Thank you for standing by. My name is John, and I'll be your conference operator today. At this time, I would like to welcome everyone to the Kura Oncology ASH 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 this 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 call over to Troy Wilson, President and Chief Executive Officer. Please go ahead. Thank you, Operator. Good morning, everyone, and welcome to our ASH Investor Event. I'd like to start by turning to slide number two. Today, we're going to be making a number of forward-looking statements, and we would refer you both to our website and to the SEC's website for more information about Kura Oncology and the risks and uncertainties of an investment in the company. Turning to the next slide, slide three, we're very fortunate to have with us today two of the investigators on the KOMET-007 study, Dr. Amir Fathi, who is the Program Director of the Center for Leukemia at Mass General, as well as Associate Professor of Medicine at Harvard Medical School, as well as Amer Zeidan, who's the Chief of the Division of Hematologic Malignancies, Director for Hematology and Early Therapeutics Research at Yale, as well as an Associate Professor of Medicine at Yale University. I'm also joined here by two members of Kura's senior leadership team, Dr. Mollie Leoni, who is our Executive Vice President of Clinical Development and the clinical lead for our menin program, as well as Brian Powl, who's our Chief Commercial Officer. The two doctors are going to go through some slides related to the data. Then Mollie will take you through a couple of slides as to how that data will roll out into our forward development plan. And then we'll end with a slide or two on the commercial opportunity that's beginning to come into focus for the menin inhibitors in acute leukemia. With that, if we could turn to slide number four, I will turn it over to Dr. Fathi. Thank you so much, Troy, for the kind introduction. I'm happy to be here and appreciate speaking with you all this very early morning. Ziftomenib, it's a key inhibitor of the menin pathway, a foundational target in AML. In 35%-40% of AML patients, leukemogenesis is driven by either NPM1 mutations or KMT2A alterations. These are upstream regulators of key genes critical for AML progression, including HOXA9 and MEIS1. KMT2A, also known as MLL and NPM1, sit upstream of major AML targets, which also happen to be promoters, key promoters of leukemogenesis and development of AML in patients. Therefore, inhibiting the menin-KMT2A complex downregulates HOXA9/MEIS1, leading to differentiation of leukemic blasts into more mature myeloid cells and ultimately a response. Ziftomenib is a potent, highly selective investigational menin inhibitor, as I mentioned, an inhibitor of the menin-KMT2A complex, and has shown clinical activity as monotherapy in adults with relapsed or refractory NPM1-mutated AML. Next slide. As a way of background, KOMET-001 was a phase I/II study of ziftomenib in relapsed or refractory AML. There were multiple phases to this study. The phase IA was a dose escalation, which explored multiple dose levels of the drug given once daily to assess the safety and tolerability, pharmacokinetics, and get an early sense of the anti-tumor activity of the agent. That followed according to the guidelines per the Project Optimus from the FDA to explore specific cohorts, in this case, a cohort of 200 mg daily and another of 600 mg daily, to further explore the safety of pharmacokinetics and clinical activity and to pick the right dose ultimately for expansion, which was explored in a phase IB expansion cohort of 600 mg daily, a dose found to be most optimal in terms of pharmacokinetics and activity. Following that, the phase II portion of the study ensued, which looked at 600 mg daily with a primary endpoint of composite remission, CR and CRh, as well as multiple important secondary endpoints, including duration of remission, transfusional independence, MRD assessments, and also safety, tolerability, and adverse event profile. Now, to move on to the data that we presented last evening, the KOMET-007, and my focus especially will be on the phase I combination study of ziftomenib plus venetoclax and azacitidine in relapsed or refractory patients. Dr. Zeidan will speak about the upfront study in combination with intensive therapy. Specifically, in regards to the combination of ziftomenib, venetoclax and azacitidine, this was among patients, adult AML patients with either NPM1- mutated or KMT2A- rearranged AML who were relapsed or refractory to prior lines of treatment. There was a dose escalation that looked at multiple dose levels. There was also a dose de-escalation level, which we didn't get to because we did not need to dose de-escalate. There was dose level one at 200 mg, dose level two at 400 mg, and dose level three at 600 mg of ziftomenib in combination with azacitidine and venetoclax followed thereafter with what we're planning on doing, which is a dose expansion looking at the ultimately the selected dose, which in this case was 600 mg daily among both relapsed and refractory as well as newly diagnosed AML patients with the primary endpoint of assessing for DLTs, adverse events, and other key secondary endpoints of response. Ziftomenib was started on day eight of cycle one and was thereafter administered continuously daily. Venetoclax was administered as per the label in 28-day cycles, but there were multiple guidance statements within the protocol to help with dosing and adjustment to optimize patient safety. Azacitidine was also administered per label on cycles from days one through seven of each. Next slide, please. So, this slide provides you the baseline patient characteristics for this cohort of patients, which, as I mentioned, included both NPM1- mutated as well as KMT2A- rearranged patients. Both of these groups are provided here, 26 patients with NPM1 mutations and 28 with KMT2A rearrangements. The median age for all patients as well as those within the individual groups are provided here. And I think they break down relatively as would be expected within each mutational subtype. I'd like to perhaps focus your attention on a few of the rows here that I think are relevant. One is the median number of prior therapies. As you can see, there's a wide range of multiple prior therapies among these patients. And I think this is important. When we do studies among relapsed and refractory patients, oftentimes we don't get as uniform a patient population, in fact, far from it, than we would in newly diagnosed cohorts of patients where patients in this situation ultimately receive multiple different lines of treatment with varying degrees of intensity, and depending on the study, also potentially include transplant. It oftentimes can make interpretation of data across studies quite difficult, but there was a range of prior therapies among these patients. As you can see, some of these columns have all patients. There was anywhere between one to eight lines of prior treatment, and those prior therapies included, as I mentioned, stem cell transplant, venetoclax, as well as prior menin inhibitors. Up to 20% across all patients received prior menin inhibitor therapy, and that's an important consideration as you look at this data. Next slide. Safety and tolerability of ziftomenib is described here in the form of treatment emergent adverse events that occurred in 20% or more of all patients. I would just say this is a busy slide, and you're welcome obviously to look through it. There was not, I don't think, any significant trend that would make this any substantially different than what you would expect from azacitidine and venetoclax alone in such a relapsed or refractory patient population. What we generally see with this combination was also seen here with the triplet, which included cytopenias that occur during repeated cycles of treatment. Now, we've divided up this table according to all of the information, including any grade toxicities, including non-hematologic events, and have focused more clearly on hematologic events that occurred grade three or higher in the final three rows. Next slide. Now, the key adverse event for menin inhibitors in general, a class effect, is differentiation syndrome. This was seen in four patients. Three of the four were KMT2A- rearranged patients. The events that occurred were grade two and grade three, and all of them were manageable with standard approaches to differentiation syndrome. As has been previously said by various investigators, including myself and Dr. Zeidan, differentiation syndrome probably would end up being a more prominent occurrence in monotherapy studies or monotherapy scenarios as opposed to combination scenarios, mainly because we think that limiting or decreasing the bulk of the disease probably has an effect on decreasing the incidence of differentiation syndrome. The less leukemia you have to differentiate, the less likely you would think that you would have differentiation syndrome. As I think we are starting to see that here in studies, particularly in the upfront setting where traditional treatment tends to be more effective. Among these patients, there was no ziftomenib-associated QTc prolongation, and no dose-limiting toxicities were noted at the dose levels tested. Next slide. Here is the clinical activity in response to evaluable patients. These would be defined as patients who have one or more response assessments or who were alive. The composite remission information is provided at the top row for both NPM1- mutated patients as well as KMT2A- rearranged patients. In total, 50% of patients achieved a composite remission, 68% achieved an overall response, which included CR, CRh, CRi, or MLFS. This was higher in NPM1- mutated patients than it was in KMT2A- rearranged patients in whom composite remission and overall response were lower, but nevertheless occurred in about overall response in a third of patients that were treated. We also, on the poster that we presented yesterday, provided information for both