Risk factors that may cause actual results or events to differ materially from those described in these forward-looking statements. Now, a little bit about the agenda. Before we begin, I'd like to quickly walk you through today's agenda. I'll start with some opening remarks to set the stage for our discussion. Then, Dr. Omer Jamy will provide important context on the AML treatment landscape, including current standards of care and areas of unmet need, and how GPS and SLS009 fit within it. From there, Dr. Panagiotis Tsirigotis and Dr. Dragan Cvicic will discuss the mechanism of action and differentiation of GPS, along with a phase III REGAL trial, and will walk us through the clinical and commercial overview of the study. We'll then turn to our second program, SLS009, beginning with Dr. Philip M. Rein, who will outline the scientific rationale for SLS009 in high-risk and Venetoclax-refractory AML. Dr. Cvicic will then present recent efficacy and safety data from the phase II trial and share insights from recent FDA discussions. Dr. Sharif Khan will offer his clinical perspective based on real-world experience treating AML patients. Finally, we'll wrap up with a Q&A session of questions we have received from our analysts and investors. Then we'll have final closing remarks. We're hosting this R&D event to give our scientific and clinical community, as well as our shareholders and partners, a deeper look into the innovation that drives SELLAS. Today is about more than data. It's about the science, the strategy, and the vision that define our work and the long-term value we're building. As I've stated many times before, the work we do at SELLAS is not for the faint of heart. Our commitment to patients and stakeholders requires courage, resilience, and an unshakable belief in the transformative potential of GPS and SLS009 to change lives. Together, we're developing treatments that hold the promise to change the treatment paradigm, to be disruptive in the future for patients battling cancer, a responsibility that humbles and drives me, as well as everyone here at SELLAS, every single day. I'm grateful for the SELLAS team's extraordinary efforts getting to this pivotal time for the company. I can assure you that this group is dedicated and committed to seeing GPS and SLS009 make a difference in patients' lives. Over the past years, we continued to present positive clinical and key regulatory news across our programs. I strongly encourage you to focus on the long-term potential and the exciting milestones that lie ahead. We appreciate the support of our institutional investors and the fact that a meaningful portion of our shareholder base is retail, who understand the great potential of our clinical assets and pursue to add to those physicians' portfolio of treatments in their battle against devastating disease. At SELLAS, we believe that rigorous, high-quality science is the foundation of meaningful therapies and ultimately of lasting value for patients and shareholders alike. The strength of our pipeline and the consistency of our results reflect that discipline and our focus on delivering both patient impact and sustainable growth. To that end, we have significantly strengthened our balance sheet this week with the additional $31 million in gross proceeds from outstanding warrant exercises, which not only allows us to see through key clinical data for GPS and SLS009, but also allows us, particularly in such a volatile market, to keep and accelerate the momentum and deliver on our clinical programs. When I founded SELLAS, it was driven by a simple conviction that science, when pursued with focus and integrity, can truly transform patients' lives. We set out to build an oncology company that blends breakthrough innovation with rigorous execution and strong capital allocation discipline. Our first major step was the development of GPS, a novel WT1-targeted immunotherapy designed to address a range of cancers through a differentiated mechanism. Over the years, GPS has consistently delivered positive and encouraging clinical results, reinforcing our scientific foundation and our commitment to patients in need. Building on that success, we advanced into the next frontier of targeted or precision oncology with SLS009, our highly selective CDK9 inhibitor. The preclinical and early clinical data have been compelling, showing significant activity across aggressive leukemias and beyond. This diversification and the complementary nature of both assets, from frontline treatment with SLS009 to maintenance with GPS in AML, position SELLAS as an emerging leader in targeted cancer therapeutics. Today, we are a late-stage oncology company with a clear mission: to bring forward innovative therapies that extend and improve patients' lives while driving sustainable, long-term value for our shareholders. We've achieved this through focus, discipline, and steadfast belief in our science and our team. The journey hasn't always been easy, but it has always been purposeful. As we look ahead, we do so with the same determination that got us here: to deliver on the promise of innovation and to make a lasting difference in the fight against cancer. To help us explore the significance of our programs and their potential in the evolving oncology landscape, we're joined by an exceptional group of key opinion leaders, as well as our Chief Development Officer, two experts in the fields. It's my pleasure now to introduce them. Dr. Omer Jamy is an Associate Professor of Medicine at the University of Alabama at Birmingham, in the Division of Hematology and Oncology, and an Associate Scientist in Experimental Therapeutics at the O'Neal Comprehensive Cancer Center. He serves as a Principal Investigator of the phase III REGAL trial at UAB and is also a Principal Investigator in our SLS009 program. Dr. Panagiotis Tsirigotis has been a Professor of Hematology at the National and Kapodistrian University of Athens School of Medicine in Greece and Scientific Director of the Transplantation Program of the Hematology Unit since 2010. He's an investigator in the phase III REGAL trial. His clinical work focuses on acute myeloid leukemia (AML), with particular emphasis on cellular therapies and the application of immunotherapy methods to prevent leukemia relapses. Dr. Tsirigotis serves as President of the Acute Leukemia Working Group of the Hellenic Society of Hematology and Vice President of the Hellenic Transplant Organization. Dr. Philip M. Rein is an Assistant Professor of Medicine at Harvard Medical School and a physician at Massachusetts General Hospital, where he is part of the Cancer Center, Leukemia, Cellular Immunotherapy, and Hematology Oncology departments. He specializes in treating adults with acute and chronic leukemias, myelodysplasia, and myeloproliferative neoplasms and leads multiple clinical trials exploring novel treatment approaches. Dr. Rein has conducted research with SLS009 and is an expert in cycle-independent kinases. Dr. Rein also serves on our Scientific Advisory Board. Dr. Sharif Khan is a hematologist at Bon Secours Health System in Greenville, South Carolina. He's a highly rated specialist in indications such as AML, myeloproliferative neoplasms, multiple myeloma, non-Hodgkin's lymphoma, and bone marrow transplantation. In addition to his clinical care, Dr. Khan is a researcher for cutting-edge breakthrough therapies and started the CAR T-cell program at Bon Secours Health System. He serves as an investigator in both the REGAL trial of GPS and the SLS009 clinical program. Before I turn it over to our key opinion leaders, let me start with our pipeline. We have two highly differentiated clinical stage assets, each addressing significant unmet needs and each with first or best-in-class potential. First, Galinpepimut-S, or GPS, our late WT1-targeted immunotherapy, continues to demonstrate meaningful clinical benefit across multiple hard-to-treat cancers. GPS has shown consistent positive trends in overall survival, durable immune responses, and a favorable safety profile across a broad range of indications, including AML, mesothelioma, ovarian cancer, and multiple myeloma. Our most advanced program is the phase III REGAL trial in acute myeloid leukemia, a global, randomized study evaluating GPS in patients who have achieved remission but remain at high risk of relapse. The rationale is strong. The data to date are compelling, and the unmet need remains clear. We expect our 80th event by year-end. As you are aware, this is an event-driven study, and we are blinded to study outcomes. Survival times in REGAL indeed appear unexpectedly long, and due to significantly longer than expected survival, the timing of the final analysis is difficult to predict with any certainty, and the 80th event may occur at a different time than currently expected. Should that event occur later than anticipated, from a mathematical standpoint and the fact that we administer GPS to patients even three years out, every passing month may increase the probability of a successful study due to a potential GPS effect, as we have seen in our previous CR1 and CR2 studies, far surpassing median overall survival versus standard of care. When the 80th event materializes, we will inform the public, which represents the most important near-term catalyst for SELLAS. A subsequent positive outcome could position GPS as the first-in-class maintenance therapy in AML and unlock significant commercial potential. Furthermore, there's been significant interest in evaluating GPS in combination with bone marrow transplant in AML, an area that Dr. Tsirigotis will likely discuss further in his remarks. Turning to SLS009, also known as tambiciclib, our highly selective CDK9 inhibitor, this is a next-generation targeted therapy with a broad applicability across hematologic malignancies and the potential for activity in solid tumors as well. Our trials have generated compelling clinical data showing strong response rates, as well as overall survival benefit in relapsed-refractory AML patients. These results position SLS009 as a potential first and best-in-class CDK9 inhibitor, clearly differentiating it from earlier, less selective agents in the space. Following discussions with the FDA, we will advance SLS009 into the frontline setting in both newly diagnosed AML patients and those who have not seen an effect with Venetoclax and azacitidine alone after two cycles. Furthermore, we are conducting transcriptomic, genomic, and proteomics analyses, among others, with esteemed academic institutions and utilizing an AI model to further predict patients that will most likely benefit from our SLS009 treatment and gearing our clinical development efforts accordingly. As far as I'm aware, we're the leading company in this space with this level of data, and Dragan will address this in more detail later. Clinically, we expect to advance our SLS009 program in the frontline setting both newly diagnosed as well as early refractory patients by the first quarter of 2026 and expect initial data later that year, which will help define the registrational development path and potentially lead towards accelerated approval. I would now like to turn it over to Dr. Omer Jamy, who will provide additional perspective on the AML treatment landscape and discuss how both GPS and SLS009 fit within it. Dr. Jamy. Thank you, Angelos, and good morning, everyone. It's my pleasure to be here. My name