Good day, everyone. My name's Stefan, and I'll be your conference operator today. At this time, I'd like to welcome you to Kura Oncology's Investor Call to discuss the long-term results of ziftomenib and 7+3 in newly diagnosed AML. All lines have been placed on mute to prevent any background noise. After the speaker's remarks, there'll be a question and answer session. If you would like to ask a question during this time, if you've joined via the webinar, please use the raised hand icon, which can be found at the bottom of your webinar application. To allow everyone the opportunity to participate, we ask that you please limit yourself to one question and one follow-up question. If time permits, at the end of the Q&A session, we'll invite you to rejoin the queue for additional questions. At this time, I'd like to turn the call over to Troy Wilson, President and Chief Executive Officer of Kura Oncology. Please go ahead, Dr. Wilson. Thank you, Stefan. Good morning, everyone. We're coming to you from Stockholm, Sweden, the European Hematology Association meeting, we're delighted to share with you the latest update from our frontline results of ziftomenib with 7+3. If we could please go to the next slide. In today's presentation, we're going to be making forward-looking statements, of course, we'll refer you to our website and the SEC's website for more information about Kura Oncology and the risks and uncertainties of an investment in the company. You can take us to the next slide, please. It was just a couple of weeks ago that we came to you from ASCO, where we brought you an update on our darlifarnib program. We're really at a point now where we're executing across the company. The KOMZIFTI launch is going very well. We have robust new patient starts and early momentum. Today is part of our effort to help provide data and talk about how we think we can advance ziftomenib to achieve our goal of addressing up to 50% of AML patients. This is the next in a number of important readouts around the program. If we can please go to the next slide. I'm joined this morning by two other participants, Dr. Amer Zeidan. Dr. Zeidan is Professor of Medicine at Yale Cancer Center, as well as Dr. Mollie Leoni, who of course, is the Chief Medical Officer of Kura Oncology. We can go to the next slide, please. The agenda for today is Mollie's going to spend just a moment or two on the results that were published in *Blood* on the combination of ziftomenib and venetoclax and azacitidine in the relapsed refractory NPM1 mutant AML setting. Dr. Zeidan will take us through the presentation at EHA, where he'll discuss the long-term results for ziftomenib and the 7+3 combination in the newly diagnosed NPM1 and KMT2A populations. Mollie's going to take over and relate the results from the 007 trial that Dr. Zeidan is discussing to how you should think about our ongoing KOMET-017 study in frontline AML. If we could go to the next slide. With that, I'll turn it over to Mollie. Mollie? Thank you, Troy. Now that ziftomenib or KOMZIFTI is approved as a monotherapy, Kura has been dedicated to generating data in the combination setting. To this end, we have a robust development program that has the ability to benefit patients with menin-dependent AML across the treatment continuum. Next slide. In today's presentation, we will be discussing two important pieces of the continuum, the combination of ziftomenib with venetoclax and azacitidine in a relapsed refractory setting, and a combination of ziftomenib with 7+3 in the frontline setting. Both of these data sets come out of the KOMET-007 trial. The sample sizes have been robust and able to support and inform the KOMET-017 registrational trial that is evaluating ziftomenib in newly diagnosed patients. While frontline data and their applicability in the KOMET-017 trial are a primary focus of today's presentation, we wanted to begin with an important update in relapsed refractory setting. Can we go to the next slide? The important results of ziftomenib in combination with venaza in the relapsed refractory setting have recently been published in "Blood." Moving to the next slide. The results are very important to patients, relapsed refractory NPM1 mutant AML. This study enrolled patients that were heavily pretreated, many of whom had already received venetoclax-based therapies. In the venetoclax experienced patient population, where we would expect minimal patient benefit, we saw a 48% ORR, with 24% achieving a CRc of significant durability. Importantly, we saw in patients that were ven-naïve an 87% ORR, with 70% of patients reaching a CRc with a meaningful duration that appears to have also translated into survival for these patients as the median OS has not been reached. These data are remarkable when we consider the poor ORR and OS expected for these patients. These deep and durable responses exceeding what one would expect with venaza alone in this relapsed refractory setting with a well-tolerated combination regimen speaks volumes with regards to the importance of menin inhibition early in the treatment paradigm. With that, I will pass it over to Dr. Zeidan, who will discuss the data surrounding zifto's use in the frontline setting. Thank you so much, Dr. Leoni. I'm going to be talking about the combination in the frontline setting with ziftomenib. This is a presentation we will be doing in EHA meeting this weekend. Next slide, please. These are my disclosures, including consulting for Kura and Kyowa. As you just heard, ziftomenib is an oral menin inhibitor that is given once a day that has been already approved as a potent selective inhibitor in the relapsed refractory setting for patients who have refractory leukemia, acute myeloid leukemia with NPM1 mutations. At the same time, it has shown promising preclinical activity in combination with standard of care therapies that we have been using for AML for a long time, including intensive chemotherapy with 7+3, and as you just heard, with AZA and VEN. The KOMET-007 has been exploring these combinations in a large ongoing international study that includes dose escalations as well as dose expansions, both in the frontline setting as well as in the refractory relapsed setting for both subsets of leukemias that have been shown to benefit from menin inhibition, primarily NPM1 and KMT2A- rearranged leukemia. Next slide, please. The focus of the presentation in EHA this year is going to be on the frontline combination with intensive chemo 7+3, and this is in patients who are deemed to be fit to receive intensive chemotherapy by their physician. The way the trial was conducted is that we had two separate cohorts, one for NPM1 and one for KMT2A- rearranged leukemias. Both of those underwent a dose escalation, starting with 200 mg, 400 mg and then 600 mg of ziftomenib in combination with 7+3 in the dose escalation phase. That went subsequently into a dose expansion phase using the optimal dose, which was determined to be 600 mg of ziftomenib. And what we are presenting in the meeting is all the patients who have been enrolled on both the dose escalation and the dose expansion parts of the study that have received the optimal dose of 600 mg, which I would note is the dose that's also being tested in the randomized registrational phase III trial that you will hear about later in this meeting. Here you can see the patients who were enrolled in terms of their disposition. We are presenting data in 99 patients, which I believe is the largest experience in the frontline setting reported to date of any menin inhibitor in combination with intensive chemotherapy. 