Great. Thanks, everyone, for attending us at the Stifel Virtual Oncology Event. Really happy to do the next fireside chat with Kura Oncology. My name is Brad Canino, hosting Troy Wilson, President and CEO of Kura. Let's maybe start off with the state of the business and priorities for the rest of the year, Troy. Sure, Brad. Thank you to you and Stifel for inviting us to participate in the conference. In terms of the state of the business and the priorities, as you saw this morning, we announced we've submitted our new drug application for ziftomenib in relapsed refractory NPM1 mutant AML. We are going to be doing everything we can to support the agency's review. We will have more updates on that as the year progresses. In connection with that, we are increasing our pre-commercial activities to support the launch of ziftomenib in that indication. Looking beyond the initial opportunity in relapsed refractory leukemia, we are now in the process of study startup for the two phase III trials under the KOMET-017 protocol. That is ziftomenib in combination with intensive chemotherapy and with venetoclax and azacitidine. We provided some important regulatory updates on that earlier this year. We should be initiating the KOMET-015 study, which is evaluating the combination of ziftomenib and imatinib in GIST patients. We've guided to the first half of the year. We are looking to initiate one or more expansion cohorts for our farnesyl transferase inhibitor, KO-2806, in combination with cabozantinib, looking forward to providing an update on those studies, both for KO-2806 and tipifarnib in the second half of the year, potentially at ESMO. From a cash perspective, obviously, we remain in a very strong cash position. We had approximately $750 million in cash. I think I've said previously, we stand to receive up to $240 million in milestones under our collaboration this year. That gives us the resources and the stability, the de-risking that we need to be able to prosecute these different programs across the business. Great. Let me add my congratulations on today's announcement. It's great to see such an expedited submission for the NDA for ziftomenib. Now, what is the process from here and what regulatory pathways can you leverage for [inaudible]? Yeah. So we've submitted the NDA. Obviously, we have breakthrough therapy designation for NPM1 mutant AML. We also have fast-track designation. We're going to be seeking priority review. I get this question often. We've seen no impact from the changes underway at HHS and FDA. It may be that the hematology oncology section of the oncology division is more insulated. We see the same people, whether it is the guidance that we obtained from them on the frontline studies or leadership members of the review team. We're going to be working with them, Brad. First of all, we'll be awaiting formal receipt for review from FDA and, in connection with that, a PDUFA date. I would expect that that will be in Q2. At that point, we'll obviously disclose that. Once that happens, we'll be doing everything we can to support the agency in its review of the application. I think we'll continue to take advantage. All the track has been laid between the BTD, the fast track. Now it's really a matter of how quickly can we respond to requests for information and get the agency the information that it needs. Now, you released the top-line result with the NPM1 relapsed refractory setting as successful as a monotherapy for ziftomenib, KOMET-001. How should investors think about the profile? Because obviously, we have not seen the data yet, and those are forthcoming at a medical meeting. Yeah, yeah. As we said at the time, I'll say it again. The benefit-risk profile for ziftomenib is highly encouraging. The safety and tolerability were consistent with prior reports. I think of this in stages, Brad. I'm charged to look beyond the initial launch. I think we're going to be very competitive in the NPM1 setting. We're hopeful that we will have the data to present at a major upcoming medical meeting here. We'll obviously update you on that when we're able. I think we'll be very competitive in the relapsed refractory setting. We're also looking to share data from the ongoing KOMET-007 study, which is now evaluating ziftomenib in combination with intensive chemotherapy and venetoclax-azacitidine in newly diagnosed patients in the frontline setting. Again, we're guiding to the intensive chemotherapy combination data potentially at EHA, the venetoclax-azacitidine data potentially at ASH. The reason that that's significant, Brad, is you would expect, even with a monotherapy approval, that some physicians are going to be using these agents in combination. That's really how they're intended to be used, whether that's in the relapsed refractory setting or ultimately in the frontline setting. I think the overall profile will be as important as that monotherapy profile. I think we're going to stand tall on both counts, looking forward to, again, multiple data updates throughout the year. How will you and your partner approach commercial strategy? Will that change depending on if ziftomenib is the first or second menin inhibitor approved in the NPM1 setting? Yeah. I mean, as I've said, we are going to do everything we can to work with the FDA to support its review timelines. The initiation of our pre-commercial readiness activities have put us on a strong path to commercialization, and we'll prepare well for a competitive launch. We're assuming, Brad, I think it's safe to assume we're going to be even with the competition or even a little bit behind. It's always good to be paranoid. We are preparing to have a very meaningful commercial presence between us