is Omer Jamy. I'm an Associate Professor at UAB. I focus mainly on leukemias and allogeneic stem cell transplantation. Today, I'll be talking a little bit about AML and a couple of agents with SELLAS Life Sciences Group that I've had the opportunity to work with over the past several years. This first slide will focus on the diagnosis, progression, and standard of care treatment for acute myeloid leukemia. We've made significant progress in understanding the pathogenesis and biology of acute myeloid leukemia over the past 10 to 20 years. That has fortunately led to the approval of several drugs for the treatment of AML, whether it be in the frontline setting, in the maintenance setting, or in the relapse refractory setting. Despite the approval of several drugs, the outcomes of patients with AML still remain modest, and there's a lot of room for improvement. Therefore, we continue to figure out how further to improve outcomes for our patients. I'm just going to walk you briefly through the journey of a patient with AML when they're first diagnosed. When you have a patient with a newly diagnosed AML, you can treat them with either intensive chemotherapy for a fixed duration, which is a traditional chemotherapy with the addition of targeted agents if there are any specific mutations available, or you can treat them with a hypomethylating agent or Venetoclax, broadly termed as less intensive chemotherapy, which is usually continuous in nature. You can add another agent to this combination in the setting of a clinical trial if there are any targetable mutations present. What makes you choose one regimen over the other is dependent on several factors, mainly patient-dependent factors such as age, comorbidities, performance status, and then disease factors such as what particular molecular and chromosomal abnormalities are present that may indicate that there's a higher chance of responding to one type of therapy compared to another kind of therapy. With all the advances we've made, approximately 2/3 of the patients in the upfront setting are able to achieve complete remission. This is speaking for all comers, whether they're treated with fixed-duration chemotherapy or continuous chemotherapy. After they achieve remission, if they have favorable risk disease where you think you can treat them without needing a transplant in first remission and there's potential for cure, some of those patients undergo observation. Those that may benefit from a stem cell transplant in first remission undergo transplantation. As we all know, many patients whose disease may be eligible for transplant are unable to proceed to transplant for various reasons. Those could be patient factors, socioeconomic factors, disease-related factors, or donor availability. In those patients, you apply a maintenance strategy, whether that's with a hypomethylating agent alone or a hypomethylating agent plus Venetoclax or a targeted agent in the setting of a clinical trial. With maintenance, the survival of these patients is approximately 18 to 24 months. We still see that there's a lot of room for improvement in this setting. On the other hand, when you treat these patients with frontline therapy, if you focus on the extreme right and left on the top and they don't respond to therapy, survival is really poor for these patients, unfortunately. If they were treated with intensive chemotherapy and were unable to achieve remission, you're looking at a survival of approximately six to eight months, whereas if they were treated with a hypomethylating agent plus Venetoclax combination and were unable to achieve remission, that survival post-Venetoclax, which several groups have published, including our own, is around two to three months, so very short. When you have patients who either are refractory to their frontline therapy or unfortunately have relapsed after achieving first remission, you treat them in second-line therapy either on a clinical trial or if there's no trial available, you basically treat them with a combination of drugs approved in the frontline setting, which they may not have seen before, or if they may have seen before, but you may use them in a different combination. It is basically coming down to either fixed-duration intensive chemotherapy plus/minus targeted agents or continuous therapy or less intensive chemotherapy with hypomethylating agent and Venetoclax plus/minus targeted agents. Every time the leukemia comes back, it is a little smarter than before. It's a little stubborn. It's a little difficult to get it into remission again. If you look at the proportion of patients that achieve a second remission, it is less than the proportion that would achieve a remission if they were newly diagnosed. You would think around 30% to 50% of patients go on to achieve CR2, whereas the rest of them, unfortunately, are not able to achieve remission after having relapsed disease or being refractory to frontline therapy. For those who achieve CR2, if your patient is eligible, nearly all of these patients deserve a consultation for stem cell transplantation and should proceed to stem cell transplantation if they are eligible. As we know, there are barriers to transplantation. For the vast majority of these patients, you need to have some sort of maintenance strategy, for which currently there is no FDA-approved agent. Physicians like myself would use either a hypomethylating agent plus/minus Venetoclax combination or a targeted agent to try to maintain that second remission, which we know without transplant is very difficult to maintain. Studies have shown in the past that the survival of these patients who achieve CR2 and are unable to proceed to transplant is approximately eight months. This slide basically highlights a couple of areas of unmet need. Number one, what to do for patients in second remission who are unable to go to transplant. Number two, what to do with patients who, unfortunately, are refractory to Venetoclax-based therapy. I have been working with two agents with the SELLAS Life Sciences Group, one being Galinpepimut-S, which is a vaccine against Wilms Tumor 1, as a maintenance strategy for patients in second remission who are unable to go to transplant. Some of the earlier phase data for Galinpepimut-S looks very promising. When it was studied in patients who were in first remission, where, as I showed on the slide above or at the top portion of this slide, the standard of care median survival is around 18 to 24 months, survival with Galinpepimut-S was median survival was upwards of 60 months or five years in that study. When they looked at the same agent in earlier phase studies in second line or beyond, where the standard of care survival is approximately eight months, they demonstrated a 21-month overall survival in that population, so significantly higher than what is currently published as the standard metrics. The other agent that I've been working with is the CDK9 inhibitor or SLS009, where we treated patients who were refractory to or did not respond to Venetoclax, where, as we previously discussed, the median overall survival for these patients is two to three months. On this trial, which was a phase I, phase II study, we showed that the survival for these patients with the addition of SLS009 as a means to overcome resistance to Venetoclax improved survival to almost eight to nine months. This highlights the important results and the advancements with these two agents in areas where we really need agents to help improve outcomes for some of our patients. Moving on, a lot of users use azacitidine or any other hypomethylating agent plus Venetoclax to treat patients with relapsed or refractory AML. We still see that there is a lot of room for improvement even in that setting. These are the AVALON study results that I'm presenting over here, which actually looked at real-world evidence of the efficacy of Venetoclax plus hypomethylating agents in patients with relapsed acute myeloid leukemia. With the combination you see over here, approximately a third of the patients were able to achieve a composite complete remission. One third as compared to, as we discussed on the previous slides, upfront, 2/3 achieved remission, second line maybe half of them achieved remission. Real-world data is usually less than what you actually see in clinical trials. Out of these patients, out of the patients who achieved remission, slightly more than 50% were able to proceed to transplant, but the rest were not, again, due to various reasons. If you look at the duration of response in this study, it's 8.3 months, but it does appear to include patients who got a transplant as well. For patients who are unable to proceed to transplant, it is likely to be lower than that. When we discuss survival for this population, again, replicating previous results for patients who relapsed on azacitidine and Venetoclax, the median overall survival was 2.4 months. What is even more surprising is that even if patients had a transplant, the median overall survival was 10.7 months, just giving you a sense of how aggressive some of these, how aggressive these diseases are and difficult to treat, especially if they've relapsed. The median, if you look at this data, what you can take home from this is that maybe the median overall survival of patients in CR2 who did not proceed to transplant is around six to eight months. If you compare this to the earlier data with Galinpepimut-S in earlier line studies where patients in CR2 who did not undergo a transplant, the median overall survival was 21 months. Having used Galinpepimut-S in the phase III REGAL trial, it is an agent which does not come with any myelosuppression, which is associated with most of the chemotherapy agents that we use to treat acute myeloid leukemia. It is a very tolerable profile. Importantly to note is that patients phase III REGAL trial could not have had a transplant prior to enrollment. All of the patients enrolled on the CR2 did not have a prior allogeneic stem cell transplantation. What are some of the areas of unmet medical needs in acute myeloid leukemia? After going through the previous two slides, we believe that a lot of patients need to go to stem cell transplantation, but unfortunately, the vast majority cannot. We think that transplant is potentially curable for a lot of acute myeloid leukemia patients. The reason I say potentially is because there is still a significant risk of relapse after transplant that could depend on what is the disease state before transplant, what is the intensity of the conditioning you use for transplant. Although our intention is always to cure with transplant, cure is never guaranteed with transplant. In addition to relapse, you have other complications of transplant contributing to non-relapse mortality, such as graft versus host disease and infectious complications. Therefore, not all of your patients who need a transplant will be able to go to transplant. Those who do, maybe more or nearly 50% of them will relapse, unfortunately, even after transplant. For patients who are unable to go to transplant, their treatment usually consists of either intensive chemotherapy or less intensive chemotherapy. Less intensive chemotherapy is usually a hypomethylating agent and Venetoclax combination, which is the current standard of care. As we've seen before, if you were responding to Venetoclax and stopped responding or you were refractory