Good morning, everyone. Thank you for joining us at the Ryvu Therapeutics conference with regards to RVU120 Phase II Program Progress and Update. I would like to pass the microphone to Mr. Paweł. We encourage you to ask questions, and we will do our best to answer them at the end of the meeting. Good morning, ladies and gentlemen. It's my pleasure to host you today at the Ryvu Therapeutics press conference, an investor conference, when we will be discussing the progress of RVU120, our most important asset in Ryvu's pipeline. Today, I have the pleasure of having with me Dr. Kamil Sitarz, Chief Operating Officer, responsible for clinical operations at Ryvu, and Dr. Hendrik Nogai, our Chief Medical Officer. My name is Paweł Przewięźlikowski. I'm the Chief Executive Officer of Ryvu Therapeutics. Today, we will be both reviewing the current data as well as presenting some forward-looking statements about the future of Ryvu development programs. So, all of the predictions about the future are obviously non-binding. Ryvu Therapeutics is an oncology company developing first-in-class or best-in-class therapeutics. The most important asset in our pipeline is a fully-owned CDK8/19 inhibitor, RVU120, that is currently in four ongoing Phase II trials. The second clinical asset is called SEL24, licensed to Menarini, and we are currently developing the program with their support. Behind RVU120 and SEL24, we have a full plate of preclinical programs, most importantly, RVU305, an MTA-cooperative PRMT5 inhibitor in IND enabling studies, other synthetic lethality programs, as well as immuno-oncology collaborations with BioNTech and Exelixis. Ryvu currently employs more than 300 people. We are listed on the main market of the Warsaw Stock Exchange, and we are part of the mWIG40 index. Our cash runway allows us to perform research and development of all of our programs at full speed until the first quarter of 2026. If you look at Ryvu's pipeline, you can see that we are conducting a robust development program for RVU120. The program is currently in four ongoing Phase II trials that we initiated in 2024. RIVER-52 is a study of RVU120 as a single agent in acute myeloid leukemia in relapsed refractory patients. RIVER-81 is a study in AML in a combination with venetoclax, and it's important to mention that we are dosing patients who have already received a venetoclax-based regimen with hypomethylating agents, so in many cases, these are third-line patients. The third study is REMARK. It's a study in lower-risk myelodysplastic syndrome that we are conducting in collaboration with the EMSCO network. It's an IST, and the fourth trial that we initiated just two weeks ago is POTAMI-61. It's a study in myelofibrosis, which is also a blood cancer. We are also wrapping up the study in solid tumors, which allowed us to provide additional safety data, some signals of efficacy in adenoid cystic carcinoma, as well as try different dosing regimens of RVU120. SEL24, our next clinical project, used to be developed in acute myeloid leukemia, but now, with the support of our partners from Menarini, we are going to launch another study in diffuse large B-cell lymphoma. Several sites are already open, and we are expecting to dose the first patient very soon. Behind the clinical pipeline, the next project that could make it to the clinic we are targeting completion of IND enabling studies in Q4 2025 is RVU305, which is a potentially best-in-class MTA-cooperative PRMT5 inhibitor for the treatment of various solid tumors. Behind this, we have a Werner helicase program that can be used both as a single agent, as an ADC, multiple undisclosed internal programs, and two very important collaborations with Exelixis on STING antibody-drug conjugate, and a multi-target collaboration with the German oncology powerhouse BioNTech. Now, I would like to give over to Hendrik Nogai, who will tell you more about RVU120. Thank you. Thank you. Hello, everyone. I'm delighted to meet you all here in this webinar and in this conference room. My name is Hendrik Nogai. I'm the Chief Medical Officer at Ryvu. First, I would like to give you some background on RVU120. RVU120 is an inhibitor of CDK8, CDK19 kinases. These molecules are a component of the mediator complex. This is a rather complex biology. Essentially, the mediator complex is involved in regulation of mRNA transcription, and mRNA are the progenitors of proteins. This pathway is very important during embryonic development. Importantly, and this is also why we are using it as a target, this pathway is often reactivated during cancer transformation of cells. Addressing and inhibiting this pathway is suggested to show beneficial effects on many different cancer cells. We designed RVU120 as a highly selective and highly potent small molecule. RVU120 has a lot of beneficial features. So, I mentioned the selectivity and the potency, but also, there's a low risk of drug-drug interactions. And this may seem as a detail, but actually, it's quite important because, especially in acute myeloid leukemias or in other hematologic malignancies, patients have to use antifungals, and these antifungals are very sensitive to drug-drug interactions. So, a lot of drugs in this patient population have liabilities in terms of combinability with antifungals. So, we can avoid this with RVU120. RVU120 is also easy to formulate. It's an oral drug, and it has been shown in non-clinical models, but also in clinical data, that the safety profile is rather favorable, which is due to this high selectivity profile of RVU120. I mentioned that CDK8, CDK19 pathway is often activated in many different cancer cells. So, we see a broad opportunity space for RVU120. We see opportunities in hematologic malignancies, but we also see opportunities in solid tumors. And as you have seen in one of the prior slides, we have currently four Phase II studies open with patients with hematologic malignancies, but we also tested RVU120 in patients with solid tumors. And