Good morning, everyone. Thank you for joining us. This is the Kura Oncology ASH investor event, and it's a pleasure to have all of you with us. If you haven't, feel free to get some food, some beverages, and get comfortable. The plan is we're gonna try to go for about an hour, just so that everybody can set expectations. We're gonna try to get Dr. Erba and Dr. Wang out of here at a reasonable time. If we can have the next slide, please. Obviously, as part of this being a Kura sponsored event, I do have to give you the forward-looking statement. You can look either at the SEC's website or our website for more information about the company and about the risks and uncertainties of an investment in the company. I will tell you that I believe both the oral presentation and this presentation will be available on our website if you wanna take a look, so d on't feel like you need to take pictures or anything. They will be available to you. If we go to the next slide, the agenda. I'm going to turn it very shortly over to Stephen to introduce himself and the others here on the dais, and then you can see the agenda here. I will tell you, we're not intending to take questions during the session. I would expect we'll probably go 30 minutes or so. We'll take questions at the end. We're gonna take a combination of questions both from the people here in the room, as well as we have a number of people dialed in on the webcast. That's our intent. When we get to the Q&A session, you know, we'll take as many questions as time permits. Again, welcome. With that, let me turn it over to Dr. Stephen Dale to introduce himself and our other panelists. Thank you, Troy. A very warm welcome, just to echo Troy's welcome. It's great to see you all here. Thank you for taking the time to join us, and also to our attendees on the webcast as well. I think I've spoken to some of you, albeit through Teams most of the time, or Zoom. I'm Dr. Stephen Dale. I'm the Chief Medical Officer here at Kura Oncology. These are very exciting times for Kura, extremely exciting times. We're gonna go through again and walk through our highly encouraging data that I'm sure many of you, if not all of you, saw Dr. Erba present just earlier, giving these patients in such a difficult-to-treat population hope for the first time. With that said, it's with great honor that I introduce two of our esteemed investigators who have joined us today, Dr. Eunice Wang of Roswell Park, and also Dr. Harry Erba from Duke University School of Medicine. It's important that we get across how important menin inhibitors are to our patient populations. Dr. Erba and Dr. Wang will go through that in more detail now. Without further ado, I hand over to Dr. Wang. Thank you very much for the opportunity to speak to you today. This is a disease that Dr. Erba and myself face every day in our clinics and on our inpatient wards. For us, this is our daily reality. I'd like to introduce you to the two subtypes of acute myeloid leukemia that both he and I have been struggling to treat over the majority or all of our careers in leukemia therapy. There are many FDA-approved targeted therapies for acute myeloid leukemias, but currently, there are no approved targeted therapies for these specific biological subtypes of acute myeloid leukemia. An NPM1 mutant AML represents a third of newly diagnosed AML patients in this country. These patients often are found to have not only NPM1 mutations but other co-mutations. Although some have postulated that these patients with NPM1 mutant disease do "better with standard chemotherapy," they still remain a patient population of unmet need. About more than about 1/2 of these patients will relapse, and the recommendation is, even after achieving remission, that we often do need to still consider allogeneic stem cell transplantation in many of these patients. The five-year overall survival currently is only 50%, and the median overall survival in patient whose disease recurs after upfront therapy is only 6.1 months, and that's 50% of 15% of all newly diagnosed acute myeloid leukemia patients. KMT2A, formerly known as mixed lineage leukemia or MLL gene rearrangement, has been described in approximately 1,000-2,000 cases of AML per year and constitutes what we would feel is a smaller fraction of newly diagnosed AML cases. Per the European LeukemiaNet and other prognostic classification symptoms, the presence of a gene rearrangement involving the KMT2A gene is associated with intermediate to poor prognosis, meaning that the estimated five-year overall survival in these patients is less than 20%. These patients have traditionally been the ones who present with recurrent disease at a very early stage and have an overall survival that is very limited and in the range of months. Patients you can see here often undergo second and third line therapy, and many of them are not cured, even with the administration of allogeneic stem cell transplantation. What is ziftomenib? Ziftomenib is a potent and selective oral inhibitor of the menin KMT2A MLL complex. We've known through cytogenetic analyses that patients who have rearrangements involving the KMT2A gene biologically have an epigenomic complex involving the KMT gene and about up to 80 different partner genes. This complex interacts with DNA and affects transcription programs, specifically transcriptome programs governed by genes such as HOXA9 and MEIS1. Perturbation of an upregulation of these transcriptome programs leads to active leukemogenesis, as is the primary biological pathogenic lesion that leads to leukemia in any KMT2A rearranged leukemia. We also know through correlative studies that patients with NPM1 mutant leukemia, even though they don't have a set of genetic rearrangement of the KMT2A gene, have involvement and expression levels of genes and transcriptome profiles that closely mimic what we see in KMT2A rearranged acute leukemias. This complex, the KMT2A rearranged complex or similar complexes in NPM1 mutant disease, are activated by binding between the KMT2A protein and the menin protein. The menin protein, it, as we know, has been involved in many solid tumor syndromes, and is involved again in very key biological underpinnings of leukemogenesis as well as other solid tumor genesis. The binding of menin and KMT2A is necessary for the activation of that leukemogenic complex. The ziftomenib is a protein-protein inhibitor. It blocks the interaction between the menin protein and the KMT2A, which is necessary for activation of that complex. By blocking that interaction with a targeted, highly potent and specific inhibitor such as ziftomenib, we're able to down-regulate DNA transcription of many genes, which then lead to differentiation of these immature myeloblasts and eventually terminal differentiation and cell apoptosis. Next slide. The KOMET-001 is a first-in-human clinical trial of ziftomenib in patients with relapsed and refractory AML. This trial has been divided up into phase I-A and a phase I-B cohort. Phase I-A cohort is a dose escalation cohort, first- in -human, where the drug was given as a monotherapy once a day at doses starting from 50 mg all the way up to 1,000 mg. Early dose cohorts were postulated to probably be under the pharmacokinetic efficacy level. Single patient cohorts were done until we saw evidence of some clinical activity, and then the cohorts were expanded to three patients each. The main goal of phase I-A dose escalations portion was to establish safety, tolerability, evaluate drug pharmacokinetics, and look for early evidence of antitumor activity. Given the early nature of this first-in-human study, patients were enrolled on this study in the absence of or agnostic of any mutations. Any patients with relapse and refractory disease could have been enrolled in this cohort. I'm gonna describe the results of phase I-A cohort and then turn it over to my colleague, Dr. Erba, to present the data from phase I-B cohorts. Phase I-A cohort involved 30 adult patients with relapse refractory AML with mutation