49 patients had NPM1 mutations, and 50 patients had KMT2A translocations. You can see that at the time of this data cutoff, which was April 10, 2026, the median follow-up at that point was 17.6 months for NPM1 and 11 months for KMT2A translocation. At the time of the cutoff, 90% of the patients with the NPM1 and 62% of the patients with KMT2A, patients were still on study, either on treatment phase or in the survival follow-up phase of the study. Next, please. These are the baseline characteristics. I would note for the NPM1 mutation, I think this is important as you interpret the results, that the dose escalation part of this study required patients who had NPM1 mutation to also have what we called factors that make them adverse risk. They had to be either older than 60, or they had what we call therapy-related AML, or they had adverse cytogenetics. All of these predict worse outcomes. Those were the patients who were treated in the dose escalation part. Once we have gone to the dose expansion part of the NPM1 mutation patients, it was open for all newcomers. What this resulted in is that the median age of the patients who had the NPM1 mutations in this study was 60 years old. Half of them were older than 60, basically. While the KMT2A- rearranged patients were slightly younger with a median age of 43. We have slight predominance of females on this. Some of the patients, as you can see here, had co-mutations, as is expected in this setting, including a small number of patients who had FLT3. The FLT3 patients, who had those mutations, were generally considered to be too low to receive in terms of their variant allele frequency, to receive a FLT3 inhibitor or had a FLT3-TKD. Next, please. These are an overview of the side effect profile. What you can see here is the treatment emergent adverse events that occurred in 30% or more of all patients. This does not really add much in terms of the safety, beyond what we have seen in previous presentations from this study. Primarily, most patients will experience treatment emergent adverse events because this is given in combination with intensive chemotherapy, and the safety profile is very well recognized in this setting. I think the primary conclusion from this dataset is that it does not seem that the addition of ziftomenib to 7+3 is causing additional toxicities. What we are primarily seeing here is count suppression in the form of thrombocytopenia, neutropenia, as well as febrile neutropenias, some GI side effects in the form of diarrhea, some pruritus. However, again, all of these are within what you typically expect with no new or unexpected adverse events with the longer-term follow-up of this patient cohort. Next, please. This slide, on the safety front, is looking at the severe treatment emergent adverse events defined as Grade 3 or higher that occurred in at least 10% of patients. Again, the same focus in being count suppression, which is primarily driven by the intensive chemotherapy that's given to those patients, as well as a small incidence of other things such as pruritus and GI side effects. What is important to note is that the treatment adverse events of interest, such as differentiation syndrome and QTc prolongation, occurred in a small number of patients. For example, differentiation syndrome occurred only as a Grade 3 in four patients. There were no Grade 4 or Grade 5. All of these DS events completely resolved with protocol mitigated interventions, and three of them were actually able to continue on ziftomenib therapy. The same thing for QTc prolongation. There were three cases that were Grade 3 that were assessed by the investigators, and there were no Grade 4 or higher, and all of them resolved, and the patients were able to continue on therapy. Next, please. I think here we are seeing, in my opinion, the most impressive data of this presentation in the next two slides, focusing on the responses and the survival data. I'm going to present the data, kind of, looking at each cohort separately because I think there's important differences between these patients that are important to note. I would start by the complete response, which is really understood in the context of intensive chemotherapy to be one of the most important endpoints to achieve in this setting. What you can see in NPM1 mutated patients, out of a relatively large sample size for a phase II trial of 49 patients, we are seeing a stable CR rate of 94%. This number actually, over the previous three presentations we had of this dataset, not only has been in this range, but actually went up, indicating the stability of the CR rate, which again is, I think, one of the highest we have ever seen in the context of intensive chemotherapy for any acute leukemia patient subset. Again, most of those were full CRs, meaning you have complete count recovery. The MRD negativity, which is another indication of the depth of the response, was observed using local assessment in the vast majority of patients. For the NPM1, it was observed in 85%. I will be talking about the central MRD negativity, which is we are presenting for the first time in this presentation in the next slide. I would also observe that the median time to CR MRD negativity was quick at one and a half months. When you look at the KMT2A, again, those patients generally have a more severe disease. They are generally expected to have worse outcomes than the NPM1, and this reflects what we see. At the same time, I think those outcomes compare favorably to what we typically expect with 7+3. For example, the complete response rate was 82%, the composite CR was 90%, again, the CR MRD negative CR was the majority of patients at 86%, and it was observed to occur relatively quickly with a median time to MRD negative CR of 0.9 months. Next, please. Here is the central molecular MRD negativity, this is important because MRD negativity locally has been assessed by different methods, including flow cytometry and genetic studies, but also it was done locally by different centers. Here the advantage is you