to Venetoclax, your median overall survival is only 2.5 months. This is where SLS009, the CDK9 inhibitor, has shown to extend survival for these patients by two to four times after they've not responded to Venetoclax based on the clinical trial that I'm participating in. We wait for more data over there as well. This is a very exciting finding because it actually gives us a sense of trying to overcome resistance to Venetoclax and improve outcomes for most of these patients and maybe even potentially bridge them to a transplant. What about patients who are on this therapy and are responding and are doing well, meaning who are on hypomethylating agent and Venetoclax and they are in remission but they cannot go to transplant? What does their trajectory look like? For most of us who are very used to giving this agent in clinical practice, we realize that with time, if you keep on giving this regimen every month, every six weeks, you will encounter cumulative toxicities. One of the main side effects of giving this combination indefinitely is that you cause bone marrow toxicity leading to myelosuppression and low blood counts, which sometimes leads to temporary reductions or dose reductions, temporary interruptions, or even sometimes permanent discontinuation of the agent because your patient's not able to tolerate this regimen because of very low counts. This is even more important for people who are in second remission or beyond because they've already got a bone marrow which has seen so much chemotherapy before. Their bone marrow microenvironment is sort of compromised. We would expect them to have more side effects when it comes to myelosuppression and cytopenias. We don't know how long they will tolerate this regimen for. A lot of studies these days, including standard of care practice, is to reduce the dose of Venetoclax or alter its schedule either by giving it for less days or reducing its dose in most of our patients. We do know that although we get responses with this agent, those responses are not very durable and most of the patients will eventually relapse. This hypomethylating agent and Venetoclax combination is unfortunately not meant to be curative in nature. We need areas to improve upon these outcomes further. To summarize, a couple of areas of unmet needs which we've discussed over here are what to do for patients who have achieved remission but are unable to proceed to transplant. As we've already discussed, in the frontline, the median survival for these patients is 18 to 24 months. In second remission and beyond, it is eight months. We've already seen GPS data from earlier phase studies where the frontline data, the median survival is more than 60 months. In the second line setting, the median survival is 21 months, significantly higher than what has already been published. Really looking forward to the results of the REGAL trial. Of course, we don't know the survival status between both the arms, but we hope that the previous trials will be replicated. The longer duration obviously implies that the patients are living longer, which would be in keeping with previously confirmed GPS outcomes. With that, I'd like to end my presentation. Thank you. Thank you very much, Dr. Jamy, for the insightful overview. It's really my pleasure now to turn it over to our Chief Development Officer, Dr. Dragan Cvicic, as well as Dr. Panagiotis Tsirigotis, to provide an overview of the REGAL Study. Thank you, Angelos. We will start with Dr. Tsirigotis discussing the science behind GPS in the context of his long experience with similar agents with attempts to extend survival in patients in remission in his clinical and scientific practice. I will hand it over to Dr. Tsirigotis now. Thank you very much for this kind invitation. For me, it's an honor to be here and working with this excellent project. I know this vaccine. The first time I was aware of this vaccine was 25 years ago when I was a trainee in Israel in Hadassah Medical Center. At those times, the peptides that we used for vaccination were one or two peptides, so it was restricted only to certain patients with certain HLA alleles. From that time, I remembered, and I was really enthusiastic because I saw patients that they have a decrease in the blast cells in the bone marrow and in peripheral blood. When I met Angelos, I was really enthusiastic to participate in this trial. Now, why WT1? WT1, to my opinion, is an ideal target for immunotherapy for many reasons that I'm going to explain to you briefly. First of all, WT1 is not expressed under normal circumstances or normal hematopoietic stem cells. It is only expressed at tiny amounts in certain subpopulations like myeloid progenitors. However, WT1 is overexpressed in almost all AML. More than 95% of patients with active myeloid leukemia overexpress WT1, and this is not related to any mutation. It is also overexpressed in many other hematological malignancies and also in solid tumors. The story here is that when WT1 is overexpressed, it becomes highly immunogenic, and the immune system can elicit an immune response which is directed against the leukemic cells. WT1, under these circumstances, is considered as a tumor-associated antigen that is cancer-selected, cancer-specific. That's why when we target these, then we can avoid the killing of the normal stem cells, and this is really important. Something that is also very important is that WT1 is proteolized by the proteasome and creates a number of peptides with multiple epitopes. Therefore, it creates multiple antigenic targets, and we know that the more the antigenic targets, the less the possibility of immune escape. This is really important. Another important thing is that it can activate not only CD8 cells but also CD4 cells. For all these reasons, GPS was designed as a vaccine that can elicit strong immune responses against WT1. Because the overexpression of WT1 remains constant through all phases of acute myeloid leukemia. Therefore, GPS is really a very important drug to be used not only in those patients who are in CR1, but also for patients who are in CR2 and also for patients in the post-transplant setting. This is something that is really important because we all know that the major limitation of allogeneic stem cell transplantation for high-risk acute myeloid leukemia patients is the high relapse rate. We need maintenance treatment for prevention of relapse in the post-transplant setting for this patient. So far, I have to say that all previous trials that tested various combinations of drugs for maintenance, they failed. I'm going to say a few things about VIALE-A. Aza plus ven tested as maintenance post-transplant, and this trial closed prematurely because of lack of efficacy in the experimental arm. Moreover, it was a lot of toxicity, and there were also deaths because of severe myelosuppression in the transplanted patients that they received this kind of drugs. The same also is true for MORPHO trial, as you know, that give the reading failed to show a survival advantage in patients who receive it as maintenance in the post-transplant setting. I think that, and I strongly believe, and my plan is to have a trial to test the efficacy of GPS as a maintenance in the post-transplant setting because I strongly believe that it will make a huge difference in these settings. Now, let's see a few things about the mechanism of action, which is really simple. You know, never forget that great things are always simple. What is GPS? GPS is a mixture of peptides from WT1, and you simply inject them subcutaneously in combination with Montanide, which is an immunoadjuvant used in all the kinds of vaccines. Also, at the same place of peptide injection, we inject GMCSF, which is a cytokine. The reason we do this is that because GMCSF activates immune cells and recreates many immune effectors in this area, in proximity to the peptides like monocytes and most importantly, antigen-presenting cells like dendritic cells. Dendritic cells phagocytose these peptides, and then they move to the regional lymph nodes when they present these peptides to T cells. Now, antigen-specific T cells for these peptides are activated, become they undergo a phase of expansion and finally differentiate to immune effectors like cytotoxic T lymphocytes. These immune effectors there travel through over the body. When they meet the cells that they, the leukemic cells that they have, I mean the peptides on the cell surface in the context of HLA, they recognize them. By using T cell receptors, they attack them and kill them. One important thing here is that these immune effectors do not attack normal cells simply because normal cells do not overexpress WT1 peptides. This is very important because that makes GPS an extremely safe drug. This is not only a theory. This is practice because we see this in the clinical practice. None of the patients have any problem with GPS. GPS is not a myelotoxic agent. This is something very, very important because most of the drugs we use as maintenance induce myelotoxicity, and this causes many problems. GPS is not myelotoxic because GPS does not have any effect on the normal cells. This is very important. The only thing you have is just irritation in the place of injection. I would like to stress several points. I would like to stress these points because these are the reasons that make GPS the most promising vaccine so far. GPS consists of a mixture of many different peptides that are derived from the WT1 protein. This is very, very, very important for two reasons. First, these peptides can be bound to many different HLA alleles. GPS is not an HLA-restricted drug. You do not need to check the patient before this administration for HLA. You do not need any HLA typing. As we do, we do this in the past. In the past, when we have only one or two peptides and these peptides, they were specific, HLA-specific, then we had to test patients for HLA. Only a few patients were eligible for these peptides. Now, GPS is a universal drug. You do not need to test HLA in that. This is really, really important. The other thing is that the multiplicity of epitopes results in many different antigenic targets. This is very important because the more the antigenic targets, the less the possibility of immune escape. This is a basic rule in immunotherapy. Another important thing that I want to make it clear is that the peptides in GPS are not like the old peptides. There are heteroclitic peptides, and heteroclitic peptides are products of artificial intelligence. By changing a little bit the amino acid sequence of these peptides, you can make it more immunogenic. These peptides are capable of eliciting strong immune reactions against these peptides, and this makes them very effective. You can prevent the mechanism of tolerance, which is observed with the use of other peptides. Finally, another important thing is that these peptides do not activate only CD8 cytotoxic cells, but they also activate CD4 cells. This is very important because antigen-specific CD4 cells are required because they give help for better cytotoxicity, but also they maintain the effect of the CD8 cells. For all these reasons, I think that GPS is currently the most promising vaccine that we have. Now, this is the REGAL trial. The REGAL trial was a prospective, is a prospective randomized trial, including patients in CR2 or less CR. The patients were not eligible to have intensive chemotherapy, and they were not eligible to have a transplant, which is, as we all know, and Dr. Jamy said before, that if you are in a state of CR2, the only way to have a prolonged survival is to undergo allogeneic stem cell transplantation. These patients were ineligible. 