor. Even heterogeneous tumors are eradicated. So this is really, really encouraging and, you know, has a great potential. All right. That was my last slide. So I'll hand over to Peter, our CSO, that will talk about ATOR-4066. Thank you, Laura. I'm gonna present ATOR-4066, and this is the first program that we have developed and built on the Neo-X-Prime platform. I'm really proud and excited to share some of the data that shows that this molecule can take CD40 targeting to the next level, and deliver on improved efficacy, tumor efficacy in key indications. ATOR-4066 is built on the Neo-X-Prime platform. The format that we use is the Ruby format that Laura just talked about, and this ensures that we will have a molecule that can be efficiently produced and will be stable and safe for the patients. The antibody targets CD40 on one end with two binding arms, and then two binding arms to a tumor target called CEACAM5. CEACAM5 is highly expressed on the surface of many tumors. It's involved in tumor metastasis and spread, and it's importantly, it's also highly expressed on tumor-derived vesicles, exosomes, and this is important for the mode of action, as you just heard. So I'm gonna present some of the data that shows that this molecule really has outstanding functional properties. So it has a strong safety profile and based on the design and the large therapeutic window, it—we can show that it takes CD40 targeting to the next level based on the activity in on the tumor, anti-tumor activity. And we can also show what Laura just described, is that we can affect also in heterogeneous tumors. And looking forward, we can see that there are opportunities both in hot tumors and in cold tumors. So colorectal cancer, gastric cancer, and other indications. Right. So when we designed this molecule, the mode of action as Laura described was a hypothesis. And now we have data that shows that ATOR-4066 can deliver on all these steps. And what we show here in this slide is in the top left, you can see an example of how ATOR-4066 delivers on conditional activation of dendritic cells. So it activates, you can see the green line, it activates dendritic cells, but only in the presence of the tumor antigen. This means that the activity will be localized to the tumor and have a better efficacy and safety profile. Secondly, on the top right, you can see that when we add CD40 expressing immune cells together with tumor debris, and the CD40 expressing cell here is in blue, and the small orange dots is the tumor debris. You can see that when you add ATOR-4066, you start to cluster these, and this is what enhance uptake of tumor neoantigens, and can then spoon-feed this material and show it to T cells, instructing them to kill off the tumor. In the bottom left, you can see sort of what this results in. We activate the dendritic cells conditionally. This results in an activation of T cells that then can go off to kill the tumor. In the end, as you can see on the bottom right, is that all these parts together results in a superior anti-tumor activity. In this model, we have tweaked it, CD40 monospecific antibody doesn't work well in this model. But when you add this bispecific antibody, you cure all of the mice. You can see the green line showing that 100% of the mice survive over time in this experiment. What you can take away from this is that the mode of action results in superior anti-tumor activity, and the activity is conditional on binding to CEACAM5. CEACAM5 is a tumor target that is highly expressed in many indication. This is just an example of a few selected indications, but it illustrates that in, for example, colorectal cancer, gastric cancer, lung cancer, there are a number of patients, and you can see each dot here is the expression level in one patient. You can see that there is a large proportion of patients where CEACAM5 is really the best target available for a Neo-X-Prime bispecific. What you also see that there is a spread between these patients in the expression level, and that means that we have a personalized medicine opportunity. We can target and select the patients that can respond best to the treatment. And fortunately, there are already validated assays to identify CEACAM5 positive patients, so that's not something that we need to develop and invent in-house, and I think that's quite an advantage. Laura talked about this earlier, and this is the data to show you how ATOR-4066 can deliver on antitumor activity also in heterogeneous tumors. So in this tumor model, we use a model system where we have two sort of steps that we don't usually do. First of all, the tumor is such that only half of the tumor cells in the tumor actually express CEACAM5. Secondly, we treat the tumor when it's really large, making it more difficult to cure the mice at day 10 here in this example. And still under these conditions, we cure almost all the mice, and we get a rapid antitumor activity going. So what about human setting? Well, when you look at the data from mice, we can see now that we can translate that into the material from human patients. So in this experiment, we have taken actual human tumor samples, dissolved them, so we have individual cells from the tumor, that is the tumor cells and the