and our partners at Kyowa Kirin. And we'll be competing for share of voice and looking to win over as many patients as we can. I think we'll be ready when the time comes. Now, what are your insights from Syndax 's revumenib about the potential sales opportunity in relapsed refractory AML for menin inhibitors as we've seen that launch? Yeah. The preliminary insights say there's a growing awareness of menin inhibitors in the relapsed/refractory AML setting. Because of the specialty pharmacies that our competitor is using, you don't really have visibility into what's going on there. You can see certain aspects, but not others. We do believe, and we hear from our feedback, physicians are looking for products which they believe offer the best benefit-risk for their patients. I think we're going to see, again, that's part of why it's helpful to have multiple sponsors working in the space, the initial relapsed/refractory data, then the combination data, other combinations that will feed. You're looking for awareness. You're looking for both the class and of ziftomenib in particular. The fact, Brad, that we're targeting, again, potentially ASCO, potentially EHA, potentially ASH, we're looking to get that data out to the physician and patient communities. That is going to be our job for the next several years, again, in partnership with Kyowa Kirin. I think we're well set up to do it. Now, you mentioned moving to combinations and the priority there as well. Remind us, what was the combination profile that you think ziftomenib demonstrated in the phase I dose escalation data for those combos that we saw at ASH last year? Yeah. Let's start with the intensive chemotherapy side. There, we saw, from the interim analysis of the phase I portion, we saw a 100% CR rate in the NPM1 mutant setting, an 83% CR rate in the KMT2A rearranged first-line adverse risk setting. We had 100% of the NPM1 patients and, I think, 96% of the KMT2A patients alive as of the data cutoff, with a median follow-up of 31 and, I think, 19 weeks, respectively. That bodes well. We'd also, Brad, seen, and this was a surprise from what we were expecting. The KMT2A patients, for the most part, go on to transplant and then, in our experience, back on to ziftomenib. The NPM1 patients, many of them are electing to delay transplant or forgo transplant in favor of staying on ziftomenib as continuation therapy. That's a compelling benefit-risk opportunity for them. They avoid the complexities, the comorbidities of transplant. They're just taking ziftomenib as a once-a-day oral pill. It's also important for investors and our business from the commercial standpoint. As you look toward a data update middle of the year, look really to durability, Brad. That's going to be the question, right? That's what's ultimately going to drive the commercial case here, is are we able to keep these patients in response for prolonged periods of time? Shifting to the venetoclax-azacitidine setting, what we saw there, again, we were asked, FDA requested that we do the dose escalation in the relapsed/refractory setting, primarily because your goal there is safety and tolerability. We didn't see any issues as far as combinability. We were able to continue to dose escalate. As you look to a data update, again, probably now in the second half of the year, potentially at ASH, I would look now to the expansion cohort, which will be the newly diagnosed patients. There, again, now in the VEN+AZA, of course, patients do not typically go to transplant. If they did, they would go to intensive chemo. What you are looking there is, can you keep patients in response? Can you deepen the responses? I would say we are encouraged by the data that we are seeing. We would not be accelerating development of the KOMET-017 phase IIIs were we not seeing very promising data from the KOMET-007 expansion cohorts. Those, I think, will be two pretty meaningful updates, middle of the year and end of the year for intensive and non-intensive, respectively. You covered the difference in the patient baseline characteristics from the dose escalation, which we've seen, to the dose expansion, which we will see this year. Do you see the expansion cohort data as a way to reiterate the profile you've already shown, or is there going to be a new focus or additional data points for investors to focus on? I think new data points, right? For durability, the commercial case here that folks are trying to wrap their head around is how large is the frontline opportunity. I'm pretty simple, right? It's number of eligible patients x price point x duration of therapy. The number of eligible patients for the class is approximately half of all of the incident population each year, about 10,000 patients. The price point's been established by one of our competitors. Now the variable you're looking for is duration of therapy. That, I think, Brad, is what you're looking for from both of those frontline studies, both the 7+3 and the VEN+AZA. You're going to see a higher response rate in both settings. The response rates, I mean, intensive chemo has a pretty high response rate to begin with. VEN+AZA's more modest. You can improve upon it. What we're seeing is you can improve meaningfully on both of those. Importantly, we think extend the durability and give patients a more long-lasting clinical benefit. That's the new data from both of those cohorts that you're going to look for. I think the safety profile, Brad, should be fairly consistent. We've not seen DS. We're not seeing QT. We're not seeing any DDIs or any challenges with combinations. That's why those cohorts are enrolling so quickly. It will be about magnitude of clinical activity, depth of response in terms of