All right, welcome everyone to 2025 Jefferies Global Healthcare conference. My name is Roger Song, one of the senior analysts covering MedCap Biotech in the U.S. It is my pleasure to have the fireside chat with our next presenting company, Kura Oncology. We have full crew here, CEO Troy, we have the commercial officer Brian, and then we have CMO Mollie. Welcome. Thank you. Thank you. Excellent. All right, so off the press, we have this ASCO presentation. We all are coming from Chicago a couple of days ago. What are the key highlights you want to have for the audience who may not attend that meeting, although they should, they should? We can drive the drill down some of the details. Sure, Roger. Thank you to you and Jefferies for putting on the conference. We did do an analyst-investor call immediately after ASCO. If people want to listen to it, they can find that on our website. In terms of what people should take away, I think most importantly, you know, between our data and our competitors' data, you now have two positive trials saying that, you know, this is a mechanism that works in AML. These are likely to be real drugs. They're likely to be approvable. We can talk about how they differentiate from one another and the labeling and so forth, but that's, I think, an important step forward. You see a meaningful CR/CRh rate. You see, in terms of 23% for the phase two portion, you see importantly 16.4 months median overall survival for the responders. That's significant when you think about the overall survival in relapsed refractory leukemia typically being sort of three months. That says that these drugs are really doing something for those patients who respond, and that is all responders, not just CR/CRh. You see importantly ziftomenib is active in, you know, it's consistent, consistently active. It doesn't matter on the line of therapy. It doesn't matter if the patients have had transplant. It doesn't matter if they've had prior venetoclax. You're seeing a consistent level of activity. That's all good. That's all on the activity side. On the safety and tolerability, you're seeing, you know, importantly no myelosuppression differentiation syndrome that is well managed. We know that that is a class effect, and yet with ziftomenib, you know, the physicians are able to manage it very effectively. You don't have clinically meaningful QT prolongation. We did have, you know, several instances of investigator-assessed QT, but, you know, that is, there are reasons for that, there are, you know, other explanations. There's not really a QT signal there. I think good combinability. It's once a day oral dosing, you know, very convenient and very easy to use. I think two things, Roger, is as we look at the benefit-risk in the monotherapy, we think it compares potentially very favorable to our, you know, the one approved menin inhibitor. I'll just, I'll put a plug in here now because I know we're going to come back to it. We're looking forward to sharing the frontline 7+3 combination data at EHA on June 12th. There, I think you'll see why we keep stressing the importance of safety, tolerability, combinability, the absence of myelosuppression. These agents are going to be used in combination, and that's where you're really going to start to see, I think, what ziftomenib can do in a combination context. So those are the key takeaways. You know, we now have a PDUFA date of November 30, and we're just super excited to keep moving the program forward. All right, well said. I don't think in any ambiguity there, this ley line RNR, NPM1, AML data is, you know, absolutely impressive in terms of the details and the consistency, the differentiation on the safety profile. For sure, it's very clear. Before we talk about the first line, which should be the next focus, you have the PDUFA date, November 30, and then priority review with BTD. That's the only and the first BTD for this setting. How should we think about, you mentioned, you gave us some teasers here to differentiate differentiation in the label, right? How should we think about this profile? You can expect the label different from other, you know, menin inhibitor. Then we talk about the commercial dynamic for that setting before we move on to the first line. Sure. Can you do the differentiation as well? Sure. Thanks, Roger, for the question. Yeah, we think that, you know, the data and the, as we said, that we presented earlier this week and the data we've seen from some of our competitors, from an efficacy perspective, are largely kind of price of entry, I think, into this space. You know, CR/CRh, duration response, things like this are based on feedback we've heard seem to be, you know, comparable and I think an important step for getting product available for patients in this setting. I do think within the label is hopefully as we get into some of the ability to combine with concomitant medications, not have to dose adjust. Those are some important things that I think we think we'll be able to articulate in the label. The safety profile, I think also as being safe is going to be important. You know, some of the work we've evaluated as a pre-commercial team right now is try to understand like where some of those differentiation points may be. Something which may sound simple, but once daily dosing is meaningful. I think that's been meaningful from what