Hello, everyone, and welcome to Faron's Capital Markets Day. I'm Juho Jalkanen, the Chief Executive Officer, and the first Capital Markets Day under my rule. I've been waiting for this day. It's an exceptional, exciting day for all of us, and it's gonna be a pretty hefty session of two hours. We're gonna have a break midway through, just a short break. And for all of you, we have a live audience here, so great to see so many of you. And one thing also about housekeeping is that, as many of you are aware, we cater a wide audience, from retail, to generalists, to industry experts, so this day is for basically everybody. So some of it is simple, some of it is a bit more technical, but hopefully, hopefully, everybody will walk away from today of more understanding on what we do, what we aim to accomplish. That's the key for today. We will be making forward-looking statements, and if I may, even some bold forward-looking statements, so classical disclaimer. Then to today's agenda. So I'm gonna talk about the vision, what we aim to accomplish. The thing is that in its history, Faron has come to the point where we could partner. We could start splitting the cake, so to speak. But before we start splitting the cake, it's time to look at the big picture and understand how big is that cake and how should we split that cake? This is extremely important. And for you guys to understand that, today, we're gonna first take you into the latest data from the trial by a wonderful physician, the principal investigator, Mika Kontro, the latest follow-up data. Then we've conducted market research in MDS, and we have an expert talking about that. Now, again, just to educate the audience, pricing Bex or exact sales figures, those are confidential company secrets. We will not be giving them away, but we will tell you what's out there, how are other priced drugs priced, what do physicians, payers think about the profile of Bex? Is there willingness to prescribe? What's the likely market going to be? So that's what we're gonna give. Then, a part of the big vision, our new CMO is gonna discuss his view on development in solid tumors and other indications. And then last but not least, the science part, Dr. Hollmén, our Chief Scientific Officer, will talk about who benefits from Bex and why. 'Cause there's an extremely strong scientific rationale in our planning, and that's what we're gonna discuss there. I want to spend a moment talking about the new management and these people. There are no expensive hired guns. This is people that eat, drink, sleep, Bex. They think about it relentlessly, twenty-four/seven, and work for you guys. We got Dr. Maija Hollmén. She's a world-leading immunologist in macrophages in cancer, and I guarantee the person that knows the most about CLEVER-1 and Bex. Then we got Mr. Wichmann, our CFO, probably has the most life science transactions out of Finland under his belt. Then [our] CMO, Dr. Bono, running the comprehensive cancer center from the local university hospital, has seen probably the most oncology clinical trials as anybody in Finland. Look at these people, and they sleep, drink, eat this drug all the time. It's just wonderful working with them. Who am I then? I'm the nobody, I guess, but I'm the hybrid of all these. I'm a practitioner by heart, but a businessman for my brain, always trying to optimize, looking for the best outcome, and I do that even in my sleep. But don't worry, I sleep well, so you don't have to be scared about that. But most importantly, I am the safe guardian of your investment, and what have we delivered under my rule so far? An exceptional EUR 30 million raise. Everybody thought that's not possible. We've continued to produce excellent data. We took that data to the FDA, and FDA blessed us with a Fast Track designation, accelerated approval possibilities, and I knew that's key for partnering. So I brought to the table the optionality to partner at this stage. But should we? We're gonna discuss that in more detail, 'cause there's a lot at stake, and you need to understand what's at stake here, 'cause we are the industry-leading macrophage reprogramming agent. So if you thought I would stop here, and take a deal, and be happy with it, then you didn't know me enough. We ain't stopping here. So let's go into the vision... and this is a very simplistic approach, 'cause I think a lot of people overcomplicate stuff. People say cancer is difficult, immunology is difficult. Yes, they are, but there are certain clear principles by if you work by them, it's not so difficult. So I'm gonna start with this. You all know it. Everybody knows it. Everybody's trying to cure cancer, but why can't we? There's still so much to do in the field of cancer. It's because of treatment resistance. There's hundreds of the cancer treatments out there, hundreds of molecules in development, but still, this is ultimately the reason why cancer keeps on growing and drugs don't work. But what's the key for treatment resistance? Go to a congress. People say it's the macrophages. Again, they're 50% of the tumor mass in nasty, non-responsive cancers. So something has to be done for the macrophages to have the next big win in cancer. And surprise, surprise, CLEVER-1 is the master regulator of an immunosuppressive macrophage. CLEVER-1. And what's ultimately the best drug? And we've been, again, working with this for twenty years. This is ultimately how you want to tackle CLEVER-1 as a target: Bex. So this is not difficult. This is very simple. Albert Einstein said, "If you can't put anything in one sentence, you haven't understood it." So this is ultimately what we want to accomplish. Have Bex as a cornerstone treatment for all cancers where CLEVER-1 macrophages are the source of treatment resistance. What does this mean? This means a hell of a lot of patients we can possibly help. And the more patients we are able to help, the more return on your investment. That's how it works, and we're talking astonishingly big numbers here. Then we're gonna show you why we believe we can pull something like this off. 'Cause the thing is, how to eat an elephant? One piece at a time. So to achieve our goal, how can we do that? 'Cause we're small. What we can pull off is a series of smart, cost-effective, phase II proof of concept trials, meaning that Bex can work here, here, here. It's not running global phase IIIs. Those are left to commercial partners. Those are huge operational endeavors and cost a lot of money. That's not our ballgame. With our resources and people and know-how, we should be doing these smart phase IIs. That's how we can achieve this. And behind this all, I talked about the management, but today, Dr. Bono is gonna present our scientific advisory board. It's. I'm gonna say, it's the best in the world. There's names pharma companies drool for. You can't buy these people with money. They don't come for the third PD-1 or the next generation TKI. They come for treatments that possibly, possibly will change the treatment of cancer for good, and that's why they come and join us. They will be designing these trials with us. They are the best names in the world, and I, I can guarantee you, no other Finnish company will ever see a scientific board like this. No other company, possibly in the world. It's a lot said, but it's true. So, us as a company, our high-level strategy, we're not losing our focus. Don't worry about that. We aim to become a revenue-producing company through the data we're producing in MDS. It's gonna happen through partnerships still, and first approvals in the area. Then, as resources allow, we're gonna start spinning out those proof of concept phase II studies, showing again, we can, you know, help these patients, we can help these patients, we can help these patients. The more patients we're able to help, the more return on your investment. Like I said, in the orange text on the right, we're at the point that we could start splitting the cake. It's a big cake. How do we split it up? These decisions we as a company are going to make, are gonna be crucial in how the cake is split. Questions, please. Let's take a seat then. I'm gonna take my glass with me. Okay, Juho, let's go straight to the, straight to the point. No, no hesitation. Sure. Okay. You gave some news on the partnership, and everybody is interested in the partnership, so can you please go through the status of that again and where you are at now? So I can't go into details. People must understand also that these negotiations are under extreme confidentiality, but we have received term sheets. There are term sheets on the table. And a part of those is how do you split the cake? And we see the cake as being pretty big. They don't necessarily see the cake as big, or more data needs to be produced in such areas to see how big is the cake. So that's the current situation in partnering. You said things are going according to your plan, so what is the plan exactly? Plan, again, was originally when I started out, is deliver the option to partner during this year, and I knew it would happen with the FDA feedback. I was anticipating that this is what they would say, so that triggered the deal making is now possible, but at the moment, again, there's a lot of options on the table, and we as a company have changed dramatically, what we were six months ago. It used to be the case that we were more, "We get what you can," kind of, but now it's like we're getting offers of deals, money, so forth. We're in the driver's seat. We get to make the decisions. So, we as a company have completely changed on where we're at and what we take or will take, and we need to take advantage. Again, not to be too greedy or anything like that, but optimizing the business case, the end result for investors. Your goal is still 2024? It's like we discussed, actually, in the H1 results. You asked me, "Well, Juho, wouldn't it be... You know, wouldn't you get a bigger, bigger deal after the full phase II readout?" That's pretty soon. It's, you know, it's in about six months, and yes, the deal size will be bigger then. Good. If there's meaningful ways of funding the company over that, then yes, we will probably be the best interest of the investors to see the readout and the deal size at that point. Okay, and the key thing is now collecting data for BEXMAB phase II. So where you are at now, and what kind of progress have you made since the previous update from May? Enrollment is going well. New data will be presented at ASH. I'm not gonna go into too much of that, because Mika Kontro is gonna come up next and talk about that. But it's again, going according to plan. We're on schedule to deliver the readout. It's looking good. The recruitment should be ready by January, right? Yes. We were, again, mentioned we were aiming, especially for the relapsed/refractory population by the end of the year, but we started, according to the FDA guidance, also enrolling frontline populations. That looks it's gonna go into January, but not too far. How confident are you about that schedule? Well, I'm gonna have to rely on Petri coming up later, but he tells me, "You can be confident. Okay, reminder, if there's any questions from the audience, please raise your hand, for example, at this point. Okay, let's start from there. I think we have a mic coming up. Hi, I'm Laura Landro. Just wanted to ask, how much bigger, if there's anything you can comment on this, how much bigger can the deals be after another six months so that it's worth the wait? And have these numbers been discussed with the possible partners? These numbers have been discussed, and deal size. I don't want it to be too specific. It's significantly bigger. Okay, so not double, triple? About so. Okay. Thank you. Hello. Assuming that you kind of can share the cake, how about the proceeds, the money that you get? Are you going to buy more eggs and flour and kind of start making new cakes or distributing it, or what? So again, it's a part of how to split the cake, talking about the partnership. We as a company, I would see we would be producing those smart phase IIs in solid tumors while a partner goes off and commercializes in leukemia. So that would be our role, again, maintaining value, generating value. But there's also possibilities of taking a new thing, a new egg into the basket, starting development on that. But again, that's preclinical. Early-stage development doesn't cost that lot. So it's that question of could we actually, you know, give dividend or something like that, that's a bit premature, I would say, to answer that. There is that possibility, but I would say we got good things bubbling under the surface that we could put in the pipeline and start again doing this. Faron was established as an entity between industry and university to take the best academic science, promising molecules, make actual drug development programs out of them, put them out at end of phase II, and they do it again, and do it again, do it again. 