dendritic cells, and what have you. Then we just add that to a test tube and add 466. And in this setting, we can show, and you can see. Start to look at the left, you can see that we actually are able to activate the immune system in a similar way as we see in the mouse models. You can see that one of these four, actually, you don't see any response, and that was in sort of a serendipity control because it turns out that this patient didn't have any 5T4 expression at all. The rest of them had some expression, but still heterogeneous, but they had expression. So it shows that, first of all, the 5T4 levels in tumor material can activate immune cells from the patient, but you need 5T4 to do it, so it's conditional activation. And to the right, you can see this in more detail. So this is a similar experiment where we look at the individual cells. So you look at the macrophage activation, and the macrophage and dendritic cell activation, that results in T cell activation, as you can see to the right. So with this data, we can show in a human—with human tumor material, that we get the same type of activity as in the mouse data. This indicates and shows that there is a potential also for single agent activity of this drug. But having said that, when you look at the development of drugs in oncology, most is done in combination. We have so circling back to what Sumeet talked about earlier, we can see that there is a great opportunity for ATOR-4066 to enhance the effect in indications where IO already is approved, but the efficacy is not good enough. One of these data sets is shown here, shows that when you combine ATOR-4066 with PD-1, we actually get synergistic effect on T cell activation. So clear potential here. And there's also, of course, then an opportunity to build on the success of nivolumab and combine with chemotherapy. So amazing opportunities for ATOR-4066 and CD40. There are other players in this field as well, including Roche, AstraZeneca, BioNTech. But, and I'm not going to go into this in detail, but what you can take away from this is really that, there's only one other drug, the drug developed by an early stage program by Roche, that fits together with Alligator's ATOR-4066, that takes full advantage of targeting CD40 and drive efficacy, and, and have a, drive the efficacy and the safety in an optimal way. So overall, if you look at the field of CD40 bispecifics, ATOR-4066 is very well positioned in this field. To that, I'm gonna thank you for your attention here, and I think there is question time for a few questions. Yeah, thank you. Thank you, Peter. Very, and Laura, very exciting. Definitely, the next step after nivolumab. We are running a little bit late here Friday afternoon, so let's just have one single question for the audience before we, and that's you, Richard. You are fast. Does ATOR-4066 compete against personalized vaccines? So personalized vaccines are a sort of a completely different approach. It aims to the same end of getting an immune activation towards the tumor. The advantages of ATOR-4066 is that it's, it's makes the patient making its own personalized vaccine, basically. By giving ATOR-4066 and having this effect on T cells, in the end, what we get is a personalized and living drug in the patients. We get multiple different T cells that can recognize the tumor and kill off the tumor in multiple sort of attacks. Okay. Thank you, Peter. Thank you, Laura. Next up is Sumeet again, who will briefly introduce you to the other part of Alligator's portfolio, our 4-1BB monoclonal and bispecific antibody. Sumeet, take it away. Thank you. So similar to CD40, 4-1BB is another key activation and proliferation signal for T cells, and even more importantly, T cells that infiltrate into the tumor. By binding, so basically we have a couple of molecules that are directed against 4-1BB in the Alligator pipeline. One of them is our proprietary molecule, ATOR-1017. And by binding to the 4-1BB, this molecule results into an enhanced activation of the T cells. But importantly, this also has the potential to rescue the T cells from getting exhausted, because that is being postulated as one of the important mechanism for the failure of various immunotherapeutic approaches. So this approach has a lot of promise in terms of being developed further as an immunotherapeutic approach. The first generation 4-1BB antibodies have sort of so far not been successful in demonstrating the benefit, mainly because of the poor efficacy that was shown or that they resulted into a lot of systemic activation of the T cells, or even some of the safety limitations. However, this is still a very relevant target from a drug development point of view. And again, many large as well as smaller pharma and biotech companies are pursuing this mode of action. So in our portfolio, we have two 4-1BB directed molecules, ATOR-1017, as I earlier mentioned, which is through the phase I first in human development, and I'll talk about that in a second. The second molecule is ALG.APV-527, and I'm going to call it just 527 for the sake of simplicity. This is a molecule that we are developing in partnership or collaboration with a US-based biotech called Aptevo, and that's why it has the APV within the name of