agnostic enrollment. Out of these patients, we saw that we were able to quickly escalate from 50 mg. Starting at 100 mg-200 mg a day, there was evidence of some clinical activity, and the cohorts were subsequently expanded. In these patients, there were no significant toxicities at early stages. There was no evidence of QTC prolongation and no evidence of any significant need to dose reduce or alter the dosing based on its interactions with CYP3A inhibitors, such as antifungal azoles. In the 400- mg dose, there was one dose-limiting toxicity of pneumonitis or aspiration pneumonia. At the 1,000- mg dose, there was a patient who developed a differentiation syndrome and subsequently had to have the dose reduced to 800 mg. There was also evidence of early tumor activity. There were two patients in phase I-A who achieved a complete remission, one of which was MRD negative and one of which was MRD positive. One patient had an NPM1 mutation and has remained on therapy at 200 mg now for over 31 months. This patient remains in CR on monotherapy. There was no evidence of an NPM1 mutation and no evidence of a KMT2A rearrangement, but had SETD2 and RUNX1 mutation characterizing their disease. This patient also achieved a complete remission at a low dose of drug. This brings up the question of whether further patients who do not have the target mutations may also at some point be a candidate population for further evaluation of this drug. Based on the promising evidence of some clinical efficacy and stability of disease in 30% of patients treated on phase I-A, the decision was made to proceed on to phase I-B validation cohorts. Dr. Erba? That's me. Thanks, Eunice. Dr. Wang has been involved in this program since phase I-A. I joined it during phase I-B, and that was helpful to me to be able to learn from my colleague, Dr. Wang, about this drug and managing patients receiving it. I'm gonna show you excerpts of the presentation I made this morning. The first thing I'd like to say, though, is hats off to Kura for paying attention to the FDA guidance with Project Optimus, which is definitely going to be a, something that the FDA will look at for new drugs applications, especially targeted therapy. The idea here is to avoid the mistakes we've made in the past with the development of some drugs. I will mention, one that I've been involved with, Quizartinib or AC 220, where the dose was ramped up very high, to the point of toxicities, especially QT prolongation. It became clear afterwards that the biologically effective dose, the one that hits its target, was about, you know, 10% of that maximally tolerated dose. All the phase I work had to be redone to finally get to a recommended phase II dose. Kura has taken this Project Optimus initiative to heart, and what we did here is we looked at the patients who were in phase I-A, who achieved a response of any type showing biologic activity in the two lowest doses. Those were 200 mg and 600 mg. What you can see here is that, of course, we did see treatment-emergent adverse events in these patients. As AML doctors, Eunice and I can tell you that every patient on an AML trial will have a treatment emergent adverse event. These are very ill patients. But what was remarkable is in the NPM1 mutated group, there were no grade 3 treatment emergent adverse events in either the 200 or the 600 milligram dose in NPM1 mutated patients. We had quite a population of NPM1 mutated patients. You could see it was 20 patients, not a huge number by, you know, breast cancer cardiac studies. But in our world, in a phase I study, this is quite remarkable. I will tell you that part of the reason for this is the activity that we were seeing and the tolerability that we were seeing that made this an attractive drug for investigators to offer their patients. Later on, Eunice is gonna tell you about a specific 22-year-old man who got this drug very early in his disease course. In the KMT2A rearranged patients, we did see some signal of the tolerability issue, and that was with differentiation syndrome, which I'll explain more, and then, of course, febrile neutropenia. We saw febrile neutropenia with KMT2A rearranged, and it begs the question, why didn't you see febrile neutropenia in the NPM1 mutated group, at least not grade 3 or 4? One thing that you have to understand about drugs that lead to differentiation, like the IDH inhibitors, is that we like them for our patients because one of the first things you see is recovery in the neutrophils. The major cause of mortality in AML patients is neutropenic infections. This, I can't say that's why we didn't see it, but it is definitely something that we all saw with our patients very early on in the course of therapy. Next slide. As I mentioned, if you look specifically at the differentiation syndrome with ziftomenib, we saw four out of the 20 patients in the NPM1 mutated group have what appeared to be a differentiation syndrome. Only one of those was grade 3. You might say, "Well, what's not grade 3?" I had a patient, for example, who I was managing. He was in a different state, actually. He had my cell phone number, and sometime around Christmas time, last year, he ends up in an outside emergency room because he had retained some fluid. Didn't have any fever. His white count was starting to go up, no hypoxia, doing well, good performance status. I talked to the physicians at the emergency room and said, "Start dexamethasone," and his symptoms went away very quickly, which is probably the best way to identify differentiation syndrome. Only one out of 20 actually had differentiation syndrome. What's also remarkable about when we see differentiation syndrome in the NPM1 mutated group is that in this case, you actually do see responses, complete remissions afterwards. 75% of the patients who had differentiation syndrome with this drug achieved a response. That's because, as we'll show you, this drug does work by differentiation. It's distinguishable from the IDH inhibitors, where we saw differentiation syndrome, but the level of response in that group was 50% or less. It begs the question, why? Why is that there, that difference? I'm gonna come back to it in how we distinguish menin inhibition in the NPM1 mutated group from what we're seeing with IDH. Now, in the KMT2A rearranged patients, it was a different story. There we did see more differentiation syndrome and higher grade differentiation syndrome. You could see a very rapidly rising white blood cell count in these patients, and it could look like blasts. Many patients will come off. Their investigators took them off treatment to give them something else. I actually, in treating some of my patients, didn't do that because I actually had patients that had no other options, had been through everything else that they would accept. This was their last chance. I had no other option but to manage the leukocytosis that we saw with hydroxyurea, and you can get them through that point. Not every investigator had that experience that I had. You see in our analysis of KMT2A rearrangement, you look at the swimmer's plots, there are some patients who came off very early for apparent progression. Which I think is unclear since they didn't stay on if it truly was progression. Nonetheless, this is what we saw. Why did we see differentiation syndrome like this? It was atypical, too. It was not the classic differentiation syndrome that we've seen with acute promyelocytic leukemia, where the white count goes up, the cells all differentiate, they respond quickly to steroids, and they all achieve a remission, okay. This is different. In the KMT2A rearranged patients, we were seeing very atypical presentations. To give you an example from the, three of the five patients that I had so far on this study that, six patients, sorry, that I've treated on this study. Three of them had the KMT2A rearrangement. Three had the NPM1 mutation. Of the three who had the KMT2A rearrangement, one of them had actually initially presented with her leukemia about a year before. Was