'Cause, again, industry is so far away from academia. There's a lot of good science, but there's not a lot of entrepreneurship, or there's not bold scientists that will actually go and run a company. So that's what ultimately Faron as a company set out to do. So yes, we would be doing that again and again, and then repeating the cycle. Any more questions from the audience at this point? Okay, let's take some from the chat. When discussing partnering, is it on an indication by indication basis, or are some partners looking at multiple indications? Mostly, pharma companies look at multiple indications 'cause they wanna be controlling on what happens. And I can mention this is a part of the negotiations we're having on pharma companies, especially big ones, hate indication splitting, 'cause if they, you know, make a big bet on a drug, they don't want anybody necessarily fooling around somewhere else, doing something with it. They wanna be controlling it all. Another one, earlier this year, analysts estimated that the industry is looking for smaller, easier to integrate companies. Sorry, due to technical issue, I lost the question here, so the other part- All right. But, is that something that... how do you see that? Is that something that you fit, or how do you kind of adapt to that situation? Actually, we fit that extremely well, 'cause we're a little over twenty people, clear-cut molecule with a lot of potential. We're an easy integration or easy build-in, easy swallow, I would say. Okay, and do you need new patents if you'd study new type of cancer? The current monopoly ends at 2037. You can have indication-specific, but there's also, for solid tumors, a biomarker-driven, patient selection-driven approach for big cancers like breast, lung, will be needed. Petri is gonna talk in a minute about that. So there is patentability going further in some of this data we generate in solid tumors. Okay, I think the rest of the questions here have been covered, and some of them are for later presentations. So thank you, Juho, and let's welcome the last next speaker, Dr. Kontro. Thank you, Antti. Thank you for the kind invitation to come to speak about bexmarilimab in myelodysplastic syndrome. I will be concentrating on the data on relapsed, resistant MDS patient population. Basically, these patients have failed azacitidine or other hypomethylating agent, which is kind of the cornerstone for MDS treatment. I will be also updating the data from May update. Briefly, about myelodysplastic syndrome, this is actually one of the most common hematological malignancies in elderly patient population. The median age at diagnosis, it's approximately 76-78 years old, and these patients are currently treated with HMAs, hypomethylating agents. We basically have two HMAs on the market currently. One is azacitidine, and another one is decitabine. Then basically, approximately 50% of the patients achieve treatment response for these compounds. Unfortunately, these responses are rather short-lived, so even though the patient achieves treatment response, most of the responses are lost during two years from the therapy start, and then we are facing so-called HMA-failure MDS, and this patient group actually carries very dismal outcome. The patient typically suffer from anemia, thrombocytopenia, leading to continuous transfusions. They do have neutropenia, leading to infections and frequent hospitalizations. Unfortunately, when we have HMA-failure MDS, the outcome of the patient is extremely poor. Previous historical controls show that the overall survival is between four to six months, and very seldom patients actually have longer outcome compared to that. So how does bexmarilimab fit into the picture? As was already introduced by Juho, this is a CLEVER-1 inhibitor, and in hematological malignancies, CLEVER-1 inhibition on the monocytes, it makes the monocytes immunoactive from their previous immunosuppressive state. Basically, after that, they recruit other immunological cells, most importantly T cells, leading to immune activation, and that's basically is already enough to destroy the blast cells. But in addition to that, previous, yet unpublished data shows that bexmarilimab also has a mode of action of deactivating the energy production in the blast cell, and basically, this offers kind of dual inhibition for the cancer cell and aiming to get a treatment response. I will next briefly discuss about the BEXMAB trial design. The trial has been now ongoing approximately 2.5 years. So in the phase I part of the trial, the participants receiving doublet therapy, doublet meaning azacitidine and bexmarilimab, we have recruited patients with frontline higher-risk MDS and CMML, chronic myelomonocytic leukemia, also relapse-resistant AML, and importantly, those MDS and CMML patients that have failed previous HMA-based therapy, and this is the patient population that we have then been treated with azacitidine and bexmarilimab, and the first cohort or indication that we have taken to the phase II is the relapse-resistant MDS patient population, so basically HMA-failure patient population. As you have mentioned, we also have been currently expanding the patient numbers for first-line MDS, and the reason for this is that also in that patient population, we see quite promising initial activity. One mention about the relapse-resistant MDS patient population, so basically this is a randomization for three or six milligrams per kilogram per one patient in combination with azacitidine. These are our current trial sites. We have very active sites here in Finland, Helsinki, Kuopio, Tampere, and Oulu. We have excellent U.S. sites, including MD Anderson, City of Hope, Yale, and University of North Carolina, and as mentioned, there will be two additional sites starting in the upcoming weeks. I will briefly discuss about emerging biomarker data. With biomarker, we mean that what are kind of the predictors of the response? And first of all, I think what is very important to see, on the left-hand upper corner, is that we see very good target engagement, so, CLEVER binds to its target. Below that, we can see that HLA-DR expression increases when the patients received bexmarilimab plus azacitidine therapy. This is important because HLA-DR, it's kind of initiating event into immunological cascade, so basically, it's antigen-presenting molecule, and which then will recruit the T cells, and on the right-hand side, we can see that when we are treating the patients with aza plus Bex, we see increased numbers of CD4 cells, which are kind of helper T cells, but also, most importantly, CD8 cells, which are kind of the cells that are responsible for cell killing in MDS and AML. We have some initial data also predicting response. We see that the patient that have higher HLA-DR expression during the therapy are the ones that are... have the highest likelihood of responding, whereas when we are looking at the baseline, meaning before therapy, the T-cell levels, the higher T-cell level reflects the higher likelihood of patient achieving treatment response for aza plus Bex. Next, safety data, efficacy data. This is our current safety data from relapsed/refractory MDS patient population, so-called HMA-failure patients. In this patient population, we had only four bexmarilimab-related adverse events, including nausea, peripheral edema, fever, infusion-related reaction, and all these adverse events that were related to bexmarilimab, they actually were mild, being grade one or grade two. We didn't have any serious adverse events related to bexmarilimab, but certainly, given the patient population, we did have several serious adverse events. They were considered to be related either to azacitidine, which is the normal therapy that the patients would be receiving, or then they were considered to be related to underlying disease. This is the slide that was already presented in May. The data showed at that point that median overall survival is 13.4 months, but at the time the follow-up time was actually rather short, so this was still a bit uncertain, and I have now here the updated data. So first of all, the median follow-up time has now been increased from 135 days to 275 days, meaning that the median follow-up is approximately 9.1 months. We see good marrow responses. Eight out of 14 achieved marrow response, being complete remission or marrow complete remission, meaning that the blast count is under 5%, and altogether, 11 out of 14 HMA-failure MDS patients actually achieved treatment responses. This is basically calculating in also the hematological improvements. At last readout, there were two patients that were bridged to allotransplant after aza, and now we have a third patient. So basically, three patients have now been allotransplanted after the azacitidine bexmarilimab therapy. And then getting back to the overall survival, it has remained unchanged. Currently, the overall survival continues to be 13.4%. As mentioned in the very beginning of this presentation, kind of the historical control of data from HMA failure to, for overall survival is approximately five to six months. Of course, it's always a caveat to compare with the historical controls, but I think that the overall survival median that we currently observe being 13.4 months, it certainly is promising. And I think it's what is interesting is that the median time on bexmarilimab treatment for these HMA failures, it's approximately 8 months, perhaps being an indication of low level of treatment-related toxicity, as was already discussed on the AE slide previously. But that was very short update on our current status, and happy to take any questions. Okay, by the way, I didn't properly introduce myself, so my name is Antti Siltanen, and I'm an equity analyst from Inderes, and will be moderating the questions for Faron. Okay, let's start with a broad question from chat. How do you see current bexmarilimab data as a clinician? As mentioned previously, regarding the overall survival data being over 13 months, it certainly is promising. Given the overall response rates, approximately 11 out of 14 do achieve some kind of response. Again, that's promising, but of course, being a clinician, I always want to see more data, and then, of course, in that sense, also the readout after the phase II will be highly crucial and highly interesting. If I put it this way, we are going in the right direction with both responses and survival. Now, the first-line MDS patient population and the r/r MDS is the patients are quite different, so can you talk a little bit about how you see bexmarilimab in relation to these two conditions, and what are kind of the opportunities for both populations? Yeah, that's a great question, and it's perhaps easier to start from relapsed, resistant patient population. So after HMA failure, we currently don't have any approved compounds for that patient population. And as mentioned, 50% of the MDS patients don't achieve treatment response, and the remaining 50% will lose the retreatment response. So I think that that's the highest unmet medical need. As I have been discussing previously in these events, I think that also, as mentioned, given the numbers, we do have room for improvement also in the frontline MDS. So I think that these are the two most interesting patient populations for bexmarilimab. Yes. A straightforward question: Is it easy to enroll patients? And maybe this is also related to the two new U.K. centers, so do you need those U.K. centers to enroll quickly enough, or was there another reason for that? Well, of course, given any trial, there is always need to recruit faster. But I think that it has been rather smooth to recruit patients. We have excellent sites in Finland, in addition to Helsinki, that have actually been very active in recruitment. And I think that also what has been on our side is that in Finland, the patients in general are highly motivated to take part in the trials and academic studies. So I think that it has been rather straightforward to include patients. I think that regarding bexmarilimab, there has been kind of new angle for recruitment, is that the patients are aware of the compound being available for MDS patients. And I have been doing clinical trials for over 10 years now, and I'm currently running our clinical trial unit for hematology in Helsinki. This is basically one of the first trials that patients actually contact the physicians or study nurses directly to ask the possibility about getting into the trial. So there certainly is kind of a new activation also for the patients in that sense. Are there differences between the first line and the R/R patients? You mean with recruitment? In terms of enrollment. Yeah. I think that in first line several patients can receive azacitidine treatment option, so it has been in a sense easier to recruit those patients that have HMA failure because there is no treatment options for that patient population yet. Yes. So how about any questions from the audience? Okay, let's continue from the chat. So can you explain what is meant by mCR or marrow complete remission, and is there any relationship with overall survival? Yeah, that's a great, great question, because I will be quite broad, sorry about that already now, but so basically, regarding MDS response criteria, it has been rather old. The current criteria were established already 2006, and basically, all MDS trials are currently utilizing those. They were revised last year, and for example, regarding the mCR, the