we did not devalidate the concept of using it in solid tumors. We just focused our attention and our resources on the hematologic malignancies because this is where we see the lower-hanging fruits and the easier path to development. I would like to mention, though, that just very recently, there was a high-profile manuscript published, and this manuscript described the relevance of CDK8 inhibition in patients with medulloblastoma. Medulloblastoma, based on the currently available non-clinical data, remains a valid opportunity, as well as adenoid cystic carcinoma, where we had seen some initial signals in the clinical trial. Okay, but I will focus on the hematologic malignancies first. We have conducted and completed a dose-finding study in patients with acute myeloid leukemia or high-risk MDS. In this study, we were able to collect important information that guided what is still guiding the current development of RVU120. We saw, across different dose levels, different signs of clinical benefit. This benefit included clearance of blasts, but also included hematologic improvement, which is an important endpoint for patients with hematologic malignancies. We also see reduction of bone marrow fibrosis in at least one patient. We have seen these signs of clinical benefit, especially in certain selected patient populations, so namely in patients with NPM1 or DNMT3A mutation. Also, the patient population with high-risk MDS seemed to be quite sensitive to RVU120. On top of this, we could also confirm the safety profile. During dose escalation across all dose levels, we have not seen a single dose-limiting toxicity. We were able to dose patients at levels that allowed 50%-70% of target inhibition, which is expected to translate into robust efficacy in clinical studies. Now, in a little bit more detail, so I mentioned the blast reductions, the blast clearance, and I would like to highlight one patient that we have treated in the Phase I study. This patient had experienced prior lines of therapy. His AML did not respond or relapsed. When starting treatment with RVU120, the patient had about 50% of blasts in the bone marrow. Already, after two weeks of treatment, these 50% blasts have been completely eliminated. So, the bone marrow turned out to be free of blasts. And on top of it, the patient had skin lesions, so leukemia infiltrates in the skin. And also, these skin lesions that are poor prognostic markers completely disappeared. So, the patient achieved a complete response, and also, the hematologic count fully recovered. So, this was a very promising signal that we have seen in the Phase I study. What we have also seen is that more than 20% of patients achieved hematologic improvement. And this included patients with transfusion independence. That's a very important endpoint for patients with low-risk MDS, and this is also why we started a study in this population. And lastly, I would again like to highlight the patient that achieved a reduction of bone marrow fibrosis. Reduction of fibrotic tissue is something that is hardly seen with any drug currently in clinical development. This may turn out to be a very important feature of RVU120. Now, all these data together form the basis of our current clinical development plan. Paweł already mentioned it. We're testing RVU120 now in four Phase II studies. The first one is testing RVU120 as a single agent in AML and high-risk MDS. Second one, in combination with venetoclax. Again, it's important to know that this is tested in patients that had experienced prior venetoclax and failed treatment. POTAMI-61 is testing RVU120 as a single agent and in combination with ruxolitinib in patients with myelofibrosis. Lastly, we have the REMARK study. This is done by the EMSCO network as an investigator-initiated trial. This study is looking at the hematologic improvement and transfusion independence in patients with low-risk MDS. Now, I would like to hand over to Kamil to show you a little bit how we do in terms of operational conduct of these studies. Good morning, ladies and gentlemen. It's my pleasure to present some numbers that stand behind our Phase II studies. Maybe starting with the enrollment. So, two of the four studies that we were discussing previously were initiated in the beginning of the year. Then, we also had remaining two studies, being more precise, our low-risk MDS REMARK and POTAMI that joined in the second half of the year. But what can be observed is that the enrollment has significantly picked up, especially Q4 this year, with the numbers that we are hoping to see by the end of the year being almost three times higher than what we have observed in the first three quarters of the year. From this perspective, keeping in mind also the sites that we have activated, that I will be discussing in a second, the enrollment kind of reached the level that we were expecting, and we hope to keep this trend unchanged. Another element that is worth to kind of pay a bit of attention to is also the time needed for the evaluation of the patients. It differs between different studies because the endpoints that we are looking in our AML study, both monotherapy and combination, as well as myelofibrosis and low-risk MDS, they change. This is why when the patient gets enrolled into the study and starts dosing, we need still some time in case of POTAMI. We're talking about multiple weeks that is needed for disease assessment. And this time, obviously, tells us whether the patient responds properly to the therapy. With this in mind, also a bit of our global footprint for the studies. As Kamil presented, Ryvu currently enrolls patients in multiple countries in Europe and also in Canada. Our footprint in Poland is quite strong, with over 30 sites activated. But then, we are also in Italy, Spain, France, Germany, and, as mentioned, Canada. Additional countries, both in Europe and outside, will be planned according to the study conduct and needs of potential expansions. As of now, the number