120 patients enrolled in this trial, and the patients were randomized to receive either the GPS vaccine or the best available treatment. The only available treatment that we have for patients who are in CR2 is give them maintenance with a single-agent hypomethylating agent. We can give them HMA in combination with Venetoclax, or we can simply observe them. Patients who receive GPS, they receive GPS every two weeks for the first 10 weeks, and then they receive it once monthly for one year. As you said, as you listened before, it seems because we don't have the 80 events so far, it is clear now that the median overall survival for the whole group of patients that are enrolled in the REGAL Study, it will be more than two and a half years. This is really, really important. You will allow me to say that I'm totally convinced that this is not due to the best available treatment because we know, and Professor Jamy said before, that if you use Venasa in the setting of CR2 as maintenance, the median overall survival is just a few months. I'm pretty convinced that this prolongation in overall survival is due to GPS. Because we treat patients and we see these patients, that's why our request to SELLAS was to allow us to continue treatment with GPS because, you know, as a physician, if I see that my patient is getting benefit from a drug, then I'm really reluctant to discontinue this drug. Now, the maintenance phase is extended thanks to SELLAS, not only for more than three years, but even more. This is really, really important. We know from previous trials that the vaccine is effective. We know this. There are published so far that we have two phase II trials. The first one was GPS was administered in patients of all ages in CR1. These patients were not eligible for allogeneic stem cell transplantation. The results from this trial were really impressive because the median overall survival has not been reached yet. It is estimated that the median overall survival will be something like more than six years. If we see the historical control for those patients who are not eligible for allogeneic stem cell transplantation in CR1 and for all ages, the median overall survival is approximately 18 to 20 months. This is really very convincing data that GPS actually works. The second study is in patients with a median age of 74 years old that they were in CR2. As you can appreciate from the slide on the right side, the median overall survival again was significantly prolonged as compared with the control group. Finally, I want to say a few things about the immune responses. We can move to the next. This slide is very important in my opinion because, as you can see, in the phase II study, when GPS was administered as maintenance of the second remission, a group of patients was tested to see if these patients after GPS had an immune response to WT1. You can do this with various techniques like immunophenotype or many other tests. What we observed is that 64%, almost 2/3 of patients, actually had an immune response after GPS administration. The important thing in this trial is that the patients who actually have an immune response to GPS are those patients who actually have a significant prolongation in disease-free and overall survival as compared to those who didn't manage to mount an immune response to WT1. This is a proof of the concept that this vaccine acts through the immune activation and by creating immune effectors that destroy the leukemic stem cells. Finally, the REGAL Study in a subcohort of patients that also tested for the presence of immune response against WT1, surprisingly, we observed that 80% of the patients managed to have an immune response against WT1. With this, I think that I conclude, and I strongly believe that GPS is a really promising agent. My plan is actually to persuade the people here to make a trial in the post-transplant setting when I think that it will be really, really effective. I have to say that I'm really enthusiastic about this drug. Thank you so much. Thank you so much. Thank you, Dr. Tsirigotis. I will now move to a bit more mundane and technical aspects of the trial. Dragan Cvicic, I'm heading clinical development at SELLAS, and I will give you a summary of the data. Let's stay related. I mean, not the data because we don't know the efficacy results as a company, as the trial is blinded. We do know that we have completed enrollment last April, early April. When I say last April, I mean in 2024. 126 patients were randomized one-to-one into the study arm and the control arm. The trial was multinational. We conducted a trial in three regions: U.S., Europe, and Asia. 11 countries participated with the highest enrollment in the U.S., and the U.S. and Europe accounted for approximately 75% of the patients enrolled, which makes the patient population representative of the U.S. patient population. It meets and exceeds FDA guidelines on pivotal trials patient demographics. Importantly, the last patient was randomized about 19 months ago. We have heard in previous presentations that expected survival in this patient population treated with currently available care is around eight months or so. We are encouraged by what suggests to be longer than expected survival in our trial. Obviously, we have to wait for the results that will become available, as Angelos said once, that the sufficient number of events has been reached, which gets us to survival of these patients again and the number of events because survival is the key metric of the REGAL trial. It is the primary endpoint in the trial. Just as a brief reminder, we are comparing survival of patients in the study arm, meaning patients receiving only GPS as monotherapy, against the survival in control arm, meaning patients receiving best available therapy defined as physicians' choice of Venetoclax combinations with hypomethylating agents or hypomethylating agents alone or low-dose cytarabine, which are all available treatments. There are no other treatments that are available today. None of these treatments have been approved in these settings. Therefore, we cannot call it standard of care, but this is conventional care, meaning the only ways in which these patients are treated today. When we said physicians' choice, what dictates physicians' choice is, as previous presenters have said, lots of toxicity with the available treatment, right? Because of the toxicity, they have to make a decision on what patient indeed can tolerate in these settings. The control arm is truly a real-world experience, right? It's not artificial in any way, shape, or form. Now, when we say that survival is the primary endpoint, I just want to clarify here, as we got some questions in the past where people would ask about median survival. I just want to say that median survival is one endpoint, right? The actual endpoint for this trial is hazard ratio. The difference is that although these are closely related measurements, and usually, commonly, we express this when we discuss it as median survival, and that's how it's, you know, that's what physicians and patients remember, actually, median survival is not used as the primary endpoint because median survival is, although correlated, different because it's a snapshot of one time point in the patient treatment. Basically, you are reporting that a patient who's in the middle of the survival curve has lived for, for example, 10 months. Then you say the patient who's in the middle of the survival curve of the comparator has lived for, say, 11 months. You would say it's 10 months versus 11 months. That's not in itself a provable endpoint. The provable endpoint is hazard ratio because it tracks patients over time and compares their probability of survival at all time points. Hazard ratio is reported as a proportion between the arms. For example, if we say hazard ratio 0.636, that means that overall, over time, patients in one arm had a probability of dying of 63.6% compared to the other arm. In other words, almost 40% lower, right? That's really what we are going to be looking for. That's why we need 80 events so as to be able to tell over time to make an ironclad conclusion of which trial benefits, which arm, which treatment benefits patients more, and how much more. This can be shorthanded in a way by correlating it to median overall survival. If median overall survival, for example, is eight months for control arm and 12.6 months for study arm, then this would imply that the hazard ratio is going to be met. This is just a way to explain this more intuitively. Now, in the initial assumption, we expected, and Angelos spoke about that as well in his introduction, we expected that final analysis, that 80 events, and therefore final analysis would occur approximately 12 months after the last subject is randomized. We thought it may occur then sometimes in the second quarter this year or at the latest in the fourth quarter. Now we know that 80 events have actually not occurred 12 months later and have not occurred even 19 months after enrollment completion. As my predecessor and other presenters have said, what's really important here is that this is a very encouraging, potentially a very encouraging sign because we are seeing, you know, longer than expected survival, which is, again, we cannot say that this is because of GPS at this point until we actually see the data. This is an encouraging sign. Now, I'm going to switch to just addressing briefly the market size. AML is rare. It is rare enough to qualify as an orphan disease, but it's actually not that rare. It's actually the most common leukemia, the most common type of leukemia, and I would say by far the most common. There are around 77,000 patients in the U.S., European Union, Europe's five biggest markets, Japan, and China who are diagnosed with AML each year. Out of those patients, and these are the markets for drugs, right? These are the largest markets for drugs. In the U.S., there's almost 22,000, actually closer to 22. We have 21, but at this time, it's getting more like 22. The incidence is increasing. Almost all of these patients, as my colleagues have said, 97% of these patients express WT1, right? A vast majority of patients get treated because in the absence of treatment, AML is invariably lethal. There are no patients who can survive AML without treatment. As we have learned, unfortunately, most of the patients cannot survive it even with treatment. Complete remissions are actually in these largest four markets are actually closer to 50%-55% because the United States has probably the highest rate of success in treating. Nevertheless, in the absence of transplant, all the patients, almost all patients will relapse. Now their probability of getting into the second transplant, sorry, into the second remission is now much lower, as we've heard. Altogether, in the end, there's about 15% of patients who end up in CR2. These are the patients that GPS is focused on. Now, in the frontline, in the first line where we are developing tambiciclib, we estimate that approximately 50% of the patients would benefit from tambiciclib. Of course, all patients in CR1, we believe, would