mCR isn't currently considered to be optimal response criteria, and then we have had also internal discussion with investigators and Faron team that we also could evaluate the responses using the criteria that were recently proposed and have been implemented. But then again, when we are kind of currently evaluating different trials and the outcomes on the ongoing trials, for example, AZA plus VEN trial, so then it's easier that we still do use those previous response criteria. Yes. Okay, how long can you stay on Bex? Do you continue the bone marrow transplantation at some point, or can you also shift back to earlier failed medications? I'm not 100% sure if I understand the question correctly, but I, I can allude that the longest lasting patient that I have has been receiving aza plus Bex now for approximately 2.5 years. If we go to allotransplant, as per protocol, we don't have a possibility to continue aza Bex so-called maintenance therapy. In that sense, if we would need something else, we could go, for example, azacitidine as a maintenance therapy after allotransplant. But basically, I don't see a need for a kind of step-down therapy, because at least this far, we haven't had toxicities that would have urged us kind of to do step down from aza plus Bex to, for example, aza monotherapy. There is a question: is median overall survival increasing from 13.4 months? And maybe I could also kind of add to that. Can you explain a little bit what the 13.4 months of overall survival means, considering that there are some transplant patients and so can you explain a little bit about that? Yeah. ... number and how that has developed? Yeah, that's a, again, excellent question. So median overall survival, it's basically a Kaplan-Meier estimate, which is a statistical method. But so basically, if you have 100 patients and you put them in the row, and you take the patient number 50, and what is kind of the overall survival median for that patient is, it's roughly, it's not exactly, but it's roughly kind of the estimate of that. With regard to what does 13 months mean in relation to previous historical controls, if we don't do anything, we just have the palliative care, the overall survival is between four to six months. So with this information that we currently have, we certainly have prolonged overall survival compared to previous standard of care in that patient population. So can we expect to see longer overall survival? Yes, we can. So there are patients that are still on trial, and those can actually move the overall survival basically in both directions. There's a question, what can go wrong in terms of next data readouts? Maybe this is a statistical question on. Yeah, that's something that we can leave to the Faron statistician. But, yeah, as mentioned, what we always need is that we have enough data and we have a concrete kind of data to make and draw conclusions. At this point, as mentioned, I consider this data very promising, but of course, as mentioned, it's always good to see more data. Yeah, and if you think about the responses and how quickly you see those responses, so based on that information, how long do you think you have to follow the patients after the recruitment is finished to kind of get enough information on the responses? Yeah, that's basically two-sided question in a sense that, we do see responses faster than, compared to azacitidine only. Azacitidine-only therapy produces the treatment responses in four to six months, and for bexmarilimab, we see that faster. I don't have the exact cycle number, for that, but it's faster. And, and then regarding the overall survival, as shown today, the initial data in May was immature. Now, we have more mature data that we can evaluate. So of course, the overall survival, which is the most important in a sense, it always takes time to mature. Good. Is it reasonable to say that for responses, something like six months or? Uh, yeah. You should see most of the responses by six months. Is that fair? Yeah, yeah, yeah. Ready for responses. Yes. ... exactly, yeah. But for survival i t's six months, it is short. Yes. Yeah. Okay, I will check again if there's any questions from the audience. Okay, if not, let's welcome the next speaker, Mr. Ralph Hughes. Please. Hello there. My name's Ralph Hughes. I'm a Senior Vice President at PharmaVentures, which is a transaction advisory firm and, strategic, advisory firm. Can we have the next slide, please, and the next one? As you heard, there's a disclaimer in terms of, what we can and what we, cannot say, what this report is about, and more importantly, what it's not about. I'll cover off some of those points on the next few slides, though. If we could move forward. I'll start off by telling you a little bit about us, who we are, what we do. We'll talk a little bit about, the patients, the epidemiology, and the market overview. We'll talk about some of the KOL insights that we've been able to get out for Faron. We'll look at the patient population, and we'll look at some of the pricing and payer insights. Next slide, please. Thank you. So PharmaVentures is a leading life sciences and healthcare advisory firm. We provide advice, guidance, and transaction support for business development and licensing. We also provide primary research, KOL research. We do valuations, and provide kind of strategy, input, and M&A guidance as well. So, we operate primarily in the pipeline and in the context of business development, with most of our strategic advice and primary research. Next slide, please. So Faron asked us to try to understand what the market landscape is going to be like for bexmarilimab when it launches into the market. In order to do that, we reviewed the bexmarilimab target product profile with payers, with KOLs, and we developed an epidemiology-based model. I'll provide some of the insights from this work over the next few slides. However, the information that we provide here is not investment or financial product advice and should not be taken as a basis for making an investment decision. We will be providing feedback from payers, from KOLs, and some epidemiological insights, but that's it. So, the scope was across the U.S., Germany, and France in terms of payers, and with KOLs, we picked across the U.S. and Europe. We got two KOLs from Germany and Spain, from Europe, and two from the U.S. They were hematologists, and with extensive experience in both patient care and research, and are actively involved in both MDS, AML, and in various clinical trials. The payers, we focused in... Well, we looked at the U.S. primarily, and the insights I'll be providing today will primarily be affecting the U.S. But we did also look at payers from Germany and France as two of the most difficult but also impactful markets from a pricing and market access environment. We also developed an epidemiology-based model. We started off with incidence data, and we layered in various stratification factors, which I'll talk more about shortly. The next slide, please. And one more. So the epidemiology-based patient flow is very complex. MDS has multiple lines of potential lines of therapy. And it also has multiple elements, such as anemia. It has high, medium, intermediate, and low-risk patients, causing the actual sub-stratification of the epidemiology to be quite complicated. We built out this model with cannibalization of different populations between high risk and low risk and between first-line and second-line treatment. So that's. And you'll see later how that interacts, how that cannibalization and how the different flow of patients interacts with each other in terms of the way the epidemiology plays out and the sub-stratifications that we've put on it. Next slide, please. In terms of the epidemiology that feeds into the model at the very highest level, we used a GlobalData report on MDS, which has a patient-based analysis, data from primary sources, as well as KOL insights and a prescriber survey. A very, very thorough piece of work, which we're very lucky to have. However, it ends in twenty twenty-eight, so from then on, we extrapolate using incidence rates that we found in literature to show how the population will continue to grow. And as you can see, there's a slight flattening of the curve because we don't feel that it's going to continue to grow at the same rate as it was up until that point. There is also some population growth factored in there as well. However, I will just point out that this is an incidence-based model. It is not a prevalence-based model. Now, for MDS, that is potentially a bit of an underestimation because these patients certainly in the low-risk population may well live more than one year. An incidence model is generally much more common in oncology because the survival rate is generally quite low. So in the high-risk population incidence is probably more relevant. In the lower-risk population, it may well be an underestimation of the number of patients that are affected by MDS. Just wanna make sure that's quite clear before we move into the rest of the slides. Next slide, please. We also pulled together a list of the current treatments that are available in this space. Now, the reason that we have the prices here is because this is one of the pieces that we shared with the payers and with the KOLs to try and understand the pricing. So what we found here is that. And of course, we've got both the U.S. and the European prices in here. There are obviously existing treatments, so we've got venetoclax, we've got HMAs. A lot of those are generic, but there are also some branded versions in the market. And then in the low-risk space, we've obviously got Rytelo and Reblozyl. They're commanding prices that are quite significant in the $300,000 per year, or $25,000, or $23,000-$25,000 per month. So quite significant price tags to a lot of these. We've also factored in some of the resourcing costs, so we've got transfusion monthly cost of transfusions and the cost of a hematopoietic stem cell transplantation. Now, some of those are comparative, and some of those are outcomes. So an HSCT is obviously an outcome or positive outcome of this treatment. But transfusions is something that this product should replace by providing better outcomes. Next slide, please. So how did the KOLs respond to the target product profile? So if we go to the next slide, please. First of all, we covered off some information about what is the unmet need. Although most patients will receive treatment for MDS, half will fail to respond to first-line treatment, and most will stop responding within two years. Therefore, improved response rates, duration of response, and overall survival were seen as the biggest unmet needs in high-risk MDS. You can see on those graphs down the bottom there, so that the KOLs defined the distribution of populations between the low, intermediate, and high risk to be about a third, a third, a third. Although the high-risk population seems to be the place where there are the most patients, but that may well be a factor of the fact that we're talking to clinicians or KOLs who see the most severe patients. There may be a little bit of selection bias included in that number. In terms of the KOLs estimates on how many patients were refractory to first line, the average was around 51%. As I said before, about half patients failing to respond to first line. If we come on to the next slide, please. Given that unmet need, does Bex meet that unmet need, and how far does it go? The KOLs generally agreed that the response rates that we have seen, and the predicted overall survival that we're going to see in the TPP, in both first and relapse refractory patients, would represent a very significant improvement on the current standard of care. We've included some of the quotes down the bottom there from some of the elements they said in response to the response rates in first-line, response rate in high-risk, and the overall survival. The first line, they felt, was very, very impressive. Eighty percent was a very, very significant number, and they felt very, very, very happy with that. In the second line, a 20% relapse refractory- sorry, in the relapse refractory population, a 20% response rate was considered to be very, very high in a- because it's a patient population who, where nothing is working currently. So actually, that's a pretty significantly positive result in those patients. And an improvement on overall survival was also seen significantly. You can see there are some quotes at the top there as well, about how this may well become a new standard of care. For example, "This may well become a new standard of care if these results are realized." So you know, a very positive reaction to the target product profile. Next slide, please. It was considered that it would have the most potential benefit in first-line, high-risk MDS patients. And the reason for that is because, as we saw on the previous slide, they have the greatest capacity to benefit. Relapse refractory patients, while obviously an area of very high unmet need, they've already had failures, so the probability of things working reduces significantly. So while this is a very, very important target population for to target immediately for