Good morning. My name is Krista, and I'll be your conference operator today. At this time, I would like to welcome everyone to the Kura Oncology Virtual Investor Event. All lines have been placed on mute to prevent any background noise. After the speaker's remarks, there will be a question-and-answer session. If you would like to ask a question during that time, simply press star followed by the number one on your telephone keypad. If you would like to withdraw your question, again, press star one. Thank you. I would now like to turn the conference over to Troy Wilson, President and Chief Executive Officer of Kura Oncology. Mr. Wilson, you may begin your conference. Thank you, Krista, and good morning, everyone, and thank you for joining our call. I want to welcome you to our call to describe the preliminary clinical results from our KOMET-007 study. I'm here with my colleagues, Dr. Mollie Leoni and Dr. Stephen Dale. We're joined by Dr. Amer Zeidan and Dr. Amir Fathi as well, two investigators on the study. Each of them will take a turn in walking you through this set of slides. If we turn now to slide number three, we will be making on this call forward-looking statements. And I'll just want to draw your attention to our website, to the SEC website for more information about the risks and uncertainties in an investment in Kura Oncology. With that, now turning to slide number four. This is an important day. This is a day that we at Kura have been waiting a long time for. When we started this program, with z iftomenib, with a menin inhibitor, our goal was to transform the treatment of acute leukemias. And today we, we want to share with you what we think is a big step forward in that direction. That's an ambitious goal. It's not an unprecedented goal, however, and in the next couple of slides, want to just walk you through two examples that give us optimism as to why we might be able to achieve this goal. The first is here on slide number four, and that's the example of an immediately adjacent leukemia, namely acute promyelocytic leukemia. This is one that arises from an abnormal fusion protein, the PML-RARα fusion, that's quite similar, actually, to the menin-KMT2A, in that it creates a promyelocytes which proliferate uncontrollably. Prior to the advent of ATRA and arsenic trioxide, this was a nearly invariably lethal disease. However, upon the introduction of all-trans retinoic acid and arsenic trioxide, which, incidentally, has a very similar mechanism of action to ziftomenib, namely, that it differentiates promyelocytes, we've now seen a remarkable transformation in the standard of care for acute promyelocytic leukemia, and you see that at the bottom. Today, now we have an 89% overall survival at 10 years in patients with APL. So that gives us optimism. Turning to the next slide, slide number five, again, an example in the hematologic malignancies, this one with multiple myeloma. Prior to the 2000s, as many of you know, myeloma was nearly a death sentence. Very few treatment options, and patients were lucky to have a median survival of two to three years. And then there was a renaissance. We saw the immunomodulatory drugs, the proteasome inhibitors, then the CD38 antibodies, and so forth. And now we're at a point, because of these combination therapies, where many patients have the hope of actually living with their disease for more than 10 years. And this is an example that we like to use because IMiDs have really become a cornerstone of treatment. They're used in combination with almost everything. They're used throughout the continuum of care. And what these combinations have done is to transform the standard of care in multiple myeloma, and by virtue of that, transform the market. And at peak, the IMiDs were driving peak sales of greater than $15 billion. So it's a tall order, what we're seeking to do with acute leukemia, but we have great optimism. And my colleagues and I and our distinguished investigators on the phone are looking forward to walking you through that. With that, now we'll start to get into the data, and I'll turn it over to my colleague, Dr. Stephen Dale. Thank you, Troy. Just going to the next slide, that's slide seven. So thinking specifically about ziftomenib, we firmly believe that the drug will have the potential to evoke a paradigm shift in the way that these patients are treated. To date, there has not been a standard of care. Ziftomenib provides these patients with horrendous prognosis in both genetic subtypes to have an effective treatment. Ziftomenib targets foundational mutations at the core of up to 50% of AML. Importantly, our clinical data is compelling. I'll repeat that, is compelling, and as such, clearly supports combinations with standard of care in frontline disease. In combinations, both in frontline and relapse refractory, we see good safety and tolerability, and as such, it enables continuous administration of the medicine. One of the areas which I know understandably, there's been a lot of interest and focus, has been on differentiation syndrome and whether this can be effectively mitigated in the KMT2A patients, where we see a higher frequency, and severity of extramedullary disease. We are thrilled that our combination data show that the risk of differentiation syndrome is mitigated with our combinations, both in KMT2A and NPM1. We do not see any drug-drug interactions. Our clinical activity is highly encouraging, and the enthusiasm of our investigators has been amazing, and I use that word because it really is. And proof of that, of course, is with our enrollment rates just going way over in acceleration over what the target enrollment rates are. Again, just showing that the drug works, the drug works exceptionally well, and therefore, investigators are keen to put their patients on, certainly for the combination studies, to give their patients a chance. And overall, it's important, again, to understand that this drug is well-tolerated. It has clinically meaningful efficacy data, which our investigators will walk you through shortly, and it definitely will be best in class. So if we move to the next slide. So it's with great pleasure that I can introduce two of our esteemed investigators who are also world leaders in hemato-oncology, and we are humbled by the fact that they have been so supportive of the ziftomenib program, and we'll talk to you more around their patient experiences a little bit later on. Dr. Fathi, Program Director for the Center for Leukemia at MGH, and also Associate Professor of Medicine at Harvard Medical School. Dr. Amer Zeidan is Interim Chief of Hematologic Malignancies at Yale, and we are delighted that both of these investigators are taking time to join us today. With that said, I'll hand over to Dr. Fathi. Thank you so much, Dale and Troy, for going through the slides and for having me today. It's a pleasure to be here, from not-so-sunny, Boston. I was tasked today to go through some of the data on the monotherapy experience of azacitidine from the KOMET-001 study. This data was predominantly at EHA this past summer at the late-breaking abstract session. Without further ado, let us advance to slide 10. This slide provides you with a general idea of the schema of the KOMET-001 trial. It started with a phase I -A dose escalation, where we started with a pretty low dose of 50 mg daily and quickly dose escalated all the way up to 1,000 mg daily. Looking at various subpopulations of AML, mainly focusing ultimately on NPM1-mutated and KMT2A-altered disease, with a goal of assessing safety and tolerability, the pharmacokinetic markers, pharmacodynamic markers, and ultimately getting a preliminary sense of activity. It is important to mention that this study was among the first to be designed and applied with the Project Optimus from the FDA in mind, where ultimately we wanted to validate certain doses as we were escalating and investigate them to both optimize, hence Optimus, the tolerability as well as activity, of the drug, to find doses that were most likely to be active and at the same time safe for patients. Given that, ultimately two doses, 200 mg daily and 600 mg daily, were chosen to further investigate the phase I goals of the study, namely safety, tolerability, as well as correlative science related to these agents. These cohorts were expanded and further studied. Ultimately, 600 mg daily was chosen to be the most pharmacokinetically and pharmacodynamically optimized dose, and that was used in the phase I-B expansion that specifically looked at that dose for specifically NPM1-mutated AML, and that has since led to the larger phase II registration-enabling study with a dose of 600 mg daily, again, with a primary endpoint of composite remission, as well as multiple secondary endpoints with the key ones being duration of remission, transfusion independence, MRD assessments, and obviously, safety and tolerability again. Next slide, please. This slide just gives you an idea regarding our general observations over the period of dose escalation and key pharmacokinetic profiles of the drug. As you can see, with an increasing amount of dose, there was a plateauing of the system and an exposure at around 600 mg daily based on the mean AUC parameters. That basically told us that we were pretty good at 600 mg, which was a dose that was safe and well-tolerated and led to very ideal and optimal