benefit from GPS. That's really, in a nutshell, the technical aspect of the trial and the market size. With that, I thank you. Thank you. Thank you, Dragan, and thank you, Dr. Tsirigotis, for this detailed and exciting discussion, really, of our REGAL Study and the potential GPS holds to alter the GPS treatment paradigm. I think, Dr. Tsirigotis, you made a very strong case to support you with the post-transplant work with GPS. Thank you. At this point, I would like to switch our discussion to our SLS009 program and invite Dr. Sharif Khan and Dragan to provide an overview and thoughts around SLS009 and our differentiated asset versus other CDK9 inhibitors in development and treatment of really the hardest-to-treat AML subgroups, including those with TP53 mutations. We'll talk about our biomarker strategy and upcoming trial design and how it all really comes together finally to hopefully benefit patients in dire need of effective and safe treatments in AML. With that, I'll turn it over to Dr. M. Rein, please. Thank you, and greetings from Massachusetts General Hospital in Boston. I will try to dig deeper into the rationale of why we're excited about SLS009 for the treatment of acute myeloid leukemia. As you've heard, the outlook for these patients is really not good. The azacitidine-Venetoclax combination has become much more popular over the last year or two. In fact, more and more younger patients are receiving this combination rather than intensive chemotherapy. As you can see, even though the combination is better than azacitidine alone, the median survival here in this older population is 14 months, and few patients actually are being cured. We know the outlook for these patients is largely driven by the mutation analysis. Not all mutations are bad mutations, but there is quite an assortment, as you can see here, of mutations that's being looked at. In Europe, by Dohner and the Mayo Clinic and others, are starting to develop a classification of high-risk patients that really have a very poor prognosis. As you can see here, p53 mutations, RAS mutations, KMT2A rearrangements are very poor prognostic indicators. KMT2A is a new classification for MLL rearrangements. As you may recall, the menin inhibitors are very popular right now, and they act in that pathway. In these high-risk groups, the remission rates are poor. They're like 20%, and the overall survival is only two to seven months, unlike the others. We're excited to work with this group and try to make some progress in this unmet need. Why target CDK9 with SLS? There are good reasons to target CDK9. It is required in RNA polymerase activity and hence protein synthesis. A lot of leukemias are generally dependent on high levels of metabolism, that is, protein synthesis, to stay alive. More specifically, these leukemias are dependent on short half-life molecules like MCL1 and MIC. I'm sure you've heard of MYC before. MCL1, over the years, has been a favorite target in acute leukemia, and few have been able to target MCL1 for various reasons. By targeting protein synthesis, you don't have to target it directly. It has a short half-life, and you just have to stop protein synthesis, and it goes away very quickly. We have been doing some testing in the laboratory, and we can show, as others have shown, that with just a six to eight-hour exposure at very low concentrations, 20 to 50 nanomolar, it kills practically all leukemia cell lines very handily. Why combine it with azacitidine and Venetoclax? There actually are good reasons to do that. They're somewhat synergistic. I'll go over that in a minute. We are targeting mainly older patients, which is the vast majority of leukemia patients. Already, the standard of care is azacitidine-Venetoclax, so it's very simple to design a trial where we just add SLS009 to what people would be using anyway. In our lab, we show synergy in the early studies, phase I, phase II. It looks like it can be synergistic with azacitidine-Venetoclax. I'll now go over some of the details of why scientifically this makes sense. There have been other CDK9 inhibitors in clinical trial already. You may recall flavopiridol has been in clinical trial for quite some time. They have been fairly toxic, and it's mainly because when you look at the assortment of kinases that are inhibited, they are not very specific and therefore more toxic. SLS009 is very specific for CDK9, and therefore it is much better tolerated than the other CDK9 inhibitors that have been tested. If you look at the picture to the left, I'll just briefly tell you exactly how this works. RNA polymerase is depicted in green, and it's going along DNA making messenger RNA. However, generally in most cells, RNA polymerase is halted very quickly, waiting for PTEFB, which is in blue, to allow it to proceed further to make messenger RNA and protein synthesis. As you can see there, CDK9 is a controlling protein for PTEFB. Until it gets involved, the negative elongation factor in red, NELF, holds RNA polymerase in check. When CDK9 is activated, NELF is ejected from RNA polymerase, and messenger RNA is now synthesized as expected. Listed there are some CDK9 inhibitors that prevent this process. On a molecular level, that is what is going on. When cells are exposed to SLS009 or any other CDK9 inhibitor, protein synthesis stops abruptly, perhaps for eight to 12 hours. The short half-life molecules disappear, like MCL1, and under many circumstances, that's enough to trigger apoptosis and cell death. Venetoclax does not interact with those proteins. Venetoclax interacts with BCL2, which in conjunction with MCL1 keeps cells alive and affords the resistance to chemotherapy treatment. When you attack cells with azacitidine along with Venetoclax and SLS009, you pretty much initiate cell death and then block the resistance mechanisms, the main two resistance mechanisms through BCL2 and MCL1. I'm just going to touch on briefly special cases as listed below. You may have heard of menin inhibitors, which are very popular right now. Menin triggers the MLL KMT2A pathway, which leads to upregulation of HOXA9 and leukemia. The menin inhibitors appear to be quite active and have a future. It may be that SLS is very similar to the menin inhibitors in the way it works, and I'll show you that in a minute. SLS has also been effective in a high-risk population with the ASXL1 mutation. Many patients have that, and it's a high-risk resistant population of leukemia. However, SLS seems to be quite active in that population. We've seen that in the early clinical trials, and I'll show you why in a minute. Finally, the p53 mutation patients are highly resistant to conventional chemotherapy. It's a huge unmet need, and it may be that SLS has an answer for that population as well. Here is a diagram for the menin MLL KMT2A HOXA9 pathway. As you can see, that purple circle there is menin, and that triggers this pathway to leukemia, and the menin inhibitors act at that level. If you look down the road here, you see PTEFB in orange that's controlled by CDK9. If you inhibit PTEFB, that pathway is shut down just like the menin inhibitors will shut it down. To see that is kind of exciting because it's a big unmet need in the KMT2A mutated patients. Initially, we were kind of curious as to why the high-risk ASXL1 patients seem to respond nicely to SLS. As you can see here, full-length ASXL1 in the orange box does not bind to BRD4, and so this pathway is not triggered with wild-type ASXL1. However, when you mutate ASXL1, it binds BRD4, triggers, guess what, PTEFB and RNA polymerase, and it stimulates protein synthesis. If you inhibit CDK9, this pathway is halted. The biggest problem we have is p53 mutation and no cells. In this diagram, BAX and BAK are your executioners causing apoptosis or cell death, and they are controlled, held in check mainly by MCL1 and BCL2. BCLXL is a minor player here. If they are held in check, the cells do not die. If standard chemotherapy comes along, triggers p53, suddenly it causes release of BAX and BAK through MCL1 and BCL2. If you don't have p53 or if it's mutated, conventional chemotherapy has nothing to work on. MCL1 and BCL2 continue to hold on to BAX and BAK, and you don't get the cell kill that you expect. You get resistance. Now, if you have Venetoclax interacting with BCL2 and you have SLS009 causing MCL1 to disappear because it has a short half-life, suddenly BAX and BAK are released and you get the cell kill you were hoping for, even in the absence of p53 or mutated p53. We've seen some responses in patients with the p53 mutation already. That is truly exciting, as that is explained. I'm going to stop here. In conclusion, we're excited about adding SLS009 to the now very popular azacitidine-Venetoclax regimen. We will see in a randomized setting just how good this is. I'm excited, and I think it may be a positive experiment. Thank you. Thank you very much, Dr. M. Rein. Really appreciate you. I think with that, we'll turn it over to Dragan to discuss the trial design, the upcoming trial design, and discussions with the FDA and some of the, what I feel, not only really exciting biomarker work, but it's really, I think, as I mentioned in my earlier statements, as far as we know, we're really the lead company having done transcriptomic genomics and proteomics work and to utilize that data then into really our trials. Dragan, with that. Thank you. Let me start by providing the results of our phase II trial. That's the basis for the next trial that I will also address. It looks very complicated, the design of the trial, but it's actually not that complicated. I think that what we need to say here is that all the patients who were enrolled in this trial were relapsed after or refractory to Venetoclax-based therapies. The design of the trial, because at this point, this trial is a single-arm trial, right? We wanted to have a control built into the trial, into a single-arm trial. The way to build a control in is to have patients who we know failed Venetoclax-based regimens. By definition, their response rate is zero to Azavan alone to Venetoclax-based regimens. Again, all the patients were relapsed and refractory to Azavan. Importantly, we did not provide any exclusion criteria which would limit the number of previous exposures. We had patients who were actually, you know, really at the end of their line, who were beyond the graphic on the slides that I've discussed earlier in terms of the market size. They were, you know, on the far right of that slide. Now patients who did not benefit from Azavan, right? Here's what we had. We had these patients. You can see here their characteristics. Per the FDA request, the patients were the trial was designed to follow the guideline of Project Optimus, meaning that we explored three dosing regimens to come up with the regimen that has the best combination of safety and efficacy, right? 