prior venetoclax exposure as well as prior menin inhibitor exposure. This is a table that provides the venetoclax. As you can see, a sizable proportion of patients had prior venetoclax exposure. Most people, I would say all experts in the leukemia field, know that once a patient has been exposed to a definitive round of venetoclax-containing therapy, oftentimes what follows has to have a substantially reduced likelihood of response. In this case, among patients who received prior venetoclax, actually in NPM1- mutated patients, more than a third actually achieved a composite remission, which I think is remarkable, I would say. And 15% of patients with KMT2A rearrangements also achieved a response. We had more limited data for patients with menin prior menin inhibitor exposure, but two patients did have an overall response among prior exposed patients. Next slide. We provided this table just to provide a sense of sort of count recovery because I think that's an important consideration for patients who receive the combination of HMA and venetoclax combinations and now triplets. As you can see here, baseline to neutrophilic and platelet recovery ranged from lower to higher numbers, but in general did not differ substantially, I would say, from what you would expect in patients in the relapsed/refractory setting receiving azacitidine and venetoclax, with the majority of patients achieving count recovery as would be expected by the end of each cycle. Next slide, conclusions. In the ongoing KOMET-007 study, ziftomenib, a potent and selective menin inhibitor combined with venetoclax and azacitidine, was deemed to be well tolerated, which was the main objective here at all dose levels tested, and continued to demonstrate promising clinical activity in this relapsed/refractory NPM1- mutated and KMT2A- rearranged AML population. The ziftomenib combination therapy was well tolerated in the sense that no dose-limiting toxicities nor any ziftomenib-induced QTc prolongation were reported. Differentiation syndrome occurred in four of 53 patients receiving ziftomenib. All were grade three or less, including in three KMT2A-rearranged patients and one NPM1-mutated patient. All patients had resolution of differentiation syndrome with appropriate standard management. Clinical activity was demonstrated in the treated patients, including in prior menin-experienced patients in the NPM1-mutated group. Among the response-evaluable patients, the overall response rate was 68%, and the composite remission rate was 50%. In the same population of patients with prior menin exposure, the overall response rate was 50%, and composite remission was 36%. We also saw that a third of patients with KMT2A rearrangements also responded, including those with prior venetoclax exposure. So, based on these encouraging initial results, a dose expansion phase is currently moving forward, evaluating this triplet combination in both relapsed/refractory and newly diagnosed patients. Thank you so much for your attention. And I'm going to hand the floor over to Dr. Zeidan. Thank you so much, Amir. It's a true pleasure to be here talking about, I think, very exciting results from this ongoing trial, so Dr. Fathi covered very well the rationale for combining ziftomenib with various forms of standard of care chemotherapy in the relapsed/refractory setting, but here, I think the combination with intensive chemo is also very important, and I wanted to highlight a couple of things that are in general oncology development, that most of the novel drugs will be developed in the relapsed/refractory phase where they show safety and efficacy, and then they would be moved upfront in combination with other standard of care agents where there is non-overlapping toxicities and synergistic activity where we can have the best chance of making a very significant impact on the patient chance of survival. This paradigm has been followed in multiple hematologic malignancies, including acute myeloid leukemia. When we look at the experience, for example, with FLT3 inhibitors, you see responses in the range of 20%-30% in the relapsed/ refractory setting. Then once you go to the frontline setting in combination with intensive chemo, some of those agents have become part of the standard approach of treating patients. This is, I think, a very big part of why we designed this combination in the frontline setting, part of the study in combination with 7+3. Patients who are being fit for intensive chemotherapy will receive 7+3. Here, in this phase I study, we had a dose escalation, which was phase IA, which used the same doses that Dr. Fathi mentioned, 200 mg, 400 mg, 600 mg, as you can see in the schema slide. Patients were enrolled in independent cohorts of NPM1 or KMT2A- rearranged patients. What you can see also clearly here is that while those patients had NPM1, those patients were considered to have high risk. Why is that? Because we know what NPM1 generally indicates, a favorable prognosis in the frontline setting. Once you look at patients who are older than 60 and patients who have therapy-related disease and patients who have poor cytogenetics, those patients actually have poor outcomes. Relapse is very common. Many times they would be recommended for bone marrow transplantation. This was an ideal patient population to go initially to look at the safety and get a sense about the preliminary efficacy. The primary interest in that part of the study was looking at description of safety using DLT and adverse events, and then secondary endpoints looking at efficacy focusing on CR and CRc. Ziftomenib, similar to the azacitidine cohort, was given continuously. It started on day eight and was given during induction, during consolidation, and subsequently was given on a maintenance course. The maintenance was allowed to be given after chemotherapy or after bone marrow transplantation. What I'm going to present today is the result of the dose escalation part of the study, the phase IA. I would note here that there's already an ongoing phase IB looking at expanding the results or expanding the trial to understand on a bigger scale how the combination performs. On the next slide, you can see the baseline characteristics of the 51 patients that are going to be described in this presentation. You can see the breakdown between NPM1- mutated patients, which were 24, versus the KMT2A- rearranged patients, which were 27. You could notice that patients with NPM1 were a little bit older, with a median age of 66, because, again, this is by design that those patients were required to be either older than 60 or have therapy-related disease or poor cytogenetics. That reflects their poor prognosis. You can see the distribution of the co-mutation, which again is very similar to what you would expect in this type of patient population. I would note that patients on study, and I think you can quickly see this is relatively a shorter follow-up, but you can see that many patients are still on therapy. 45 patients out of the 51 are still on study. S o in the next slide, when we look at the safety, and I think here anybody who has treated patients with acute myeloid leukemia can quickly tell by looking at this slide that these are the side effects. While they are very common, but it's extremely common to have everybody essentially on intensive chemotherapy will have grade three and four adverse events in general, and the reason for that is that intensive chemo will lead to count suppression. There is often some GI side effects. So, when you look at this in terms of the combination, and although there was no control arm in this particular study, indirectly, when you compare data from other studies that look at 7+ 3, you can see that the treatment emergent adverse events are in line with what you see with 7+ 3. So, here specifically describing the treatment emergent adverse events that occurred in 30% or more of patients, you can see that the categories basically fall into the blood count suppression, which is again very common with intensive chemotherapy, as well as febrile neutropenia and some GI side effects. And this is, I would note, are adverse events regardless of attribution and of all grades. I think a very important note or observation that we made that on the dose escalation, it did not seem that the rate of the treatment emergent adverse events correlated with the dose, which allowed us to escalate to the highest dose, 600 mg. In the next slide, we are describing the safety and tolerability, but looking at the treatment emergent adverse events that were grade three or higher that occurred in 10% or more of patients. Again, this is regardless of attribution. The same observation that we made earlier stands here that most of those side effects are what you typically see in patients with acute myeloid leukemia who are undergoing intensive chemotherapy. I would note here that you can see that the GI side effects are not seen because most of them are mostly grade one and grade two. What you are seeing is the febrile neutropenia and the blood count suppression, which is very typical with this type of intensive chemotherapy, along with a low number of infectious complications. But importantly, we did not observe any dose-limiting toxicity at any dose level. We did not observe any ziftomenib-associated QTc prolongation. And to support the idea that the combination is not only important from a synergistic point of view, but also to mitigate the risk of the differentiation syndrome, you can see here that there was only one case out of the 51 patients of a patient who developed differentiation syndrome, which was grade three at the NPM1- mutated cohorts at the 600 mg dose. But this patient was actually successfully managed and was able to remain on treatment. So, next slide. I think this is clearly the most exciting slide, and I think generated huge interest during the presentation and subsequent to the presentation, is, in my opinion, extremely impressive clinical data. It's still relatively a small number of patients and limited follow-up. But when you look