treated by an internist with vitamin B12 because she was anemic and her gums were swollen. That all turned out to be leukemia in her gums, as these monocytic leukemias with KMT2A rearrangement often have. With standard chemotherapy, that went away. What was interesting is that when she went on the study, her white count went up and her gums were swollen. My colleagues who were seeing this patient were like, "This drug isn't working. Take them off, do something else." I had to remind them, in that patient, there was nothing else. It was a woman who'd had breast cancer, which I'm gonna come back to in a second, and got intensive chemotherapy and had therapy-related AML, and already gotten intensive chemotherapy, and already got HMA venetoclax. There were no other options for her, and she couldn't, and she did not wanna get a transplant ever. This was the only option. All I did was manage it with hydroxyurea and dexamethasone, and lo and behold, during the second cycle, it all goes away. She actually develops other signs of differentiation later on with a sinusitis and a lot of neutrophils in her right on left knee and then her right wrist. I had another patient who presented initially with his AML, had sinus involvement. When he responds to this therapy, he developed progression, apparent progression in the same sinus from differentiation syndrome. It's a very atypical course, and we think the reason I think we're showing it on the next slide. Why don't we go to that? We think the reason for this is that the ziftomenib accumulates in sites other than the marrow and the plasma. Here you see two other sites or three other sites, the brain, the heart, and the spleen. This is obviously preclinical data that we have here. You can see accumulation with high tissue penetrance as ziftomenib. That's a good thing, right? 'Cause you wanna be able to treat the leukemia wherever it is. On the other hand, it led to very atypical presentations of differentiation syndrome that could look like progression of the disease if you weren't expecting this, and we weren't expecting this at the beginning. It's not that the drug doesn't have activity. It has incredible activity in KMT2A rearranged patients. I think we have to optimize the dose and more importantly, what concomitant medications we use in that group of patients. The next slide now shows us the response that we were looking at in the NPM1 mutated patients, 20 patients there. You can see we had six true complete remissions and another a response for a total overall response rate CRC of 35%. We had morphologic leukemia-free state, it goes up to 40%. True CR, 30%. What's really impressive to me about this data is the concomitant mutations that were seen in patients who had a response. We know that patients who present with AML don't have just one mutation. The median is four, with older age, it's even more than that. We have learned with other differentiating agents, such as the IDH inhibitors, the more mutations you have, the lower the chance of response. Mutations that are in the Ras- MAP kinase pathway, Ras mutations and FLT3 mutations, do not respond very well to IDH inhibitors. Here, although we don't have a full data set yet, we have been able to analyze the data from the sites of the patients who responded. You can see we have eight overall responses. In those patients, we saw FLT3 ITD mutations. We saw IDH1 or IDH2 mutations, Ras mutations, complex numbers or high numbers of co-mutations. Why are we seeing this? I think it really belies the biology of NPM1-mutated AML. This is an event that occurs much sooner in leukemogenesis. In fact, NPM1-mutated MDS probably doesn't occur. It's probably a myeloid leukemia, AML, that's just caught before the blasts have really taken off. It's the biology of the disease here that's important. Remarkable to me, we've seen these responses. We're talking about combinations of drugs, but we've seen responses in patients who weren't getting a FLT3 inhibitor, and remarkably, in patients who were not getting an IDH inhibitor at the same time. In fact, Mollie will remember, I panicked a little bit on my last patient because she had an IDH mutation and an NPM1, and in the first cycle, she didn't really have a complete remission yet. I was thinking, "Is there any way we can amend the study to add in an IDH inhibitor?" By the time we would have done that, it would have been like, you know, God knows when. Well, just by sitting tight on her, 'cause again, she didn't have other great options other than to switch, she went into a complete remission that's ongoing at six months with, that's MRD negative by flow, and the NGS panel can just barely detect NPM1 and IDH mutations. The take-home point here is we are targeting something earlier in leukemogenesis. As I mentioned, because many patients were taken off early because of a rapid rise in the white count, this extramedullary disease that would be flaring, we saw very few responses. Does the next slide show the... Yeah. What you can see here is it's not that they don't respond. If you look at the red and pink bars, those are the KMT2A rearranged patients, and you can see there are blast reductions. Although some of those blast reductions look pretty trivial, keep in mind you're not looking at how long these patients actually were able to remain on treatment. Part of the problem is shown on the right, is that the white count goes up very quickly in the first cycle. You have to be ready to get that under control with hydroxyurea, is what we typically would use. Next slide. Here's the swimmer's plot that I was talking about. You know, what you would love to know is, well, what's the duration of these responses, okay? You know, we love telling you about the patients who are doing well for a long period of time, like, our colleague, Amir Fathi, having a patient who's been on therapy for over two years on the 200-mg dose from the cohort that Eunice reported on. We have in this cohort another patient who's remained in remission for a long time. With the follow-up on therapy of only four to five months, we don't actually have a median survival. We don't have a median duration of response that we can report to you. The best we could do is show you the swimmer's plot. We're very excited about what we've seen in the NPM1-mutated group. This is at the 600- mg dose. Based on target knockdown, we're actually decreasing HOXA1... HOXA9 and MEIS1 levels with 600 more than 200. A level of PK supports 600. The correlative data, PK/PD, and the clinical data and the safety data all supported in unison the 600- mg dose. The FDA has agreed on that, and we are about to open up the expansion phase of 600 mg as a single agent in the relapse refractory setting. Just before I leave this slide, you know, I didn't present this this morning. I felt badly not presenting it, but I didn't have a lot of time. Look at the top part, the KMT2A. I didn't really focus on it, but just remember, that drug has activity there. If you look down at the bottom, you have five patients being taken off very, very quickly within the first cycle of therapy because we're seeing that blast count go up. Although, you know, I don't have a crystal ball to know what would happen if they stayed on, I would imagine that many of those patients, like my patient, may have actually ultimately had a response. If not a morphologic leukemia-free state and able to get to a transplant, maybe even a CR. Next slide. I'm gonna turn it back to Eunice to go through four of the patient cases. Oh, I did wanna say one other thing about KMT2A rearrangement. When you look it up, you're gonna be thinking about pediatric patients with ALL. That's where it's really more common. They have a really poor prognosis. Let's not forget about people who are receiving anthracycline chemotherapies, topoisomerase II inhibitors for another cancer and then get therapy-related AML with KMT2A rearrangement. That's a thing that has a really bad prognosis, and these are patients who've been beaten up by prior