are using one highly sensitive genetic test that's done in a central lab, giving you, I think, a lot of confidence in the findings. Here what you can see is that the MRD negative composite CR was also quite high, as you can see, and we looked at it at two different thresholds using 1.1%, one in a thousand, which was observed in 79% of patients. Again, this is only in NPM1-mutated patients where MRD negative CR has been really, I think, shown to be a surrogate for long-term outcomes, including EFS and OS. For using the threshold of 0.01%, or one in 10,000, it was observed in 56% of patients. Again, those MRD negativity results were obtained relatively quickly with a median time of around 2.2 months. By the second cycle, by the end of consolidation one, which generally has been considered the most important endpoint time for the MRD negativity, all of those patients who have achieved MRD negativity have already reached it by the end of the second cycle of intensive chemo, which is usually the end of the first cycle of consolidation therapy. Next, please. Concurrent with the safety profile that I think was impressive and the fact that we think one of the problems of adding drugs to intensive chemotherapy in general has been the concern about additional myelosuppression, which can translate into adverse events. I think one of the most reassuring aspects of this particular combination is that it does not seem to add additional myelosuppression. This is here reflected by the time to count recovery with a neutrophil count of more than one and a platelet count of more than 100, which constitute the CR. You can see that the median time to count recovery for both was around 28 days, which is what we generally see with 7+3 itself. That suggested that the myelosuppression is not being worsened by the addition of ziftomenib to intensive chemotherapy. Next, please. These are swimmer plots that demonstrate the durability of the response. It's not only a very high rate of complete responses, but those CRs appear to be durable, as you can see in this figure. With the median follow-up of 17.6 months, the median duration of the CR, and this is for the NPM1 mutated patient cohort, was not reached. At 12 months, 80% of patients were still in CR. Ten patients underwent a transplant of the NPM1 mutated patients, and most of those patients were able to continue on maintenance, which was allowed on the protocol, in which ziftomenib, again, was started on day eight and was continued throughout. The protocol allowed the patients to go into maintenance either post-transplant, if their physician elected to go to transplant, or after the completion of consolidation chemo. Most patients were able to proceed to the maintenance phase. 31 patients were able to do that. Eight of them were after on-study transplant. Only eight patients discontinued at any point due to relapsed or refractory disease, with a very low rate of discontinuation due to adverse events, only four patients, one of them only was ziftomenib-related. Next, please. In the KMT2A- rearranged leukemia, again, we see here the durability of the responses, noting again that this patient subset have a higher risk disease and generally, not only they have a lower chance of achieving responses with 7+3, but generally their durations are lower. I think when you look at the data in combination with ziftomenib, you can see that these data are exciting. Here, with a median follow-up of 11 months, the median duration of CR was 12 months. Most of those patients have undergone transplant, again, reflecting the belief by the physicians that those patients are at high risk of adverse outcomes and relapse. This is why most of those patients are being geared toward transplant in general, whenever possible. Many of those patients continued on ziftomenib maintenance primarily after the transplant performance. 10 patients discontinued due to relapse or refractory disease and seven due to adverse events. Only two of them were ziftomenib-related. Next, please. I think, in my opinion, this is the most important slide in this presentation. If I was going to show one slide summary of what I think is most exciting, this would be the one. This is what you can see here is the overall survival curve in NPM1-mutated patients. You can see a very nice, almost straight line with the survival. Of course, here, after a median follow-up of 17.6 months, the median overall survival was not reached. At 12 months, the overall survival rate was an impressive 94%. I would add here, one of the things that we also monitor when we give patients intensive chemotherapy is what I call induction mortality or early mortality, which is the chance of dying the first 60 days from complication. This was very low at 2%, which again, is extraordinarily low. Remembering again that this is a large international study. Those patients were treated in many centers. This was not only one highly specialized single center. I think to see such a low induction mortality is quite impressive. The other point I would make also is that those patients, as I mentioned at the beginning, those are older and higher risk than your average patient because of the patients who are included in the dose escalation part of the study, in particular, the median age was 60. When you try to compare historically, generally, in terms of the CR rates, in terms of the durability of the CR, as well as the overall survival rate, I think these numbers compare very favorably. At the same time, this is combined with good safety, where time to count recovery is only 28 days, and the risk of adverse events is generally along the lines of what you expected with 7+3 itself. As you can see, most of those patients are still alive and continued on study, and we will continue to follow these data till maturity, on the longer run. Next, please. These are similar data for the KMT2A- rearranged patient subset. Again, the outcomes here look a little bit worse than the NPM1, but this reflects the higher risk nature of this particular entity of acute leukemia. Still here, with a follow-up of 11 months, the median OS was not reached. 