at the number of responses that were observed in both cohorts, but in particular in the NPM1 cohort, so out of the 23 patients who were treatment evaluable, 100% of the patients responded with a complete remission. And I would note here that this is not composite CR or CRh. This is 100% full CR, which is something that you do not often see with these therapies. And when you look at the MRD, which is the disappearance of the measurable residual disease, which we think correlates with long-term outcomes in the context of intensive chemotherapy, around 3/4 of those patients achieved MRD negativity. Although this approval was local based on local results, I think, again, this is very encouraging. When you look at the KMT2A- rearranged patients, I think you are seeing similar results. I would note this is a much more difficult treatment patient population to treat, but still, out of the 23 patients that were efficacy evaluable, 83% of them achieved complete responses, so when you add to this that the NPM1- mutated patients were, as I mentioned earlier, the higher risk, the patients who are older or have therapy-related disease, I think these results really speak for themselves, and in the next slide, you can see, I think, a very important observation that we have been making across the study in terms of how these new therapies can lead to novel approaches in the management of patients with acute myeloid leukemia. This is actually a 60-year-old patient within the NPM1- mutated cohort who was treated with 7+3 and ziftomenib. And you can see here in the bone marrow, which is the first column at the diagnosis, you can see some pictures. For those of you who are familiar with this kind of picture, this represents stains from the bone marrow using H&E stains, CD34 and NPM1. And what you can see, this NPM1 is actually a very nice stain that we use in our institution, other institutions, that stains the cytoplasmic localization of the mutations. So, it gives you a quick idea about having a patient with NPM1 mutation. This is important because you can relatively, using this, diagnose the patients faster than waiting for the results of the next-gen sequencing. So, we quickly knew that this patient was a candidate for the trial. We put the patient on the trial. Then subsequently, on day 21, what you can see is that on the top picture, our pathologist, when we did the bone marrow, and the reason why we do a bone marrow in the middle of the treatment is sometimes we give additional chemotherapy to make sure that the patient will go into remission if there was a significant amount of leukemia. However, the pathologist was concerned that there was residual leukemia. They actually counted what they called 30% blast. However, we observed that the patient actually was doing well. The platelet count was already recovering. Over the next few days, the platelet count went from the 20s to the 70-80 range. Then subsequently, when we looked at the flow cytometry, we could see a change from the baseline immunophenotype, as well as the NPM1 PCR came back much, much lower than it was at the beginning. It was at the beginning 38%, and at that time, at day 21, it was 0.08%, like less than 1 in 1,000. Based on this, we decided to not treat the patient with additional intensive chemotherapy and waited on the patient. Two weeks later, we repeated the bone marrow. The patient actually had full count recovery. You can see that the morphologic blasts completely disappeared. The NPM1 immunohistochemistry completely disappeared. The PCR became very minimally detected and subsequently disappeared after the first consolidation. I think this case highlights that it's very important in the context of adding differentiating therapy to intensive chemotherapy that there should be a judgment given about whether to give additional chemo. I would argue that we have seen similar patterns with some of the other differentiating therapies that lead to terminal differentiation and apoptosis of blasts. And I think if these hold up, especially the very high CR rate, I think we probably can get rid of the day 21 bone marrow altogether. But of course, we need to see additional follow-up. Now, in the next slide, you can see the duration of treatment and preliminary clinical outcomes in patients in the NPM1- mutated cohort. Here the follow-up is relatively short at 31 weeks. But you can see that essentially all patients are alive. So, basically, there was no treatment-related death during the induction, which again is something that is a risk of leukemia. We can see here that the median duration of CR was not reached. The median survival was not reached. And patients were able to proceed to transplant. Five patients went to transplant in this cohort, and two of them were allowed to go into the maintenance after their physicians discussed with them, and they chose to do that. But importantly, there were no discontinuations due to adverse events or relapse. Similarly, in the next slide, you can see similar observations for the KMT2A- rearranged patients. Here, the follow-up was a little bit shorter at 19 weeks as a median. But similar observations that most of the patients were alive, 96% at the time of this data cut. The median duration of CR was not reached. The median overall survival was not reached, and more of those patients went to transplant, reflecting the very aggressive nature of this subtype of leukemia, and this is why I think most physicians and patients will still try to go for transplant. Next slide is an analysis similar to the one that Dr. Fathi described for aza/ven. We tried to look at the count recovery. Why is that important? Because one of the concerns when you add any agent to combination therapy, including intensive chemo, is prolonging the period of myelosuppression, and that can lead to infectious complications and other things, and actually, this derailed the development of several agents, which we found promising, and once you combine them with intensive chemo, you get prolonged myelosuppression, which could be a problem. Here, we observed very nicely that when you add ziftomenib to 7+3, that the time to count recovery, which is generally assisted by ANC of more than 500 or 1,000, or platelets more than 50 or 100,000, that the median time to count recovery did not appear different than what you would expect with 7+3, and also, importantly, did not seem to vary across the different dose levels or by the cohort, and I think you could even make the argument that the median time to recover might be a little bit shorter as you go up on the dose, but I think this remains to be seen, but this is extremely encouraging, in my opinion, because this is one of the issues we have seen historically with other drugs when they are added to intensive chemotherapy. In the next slide, you can see our conclusions from the ongoing KOMET-007 study that when ziftomenib is combined with intensive chemotherapy, the treatment was very well tolerated in all the dose levels in patients who had newly diagnosed adverse NPM1- mutated disease or KMT2A- rearranged AML. We did not observe any dose-limiting toxicities. We did not observe any ziftomenib-associated QTc prolongation. The occurrence of on-target differentiation syndrome was only in one patient, which was 2%, grade three, successfully managed, and the patient was able to remain on therapy. Importantly, as I mentioned, the ziftomenib did not seem to interfere with count recovery. The dose did not seem, the higher dose, 600 mg, which was chosen for expansion, to particularly, again, did not seem to impact time to count recovery. Very exciting for us and clearly to our patients is that we observed very high CR rates. And again, I would say this is CR, not CRT. All CR, 100% in the NPM1- mutated patients, 83% in the KMT2A- rearranged patients. And 3/4 of those patients achieved MRD negativity at one point during their treatment using local HSCT. And at the time of the data cut, the vast majority of patients, 50 out of the 51, were alive. So, taken together, I think this data is clearly supportive of further development of ziftomenib in combination with intensive chemo. And actually, the subsequent expansion cohorts on this study are looking at all patients with NPM1, regardless of the age, regardless of previous treatment, as well as patients with KMT2A- rearranged disease. I think we look forward to make better understanding of the durability of the responses, as well as the tolerability of the treatment, and have a better sense about how this treatment is going to fit in the future management of frontline treated patients with acute myeloid leukemia. Thank Thank you. Perfect. Thank you, Dr. Zeidan and Dr. Fathi. We can go to the next slide now. We're going to turn it over to Mollie to take us through how these results are now incorporated into our forward development plan for ziftomenib. All right. Thank you, Troy. Onto slide 26. Our goal has always been to get ziftomenib to the broadest population that could potentially benefit. In order to do that, we have been executing a broad ziftomenib development plan to generate a large amount of pertinent data. In that top red box, this is what we are executing in collaboration with our partners at Kyowa Kirin. The top line shows you our monotherapy registration-directed trial, where you should expect to hear top-line data in early 2025. In that trial, we're also evaluating ALL patients and non-NPM1, non-KMT2A- rearranged patients. All of those cohorts are now dosing. As KOMET- 007 has been described today on the call, we are successfully through the dose escalation portion and into the dose expansion or dose validation portion for all cohorts being enrolled. KOMET- 008 is our relapsed/ refractory combination trial, where you're combining with agents such as gilteritinib, FLAG-IDA, and low-dose AC. All of those cohorts are also enrolling during the dose escalation portion of this trial right now. And if we go on to the next slide, the information that we generated and that was presented this weekend at ASH is now truly our