chemotherapy, their prior cancer. In having drugs that are menin inhibitors, even as single agents, but definitely in combinations with lower intensive therapy, really would be a breakthrough for that population of patients to get them to transplant. I think I see about two or three breast cancer patients every year exactly with that scenario. Eunice. I think it's best when we talk about the data to talk about individual case studies because I feel that sometimes we lose that when we look at these waterfall plots and survival curves. Given our personal experience with the drug, we'd like to just walk you through some illustrative case reports. This was the patient in the phase I-A study, being treated at a first-in-human study, 200 mg of Ziftomenib. You can see young patient, 44-year-old woman with a NPM1 mutant and co-mutations in DNMT3A and IZF1. Now, I would like to highlight that, out of the 30 patients treated in phase I-A, the median number of prior therapies was between three and four prior therapies. About 3/4 of patients had received prior venetoclax-based therapy. Seven patients, as including this patient, had prior stem cell transplantation. These were patients that were really appropriate probably for hospice, and it was only at these academic centers that we continue, some of us, to pursue, given the young age of the patients, giving patients like this additional therapeutic options on a phase I study. Looking here, you can see the list of the prior therapies she's gotten. She's gotten not one, but two allogeneic bone marrow transplants and about five conventional chemotherapy drugs as well as multiple experimental drugs. I think that most of us would have largely abandoned therapy on this young individual early on. She initiated ziftomenib at 200 mg. She had no evidence of DS. Had some treatment-related AEs, grade 4 lipase increase and grade 8 pancreatitis, which resolved. She was the only patient on phase I-A to have, I think pancreatic abnormalities. Had a grade 3 pulmonary embolism during cycle 17. You can see that she achieved, after one cycle of therapy, a CR MRD negative after failing eight, nine lines of therapy. This MRD negative CR has been maintained on 200 mg of drug. She's currently at cycle 31, so she is our long-term survivor. This is my patient, a 61-year-old gentleman, NPM1 FLT3, ITD, and IDH2 mutant AML. This is a very common cohort of patients with these triple mutations. Got standard upfront therapy, 7+3, and a FLT3 inhibitor, midostaurin. Was on midostaurin maintenance with high dose consolidation when he relapsed. Treated again with FDA-approved FLT3 inhibitor, gilteritinib. Relapsed again after several months. At that point, really, the decision was: should I give him a FLT3 inhibitor, an IDH inhibitor, or should I target the NPM1? I just took a leap of faith and said, "I am going to target the NPM1." Again, one would have said, "Well, you have agents to target the other things." Dr. Erba would have said that wouldn't necessarily would have been I would have done. We took a risk and gave him the ziftomenib at the 600 mg cohort on the phase II expansion. We started the drug, and literally, like, the white count started immediately going up. His white count was three, then it was 10, then it was 17, then it was 25. He started developing severe bone pain. I ended up admitting him on day three. He was hypotensive. His white count went up and up, went up to 58,000, we felt very strongly that this was not that his disease suddenly decided to become hyperproliferative, but this is really consistent with clinical evidence of differentiation syndrome. We, unlike many investigators, kept him on study. He received cytotoxic chemotherapy, aggressive steroid use, for management of the differentiation syndrome, he was an inpatient. We noticed after we instigated some of these mitigation strategies that his white count started to go down, then maybe his last count was starting to go down, he became cytopenic. We repeated his marrow after cycle 1. You can see here on the right-hand side, baseline bone marrow, 75% blast, 40% cellular. At our cycle 1, day 28, again, after one cycle of ziftomenib, he had a hypercellular marrow, 95% granulocytic hyperplasia consistent with differentiation and no evidence of blast. He was still MRD positive at that point, we knew that he still had residual disease that was differentiating, but my hematopathologist was completely baffled as to what was going on, and she was even asking me, did I mix up the patient's bone marrows and maybe this is a different patient, looked more like a myeloproliferative disease. We continued on the therapy. He achieved full count recovery at cycle 3 and has been an outpatient for several cycles since then. He did subsequently relapse, but he enjoyed six, seven, eight months as an outpatient after his initial cycle 1 therapy. Remarkable evidence of biological activity again. Can I interject? I'm sorry. Sure. I know this is supposed to be your four slides, but... Feel free to interrupt me at any time, Harry, as always. At least I'm letting you talk this time. She always brings up a prior meeting where I didn't let her talk. We're like old- Yeah. ... you know, like an old married couple. Speaking of which, not even my wife of 10 years can predict what I will and will not do. Mm-hmm. For this patient here, I completely agree with your decision. The patient already failed a FLT3 inhibitor. My patient I recently put on had a FLT3 TKD mutation. I had to tell her about gilteritinib, but I think the response rates are lower there. She had an IDH2 mutation. I had to tell her about enasidenib, but the median time to response is four months. Like your patients do with you, they say, "Well, you've gotten me this far. What do you suggest?" Based on what we were seeing in the trial, especially with the combination of NPM1 and FLT3 mutations and IDH mutations, and the rapid response in the NPM1, I said, "Well, we could always start with the menin inhibitor that we have, ziftomenib, and if it doesn't work, then we could think about those other things." She agreed and is now in a CR. I wanna emphasize, you think of these FDA-approved agents. I wanna remind you that gilteritinib for relapsed and refractory FLT3 mutant disease has a true CR rate of 30%. Enasidenib, which is approved for relapsed and refractory IDH2 mutant AML, also has a true CR rate of about 20%. With the ziftomenib data that we have from our phase I-B, we have a true CR rate in 20 patients of 30%. The response rates that we're seeing with monotherapy with the ziftomenib are similar to the response rates of FDA-approved other targeted therapies for acute myeloid leukemia. I just want to emphasize that, and that is why looking at this patient's mutational profile, it's really a toss-up whether we should be offering a FLT3 inhibitor or whether we should be offering an IDH inhibitor or whether we should be offering an NPM1 targeted therapy. Moving on to the next case, one concern has been what about the lack "of responses" in patients with KMT2A rearrangements? I would argue that this is a difficult disease to treat with a different biology, different manifestations. As Dr. Erba showed you during his ASH presentation, there is stable disease" no responses" and then there's evidence of clinical efficacy. In this 47-year-old woman with KMT2A rearrangement, TERT and BRAF mutations, who had received, again, you can see one, two, three, four, five, six, seven different therapies, including donor lymphocyte therapy and radiation, initiated on ziftomenib. By the end of cycle 2, within a couple of months, clearing of the bone marrow blasts. You can see here after two cycles, evidence of that tissue penetration improvement in multiple sites of extramedullary disease. We're not talking about one small area. We're talking systemic clearance of marrow blasts and systemic clearance in extramedullary tissue. I can tell you right now that clearance of extramedullary disease is not seen with many targeted therapies and