pharmacokinetics for patients to hopefully achieve the activity which we were hoping to see at the time. The drug has been very well tolerated, considering what we currently have for agents in AML. I want to remind the audience that, and I suspect Dr. Zeidan would agree that for, you know, I think every time I say this, it seems like a decade passes, but since the late 1960s, we have not had that many effective regimens for AML. We've had induction chemotherapy, and nothing much changed until approximately six to seven years ago, when there was a flood of targeted therapies and antibody drug conjugates and other approaches, novel approaches to treatment. And we've had eight or nine approvals since, including IDH inhibitors and FLT3 inhibitors. And it's been an exciting time because everywhere, every time, every few years, you, you potentially find something that comes along that potentially has activity in a subset of AML. And this, menin, seems to have a particular role in patients who have NPM1 and KMT2A alterations, as predicted by preclinical efforts in these leukemia subtypes. In terms of the safety and tolerability of the drug, it's certainly much more tolerable than traditional intensive chemotherapies. The one adverse event that we all have heard about that does occur with this class of drug is differentiation syndrome. But there is a differential in terms of its strength and presentation with NPM1 mutated disease versus KMT2A altered disease. With NPM1, in general, it tends to be milder and can be managed with traditional mitigation strategies, including steroids, cytoreduction, and other efforts. It does tend to be occurring at a higher rate and more severe with a KMT2A altered disease, as has been seen also with other menin inhibitors and seems to be a class phenomenon, as has been also been shown with other agents. It occurs at a higher proportion, 38.5% at 200 mg and 37.5%, approximately similar at 600 mg, so not much different. It would make sense that a way to potentially mitigate the effect of this drug in promoting differentiation syndrome, KMT2A altered disease, would be to combine it with traditional chemotherapy or conventional chemotherapy strategies to help bring down this leukemic cell population and decrease the burden of cells that are going into differentiation. It is important to mention that DS is an on-target adverse event, and it represents the underlying mechanistic activity of the agent, because ultimately it triggers the differentiation and maturation of cells, which is what we want, but can trigger, if it's too robust, a cytokine-mediated inflammatory process that can be clinically significant in patients. So thereby, if you decrease the proportion of cells that might be prone to differentiation with concurrent chemotherapy, you would in turn decrease the likelihood, theoretically, of severe differentiation syndrome. So that is an important consideration for this particular subtype of AML. There are other adverse events that were looked for and assessed during the clinical trial. We did not see any substantial evidence or any clinically meaningful QT prolongation. That is quite important in our field, probably more so than other fields. Patients that undergo treatment for AML frequently are on many other medications that can prolong the QT interval, including nausea medicines, antifungal agents, antibiotics, sometimes psychiatric medicines. All of these can prolong the QT. And when you have that in the background and you have a drug that potentially prolongs QT, it can become a problem. And you know, in our field of doing clinical trials and drug development, QT prolongation is often a factor that we look at, and we worry about. But with ziftomenib, that has not been a clinically impactful issue on clinical trials. The other important factor when it comes to novel agents in the treatment of AML, because AML is a marrow-based disease and because many of the treatments that we have suppress blood counts, patients who receive treatment for AML oftentimes suffer from various degrees of cytopenias and often from severe degrees of cytopenias. And by cytopenias, I apologize if I'm speaking in the shop a little bit here. Cytopenias refer to low blood counts. So, if because of the disease or because of the treatment, a patient has a very low platelet count or a very low white blood cell count, they are prone to infectious and bleeding complications, which can impact the safe conduct of the trial, the success of the agent you're trying to develop, and ultimately, and most importantly, the safety and tolerability that patients have to go through. So it is important to assess also the propensity of individual drugs as they go through development in terms of marrow suppression and promoting cytopenias. In the case of ziftomenib, our experience has been, at least with the monotherapy study, that which is what I'm tasked with presenting today, that once patients achieve the response. Meaning that they've achieved a remission, and we know that the drug has achieved its ultimate goal of gaining a marrow response. With, you know, continuing treatment, these patients did not have substantial decreases in platelets and neutrophils at the doses we were using, which was ultimately 600 mg daily. And that's important. That means that patients in a state of remission can continue to benefit over time without a worry that we would need to dose adjust, that we would need to worry about decreasing the dose and potentially decreasing the impact and efficacy of the drug, and allow the patient to have as much benefit for as long as possible. Ultimately, the durability is quite important. Next slide, slide 13. So this slide provides you some of the data on activity. Again, very similar to what I presented at EHA. The same data is presented here. This provides the best overall response for our NPM1-mutated patients. The complete remission rate was 35%. The composite remission rate, which included a patient with CRi, was 40%, and an overall response rate, which was a patient with MLFS, morphologic leukemia-free state, which I believe, if they would have recovered, their counts would have also been a remission, was 45%. The overall response rate for the KMT2A group is also provided here. The data, and I think this is a small number of patients, but it's for comparative purposes that on NPM1-mutated patients, on FLT3-mutated patients, and on IDH-mutated patients is also provided here to give you a sense in terms of how they may compare historically. Patients, regardless of whether they have FLT3 mutations or IDH mutations, responded at similar rates in terms of a complete remission. And it's mentioned here, and perhaps it should be mentioned more prominently because it is quite meaningful. The number of prior treatments for our patient population was quite dramatic, you know. So it had median number of three prior treatments. That's substantial. These are patients that ultimately didn't have many options at that point. We don't have many options for AML historically, and if they've already received two or three prior treatments, oftentimes there isn't much that you can offer them. So the fact that you could potentially salvage a highly resistant, challenging disease at that point is remarkable. So in sum, the high activity, durable responses, and favorable safety profile suggests that the potential for ziftomenib to become a backbone in AML in the future is strong. I think I have one more slide here. And this circle plot here provides you a general sense of why the investigators associated with this trial, as well as the group of leukemia docs in general, are excited about menin inhibitors. The clinical activity is strong. I mean, the data that I just presented here with NPM1-mutated AML in the relapse refractory setting, in the setting with multiple prior lines of treatment, with a remission rate of approximately 40%, is remarkable. I would say if not more important, as important is the safety and tolerability. The drug-drug interactions were not a challenge. We didn't have to dose reduce, dose adjust, do these gymnastics during the clinical trial. The QT prolongation wasn't a signal. The differentiation syndrome was there, but it was very manageable with NPM1-mutated disease and ultimately with the KMT2A group, our approach was to try and focus our attention ultimately on combinations. There may very well be, and there's data that is emerging, that there could be synergistic potential for menin inhibitors as well as other standard treatments for AML. I didn't get into it, but a substantial number of our patients achieved molecular residual disease clearance per institutional tests that were performed on study. That suggests a depth of response, which in general translates to a durability of response, which is good for our patients. As some in the audience probably know, resistance to menin inhibitors is a phenomenon that has increasingly garnered a lot of attention with various menin inhibitors. That is an area that is important for us to try and figure out and understand as we explore, certainly, combinations in the future to ameliorate that risk. I think all of this put together, you know, the fact that patients don't have to adjust their drugs, the fact that it's generally well-tolerated, the fact that a high proportion of patients respond and continue to