focus as we turn to the frontline and our frontline pivotal trial. And that frontline pivotal trial is called KOMET-017. And I will remind you, it is fully funded now through to the end results and expected to start in mid-2025. Within the study, there's two independently powered phase III randomized double-blind studies. And the populations will enroll adult frontline AML with either KMT2A or NPM1 mutations. And depending on their status, they will enroll into the non-intensive therapy, which would be the ziftomenib + venetoclax + azacitidine versus placebo, or the intensive therapy study, which would be the ziftomenib versus 7+3 versus placebo. We expect about 150 sites in 20 countries. This will be a very broad development project that we are undertaking. Thank you, Mollie. And just to give a few comments now about how particular these frontline results are reflected in the commercial opportunity, Brian's going to take us through a couple of slides here at the end. Thank you, Troy. Next slide, please. Slide 29. Just summarizing the development plan that Mollie outlined, we are building a strategy to support development in up to 50% of AML patients where the menin and KMT2A pathway is a driver of disease. We see that across both NPM1, KMT2A- rearranged, as well as other mutations. We have, of course, with our earlier stage development in the KOMET-007, KOMET-008, a number of combinations. In the frontline setting, we'll have KOMET-007 with both ven/ aza 7+3. We're also initiating, we'll be initiating next year a quizartinib combination as well here. With this broad development plan, we see potential to reach a large number of patients, as I mentioned, up to 50% of the patients. If you go to the next slide, please. Where we see is this overall, this market potential, I wanted to just give an outline as to where we see this potentially reaching is exceeding up to $7 billion potentially per year. When you look at the breakdown of patients on the left side, where we see there are potentially up to 50% of AML patients that may benefit from the menin inhibitors, we realize that while there are a lot of options for patients right now, there's still a very high unmet need in AML. This includes patients who are considered to have both poor and favorable prognosis. According to the epidemiology, we think that there is an opportunity to treat up to 10,000 patients per year in the U.S., both through the intensive and non-intensive chemotherapy populations. We think that the data that was discussed today leads us to support the potential combinations in both 7 + 3 and ven/aza in the frontline setting. We believe that the ability for patients to remain on therapy allows for a potential sustained treatment between 12 to 24 months of treatment or more. With analog pricing of other currently available therapies in the AML space, we believe that this leads to an anticipated market potential exceeding $7 billion a year for the menin inhibitors in the first-line setting alone. Given if ziftomenib has the opportunity to reach this market, we think that there is a peak sales potential of up to $3 billion per year in the United States. Great. Thank you, Brian. We can turn to the next slide and actually just the one after that. This will be the last slide before we wrap up and take questions. So, we were very pleased to have the presentation of the results from the dose escalation portion of the KOMET-007 study. Looking forward to next year, we anticipate releasing top-line results for our KOMET-001 registration-enabling study in NPM1-mutant relapsed/refractory AML in early next year. We, looking forward, plan to give you updates from the KOMET-007 study, both further updates on the dose escalation portion as well as insights into the dose expansion cohorts for both the intensive and non-intensive treatment regimens, as has been mentioned. We are looking forward to commencing the KOMET-015 study, which is a combination of ziftomenib and imatinib in patients with advanced gastrointestinal stromal tumors who have progressed on prior imatinib therapy. In another application of menin inhibitors, we intend to nominate a next-generation menin inhibitor development candidate, and of course, as Mollie mentioned, we are moving very aggressively now to initiate the KOMET-017 registration-directed trial in combination with both venetoclax / azacitidine and 7 + 3. Looking at the pipeline, there are a number of other key milestones that we're looking forward to sharing with you throughout the year. As was mentioned, we're in a very strong position now, both with the cash we have on hand and our recently signed partnership with Kyowa Kirin. Our 017 study is fully funded. We are currently looking forward to planning either a FLT3 frontline study and/or a post-transplant maintenance study. To Brian's point, really, now we have both the financial and the operational resources to maximize the value of ziftomenib per patient. With that, just to summarize, where we are with Troy now, looking across hematologic malignancies, solid tumors, which we'll talk more about, and diabetes, we think we can create a lot of value for patients and our shareholders. With our partners at Kyowa Kirin, we are intending to compete aggressively in that frontline patient population. That is really the blockbuster potential. We are hopeful that not only ziftomenib, but the other menin inhibitors will help to transform the standard of care for patients with AML, and if that happens, then, as Brian indicated, we expect to transform the market. As part of that partnership, I'll just remind you that we retained some key strategic rights, including commercial control, global development, and the ability to book sales in the U.S. Those were key rights to maintain the investment thesis for Kura. We are fully funded at this point with our collaboration and our cash on hand all the way through to commercialization in that frontline. That puts us in a very strong position. We are seeing a number of players in the menin space, and things are going to start to go quickly. So, we're happy now to have both the financial and the operational resources. Then, again, onto our pipeline, a number of exciting updates early next year. With that, Operator, we'll conclude the formal presentation. We're happy to take, all of us here are happy to take questions from those on the call. Thank you. We will now begin our question-and-answer session. As a reminder, if you have dialed in and would like to ask a question, please press star, followed by the number one on your telephone keypad. If you would like to withdraw your question, please press star two again. Your first question comes from the line of Li Watsek with Cantor Fitzgerald. Please go ahead. Hey, good morning and congrats on the data. Troy, can you talk a little bit about your confidence in frontline aza/ven combination? And how should we think about the read-through from the aza/ven combo data that you just shared in the salvage setting? Sure, Li. I mean, I'll just make the, I think, the overarching comment, and then maybe I'd ask Dr. Zeidan to add his thoughts. The most important takeaway from that relapsed/ refractory data is the safety and tolerability in combination with venetoclax and the fact that we were able to cleanly declare 600 mg as the going forward dose. The safety and tolerability profile, and in particular, the lack of AEs, I think, sets us up very nicely now to be able to move forward into the frontline combination. But I am not the expert. Let me let the expert actually comment on if there are any other key takeaways. No, I fully agree with this. I think the data clearly demonstrates the safety and tolerability, but also, I think, the clinical activity in the relapsed/refractory setting, which we generally know, especially after previous venetoclax exposure, previous menin exposure, those patients generally do not respond very well. So, to see the activity that we have seen in the relapsed/refractory setting, I think this is going to translate into, I think, very impressive activity in the frontline setting. So, I don't think I have any concerns about movement in the frontline. Okay. And I guess for both doctors, can you share your thoughts on the potential of using MRD negativity as a potential target endpoint in frontline? And what is your view on using flow versus PCR-based methods to measure MRD? So, I guess I'll start. This is Amir Fathi. So, there isn't a substantial amount of precedent when it comes to MRD assessment as a primary endpoint in clinical trials, but there is some limited amount. So, I think the regulatory agencies, from what I understand, are increasingly interested in looking at MRD as a potential surrogate endpoint, and that might be a way to potentially get to an earlier understanding of the promise of these agents in combination in larger placebo-controlled studies. And I think this, and I don't want to speak for anybody, but I think just broadly speaking, such a study might be a good opportunity to potentially pursue that here. As far as NPM1 MRD or flow MRD, I let Dr. Zeidan speak for himself. But for NPM1- mutated patients, generally speaking, the standard approach that we use is an NPM1-specific PCR test to inform us regarding decision-making following induction and consolidation chemotherapy, specifically regarding the decision to pursue transplants versus not, because historically, not all NPM1- mutated patients require transplant. So, if you are able to demonstrate MRD negativity after two cycles, generally, of intensive therapy, you may not need to pursue transplant as a modality for pursuing cure. As far as flow, flow is increasingly used now at academic centers as an assessment for MRD. But in terms of making decisions regarding choice of treatment, it is more limited in scope. So, I would say that in the clinical setting, in what we do day-to-day, for NPM1- mutated patients specifically, NPM1 PCR is the go-to. But I'll let Amer follow. Yeah, I think I agree with all of this. I would note that my sense, again, having discussed this