typically requires giving high-dose cytarabine-based regimens to get this level of systemic clearance of disease. This is typically not what we see with other targeted therapies. I've not seen it with any of my other targeted commercially available agents. This led, although this is technically not a response, obviously, you can see here the clinical benefit for this patient. Next slide. The last patient, which Harry has also mentioned, again, represents a sort of a leap of faith in one of our clinical investigators. This was a 22-year-old gentleman with NPM1 mutant AML, presented with newly diagnosed AML. He was in the military and was in a different city than when he lived, when he was diagnosed and was admitted to the local academic center and received standard induction chemotherapy with a 7+3 regimen. Unfortunately, did not respond to this regimen. At this point, one could have argued that he should have gotten high-dose cytarabine regimen. He should have, he should have been given another experimental therapy with no better known efficacy. Many things you could have offered this patient to get him into remission. Again, the investigator said, "Well, in contrast to the other patients, every other patient I have presented here has been treated with multiple lines of therapy" in phase I-A, between three to four lines of therapy. This patient had one1 line of therapy. Taking that leap of faith, giving ziftomenib single agent therapy, 600 mg, was associated with a very potent biological response. Immediate development of differentiation syndrome. As we saw, 70% more patients who developed differentiation syndrome had evidence of an overall response. That was an encouraging sign. After one cycle, 28 days, evidence of a MRD negative complete remission. Now this patient was able to return home and is now awaiting a transplant in his home center after he could have died. He could have never made it out of that academic center. He had refractory disease, now he's proceeding on to a potentially curative allogeneic stem cell transplantation. We do believe that moving this agent earlier in the treatment course, having less pre-treated patients, may, as we know, each line of therapy that we give alters the clonal burden that selects potentially for therapy-resistant clones. Moving any agent earlier up in the treatment cycle, first line, second line, in the salvage setting, could lead to higher responses. The fact that we have responses of 20%, 30% CRs in patients who had seven prior lines of therapy suggests the power of a targeted agent for this particular disease. Next slide. Do you want me to do a summary? In summary, we feel that ziftomenib demonstrates an encouraging safety profile and excellent tolerability. The events that we're seeing, treatment-related, are consistent with the mechanism of action of this agent. We see, interestingly enough, this drug is a once-a-day oral inhibitor. There is no evidence of drug-induced QTC prolongation. There is an on-target expected differentiation syndrome, which is associated with at least in NPM1 patients with potential response and with the high biological activity. We see that the clinical activity of ziftomenib by pharmacokinetic analysis and clinical efficacy seems to be optimal at this time at the 600- mg daily dose for NPM1 mutant patients. There is pronounced evidence of clinical activity at a 30% CR rate in a cohort of 20 patients treated to date. We also see encouraging high levels of ziftomenib tissue penetration, which potentially is evidence of the potency of this agent to bind and inhibit these mutant cells, even in sites of extramedullary disease, where we did not even see PET avid disease initially. We're not suspecting it. We've seen this drug react with hidden tumor cells. The monotherapy data, however, does demonstrate that there is a role for potential combination strategies, and this might be an excellent agent to bring into combinatorial regimens with backbone chemotherapy, given the lack of predicted adverse drug-drug interactions. Given the fact that one of the ways that we mitigate differentiation syndrome in our patients who develop it is to give them cytotoxic chemotherapy 'cause the immediate eradication and destruction of rapidly differentiation cells could dovetail very nicely with the clinical efficacy that we're seeing with the biological agent. We are hoping that by combining this via rational study designs, that we can keep patients on study that are having rising counts and maximize their time on study with disease control to reap the clinical benefits of prolonged administration. We think that oral once-a-day dosing is a convenient administration, and can be very easily combined with current standards of care, as Dr. Erba mentioned in his presentation. I'm turning it over to... Can I? Okay. Just add on one more thing. We've focused on the beginning when we start ziftomenib and the toxicity. The other thing I've seen in my own patients is once they achieve that remission, the quotes from my patients, "I don't even know that I'm taking a drug." Exactly. Right. Like, my patients are coming back once a month. Yeah. They're not transfusion dependent. There's no side effects. They don't lose their hair. They're not transfusion dependent. This is, for them, like a miracle drug. Yeah. GI tolerance has been, in my patients, exceptional. No nausea, no vomiting, no interactions. No, no need to change their cardiac meds or their azoles or other interacting medications. I mean, it's truly, once you get through cycle 1 and cycle 2- Mm. ... if you achieve a response, that tends to be maintained. Yeah. My 75-year-old patient went back to playing tennis three times a week- Yeah. ... on this drug. Stephen? Thank you, Dr. Erba. We had a very positive interaction with FDA recently as an end of phase I meeting. As you heard Dr. Erba in his talk this morning, FDA agreed our recommended phase II dose to push forward into phase II at 600 mg for our NPM1 patients. I think it's important to understand what led up to that and the challenges that FDA have placed in terms of phase I oncology. I think everyone in this room now is fully aware of Project Optimus. It seems to be bandied around almost weekly now or daily. It's incredibly important. The standards FDA have set now have come well away from all of the traditional phase I oncology methodologies that we know and love. Our 3 + 3 designs, our rolling six, hitting MTD, then doing a cohort expansion, and then moving into phase II. Those days are gone. Those days are gone. FDA now are looking for the lowest optimal pharmacologically active dose. Kura Oncology, it's important I say this, because we're ahead of the curve. The menin team already were thinking about how could they look across a range of doses, you know, about the 200 and 600 mg, but how could we meet FDA's strict requirements following phase I-A study? Even before it was well known, we were already looking at designing the phase I-B as a randomized by dose study with a strict futility hurdle built into it. Not normal practice for phase I. The number of patients in the KO-539 ziftomenib phase I far exceeds what you would normally see when you add up what was in phase I-A and phase I-B. The team have successfully navigated through these challenges, and have helped set a gold standard, a new gold standard for how you navigate. To give you a sense, during the end of phase I meeting, that we attended recently, FDA even made a comment, one of the assessors made a comment to us to say that they were pleasantly surprised at our NPM1 data and our approach. Not every sponsor are doing studies like this, to meet the tough requirements. FDA were very clear that, having reviewed our end of phase I package, because remember, of course, we have to send a full end of phase I report to FDA that has a full report of all of the clinical pharmacology, all of the clinical data and all of the safety data. What FDA are looking for all of the time is what's the optimal benefit risk assessment. Everything