the drug. Overall, the mode of action is very similar to ATOR-1017, with a key difference, of course, that comes from how the molecule is structured, such that it binds not only to 4-1BB, but on the other hand, it also binds to a well-known tumor-associated antigen called 5T4. So it's also a different format from an antibody point of view, that it comprises of a single chain, a variable fragment of the antibody. Importantly, the mode of action is such that the activation happens only when the molecule binds to both 4-1BB on the immune cells, as well as 5T4 on the tumor cells, such as so that it prevents overall activation, but only does it when it is in the tumor cell and in the tumor tissue and in contact with the tumor cells. For this molecule, a phase I study has been initiated earlier this year, and it is on its way. So very briefly, the data from our proprietary 4-1BB molecule, the phase I first in human study comprised of 25 patients who underwent dose escalation through multiple dose levels. Safety-wise, this demonstrated excellent safety and tolerability without any dose-limiting toxicities, and the maximum tolerated dose was not reached for doses even as high up to 900 milligrams, administered as a single dose. From a pharmacokinetic point of view, the PK profile is, you know, excellent, dose-dependent, and importantly, that also shows signs of clinical benefit for several patients in the trial, in the form of, like, approximately half of the patients resulting in a stable disease with the single-agent treatment with ATOR-1017, and several of them with difficult-to-treat tumor types, demonstrating a durable, stable disease for longer than six months. Again, as I mentioned, the PK profile that we see on the left panel appears quite dose dependent and very favorable. That allows a dosing of with the molecule every three weeks. And importantly, on the right-hand panel, we see the mode of action or the biology confirmed in the form of increased activation and proliferation of T cells that were measured in the periphery, as well as importantly, a surrogate biomarker for the molecule that is seen in the peripheral circulation in the form of soluble 4-1BB. And that gives a good hint that this drug is demonstrating its biology as expected for the mode of action. And of course, ATOR-1017 is through the first-in-human phase I, and we are currently preparing for the phase II development, but also basically hoping to partner the program with another pharma partner to continue its subsequent development. So briefly coming to the ALG.APV-527, the bispecific 4-1BB antibody. Again, as I mentioned, the activation is dependent on the binding with 5T4 as well as 4-1BB, and we see a very good sort of dose-dependent activation of T cells and NK cells. The data are also consistent in preclinical mouse models, where a good survival was demonstrated with the increasing doses of the antibody. And again, we believe that also based on literature that this can trigger a long-lasting immunological memory that forms the basis of this bispecific antibody being taken into clinical development. And the phase one trial was initiated earlier part of this year. It's currently going through the dose escalation phase, which is currently on track, and we are hoping that the first sort of relevant results from this bispecific phase I study will be available in the second part of next year. So we have to wait here a little bit and stay tuned to how the data evolve... I think I'll pause here, and maybe do we probably take more questions or continue? Okay. We can take a question or two on the 4-1BB portfolio. Or no questions. We'll take no questions. Thanks a lot. Okay. So what does all this then come together to? We've heard about mitazalimab, our ongoing phase II study. We heard from Gregory Beatty, that the safety profile of the molecule, the efficacy profile of the molecule, the way that we put mitazalimab in play in the clinic before chemotherapy, the patient selection, and the way we conduct a trial is unique and positions mitazalimab well in this disease. And the interim data that we discussed, both in terms of response rate and especially durability of response and overall survival or survival outcomes looks very, very interesting ahead of our phase II top line readout in early Q1. And I also noticed that. ... Dr. Beatty clearly stated that the next obvious development point for mitazalimab would be a randomized phase III study. So how are things then looking together for mitazalimab in the months to come? We expect to and we are very much on track with the trial, so we expect to read out data, as I said, early Q1 next year. We have validated to a large extent the manufacturing process commercially and for phase III. And together with our dialogue with the FDA later in the year, this will inform us on when we will be able to initiate such a pivotal trial, most likely together with a pharma partner. As you can see from the slide, the molecule has orphan drug designation both in the U.S. and in Europe. That will, amongst other things, sort of facilitate a somewhat easier regulatory process. We also heard about ATOR-4066, and how that may take CD40-based therapy to another level, potentially, as a