in various settings with different stakeholders in the field, that the MRD negativity certainly is, I think, gaining increasing acceptance as an endpoint, especially in the setting of intensive chemotherapy, where I think it has been consolidated very well to correlate with long-term outcomes. Historically, the guidance on clinical drug development in AML for MRD has focused on flow cytometry. But I think there has been a lot of data in the last few years looking specifically at NPM1 negativity by genetic assays. And I agree with Amir that high-sensitivity PCR is the way to go. And I think while we don't have currently an approval so far using MRD negativity in AML, I'm very hopeful that this would be the first study to do that. I think the appetite from the regulators is certainly there. And I think the correlation data is certainly there. So, in aza/ven, I think the data is not as mature in terms of the correlation between the MRD negativity and the long-term outcome, but the body of evidence certainly is increasing. So, I have high confidence that this could be, I think, an approvable endpoint. Just to add to that, Li. We've guided for everyone on the call, we will be meeting with the regulators, both in the U.S. and in Europe, early next year, and intend on providing feedback to you, their feedback to you as part of more details around the KOMET-017 study. Our base case is that there is not an accelerated path, but as has been discussed, there are some good arguments that we're going to put forward to the regulators. We'll do our very best to argue for an accelerated endpoint, particularly in the context of intensive chemo. Look forward to early next year for us to give more color on those discussions. Thank you. Your next question comes from the line of Jonathan Chang with Leerink Partners. Please go ahead. Hi guys. Good morning, and thanks for taking my questions. For the docs on the call, given the totality of the data sets across the menin space, what do you see as the key differences on the safety profile between the menin inhibitors in development? And how could that impact, if any, the opportunity in frontline combinations? Thank you. Hi, it's Amer Zeidan, I can start. I think based on not only the clinical trial data, but my own experience having treated many patients with this agent, it's certainly one of the easiest agents to get. And many of the drugs that we use in leukemia and oncology will have some certain load of side effects, which might not be severe, but the patient might feel them, might not discontinue because of them, but they will tell you about it. In the context of this particular drug, my own personal experience, I have not had a patient who mentioned any kind of side effect that was significant in any way. And when you look at the data, I think it's clear that the addition to intensive chemo is not worsening the most concerning kinds of side effects, especially the cytopenias. But I would add, when you compare the space, having a drug that's given once a day is, I think, a huge advantage because drugs that are given twice a day, I think, especially in older patient population, can be challenging to take in the long run. We use a lot of drugs that interact with some of the novel agents, such as azoles and QTc-promoting drugs. And this certainly has been a pain. If you work in any of our clinics, this can take a significant amount of time to make sure those drugs don't interact. So, I think just having the option of having a drug that does not have major interactions with antifungals, which we often use, and not having any issues relating to the arrhythmias and needing to do frequent EKGs, not in the context of combination, the risk of differentiation syndrome also becomes much lower. I think I might be biased here, but I think my own opinion is this is the best-in-class agent. But clearly, I think on the efficacy front, I think the data to my eye looks better, but I think all of the current studies are relatively smaller and with limited duration. But I think all the right signals are currently there with the clinics. So, I've had a relatively limited experience in terms of, and I think most of us have. I mean, we kind of have our own experience with the menin inhibitors that have been open in clinical trials at our sites. So, I've had substantial experience with ziftomenib, and I agree with Dr. Zeidan that it has been a good experience. I would say that I, as a leukemia doctor, I'm very pleased with the fact that we now have this class of drug and that multiple companies are pursuing them as good for us and good for our patients. Does it matter if a drug does not interact with other agents? Of course, it does. You have to worry about things like antibiotics, antifungals, other agents, anti-nausea agents you may have to use in leukemia patients. That's an important consideration. Does QT interval prolongation matter? It can in certain scenarios, although I would also say that there are a variety of agents that we use that prolong QT in AML, and we manage those as well. But in certain scenarios, it can be impactful. Does the incidence of differentiation syndrome have an impact in our consideration? It does. This is perhaps the biggest aspect of care with menin inhibitors because it's a class effect, and it's a potentially lethal class effect. So, I think increasing the amount of information and knowledge and experience among physicians that are using menin inhibitors is exceptionally important. And my own personal opinion is this is specifically more relevant to the KMT2A-rearranged AML, in whom we have seen a perhaps a slightly, although maybe not statistically significant difference, but perhaps a slightly higher occurrence and a more substantially severe occurrence. So, I think all of these considerations are important in terms of looking at these agents. Understood. Thanks for taking the questions. Thank you, Jonathan. Your next question comes from the line of Jason Zemansky with Bank of America. Please go ahead. Good morning. Congratulations on your conference updates and thank you so much for taking our question. I wanted to circle back on the relapsed/ refractory data, and maybe this is one for your KOLs, but can you speak to what we're seeing in the responses between the menin-experienced and naive patients in the KMT2A population? Why do you think we're seeing these trends, appreciating that the data are still somewhat early? So, if I understand the question correctly, and correct me if I'm not, the question is related to prior ven exposure and prior menin inhibitor exposure in patients that were treated in the relapsed/ refractory group of patients. I think this is an important consideration, and we've had a series of conversations over the course of the last few days around that. I think all of us in the leukemia field, I suspect Amer included, have long struggled with interpretation of results from relapsed/ refractory clinical trials of AML. And I think what ends up happening when you do not have head-to-head data is a variety of clinical trials that are done in varying patient populations with varying number of prior exposures to therapeutic agents that range from anything you can imagine, from combinations of chemotherapeutic agents to, in more recent years, IDH inhibitors, FLT3 inhibitors, menin inhibitors, transplant, and perhaps most relevant, venetoclax. So, depending on the proportion of these patients treated on these relatively small patient populations that range from, I don't know, the teens all the way up to 80 patients, you're going to have varying degrees of results in patients who are treated, whether that's a relapsed/refractory cohort of patients receiving chemotherapy or targeted agents. So, I think it is very difficult for us, who are experts in the field, to interpret this data in the greater context. And I think, unfortunately, for you guys who are outside of this realm to sort of make that comparison. but unfortunately, in my view, it's just fact. It's just a feature of where we are, and it's very difficult in relapsed/ refractory settings to compare data in that fashion because the patient populations are different. and adding to that, some patient populations are single-center experiences. Some are multiple different patient populations from sometimes national or global groups. So, I think it is difficult to make those interpretations. Now, going, I guess, specifically to your questions, this prior venetoclax and prior menin inhibitor exposure and the proportion of patients who have had that in clinical trials in relapsed/ refractory AML matter, of course. I mean, historically, I mean, I'll let Amir speak to this as well. I kind of consider venetoclax so far as, unfortunately, the great closer. It either works for you for a while or it doesn't, but after that, unfortunately, nothing else seems to accomplish what you want to accomplish, mainly because the therapeutic resistance that emerges, those pathways that are underneath that resistance to venetoclax oftentimes overlap with resistance profiles to other agents that we have available. So, whatever you end up giving a patient following venetoclax, not in every instance, but in most instances, ends up being ineffective. So, in a scenario like that, when you even with that, you get something like, I don't know, 36% it looked like in these NPM1- mutated patients who still respond to menin inhibitors in combination, I think that's promising. I think that tells you, albeit in a small cohort of patients, again, with all the correlates that I just mentioned, that is promising, and that's something worth pursuing. Also, 20% of these patients have prior menin exposure. That's nothing to be laughed at. Do we expect less exposure to a menin inhibitor in patients who have been previously progressed on a menin? Of course. So, I think all of these things have to be taken within context, and I think it's important for us to consider it. Yeah. So, I agree with everything Dr. Fathi mentioned. I would add from a different angle in a broader context, when