is about benefit risk. Optimal efficacy, optimal safety, where can you find the balance? That's what the end of phase I report showed. In addition to that, we also took the opportunity to, as an addendum, to send the phase II protocol, with the end of phase I report and with the briefing document. Many of you will probably know that that's atypical. Normally, you wouldn't do that, but we felt it gave a strong opportunity for FDA to have an early look at our phase II pivotal registrational design to save time because we already had the protocol. FDA in the same meeting not only gave the green light to our recommended phase II dose to push into phase II, but also gave the green light to move forward with immediate effect with our phase II study. With that in mind, we're looking to recruit enroll the first patient in Q1 next year. We are good to go. Everything is on track for moving quickly into the NPM1 patient population. Of course, as Dr. Erba and Dr. Wang have beautifully articulated, we also see response, albeit okay, it doesn't meet the many formal response requirements for CR/CRh, but we see strong activity in KMT2A. We will be looking to use dosing in combination to address those patients with KMT2A, chiefly using a staggered dosing approach, so a debulking approach with a cytoreductive agent first before introducing the menin inhibitor. We're gonna have multiple combination studies in NPM1 mutant, looking at both frontline and also relapse refractory and looking at KMT2A patients. Mollie will walk through that very shortly. Of course, the potential to address 35% or more of acute leukemias. I would like to personally congratulate the team on this. This is an incredible achievement in an environment where FDA are really pushing back. As all of you, I would say in this room know that big pharma, large pharma are getting pushed back, even being called back from phase III to redo their dose optimization. This is a success story, but most importantly, a success story for these patients with such high unmet medical need. Mollie. Well, thank you. Yep. I'm gonna go over some of the combinations that we're planning, and I will try to keep it brief so we can get to the question and answer period. As you've heard us all allude to, the best way to treat AML patients is by getting to them earlier and in combinations. That's why we have designed two comprehensive trials to generate safety and dosing data in a vast amount of potential combinations so that we can arrive at some safety data and some dosing optimization for all of these potential combinations. While we'll be generating a breadth of data, we will be prioritizing combination data generation in combinations we know will cover the vast majority of our patients and where we've already seen the evidence pre-clinically of synergy, namely venetoclax combinations and gilteritinib combinations. With that, as you can see, we will be starting off with our NPM1 mutant patient population path. Of course, this is the majority of your AML patient population. One out of every three AML patients that walk into Dr. Erba and Dr. Wang's offices is going to have an NPM1 mutation and thus be addressable with a ziftomenib combination. While the prognosis may be different from some of the others, it is still something that is not a good leukemia to have. There's no such thing as a good leukemia to have. Addressing it early and making sure that we keep these patients from relapsing is of utmost importance, because once they relapse, the prognosis is extremely poor. We will be looking to get to these patients in both the frontline and the relapse refractory settings and combinations for both the fit and unfit. Venetoclax, gilteritinib, FLAG-Ida combinations, and IDAC/LDAC combination, as well as 7+3. While we're doing post-transplant and continuation therapies in all of the trials, we will also be doing a dedicated post-transplant maintenance trial as well. If you go to the next. For our KMT2A rearranged patient population, and I will tell you, the FDA specifically asked us how we would be addressing this patient population. They are very interested in us getting back to this development path as well. These are the combinations we will be looking at. We will be eliminating some of the combinations we're doing for NPM1 just for feasibility reasons. We will be doing largely the same combinations by approaching it from this way as well. It'll actually get us started on our ex-U.S. path as well because you need combination and randomized studies in order to register outside of the U.S. Having these combination strategies started will get us on that path to be a global, a global option for patients. You will see here again the venetoclax combinations, FLAG-Ida, IDAC/ LDAC, and the 7+3, as well as, of course, the maintenance therapy. Again, the maintenance and continuation therapies will be designed throughout our trials. As we've described in the phase I-A, we absolutely saw that there are other subtypes that are potentially MET-independent. We want to get back to them. We also want to get to the ALL population and to our pediatrics population. We are going to do that now, optimizing that in the monotherapy before bringing it into the combination setting. With some of our collaboration partners, we will be getting into the pediatric setting in a much more in-depth way, in combinations for AML patients and for our ALL patients. The way we are doing it, this is the way you can go to the next one. This is how all the pieces fall together. We will be doing the monotherapy still in our KOMET-001 that continues on. Our NPM1 mutant registrational portion, as Stephen said, will start in Q1. We will be optimizing our non-NPM1 and KMT2A in the monotherapy setting before bringing it into a combination. We'll also be doing the same with ALL patients. We will then be doing the majority of our frontline work in what we're calling KOMET-007, although there will still be some of our relapse refractory work as we might as well include our venetoclax also in that, in that portion of the study as well. We will be doing the majority of our relapse refractory AML work in what we call KOMET-008. That will be where you'll see our gilteritinib and our FLAG-Ida, as well as our LDAC/IDAC combination. Then in partnership with some of our investigators, we will be doing our post-transplant maintenance that I referred to, and then our pediatric studies with our ALL and our AML. That wraps that up, and we can move on to question and answer. Great. Let me thank the four speakers for that. That's really helpful to set the foundation. We have time to take a few questions. I would ask, we have a question here in the front. Got it? Okay. I'd ask you if you ask a question, we're gonna try to alternate between the live audience and the webcast audience. Can we do Jonathan? Can I ask you to please just identify yourself before you ask the question? For the webcast. Yeah. Hi, guys. Jonathan Chang, SVB Securities. Congrats on the progress, and thanks for taking my questions. First question, what are your latest thoughts on the differentiating features of ziftomenib in the menin inhibitor competitive landscape after the ASH presentations today? Second question, what are your thoughts on applying for Breakthrough Therapy Designation? Sure. Stephen, do you wanna take that second question? Sure. On Breakthrough Therapy, maybe Mollie, you can take the question on differentiation from competition. Thanks, Jonathan. Yeah. For Breakthrough, so in short, the answer is yes. We will be applying for Breakthrough Designation. Interestingly, FDA in the phase I meeting actually brought this up as well to ask whether or not we would be submitting a BTD application. It did actually come up from one of their assessors. In effect, of course, we're gonna use all the regulatory tools that we have at our disposal to expedite development. This is just one of those tools. Yes, we'll be looking to do that, of course, in NPM1 patients. As far as what do I think is