respond, the fact that this then translates to decreasing symptoms, decreasing transfusion needs, all of that impacts quality of life. And as a leukemia doctor, considering the fact that the median age of diagnosis now is around 70, that means that half of our patients are in their 70s, 80s, and 90s. Many of these patients are not candidates for transplant or intensive therapies, and quality of life for as long as possible is quite important. And the last thing I'll say is the pharmacoeconomic benefit. And I think over time, if you have less time in the hospital, less complications, that certainly has an impact on the global, larger, perspective of, cost and burden to the healthcare system. And with that, I will pass the slides along. Amer? Thank you so much, Amir. And for those of you who actually can confuse Amir and myself, don't feel bad because we actually both trained at Hopkins, and this happened to me all the time where people confuse both of us. So it's really a pleasure to be with Amir on this call. It's also a pleasure to be here on this call because I think this is very exciting field. I think you heard very eloquently why the menin inhibitors and ziftomenib, in particular, are going to change the way the treatment of AML is being done in the relapse setting, but importantly, for those patients who have more difficult disease in the refractory relapse setting. But also, we know in hematologic oncology in general, the most important advances in the shape of the disease and in terms of adjusting the natural history of the disease happens when we combine promising drugs with a backbone of standard therapy, because this will overcome the multiple and overlapping resistance mechanism that these malignancies will exhibit to therapies. And Stephen outlined a very nice analogy in multiple myeloma with the IMiD. Because of all of these reasons, and in particular in this case, because combination therapy also is going to mitigate the risk of differentiation syndrome, having a combination-based approach with menin inhibitors, with ziftomenib, seems very appealing, and many of us were looking forward to starting this trial, which I think is the first or, and the most advanced, as far as I know, in terms of combining a menin inhibitor, in terms of a clinical trial in patients with acute myeloid leukemia. It's really also a pleasure to see a rapid approval. There is a lot of excitement about this trial and about these combinations, and pace of approval to this trial has been outstanding, and it's really an honor to have the first data, the first look of data in terms of public release. I think, many of us were excited and happy to see, the data that I'm about to show you. Next slide. So many of you are familiar with the design of this, study. It's a little bit complex, so we broke it into two different, slides. Here you can see that, this study, which enrolled both frontline and relapsed/refractory AML patients. In this slide, you are seeing the frontline, treated patients. So those patients who are candidates for intensive chemotherapy, which as many of you know, the standard backbone is 7+3, which is cytarabine and daunorubicin. And this has been the backbone for many, many years, more than 40 years in AML. Most recently, some of the drugs that were very, active in the monotherapy settings, such as FLT3 inhibitors, were combined with this backbone and led to improvement in overall survival. For example, with a FLT3 inhibitor such as gilteritinib or midostaurin, those are commonly used now these days, basically in combination with chemotherapy and quizartinib, clearly. So I think here the paradigm is very similar to try to add ziftomenib to 7+3 in the specific subsets that are more susceptible to ziftomenib, which is, as you know, the NPM1 and the KMT2A rearranged leukemias. Those two cohorts were enrolled separately, so they're the cohort for each molecular subset. It was a dose-escalation study in the initial phase, as you can see here. We started with the 200 mg dose, and we treat at least six patients in each dose level, and then you escalate. The currently enrolling dose for the frontline-treated patients is the 200 mg, and you can see that subsequent to the selection of the dose, there will be expansion and validation of this dose level. The drug, ziftomenib, is being started at day eight after the intensive chemo part is done with cytarabine and daunorubicin. Important to remember that patients who had NPM1 mutation, who were enrolled during the dose escalation, also had what we classify as adverse risk. Those patients basically had to be older than 60 or had to have treatment-related AML, or had to have adverse risk cytogenetics per the ELN. This is important to remember because while frontline treatment of NPM1 disease is generally associated with favorable outcomes, those patients who have adverse risk, like those patients in this category, don't do very well. I think this is important when you add a combination, when you are thinking about the results that we are going to show you. In the refractory relapse setting, ziftomenib was combined with venetoclax azacitidine. As you know, venetoclax and azacitidine is a standard of care in older patients with acute myeloid leukemia who are unfit for intensive chemotherapy, but it's a commonly used salvage therapy as well in the relapsed refractory setting. The design here is very similar to separate cohorts, dose escalation. As you can see, this, these cohorts moved a little bit faster in terms of the approval, so we are already at the 400 mg level, and eventually, this will expand into expansion and validation cohorts, as you can see in the associated diagram. This is important because I think eventually, these therapies are going to move to the frontline setting, where again, I think it's going to be the biggest dent on the natural history of the disease. Similar to the intensive chemo, the ziftomenib was started on day eight after the completion of the azacitidine concurrently with venetoclax. So here, going to the results in the next slide, you can see here the patient demographics and baseline characteristics. As a reminder, this is the first look of the 20 patients, the first 20 patients who were enrolled in the study, and these are preliminary data as of January 11, 2024. So you can see out of those, 20 patients that were enrolled in the trial, the most important or one of the first things to note is that most of those patients remain on the trial as of the data cut-off date, 16 out of the 20, 80%, which again, is encouraging that most patients are still remaining on the trial. You can see a breakdown of the characteristics of patients by cohorts here. The relatively small numbers when you break it down by cohorts, but you get the sense that, the median age is older, as you'd expect in patients with AML. The median age was 55. Most of the patients on this data cut were females, 13 of them. 11 of the patients had NPM1 mutations, and nine of them had the KMT2A rearranged leukemia. Of those patients, you can see that NPM1 mutations were mostly in the relapse setting. Seven out of the 11 were in the relapse refractory setting, and the same thing with the KMT2A, where eight of the patients were in the relapsed setting, eight out of the nine. And then importantly, for those patients who had been in the refractory relapse setting, you can see that those patients were heavily pretreated. You can see the number of prior lines and regimens. Several of those patients had been through transplant, 47%, almost half of them, which is, you know, those patients are not easy to treat, generally have very poor outcomes. 50% had previous hypomethylating agents, and importantly, 67%, 10 of them, had previous exposure, exposure to venetoclax, which is a subset of patients that do, do extremely poorly, based on evolving clinical literature after failure of venetoclax. So this is clearly in the refractory relapse setting, a very tough cohort of patients to treat. Next slide, you can see the safety data, again, with the using the same cutoff of January 11, 2024. This is a sick patient population, as many of you know, so it's very common to see adverse events, treatment emergent adverse events. This is consistent with the underlying disease as well as the backbone therapies. But when you look specifically at the ziftomenib-related adverse events, which are grade 3 or higher, you can see again that the drug is very safe. I think most importantly in my mind is, the fact that, differentiation syndrome was largely mitigated. There were no DS events reported at this data cutoff. There were no QTc prolongation, as Dr. Fathi nicely outlined, and this is especially when you think that, it's commonly. It's very common to use drugs that prolong QTc, such as antifungals, et cetera, in the management of those patients, and it's a true headache to try to replace these drugs or adjust them. So it's really nice to have a drug that does not do that because it makes life much easier during the induction treatment. There were no dose-limiting toxicities observed. There did not appear to be a delayed hematologic recovery, allowing continuous administration of the drug. So we were truly pleased to see the safety profile emerging so far. We have been able to kind of enroll patients without thinking too much about the added toxicity, which is always a concern