60-day mortality was still good at 4%, and 62% of those patients were still on study, either on the treatment or on the follow-up phase of the study. The 12-month survival was 71%. Next, please. I think in conclusion, in this analysis from the KOMET-001 study, which, as I mentioned at the beginning, I believe to be the largest data set of intensive chemotherapy-treated patients who received it in combination with a menin inhibitor that has been presented to date. The combination was very well-tolerated with a safety profile that is consistent with previous reports and also doesn't seem to be significantly different than 7+3 by itself. In particular, when it comes to lack of additional myelosuppression, quick time to count recovery, and I think the adverse events of special interest, in particular differentiation syndrome, seems to be very largely mitigated. This is one of the advantages of giving a combination of chemotherapy along with the menin inhibitor, not only to enhance the synergistic activity and the efficacy, but also it mitigates the risk of the differentiation syndrome. Beyond the safety, I think the clinical results are extremely exciting, in particular the NPM1 cohort with a CR rate of 94% and a CR that is very durable. The median duration has not been reached, and 80% of those in CR were still in CR at 12 months. The median OS not reached, and OS at 94% for NPM1 patients at 12 months. Similarly for KMT2A, a high rate of complete remission of 82% with a median CR duration and median OS that were not reached. I think all of these data support the ongoing registrational phase III trial, KOMET-017, for the intensive chemotherapy part of it, that combines ziftomenib with 7+3 against the randomization to 7+3 by itself. With that, I think this is the last slide. Thank you. Thank you. Every time I see those data, I get more excited and more confident in our ongoing frontline registrational trial, the KOMET-017 trial. I want to highlight that the experience with KOMET-007 has been able to inform the development of this important registrational KOMET-017 trial. With that, the basics of KOMET-017. The trial was designed to generate clinically and registrationally relevant data for global markets. The trial contains two large, independently, and conservatively powered phase III studies, which have the ability to detect clinically meaningful benefit for patients. We're enrolling across North America, Europe, and Asia Pacific with the intention of generating a geographically diverse data set pertinent to all major commercial markets. However, our trial sites have a limited focus on markets that potentially have significant differences in their treatment paradigm, thus reducing potential risks to KOMET-017 that could manifest via differences in clinical practice or supportive care. This multi-regional clinical site footprint will support commercial readiness by building investigator experience and familiarity globally. Our ultimate goal with the design of KOMET-017 was to optimize for speed, just as importantly, for regulatory and scientific credibility, statistical probability of success, and commercial relevance. KOMET-007 data are instrumental in facilitating this design. If we go to the next slide. First and foremost, the safety and tolerability emerging from the KOMET-007 trial is reassuring for the conduct of KOMET-017. The overall safety profile for ziftomenib in combination with 7+3 is consistent with that seen with the 7+3 backbone. The rate of differentiation syndrome, a known risk when administering a differentiating agent like ziftomenib, is considerably decreased compared with monotherapy rates. The events have been readily resolved with supportive treatment. QT prolongation was seen infrequently in the trial. When events were detected, they each had causes likely unrelated to ziftomenib therapy that were resolved so that treatment could continue. The concurrent use of zifto with 7+3 does not result in delayed count recoveries for these patients. Neutrophils and platelets return to normal ranges within 28 days of treatment initiation, indicating no additive myelosuppression with 7+3. Finally, the addition of zifto to this backbone regimen does not adversely affect induction-related mortality rates. This totality of data from the KOMET-007 trial supports and recommends the ongoing registrational KOMET-017 trial. Going to the next slide. Even more striking is the efficacy we are seeing that more than recommends continued momentum in the KOMET-017. Here I am focusing on the NPM1 mutants solely because they will make up the majority of patients enrolled into the registrational trial. However, as you can see in Dr. Zeidan's presentation, the same apparent benefits and outcome measures are seen with the KMT2A patient population. Starting with the CR rate, we are seeing even our older patients having a 90%-100% complete response rate, far exceeding the expected benchmarks of 56%-88% for this patient population. The 7+3 portion of KOMET-017 was designed to have an accelerated approval endpoint of CR MRD negativity in the bone marrow. The reference for this in NPM1 patients is 44%. We saw 56% of our patients achieve this bone marrow MRD negativity, which again supports the design of KOMET-017. The most important of outcomes is the overall survival. MRD negative CR is expected to predict an improvement in overall survival. Our median OS has not been reached for NPM1 mutant patients, but at 12 months, 94% of the NPM1 mutant patients are alive, in sharp contrast with historical numbers ranging from 45%-80% in these age groups. Again, this supports and recommends continuance of the KOMET-017 registrational trial as designed. If we go to the next slide. What we have seen with the KOMET-007 trial gives us great confidence in KOMET-017. With KOMET-017, we have put additional measures in place. Important among them is central MRD testing. Having a central method in place improves reliability and maintains regulatory standards. With local MRD testing, there are multiple laboratories performing different types of tests with the likelihood of creating site-to-site variability and making comparison difficult. With central MRD, samples are tested at a single lab with the same test, allowing uniform assessment in accordance with regulatory requirements. Moving to the next slide. Assessing the MRD in this uniform way allows us to translate these deep molecular responses we have been seeing into an accelerated path towards value creation in frontline NPM1 AML. As a reminder, MRD negative CR is the co-primary endpoint for accelerated approval in the KOMET-017 trial. As data has grown in the field, MRD negativity has consistently emerged as a predictor of long-term outcomes. The bone marrow MRD negativity we are seeing in 007 compares favorably with historical benchmarks. These data that we believe are predictive of outcomes in O17 are clinically meaningful and appropriate to support FDA accelerated approval. Moving to the next slide. As Dr. Zeidan was referencing, ultimately, it's this slide that tells the story better than any of us actually can. An OS survival curve for AML that extends at this level over a 24-month period. I don't know what other endpoints could actually matter more than that. The median EFS and OS have not been reached. The 12-month OS is superior to 7+3 alone. These data all tell you that menin inhibition is an important part of the treatment paradigm, and that treating early with the combination appears to