you look at, we have over 13 drugs approved now in the last seven years. And when you look at most of these, they were tested first in the relapsed/refractory setting. Take an example like FLT3 inhibitors, like that. The response rate generally as a single agent in the relapsed setting is generally in the range of 20%, and the median duration is generally in the six-month range. So, this is a very difficult patient population. I think the biggest value of all of these agents basically translates once you move them earlier in the treatment, in the combination with. Why is that? Because the goal is to prevent the patients from getting to the relapsed/ refractory stage. Once you are in the relapsed/ refractory stage, it's really very tough. The leukemia mutates all the time. It develops resistance to different drugs. So, the goal is to hit the leukemia as hard as possible from the get-go with the best drugs you have so you don't have to deal with that situation. I think if you can achieve that with an upfront treatment that combines several drugs and then for the patient to stay on one pill, I will tell you the vast majority of patients will not mind to be on one pill for the rest of their life. I always tell my patients, if I can treat leukemia, like I treat diabetes or hypertension, and you are taking a pill, and you are doing very well, and you are alive, this is something that most patients will choose. I think the data in the refractory relapsed setting is promising, but this is, as Dr. Fathi emphasized, a very difficult patient population to get the kind of overwhelming results. I think in my mind, the major takeaway is this is a drug that's very easy to give. Patients can stay on it for years and years, in my opinion, probably without having significant side effects. And it seems to be very synergistic initially with the chemo, leads to very early responses, which I'm hoping will translate into long-term survival and not even having to deal with this issue in the relapsed/ refractory setting. Got it. I appreciate the in-depth color. Your next question comes from the line of Roger Song with Jefferies. Please go ahead. Great. Congrats for the data update and ASH. And then thanks for taking the question. Two from us. One is a multi-part question related to the transplant and the post-transplant maintenance. So, just curious for doctors, following ziftomenib treatment, how you make a decision you will move the patient into transplant and how you're going to make a decision to put them back on zifto post-transplant, specifically the difference between the NPM1 and KMT2A patient. And then if you have any experience with other menin inhibitor, how do you see the difference between zifto versus other menin inhibitor in terms of the decision for transplant and the post-transplant maintenance? And then I have a follow-up question. Thank you. Yeah. So, this is Amer here. I can take this question. It's a little bit kind of complicated. The decision about bone marrow transplant is a tough decision. I can tell you that if you ask any patient, nobody wants to go for bone marrow transplant. This is a procedure that's toxic. Some patients would die initially. Some patients would develop lifelong complications, including things that affect their quality of life and recurrent infections such as graft-versus-host disease. So, the reason we recommend it is the risk of relapse, generally in certain subsets of leukemia, including clearly KMT2A-rearranged patients. But some subsets of NPM1- mutated AML, like those that were enrolled in the dose escalation part of the study, especially the older patients, the patients who have therapy-related disease, there is a substantial risk of relapse. And this is why transplant is often discussed with those patients, and some of them will choose to go with it. However, I can tell you most patients will probably, if they can have an alternative, they will probably not want to go to transplant. This was at the discretion of the physician in discussion with their patient, and I'm sure every one of us wants the best for our patients. Every one of us discussed with their patients. What I can tell you in my own personal experience is many patients, after you have this informed discussion with them in the NPM1 cohort, for example, those patients were not enthusiastic to have transplant. And when they heard that there is an option of staying on one pill post-treatment for years and years, and you could potentially still have a second bite at the apple, if you want to put it this way, should they be in a relapse, you can still go to transplant. I think several of my patients who are older than 60 chose not to go to transplant. But I think in terms of one of the nice aspects of this study, and again, I have to give credit to the study team in making this study very patient-centric, that even if the patient decides to go to bone marrow transplant, we still have the option to restart the drug after transplant, as long as the patient meets certain conditions, which are having reasonable count recovery, not having graft-versus-host disease. Compared to some of the other agents that are used in the post-transplant setting, the same considerations we mentioned earlier. If you have a drug that is very myelosuppressive, it's very difficult to give post-transplant. If you have a drug that interacts with QTc or prolonged QTc or interacts with some of the agents we use to prevent graft-versus-host disease, it's difficult to give post-transplant. Here, with ziftomenib, it was relatively easy to start patients. I think this is what you can see reflected in the trial, is that four patients in the KMT2A-rearranged cohort went to transplant because those are the patients who I still would recommend going to transplant in general with a post-maintenance approach. I think on the NPM1, in my opinion, one of the biggest wins that we could have out of this study is actually to avoid transplant in the vast majority of NPM1- mutated patients by going through the combination and just staying on ziftomenib. I don't have much to add, and I don't want to upset my transplant colleagues because I work with them. Yeah, the less transplant overall, the better, I think. As Amer just mentioned, there is probably a difference in NPM1 and most subtypes of KMT2A in terms of how we proceed with potentially curative paradigms. NPM1 historically has a non-transplant path to cure, but the goal here is to get more people on that path, right? Because many people can't get on that path. They don't achieve a sufficiently deep response, sufficiently MRD negative response. So, if you're able to increase that, and hopefully this data is pointing in that direction, you will increase the number of patients that are going to be cured and may not need transplant to get there. With KMT2A, maybe it's another discussion. Maybe it's that we are able to get more people on the path to transplant to give them a chance at cure. Because among, and we were again talking about this at the poster session yesterday, among the most difficult, hardest group of patients that I treat is this KMT2A- rearranged patients. Over the course of the last 15 years, I've had so many tragic cases. These patients present aggressively. Many of them have had prior exposure to chemotherapy and have developed therapy-related disease. There is a lot of emotional turmoil. There is a lot of extramedullary manifestations, so it's a tough disease to treat, oftentimes resistance treatment, particularly in the relapsed/ refractory setting, so I think if we're able to get responses and get patients to transplant, that would be. Yeah, sorry, go ahead. Yeah. I fully agree with. I mean, actually, I wanted to highlight one particular patient I enrolled on this study because this is exactly what Amir mentioned. This is a patient who had a history of breast cancer, who had received multiple lines of treatment, and she presented to our institution with a very high white cell count, and we really wanted to put her on the trial because we know that patients with KMT2A- rearranged disease have a significant chance of relapse. And without transplant, generally, the chance of cure is low. But we struggled with a patient who was older than 60, had previous chemo exposure, cancer exposure, and we actually had some doubts even whether she can tolerate the intensive chemotherapy. But after discussing with the patient, we decided to go ahead with the trial, and she got 7+3 with ziftomenib. And she actually was able to achieve a remission. She was able to go to transplant. And she's currently on post-transplant maintenance with ziftomenib. And I think, again, this is along the lines of what Dr. Fathi just mentioned, is potentially a way to hopefully achieve cure for some patients who otherwise, I think, have an extremely low chance of cure even with transplant. So, I think the treatment here complements both aspects of trying to prevent some patients from needing to go to transplant, but if you do need to transplant, to maximize the chance of the cure so that the disease will not relapse. Roger, did you have a follow-up question? Yes. Thank you. Thanks for all the comments, detailed comments. So, my next question is related to the R/R, the relapsed/refractory population. So, given this, the most updated of the aza/ zifto combination data, what is the read-through from this trial to the ongoing pivotal monotherapy for zifto? If you can comment on the patient baseline, maybe prior therapy, and then maybe comment on how confident you are around the guidance or the expectation you have been giving us in terms of 20%- 30% CRc/CRh for zifto monotherapy in the R/R population. Thank you. Yeah, Roger. Let me take that, actually. So, we haven't said anything at this point about the patient demographics for the pivotal other than it's largely consistent with the IB. And we keep reiterating the goal for that study is 20%-30% CR/CRh. Nothing's really changed. I wouldn't take any sort of read-through from the 007 data into 001. That 001 guidance remains intact. Next