of sites within all those four studies exceeded already 100 activated sites, and we plan to see a number above 110 by the end of the year. With this number of sites and also commitment from investigators, because we are in frequent discussions with them and we hear feedback about the therapy, and we are convinced that the machine standing behind our studies is sufficiently prepared to enroll patients at the right pace and allow us to look also for the efficacy signals. Giving a little bit of summary before we move more specifically into individual studies, in our RIVER-52 study, what has to be kind of indicated is that the enrollment that we have seen in the first three quarters was significantly increased in quarter four. A number of patients that currently are in the study were enrolled relatively recently, especially in the NPM1 mutated cohort. We have so far seen that one of the two evaluable patients seen a 50% blast reduction. We have more patients that were enrolled into this cohort, but they have not reached yet the stage of disease evaluation. With additional patients, we are also seeing disease stabilization. What else needs to be mentioned is that with this level of enrollment, as we see right now, data from approximately 10 plus patients from each cohort, so namely NPM1 mutated, DNMT3A mutated, and high-risk MDS, is expected in the first quarter of 2025. Moving into RIVER-81, what's important to mention, this study is divided into parts. The first part was dedicated to dose escalation of both agents in a combination, and we have successfully completed nominating the highest dose of both agents to part two. This part two has already also got triggered. As of now, we have enrolled over 10 patients into stage one of part two. What else is worth to mention is that out of eight patients that were treated with RVU120 at 250 doses, just to remind you, this is our recommended Phase II dose. And our post-baseline assessed, we have seen one complete remission, and Hendrik will be discussing that more in detail. With POTAMI and REMARK, these studies, as mentioned, were initiated towards the second half of the year, POTAMI this month. So, we are in progress with enrollment. We see great commitment from the sites and support. So, we feel confident that enrollment will move to allow us to have some initial efficacy data in Q2 next year. So, with all of that in place, just to kind of wrap up, so we see first signs of efficacy in Phase II. What's important, we have a number of patients right now on all of the studies, and we hope to present more efficacy data in the first quarter of next year. That also drives me towards commercial opportunity because, obviously, apart from an obvious medical need in patients, there is also the commercial background of the therapies. Specifically in AML, the two studies that are currently run, so RIVER-52, our monotherapy study in relapse refractory AML, but also specifically looking into NPM1, DNMT3A mutations, but also RIVER-81, which is in AML but looks specifically into a population of patients that are refractory to prior venetoclax treatment. So, both of those studies, they create a market opportunity with several hundred million dollars. But what else we see currently is that with good data from the combo study, we might be looking also into going into the higher lines of treatment for the patients, so moving from the relapse refractory setting into newly diagnosed AML patients. And obviously, this also increases the size of the market that can potentially be addressed by RVU120 in different therapeutic options. And with that, I will hand over to Hendrik to focus on individual studies. Thank you. Yeah. Thank you, Kamil. So now we can look a little bit closer into the individual studies. So I will start with RIVER-52. This is the study testing RVU120 as a single agent. And as I mentioned already, so we see differential sensitivity of RVU120 in different patient populations. So this is why we focus on certain subsets of patients. So namely, we focus on patients with NPM1 and DNMT3A mutation and on patients with high-risk MDS. So the NPM1 and DNMT3A concept is not just based on the observation that we have made in the Phase II study, but it's also based on preclinical predictions, and there's also biological concept. So these patients or these leukemia cells, they depend on a certain genetic program. The homeobox genes and RVU120 is able to inhibit homeobox genes, which we could show in preclinical data, but we could also nicely confirm this effect in the patient that achieved a complete response. Overall, we have a good rationale to focus on these patients in order to increase the probability to success of the study. This is how the study is designed. We are currently in part one of the study. We have now three cohorts open. One for patients with NPM1 mutation, one for patients with DNMT3A mutation, and the third one for patients with high-risk MDS. We plan to treat 10-20 patients in each cohort. We will look at the clinical benefit. Only when we see a sufficient CR rate or sufficient level of clinical benefit, we will then open part two and aim for, yeah, a more confirmatory study with the goal of an approval pathway. We are currently planning to have 80 sites globally in order to run the study. Of course, we have to pass the gate after part one before we open part two. Now we are looking at the patient data. What you see here is the swimmers plot indicating the time on treatment. What you see, and this is also in line with what Kamil just explained to you, the majority of these patients just entered treatment. They are still ongoing. Out of a total of 30 patients, 14 are ongoing. Many of those did not have a first post-baseline assessment, so we cannot determine the response to RVU120 yet. So we have to take this with a grain of salt. So this is evolving data, and we will be able to tell more in the first quarter of next year. But as of today, it's very preliminary. Still, we