monotherapy. Here, we are early in the IND-enabling activities, and we see this molecule to be IND-ready sometime in the second half of 2025. We would have loved to move this molecule much faster towards the clinic. We believe that it has the merit to do that, but we have shown some high level of financial discipline during the last period here, meaning that we have focused our resources on bringing mitazalimab towards pivotal development as fast as possible. If we move to the 4-1BB pipeline, we completed the phase I study in with 1017 during 2022. Again, an asset where we believe that there is a lot of merit. It's clearly an asset we need to find a partner to develop this molecule with. Those are ongoing, so whether we start a phase II in the first or second half of 2024 is hard to say at this point in time. Finally, 527, as Sumeet alluded to, is currently in a phase I study in the U.S., where we are dose-escalating the molecule as a single agent. And we expect to see the top-line data from that sometimes in the second half of 2024. And we are currently, together with AbbVie, discussing how the next phases of such a phase Ib, phase II trial then look. So a pipeline with a lot of promise, with a lot of upcoming value inflection points, and definitely a news flow that is worth following. So just to reiterate what we have been doing the last couple of years, I think we can say safely that we have delivered on several of the promises we made. We have taken mitazalimab into and almost through phase II in a very proficient and effective way. We have delivered on our other clinical programs. We have taken 40-66 from merely an idea, a concept, and now to a molecule that is actually worth developing towards first-in-human trials. We have entered into a couple of important agreements, MacroGenics, Orion, and we've delivered on these programs, reaching a number of milestones that we have been communicating in our collaboration with Orion. So what is in the making for the next couple of years? Of course, mitazalimab. We need to get mitazalimab into pivotal trials with a partner. We think that is going to be fantastic for the patients. Need to get mitazalimab to the patients as soon as possible. We need to go beyond monoclonals in CD40 therapies by developing ATOR-4066 towards the clinic. As I said, that's sort of late 2025. And then we also will deliver on the first in human and dose escalation or sort of dose expansion and combination trial with the ALG.APV-527. And finally, we, of course, need to deliver on our existing partnerships, and then I can promise you that we are working hard to expand the partnerships we have, and also enter new partnerships, both as I talked about mitazalimab, but definitely also on our technology. Then the longer term aspiration, we believe that we can have a number of our proprietary assets in the clinic by 2030. I think three is a good number. If we look at the current and expected future partnership pipeline, we can also see a handful of these molecules be in the clinic by 2030. Data allowing, and if the allowing, we think that a faster approval than 2030 is definitely possible for mitazalimab in pancreatic cancer. Here it says 2027-2028. I think that is very much within reach, and with the current sales projection right now, I think we will see a profitable project and a profitable company within a handful of years after that. So with these words, I will stop now and take any questions from the audience initially, and then we'll see if there's any questions from online. Okay. If you could talk about the business development for your lead assets and also regarding sort of the next generation of ATOR-4066, would that be sort of a package, or how do you see that? Yeah. Structure? If If you would like to, it's... I guess it's depending on the taker as well, though. It takes two to tango- Yeah. Absolutely. So, you know, I'm always reluctant to talk specifically about this because it's a binary outcome. But let's say that we have more than 20 companies from global pharma to big global biotech that are very interested in mitazalimab for various reasons, whether they have a hole in the pipeline, they are vested in pancreatic cancer already, so on and so forth. Our intention is to... And we are lining these people up. Some of them are already doing due diligence, meaning that they signed a CDA and looking at data. Once we have data in early Q1, we will start a structured process with these, a tier process, and hopefully, we will end up with a handful of companies that are really, really interested once they've been into the data room and looking at that. I would say we have de-risked that, and you know, I've been on the buy side for quite a long time before or in my earlier life. I think some of the risks of a molecule like mitazalimab, we've taken away. When we come to January, I say we have data on efficacy. We probably also have a number of response correlations with that substantiating the clinical data. We have a manufacturing process that is sort of ready to go for phase III manufacturing. We have clarified the pivotal program or the boundaries for the pivotal program with the FDA, so on and so forth. So I think we have all the components to make a significant