bexmarilimab, actually, the first-line treatment is where the greatest or the most significant benefit is likely to be. So they expressed that opinion quite clearly. However, they wanted to make it clear that it is in the context of venetoclax. So as long as bexmarilimab performed either better or safer than venetoclax, then they would see it being used in a very significant number of patients. They were talking about, in first-line, high-risk patients, around 75% on average, and in relapsed/refractory, even higher number, 84%. But that first-line number is going to be determined somewhat by its comparison, not necessarily head-to-head, but its comparison with venetoclax in terms of clinical usage. Now, obviously, 80%-90% is not the sort of market share one would generally put into a model. But it does show the enthusiasm from the KOLs that we see there. Next slide, please. In terms of eligibility letters. They all agreed that the mechanism of action was very, very encouraging and that immune modulation was a promising approach in MDS. It's been tried in other places, but they've not seen much of it in this space. The KOLs were not familiar with CLEVER-1 as a target, but they could see the logic of it very clearly, and they absolutely understood how it would work, and definitely were supportive of the synergy with HMA. They compared it to approaches that are being used in other cancers, and again, could see the logic and the mechanism of action working very promisingly. So again, there were no, if you'll excuse the pun, antibodies to using this in this space. And you can see there some pretty helpful quotes from some of the KOLs. Next slide, please. One more. So this is just a slide to basically bring together some of the epidemiology that we saw at the beginning, and then to layer in some of those stratification figures that we used. So you'll see on the slide, on the graph on the left here, that. And sorry, this is just the U.S. So there is a. We have other. We did do a model for Europe, but just in terms of keeping things simple, we just focused here on the USA as it makes up a very, very significant probably the largest market for this product. So on the left-hand side, you can see there the number of patients at peak is around nine thousand, and obviously this is a rare condition, so a peak at nine thousand is still fairly significant. And that is using market share projections that are much lower than the 75% that the KOLs were talking about, because we're factoring in the elements of things like competition, and you know, other elements like that. On the right-hand side, you'll see what I was talking about in terms of the cannibalization of different lines of therapy. So what we have is, for example, the launching into the second line or relapsed/refractory high risk initially, and we see fairly rapid uptake in that space. We then see that being essentially cannibalized by the launch of the first-line indication, and then we see it flattening off. We then, a few years later, we have the low-risk population launching, and then we see similar dynamics going on there as well. Now, what we also see is a flattening out. So we've predicted a fairly rapid uptake in this patient population. I think it's three years, three to four years to peak. And then we see it flattening out, but not entirely flattening because obviously there is some population growth going on there as well. In areas of high unmet need, rare conditions, oncology, a rapid uptake like this is not unusual, and this is based on analogues, and also commentary from the KOLs as well. There is additional market research ongoing to confirm some of these assumptions, and hopefully, that'll nail down those assumptions in a little more detail. The patient numbers are adjusted for compliance, as well. So next slide, please. So this is the... So we come on to the payers now, and this, again, is just focused on what we see in the U.S. Next slide, please. So in the U.S., we obviously, we've just had Rytelo launch in the low-risk MDS population, so that's Although it's low risk, it's a relatively useful pricing benchmark to have a look at. So, the payers generally felt that in this space, and given the TPP that they saw, and the fact that it is oncology, and the fact that it is rare and particularly in the high-risk population, that they were going to struggle to put any barriers in place to the use of this product, pretty much at any price. They saw Rytelo price, and they felt that, in general, prices around that are not unrealistic. The benchmarks that we saw earlier, in terms which we're talking about prices of somewhere between $23,000-$25,000 per month, again, not unrealistic in terms of where they would expect the price to be. They talked about the price of Rytelo specifically as being achievable. Some payers would like to see prices that were lower and would try to put some restrictions in place. However, those restrictions are unlikely to be particularly strong restrictions, because, you know, because it's oncology, they will really struggle to put significant restrictions or negotiate significant discounts in that space. A little more detail on the next slide about the specifics of what the payers said. On the left here, one of the payers was suggesting that EUR 22,000 per month, we probably wouldn't see much restriction at that point. If we moved up to EUR 25,000, they might try to consider a value-based agreement. They would be trying to manage it through prior authorizations. But again, this would be restricted to it would be a PA to label rather than anything anything more stringent than that. But in terms of just making sure that the right patients are getting it, that's where the PAs are going to be, and that was fairly consistent across all the payers. In terms of the payer on the right, they said EUR 25,000, it's gonna be left up to the clinician. There's no coi nsurance, there's not gonna be any issues with that. They're just gonna pay it. Next slide, please. A little more detail here. Again, same kind of story from the payer on the left. They would be trying to think about how can they just manage it and make sure it's not being used in any patients that's inappropriate, but again, EUR 25,000 wasn't- they didn't have many concerns about that. Payer on the right did want to try and put some more restrictions on it. However, did recognize that they would struggle to do that necessarily, but would like to see prices further down at around EUR 18,000 a month. So I think it's fairly clear that the pricing is not going to be a huge challenge in these patients, which is not something I find myself saying very often. But it's interesting to see how this is going to be put in place. So I think that's my last slide. And yeah, I think it's the Q&A session now. Thank you very much, Ralph. Very, very comprehensive work and interesting data. I will start with the chat. So did any of the findings surprise you in this case? No, I didn't think so. I mean, I think the pricing element of it was interesting, that I felt there was gonna be a greater reluctance to pay the Rytelo price. I didn't think that bexmarilimab necessarily there would be such significant reluctance because it's high risk, it's patients with very large unmet need. So again, I wouldn't say there was much of a surprise there, other than the fact that I thought they were gonna come down harder on the restrictions. In terms of how the clinicians responded, I suppose a little bit. They were very strong on the venetoclax, certainly in the first line. But it's venetoclax's position in first-line MDS. I'm not entirely sure about that, so it seemed a little strange that they were talking about that in with such strength. But no, I think overall, maybe I've just been looking at these results for too long, and so they don't seem surprising to me anymore. But no, they seemed fairly in line with expectations. We had previously done an economically justifiable price model, which gave us a very similar pricing result to what we were expecting. So actually, again, we were kind of ready for that price, and it is justifiable from an economic point of view as well. On the pricing, I was wondering if you could comment a little bit on, in general, when a drug is used as a monotherapy versus combined to another drug, how does that affect the pricing typically? It's a very, very good question. I don't think there is a typical way in which that happens. I think it comes back to the value that it brings. You know, if you're adding several months of overall survival, then I think certainly in the U.S., they're gonna struggle to argue that it shouldn't be paid for. In this case, it's HMA, which is generic, so it's not gonna add a huge amount. So in that, in this case, you could treat it like a monotherapy. Unless you're using one of the branded HMAs, which I think if you're adding this to, I think hospital payers would struggle to, or insurance companies would struggle to reimburse or cover both. But I think if you're using the generic HMA, I would see this more like a monotherapy. There's a question on comparison to other drugs. So based on your work, is there any possibility to do some kind of comparison to other cancer drugs or immuno-oncology drugs? In terms of benchmarking the price? Maybe in general of your findings and your research on bexmarilimab, and did it so were there some kind of obvious differences to other cancer drugs in pricing or other points of view? We didn't look at that. I'm not sure I can answer that question from the point of view of the work. I think the pricing, I can say, isn't miles away from where other products are placed, are priced, other immuno-oncology products. Some of the bigger ones that have been around for a little longer and are used across multiple different indications, the prices may well have come down since launch. In terms of pricing, they're this is probably gonna be higher, certainly at launch. But that's, and I'm talking about sort of confidential pricing here rather than the list pricing. Hard to say precisely what that is because obviously it's confidential, but it's fairly standard that the price, the net price would be changing over time. So as you launch this product, it's gonna be priced slightly higher to other ones. But again, I don't know what Faron have decided to do in terms of the way they're gonna launch it, how they're gonna price it, how they're gonna launch it. You know, we're just providing insights about what's possible. So I guess in answer to that question, the pricing is not way off what other immuno-oncology products are, and in terms of the clinical data, you know, I think it's bringing something quite exciting to an area that hasn't had much. So again, I think it's kind of a new immuno-oncology in a space that hasn't had any immuno-oncology. So, that kind of excitement coupled with the significant unmet need, I think it's a real opportunity here. Okay, there's a question on, I guess, on the kind of different stakeholders that would benefit possibly from bexmarilimab. So the question is, "Are there additional motivators, such as potential cost savings, beyond the humanitarian benefits?" So kind of maybe you can talk about the kind of the- Yeah. ... different stakeholder points of views. Yeah, really, really interesting question. So I think certainly. So we did talk about this with the payers, you know, what is the, are there any cost savings that we might see in this space? Obviously, there is a certain rate of infusions that happen, certainly in the lower-risk patients. So, I mean, there are infusions happening in the high-risk patients, but compared to decitabine, it's fairly low priority. But in terms of the lower-risk patients or the intermediate-risk patients, frequency of infusions and the cost of those infusions becomes quite important. Also, I'm gonna butcher the way this is said, erythropoietin-stimulating agents as well, you know, bringing down the price of those, because they can be quite pricey. Although obviously there are now some generics or biosimilars in that space, so it's a bit of a less of an issue than it was. So yes, there are some cost savings that can be made there, and there was also mention of hospitalizations in this population as well. You know, there's a lot of monitoring and so on. So if you can bring some of those costs down, there will be some benefit on that side. Obviously, there is also on the other side, you are potentially increasing the cost because more patients are gonna make it to HSCT. More patients are gonna make it to bone marrow transplant, which is obviously a very expensive procedure. But compared to the life, you know, the life and the quality of life gain that you get from that, it's fairly insignificant, I think. So if you look at it from a cost-effectiveness point of view, which I know is not very de rigueur in the States, you actually see a fairly significant benefit as a result of getting people to stem cell transplant, even though it's so expensive. So yeah, there are lots of factors that are considered within this, but yeah. Okay, so how about from the audience? Any questions to Ralph? If not, I will finish with a very, very straightforward question from