see some important information. And first, I would like to highlight that we did not identify any new safety signal. So this is now the first time that we treat a broader patient population with RVU120 at the recommended Phase II dose. And it's very reassuring that we have not seen any new safety concern. What is also important is that we were able to confirm the pharmacokinetics of RVU120. It is possible to get the drug into the patient to achieve a relevant concentration in the circulation. These are all features that are important to learn, although not yet informing us sufficiently about the efficacy. For efficacy interpretation, the data is still immature. Still, I would like to highlight the patient with NPM1 mutation that you see here colored in purple. This patient had a nice reduction of blasts to more than 50%. So, I mean, it's not meeting complete response criteria, but certainly, it is indicating that the cells were reacting to RVU120 treatment. I mentioned the safety profile for RVU120. Seeing on this side, we are trying to compare it with other drugs that are currently in development in the same patient population, so in patients with the NPM1 mutation. Of course, this comparison is not really valid because you should not do any cross-trial comparisons. But still, I mean, this is the best data that we have. And we see that at least numerically, RVU120 is showing a better safety profile in almost all categories. So these are relevant categories. And notably, we do not see any QTc prolongation. So QTc prolongations are, yeah, a change in cardiac rhythm. So it has the risk of severe cardiac arrhythmias. So this is a liability for, especially the first menin inhibitor, revumenib, in which about 25% of patients this QTc prolongation is seen. We do not see it as a signal at all. And also differentiation syndrome, which is sometimes difficult to manage, is something that we do not observe with RVU120, but it is seen in about 20% of patients with the menin inhibitors. Also, the rate of infections and liver damage seems to be very comparable, if not better, than with the menin inhibitors. So I mentioned that all the efficacy analyses are very early and preliminary. So we should not over-interpret it. But we still wanted to, yeah, show some of the data and just to give you an idea of what we're currently seeing. So here on this plot, you see the patient with NPM1 mutation. And in the upper right corner, you see the bone marrow blast, so the green and the purple line. And you see that there is a reduction from 17% or 18%. So depending on the assay of quantification, down to almost, so it's like 8% or 7% or 8%. So the cutoff of a complete response is 5%. So the patient was close to it, but still not reaching it, but still a relevant decrease. Now, one reason why this patient may not have achieved a complete response and why this patient also then progressed in the fourth quarter is shown on the lower left corner, so this analysis shows you the presence of different clones, so different mutations in different leukemic cells, and you see that this is not just one clone in this patient. It's actually at least three different clones, and only one of these clones is carrying the NPM1 mutation. So this patient was really hard to treat, also because the patient failed prior lines of therapy, so I think with this outcome, I mean, although not meeting any approval endpoint, I think it is indicating that, yeah, the treatment of RVU120 was effective on at least some clones. On the same level of evidence, so with the same level of caution, we would like to show you additional patients. So again, I would like to highlight that these patients did not meet any objective response criterion or not any approval by endpoint. But in the cohorts of DNMT3A mutation and also in a patient with high-risk MDS, we have seen some, let's say, interesting clearances of blasts. So between the start of treatment and then the first disease assessment, and you can see it from the lines, there is a reduction of blasts. All these patients are still ongoing. So it is possible that these patients convert into a more objective response. But again, I mean, it's preliminary data. We don't want to oversell it, but also we do not want to hide anything. So, I mean, this is, at least in my view, another support of evidence that we should continue the study and that we should wait for more data and for mature data, especially. Okay. This is just, again, a highlight on the enrollment rate. You see that there's a significant increase of enrollment, especially in the last few weeks and months. We are now on track to follow these patients to collect more data. And within the next few months, we will be able to tell if the effect of RVU120 is good enough to continue the study and to open part two with the aim of an approval. Okay. In summary, again, I will mention again that the data is immature. We cannot make a final assessment of efficacy. We do see some initial signs of activity, so initial promising signs. This motivates us and also investigators to continue enrollment of patients. And so with the improved enrollment rate that we have seen recently, we will have more robust data in the first half of 2025 that will proper decision-making and then also gating part two of the study. Okay. Second study is RIVER-81. So this study is testing RVU120 in combination. And the reason why we selected venetoclax as a combination partner is based on very robust non-clinical evidence. So we could not only show a very strong synergy between RVU120 and venetoclax, we can also describe the mechanism why RVU120 can overcome resistance to venetoclax. It is known that MCL-1 is an important, maybe the most important mediator of resistance to venetoclax. It is commonly upregulated in patients that fail venetoclax treatment. Because of this observation, MCL-1 inhibitors have been tested in this setting. However, MCL-1 inhibitors turned out to be truly cardiotoxic. They had