question. Got it. Thank you. Your next question comes from the line of Peter Lawson with Barclays. Please go ahead. Great. Thank you so much. Thanks for the detail and a couple of questions for the KOLs on the call. Firstly, would be when a patient discontinues, when you're thinking about the frontline from your experience with relapsed/ refractory, would you typically discontinue the patient for the chemo component or the remaining component or both? And then just the idea of delaying transplant in the frontline setting, do you think that's becoming more accepted by your colleagues? Once a patient hits MRD negative, they actually kind of talk through that. Thank you so much. Yeah. So, I can start with, this is Amer Zeidan. A nd I can start with the second part of the question about the idea of delaying or not even going to transplant. I think there's actually an increasing literature that suggests that patients who convert into MRD negativity in the NPM1- mutated cohorts, including older patients, which again is the group of patients we generally thought of as needing transplant, if you convert into MRD negativity using a very high sensitivity assay, it's unlikely that you would relapse even without transplant, and I think there has been an increasing use of this assay in the clinic. So, as a matter of acceptance, I think the acceptance is already there, but clearly we would prefer to have high-level randomized data to support that decision. So, I think by extension, if you have therapies that can increase the chance of the patient being MRD negative, as Dr. Fathi mentioned, I think most of us accepted within one to two cycles of consolidation, then I think that is going to translate into less number of patients going to transplant. But I think most of us will probably choose to keep the patient on a maintenance approach. In that situation, potentially with maintenance. Now, to your first question about the discontinuation, so the way it works with acute leukemia intensive chemo treatment is that the intensive chemo part of the treatment is actually time-limited. So, you don't keep going with intensive chemo. So, the chemo is given with 7+3, and then you give high-dose cytarabine around six months, and that's in combination with ziftomenib. And then you are done, and then you just continue with the ziftomenib by itself if you and the patient so choose. So, I think the rate of discontinuation was extremely low here, clearly. Again, my personal experience, this is one of the easiest drugs to deal with. I have worked with many oral drugs for leukemia. Almost always you'll have some kind of side effects. Here, I can tell you most of the patients really never complain about any specific side effects. And in the bigger picture, the main issue is actually the intensive chemo. I don't have anything to add to that. I think that Dr. Zeidan summarized that pretty well. Thank you, Peter. Great. Thank you so much. Yeah. Next question. Your next question comes from the line of Ren Benjamin with Citizens JMP. Please go ahead. Hey, good morning, guys. Thanks for taking the questions and congratulations on the data. I may have missed this, but can you talk a little bit about the MRD negativity rates in the zifto and aza combo in the relapsed/ refractory setting? And I guess as we think about the frontline opportunity, what kind of degree of improvement would you like to be seeing in the frontline opportunity versus just ven/ aza alone? And we're seeing some competitive data in the landscape coming out where you're seeing like 95% CRc rate for menin with ven/ aza in the frontline. Kind of feel like there's not much more improvement that we can see. So, do you think in the frontline setting, this largely becomes a competition from a safety perspective as opposed to efficacy? Then I have a quick follow-up. Do you want to take that question on the MRD negativity? Sure. For the ven/aza data that you saw presented, because we had a sparsity of samples that were tested at the local level, we actually have collected them rather routinely for central testing, and we will be doing the centralized testing and sharing that data with you at a later time. Ren, what was the second part of your question around ven/aza in the frontline? I want to make sure I understand what that question is. Sure. I guess I'm looking for from the KOLs maybe what degree of improvement, right, might you see over ven/aza by itself when you add something like zifto. There's been some competitive data, right, that's come out showing a menin inhibitor in combination with ven/aza in the frontline showing like a 95% CRc rate, right? And I kind of feel like there's not much more in terms of improvement that other agents might be able to bring. So, in the frontline setting, if you get similar sort of efficacy, which I'm going to assume that across the class you might see similar efficacy, does it just become a competitive—does the competitive landscape ultimately focus primarily on safety in the frontline issue? And that's what drives the incorporation of the drug. Yeah. I just want to make one point, Sam, as I'm very interested in Dr. Fathi's opinion on this. I think when you look at any kind of data, when you quote response rates, it's very important to look at what is the patient in which the response rate is being quoted. So, there are several components to this. It's the early toxicity, how many patients actually fall off because they have toxicity and they never make it to the response assessment endpoint. So, I do think when you look at any study, including some of the ones you mentioned, it's important to look at the denominator of that response rate. The reason I mentioned that is, again, I want to highlight that the combination with the intensive chemo in relatively older patient population, the patients who got 7+3 on our study had a median age of 66 in the NPM1 cohort. When you look at the 24 patients, basically everything, one of them was alive. 23 out of the 24 made it to that efficacy endpoint. And that is in combination with intensive chemo. So, my assumption is in combination with aza/ven still a very significant number of patients will make it to that efficacy point. Why is that important? It's because, again, there are other combinations that I think might have more toxicity and that those patients might not necessarily make it to the efficacy endpoint. So, I do think I would not take all the data at face value, and I think it's very important to dig into those kind of details of numbers. But I would say, I think in terms of how you can improve above that is the level of the MRD negativity, for example. I think that could be a differentiator. Of course, ultimately, with all of these treatments being able to continue on treatment long-term, the tolerability long-term is going to be higher. Because you could have short-term responses, but you cannot stay on treatment long-term because of the side effects that you have with some of the other drugs. I think you have to look at multiple aspects, not only just one number. If I understand, I think, and correct me if I'm wrong, but I think the spirit of the question is if ultimately the menin inhibitor class is so good that we get to sort of this maximal effect across all menin inhibitors, in that scenario, what are we doing? Listen, if we get there, great. I'm not sure if we're necessarily going to get there. I mean, I think so right now the bar is what we have with VIALE-A, which is a composite remission rate that hovers in the mid-60% range. So, I think if we improve upon that in a statistically significant, clinically relevant fashion, we've succeeded. And many of these menin inhibitors that are out there now - and again, I'm speaking for myself - are effective, are good drugs. And when these types of scenarios happen in oncology, and I've been at this now, unfortunately, for a long time, yes. I mean, I think the distinguishing factors are the group that is conducting the studies, the study design, the patient population, the sites that are involved, ultimately the tolerability of the agents that are a part of it. All of those are going to be differentiating factors in terms of the ultimate success of an agent. So, it's not necessarily for us the drugs that we want to succeed. When there are many drugs that are good, ultimately those factors have a substantial effect on the success of an agent. And for us, the ultimate utility of those patients for—the utility of those drugs for the patients that potentially can benefit from them. So, I think it is important to keep those things in mind. But I do agree with Dr. Zeidan. Right now, the amount of data that's out there is limited. So, I think coming up with an idea that almost 100% of patients are going to respond, it's hard for us to sort of know that a priori. Got it. Thank you very much for that. And maybe just a quick follow-up. In the ven/aza combo, I believe about around 40% of the NPM1 patients had FLT3 co-mutations as well. I'm kind of curious, was there any insights or read-through that you saw from this data that you might employ in KOMET-008? I don't think we've looked at that yet. I think probably folks are going to look at it, and probably later iterations and publications are going to have it. I could point you to the data from the monotherapy experience. There wasn't a substantial difference among patients who overall and those who had FLT3 or IDH mutations in terms of response. I don't know what this is going to look like, but I wouldn't be surprised if it's similar. Excellent. Thank you guys very much. Thank you, Ren. Your next question comes from the line of Charles Zhu with LifeSci Capital. Please go ahead. Good morning. This is Peter on for Charles. Congrats on the data. Just a quick kind of follow-up to the last question. In the frontline, how would you think about count recoveries versus MRD negativity? For example, is it more important to get the blood counts to recover quickly or to get to that MRD negative status just in terms of thinking about which treatments you would use? Thanks