the chat. "In summary, according to your presentation, yearly revenue from Bex in U.S. only may be about $2 billion-$3 billion. Is that correct? ... I can't really comment on that. But you know, if you're a mathematician, then I'm sure you can work that out. Thank you very much, Ralph, for the presentation. We will take now a five-minute break and continue with the next presentation. Good afternoon, everyone, and welcome to the second part of the Capital Markets Day. My name is Petri Bono, and I'm really delighted to tell you about establishing bexmarilimab as a cornerstone treatment for solid tumors. I will have three parts in my presentation. First, I will tell why our approach with bexmarilimab is unique way to treat cancer. And then the second one will be the Bex, that is the solid tumor pipeline, what we want to do in order to treat solid tumors better than the currently available immune therapies. And then the third part will be the already announced scientific advisory board. So I will present a little bit more into detail that who will guide us also when it comes to scientific issues in future. So let's start about the general big picture, about the playground where we're playing, and about how immunotherapy is or has been evolving as a cancer treatment option. At the moment, FDA has already approved 13 different immune checkpoint inhibitors, or PD-1 or PD-L1 inhibitors, to treat 20 different cancer types. And while these immune checkpoint inhibitors have advanced significantly cancer immune therapy, so lot more effective and new personalized treatments are still needed. Diversity or heterogeneity among cancer cells within and between tumors is a major cause of treatment resistance, and in Juho's introduction, we heard about how important is the treatment resistance, because the treatment resistance is the phenomenon that leads to cancer progression and eventually to the death of the patients. And then, about targeting resistance mechanisms that are related to the non-responsiveness of approved immune therapies, how they form the basis of improving outcome of solid tumor patients. And the figure shown here in the right, it's taken from the American Association for Cancer Research, their annual report that was published about a month ago. So that's a fairly well-updated figure, what's currently approved and what's not. So most importantly at the moment is that despite all the hype, so most patients actually do not benefit at the moment from current immune therapies. It's roughly 20%-25% of patients who benefit, and the majority, the largest part of the cake, are those ones who don't get the benefit. Primary resistance is very common, and they don't i mmune therapies don't work in tumors with low immune activity and T cell infiltration, and pharma companies, they are, basically all looking for new solutions for turning cold tumors immunologically hot, and they are doing it by different, combination, combinational approaches, mostly by combining PD-1 inhibitors, to inhibitors of, TIGIT, LAG-3, TIM-3, or other, targets. That are all completely different, targets, that is CLEVER-1. However, the complexity of cancer immunity and the tumor microenvironment and the diversity of cancer types makes it very challenging to develop any universal, one drug fits all, as a therapy, and a lot more personalized approach is required, and therefore, we are in a unique position also. After my presentation, our Chief Scientific Officer, Maija Hollmén, will tell a lot more how we can tailor the BEXMAB treatment to the right patients. Macrophages, they are key players involved in the primary and secondary treatment resistance, and most importantly, CLEVER-1. So it's a major regulator of macrophage function, and therefore targeting or reprogramming the macrophages with anti-CLEVER-1 antibody, bex, represents a novel way to overcome immune evasion mechanisms that are linked to either non-responsiveness of cold tumors to the approved immune checkpoint inhibitors, or then to link to the acquired or secondary resistance to these anti-PD-1 inhibitors. This cartoon is trying to show that how CLEVER-1 targeting has multiple effects on boosting immune cancer immunity. In the figure on the lower left corner is the most important part is that CLEVER-1 has a role how antigens are being presented and how they are released to get recognized, and since CLEVER-1 as such is trying to show a signal that hide, and so with anti-CLEVER-1 treatment, it's possible to increase the antigen presentation, which leads to increased cytokine production, like increase of IL-12 or TNF secretion, which leads to increase in T cell function, T cell killing of the tumor cells, and also better recognition of the tumor cells. These are multiple actions, and they can all be achieved by targeting the CLEVER-1 receptor by anti-CLEVER-1 antibody bexmarilimab. And most importantly, this means that with Bex, it we can enable checkpoint inhibitors in patients who do not benefit from the currently available cancer therapies or immune therapies to become responsive to them. In MDS, Mika Kontro just presented how Bex can sensitize the MDS cells, the blasts to azacitidine. So basically, when we combining Bex with PD-1 inhibitors, so a little bit in a similar way, we are sensitizing the tumor cells or the tumor to PD-1 inhibition by combining both anti-PD-1 antibody and anti-CLEVER-1 antibody, bexmarilimab. And before we go to the actual pipeline, and so couple of slides as a reminder, what have we learned from the first-in-man trial that was performed in solid tumors? Actually, I was privileged to be the global principal investigator in that study that started enrolling patients already at the end of 2018, and the results have been published last at the end of last year in a prestigious scientific journal. We were able to show the proof of principle of modulating tumor microenvironment with Bex. 216 patients were treated across different 10 different cancer types, and targeting CLEVER-1 with Bex, it was extremely well tolerated. We were able to find the recommended phase II dose, 1 mg per kilo every three weeks. That's also supported by the FDA, and we were able to show that we can, with Bex, convert these intratumoral macrophages to support adaptive immune responses and to launch interferon gamma signaling. Bex monotherapy, so it or in these patients, it modified the tumor microenvironment, which led to increased survival in late-stage cancer patients. This is important. These were really, really late-stage cancer patients. For example, the ten ER-positive breast cancer patients, the median number of different treatment regimen, not treatment lines, was eight, meaning that the Bex treatment was the ninth type of treatment that the patients were treated with. It, of course, varied between different tumor types, but it was on average three or four median lines of therapy. The breast cancer patients, they were the most heavily pre-treated ones. It means for oncologists that it's extremely challenging to get any kind of response or clinical benefit to the patients. What we were able also to show is that a low baseline immune activation, so it associated with clinical benefit for Bex. And we are able to measure this by measuring interferon gamma or TNF levels. And since it's not the change of the levels, but rather the baseline level, so that can be used as a predictive tool to select the patients who would benefit from the treatment. We were also able to show, as shown in the left part of this slide, that the patients with higher survival, shown in red with disease control, they were exactly the patient who had the increase in the interferon levels during the first cycle of the treatment. So exactly that was seen earlier in preclinical models. So, we were able to show that also in this phase I study for the first time in patients, so that biologically, we can see the effect that we were expecting as a single agent treatment with Bex in very late-stage cancer patients, then about the summary of this safety and efficacy. First of all, treatment-related adverse events, any grade events, only 45% of the patients had treatment-related adverse events. Go and have a look of any PD-1 inhibitor trial, any tyrosine kinase inhibitor trial, any chemo trial. This is usually 99% or 100%. So means that Bex treatment, a single agent, it was well tolerated, fits well, very well in line. What Mika just showed in the first combination trial ever with Bex, with any anti-cancer agent, in MDS, it was with azacitidine. The most frequent ones are listed there. So I go to the right side, which is the efficacy part, the disease control per cohort. So we can see that there were cohorts where we didn't see responses, but marked both there is five different cohort types where we got disease where we got patient benefit by disease stabilization and shrinkage of some shrinkage of the tumor sizes in melanoma, cholangiocarcinoma, gastric adenocarcinoma, hepatocellular cancer, and ER-positive breast cancer. For example, in ER-positive breast cancer, 33% of the patients had stable disease as best response. Out of these melanoma patients, half of them were pre-treated with double immunotherapies, and all of them were pre-treated with at least single-agent anti-PD-1 therapy. About the survival outcome of the trial. More than three times longer survival for the patients who were interferon low at baseline and benefited from the treatment. It's shown on the right side. That's the Kaplan-Meier curve of the overall survival, where you can see that the benefiters, ones marked on red, survived significantly longer. Of course, this might be a selection of patients who have been progressing more slowly and therefore also progressing more slowly in this trial, which is of course a weakness of an open-label, single-arm study. For that purpose, we made two things. First of all, the overall survival was done by landmark, so-called landmark analysis, and the other one was that we also had a look at the duration of the previous therapy before entering the MATINS trial. And actually, the duration of the previous therapy was exactly similar between these two groups, so that the rate of progression were similar when they entered the MATINS trial. So we certainly believe that the effect was due to the bexmarilimab treatment, why these patients survived longer. And then when we go more in depth of the results, so it's actually patients with cold tumors that responded to treatment, cold tumors that were either interferon-low or TNF-low at baseline. That correlates well with also the immunohistochemical staining result of the tumors when we stain the tumors for CLEVER-1 positive macrophages. There on the gray box, you can see that the intratumoral CLEVER-1 positivity score, the median score in the middle, so it's significantly higher among patients who had disease control versus among patients who did not have disease control, indicating that immunohistochemical staining of intratumoral CLEVER-1 might be a good biomarker to select the patients. Then, if we have a subgroup analysis of the bexmarilimab of the MATINS study, where 216 patients were treated altogether, and this is an example of the melanoma results. We know from melanoma, it's shown on the left side, that not actually all melanoma patients either respond to anti-PD-1 therapy. Melanoma is by far regarded as the hottest tumor in the field to get the benefit from anti-PD-1 treatments. We can see on the left side that in an analysis of the tumors according to the interferon status, so the ones shown on red, so actually they didn't survive that well because they were interferon low, and they were in an immunosuppressive state when they were treated with the anti-PD-1 inhibitor. There on the right side in the figure, that's from the MATINS trial, melanoma patients, and exactly vice versa, the result. The ones shown on the red, the flat curve, they are the ones who were interferon low. They are typically those melanomas who don't benefit from anti-PD-1 treatment. On the other hand, the blue ones in MATINS were the hot, hot melanomas who didn't seem to benefit from single-agent bexmarilimab after they failed with a PD-1 inhibitor. And then probably to the slide that may be one of the most interesting slide of my presentation to the audience. And this is the Faron solid tumor pipeline. And first of all, in the upper row, a reminder that the MATINS trial that went to the end of phase II, that was a single-agent trial, Faron sponsored. And the plan is to have their three new trials in solid tumors that are already ready to be launched in a clinical state. And then we have baked a new cake also, that is there still, the treatment little bit to be confirmed in future, but that's lymphomas, and that will be also a Faron-sponsored study, and there will be a slide I will tell about the background, but this is at the moment in preclinical stage. About these bexmarilimab plus PD-1 combination studies, some of them will be on IO naive patients, so patients who are cold tumors, who have never received any anti-PD-1 treatment earlier, since they are not likely to benefit from the treatment. And then some of them will be hot tumors who have been treated with