58 patients treated across all cohorts, and you can see the number of patients per cohort. You can also see that the vast majority of patients, 51 out of 58, were AML myelodysplasia with myelodysplasia-related changes. The reason for that was that we designed the trial so that the vast majority of patients would be AML-MRC. The reason for that is, as Dr. M. Rein discussed in his presentation, that they have certain genetic changes, certain biomarkers that indicated, per Dr. M. Rein and other scientists' work, that they would be particularly susceptible to the treatment with our drug. Another area of focus was patients with myelomonocytic AML or myelomonoblastic. Patients classified as M4 or M5 patients in the French American British Classification of AML. We had a decent number of patients of that type, again, by design, right? Because, as Dr. M. Rein focused on the role of MCL1, it is believed that, based on the data, right, that MCL1 plays a much larger role in these particular subtypes of AML. The median number of prior therapies was two. As you can see, in some cohorts, it was even three. You know these patients were refractory not only to Venetoclax-based combinations. They were refractory also to chemotherapy, and they were also refractory to other experimental drugs, new drugs like CAR-T and so on, right? Very, very patients truly at the end of their line. Now, I'll start first with the safety data. Right off the bat, I'm just going to give you a review of this. What's important here is you know, you have really different safety profiles, as Dr. M. Rein said. Other CDK9 inhibitors, because of their propensity to bind to other kinases, have various side effects. Now here we wanted to check in the phase I trial. We have shown very little toxicity as a single agent. Now we wanted to check whether adding this to Azavan regimen will result in more toxicity. As you can see here, first of all, there were no dose-limiting toxicities at any dose level, right? When you look at all these cohorts, right, very little toxicity. You can also see, if you look at the far right, just to make it very easy to follow. If you look at what really matters here is all those levels, far right columns, and you can see side effects of any grade and side effects of grade three and higher, which are considered more important side effects, right? Those that can limit the use of the drug. You can see here, it's really, what we are giving here is not a selection of side effects, representative selection of side effects. This is truly all the side effects that occurred with at least 5% frequency. You can see the list is very short, and you can also see that there are very few hematologic toxicities. My colleagues before were key opinion leaders were talking about the importance of myelosuppression. You can see that myelosuppression of high grade is occurring between 5% and 6% of the patients as an additive effect of our drug, right? You can see that there were some gastrointestinal disorders, but they were all low grade and easily treatable and self-limited. We had really, really good indications of safety here. That's very important because it allows us, for any drug, it's important that the safety is not limiting its use. We are in a position where we can say here that the safety is not limiting its use. Now, even though there's very little toxicity, it appears another important thing is obviously efficacy. If you look at efficacy at the dose level, optimal dose level that we are using now and moving forward, you can see that response rates. Bear in mind again, these are response rates that are in addition to whatever has been achieved before with Azavan. You can see that response rates and survival far exceed what could be expected and what our original goal was. Really in AML-MRC patients, 44% altogether. In AMM patients, M4 and M5 patients, 50%. Importantly, now the number of patients with TP53 mutations was not very high, but importantly, it's 57% response rate, which confirms what Dr. M. Rein was hoping to see because of the mechanism of action. We have discussed, Dr. M. Rein discussed some of these biomarkers and c-Myc, MCL1, and then also other biomarkers, ASXL1, other AML myelodysplasia-related mutations, and transcriptomic markers, proteomic markers that measure the translation of genes into proteins and then interactions of proteins. We have done lots of work in this field, and we are continuing. Let me just give you a brief illustration. We already know that MYC and MCL1 are directly affected by SLS009 CDK9 inhibition, right? That was explained by Dr. M. Rein. We also know that MCL1 is a protein that confers resistance to Venetoclax and that overexpression of MCL1 is found with high frequency in myelomonocytic types of leukemia, M4 and M5. That's why we had particular interest in that. Leukemia cells that overexpress MCL1 but have low expression of BCL2, which is the target of Venetoclax, right, should be particularly sensitive to SLS009. Dragan, I think you may want to go to the next slide. I think it's okay. We need to prove this in clinical trials, yes. This is an example of what we've done so far. We are continuing this work. Just briefly, if you look at the red oval, these are leukemia cells, and you see that they're very cold to BCL2, very low levels of BCL2, but very high levels of MCL1. Now, what actually happened with this patient? You can see here that leukemia cell, leukemic monocytes, and leukemic blasts here before the treatment, after treatment with Venetoclax, but before treatment with our drug, and then after treatment with our drug. We can connect here, tie together clinical features, biological features, mechanism of action, and predictive values. That's a big focus of our work. Now, based on that, all of that, we've designed this new trial with input from the FDA, which agreed that safety and efficacy data are sufficient to justify a first-line study and recommended that we move the development into frontline because we now know, based on these biomarkers that Dr. M. Rein and I discussed, we actually can identify patients who are unlikely to benefit from Venetoclax-based standard of care before they even get treated. The FDA also puts specific emphasis on MCL1, which they want us to, and we are doing that, as you've seen, explore further as the biomarker. The proposed trial, the trial that the FDA proposed, is going to be conducted in two groups, right? Two settings. The first setting will be patients with AML-MRC biomarkers and/or M4 and M5 biomarkers and/or Mayo based biomarkers. These patients will be randomized one to one to receive Venetoclax and azacitidine alone, which is the current standard of care. These are all newly diagnosed patients or received other than plus our drug. Then we have a very direct comparison prospective trial. In the setting two, which we designated as group five, we are going to enroll patients who started already on azacitidine and Venetoclax, went through two cycles, but did not benefit from azacitidine and Venetoclax. Standard of care is four cycles. If the patient did not benefit in the first two cycles, then the probability of response is very, very low. They also develop features that we believe will make this patient particularly amenable to our drug. We have two options, two possibilities that we are exploring. We have an ability to develop our drug in one settings or the other settings or both, right? That's really where we are. We are now getting ready to commence this trial in the next quarter. Great. I think with that, Dr. Khan? Yeah. Hello. Good morning. Thank you for inviting me to this symposium. My name is Sharif Khan. I did my fellowship in hematology and then in stem cell transplantation. I'm a community hematologist. By definition, that means you work in a small town with a medium-sized hospital or a large hospital. My previous position was at the Geisinger Health System. I was there for 11 years, and I've been here at Bon Secours over nine years. My area of practice includes acute myeloid leukemia, acute lymphoid leukemia, CML, CLL, MDS, Hodgkin lymphomas, T cell lymphomas, B cell lymphomas, autologous transplant, allotransplants, CAR T cells, and BiTE therapy. I also participate in clinical trials. I also treat a number of benign hematology patients with ITP and iron deficiency and sickle cell. It's a kind of an old school job. We do everything. Before opening a clinical trial at my center, I have three criteria. Number one, based on the information available, is this likely to benefit my patients? Number two, are the logistics such that it would be acceptable to the patients? Can we get it? Number three, do we have these kinds of patients in clinic so that we can enroll in a meaningful manner? Those are the three criteria. That's why I participated in the REGAL study. I was also part of the phase I in GFH 009, and then the phase II on SLS009 and enrolled patients in multiple cohorts. I'd like to keep this simple, and I will put the results that Dragan shared with us into more of a clinical context and summarize things. In clinical practice and in the studies that we've seen, when patients fail Venetoclax-based therapies, whether it's first line or second line, their prognosis is terrible. Most of them don't live more than a couple of months. In the VIALE-A study, which led to the approval of Venetoclax, the patients who were non-responders who did not respond, their median survival was only a couple of months, and that was in the first line. In second line patients, patients who were treated with Venetoclax combinations, their median overall survival is about just over two months. Overall response rate is low at 30%. It's really, really dependent on the mutations. If you have unfavorable mutations like ASXL1 and the RAS mutations and TP53, you're not really going to respond. It'll be barely in the low single digits. If you have the favorable mutations like IDH1, IDH2, and NPM1s, about half the patients responded. If you have patients who stopped responding to Venetoclax-based combinations and were treated with something else, the overall response rate was only about 15%, and median overall survival is just over two months. That was also heavily dependent on mutations because if you had the bad mutations like the RAS mutations, ASXL1, TP53, nobody lived a year, and median overall survival was just over two months. If you didn't have the bad mutations, then 42% made it to one year with median overall survival just over four months. Patients who didn't respond to Venetoclax-based combinations or relapsed after initial therapy, whether it was first line or second line and were treated with another agent, their overall response rate was in the single digits, about just over 5%, and half of them didn't make it beyond two months. For first line refractory patients, the median overall survival is about just over two months. For second line refractory patients who are refractory to Venetoclax-based therapy, it's under two months. It's actually dismal. None of these patients were obviously continued on HMAVEN once they progressed, unlike in our SLS study. They were treated with other treatments. In our study, we compared the data from our real-world reported numbers to what we saw. Could we see the next slide, please? Yeah. Over here, if you look at the AML-MRCc patients, myelodysplastic-related changes that had mutations like ASXL1, EZH2, and SF3B, SLS009 did really well. Almost half the patients responded, whereas traditionally, if you treated them with something else, response rates are in the single digits. If you looked at the criteria, the Mayo criteria patients with the RAS mutations and P53 mutations, nobody responded to currently available therapies, whereas in the SLS cohort, it was about just over half the patients. Dragan's already described the myelomonocytic population and its dependence on MCL1. We have excellent biomarkers now that can, number one, predict the patients