negative effects on the heart muscles. Therefore, this development path was discontinued. With RVU120, we can now see that we can induce degradation of MCL-1, so not inhibition of the MCL-1, but degradation of MCL-1, thereby changing the resistance pathway to venetoclax without seeing the cardiotoxicity, so without seeing the negative effect on the heart muscle. On top of it, we also see very strong activity on leukemic stem cells, which could then also be important to maintain a response and to prolong the duration of the response. The important feature of the RIVER-81 study is that we only include patients that were previously treated in the first-line setting with venetoclax. These patients had seen venetoclax, they failed treatment, and they are now re-exposed to venetoclax, but now in combination with RVU120. The first part was the dose escalation part. We successfully completed this dose escalation part. The safety profile of RVU120 allowed us to use the highest doses of both compounds. So that's also a very reassuring finding. And we just recently opened part two for enrollment. So here you see the different cohorts. So we had three dose levels in part one with different numbers of patients. And now we selected the highest dose and started part two enrollment. What is also important to mention is that, again, looking at the pharmacokinetics, so there is no drug-drug interaction between venetoclax and RVU120. So it's a very good combinability in terms of safety and in terms of pharmacokinetics. Okay. Now focusing more on the efficacy readout. So in dose escalation, we have not used the full doses. So, I mean, please also keep this in mind when looking at the responses. Part two was just recently activated. We have many patients currently on treatment. Ten or 11 patients started treatment recently. They have not yet received their first post-baseline assessment. We cannot say anything about the efficacy. But when you look at cohort two and three, these are the two cohorts where we used the highest dose of RVU120, you see some patients that had benefits. We had a patient, the first patient that you see here on this plot, there was a patient with a decrease of bone marrow blast. This patient is still ongoing. There was a decrease from 20% at baseline down to 9% in flow cytometry, still exceeding the 5% threshold. But again, the patient is still ongoing. Maybe this is converting to something even better and more objective. Very important is to highlight the patient here in purpose. So this patient achieved a complete response. And I have more details on this patient on the next slide. And in cohort three, we have one patient that actually had a reduction of bone marrow blast to below 5%. And the investigator assessed this patient as a complete response. However, we are a little bit, yeah, more careful, more conservative because the baseline blast count was rather low. And we would still like to see some more confirmative evidence before we call this a complete response. But one patient clearly had a confirmed response. And this patient is shown here on this slide. So this patient, 82-year-old female patient, received venetoclax as a second-line treatment as a first-line treatment for almost two years with an initial complete response. But then after this almost two years, the patient then progressed and lost the response to venetoclax. Just a few weeks after a treatment break, the patient was then re-exposed to venetoclax in combination with RVU120. You see on the purple and green lines on the right upper plot that there's a very nice decrease, actually a complete clearance of blasts in the bone marrow. This was associated also with an increase of platelets, so the green line in the plot below, and an increase of neutrophils, so hematologic recovery constituting a complete response in this patient. Unfortunately, this patient decided to withdraw from the study because of, yeah, tolerability. I mean, the patient was not initially treated at the site, so the patient was referred. He had to commute to the study visits. As you can see, 82-year-old female lady, so not in the best condition. The patient then eventually decided, despite the very good outcome, that she did not want to continue on the study. And then this is also when the platelets dropped again. And I mean, we continue to collect information on this patient. The patient is still in complete response in terms of the blast clearance, but does no longer participate in our study. This is the second patient. This patient with less than 5% of bone marrow blasts in the first disease assessment. You can see that the baseline blast count was already quite low. There was also no associated improvement of the platelet count. This is why we are a little bit more careful. But again, the investigator assessed this patient as complete response. And this assessment is what we currently have in the source documents. This patient is very difficult to treat. Also, we experienced prior venetoclax-based treatment. This patient has a very difficult molecular background. The patient has TP53 mutations, actually biallelic. On both alleles, TP53 is mutated. This is known to be a terrible prognostic marker. These patients do not have any option at all. Having this patient on treatment, reduction of blast is already a very good outcome. Okay. I mean, so I think this is just repeating what we said before, right? The purple line showing the enrollment rate. I mean, this is nicely picking up. Now with the opening of part two, we also have more slots available. We are well on track in completing at least the first stage in the part two. This will also allow us to make an informed decision on the further progress of this study in the first half of next year. Now, trying to better understand the options that this study will bring us. If we continue to see complete responses in this patient population, we have a reasonable chance to aim for an accelerated approval based on a single-arm