have a positive benefit/risk balance that we will continue to explore, not only in the relapsed refractory setting, as we showed you in combination with venetoclax, but also for newly diagnosed patients. With that, I will pass it back to Troy. Thank you, Mollie. If we could go to the next slide, please. This is part of our initiative with the launch underway, in the relapsed refractory NPM1 setting. As we've guided, we think that total addressable market opportunity in the U.S. is $350 million-$400 million. As both Dr. Zeidan and Dr. Leoni mentioned, the goal is go earlier, go in combination. You can see that as we work our way up the curve. Ultimately, I think the data support this, we're optimistic that if the KOMET-017 studies are successful, we could be poised to achieve a much more significant U.S. total addressable market of up to $7 billion. I think you can see why we say that now. The goal is to get these patients into response and then keep them on continuation therapy. Many of those NPM1 patients, in fact, did not go to transplant. They're just remaining on ziftomenib cycle after cycle. We go to the next slide, please. Where we are today. Again, a couple of weeks ago, we talked about darlifarnib. This week we're talking about ziftomenib on the left-hand side. The launch is going well. We have robust momentum, gaining market share. We are firmly focused on continuing to advance ziftomenib through a variety of different combinations to address up to the 50% of AML patients that we think could benefit. The 007 results, although they are phase I-B results, we think that they support a best-in-class profile among menin inhibitors and that they continue to de-risk the ongoing phase III registrational studies. Both Dr. Zeidan and Dr. Leoni said it well. The survival data sort of speaks for itself. We're very excited. The enrollment in the O17 studies is going very well. We're hopeful that with this data, it will only accelerate and we remain committed to transforming the standard of care for patients with acute leukemia. Next slide. With that concludes our prepared remarks, and we'll now go to a question and answer session. Stefan? Thank you. We'll now move to our question and answer session. If you have joined via the webinar, please use the raise hand icon, which can be found at the bottom of your webinar application. When you're called upon, please unmute your line and ask your question. We'll now pause for a moment to allow the queue to assemble. Again, we please ask that you limit yourself to one question. You're welcome to reenter the queue for any follow-up questions. Our first question will come from Li Watsek with Cantor Fitzgerald. Please unmute your line and go ahead. Hey, guys. Thank you very much for taking our question. Very impressive OS data. I guess just given impressive durability of the response and OS rate, what is your best estimate for duration of therapy in the frontline setting? Mollie, would you like to I don't know if we can answer that question, but would you like to try? It's certainly still evolving. You can see that it's going to be, at worst, about 24 months, is what it looks like at this point. These patients are, in general, very successful on treatment, getting into a response, and then staying on treatment, with the monotherapy once they're in their response. We don't have the exact answer yet because thankfully for these patients, their treatment is still ongoing and we're still able to follow them to get additional information. Great. Let me just clarify. Those of you who want to ask a question, if you'd like to ask a question and a follow-up question, please feel free. We're going to limit it to just one question and one follow-up, but you're welcome to get back in the queue. Going forward, one and one is fine. Stefan, next question. Our next question will come from Jason Zemansky from Bank of America. Please go ahead. Jason, your line is unmuted. Please go ahead. Okay, we'll move on from Jason in the meantime, we'll move on to Phil Nadeau from TD Cowen. Please unmute your line and go ahead. Good morning. Thanks for taking our question. Congrats on the data. We have a question on the MRD negativity rates. What level of MRD negativity is correlated with survival? Is it the lowest threshold that you presented or the second threshold? Then kind of as a follow-up to that, how is MRD negativity going to be used to decide on the treatment plan for patients? Which patients would go to transplant, which ones would be more minimal to maintenance therapy without transplant? We're curious to hear your thoughts on that. Thanks. Mollie, do you want to start with that? Yeah, sure. We showed you multiple MRD cutoff points because it would allow you to compare to maybe the local values, and that's why we showed you the less sensitive and the more sensitive values. Obviously, the more sensitive you go, the more predictive things generally tend to be. However, more data is going to come out over the next year or so that are going to show you, probably even at less sensitive levels, that the MRD negativity is quite predictive of survival in these patients. I would offer it over to Dr. Zeidan to give his opinion on how this is going to influence treatment in the coming months. Yeah, I agree. I think the more sensitive the test and the deeper the response, we believe is correlating with longer-term outcomes. I think when it comes to how people are influenced, there has been generally with NPM1 kind of AML, a general practice that if the patient is still MRD positive beyond the first consolidation cycle or subsequently turns from negative to positive, the standard approach has been in patients who are otherwise a transplant candidate is to consider transplantation. There is a separate question about whether these patients need to receive a treatment that can convert them to negativity before they proceed to transplant. I think that reflects the field belief and supports the clinical observation that MRD positivity beyond two cycles generally correlates with poor outcomes. I think certainly, this is influenced in terms of how we kind of counsel and treat these patients. Thank you, Phil. Phil, maybe I'll just add a thought or two. We wanted to be really clear and break this down because we see a lot of numbers for MRD negativity getting discussed. The treatment decisions are based on the local values, but ultimately, to support an application for accelerated approval, the FDA requires the central testing with that level of rigor that Mollie described. That's why we're breaking it down for you. Both of them look to be quite clinically meaningful. When one is thinking about are you going to meet the bar for an accelerated approval, you really need to be now talking about the central values. Hopefully that'll provide some