who will do very poorly on available therapies, and those same biomarkers seem to predict a pretty decent response to SLS. Could we, is there that other slide we were going to check or no? Okay. Can we go back one? One of the things we know is that patients whom we treated in our study had a response rate. If they'd received previously two or more therapies, their response rate was like 30%, 40%. If they'd received one previous therapy, it was 60%, right? Dr. Wang has also presented some data in ASCO last year that said that the same regimen can produce much better responses in patients who were treated earlier. In the future study, which the FDA wants, we're going to be treating in that one arm patients who have received zero prior therapies. Two prior therapies for these patients who don't respond, it's 30%. One prior therapy, it's 60%. We expect that with zero prior therapies, it'll be a number much above 60%. The survival on what we've seen historically for these patients is about two months. The survival we've seen in some of these cohorts is about five or six months or more, eight months sometimes. That's the background on which the new study is going to be started. My expectations are heightened by the FDA's request to move into the frontline because when we look at all the data from the past, we should be able to hopefully, and it's not unreasonable to believe that our numbers should be better because all we're expected to beat is a response rate that's in the single digits and a survival of two months. We've already shown numbers in the phase II that are multiples of that. That's why I'm really excited and looking forward to the new frontline therapy trial. Thank you. Thank you, Dr. Khan. It was very interesting to get the clinical context and how all of this fits in, which obviously, as you know very well, gets us really excited. Again, just want to thank Dr. Khan and, of course, Dragan for this very informative overview. I think, as you heard from our experts, we're indeed on the cusp of potentially bringing transformative drugs to patients in need. I would just like to add a few remarks and summarize some key points that you heard. Regarding GPS in the REGAL study and beyond, I'm really pleased to report that we have not observed, as you heard, any intolerable toxicities in our patient population. Although toxicities are commonly observed with therapies used in the control arm, physicians are allowed to modify the treatment regimen in any way they deem necessary. This includes the option for observation, which for the purpose of the trial is considered a valid treatment option. Due to regulatory reasons, as the study sponsor, we lack specific information on the outcomes of study participating patients, including data on how many of them relapsed, but have not passed away yet. As I mentioned at the beginning of the event, although we do not know survival outcomes per treatment arm, from a mathematical standpoint, every passing month may increase the probability of a successful study due to a potential GPS effect, as we have seen in our previous CR1 and CR2 studies, far surpassing median overall survivals versus standard of care. When the 80th event materializes, we will inform the public, which represents the most important near-term catalyst for SLS. The determination of the relevant survival outcomes, including the final analysis, belongs to the Independent Data Monitoring Committee, the IDMC. During the next IDMC meeting, when scheduled, the IDMC will analyze the accumulated data and assess the safety and efficacy of the treatment. Statistical significance, as Dragan alluded to in our REGAL trial, will be achieved by an estimated hazard ratio for overall survival of 0.636, corresponding to an overall survival of 12.6 months versus 8 months for GPS versus BAT, respectively. The IDMC must not disclose event rates and clinical data to us, so we will not know in advance when the 80th death has been reached. Once it happens, we will inform the public. As for SLS-009, I think the results to date, as you have seen, have been extremely encouraging. I mean, they represent an important advancement, I would say, for SLS-009. As a reminder, our upcoming trial and with the input by the FDA, we were actually pleasantly surprised because we have had really constructive discussions with the agency and, you know, met with them within a short period of time, numerous times. We are very, you know, pleased with the FDA interaction and their support and constructive feedback. We will administer SLS-009 in the frontline setting, as we discussed earlier, as well as in patients who did not respond to Venetoclax and azacitidine after two cycles. The goal of the next study, in addition to safety, is going to be to assess the efficacy of SLS009 as an add-on therapy, measured by at least a 50% increase in complete response rate compared to control arm percentage, an increase in overall survival by at least 50% compared to control arm, and finally to confirm the predictive properties of biomarkers identified in the previous trial and to compare and confirm with our transcriptomics, genomics, and proteomics work that we're really very proud of. Switching briefly to finance and our recently completed $31 million financing this week, we're extremely pleased to have significantly strengthened our financial position with that transaction of $31 million in gross proceeds, as well as the close to $24 million gross proceeds we brought in last month. This funding will enable us to reach our important upcoming milestones, notably the final analysis for our phase III REGAL study, continue to build out our corporate infrastructure for GPS, our upcoming SLS009 trial, and pertinent study data in 2026, and potential expansion of this study while further pursuing regulatory and business development and licensing efforts. We are really extremely excited about the potential to use the data towards an accelerated approval path and/or quickly move into a registrational study with our CDK9 inhibitor based on the predictive biomarkers we have identified in addition to other solid cancer indications that these biomarkers express. This financing gives us additional firepower, if you will, to execute on our objectives. This journey ahead is filled with promise, and we're just really excited about the evolution of our company. I think with that, maybe it's time to switch into the Q&A session, John Francis, if you want to. Sure. Thank you, Dr. Stergiou. Appreciate that. As you can imagine, we received many questions from the audience. We are going to group the questions by clinical program, starting with GPS. Then we'll move to the SLS009 program. At the end, we should have time to answer SLS corporate-related questions. The first question is for Dr. Cvicic. Can you talk about the enrollment strategy, how the enrollment strategy has evolved since the phase III REGAL trial began in 2020? For example, one of the recent protocol changes allows patients who remain in remission after 52 weeks to receive treatment every two months during the second year, and after two years, every three months. Can you help us understand the rationale behind these changes? Does this mean there are GPS patients who have remained on therapy for a much longer period than originally expected, 10 to 15 months? I believe you have to unmute, Dr. Cvicic. Sorry, apologies. No worries. First, let me state that protocol amendments are a common practice throughout clinical trials. Indeed, we had protocol amendments. We do not have insight into how patients are surviving per arm, which, as I mentioned before, but we can say in response to the question that the trial has obviously been lasting longer than expected, and more patients are alive than we initially projected. Okay. Our next question is for Dr. Tsirigotis. Regarding the 80 events we are expecting, it seems that the longer it takes, the better the outcomes are for patients. Do you share this interpretation? Yes, of course. I think that it's pretty clear that we are going to have a prolongation in overall survival for the whole cohort of patients enrolled in REGAL as compared with historical controls. I would like to stress the point that, to my opinion, as a physician, because I work with patients, if you see what is the outcome of those patients in CR2 who are receiving Venetoclax, you can see from the data that the median overall survival is a few months. I'm convinced. I can say I'm totally convinced. Of course, we have to see and wait for the final result. I strongly believe that this prolongation in overall survival is due to the GPS effect as maintenance treatment. Okay. Thank you. The next several questions are directed to Dr. Stergiou, and the first of these relates to several aspects on GPS manufacturing. Can you explain the preparation of your GPS manufacturing capabilities and CMC work? Where is GPS manufactured, and how complex is the manufacturing process? Is that process, is the production outsourced? Yeah, I'll try to keep it simple. The drug substance or the peptides of GPS, those are manufactured at Polypeptide. If I recall correctly, it's in Southern California, which has extensive experience and expertise in peptide manufacturing, really for the global market. That's the drug substance. Then we have the final product, which is called the drug product, and that's manufactured at PCI Lab Services, LS&E in New Hampshire, which really has experience with manufacturing sterile lyophilized products. The peptides are manufactured using, for easy use here, a standard chemical process widely used to make other small peptide drugs. The final product, again, is a sterile lyophilized powder for injection, which is a commonly used dosage form. Okay. The next question, again, for Dr. Stergiou. Galinpepimut-S has received orphan drug designation from the FDA and EMEA, as well as fast track and rare pediatric disease designation from the FDA. Do you expect a reduced review period for the Galinpepimut-S BLA? Yeah, I think so. Given GPS regulatory status and other FDA procedural guidelines, we would absolutely expect a priority review designation. However, you know, we cannot comment on what the FDA's actual review period would ultimately be. Okay. Back to one more question on manufacturing, it seems. In your presentation, you note that certain peptides in GPS are engineered and artificially mutated. Can you explain the difference between these two types and what that means? Yeah, I think Dr. Tsirigotis put it very nicely into context in his presentation. When the early discovery work happened at Dr. Scheinberg's team at Memorial Sloan Kettering Cancer Center, which is where we licensed the asset from, they screened the entire WT1 amino acid sequence for literally thousands of binders and then selected the best ones of hundreds with the methods of in silico prediction of peptide MHC class I binding. That really helped to provide optimal target for CD8 T cells. They systematically modified them to see if they could be further improved. Similar methods were used for the selection of CD4 T cell activating peptides. Longer peptides allowed for, you know, reactivity, if you will, with more epitopes, multivalency, and presentation to both CD8 and CD4 cells. As you know, we have a garnish of four peptides. Two of the peptides within the GPS mixture are native. It means that they contain the exact same amino