when you add drugs to 7+3. But here, I think there's a clear-cut sense and this is my own personal sense from treating my own patients on this trial, that the additive toxicity seems very minimal. Now, talking about the efficacy data in the next slide, we are going to start with the frontline treated patients. As I mentioned, five of the 20 patients were treated in the frontline setting. Four of them had NPM1 mutation, and one patient had the KMT2A rearranged leukemia. Again, 100%, small number, early look, but very exciting. It's 100% of those patients; all five patients achieved complete remission. Again, remember, those NPM1-mutated patients are not your standard young, fit patients who have no adverse cytogenetics. Those are high-risk, adverse-risk cytogenetics, older patients, therapy-related type of NPM1. And the expected rate of CR/CRi is generally around 1/3 in those patients. So I think, again, this is very promising in my opinion. And all of those patients were treated on the 200 mg starting dose. Now, going to the refractory relapsed, cohort in the next slide, we chose to present it in- to make the data is more easy to understand. We broke it down into patients based on the previous exposure. Why is that? Because we know the efficacy of, therapies after ven failure is very different than patients who did not receive ven. And you can see some of the baseline expectations based on the literature. For example, patients who did not receive ven, venetoclax previously and, get treated with Ven/Aza, generally, the CR rate is 35%-40% CR/CRi rate, and this is why we tend to, use Ven/Aza in the refractory relapsed setting although it doesn't have a label currently in the U.S. for that indication. On the other hand, for those patients who have KMT2A rearranged leukemia who are refractory and relapse. The response rate is much worse. Some literature quoted it at less than 10%. So when you look at those patients, first by looking at the ones who did not receive a previous menin inhibitor, some of those patients on the trial received menin inhibitors on other trial. When we look at those who were naive, did not receive, there were nine out of the 15, and out of those nine, the overall response rate was 78%. You can see that, for NPM1 was 100%, and for KMT2A rearranged leukemia, it was 50%. Again, this is patients who have, who are in the refractory, relapse setting. And, important to note that all of those patients were treated in the 200 mg. We are currently enrolling in the 400 mg. In the next slide, you will see, and I think in my opinion, this is among the most impressive data of the trial to date, is among patients who are venetoclax experienced or venetoclax failed, as I mentioned, those patients do extremely poorly. We generally don't have good options for them. The response rate has been quoted in the range of 0%-20%. The survival is very dismal, depending on the literature you look at two to three months. And especially in those who have KMT2A rearrange leukemia after ven failure. In particular, these patients do very poorly. But when we look at our data, small number, 10 patients have seen venetoclax prior to enrolling on the trial. The overall response rate was 40%. When you break it down by NPM1 versus KMT2A, it was 60% with NPM1, and most of those were CR or CRhs. Again, I think this is pretty compelling data at this early look. So I'm going to go through some case examples of some of the patients who went on the trial to give you a flavor of what we have been seeing in terms of I think the impressive activity so far. So in the next slide, you can see one of the patients that was treated. You know, not an, not a young patient. This is a 66-year-old female, so those are older patients, many of them who went on the NPM1 cohort. A lot of blast in the bone marrow, 77% blast, and you can see a number of mutations. So not only NPM1, but the patient had also bad mutations such as NRAS. The patient was treated with 7+3. Ziftomenib started on day 18, on day eight of the trial. Patient quickly achieved complete remission, and she was able, by the design of the trial, by the way, to stay throughout on during consolidation and post-transplant maintenance with ziftomenib is also allowed on this trial, which I think is very important because we know that most patients with leukemia would still relapse. And you know, there is a lot of interest in exploring maintenance options in those patients. So this patient, I think, did very nicely, and we continue to follow her on the trial. The second patient, here you can see this is an example of this dreadful type of leukemia, the KMT2A-rearranged leukemia. This is a 49-year-old female who was diagnosed with this leukemia and was treated on our study in the frontline setting. She achieved response initially, but then she subsequently relapsed during consolidation. Then she was treated on the ziftomenib in the Ven/Aza cohort in the same trial, and she was actually able to achieve remission, which was MRD negative, and she was able to proceed to transplant. And then lastly, in the next slide, you'll see the last case study that we are going to share with you today is a specific activity of ziftomenib in extramedullary disease, which, you know, was described by the investigator when ziftomenib was started after azacitidine, as you can see in the timeline of the treatment of this patient, that the extramedullary disease melted within two days of starting ziftomenib. And again, this is particularly impressive when you look at the previous lines of therapy that this patient has seen. This patient has seen intensive chemotherapy, venetoclax, DLI transplant. So this is, again, I think, super impressive to see the response of the extramedullary disease, but this patient also went on to achieve complete response with partial count recovery, CRh, and then to transplant. So in my opinion, this is an early cut of data, first 20 patients. There are still many more patients to be enrolled in the trial and much longer follow-up to be done, but we are extremely pleased to see the safety data and the preliminary efficacy data, and we look forward to continue to enroll patients and explore the full potential of ziftomenib, as in my opinion, best-in-class menin inhibitor that will likely change the way we treat AML in the coming years. Thank you so much. Thank you so much, Dr. Zeidan. If we can proceed to slide 27, I will walk through the clinical development plan we currently have ongoing for ziftomenib. Based on the safety, the tolerability, the clinical activity, and the combinability we've seen with zifto so far, we want to make sure that zifto is the market leader across combination partners and across lines of therapy. We're broadly addressing combinations to set the foundation for zifto as the backbone for menin-dependent leukemias. And to that end, we continue to enroll our monotherapy trial that's in the registration-directed portion, as described by Dr. Fathi. It is enrolling quickly, and we do expect it to complete enrollment in the middle of this year. Within the same trial, we have opened several substudies to look at other, menin-independent leukemias, the non-NPM1, non-KMT2A, rearranged leukemias that would also be able to benefit from ziftomenib therapy, as well as a KMT2A rearranged ALL substudy within the same trial. As Dr. Zeidan described, we have our ongoing combination trials with, Ven/Aza, currently in the relapsed/refractory setting and moving into the frontline setting once we complete the phase I-A. They are enrolling quickly, and again, we are already in the 400 mg cohort. The combination with 7+3 is also enrolling quite well, and we will be moving out of the adverse risk portion of the cohorts when we complete the phase I-A as well. Our 008 trial, our combination with gilteritinib, FLAG-IDA, or low-dose Ara-C, is currently open and preparing for enrollment, and our post-transplant maintenance trial is also planning to initiate and enroll the first patients this year. We have our pediatric programs that have initiated and are enrolling both in the AML and ALL subsets and are also doing well and should be enrolling this year additionally. With that, I'll pass it back to Troy. Thank you, Mollie. Just now turning to slide 29. So as you've heard from the four physicians here on the phone, we think there's really tremendous promise for ziftomenib and other menin inhibitors to transform the standard of care, not only in acute leukemia, but potentially in other serious diseases. We really see it now as a multiplayer, multibillion-dollar market opportunity. And here we're taking, you know, three approaches simultaneously. The first, of course, is to continue to execute against our monotherapy study, KOMET-001, where we've guided that we should have full enrollment by the middle of the year. That will give us, give ziftomenib access to potentially 30% of the patient population. Beyond that, as you've heard, we're quite excited to continue to move ziftomenib aggressively, both into the frontline and the maintenance. These are large, these are much larger patient populations and large commercial opportunity. Together, they have the potential to drive greater than 50% of the worldwide revenue. And as you've heard throughout this call, we really think ziftomenib is well-positioned. It has the ideal safety, tolerability, absence