clarity as we look at the menin inhibitor field continue to evolve in the front line. Perfect. Thank you. Thank you. Okay, now we'll circle back to Jason Zemansky with Bank of America. Please go ahead. Good morning. Apologies for the technical difficulties. Congrats on the great progress. Thanks for taking our questions. I guess this is somewhat theoretical. Given what you've seen from that Kaplan-Meier curve, how much do you think you could really realistically press the one and five-year survival rates? Is this sufficient to support widespread use? Dr. Zeidan, do you want to speak to that? Yeah. I think we know with acute myeloid leukemia in general is that most patients who relapse generally tend to do so in the first three years, the risk is highest in the first year, it goes down a little bit in the second year, a little bit lower in the third year. We have patients who can still relapse after five years or after three years, the number goes down significantly. Historically, some people used to use five year, I would say three year is a pretty good indicator if the patient is cured or not. I think based on how this curve is looking, we showed the 12-month as a 94%, because of the 17-month median follow-up, after the 12 months, there is some degree of censoring. When you look at the curve, it looks still quite good up to 24 months. My estimation is that if this trend continues, especially those patients are still on ongoing ziftomenib maintenance therapy, my expectation is that this continues. I would add to that, I think Troy touched on this, is in patients who are older than 60, generally, there has been an ongoing discussion in the field about whether those patients should be transplanted, because although they have NPM1, they tend to have worse outcomes, I think it was quite impressive to me the very high rate of CR on this trial, 100%. I mean, you cannot get any better than that with the menin inhibitor combination with 7+3, also the favorable, as you could see, the average survival and the CR rate is much lower in those patients with 7+3 by itself. It's clear to me that Combination is adding benefit in terms of the durability and the overall survival. I think in another year or so, we'll have a much better sense about the durability, all the early indicators are going the right direction, in my assessment. Great. If I could follow up with a quick one, to what extent is this data extrapolatable to the KOMET-007 data, of the venetoclax combination? Mollie, do you want to speak to that? As we've discussed in the past, I believe, we will be showing you an update on the KOMET-007 venetoclax frontline, as well in coming months, because we think it's important for you to be able to see that translatability as well. We have just as much confidence in the venetoclax data as we do in the 7+3 data. This just happened to be more mature and available for sharing. I think you should assume that you're going to see us similarly excited about that data. Yeah. Thanks so much for the color. Sure. Maybe Jason, just one more comment for you and the audience. Before we started these studies, we heard from all quarters, sort of a desire to move from 7+3 to ven/aza. What has been interesting is 7+3 enrollment has remained very robust throughout the phase I and now into the phase III. I think Dr. Zeidan spoke to it. This combination of ziftomenib and 7+3 provides a really compelling option for patients, particularly those who may not need to go to transplant. That's one of the things that has us excited about running the two studies as one protocol in 017. Patients and their physicians can elect intensive chemo, they can elect ven/aza. They have the option to do either. I think, we're confident that each of these two independent cohorts are going to show meaningful clinical benefit for patients. It's great to give those patients options. If we can go to the next question. Thank you. Our next question will come from Salim Syed with Mizuho. Please go ahead. Great. Can you guys hear me okay? We can, Salim. Yeah. Hi. Great. Okay, thanks. Okay. Congrats on the data. Just one for us on the safety side of this, Troy, on the QTc prolongation, I know that it was mentioned as unrelated, but just curious how those patients were managed with Zifto paused in those cases, and similarly on the differentiating syndrome for the four cases. What exactly was the mitigation protocol that was implemented here? Thank you. Sure. Mollie or Dr. Zeidan, whichever one of you wants to take that, leave it to you. I can start, Dr. Zeidan can fill in. For the QTc cases, they were all clearly attributable to other underlying issues, such as concomitant medications or electrolyte imbalances. Once those were corrected or dose adjusted, these patients were able to remain on ziftomenib therapy without any additional issues. The differentiation syndrome, we've developed that method of treatment and intervention over many years now. It does result in an interruption of therapy, although it probably doesn't need to in the combination setting. Again, these were all just Grade 3, easily resolved with supportive care, and these patients were able to continue on treatment. Dr. Zeidan, you Yeah. I'll offer my own also personal experience, as I have treated quite a number of patients on this protocol. I think some of that also speaks to the experience of the investigator in terms of working with these drugs. I think in some sites where there might not necessarily be a lot of familiarity with ziftomenib, sometimes the initial reflex would be to stop the investigational drug when they see QTc prolongation. I think to Mollie's point, and has been my own experience, is that almost always there are other reasons, such as low magnesium, low potassium, we tend to correct these. We often, in the context of intensive chemotherapy, we use a number of other drugs, in particular antibiotics and antifungals and all of these, some of them can have QTc prolongation. I actually always tell my team when we face this situation is that don't stop all drugs at the same time, because this is what usually happens, that they stop the IP and the antibiotics, it becomes tough to exactly know what's causing things. I tend to stop the antibiotic first for two, three days and then see what happens with the QTc. I can tell you when we did that, generally the QTc would have normalized without stopping the ziftomenib. I think sometimes it gets confusing when people stop the drugs at the same time. Again, there were no Grade 4s. For me, since you are able to restart all the patients back on the drug without QTc prolongation, that's also empiric proof that it probably has not been caused by the drug itself. Without dose adjustment. Yeah. Okay. Got it. Thanks so much. Thanks. Our next question will come from Roger Song with