PD-1s and become resistant to the treatment, which is actually very typical. Majority of the patients progress after 10-13 months, for example, in melanoma. So we will try to sensitize those patients with bex back to PD-1 inhibitors. Out of the three solid tumor trials, so some will be in frontline as first-line treatment, and some will be in later lines. And out of these, one will be the Faron-sponsored basket trial, shown in the second row, that we call MATINS-02, and then there will be two investigator-initiated trials, BLAZE and BexSAR, that will both be starting enrollment of patients in twenty twenty-five, and BLAZE as the first one in at the end of Q2 in next year. BLAZE will be conducted at Royal Marsden Hospital in London, U.K., and BexSAR will be conducted at Vall d'Hebron Hospital in Barcelona, both leading European cancer hospitals. About the BLAZE. The biological question there is really: Can bexmarilimab overcome PD-1 resistance in tumors that have become that have been pre-treated with PD-1s? And as I told, it's very common to become resistant, and targeting of tumor-associated macrophages is actually one very potential way to overcome the resistance, and that would represent a completely new proof of concept of reversal of resistance in this setting that is highly competitive globally at the moment. But we believe that our unique approach will be beneficial here, and this will be our first combination trial with a PD-1 inhibitor. And based on the very encouraging safety signals we have seen in combination with azacitidine in MDS, we believe that also the bexmarilimab PD-1 inhibitor will be well-tolerated. But of course, that needs to be shown, and therefore, there's, in this trial, there's a phase I running stage in non-small cell lung cancer and melanoma, among nine patients, to really make certain that the safety is in place. And thereafter, there will be two different expansion cohorts, one in melanoma and then one in non-small cell lung cancer. And at the end, there will be, in this about three-year trial, 57 patients treated. And the trial will, most likely start with initial priming with Bex before starting the combination treatment, and with a very heavy biomarker intense approach to provide translational correlates, to show the macrophage switch and immune activation in these patients. The second one, BexSAR, investigator-initiated study. Truly cold tumors that don't respond to any currently available immune therapies are soft tissue sarcomas, and there, can we turn these primarily refractory tumors sensitive to bex? And early experience with single-agent PD-1s have been disappointing so far within these tumor types. And the reason why they are cold, it's related to tumor microenvironment. That is in sarcomas, also rich in M2-like macrophages, as well as very frequent expression of CLEVER-1. And Maija will tell something about the differences between different macrophage subgroups. But M2 ones are the immunosuppressive that we want to get rid of, that we want to have a chance towards the M1 type macrophages. And the layout is shown here. Again, a running safety phase in soft tissue sarcomas, nine to 18 patients, and thereafter, a phase II expansion with 36 patients to show the preliminary efficacy among these soft tissue sarcomas. Then the basket, that is the first Faron-sponsored PD-1 combination trial in solid tumors. Can we overcome PD-1 resistance in either IO pre-treated, IO... Excuse me, in IO-sensitive or IO or IO-resistant tumors or these cold tumors? The idea there is that these PD-1 inhibitors, they've been disappointing in very many frequent tumor types, like breast, gastric, hepatocellular carcinoma, and cholangiocarcinoma. This is the logical continuation from the MATINS study. We saw a single agent activity among these gastric breast cholangiocarcinoma, so now we will attack them with a combination of PD-1 inhibitor. Then we will also have a cohort of a so-called hot tumor, although the truth is that the majority of the non-small cell lung cancer patients don't respond to first-line PD-1 inhibitor treatment. We want to combine in those, in that first-line setting, PD-1 inhibitor with bexmarilimab. And that was about the solid tumor pipeline, and then the newest key player in the field, that's the anti-CLEVER-1 approach in lymphomas. This is the slide, this is the photomicrograph taken from biobank data showing the expression of CLEVER-1 marked as red dots in various tumor types in hematological cancers. You can see there in the top middle on the right, BCL or TCL. They refer to B-cell lymphomas and T-cell lymphomas. Actually, it's of interest that CLEVER-1 is also widely expressed in B-cell and T-cell lymphomas. The question is immediately, can we increase the efficacy of standard of care agents or in those two lymphomas, or can we sensitize those lymphomas back to the treatment after failure when the drug is combined with Bex? It's good to remember that the most common lymphoma type by far is the non-Hodgkin lymphomas in contrast to Hodgkin lymphomas. That is a very different tumor type. Out of these non-Hodgkin lymphomas, the majority are B-cell lymphomas that are CLEVER-1 positive. It's attractive for us to approach preclinically and do confirmatory studies if we can sensitize those cells in a lab setting to Bex. If so, then we will move forward to the clinical trials. Of note, these B-cell and T-cell non-Hodgkin lymphomas are 45 times more common than MDSes. As a summary about our solid tumor mission with BEXMAB is that, first of all, Bex is a true first-in-class humanized anti-CLEVER-1 antibody. It's not a me-too drug. It primes the immune system to attract tumors by a completely novel mode of action. This is what makes us different from most of the other players in the field. This is why we also believe that we can establish Bex as a cornerstone drug for cancer in those indications where CLEVER-1 positive macrophages and the low interferon microenvironment are source of treatment resistance and the reason for cancer progression. Bex is potentially applicable to, of course, wide range of hematological diseases. As Mika showed data from MDS. There are also other possibilities there, and of course, the solid tumors in combination with traditional therapies and also as maintenance therapy. As shown in Mika's presentation, in CLEVER-1 hematological cancers such as MDS, there's dual mode of action and very encouraging activity that we've seen so far. In solid tumors, we believe that Bex will be the first-in-class targeted macrophage reprogrammer in combination with PD-1 inhibitors based on tumor-agnostic biomarker. Meaning based on the biomarker, not on the origin or anatomy where the tumor is arising from. And then to the last part of the presentation that I'm really proud to present to you, that we will have a really world-class scientific advisory board or medical board that will support us in the future and provide further depth and experience when planning and analyzing our trial results. The advisors are shown here, Professors Toni Choueiri from Harvard Medical School in the U.S., and Professor Thomas Powles from University of London and Barts Cancer Centre, and then Professor Amer Zeidan from Yale Cancer Center in the U.S. Professor Naval Daver from the largest and biggest and always number one ranked global cancer center in the world, from the prestigious MD Anderson Cancer Center. Mika Kontro, you're all familiar with, from the Helsinki Comprehensive Cancer Center in Finland. Then finally, a third solid tumor expert, Professor Christophe Massard from Gustave Roussy Comprehensive Cancer Center in Paris. And a couple of words from every single one of these. So after those presentations, I believe you support my view that we have a true dream team together as a scientific advisory board. First, Toni Choueiri. So, Professor of Medicine at Harvard Medical School and Director of the Center for GU Cancers at the Dana-Farber Cancer Institute, and the co-leader of the Kidney Cancer Program at Harvard. Serves at the U.S. National Comprehensive Cancer Network panel that provides the guidelines to U.S. physicians how to treat cancer. Sits in the board of ASCO. 800 PubMed indexed publications and lead indicates that multiple phase III trials lead into multiple FDA and EMA approvals. And, Toni, has been the senior author, first author in almost all of those publications, and leading those observations to approvals. Thomas Powles from London. I start from the bottom. Last December, he was named in Time in the list of the top 10 most influential people in global health. Not in medicine, not in cancer, in global health. And this is due to the landmark trials that he's been the global PI. He's a professor of urological cancers at University of London, one of and a director of the Barts Cancer Centre, one of the largest cancer centers in Europe. And he's also the editor-in-chief of the leading European oncology scientific journal, Annals of Oncology. And he's had major role in many, many trials leading to FDA and EMA approvals. 10 New England Journal of Medicine or Lancet publications, with two first author New England publications and two first author Nature publications, and these led last year to become ranked as the most important or influential people in global health. Then, a very true MDS giant from U.S., Amer Zeidan from Yale. He's an associate professor of medicine, chief of Hematological Malignancies Division, director of the Hematological Early Research, and lead of the clinical program and research team for leukemia and myeloid malignancies at Yale Cancer Center. A true specialist of MDS and AML, focusing on targeted therapies and also on immune therapies within these tumor types. 330 peer-reviewed publications, and PI in numerous phase II and III clinical trials in the areas of acute myeloid leukemia and MDS. Then, Naval Daver from MD Anderson, director of the Leukemia Research Program at the Department of Leukemia at MD Anderson in Houston, Texas. Clinical investigator with a focus on molecular immune therapies in AML and myeloid diseases, and currently principal investigator in over 25 ongoing international clinical trials in these diseases. Over 400 peer-reviewed manuscripts or publications, and sits in the editorial board of numerous hematology journals. Then, Mika. Mika is adjunct professor at Helsinki University, a consultant in clinical hematology at the Helsinki Comprehensive Cancer Center, and works as currently as Albin Johansson Cancer Research Fellow, and is a group leader also of the very high quality translational institute, the FIMM, Finnish Institute of Molecular Medicine. Mika is currently chairing the Finnish AML Group and also a board member of the Nordic AML Group. And then finally, the last one, but not the least, Dr. Christophe Massard from Gustave Roussy. That is the first leading cancer hospital in Europe, the first ever comprehensive cancer hospital in Europe, and currently ranked number four hospital in the world, and every year within the top five in the world. By far, the largest cancer center, and Christophe is running the clinical trials in Gustave Roussy. He's professor at the clinical trial unit and of course, member of the European American Associations, and has participated in over one hundred and thirty trials in the past five years, PI in the last ten years in over 50 phase I studies, and co-investigator in over 100 trials, and has published over 100 peer-reviewed publications. So with this introduction of the team, I hope I've been able to convince that the medical board, the medical support that we'll receive at this stage, when Faron is a clinical stage company, is really international top-notch. As you heard in the introduction mentioned, it's not easy to find any other biotech company having a more... Having a better scientific board that we have now been able to establish. And I'm really looking forward to also working together with them to get the guidance of the most recent developments in the field and also the guidance to the evaluation also of the study results that we will have from the solid tumors also, not just from the hematological trials. And with this, I will finish. I'm ready for Q&A. Thank you. Thank you, Petri. Why don't we start with the audience questions first, if we have any? So please raise your hand if there are any questions. Okay, if no at this point, why don't we start with biomarkers? So it seems that you have two biomarkers specifically in mind, Interferon Gamma and CLEVER-1, correct? ... Exactly. Yes. Yeah, and the other one is- Yes. ... immunohistochemical staining, the other one is a soluble factor. Yes, so now you presented the pipeline for solid tumors, so what is the role at this point for the biomarkers? Do you already know that you will be using specific biomarkers for specific indications, or is it still up for planning? The trial results will all be stratified according to the biomarker. For example, the basket trial that is sponsored by Faron, so the setup in different cohorts is very similar. So it's meaningful to combine the cohorts in order to add the number of patients that are positive for the biomarker, and to show the proof of principle there, that we