of drug-drug interactions, combinability to really position it as the market leader. And then later this year, hopefully we'll have a chance to share with you some of the work that we're doing in additional opportunities beyond AML, that we think also support additional multibillion-dollar potential. We have translational data that supports the application of menin inhibitors in solid tumors, as well as in non-oncology indications. We look forward to sharing that with you in the coming months. Turning finally to slide 30, just to lay out the upcoming milestones for our acute leukemia program with ziftomenib. As Mollie indicated there, the first three lines, we're intending to dose our first patients in the KOMET-008 study. This is the combination now continuing to expand the footprint for ziftomenib to include combinations with the FLT3 inhibitor, gilteritinib, low-dose Ara-C, and FLAG-IDA. We're intending to initiate our post-transplant maintenance program and expand the development of ziftomenib into acute lymphoblastic leukemia. We anticipate that each of these should be achieved this quarter. As I've indicated, we're expecting full enrollment in our KOMET-001 study by the middle of the year. Turning back to KOMET-007, which has been the focus of this call, we're looking forward to determining a recommended phase II dose for ziftomenib in combination with venetoclax and azacitidine, and once we have that, to initiating dose validation or expansion cohorts with Ven/Aza in frontline patients, frontline AML patients. And then in that context, we're looking forward to providing a next update for the KOMET-007 program. At this point, we haven't decided. It may be a medical meeting, it may be another company update. The next critical value inflection point will be achievement of the RP2D. We look forward to sharing more updates on this program with you. We want to thank the generous support of our investors. We're fortunate to have $570 million now in pro cash, which gives us runway into 2027 and enables us to invest aggressively in research, development, and pre-commercial activities to maximize not only the value of ziftomenib, but as well as the other assets in our pipeline. So with that, that ends our prepared remarks. Happy to take a moment, and then we'll open it up for Q&A. As a reminder, if you would like to ask a question, please press star one on your telephone keypad. We also ask that you limit yourself to one question and one follow-up. Your first question comes from the line of Jonathan Chang from Leerink Partners. Please go ahead. Your line is open. Good morning. Congrats on the data, and thanks for taking my questions. First question for the management team: What is your current thinking on how big the opportunity is for this class of drugs following the initial menin combination data from both you guys and others in the space? Second question for the investigators on the call: What would you say are the key differences between ziftomenib and other menin inhibitors in development, if any? And I guess if I can just sneak in a clarification question. Can you provide any additional color on the patients with prior menin inhibitor experience? Were these patients refractory to the prior menin inhibitor? Thank you. Sure. So Jonathan, I'm actually gonna take your questions out of order. Understanding that it's enticing to speak to the patients who failed prior menin inhibitors, we're gonna save that for a future update. There, that's an evolving story, and as Dr. Zeidan indicated, we're continuing to both follow these patients and pursue dose escalation. So we're not gonna get into what's beyond the slides. But turning back to the other two questions, you know, depending on how you run the models, the opportunity in leukemia alone, we think could be, you know, in excess of $2 billion-$3 billion for ziftomenib. And that takes into account, you know, up to 50% of patients in the front line, getting a majority of patients back on drug post-transplant, having, you know, long-term therapy in the maintenance setting. But as I indicated, I think, you know, a number of the players in the menin inhibitor space are all kind of coming to a consensus that this is likely to be a multibillion-dollar opportunity. How large could it become? You know, one, one doesn't know. I think the more we continue to see good data, good responses, good combinability, that's why I think, as Dr. Zeidan highlighted, the, the myeloma opportunity is such a telling one. Because it, if you look back in history, that's very much what we've seen there, with a steady progression of, of various combinations pushing out the standard of care. There are, Jonathan, just to add to that, other opportunities that we'll talk to. You know, we're just giving you a teaser now, but we'll look forward to sharing, as we've said, additional data and development plans and additional indications beyond the acute leukemias later this year. With respect to your question on the differentiation from between ziftomenib and other menin inhibitors, Dr. Zeidan, perhaps you could comment on Jonathan's question on that one. Yeah, of course. No, I think I completely agree with you. Clearly, at this point, the data continues to evolve in the combination setting. I mean, to me, it's clear that both drugs, or, you know, the drugs that are being kind of studied, several of them seem to lead to clinical responses, and I think eventually it's gonna come also, both in terms of the efficacy and the safety of these drugs. And I think one major difference, in my opinion, is the QTc issue, because I think, as Dr. Fathi mentioned during the call, I don't think in setting where we use many other drugs that are QTc prolonging. Such as IDH during the management of those patients, this can be a major headache. So I think that is, I think, a major differentiation of ziftomenib over other drugs. I think the other thing, in terms of the efficacy, in particular, in NPM1-mutated disease, I do think that the data seems to favor ziftomenib. It's really tough to kind of make, you know, a big kind of differential statement at this point, given where the drug development is in. But in my opinion, it would not be a bad thing for the field to have multiple active drugs, because this is, I think, how things generally move in a much more efficient way. So we would be happy to have multiple active agents. Thank you. Your next question comes from the line of Jason Zemansky from Bank of America. Please go ahead. Your line is open. Perfect. Thank you. Appreciate you taking the question, and congrats on the data. I wanted to circle back on the responses in the menin inhibitor-inexperienced patients, which arguably made up a solid portion of our cohort. Redosing has kind of been an open question in the field, especially when considering the opportunities in moving, say, from first line to post-transplant maintenance. I was curious what you thought the current potential looked like in terms of responses, and do you think the follow-up response is it independent of which menin inhibitor was initially used? Jason, it's a good question. I'm gonna take this one. Again, probably more to say about that later in the year. It's an evolving story. We have seen patients come in from the Syndax trial, the J&J trial, as well as ours. It's just early days, and as Dr. Zeidan indicated, you know, we're still learning about exactly what's needed in menin-experienced patients as to what to do. So I think it's something to look forward to for a future update. The data thus far is encouraging, but we're gonna save that for an update later in the year. Great. Thanks for the color. Our pleasure. Thank you. Your next question comes from the line of Roger Song from Jefferies. Please go ahead. Your line is open. Great. Congrats for the data. It's great, kind of to see another menin inhibitor updates in the field. So a few quick questions from us. One is for the first line. Can you comment on the enrollment? Seems a little bit slower compared to the R/R cohort. Is that due to you exclusively enroll those patients with high risk? And also, you know, just the second part of this, you know, my question is how you will move into the all-comer first line for 7+3. And curious to why FDA are requiring you to enroll high-risk first line only in your first dose escalation, and then I have a follow-up. Thank you. Sure, Roger. So the first I'm gonna ask Mollie to speak to your first two questions, which are enrollment in the frontline setting, and then the requirement for, you know, for starting in more challenging patients before we move into the broader population. Mollie, if you could. Sure. And keep in mind that enrollment comes in waves, so while in the first 20 patients, maybe there was a bigger wave of relapsed refractory, that does tend to even out over time. But it is more challenging to enroll the high-risk patients, but having to narrow down the NPM1 mutants in particular is difficult. Having to get patients in the KMT2A setting who have such aggressive disease, it's a challenge to make sure that we get them treated in time within the context of a study. Many just start backbone therapies outside of the context of a study. And why high risk? It's such a good therapy, a well-established therapy, that FDA always wants to make sure that you are not causing additional harm to patients before