Jefferies. Please go ahead. Hey, team. Thanks for taking our questions. Congrats on this impressive survival data. This is Nabeel on for Roger. Just one from us. We did see triplet therapy, at ASCO with gilteritinib, sorry, Quizartinib, necessitating dose reductions. How do you compare your menin inhibitor safety profile with regards to heme tox? Anything else we should keep in mind for combos? Thanks Mollie, you want to take that? Sure, I also am going to ask Dr. Zeidan to comment because he has some very definite feelings on this topic. I think the data shows you itself that we're not adding any hem tox. We don't have to sit there and interrupt our therapy to allow counts to recover. We don't have to change doses to allow counts to recover. When the patients are solely on the ziftomenib therapy after their consolidation, they don't have to have a dose adjustment. They're not having thrombocytopenia or neutropenia issues. We do not believe that we are having any additive myelosuppressive effects with this addition of ziftomenib. Again, I really welcome Dr. Zeidan to comment as well. No, I fully agree with this. Actually, one of the fun things, in my opinion, when you do the randomized phase III trials is when you don't have a very good sense of which patient is getting what, because everybody's recovering very quickly. This is always very exciting. I think in this particular context, as someone who has given 7+3 with FLT3 inhibitors all the time, because these are approved treatments, you could see that the time to count recovery is generally upwards of 35 days before you get the ANC and the platelets. You could easily see that the drug is adding some degree of myelosuppression, which is not the situation with ziftomenib. With ziftomenib, it starts on day eight and actually continues. You don't stop it. I don't know if you are aware of this, but with the FLT3 inhibitors, most of them, they only are given from day eight through day 21. We have to hold them, because if you keep going with them, the patient count recovery will even take longer. Here, you are able to continue throughout without interruptions, and still the patients are recovering within 28 days. I think in my opinion, this is the best empiric proof that you have, in terms of the count recovery. I would add one of the functional consequences of prolonged time to count recovery and additive myelosuppression, why we hate it, is because it leads to infections, bleeding, and inpatient induction mortality. Again, on all of these fronts, the combination is doing very well. To have only 2%, one patient out of 49 in the NPM1 die within the first 60 days. Again, remember, the median age of those patients was 60. Half of your patients were older than 60. To get intensive chemo and only have one death out of 49 and no increased significant risk of severe infections, I think all of this speaks to the lack of additive myelosuppression and the tolerability of the combination. Very informative. Thank you. Our next question will come from Jonathan Chang with Leerink Partners. Please go ahead. Hi, guys. Thanks for taking our question. Dr. Zeidan, can you discuss your experience with ziftomenib in the commercial setting? How are you using the drug currently, and how do these recent results potentially impact that? Yeah. I think the drug certainly has a safety profile that has been very good. Primarily, my use has been in the context of the clinical trial because the drug has just been recently approved, but my own experience has been similar to the clinical trial experience, in particular, in terms of how relatively easy it is to give it as a monotherapy. I would make the point that the patients, after going into the intensive chemo, whether it's in induction and consolidation, they are going to monotherapy on this particular trial in the KOMET-007 trial. This is a setting in which you can really see the isolated part of what is resulting from the drug itself, compared to when you are giving it with 7+3. In that context, I can tell you most of the patients are tolerating it quite well. Not only lack of severe toxicity, but sometimes we see what I call chronic low-grade toxicities that are not severe, but they are taking a toll on the patient life that they have to discontinue. That's not something we see with ziftomenib. Patients are able to continue on it. Again, in the setting of maintenance therapy, where the chronic use is going to be even much longer than the refractory relapse setting, I think this becomes very important. Understood. Thank you. Thank you very much. Our next question will come from Charles Zhu with LifeSci Capital. Please go ahead. Hi, good morning. This is Peter on for Charles. Thinking about the patients who have relapsed on this trial, what therapies are they getting after? Are any of them getting menin now that a couple are approved in these settings? Is there any role for menin inhibitors actually after relapse on frontline menin combinations? Thanks. Mollie or Dr. Zeidan. I don't know if one of you wants to take it. I can say from the overall study perspective, we are certainly tracking that. It's something that we have seen even within the KOMET-007 trial, where we had both frontline and relapse refractory patients. That patients that maybe relapsed after the frontline therapy, even in the same trial, then went on to our relapse refractory venetoclax, which also obviously included a menin inhibitor. I think Dr. Zeidan's experience with his own patients would probably be more pertinent. I would say historically, when you had a patient relapse after 7+3, we historically have used other intensive chemos, such as FLAG-IDA, but once venetoclax became available. Although aza-ven is not approved as a refractory lapsed regimen, it has become very widely used as a salvage regimen after intensive chemotherapy in the case of relapse, in particular for patients with NPM1 or IDH, which are thought to be subsets that are quite sensitive to venetoclax. The practical question became is what do you do with the menin inhibitors in that setting? I think this is where the Blood data that Dr. Leoni showed at the very beginning is very relevant, because right now, if you have a patient who relapses after 7+3, your question is, do I give a menin inhibitor or do I give aza-ven? You can just give all three together, where you are getting, I think, encouraging results, and you can do that indefinitely for patients who are not candidates for transplant, or you can use it as a bridge to get to transplant and then subsequently continue some form of maintenance. Now to the second part of your question, I think about what do you do if the patient has got an menin inhibitor as part of their frontline treatment? This is going to be primarily a clinical trial question, because these drugs are not approved