can select the right patients with that biomarker. Of course, we are still in the negotiations that is it feasible to do a biomarker-guided trial directly? But when it comes to study logistics, it's very different than. At the moment, it seems that the approach we will take is more that we will treat the patients and then stratify from all cohorts according to the biomarker, and then we will get enough data to show that it's the right biomarker for selecting the patients. There was recently one investigator-initiated trial in Traumakine that was actually never started. So how about these investigator-initiated trials? How confident are you that you can actually then proceed in time, and how can you kind of convince investors and also the clinicians about these projects? The BLAZE trial, that is the melanoma lung cancer trial at Royal Marsden, so that's. I'm actually the protocol writing is progressing well, and I'm confident with that one. The PI was the British PI in the MATINS study, familiar with the drug. Of course, we need to finalize the protocol of course with the other one. The sites are very eager to get these trials running. I sleep very well although they are investigator-initiated trials. I'm confident that we will get this launched. There are a lot of details and issues related to those trials, and of course, we try to make them as smooth as possible to run. One of those things will be that it's not selection criteria that you need to have a fresh biopsy from the tumor and do the staining of the biomarker, because, for example, in lung cancer, it's fairly difficult to get always a biopsy before starting the treatment. When they are refractory to the treatment, there's not usually that long time to wait, because the disease is progressing. Great. Let's take a question from the chat. So are there any plans to progress MATINS' monotherapy programs at this time? I think biologically there would be a nice rationale to do a late-stage trial or other trial with single agent bexmarilimab for selected patients. And but as you have mentioned, so of course, part of the strategy making in a company is to make decisions that what we're not going to do, and we are not a phase III company. We are proof of concept earlier phase company, and part of that story is that we will not do a single agent Bex phase III randomized study. That would be a continuation of the MATINS trial. And of course, that's a good idea. It's a very good question, but we have made a decision as a company because we are a small company to run a phase III, so it's not feasible. So we concentrate on this proof of concept type of trials that are now presented within solid tumors, but the rationale is still there behind. Yeah, and kind of the follow-up or the continuation question was that can you use the safety data from MATINS trial or will it help you in the future FDA submissions? It will definitely help, and also when planning and running these new trials, so we can move forward fairly fast after a quite short run-in safety phase. As you may have noticed, that there were nine or 18 patients in the first part of the trials, and this is partly true, that we know so much in solid tumors about the single-agent safety of Bex. Then there is a more kind of a general question. Could you tell us more about the data that supports your confidence in advancing the program in melanoma and breast cancer? I think it's simply, to me as a clinician, so it's that we saw in the MATINS trial, we treated those patients, and we saw responses in heavily pretreated patients, a single agent. So, Maija can provide a lot of other data that supports this, how actually is the ground or basis that those studies were done in those tumor types. But, I think it just fits so well to the overall picture. We have the preclinical data in with cells, with mice, then we have the single agent data. So then there's a so nice rationale that how we can combine Bex with PD-1, since it's been shown so well that macrophages actually are very important when the diseases become resistant to the PD-1 treatments. So it's, it's, in a way, what the biological rationale is almost like a low-hanging fruit. Of course, we need to test this, but that, that's something that we are getting prepared to get the studies run. And, and, the first one, we plan that first patients would be enrolled by the end of Q2 next year. So the sponsor trial will obviously be more expensive. So is it kind of self-evident that you will need to partner to undertake that trial? Yes, we need partnering in order to be... or other ways of financing to, compared to the current situation, in order to be able to run the basket trial. Of course, this is something that Juho will certainly take care of, but anyway, the planning and setup to get trial running. It takes a long time. These things need to be initiated a lot before. Yeah. You need to have, very clearly in your mind what you want to do. Of course, we will go the settings and doses and treatment lines and number of patients, and which PD-1 inhibitor to choose, in our own basket trial. These are exactly issues we want to go with our scientific advisors through, that they agree, that feel that we are, we are making the right, choices. Because there are lots of, different parameters that, can change in the trials. Thinking about your kind of competencies to undertake phase I and phase II clinical trials in solid tumors, so do you have all the competencies there from BEXMAB trial? Or do you need to kind of build, for example, production capacity or something like that, or is it more like protocol planning and to move forward? Yeah. The production capacity, of course, it's coming along the development pipeline all the time and need to be kept in mind very carefully all the time. But about the other capacities, we have it already in place, the biomarker stuff. So it's possible to use that. It's possible to initiate the studies, so they are not pending on those kind of issues. But, of course, there are lots of pieces in this puzzle that needs to be filled well before the trials are running. We do have the know-how, we do have the capacity, we do have a very good ability to select the sites, and it's very, very important when running these kind of trials, that the site selection is optimal. Earlier, in the MATINS and also in the BEXMAB trial, we've been able to select very good international sites and very, very motivated investigators from them. Okay, final, final question from the chat. Maybe indication specific, but what would be a good response rate, or overall survival in the solid tumor trials? If you think about refractory PD-1 refractory melanoma or lung cancer, so I would say any response at that stage is a good achievement, but let's say 20% response rate, so that will be already a good one, and that would be a clear proof of concept of the activity. So not more than that is required because the currently available approaches, so they have failed. So for us everything about 20%, so that would be. Now when not having lots of statistical counting there behind, but anyway, even some response is fairly low number. We don't need to try to reach to 60%, because this is the big beef where everyone is trying to succeed, and so far it's been difficult, but no one has had this clever approach that actually we are having at the moment. But what comes to then overall survival, so typically everything beyond six to nine months, so that shows that the combination is probably effective. Thank you, Petri. And our next speaker is Dr. Maija Hollmén. Welcome. Good afternoon, everybody. My name is Maija Hollmén, and I'm happy to be here to present you my scientific view on who benefits from bexmarilimab and why. Just a brief mention, I have been working with CLEVER-1 and bexmarilimab over 10 years, and with macrophages over 15 years, so I'm pretty confident to present what I think is right in our field. To not go deeper into the CLEVER science yet, I want to just familiarize you with where are we now with the current macrophage reprogramming therapies. This was a review article that we put together with my PhD student, because we wanted to understand what kind of therapies are used to target macrophages, how well they work, and are there any approved therapies at the moment that would have very nice results and clear proof of concept evidence of macrophage reprogramming? As you can see from the years going through, there has been a lot of interest starting from twenty ten that has increased substantially in introducing new targets into the field. But one particular thing that bothers me is that there are many same overlapping strategies that are used to target macrophages. I can name a few, for example, the CD47 SIRP alpha what is trying to be targeted in many trials. One other indication was to use IDO1 inhibitors, and I have to say that there were 6,000 patients treated with IDO1 inhibitors before they discontinued the study of not being effective. I have to say for this that there are many resistant mechanisms also for macrophage-targeted therapies, and they can use these pathways to overcome other therapeutic ideas to target reprogramming. Then, also, there are the indications for us. We target the scavenger receptor CLEVER-1, and we started the MATINS trial in 2018 and the BEXMAB trial in 2021, as you can see here. What is the most difficult problem in macrophage targeting? A pathologist can. You know, when you look at the tissue, you can see a pathologist stains for macrophages. So this on the left-hand side, you can see, immunohistochemical staining of macrophages shown in brown, and you can appreciate how abundant they are in the tumor. So they are really contributing some way to the tumor growth and metastasis and tumor, resistance to therapies. When we move on to these, arrows on the right, we can people talk about M1 macrophages and M2 macrophages, and there are different, continuums or expansions of macrophage plasticity. Meaning that macrophages in different microenvironments can get different stimulus, and they can polarize to different states, where they can, destroy bacteria, destroy tumors, help, adaptive immunity to combat different, infections. Or they can change to this alternative activated phenotype, which normally is the phenotype that you can see in tumors, so this is indicated in red. And these macrophages have the ability to promote tumor growth in many, many different ways. But I have to now give you a note that this kind of M1, M2 polarization can only happen on the Petri dish. This never happens in the tissue so clearly. So if we go forward, this is presenting now in the right-hand side, single-cell RNA sequencing data from real human tumors. And as you can see, they are colored based on their RNA expression in different clusters. And the more they differ, the more apart they are in this plot. So you can appreciate, you can see roughly ten different colors, so there are kind of ten different macrophage subtypes in tumors. If you look underneath, there is the macrophages that you can find from triple-negative breast cancer, or the macrophages you can find from ER-positive breast cancers. They also differ. Patient-to-patient variation, but also the tumor type that says what type of macrophages you have in the tumor. This is something that is really difficult, and we understand very little of it in regards when we want to therapeutically reprogram them. We have done a lot of research within the last five years to understand where does bexmarilimab work. For these studies, we have modeled the tumor microenvironment and the tumor-associated macrophages associated to these environments by taking patient samples and activating them with bexmarilimab ex vivo. From these studies, we have started to understand, as Petri mentioned, that bexmarilimab works very well when you have tumors that have low pre-existing interferon. And with Bex, we can change this phenotype to a cold tumor that can produce CXCL10, which is a T cell chemokine, and get interferon up. But bexmarilimab doesn't work in those tumors that have high interferon levels, high regulatory T cell levels, and actually have these IL4I1-positive macrophage subpopulation. So we can already see from the macrophages that if they would have this marker, they wouldn't respond to our treatment. And therefore, what then happens in this situation is that bexmarilimab actually lowers interferon levels, but we don't know yet whether that would be actually good for that certain cancer. But in all regards, we have now started to understand what type of tumors we want to target. Now going back to the immune checkpoint resistance and what type of tumors do respond and what don't, you can see here a graph indicated with different tumor types, and as the longer the blue line is, the more percentage of that tumor type responds to anti-PD-1 therapy. You can see many different types of cancers in the lower part, like estrogen receptor-positive cancer, head and neck squamous cell carcinoma, ovarian, that really only 10% of patients respond to anti-PD-1 therapy. And what is known about why they don't respond is that there are several resistant mechanisms that produce de novo and acquired resistance