differentiating between us and some of our competitors. It comes down to what we see as potentially our issues with getting KMT2A to the responses with the differentiation syndrome and the rather unusual presentation of it. It's the extramedullary disease. Our competitors. First, there's room for all of us at the table. As we've discussed a lot over the past couple of days, every other disease is allowed to have more than one molecule to treat a specific disease. Do I think that we have some advantages? Yes. Do I think that we can treat extramedullary disease in a much greater way? Yes. Do I think we have preclinical evidence and clinical evidence of that? Yes. Differentiation syndrome is both a plus and a minus. It is evidence of our ability to treat the extramedullary disease, and I'd actually ask if Drs. Wang or Erba wanted to further elaborate on their opinions on that. I can say the Syndax drug, I agree completely with Mollie. This is a novel class of agents. We don't have to just have one. We have many that is the most beneficial for our patients. We know this is an active class of agents. The data with the Syndax is highly promising. They have slightly different patient populations. They also had just slightly different toxicities. They had a DLT of QTC prolongation, which limited their ability to further increase their drug dose. They did have about a 16% incidence of differentiation syndrome, but they did not have any grade 3 or greater differentiation syndrome, which begs the question of whether had they not had the QTC prolongations, whether they could have further increased the dose of their drug and gotten greater clinical efficacy. We will not know the answer to that. I think that the very potent tissue binding that we're seeing, the potency and our activity levels, correlating with differentiation syndrome in NPM1, have not been shown in any other agents. Especially in NPM1. To me, I, the numbers have changed somewhat over the months as to what their CR/CRh range is. We do have a very clear signal of complete responses at 30%. I do think that we tend to have a much clearer signal in the NPM1 mutants. The only thing I would add to this is, I know from your perspective as investors, this is an incredibly important issue, but this is incredibly early, right? I mean, these are small numbers of patients. I'm glad that Syndax is developing their drug, Kura is developing their drug, and there are others, because we still have so much to learn. Drug-drug interactions, true response rates when you get into larger number of patients, combinations of therapy, you know, just, you know, so much, and the interaction of these different mutations with these different drugs, in inhibiting menin. I think, you know, it's very early. The fact that we have two drugs that target this population makes us very happy. Hopefully both will continue to be developed. I know the people who develop statins are not satisfied with just one or two statins. Leukemia doctors are no different. There's a question from the Webex. Dr. Erba, maybe I can ask you to take this. It's a twofold question. Can you comment on the unmet need for NPM1 patients, both in the relapsed refractory setting and in earlier lines? The second part of the question is, you talked a lot about the incidence of co-mutations. Can you speak to that maybe in a little bit more detail? Okay. I'll be brief on this. In the relapsed refractory setting, a number of groups are getting data together of what the outcome of these patients truly is like, it's not favorable. Relapsed AML is has a very poor outcome. Remember, the only potentially curative option then is transplant, which means patients are facing a decision about going through a procedure that has 20% risk of treatment-related mortality and significant impact on their quality of life down the road. Potentially curative, comes at a price. I clearly think that there's an unmet need once the patient has relapsed refractory disease. The real question is, will the patients get there? Well, I, absolutely. I mean, the fact that we put 20 patients on the study very quickly attests to the fact that these are the patients we're seeing. Yes, they are included in favorable risk if they don't have a FLT3 ITD, so that eliminates half of them right there. There are other co-mutations that likely do impact, and then there are patients who just don't respond. I've seen two patients with NPM1 mutation that are supposed to respond to VEN-AZA and have not. They are definitely there. Of course, from our perspective, the greatest hope is moving these things up front, so maybe not in the initial indication, but we've seen that the addition of targeted therapies to intensive chemotherapy in the FLT3 space has improved survival. We're definitely hoping that's gonna be the case with menin inhibitors improving survival there as well. You're talking about 1/3 of the patients with NPM1 mutated disease. In terms of the co-mutations, you know, we only have 20 patients with NPM1 mutation that we studied in phase I-B. I only was able to show you this data or allude to this data here, where we have patients with FLT3 ITD, patients with IDH mutations that are responding, patients with Ras mutations. As you can see, in the, there are two patients there that responded that typically don't respond to IDH inhibitors. RUNX1 may also be a target here associated with a poor prognosis. We have a lot to learn about, you know, really, how targeting menin in NPM1 mutated and KMT2A rearranged disease is really gonna impact on the biology. What I've seen so far just makes me very hopeful that we are targeting something early in the pathogenesis of the disease. Quite frankly, it makes me think of the days, early days of arsenic trioxide and ATRA in acute promyelocytic leukemia. We were getting away from chemotherapy altogether in that subtype. I don't think it'll be quite that easy here, I do think they'll add benefit to all patients with NPM1 mutated disease at the time of diagnosis. Maybe last quick comment. You've heard of the Kronos Bio study of entosplentinib that closed because of a number of reasons. This is not entosplentinib. Menin inhibitors have a clear path forward, a clear mechanism of action. It makes sense to use them, and there's incredible excitement among leukemia investigators to bring these forward. That might not have been seen with entosplentinib, but it's definitely seen with this drug. Thank you. We have time for probably a couple of more questions. Roger, you wanna go ahead and ask one? Peter, I'll try to get you next. Thank you. Yeah, this is Roger from Jefferies. Just a quick one, maybe just ask for the comment from the investigator, two investigators here. Seems the DS, differentiation syndrome mitigation strategy or the protocol is pretty critical for the further development. But just curious, how have you, if at all, communicated with other investigator, and how do they see the kinda mitigation strategy for the differentiation syndrome, particularly as you're moving to the combo study for the KMT2A outside of just using a debulking kind of a therapy to make sure there are not too much kind of a tissue disease? And how about the DS specifically for the mitigation strategy, any enhancement to be able to manage the kind of side effects? Thank you. Does one of you wanna take that? I'll take it. Okay. I think that we did see very potent differentiation syndrome with these agents very quickly, as opposed to with the IDH inhibitors, where the differentiation syndrome can occur over a matter of weeks or even months. The majority of patients that had differentiation occurred with initial cycle. The mitigation strategy that was developed was developed with input from all the investigators on the trial in terms of sharing our shared clinical experience. We do see differentiation with many other agents for AML, FLT3 inhibitors, IDH inhibitors, ATRA and arsenic. We are able to manage those, and with the implementation of the standardized mitigation strategy across all