opening it up to the broadest patient population. So starting in the adverse risk patients, patients that probably would benefit most from additional therapies, from study participation, the FDA tends to push you into testing it there, make sure you're not having additive tox or having any, detrimental effect on the efficacy rates that are usually seen, and then you can open it up into a broader patient population. We're pretty confident already that we are not seeing any reason that we won't be able to open it up to that broader patient population in the phase I-B. Thanks, Mollie. Roger, did you have a third question? Yes, just a very quick one for the R/R cohort. So understanding you want to save the response or the activity for the patient with prior menin. And can you comment on the patient, the nature of the response for those patients with prior venetoclax or Ven/Aza? Because, you know, maybe we have different expectations for those rechallenging Ven/Aza due to following the previous Ven/Aza response. Thank you. Sure. Dr. Zeidan, could I ask you to comment on, on Roger's third question about the nature of the response in venetoclax-experienced patients? Yeah, absolutely. So as I mentioned during the call, there were 10 of those patients out of the 15 who were in the relapsed/refractory setting, and out of those, five of them were NPM1-mutated, and the other five were KMT2A-rearranged. And the overall response was around 40%. Most of those 60% were in the NPM1-mutated, and the rate, yeah, three out of the five basically achieved an overall response rate. And importantly, this is very important to remember that two of those had CR or CRh, right? Because, you know, when people present in trials, sometimes they mix the morphologic leukemia-free state or things where you don't have count recovery. But this is two out of five patients with Ven/Aza-exposed NPM1-mutated patients who achieved CR or CRh. One out of five achieved CR/CRh in the KMT2A rearrangement. Now, those numbers might, you know, look on the lower end for someone who doesn't treat leukemia clinically, but what I can tell you is that azacitidine/venetoclax failure is the most horrendous setting, in my opinion, in patients with a refractory relapse setting. Those patients do extremely poorly. The literature suggests a survival rate, you know, of 2-2.4 months. The response rate, as we cited on the call, generally is very low. There isn't generally active agents in that setting, unless they happen to have an IDH or a FLT3 mutation or something like this. And even in those settings, the responses are generally not lasting. So I think we need to get big, you know, larger numbers and longer follow-up to understand the rate of response as well as the durability of response and clearly some sense of the overall survival. But what I'm seeing, based on my own experience, compared to what we use in the kind of standard of care setting where, you know, we try whatever we can or in, you know, an investigation setting, I think to my eye, the data is very compelling at this early cutoff. That's great. Thank you. Dr. Fathi, is there anything you want to add on Roger's question about the challenges with Ven/Aza experienced patients? I don't really have that much more to add. I think, you know, overall, it's very early. I think just broadly speaking, there are certain patient populations that are very challenging. And among these is that group that's been previously exposed to venetoclax. In, you know, in our hands, with standard conventional treatments, there isn't much that we can offer them, and most of the treatments that follow venetoclax have not historically been shown to be particularly effective in prolonging a durability of response. So if you have a drug or an agent that allows you to salvage patients, I think that is something that will be very welcome in our field. Thank you very much. Your next question comes from the line of Li Watsek from Cantor Fitzgerald. Please go ahead. Your line is open. Hey, good morning. Congrats on the data. A couple questions from us. I guess first, can you comment a little bit on, you know, myelosuppression, especially in Ven/Aza regimen? And since it's a, it's a combination and my understanding is, you know, the disease may have some contribution here as well. So just curious, what are the sort of the key metrics you look at to tease out the ziftomenib contribution? And then just curious about your thoughts on whether this may be a class effect or not. And the second question, maybe just make a comment on any, you know, dose disruption or reduction during the trial. Sure. Thanks, Li, for the question. So, Dr. Fathi, maybe I can start with you. If you could comment on Li's questions around, you know, the potential for myelosuppression and, and, what we've seen with ziftomenib, and then I'll ask Dr. Zeidan to also add his thoughts. But let's start with you first. Sure. And as I mentioned earlier, you know, one of the common challenges that we oftentimes have with treatments that we study and employ in AML and other marrow-based malignancies is the effect on the normal healthy progenitors themselves. And you know, treatments that we use in this space can cause substantial cytopenias, whether it's traditional cytotoxic chemotherapy, venetoclax in combination with azacitidine or decitabine. Anything that we've used historically to treat AML, at least for the first few weeks of treatment, and then subsequently with every cycle, leads to substantial marrow suppression. And every few weeks, you have to kind of hold your breath as patients drop their counts and hope that you don't get into trouble with infectious and bleeding complications. With various drugs that have been studied in clinical trials, that has also been a recurring problem, sometimes more so, sometimes less so. So I think if you have agents that over time, especially as patients achieve their ultimate response, do not lead to this, yo-yo effect of recurrent episodes of cytopenias that cycle and put patients at risk repeatedly, that is something that is, that is very welcome, and this is something that we're now seeing with some of the targeted agents that have become available. You know, IDH inhibitors, for example, are an example. Once patients achieve a response, oftentimes on IDH inhibitors, there is not this worry of recurrence of suppression of blood counts over time so that they can tolerate and benefit from it, longitudinally in a durable way. I think the data we have, at least so far from the monotherapy experience that I shared earlier, is that the patients that achieved response on that study remained in remission with very good, acceptable blood counts that did not suggest a substantial marrow suppressive effect from this menin inhibitor. I think that is an important observation. Great. Thank you. Dr. Zeidan, do you want to add your thoughts on, you know, the presence or absence of myelosuppression and any if anything if ziftomenib is contributing at all to that, to add to Dr. Fathi's comments? No, I largely agree with what Amir mentioned. I think myelosuppression clearly is a major headache that we have when we combine many of, you know, other drugs with Ven/Aza or with 7+3. Many times it's quite apparent that, you know, when you add a drug, it's, you know, causing myelosuppression. Here, my sense is that we are not seeing additional myelosuppression. This is a relatively smaller cohort with, you know, an early cutoff of 20 patients and different combinations. Ultimately, clearly, you need randomized data to answer this question definitively. But my sense is that we have not been seeing additional myelosuppression as we showed in the data, and we are able to continuously administer the drug through the different phases of the disease, induction, consolidation. Some patients are proceeding to maintenance. So I think this is certainly a setting where, you know, there is no major concern on that area. And kind of to actually allude to the earlier question that was asked, you know, about moving this to more of the non-adverse risk and even to the frontline treated patients, I personally think the safety data is very compelling to move this to more, not like more all NPM1-mutated patients. And I think there is no concern on efficacy compromise. It's actually, you know, quite effective, in my opinion, in the favorable-risk patients treated in the frontline setting. So I do hope we would be able to get the protocol to enroll in the non-adverse-risk NPM1-mutated frontline intensive treatment as well as the frontline Ven/Aza. And I think this is a huge potential for ziftomenib. Thank you, Dr. Zeidan. And Li, with respect to your third question about discontinuations or reductions, I'm going to ask, Mollie if she could speak to that because she looks across the entire study. So we are not seeing any patterns of discontinuations or interruptions. We don't have any patients that have required a dose interruption of ziftomenib to allow for count recoveries, even if they do have a dose interruption of the backbone therapy, which is a usual practice to allow for count recoveries. So really, no need for dose interruptions or discontinuations. Great. And to Dr. Zeidan's comment, Mollie, can you just speak to the audience about what's needed from an FDA interaction standpoint to be able to go to the front line and relax