trial, at least in selected regions, based on the RIVER-81 study, so after further expansion, so after progressing into part two and part three of the study. But as Kamil mentioned, we also see an opportunity to move this treatment approach into early lines of treatment. We may be able to address the first-line setting. And of note, based on our current data, we may be able to address an unselected population in the first-line setting, so not restricted to any molecular aberration. Okay. In summary, we successfully completed the part one dose escalation. We confirmed the safety profile of RVU120, in this case, even in combination with venetoclax. One patient in part one achieved a CR, and I mentioned also the other patients with some preliminary evidence of activity, and we successfully also initiated part two. Enrollment is very nice, which is also another confirmation of the trust and the confidence that the investigators have in this trial, so they are very eager to expose their patients to our treatment, and we expect the next data release in the first half of next year, and the next data release will then also tell us a little bit more on how to progress with the study, so whether to expand part two and whether to move into part three. Okay, so before moving into the other tumor types or hematologic malignancies, I would make one comment. We just returned from the ASH conference in San Diego, where you have, I mean, the global leaders meeting and discussing latest advances in hematologic research. We were happy to see now two important publications on RVU120 published not as RVU-sponsored studies, but as academic research. One study was assessing the relevance of CDK8 inhibition and RVU120 in models with ASXL1 mutation. The other one was assessing RVU120 in combination with FLT3 inhibitors. Important information. This information may also guide our further development. It is good to see that the academic research is also now getting more interest in CDK8 inhibition and especially in RVU120 because both of them used RVU120 as a tool compound. Okay. Switching from acute myeloid leukemia to myelofibrosis. We recently initiated POTAMI-61. We treated the first patient. We have a very strong rationale to test RVU120 in patients with myelofibrosis. First, I mean, there's always the feasibility consideration, the unmet medical need, but then also the commercial opportunity. Myelofibrosis is a growing market. There are a few new drugs approved. It's also a growing population, and more patients are diagnosed with this disease. We have very robust non-clinical data suggesting that RVU120 can have a unique profile in myelofibrosis. We see improvement on all the disease features. We see improvement of hematology. We see improvement of the spleen size and the liver size. Especially, we also see a reduction of bone marrow fibrosis, which has not been seen with any other drug so far. This is a rather technical side, but this shows you, I mean, the method that we are using. Actually, when I say we, it's essentially the group around Professor Raajit Rampal at the Memorial Sloan Kettering Cancer Center, who is using a very sophisticated mouse model to test different drugs in their lab. And so we see a very nice reduction of spleen size, liver size in mice. And especially, we also see a very good improvement of overall survival in mouse models. Now, this is even more technical and maybe difficult to understand. But essentially, what it says is that we looked at the interactions between CDK8 and other pathways. And the reason for looking at these interactions is to identify suitable combination partners. So we are testing ruxolitinib, a JAK inhibitor, already as a combination partner in our POTAMI-61 study. But with this analysis, we were also able to identify additional combination partners. So drugs that are currently in development, recently approved, like momelotinib and pacritinib, pending approval, like pelabresib. And RVU120 combines very well with different agents. So we can even go beyond ruxolitinib combinations, and we can combine with almost every interesting drug currently in development for this patient population. I would like to repeat this one case that we have observed in our Phase I study. This was a patient with bone marrow fibrosis, not on the basis of myelofibrosis, but on the basis of MDS. But still, it was a fibrotic tissue in the bone marrow that nicely resolved between cycle two and cycle six on RVU120 treatment. Again, it's a very interesting feature. And so far, we do not have any anti-fibrotic drugs for myelofibrosis in clinical development. The study design is pretty straightforward. So we have part A. In part A, we are testing RVU120 as a single agent and in combination with ruxolitinib in a smaller set of patients to confirm the safety of this population, to also confirm the schedule that we're currently using, and of course, to collect some initial efficacy data. If we can clear part A, then we move into part B, which is a broader population to confirm efficacy signals and to identify the most suitable primary endpoint. If we see good data in the second line, and of course, we will focus on the second line first, then we may also have an opportunity to move in the front-line setting, either in combination with ruxolitinib or any other combination partner. Okay. And the last study is the REMARK study. This study is testing RVU120 as a single agent in patients with low-risk MDS. This now is a completely or not completely, but it is a different patient population. This patient population is usually fit. The main burden of disease is anemia and the need for regular blood transfusions. This patient is not at immediate risk of fatal outcomes, so unlike patients with AML or high-risk MDS. The goal of RVU120 treatment in this patient population is to improve the hemoglobin levels, to essentially resolve the anemia, and to spare the blood cell transfusions for patients. For this study, we have a very