response rate, depth of response, and then duration of response. That's what you should look for in those newly diagnosed patients in the expansion cohorts. What level of durability and maturity do you expect to have if the data is good? Yeah. For 7+3, we'll show the 600 mg patients from the escalation as well as the patients from the phase I-B expansion. We're going to zero in on the RP2D. We'll show all of those patients as of the data cut. For VEN+AZA, obviously, the focus will be on the newly diagnosed population because that's the population of interest. That's what informs KOMET-017. Importantly, we made a shift from relapsed refractory in the escalation to newly diagnosed in the frontline. That is likely. I mean, it's still early days. We've got into the second half of the year. You're likely to see a focus on the newly diagnosed patients in the VEN+AZA cohort here in the second half of 2025. Yeah. For these durability metrics, what do you think are the right benchmarks to consider as we think about these upcoming combo data? Yeah. Let's start with VEN+AZA to begin with. From VIALE- A with VEN+AZA overall, we saw a CR rate. CR is the key, right? That is the endpoint. You saw a CR rate of less than 40%. Now, the CR rate for NPM1 mutant would be you'd expect that to be slightly higher. Maybe it's in the 50% range after four cycles. For KMT2A, it's probably a little lower. For 7+3, the data shows us CR rates for NPM1 in the 80%-90% range. However, there, you need to look at the rate and the timing of relapse. You have, again, if you look at the literature, 47% of the NPM1 patients relapse. Of those, 60% relapsed in the first year, 80% relapsed within two years. That's the Bertoli. If you go to Blood in 2018, the Bertoli reference. That's really your benchmark, Brad. The KMT2A patients in the intensive setting, you'd expect to have a CR rate closer to 50%-60% with more frequent relapses. It's going to be important to look at the evolving times on therapy in those patient populations. Each of those, Brad, gives us opportunities to demonstrate a clinically meaningful benefit in terms of MRD negative CR for intensive, CR for non-intensive, and ultimately the survival-based endpoints. Now, looking forward to your registrational studies with combos. For the chemo combo, you've proposed a trial design to leverage MRD negativity for accelerated approval. That would be a first for AML. The question is, what key questions have you answered to the FDA that will allow this endpoint to finally be used in AML after we have seen it be utilized in ALL and hopefully soon in myeloma? Yeah. It's a good question. The key question, of course, is the adequacy of measurable residual disease as a surrogate endpoint for survival. We have been a member of what's called the MPAACT Consortium. Starts with an M, MPAACT, which was founded in 2018. It was founded among Janssen, Genentech, Novartis, Celgene, I think AbbVie, Amgen, and Kronos. We petitioned and became a member. That consortium, its goal is really to establish MRD as a surrogate endpoint for overall survival in the treatment of AML. MPAACT, that consortium, worked with the academic community to conduct a meta-analysis to assess the association of MRD with overall survival. As part of our briefing book for the phase IIIs for the KOMET- 017 intensive chemotherapy trial, we shared both published and unpublished data from MPAACT with FDA as part of our briefing book. In fact, FDA asked us, "How are you in the dialogue? How are you going to demonstrate the connection?" We said, "Well, we're a member of the MPAACT Consortium." They were like, "Oh, okay. Yeah." That gave them a lot of confidence because it's a multi-sponsor effort. Finally, Brad, and importantly, the KOMET-017 intensive chemotherapy trial includes both MRD negative CR and event-free survival. There is a built-in safeguard for patients. You're not going to maintain the benefit of accelerated approval unless you can also demonstrate a survival-based benefit longer term. Now, if MRD negativity is used for accelerated approval, how should investors think about the timeline for a phase III from start to potential registration? Yeah. Good question. We have guided that we anticipate initiating the phase III KOMET-017 intensive chemotherapy trial in the second half of 2025. I think that's likely to be probably in the fourth quarter. We have also guided we would expect top-line results in 2028. We have not been more specific than to say 2028 because our crystal balls are a little bit cloudy. That will be important, Brad, when you look at the number of patients who have been enrolled in the expansion cohorts to date, and you get a sense of the pace of enrollment. I think that will give us confidence. That is what we are using to benchmark the enrollment and ultimately the trial timelines. The rate-limiting step, not surprisingly, is actually site activation in these phase III. Once the sites are up and running, enrollment goes relatively quickly. You have sort of a sigmoidal curve of site activation. I think you could see data in 2028. We are going to do everything we can to make that earlier in 2028. We feel good that we can deliver data in 2028. Yeah. Now sticking with the chemo combo for fit patients, what do you expect around transplant utilization in this trial? How will ziftomenib maintenance be employed or not? Yeah. It's a good question. As I mentioned, I think, in an answer to a previous question, we anticipate most of the newly diagnosed KMT2A-rearranged AML patients go to transplant. That is their best hope for a cure. Our experience thus far has been many of the newly diagnosed NPM1 patients who are MRD negative. This is MRD negative as measured