those initial restrictions? Sure. Fortunately, we negotiated with FDA that we would not need to return to have a discussion with them surrounding the ability to go into a broader patient population within the phase I-B. We have an independent data monitoring committee, as well as a safety monitoring committee, that are going to be reviewing the data on a regular basis and at the time it's appropriate to move into the phase I-B, and they will be able to approve the ability to move into the phase I-B and into a bit broader patient populations at that time. Thank you. Go to the next question. Your next question comes from the line of Peter Lawson from Barclays. Please go ahead. Your line is open. Great, thanks. Thanks for the update and all the insights from the clinicians. Troy, I've got a couple of questions for the team, just on the expansion beyond NPM1 and KMT2A in AML, and if you could elaborate on those additional subgroups in heme and kind of what adds to the confidence about such a move. And then second question is around the data that we see later this year in solid tumors and non-oncology indications. Is that preclinical, clinical, et cetera, degree? Sure. Thanks. Thanks, Peter. Let me ask Mollie if she can speak to our development plans beyond the NPM1 and the KMT2A patient subsets. So there is data that exists that shows about 50% of patients have some form of menin dependence to their disease, and that's based upon their HOXA9/MEIS1 expression. We obviously know that about 35% of those are the KMT2A and NPM1 patient populations, and we think we have a good idea who the additional 15% are. So we're using that knowledge and that additional data that we've generated and we've gathered from other sources in order to feed into our now non-NPM1, non-KMT2A cohort that is opened within the 001 again. And once we are finished doing some additional work around that, making sure that we are able to proactively identify, we'll move those into the combination setting as well and really go for a full menin-dependent leukemia population. Great. Thank you, Mollie. And Peter, with respect to your second question, not much more we can say at this point other than to allude to the fact that we think there are potentially multiple solid tumor opportunities as well as non-oncology opportunities. As the audience may know, we have a next generation menin inhibitor program with multiple compounds kind of working through the system. We'll give an update on those efforts, as well as our thoughts and plans and strategies to expand beyond acute leukemia a bit later in the year. At this point, today and for this discussion, we want to keep the focus very much on acute leukemia, on the KOMET-007 data, but we look forward to sharing all of that with you and the others, you know, in due time. Gotcha. Thank you so much. Sure. Your next question comes from the line of Brad Canino from Stifel. Please go ahead. Your line is open. Hi, thank you. There's been a lot of prior talk on the myelosuppression, and when I look at the relapsed/refractory patient anecdotes, I do see consistent dosing of ziftomenib, but dose holds for ven. So to the company, can you report the rates of ven dose reductions in interruptions for those 15 Ven/Aza patients? And then to the physicians, can you provide context about the implications of dosing ven not consistently to the labeled 28-day cycles? Is this a concern or no? Thank you. And then I do have a follow-up. Sure. Brad, I'm gonna ask Mollie to speak to your question about the ven dosing. Yeah. With regards to the interruptions, yes, frequently we do see the patients go off their venetoclax and azacitidine at the time of their first clearing of bone marrow, and we do the first bone marrow around day 21 of their first cycle. Then, as usually institutional practice, often at that point, when you're showing a clearance of the leukemia, you also relax the ven to allow them to have a count recovery. But I'm sure that Dr. Zeidan or Dr. Fathi could comment more completely upon their personal practices with regards to interrupting at that time. Dr. Zeidan, would you like to pick up on Mollie's invitation and talk at all about how you would interrupt Ven/Aza or Ven? Yeah. Yeah, what I would do is exactly what Mollie described. This is our practice in my institution, and I would say having, you know, discussed with many colleagues across the world, most people will not even deliver 28 days in most patients with AML. I think most of us think that is actually more ven than you need, and most patients in my practice, even with Ven/Aza alone, without any treatment, wind up on less than 28 days of venetoclax with continuous therapy. Usually more around 14 days is, I think, where most people land. And we actually, there's a lot of accumulating data that this does not compromise outcome. Actually, on the contrary, it might help the patients by reducing myelosuppression, which could lead to major infection and bleeding. So I don't have any concern on that front. My own sense is that we are not needing to interrupt venetoclax more by adding the ziftomenib, but as I mentioned, this is a pretty common practice, and our sense in general is that does not compromise the activity of venetoclax. Okay. Helpful context. Thanks. And then lastly, Troy, if I could ask, how do you think about this update showing DS mitigation in the context of the enrolled patient population? You've got four of the nine KMT2A patients having received prior menin, and it's not clear from your data there would be mechanistic differentiation occurring in those four patients. Thank you. So, Brad, I actually disagree with you. I mean, I'm the only doctor on this call who's not actually a doctor, but these patients have active disease, so you absolutely would expect differentiation syndrome. You know, just, just to set everybody's expectation, I mean, we're thrilled that there's zero events of DS. You know, is that going to continue for all time? No, likely not, right? These are differentiating agents. We will see differentiation syndrome. I think what this, what this update shows, as we've been saying for the last, I don't know, since we reported our initial monotherapy data, is that the best way to mitigate the DS is to give this drug in combination, and that's exactly what you see. You know, with an extremely potent differentiating agent like ziftomenib, are you going to see, you know, differentiation? Yes, and I think we expect to see it. But in our minds, this sort of puts to rest the question of whether we can, A, manage the differentiation syndrome, and B, you know, allow ziftomenib to begin to exert its therapeutic activity. I'll just remind everyone, there was no difference in DS. There's no dose relationship between 200 mg and 600 mg in the monotherapy, but there's a pretty significant difference in efficacy between 200 mg and 600 mg. So I think this sets us up well as we continue to study. And as you know, several of the speakers have indicated, actively enrolling the 400 mg cohorts with ven and look forward to sharing that data at a future update. Thank you. Go to the next. Sure. Your next question comes from the line of Eva Privitera from TD Cowen. Please go ahead. Your line is open. Thanks. Congrats on the data, and thank you for taking our questions. Couple from us. What was the median follow-up, and can you comment on the MRD negativity rates achieved in the patients? I'm going to thank Eva for the questions. I'm going to let Mollie comment on them, on both of them. Yeah, we haven't officially shared the median follow-up, but just to give you a sense, we started enrolling in July. These patients were all enrolled by the beginning of November. If that gives you a sense of the number of months that these patients were on trial at the time of this data cut. Then with regards- MRD. -to the MRD, we are still in the process. Most of these patients have had their MRD reported from local testing, so it's a hodgepodge of testing between flow and NGS, et cetera. We are in the process of doing more centralized testing to get more uniform testing, and of course, that will be part of our ongoing analysis. Great, thanks. And a follow-up, how many patients have gone on to ziftomenib maintenance? And maybe for the investigators, what percentage of patients do you expect to be put on ziftomenib maintenance, and how do you make that determination? Yes. So, Eva, we haven't disclosed how many patients have gone on to maintenance other than the three anecdotal case studies that Dr. Zeidan walked you through. I'll let Dr. Zeidan and Dr. Fathi speak to how they would view using ziftomenib in the maintenance setting. But we haven't disclosed that data. That'll obviously be part of a future update. But Dr. Zeidan, do you want to start and maybe speak to how you think about ziftomenib in your post-transplant maintenance setting? Yeah, absolutely. So I think, you know, there is a very clear kind of understanding that the most common reason why patients with acute leukemia do not respond to treatments is because they relapse. So many patients will initially enroll and respond in the frontline setting, but then they would relapse. Even the ones who have the more favorable subsets, such as NPM1, the most common reason why those patients, unfortunately, would die is the relapse of their leukemia. So I think there is a sense