robust preclinical background. We know that RVU120 is stimulating the GATA2 pathway. This pathway is very important in terms of erythropoiesis, in terms of forming hemoglobin, red blood cells. We also have seen initial signs of evidence in our Phase II studies. So we have seen patients with hematologic improvement with transfusion independence. And because of all the data, non-clinical and clinical data, the EMSCO network was very interested in testing our drug in patients with the lowest MDS. And therefore, we started a study, or we are supporting this investigator-initiated study. So this is testing RVU120 in patients that do not have any other treatment option. And there are a few new options now in lowest MDS, luspatercept and imetelstat as examples. And the study group around Professor Uwe Platzbecker, who, by the way, was also responsible to develop luspatercept and the imetelstat, so they managed to treat the first patient in September this year. Enrollment is very well on track. Because it is an investigator-initiated study, we do not have direct access to data. So we cannot share any outcome of the study. What we can share, though, is the enrollment rate and the site activation rate. So you can see here that the first patient was treated in September. And as of today, we have already 18 patients on treatment with several more in screening. And yeah, the number of site activations also shows you the interest of the community. And we actually do see a lot of good discussions and a lot of excitement around the study. So also here, I think enrollment is very well on track. We need 16 weeks to meet the first disease assessment per protocol. So we need to be a bit patient for the data readout. But I think we are well on track to also have actionable data in the first half of 2025. So this concludes the data review. And then I hand over to Kamil again. Thank you, Hendrik. A bit of a RVU120 outlook. To summarize where we stand as of almost the end of the year. This year, we were able to initiate four Phase II studies in RVU120. All of those studies are currently enrolling patients in six countries, five in Europe, and also in Canada. In the upcoming future, we are also looking into opening additional sites, not only within the European Union, but also outside. The obvious choice would be going to the U.S., but also the other countries to look very interesting. What else needs to be mentioned, and Hendrik briefly commented on it. Within the sites that we have already activated, we have a really, really strong investor community. We are very well supported, not only with the enrollment, but more specifically with kind of a necessary network of investigators that was very visible also at the ASH conference. We had a chance to meet with the investigators. We had a chance to participate in three advisory board meetings, so advisory meetings with key opinion leaders that kind of were able to look into our data and support us also in planning next steps. So this support is also very visible and very helpful for the program development. Coming back to the sites, the number of sites right now, we have over 100. Then we only have a number of sites that still are planned to be activated this year. But this level that we have already achieved is very well supporting each individual study with the proper enrollment. And that also resulted with a plan of dosing almost 100 patients this year. And this is pretty much in line with our expectations and what we have shared with you in the beginning of the year. So it also shows that from the kind of operation perspective, we are very much ready to deal with all those four studies in an efficient manner. And obviously, this is all supported not only with the investigators, external community, but also a strong and very committed internal team at Ryvu. So what's next? And we were talking a lot about ongoing patients, the fact that we need to wait for evaluation of those patients. And our plan is to look in the first half of next year into the data from each individual study. Just to remind you, in RIVER-52, so our monotherapy study, we're hoping to kind of those 10-plus patients in all the cohorts that are currently treated with RVU120, then RIVER-81 also will give us data from the part two. And we are also looking into first efficacy signals, both from POTAMI and the REMARK study. And with all of that at hand, we will be able to not only review the data at full, but also plan the next steps and development paths, which lead to accelerated or regular approval pathways that we are seeing for our studies. And this is also something, a very important piece of objective that we keep in mind when planning and looking into the data. So something that also is worth to be mentioned that we are very much keeping our budgets tight and in line with what we are planning. It's a lot of cost optimization efforts in place, what also allows us to keep the cash runway at the level of Q1 2026. With this, I would like to hand over to Paweł. Thank you, Kamil. So as you know, RVU120 addresses several unmet medical needs. And we have several independent chances for success. So you know that AML is a universally, almost lethal disease. Patients are relapsing even on the best available treatment, best available combinations. And it's visible with the interest from the investigator community. Once we have finished the dose escalation in RIVER-81, we had lines of patients waiting to be enrolled in the study. And as you can see from the enrollment over the last several weeks, it's really a combination that addresses very serious unmet medical needs across all countries where the study is open. We hope that RIVER-52 will also lead to strong efficacy signals that will allow for registration as a single agent of RVU120. The commercial potential, obviously, is showcased by the sales of venetoclax and the recent November 2024 partnering deal between Kura Oncology and Kyowa Kirin, where Kura received $330 million as