to anti-PD-1 therapy. One being antigen presentation. They don't have anything. They don't have a preexisting inflammatory response, so there is no point that the T cells would be able to find the tumors because you don't have any neoantigen. I have marked with asterisks the main function that we can induce with bexmarilimab, which is antigen presentation. By doing this, then, this antigen presentation capability actually can broaden the view on what type of things we can then activate due to this antigen presentation. Meaning that then we can let the T cells infiltrate the tumor, we get immune contexture in the tumor, interferon up, and that would release the resistance to anti-PD-1 therapy. Then, lastly, I want to explain one very important thing that I think nowadays should be considered more. So what is the potential of bexmarilimab use in immunologically cold tumors, as we have mentioned all along? There was this very nice publication in 2018, where they screened over 33 cancer types, and they found that each of these cancer types can be phenotyped to six different immunological classes regarding their immune activation. They can be from wound-healing type to interferon gamma dominant, and so forth. Then on the upper side of the slide, you can see different tumor types and how they constitute or what level of inflammation phenotype they have across that tumor type. You can appreciate, if we look at the CLEVER expression in these different immunological subtypes, we can see that CLEVER is highly important in those lymphocyte-depleted types, which are shown in this light blue. Whereas CLEVER is not important in the interferon gamma dominant, as I have shown you previously. So therefore, we can appreciate that we can select those tumors that have a blue, light blue, for targeting CLEVER-1, as we have a biomarker now that we can use for that targeting. So we can actually employ, bexmarilimab across several tumors once we know which ones to target, and we do know now better. So going back to the solving problems of macrophage-targeted therapies, patient selection is as important as knowing your drug, who to treat and when. So there was the problem of overlapping strategies. So we have a very novel mode of action due to targeting CLEVER-1 with bexmarilimab. We don't have safety issues, as we have found in many patients that bexmarilimab has a very good safety profile. What about the low efficacy as monotherapy? Yes, there is, there was only stable disease, but these were last-line patients and very advanced cancers. Nothing else works in these patients either. It has shown efficacy in 30%-40% of various solid tumors. However, our improvements would include treatment at earlier lines of therapy due to the good safety profile, patient selection, as I mentioned, according to the immune phenotype. We can use it broadly to sensitize tumors to immune checkpoint inhibitors, but we could also use it to sensitize patients to azacitidine, for example. And then we can use it broadly in therapies where antigen presentation and immune activation is desired. So that was it. I guess, do we have a Q&A session, or is it closing remarks from Juho? Maybe we'll do closing remarks and have a Q&A at the end, 'cause it's coming up. Yeah, sure. Thank you, Maija. Maija, you're going to catch Maija on Q&A very soon. Just some closing remarks. Thank you, everybody, for being here. It's been quite a package. But just there's one very important slide coming up. It's not actually this one, but just to those indications we were talking about, how do the markets look? First row, sarcoma there. There's nothing there. So it's, the market looks pretty bad, I would say, but it's a decent-sized population. Again, it's just old chemo. Nothing has worked. So it's a market that completely can be taken. Then again, if we look at the abbreviations are difficult for some of you, but it's B-cell and T-cell lymphoma, the second line, it's big, and the market is already big. But there's a significant need in relapsed/refractory lymphoma patients as well. Then we go to, for example, breast cancer, lung cancer, the following slides. Huge markets, absolutely huge markets. But again, we will have our role there in around 20% to 30% of patients, as Maija presented. Also, in melanoma, gastric, decent-sized markets... and especially gastric, they're at the lower end. PD-1s have not really come through and saved the day there. That's why it's still a relatively small market. So we're talking a significant piece of cake here, as we begun, out there for us to possibly take. So the outlook, this is the slide, the important slide. What's coming up next? We will have a further readout at ASH of the current phase II data to new patients. Then we're looking to have enrollment completed in around end of Q1, the full phase II response rate readout. Then we're gonna start again our interactions with the FDA. We're gonna go for breakthrough designation. We're gonna possibly gonna start a rolling process for accelerated approval as the follow-up data of the durational response and survival start coming in from the phase II data set. So there's a lot on the clinical and regulatory side, and yes, like Petri presented, there's a lot in the solid tumor pipeline. The BLAZE study, the lung and melanoma study in Royal Marsden, that has got the go-ahead. We're very, you know, strict on our cash burn. It will not affect our cash burn to the extent we've allowed that to start, and that will be producing data towards the end of the year. So a lot of stuff coming together. But again, like Petri mentioned, a lot of the solid tumor trials, we can put them together, we can have them ready to go, but as resources come in, we can trigger them and start them up. That's what we wanna do as a company. So I'm gonna invite everybody to the lounge here, and we'll have a closing round of Q&A. Come on, everybody. Okay, maybe I can start with a couple of questions for Maija, as you didn't have a kind of separate Q&A. So you talked about patient selection. So if you take a kind of practical approach, how would you then translate those findings to clinical studies? When could you kind of apply those to clinical trials? I think the right time would be in the phase III trial. At this point, we have preliminary data, but I think we need more patients to validate these, and this will be done together on the phase III trial. So we are collecting material, doing the assay that we are developing now for patient selection, and that will go on as a companion diagnostics development together with the phase III trial. Yeah. There's quite limited data on bexmarilimab, like, preclinical data on CLEVER-1 as a cancer target. So do you know of any kind of interesting studies that foreign investors should be looking for, and when would those be coming out? They will be coming out rather soon. We have to take care of the IP rights first, but then they will be coming. Okay. So maybe next year. Okay, thank you. Okay, so one of the questions was on kind of near-term cash spending. So, are you planning to on using money for solid tumor pipeline? If not, when are you planning to spend money in order to start the trials? So maybe it's good to elaborate a little bit on your pipeline plans and how that will affect spending. So again, in our spend and pipeline plan, we have allowed the BLAZE study, the lung and melanoma study, to go ahead, and it's very cost efficient. I cannot name. You know, we give drug, and we give a little support, financial support. It's not much, so it will not affect our run rate or burn rate to the extent. Following up, the next thing we would initiate is the sarcoma trial. That's a little bit more expensive. We, depending on the incoming resources, that's the next one we would trigger, and then the third one will be the basket trial, which is a pretty big endeavor to sponsor trial, and that's gonna require, I would say, significantly more resources. Partnering, if you may. Yes. But very cost efficiently, we can do the lung and melanoma and the sarcoma, but we haven't initiated the sarcoma yet. Yes. Okay, so Juho, you already talked about the outlook a little bit, but can you maybe go through again what would be kind of the next big milestones for the next six months? ASH, we're gonna come out at ASH with new data. Then the biggest thing, absolutely, for the company is the response rate readout coming around end of Q1 next year. That's absolutely, I would say, the biggest thing everybody should watch for, and like we talked, partnering, that's gonna drive deal value. So that's why it's such an important milestone. Then the regulatory interactions which will follow from that and the survival data coming in, 'cause with the Fast Track we've, we've got, then it's gonna allow rolling submission as the data comes in, and as the follow-up data comes in, if it's with good duration, the survival holds up, I'm just so interested in what, what's the FDA gonna say next? So I think those are the- Yeah. The big items in the next six months. Yeah. If we still talk about a little bit about the very important timeline. So in January, you will be kind of. The recruitment will be finished for BEXMAB. Yes. I think you mentioned in the slide that by the end of Q1, you are expecting a readout of the effects in BEXMAB. But that's quite soon, isn't it? So do you need to follow a little bit longer time before you kind of- Two to three cycles. We need at least two, preferably three. Mm-hmm. So that's two to three months after the enrollment has completed, preferably three to be certain. Again, you, like you talked with Mika, in six months, it's we've seen it already. It comes usually. We've seen nowadays that it comes even after possibly the first cycle. But to really know this, did this patient respond or not, we should look at three cycles of treatment. Then kind of working first on BEXMAB phase II, then preparing for the phase III, at this point, what would be the kind of reasonable expectations when you could start the phase III trial? We're aiming for Q4. That's- It slightly depends on partnering as well. You will need to work hard. We will need to work hard. It's... We try to put pretty ambitious but still achievable milestones. Yeah. But it's gonna be dependent. Again, like Petri said, there's a lot of pieces to the puzzle. We're not in control of all the pieces, but we like to set ambitious goals. Like I said, we got a very small but very hardworking, dynamic team. Exceptional people. Okay, let's look at the audience next. Do you have any questions from the live audience? And also, please send questions via chat. Okay, we have a little bit more specific and a little bit historical question from chat. "I've not heard Faron talk much about the soluble STAB1 in recent years. Are there initial observations that you reported still relevant in tumorigenesis? Yes, we have just been doing a lot of research in that regard, and a manuscript is currently under revision and will soon be out, so- And also some patenting around. And patenting around that, so that has taken a bit time, but yes, we are ready with that one, and it's super interesting. Okay, and can- So that's why we've been silent, 'cause we're patenting. Yeah. Okay, and can you comment on the, kind of, the clinical relevance of it? I mean, relevance for the upcoming trials, or will it kind of affect design or, or things like that? Not really, but it's more of an indication of resistance. I see. ... mechanisms for immune checkpoint inhibitors. Okay. Yeah. I guess following up on that, are there any other similar scavenger pathways that are expressed on macrophages, which may share responsibilities with STAB1? On macrophages, not really. So it seems that if we inhibit CLEVER-1 or genetically knock it down, we affect other receptors. So I think CLEVER-1 is more of the main receptor. And people commonly ask us that there is this Stabilin-2, which is a homolog to CLEVER-1, but that receptor is not expressed on macrophages. It's only expressed on endothelial cells, and that's why it cannot contribute to resistance to anti-CLEVER-1 targeting on macrophages. So I would say not really. Then we have a question on if the potential partners are interested in Bex as a monotherapy, or is the interest kind of mostly for combinations? And I guess this is about solid tumors, so. I'll let Petri answer that, who's the solid tumor guy on combos or monos. We have the same answer- Yeah. ... but I'll give it to you. Of course, the major interest is currently in the combinations, and the rationale there is so good, and it fits so well together with the PD-1s. Okay, I think we have gone through all the questions in the chat, so looking to the audience if there are any more questions. If not, I would like to hand over to Juho for the closing remarks or any other comments. Thank you, everybody. It's been a pleasure seeing you both over the internet here live. What can I say? Amazing small group of people, amazing year ahead. Like I said to some of you today, 'cause you, many of you know the reactions in the stock market today. The company's going like a train. Stock market's going a bit like that's stock, but the company's going like a train. Thank you. Goodbye.