deal. I think it has been very... Over the years, there are different schools of do you want to keep different parts for yourself? The way that we look at it at Alligator is that we need a partner that can maximize the commercial value. So Alligator, as a base case, will not keep or have preferential rights, for instance, in the Nordics. We don't think that's why we're here as a company. That is to develop drugs like mitazalimab. Then I think it's an excellent question about ATOR-4066. I think that depends a lot on the partner. But of course, if you are a believer of CD40 conditional activation, why not bundle both CD40, mitazalimab, ATOR-4066, and the technology in one sort of deal? But I think that will come up in discussions with a potential partner. And I think the number of companies that we are discussing will have quite different views on how to do these kind of arrangements. Can I ask another question? Sure. -to the team of Laura and Peter? One area that is really hot in antibodies, ADC, you mentioned that, and how could you use- Is that something that you look into with the GOLD library, or how are you in that space at all? Yeah. So I mean, the GOLD and FAB libraries can be used to generate any type of binder, right? So in a sense, we can we could enter that space, but right now we are really focused on CD40 Neo-X-Prime. But I mean, I don't know if a partner would like that would be an opportunity. But then you also need the ADC component, so toxin as well. Yeah, since I thought it was a combination, it could be working. Just speculation. It could work with the what you have in- Yeah, yeah, I think it would work both with, with the libraries and with RUBY. Yeah. Okay. But I think it's a technological possibility. And our antibody technologies, whether it's the libraries or the bispecific format, can sort of be applied across- Mm ... any area where an antibody or an antibody conjugate is sort of feasible. It could also be a radionuclide. But I think the key word for Alligator now is focus. We believe we have an edge in CD40 driven by mitazalimab and some of the data that you've seen today. I think we have a world-class technology and platform in Neo-X-Prime, and we need to, and that's what we're working on, we need to leverage that value. Going off in other trajectories will just dilute that picture. So if there's anybody that needs help with antibodies, for ADCs, for whatever, we are there to help- Mm-hmm. ... pleased to help. But for our proprietary programs, we are focusing on what we are best at, and that is, the CD40 antibodies. Yeah. This is perhaps a bit of a philosophical question. I have a background in medicine, rather in surgery. We took out tumors, and it was gone. It was easy and straightforward. However, it's not always possible, and I look upon these solid tumors as heterogeneous. That is, I was told the other day, there are 800 different surface antigens to choose between. So your antibodies or anyone else's antibodies will only fit certain surface antigens, and you can get rid of a certain amount of cancer cells, thereby diminishing the tumor. But there are cancer cells that are not treated by you or anyone else, so the tumor will come back. So I think there's needs to be a combination of things. That's why I discussed this stromal degradation, because I think it's... You need to be able to access these tumors, not only on the surface, but throughout the tumor. And then, someone should combine this because Alligator's treatment or anyone else's treatment can prolong life three, four, five, six months. Is that good? It's better than nothing, but it's not a cure. Then someone should add such as lutetium 177, that targets anything close to where the antibody is, 1-2 millimeters, and kill off, regardless of what surface antigens there are. This approach is the only one if you really want to really cure tumors, apart from the odd one that always happens. That is the approach one must work for. So, Sweet, can you please give your two cents on that? And you have two mics now, so that maybe. Oh, sorry. I think one is enough. I missed that. But yes, I think this is a very important aspect, and I mean, we keep talking about response on one hand, and on the other hand, the durability of response. And yes, eventually, the tumor progresses. But I think particularly in the context of pancreatic cancer, the therapeutic strategy also needs to evolve a bit, and a drug like mitazalimab, because we see in our trial that a lot of patients want to stay on the drug, on mitazalimab. And so one other very relevant approach to think of is maintenance strategies, in these patients that mitazalimab can be not only a part of induction regimen, but it can be even, maybe even a better maintenance treatment. Maybe, and we might need another component there. It can be a checkpoint inhibitor, it can be a TGA, it can be another mode of action. But I think that's another way to prolong the durability of response and eventually prolong the survival of these patients. But yes, I think the point is well taken, and I mean, whatever we can do here is gonna help. So can I just add a comment here? And, you know, who brought this up. Thank you for this. So exactly what—I mean, we recognize that