an upfront payment for a drug that is very likely to be approved next year. We don't have the data as mature and as good data that Kura has already, obviously, and they have a much more advanced program. But we are talking about the size of the potential market. In myelodysplastic syndrome, if Ryvu proves to be an erythroid differentiator, if patients can reduce their anemia, reduce their transfusion burden, then we obviously also have good benchmarks for the potential market size. The best-selling drug is Reblozyl, luspatercept, that sells at several billion dollars per year. Recent approval of Geron imetelstat, Rytelo. Also, the forecast sales are north of $1 billion. Especially in this disease with a lower risk of transformation to acute myeloid leukemia, the treatment is longer. If you can show for a long time that you are benefiting a patient, obviously, the potential savings are also in line with the perceived benefit. Myelofibrosis has been under the radar of drug development. There were not so many new agents since the introduction of Jakafi, maybe like 10 years ago. The last three years have seen a plethora of deals showcasing the still existing unmet medical need in this indication. Most of the programs that are approved right now as a single agent targeted therapy are JAK inhibitors. Essentially, it was very hard to identify a new class of therapeutics that would be very effective. Recently, also a BET inhibitor, pelabresib from MorphoSys, made headlines following the acquisition of MorphoSys by Novartis for more than $2 billion. It shows how needed new agents are and how needed agents with differentiated therapeutic mechanisms are. We recently hosted a hematology foundation in Kraków, and we also hosted a patient with myelofibrosis who was sharing his story with Ryvu team. And I can only say that they said, "We learned from some doctors that your drug can potentially cure fibrosis or reduce fibrosis in myelofibrosis patients." They said they were super excited to see something like that because there are no drugs essentially approved that routinely would cause the reduction of fibrosis, and we brought this story of a patient to ASH conference. And we are a little bit jetlagged today because we just came on Tuesday with a nine-hour time difference. During one of the three advisory boards that we had at ASH, we discussed this patient's story and the requirements from the foundation. I asked them, "Vera is saying that the drug that would reduce fibrosis would be a breakthrough. Is it just because Vera is from Poland and maybe doesn't have access to novel therapies or knowledge?" No, all the investigators agreed that really a drug that could reduce fibrosis in myelofibrosis would be a big change. In summary, we wish you well, or maybe let's start differently. At the start of the year, we committed to data updates from RVU120 in June. We delivered posters at EHA. We committed to data updates in December. Unfortunately, the data was immature for ASH. Our posters were not accepted. You can just see the abstract in the abstract book that we filed in July. But we wanted to give you an update. Although as you can see, the data is a little bit immature, we wish we could maybe meet with you once again in February and March, where we have more patients available for efficacy. And then we will know whether the drug has the sufficient efficacy for a potential approval in AML. The data in low-risk MDS, obviously, it's immature because if we started dosing the first patient in September, then the earliest efficacy data that we may have is in January next year. From the time, the evaluation cycle is 12 weeks. So from December, it's until March in order to have the first efficacy data. We are looking forward to have more data in Q1 for AML and in Q2, more data packages available for lower-risk myelodysplastic syndrome and myelofibrosis. Obviously, irrespectively of whether our posters will be accepted for EHA 2025 or not, I certainly hope so, we will give you some data update in June next year. I would like to thank very much the team at Ryvu, Hendrik and his medical team for designing brilliant studies and excellent contact with the investigators, strong patient management, and Kamil and his operating team for developing this enrollment machine and patient management machine that is our clinical operations team. As you know, Ryvu has always had good science, but sometimes we are struggling in operations. If I remember correctly, maybe we are dosing maybe like 10-20 patients per year at the most in our studies before. Now we are dosing 20 patients per month. So it's a big improvement. And we could scale the operations and to manage such projects. But the number of patients in the studies also shows how attractive these programs may be and how hungry the oncology community is for something that would be potentially disease-modifying and transformational in all of these therapies. And thanks again to Kamil because all of these studies are more or less in line with their budgets that we anticipated. Obviously, there are some variations, some risks, etc. But we can reaffirm our cash guidance. If everything goes at top speed, if we decide to continue all of these studies at the maximum speed and maximum number of sites, our cash will still last until early 2026. And by this time, obviously, we should be able to make important decisions about the further development of the program, as well as secure, obviously, financing for the next stage of development. So with this, maybe I would like to thank you very much for your attention. And maybe if there are any questions from our online community, then we can address them. If not, then maybe I will go over to Piotr to manage the meeting further. I would like to give a thanks to all the participants here on site and also to almost 200 people who joined us online today. Thank you very much. If you have any questions, just mail us at ir@ryvu.com, and see you with the next occasion.