that maintenance is certainly something that should be explored with different drugs. Currently, there is only one drug that kind of approved for maintenance, which is oral azacitidine, and then there are other drugs that are commonly used, which are FLT3 inhibitors, in kind of, again, depending on whether it's post-transplant or post-consolidation chemo. But my own preference, clearly, is to explore every drug in the maintenance setting because we do think that the main reason of failure of treatment in the long run is going to be leukemia coming back. So I think, you know, on this trial, I personally, whenever I have the option, I will advocate for maintenance treatment for my patients. Eventually, the question will need to be answered in much bigger studies, ideally randomized setting studies, but I do think the concept of maintenance is very important in my own opinion. Thank you so much. Thank you. Dr. Fathi, can I ask you to, if there's anything you'd like to add to that? Sure. There isn't much. The only aspect I fully agree with Dr. Zeidan here. You know, I get why folks are curious and interested in the maintenance question. And it is an important question, but ultimately, that question has to be answered with clinical trials that are focused on the question, you know? So whether, and this is just my opinion, whether a handful of patients or a few patients ultimately receive maintenance on various clinical trials that are not aimed and structured and powered to answer that question, probably does not matter as much as robust data that emerges from actual studies that are powered and structured and designed to answer whether maintenance will improve survival and decrease relapse. So I think we just have to wait and be patient and allow that those trials to be done and that data to emerge. Thank you. Let's go to the next question. Your next question comes from the line of Justin Zelin from BTIG. Please go ahead. Your line is open. Thanks. Congrats on the data, and thanks for taking my questions. Troy, I think you answered it in the, in the prior question, but I was just wondering if you could give us any color on the use of transplantation in the study, roughly how many patients went on to a stem cell transplant post-ziftomenib? And the second question I had was, given the data looks quite compelling, what will you be looking for in choosing a recommended phase II dose? Sure. So, we haven't disclosed, Justin, you know, the number of patients who've gone on to transplant. Again, this is, you know, this is an early cut of the data, promising. We'll share that in a future update. Let me ask, Mollie and then maybe Stephen to comment on what it is we'll be looking for in terms of, selection of a recommended phase II dose. Mollie, do you want to start? Sure. We've designed this trial to be incredibly thorough with regards to a recommended phase II dose, almost holding ourselves to the Project Optimus standards without being asked to. So we will be looking at all potential factors involved, especially the safety and tolerability, the combinability, the clinical efficacy, and also the exposure responses. So we do plan on really doing a very similar analysis that would be done as a monotherapy RP2D dose selection, but carrying it over into the combination setting to make sure we're really robustly assessed. Great. Stephen, anything you'd add to that? Thanks, Troy. Thanks for the question, Justin. I think Mollie's covered it. In short, we want to assess the benefit risk of where we are at a given dose. Mollie's very nicely articulated some of the parameters that we're looking at. Exposure is one of those. We need to see if there's a dose-related increase in exposure and where the plateau is. So when we talk about PK from a PD point of view, that is extrapolation that goes into determining a dose. So benefit risk, looking at the PK and PD and exposure response. Great. Should we go to the next question? Your next question comes from the line of Reni Benjamin from JMP Securities. Please go ahead. Your line is open. Hey, thanks for taking the questions, and congratulations on the update. You know, Troy, can you talk maybe a little bit about the longest duration of response that you've seen to date? And I guess, you know, maybe for the physicians as well, you know, do we not, like, care about duration of response, and it's all about getting these relapsed refractory patients, you know, to a transplant? And I guess, the final question is, you know, for the physicians, what factors do you consider as you evaluate. Let's just say there's two or three menin inhibitors that are on the market. You know, how would you go about, you know, picking one over the other? I guess another way of asking this is, why would you pick another menin inhibitor over ziftomenib? Do you think there'll be a difference between the prescription habits of academic docs versus community docs? Sure. So, Ren, on your first question, I mean, to my knowledge, and I'm looking to Mollie, I think the longest patient we've had on study is a patient who went 36 cycles in the phase I study, having failed seven or eight prior lines of therapy. I think that was notable both because, you know, there was no safety or tolerability signals, and ultimately, she didn't die of leukemia. She died of the complications, we think, of her prior therapies. Which is really, you know, such a benefit we would like to offer patients, that ultimately, if and when they do pass away, it's, you know, it's not due to the leukemia. I don't know whether Dr. Zeidan or Dr. Fathi, Ren will take up your question on, you know, the competitive landscape, but Dr. Zeidan, I'll ask you if there's anything you can comment on, you know, how you would, you know, consider different menin agents to Ren's question. Yeah, I, I think I kind of answered a similar question earlier on. I, I think, you know, it's a combination of the safety, the data, how easy it is to give and whether there's a clear differential in efficacy between, the drugs. And I think this is something that, is tough to kind of know without, you know, comparative, trials. You are trying to extend indirect comparison between, you know, different phase I, II, studies. So, my sense is that, several drugs appear to be active, and, you know, I, I think the QTc is, you know, I think a major differentiator, for ziftomenib. I think in terms of the efficacy, the NPM1 data for ziftomenib has been quite compelling, in the monotherapy and what we are seeing so far, I think in the combination setting is quite good. But we, we clearly need, need to see more data, and eventually, as I mentioned also, having multiple agents actually approved is, is a good thing for patients and for us, allows bigger studies, multiple studies, and to build up on this total therapy approach that, Stephen Dale nicely, you know, outlined in his, kind of comparison to APL and, multiple myeloma with all the differences between these diseases. Thank you. Thank you. Our last question- We'll go to the last question. Yeah. Thank you. Our last question comes from the line of Mara Goldstein from Mizuho. Please go ahead. Your line is open. Thanks very much for taking the question. I know these numbers are small, but I'm curious about the experience of patients who had prior stem cell transplant and they were lasting, remitting population for the Ven/Aza combination and what you're seeing post-treatment there for those patients that have had prior stem cell transplant. Yeah, maybe I'll ask Mollie. Mollie, can you speak to that? Yeah. Just, in very general terms, we've certainly seen, as you saw, a good proportion of our patients that have had prior stem cell transplants. We've not seen a difference in being able to get a patient to a response that has or has not had a transplant, and we've actually had some patients with prior transplants now go on to yet another transplant, post ziftomenib therapy. Okay. And if I could just follow up. Again, I know these numbers are small, but in the Ven/Aza population, there was a one-patient drop-off from CR/CRi to CR/CRh, and I'm wondering if the, maybe the doctors can speak to the significance of that. Mollie, do you wanna wanna speak to that? Yeah. So we're certainly seeing an evolution of response as well within these patients. But obviously, the count recoveries appear to be, able to occur quite quickly and quite, consistently. Sometimes you see a difference between the type of response, the CRi versus the CRh, just based upon when they start on to their next cycle. So patients might not wait for a full count to recovery to a CRh before they are initiating their next cycle, because in clinical practice, that just wouldn't make sense to them if they're continuing to try to control the leukemia. Okay. Thanks very much. Appreciate it. We have no further- My pleasure. We have no further questions in our queue at this time. I will now turn the call back over to Troy Wilson for closing remarks. Great. Thank you, Kristen, and thank you all for attending our call. Hopefully, you found it informative. We'll look forward to seeing a number of you here in the coming weeks and providing the next update on our upcoming earnings call. Thanks again, and with that, we'll sign off and wish you all a good day. This concludes today's conference call. Thank you for your participation, and you may now disconnect.