so much. Yeah. So, this is Amer Zeidan. This is a good question, but I don't think the two things kind of contradict each other. You could still achieve a reasonable count recovery while you are eliminating MRD, and this is kind of the ideal situation. And what we are seeing from early data from what we presented is we seem to achieve both of those aspects of not having prolonged count recovery that generally, if you have very low neutrophil count, for example, for, let's say, two months, that there is a higher chance of getting infections, other problems. So, you want to have your count recovery within a meaningful or relatively shorter period. Generally, we think of that as closer to less than 42 days, while at the same time trying to achieve MRD negativity. I would highlight here that the MRD negativity does not necessarily have to happen after induction. It's ideal, but I think after consolidation, the first one or the second one. So, I think it's a combination of factors. One, you are trying, when you add the treatment, you are trying not to increase the induction mortality. We did not talk about this because it did not even come in a significant way. But when you lose intensive chemo, generally, there is a number of patients who die during the first month because of complications. And when you add additional drugs, this is one of your immediate safety concerns. We did not see any concern for that here in terms of increasing the early mortality in any substantial fashion, and then having the count recovery at the right time, and then looking at the MRD negativity either after induction or after first consolidation, but the two things are not contradictory if I understood your question correctly. In fact, I would say in my own personal experience, I don't know if this has been definitively proven, and those patients who have robust neutrophil count recovery, it's, in my opinion, more likely that they're going to have a deeper response, including MRD negativity, so sometimes it's not even the fact it's mutually exclusive that they oftentimes go hand in hand, so that's the good part of this, and I agree. I mean, I think it's too early, but you're getting the sense that especially in these NPM1- mutated patients that they tend to get their neutrophils up faster. You always love to see that because you don't have to worry about prolonged count suppression and infections and complications, and that you get into a nice remission sooner. So, if we demonstrate that in a larger patient population, that's extremely welcome news. Got it. And just a quick follow-up for management. Any plans in the future to release subgroup analyses looking at MRD negativity in terms of response and potentially durability over time? Yeah. As we gather additional data, we'll definitely be doing these subgroup analyses. We just need to have enough patients to make it a meaningful dataset to interpret. But yeah, I would anticipate being able to discuss that data further next year. Got it. Thanks and congrats again. Thanks, Peter. Your next question comes from the line of Phil Nadeau with TD Cowen. Please go ahead. Morning. Thanks for taking our questions. Just two from us. I guess first, on the data presented in the relapsed/refractory population, there did seem to be a pretty meaningful difference in efficacy between the KMT2A population and NPM1 population. So, we're curious to get your thoughts on why that might be, particularly given that it looked like differentiation syndrome was manageable in both populations. That's the first question. And then second question for management, could you discuss a little bit more about how the 600 mg dose was chosen? I guess to our eye, we don't see a lot of difference in the data between the doses. So, was 600 mg really the default and was going to be chosen as long as there's no safety issues preventing it? Thanks. You can take the first part? So, I'll take the first. This is Amir Fathi. I'll take the first part, and I'll open it to Mollie to discuss the choice of dose. So, I'd love to hear what Dr. Zeidan has to say about this. I'm not surprised at all that patients with KMT2A rearrangements do worse, particularly in a relapsed/refractory setting. These patients, in general, have more resistant disease. We have to keep in mind, again, as I mentioned earlier, that a good number of these patients, including, I think, a proportion of patients in the KMT2A group, had prior menin exposure. I think it was 20%. So, multiple lines of prior treatment, already a highly challenging refractory subtype of AML. So, having a low proportion of a relatively lower proportion of response is not surprising in the least, as far as I'm concerned, especially compared to a group of patients such as NPM1 mutated, which traditionally have a higher likelihood of response. So, I think that comparison is, in my own personal view, a bit of a false errand. I think in the context of some of the data, other data that's been presented recently, again, I reiterate that in the relapsed/ refractory setting, patient population and what makes up that patient population matters a lot. So, if it's a single center experience versus a multi-center experience, that matters. If you've had a lower number of prior menin exposure and a higher proportion of prior menin exposure, it matters. The difference in prior venetoclax or transplant exposure matters. The difference in the range of prior treatments matters. You simply can't control for those things. We in the leukemia field struggle. Forget about menin inhibitors. For years, we've been trying to decide which reinduction regimen is best for AML. Is it MEC? Is it HAM? Is it FLAG-IDA? We don't know because every single study that's been done has been done in different patient populations, and we cannot get a sense of what is better. As a result, every cancer center, every academic leukemia program does what they want, and they sort of point to their own studies. This is not a dissimilar situation. I fully realize that people want to sort of get a sense of what is better, and you have to in some scenarios. But for me as a leukemia doctor, it's impossible at this setting to sort of distinguish what is what. To be honest, the percentages that I'm seeing in terms of response are not that different from another. You have to kind of look at this and hope for a better estimate of ultimately what we're going to see in terms of tolerability, safety, and activity as we look at larger patient populations. That will ultimately tell us where we're headed, but. Yeah. No, I think I fully agree with that. In my opinion, major differences in the refractory R/R setting in terms of responses across studies are very, very difficult to compare. And I fully agree the patient composition, you have to always look at this data in terms of how were your patients treated previously, how many of them have seen venetoclax. As I said, in my view, my main take on the relapsed/refractory combination data is that it demonstrates clearly evidence of synergy, some activity that the combination certainly will demonstrate. Safety to take this to the front line. It demonstrates that when you take this combination to the front line, that the dose can be taken for long periods. It does not seem to potentiate the venetoclax-mediated myelosuppression, which is a huge headache with several of the other agents and certainly could, I think, become a major player. But I agree. I think with all these caveats, I think focusing in the relapsed/refractory setting combination studies, when you have different kinds of patients cohorting to get into your studies, I think it's tough to compare across them. I would just add one quick thing is this is not the patient population that ultimately we're going to try and figure things out in, right? So, I think we're trying to get to a patient population that's much more likely to have responsiveness and much more homogeneous. And that's the newly diagnosed set. The newly diagnosed patients, hopefully, have not had prior transplants, prior menin, prior ven. So, in that sense, they're more uniform. So, I think that's ultimately, I think, I guess the main probably preamble to this is does what we see in this relapsed/ refractory setting tell us a lot about what we're going to ultimately see in the newly diagnosed setting? Unfortunately, I don't think it's going to be a clear correlate. It has not been, and it probably won't be here. So, with regards to how we selected a 600 mg dose to carry forward into the expansion, obviously extremely multifactorial. We had both an independent data monitoring committee and a study participant safety monitoring committee that really evaluated all of the data that we had in order to help decide about dose escalations and dose expansions. So, we're looking at things in addition to exposure. We're looking at, obviously, the response rates, the MRD negativity rate, but also safety, as you referred to. And as we escalate, most people are looking to make sure that safety doesn't get worse at increasing doses. We had the good fortune of seeing safety actually improve at increasing doses and increasing exposure. And that supported very heavily our decision to carry through the 600 mg dose. But all else being equal, if you can get to the highest dose, best exposure for patients without additive safety issues, that is the one that we will try to optimize for patient use. That's very helpful. Thanks for taking our questions. Ladies and gentlemen, that concludes the question-and-answer session. I would like to turn the call back over to Troy for closing remarks. Thank you, Operator, and thank you, everyone, for joining our call today. We really appreciate Dr. Zeidan and Dr. Fathi spending their time and their being very generous with their opinions and their expertise. Appreciate all of your questions. And if you have any questions, please reach out. And otherwise, we wish you happy holidays and a happy new year. Thanks so much. Please close our conference call. Thank you for your participation. You may now disconnect.