as combination of frontline intensive chemo yet. I think we are going to collect data from this trial and other trials and understand the issue of the sequencing and whether there are certain mutations that are predictive of responses to certain drugs. I think this is something that still needs time to be answered. Excellent. Thank you so much. Thank you very much. Our next question will come from Etzer Darout with Barclays. Please go ahead. Great. Thanks for taking the question. Congrats on this data update. Just given a meaningful proportion of patients proceed to transplant, particularly in KMT2A, how should we think about the relative contribution of ziftomenib versus transplant in driving the durability in OS outcomes you're seeing? Would this be something that the phase III KOMET-017 would allow to isolate to get a better understanding of the contributions? Thank you. Yeah. I actually think you've answered your own question. We don't know for sure exactly what the contribution is with the post-transplant maintenance. If it influences the outcomes, we think it does, but that's what the 017 trial is specifically designed to look at. That's why there are three arms in the trial. You can look at the effects of post-consolidation maintenance as well. You have the one arm of patients who are receiving ziftomenib during induction consolidation and post-consolidation maintenance, and that consolidation can be transplant or chemo. You have the patients that are getting zifto through induction consolidation, followed by placebo during that post-consolidation maintenance. You're getting patients that are getting placebo throughout. We really did design it to be able to answer that question. So far, we think that it's adding to the equation. Really, when you have a drug that's not bringing on additional toxicities, even with incremental benefit, it becomes worthwhile to keep the patient on. Dr. Zeidan, could you please also? Yeah. I'll add my clinical perspective actually, not only to the KMT2A, but also to the NPM1, because I think this is also relevant to some of those patients. I think it's very important to remember that with KMT2A to arrange leukemia, the vast majority of patients would still relapse post-transplant. Transplant is not something that you do and then you are all set. Most patients are still relapsing and dying from their leukemia. The community and the patients are really in need of something that would improve their survival beyond. I think when you approach these therapies, and I'll tell you, for example, if the trial is positive and the drug is available, and I will tell you, many people are already probably using this off-label. We are trying to give something post-transplant for these patients that has any chance of success because we know that their outcomes are poor, even with transplant. If you have a drug that is easy to take, that does not add to the myelosuppression, that's once a day, and it's approved in that setting, I think there's going to be a lot of interest to use it. In terms of the NPM1, I wanted to add that part because NPM1, again, is thought of as a favorable risk disease, but still a significant number of those patients will relapse, in particular among older patients who are older than 60. There is still controversy in the field in terms of recommending transplant in older patients. Some centers still recommend transplant, especially in the presence of MRD positivity. One of the things that patients find extremely, I think, intriguing about this combination, as well as the doctors, is the potential to be able to get rid of the need for transplant, even for older patients. I think something that Troy alluded to is that we only had 10 patients who went to transplant in the context of NPM1. I can't recall the age difference, but I suspect some of them were older patients because, again, this is where we tend to think of transplant for patients. I think if you have a drug that will improve the outcomes by adding it to consolidation, induction, and maintenance post-chemo, I think there will be a lot of interest in moving away from transplant completely. Great. Thank you. Thank you. Thank you very much. Our next question will come from David Dai with UBS. Please unmute your line and go ahead. Great. Thanks for taking my questions and congrats on the data as well. You mentioned that the MRD negativity is favorable compared to historical 7+3. Maybe you just can clarify how the baseline characteristics for the patients and transplantation rates in the KOMET-007 compares to the historical 7+3 cohorts. David, I'm sorry. I'm not sure I understand. Can you ask the question again? I'm not sure. You're asking how do the baseline characteristics and the transplant rates that we're seeing in 007 relate to historical precedent? Is that the question? That's right, yes. Just any thoughts on how the baseline characteristics of your. Sure KOMET-007 study compares to the historical. Yeah 7+3 treatments in the real world? Yeah. I think, David, the key slide is the slide that breaks down the CR rates by age. You've heard Dr. Zeidan speak to it, you've heard Mollie speak to it. Typically, you see a disconnect between the younger patients and the older patients. The older patients have much worse outcomes. Here, it's very early days, these are small numbers, but I think that's what Dr. Zeidan cited, is you have 100% CR rate at patients older than age 60. That jumps out at you. You're seeing lower rates of transplant because we have the ability to keep these patients on continuation therapy. It's difficult. We really made an effort to try to break down the various components of what all of you should be comparing and to give you appropriate references because we get this question regularly. We can't parse the data too much farther, I think you've heard this consistently. You're seeing great benefit in both younger and older patients, no additive toxicity, possibly the ability to prevent transplant. Everything is sort of going in the right direction. I hope that answers the question. Great. Thank you, Troy. I appreciate it. My pleasure. This was our last question for today, I'd now like to turn the call over to Troy Wilson for any closing remarks. Great. Thank you, Stefan, and thank you all for joining the call today. We're absolutely thrilled with this data. It's another step toward our goal of improving outcomes for patients with acute leukemia. I want to thank Dr. Zeidan for being so gracious with his time today. I want to thank my team, and I want to thank all of you for your questions. We're available. Most of our team is at EHA, but we're available if you have additional questions, and so you can reach out to Greg or me. We hope this was helpful and look forward to the next time. Thanks very much. We'll adjourn the call