of our sites, the severity and the impact of differentiation syndrome was actually very well managed subsequently. We feel that with the addition of cytotoxic chemotherapy in the combination regimens, that we will likely see less differentiation syndrome because the main mitigation strategies involve the addition of agents such as a single dose of cytarabine or increased doses of hydroxyurea. We actually anticipate that differentiation syndrome may be less seen in combinatorial agents. We've seen that with the combinations of IDH inhibitors with azacitidine and IDH inhibitors with standard 7+3, the incidence and the management of differentiation syndrome was not as difficult as it was with initial monotherapy. I'll just add to that APL. Remember the days when now we're using arsenic ATRA alone, but in the days when we were adding on arsenic and ATRA versus single agents showing a high rate of differentiation syndrome and then adding it to chemotherapy, the rate of differentiation syndrome went way down. We expect the exact same to happen with this combination. Right. We are finding that differentiation phenomena may be a characteristic of all effective targeted therapies for AML. Yeah. Ultimately, the mitigation strategy was necessary for monotherapy. We don't think it'll be as necessary for combinations. I'm gonna try to squeeze in maybe two more questions 'cause we've got to let Dr. Erba and Dr. Wang get on. Peter, do you want to go and then Phil, we'll do you next. Sorry. Perfect. Thank you. Peter Lawson, Barclays. just on the NPM1 patients, I'm just kind of curious how doctors would think about using a FLT3 versus IDH1 versus a NPM1 drug, potentially. where patients carry two or three of those mutations. I guess a follow-up just around zifto, as it kind of moves to earlier lines, do you expect to see better response rates? I do think that we'll see better response rates. I was very impressed with the very quick response and depth of response in the 20-year-old patient who received it after 7+3. We do hypothesize that we would see better efficacy if we weren't using patients that had failed eight lines of therapy. In terms of the targeted therapy, as Dr. Erba suggested, 50% of NPM1 mutant patients will have mutations in FLT3, and many of them also have co-mutations in IDH1 and IDH2. The path forward, as Mollie mentioned, one of the path forward is to combine the targeted therapies with menin, with the gilteritinib-targeted FLT3 therapy. Whether that would induce more differentiation syndrome, whether it would be more efficacious, we don't know. We have, however, seen responses in patients that have failed prior gilteritinib. We feel like the activity of the menin inhibitor is probably independent of FLT3, and actually may complement or ideally synergize with the FLT3 inhibitors. Yeah, I think that's the important point. These patients often show up with proliferative disease, so a drug like gilteritinib might get the disease under control instead of hydroxyurea, and then you add in your menin inhibitor. That's just to manage the patient. I think in terms of the biology, we're seeing responses. The same is true with the IDH mutations. I think we need to look at the entire dataset. Were there any patients with NPM1 and IDH mutations who didn't respond to this combination? I mean, do we really need to think about combinations or do you knock off NPM1, you block it, and then it doesn't matter what you have afterwards? We have a lot to learn. Phil, you wanna go ahead? Hi, Phil Nadeau from Cowen. Just two questions from us. First, congrats on the data, very impressive. In terms of the dose for KMT2A patients, did the FDA sign off on the 600- mg dose, or do you need to do more dose ranging studies as you move into combination? Second, is there any data on transplant, patients that went on to transplant and the outcomes post-transplant? Thank you. Mollie or Stephen, you wanna take those two? Sure. In discussions, we agreed that the mechanism of action is the same regardless of NPM1 or KMT2A. 600 is the appropriate dosing for leukemia in general. In combinations, we will of course, start at a lower dose and build back up. We will still go back to some dose exploration and combinations in order to appropriately establish the correct dose for NPM1 and KMT2As. As for transplant, you know, we've had a handful of transplants occur. We've had patients that are still in their complete remissions post-transplant, and we have other patients that are scheduled to go onto transplant as well. As you saw from our data, over 30% had already failed prior transplants. An additional probably 30% were never eligible for transplants. An additional 30% probably never want to have transplants. We think that we're probably at a rate we're expecting to see for our patients that wanna have transplants. Yeah. Just to be crystal clear. Just at 600 mg for monotherapy in NPM1 does not require any further dose optimization. Correct. Yep. Yep. We have, just room for one more question. I'm gonna take. I can't resist. I'm gonna take it from the webcast. You spoke previously about activity in patients who had prior menin inhibitors. Can you comment on that? I think we do have a slide in the backup. Mollie, do you wanna take this one? Sure. We actually have treated a handful that have had prior menin inhibitors. We were actually discussing this patient last night 'cause I wanted to get Dr. Wang' and Dr. Erba's opinion on this. This was a 70-year-old female with a KMT2A that had had prior Syndax exposure as well as other therapies as well. Came on I believe the most immediate prior was actually the Syndax drug, and came out with a 42% bone marrow blast, initiated at 600 mg. Ultimately, while we never got this patient to a full response, we got their bone marrow blast count all the way down to an 18%. We saw a pretty significant decrease in the bone marrow blast count, and we were able to keep a KMT2A patient, which are normal, very difficult to control their disease. We were able to keep her pretty steady throughout while really decreasing the blast count. I took away the ANC and platelet numbers that we had been looking at as well, but we actually got their ANC up as well and got her off regular platelet transfusions to a reduced level. We saw some pretty significant activity in a patient with prior Syndax exposure. Terrific. Pete, can we go to the milestone slide? Slide 20. This is the last slide. Just, we're gonna wrap up here. Just to remind everyone as Stephen and Mollie mentioned, the intent is to dose the first patient in the registration enabling KOMET-001 study next quarter. The KOMET-007 protocol is under review at the FDA right now. We're intending that that study will also kick off in the first half. As Mollie mentioned, the KOMET-008 study, which looks at combinations in the relapsed refractory setting, we're guiding that toward the second half of next year. Just to remind you on the FTI side, we are intending to dose our first patient in the current lung study early next year. We're in the process of screening patients now. Our goal is also to determine the optimum biologically active dose for the PIK3CA cohort in our current head and neck study, seeing some very encouraging data in that study. We are on track, as we've indicated, to submit our IND for KO-2806. That, as we'll talk about next year when we're well on the other side of ASH, that opens up a whole host of combinations with various targeted therapies. With that, let me thank our panelists, in particular, Dr. Wang and Dr. Erba for being so generous with our time. A number of us from Kura will be able to stick around here in the room afterward. I wanna be respectful of our guests' time. I wanna thank all of you for attending, for your questions, for your interest. We'll try to take as many additional questions as we can before we all have to go on to our next session. Thank you again from all of us at Kura, and hopefully you have enjoyed this presentation and enjoy the rest of ASH. Thanks so much.