by the sites, which uses a different assay than what we'll use in the trial. We're going to do a central review using bone marrow. Many of those patients who were MRD negative will stay on ziftomenib in continuation therapy and not go to transplant. The data suggests that patients who are MRD negative, transplant has a negative benefit risk. Importantly, and this is, I think, a coup for Mollie Leoni, our CMO, and our development team and regulatory team. The trial's designed, Brad, as a three-arm trial to assess the impact of ziftomenib both in the induction and consolidation portion as well as the impact of ziftomenib post-induction consolidation. You get to look at both in that three-arm study. The statistics are based on the NPM1 mutant population. That's how we expect it's going to be used. Now, what is the status of potentially working towards a FLT3 quadruplet with chemo to address the other frontline fit patients who have the co-occurring FLT3 mutation? Yeah. This is the challenge and the opportunity with AML. Just as you're getting the triplets going, people start talking about the quads. That is really the best benefit for patients. We have generated encouraging preliminary data thus far combining ziftomenib with gilteritinib in relapsed refractory NPM1 mutant AML. Remember that the co-mutations with KMT2A are so infrequent, it does not really make sense to have a separate cohort. We are anticipating initiating a combination of ziftomenib and quizartinib in newly diagnosed NPM1 mutant FLT3 mutant patients in the second half of this year. We continue to think that the FLT3 mutant population represents a significant opportunity for menin inhibitors. I think, Brad, to your question, we have some work to do just to understand how broad you want the aperture on FLT3 mutants to be. Certainly, I think we're optimistic that there's a path to combination and a pretty meaningful opportunity to drive benefit for patients, again, if you're able to prolong them in response and delay transplant, as well as a meaningful commercial opportunity. Moving to the VEN+AZA combo and strategy there, you mentioned the endpoint focus on complete response. Yep. One of the questions I have for this study, though, in phase III is, what level of dose management should we expect for venetoclax specifically in the triplet? We know that causes cytopenias. Will the FDA allow for reduction and then to control cytopenias before they require a reduction in the investigational menin inhibitor? Yeah. It's a really good question. Here, again, I have to tip my hat to Mollie Leoni and our development and regulatory teams. First of all, let's talk about kind of what do you expect. The rate for CR in VEN+AZA is lower. It's typically about 50%-60%, which is what enables it to be a CR for accelerated approval. You don't need to go to MRD-negative CR. You actually have enough of a margin that you should be able to show a clinical benefit by dosing with the triplet, including a menin inhibitor. The survival-based endpoint, of course, is overall survival. Relatively few patients go to transplant. To your question about dose management, we continue to not see any drug-drug interactions between ziftomenib and any of the standards of care. We don't have to hold or reduce ziftomenib to manage cytopenias. We were encouraged, and we shared this as part of our feedback from our meeting with FDA, we were encouraged that the FDA permitted reduction of VEN+AZA after two cycles, consistent with real-world experience, Brad. That's typically when you start to see those cytopenias begin to impact patient well-being. Kudos to my team and credit to the FDA that FDA recognizes that and actually allows us to, if you will, adopt real-world usage of VEN+AZA in the trial. That will, of course, be in both the ziftomenib arm and in the control arm. It should be better for the patients. It should lead to a better result. What type of treatment durations would you expect in the frontline unfit population? I guess there's always the question of how you think about the relative size of a market potential for the frontline fit versus the frontline unfit. Yeah. What we've guided to is that we expect 18+ months in the frontline intensive chemotherapy setting and approximately 18 months in a frontline non-intensive setting. The difference is, of course, the non-intensive, the patients are generally older. They're not as fit. That's what's driving that. It's not the therapy. At present, based on our experience, Brad, we're guiding that we think peak sales for the menin class are probably about $7 billion a year. Peak sales for ziftomenib, we think we can probably take $3 billion of that $7 billion. How you split between intensive and non-intensive, it could be 60/40 VEN+AZA to intensive. It could be 50/50. What we're seeing, interestingly, is the KMT2A frontline patients all go to intensive chemotherapy. They're generally younger. They're going to go to transplant. You're going to try to get them to a cure. The NPM1s, interestingly, if they do not have to go to transplant and you can drive a durable response, intensive chemo becomes a lot more attractive to them if they can stay on Zifto as an oral agent. That is why I say to you, let's call it roughly 50/50. It might sway a little bit one direction or the other. Okay. Great. Troy, unfortunately, we're out of time. I want to congratulate you again on the progress with the NDA. I guess as we're sitting here in this macro environment, it's a great time to be a well-capitalized company. Kudos for executing the deal with your Japanese pharma partner. Thank you. Thanks for joining us. Thanks, everyone, for listening in. I hope you have a great day. Thank you, Brad.