acid sequences as the fragments of the WT1 protein they originated from. The remaining two peptides, where we utilize the heteroclitic technology, are by design modified by an amino acid mutation. In that sense, the heteroclitic WT1 peptide carries a mutation and is presented to the native CD8 cell through the host antigen-presenting cells. As Dr. Tsirigotis said, the macrophages, dendritic cells, or monocytes. The CD8 cell gets activated and becomes a cytotoxic T cell, which now is able to recognize not only the mutated version of the WT1 peptide against which the host was immunized and does not get expressed naturally, but also the corresponding native WT1 fragment. The native fragment gets expressed and gets presented on the membrane of cancer cells in an MHC class I context. Similar events again occur on CD4 cells after cross-presentation of the WT1 heteroclitic fragment and eventual activation of the CD4 cells into effector and memory cells. The heteroclitic technology really mitigates, among others, against the emergence of tolerance. That allows us treatment over a long period of time through the administration of booster inoculations as mutated peptides are classified as non-self antigens. That's a really great detailed answer. It's a good segue for our next question, which is directed to Dr. Tsirigotis. AML can lead to the depletion of both dendritic cells and macrophages. Is this a potential issue for AML patients in CR2 who could benefit from GPS therapy but may not have enough of these cells for sufficient antigen presentation to CD4 plus helper and CD8 plus T cells? Do you measure for a certain level of APCs before administering GPS? Okay. Thank you very much for this question. First of all, I have to say that this is not completely true. From the time that we have a full-blown leukemia, of course, there is a decrease in the production of new dendritic cells, which are the most efficient in antigen presentation. Those cells that already are in the tissue, they are long-lived cells. This is not true. I mean, from the time you have full-blown leukemia, you don't mean that you don't have any dendritic cells. Now, to move a little bit, we treat patients in complete remission. The block, this block in production of new dendritic cells doesn't exist anymore. Finally, as I showed you in my presentation before, 80% of the patients who receive GPS, they manage to elicit a strong immune response against WT1. This is the proof of the principle that GPS is effective. This, again, it's an indirect way to understand that the dendritic cells are there. This is my response to your question. Okay. Thank you. The next set of questions relate to the SLS009 program. The first question is to Dr. Cvicic. Is there another example of an acute myeloid leukemia clinical program where the FDA recommended advancing the drug candidate into the frontline setting based upon clinical data from relapsed refractory patients, similar to your phase II study for SLS009? Yes, there is. I would here reference Quizartinib. The development went to its inhibitor, and we are now talking about AML directly, right? Quizartinib, they had a trial that was called QUANTUM-R in relapse and refractory patients. Based on the results of the trial, the FDA actually asked them to move into another first-line trial, Quantum- First, and the drug was approved as the frontline drug in QUANTUM-R First based on the QUANTUM-R First results. Okay. Also for Dr. Cvicic, do you consider SLS009 a next-generation CDK9 inhibitor primarily because of its higher potency and selectivity, or are there other attributes that distinguish this molecule from past CDK9 drug candidates? I will be very brief here because I can't get into lots of detail here. In principle, what dictates this drug's potency and selectivity is biodistribution, which in turn dictates pharmacokinetics and pharmacodynamics. The attributes that determine that are charge, lipophilicity, and functional groups, which then determines how the protein binding is. The protein binding, and so on, lots of these data are not public and they're proprietary. I would just say charge, lipophilicity, functional groups, and then protein binding and all that comes out of it. Thank you. Okay. Next question is for both Dr. Khan and Dr. Jamy. With twice-weekly IV dosing for SLS009, will this be seen as a logistical barrier limiting adoption, especially in community oncology practices that manage AML patients? Omer, you go first. Thank you. Even when we have our patients getting hypomethylating agents and Venetoclax, we expect them to get labs checked either at their treating center or locally two times or three times a week. I think if they're already going for that, getting the drug twice weekly should not cause any additional logistical burdens to the system. If patients enroll in this trial, they'll be taking oral Venetoclax. They'll be on Vidaza, the azacitidine. They're coming to clinic seven days anyway in that first week when on treatment. They're just going to spend an extra hour for two of those seven days getting the SLS009. It really is not going to really, you know, mean that much in terms of visits. Patients that, you know, are diagnosed with acute leukemias, they're different from, you know, with some other cancers. When you have that conversation with them, it's a sobering experience, right? Because you tell them that if you don't get treatment, you're not going to live more than a few weeks or a month or two. They're very motivated to trying to put this leukemia behind them. Understood. Okay. The next and final set of questions will focus on SELLAS corporate-related topics, all for Dr. Stergiou. How should we think about R&D spend on an annualized basis moving forward, assuming the new SLS009 study is initiated in the first quarter of 2026? Yeah. As you know, we don't give guidance, but suffice it to say, we have the strongest cash position in our history as a public company. This firepower really allows us to reach several value-driving inflection points through this year and next. Okay. Assuming success in the phase III REGAL study, can you discuss your commercialization plans, a potential European partnership, or perhaps going it alone in the U.S.? I think, as you can appreciate, we think through all scenarios and the best value propositions really for patients and ultimately our shareholders. Our commercial strategy is to be prepared, and we have to be ready to launch and market our product candidates ourselves until someone knocks us off our tracks. We continue to prepare the organization at this pre-commercial stage for the necessary infrastructure for a successful launch globally. At the same time, the team has been engaging with potential partners, and I'll come back to what I said earlier, and we'll evaluate all potential scenarios that deliver us the best value proposition for patients and ultimately for our shareholders. Given the recent capital raises, next question, you may have already answered it, but I'll ask it. Given that you're advancing two late-stage programs, how will you prioritize capital allocation between the two if both approach registrational stages around the same time? Yeah, our capital allocation strategy remains to be as cost-effective as possible while driving our assets further through the clinical development process. At this point, REGAL is approaching the finish line, and our spend has been reduced as the study has been fully enrolled for about 18, 19 months now. While we anticipate initiating a new frontline study of SLS009, as you heard, that study is not as capital-intensive as the REGAL study, and we expect our current financial position to deliver us meaningful data from the study. We remain prudent in our spend. For example, and please remember, we have only 14 full-time employees, all of us. Every single one in our company wears three, four, five hats. We don't expect additional headcount, and we have not had any additional headcount for the last 18 months. Okay. Understood. Final question. What makes SELLAS stand out from other small-cap biotechnology companies working in AML? Why should investors believe SELLAS can win in such a competitive space? I think it's an excellent question. I would say it's definitely our assets and our experienced team. You know, while AML may appear to be a crowded space, there's nothing approved in the maintenance setting in AML. If GPS demonstrates what we all hope is clinically meaningful and statistically significant survival benefit with a favorable safety profile that we know we have, we have the potential to change the treatment landscape for these patients with a targeted immunotherapy. I mean, both of our assets, GPS and SLS009, have the potential, and I've said this many times, and I'm so proud of saying it again, to be the first in class and the best in class. The former is a WT1-targeted immunotherapy, and the latter, as you know, is a CDK9 inhibitor. We welcome the new therapies that are getting to patients, that are getting patients into remission, and potentially expanding our addressable patient population for GPS. You know, Venetoclax resistance, as well as the refractory setting, is a large unmet need for AML patients. If we can reverse that resistance, as we have seen in our studies, in frontline or early refractory AML patients with SLS009, we would become a staple in the treatment landscape. You heard from Dr. Panagiotis Tsirigotis also the potential of GPS in post-transplants. Our investigational products are truly differentiated within the AML space, and we look forward to really expanding our footprint from early on to the maintenance setting. I think that would be my answer to that question. It's definitely our assets, and it's definitely our amazing team that we have here. Okay, great. That concludes the Q&A session. Dr. Stergiou, I'll just turn it back over to you for final closing comments. Yeah, I think in conclusion, we have placed great emphasis on bringing about the next stage of value creation on behalf of SELLAS shareholders. On behalf of the entire SELLAS team, we want to express our gratitude for your continued support and confidence in our company, a matter that I and we collectively do not take lightly. I also want to thank our employees who are most integral in our mission and for whom our clinical programs would not be possible without their diligent and tireless work. My sincerest appreciation goes out to all our physicians, and I really so greatly appreciate our key opinion leaders participating on this call today, our nurses, the study teams, and most importantly, our participating patients and their families. It's very emotional for me many times because we get a lot of feedback from patients, and it's just great to see, and all we want is to see smiling faces and families that really appreciate all their support for their contributions in advancing our programs. It would not be possible without them, and they're just really the cornerstone where we are today. Really collectively, let's stand firm, steady, and resolute, knowing that our work that we do today will really reverberate far beyond the walls of SELLAS. We're not just developing treatments. I've said it before, we're creating hope for those who need it the most, and together we aim to transform lives. Thank you once again to everyone, and we look forward to sharing further updates with you. Thank you.