the problem you are describing, so all cells will not express the same, TA or cancer-associated antigen. But this is what we're showing here with Neo-X-Prime, that even if they don't express, for example, in this, in this study, so only 50% of the cells are expressing the antigen, but you still get eradication of all cells because you get... You mount a response that will lead to a broad, you know, priming of T cells, T cells that will attack other cancer antigens... the so-called neoantigens. So we hope that this will solve the problem you are describing. In addition, we know, for example, the CA is likely not the TA for all indications, but we can target other TAs. Therefore, there is a platform that we can generate multiple drugs against multiple cancer indications. Okay, thank you, Sumeet. Thank you, Laura. Are there any additional questions from the audience? Richard? You have a whole list there. I mean, we have to stay here all night. ... Someone wants to stop. But maybe we could continue on this aspect. So I was wondering about metastatic cancer, if that is a low mutated type of cancer with few antigens expressed. Just continuing on this other discussion, I guess, if as long as the cancer cell has an MHC system that's working and it can express, you know, antigens, it can be attacked by the immune cells. But is the limit would be if it's so mutated that it doesn't have the MHC system, so it can't present antigens. Peter, you wanna correct that or not? Right. So if we start with the second question here. T cells do need some MHC expression, but with the effect we see with CD40, even if you have no... you still have an activation of macrophages and other components of the immune system that can help out to kill the tumors. The type of activity we get also enhance, for example, NK cells. But I appreciate, I mean, it's an issue for any immunotherapy if you lose all MHC expression. On the first question, I think the number of tumor antigens, I think this is really... If there are very few tumor antigens present, you need what CD40 can deliver. That is enhancing and kickstarting the process so that you get more T cells, more high-quality T cells that can recognize the tumor. So I think CD40 plays an important role there, in, for example, pancreatic cancer. One more, Richard? Yeah. I was wondering about the collaboration with Orion. How important is that for you? How important is it for Orion? And I guess that's really the only way you utilize your platforms at the moment, or- Uh, yes. The bispecific platform. So, how important it is for Orion, that's probably not for us to answer. But, I think it's pretty important. I think it gives Orion an opportunity to become a player in immuno-oncology. You know, a company that is a legacy small molecule company moving into biologics. And we are definitely helping them on that journey. For Alligator, it's very important. It gives us, as I said, an opportunity to develop, further develop, fine-tune our internal technologies. That's both the sort of the microbiology or the chemistry of the platforms, but also the way that we run these large programs in terms of machinery and what have you. So that has been very valuable in that. And longer term, of course, there's two new molecules or two additional molecules that it is now in the pipeline that will generate revenue. And then it's actually not entirely correct, you say that this is the only way that we are using our platforms. We have a huge belief in the Neo-X-Prime platform. So one of the things that is going on, and I'll let Peter and Laura comment on it, going on right now, is that we are undertaking a significant, what can we say? Data scientific close to AI view on some of the 800 tumor-associated antigens that are out there to find a number of proteins that fulfill a number of characteristics, making them very prominent or promising targets for Neo-X-Prime in a number of indications, where we either see no immuno-oncology drugs being available, or where we see maybe checkpoint inhibitors being available, but not sufficiently efficacious. We have not told the world so much about it. We will do that when we're a little bit further, but maybe Laura and Peter can add a comment on that. Yeah, I mean, what I can add is that one of the slides I showed is that CEACAM5 is really sort of the best target for a Neo-X-Prime molecule in certain indications, but it's not all. So there are opportunities to broaden the usage of the Neo-X-Prime platform by selecting tumor antigens that are complementary to what we can achieve with CEACAM5. Okay. Laura? Yes, I can just comment on that. I mean, the platform is something that we can easily generate several different types of binders again. So even in the stage where we haven't locked in exactly what the target can be, we can use the platform to start the generation and, you know, generate molecules that in the future will maybe enter the pipelines. Okay. Thank you, Laura, Peter. So the last question of the day, anyone? Okay, then, I wanna thank you for your attention. Thank you to Laura, Peter, and Sumeet, and also Dr. Beatty. And thank for the questions, for the engagement and the discussion, and also thanks to all of you following online. Thank you.