we've heard from both physicians, their practices, and their patients without requirement of potential QTC monitoring for cardiac monitoring for QTC prolongation, things like that as well. The dosing is also vastly simplified from what we expect to see. The dosing will be vastly simplified than what is currently in the Revumenib label due to having to consider so many drug-drug interactions. I think all around the safety and the combinability, even as a monotherapy, shines through. Yeah, and then the QT, the cardiac monitoring. That is another thing that we see pretty common. And weekly for at least a month, and then afterwards a few months monitoring. That is a forever advantage on the treatment. Right. Yeah, and just while we're on that point, Roger, if in the absence of a competitor, you know, what we hear clearly from physicians is, I would do that, right? I would do cardiac monitoring if I had no other option. But if there is another option where you don't need it, then most of them say, well, why would I do cardiac monitoring? That's important in the relapsed refractory setting. Becomes very important again as we're thinking about how can we keep these patients on continuation therapy as we go earlier. That's what's really, I think, going to pull through. You know, we're prosecuting the regulatory and commercial in the relapsed refractory, but also, as you'll see again at EHA, having experience in the frontline setting where when you look at those patients going out on the swim lanes, think about whether or not they have to come in monthly for cardiac monitoring or dose adjustments or other things. That is again where I think our safety and tolerability profile will pay dividends. Yeah, yeah, I totally agree. We know oncology is a competitive space and also for the incidence, you know, patient. I understand for one of the competitors, they got approval in another subgroup, not in this subgroup. We do not know if they will get before or after you get approval, but I think the timeline will be similar. I do not think you have a significant first mover advantage for that population, although, you know, I do not know if it is right or wrong to say some off-label use in the beginning while you are waiting for the new label. Maybe on that point, what is the feedback you are getting from the physicians? Say, okay, I have a drug, I may have some experience and I may have something that I start to use, but I have two approvals upcoming and how are I going to switch those patients, my new patient to use that? Sure. Yeah, thanks for that question. I think from what we're hearing from physicians, they're excited that there are options now for a menin inhibitor and multiple menin inhibitors on the barricade, I think may be good for them. I think they're starting to get some experience and we're happy to see that a menin inhibitor in this space is something that offers that benefit for patients. I think whether or not we become the first approved therapy or our competitor becomes the first approved therapy, I do not think is going to be as big of an impact in this space given that both of us are still new to this, you know, even if there is a few months or a year before we get our first approval, we are still new to this space and there is still, you know, kind of building our relationships other than those that we have really started to build out strongly with our clinical programs. Molly and the team have really kind of built a robust clinical program that has given a number of investigators experience with ziftomenib, and we think that will be helpful for us as we transition into the commercial setting. We are also setting up our commercial team to, you know, recognize that AML is a competitive space. We're planning to be ready for, you know, day one to get product out and to really start to engage with those customers as soon as possible and do what we're able to do compliantly to start to engage with physicians once the sales team is on board and preparing to kind of profile those physicians. We feel pretty confident that we'll be ready for that launch whenever that may come from the FDA. We're sure that we'll ensure that we'll be able to get product out to patients as quickly as possible too. Awesome. All right, good. We should, you know, move on to talk about an even much bigger opportunity for the first line. I think Troy, you already gave us some teaser in terms of the upcoming EHA presentation. Maybe just give us a little bit more in terms of what should we expect, right? You know, you talk about the swim apply for the durability and then maybe some of the other aspects we should focus on MRD and then any other data point we should focus. I think some of the biggest things you should look at, of course, we'd love a good response rate. We've had a very robust response rate in this patient population. We'd want to see a consistency of that. I want to remind you that you're going to see not just our phase 1B patients, not just the expansion patients, but you'll also see patients that came on during the phase 1A. Clearly they've been on trial a lot longer than these later patients we'll be showing you. You'll be able to see their story, their patient story, their durability, how they're doing, you know, 40+, 50 plus weeks onto treatment. You'll see through the swimmers' plots that they have actually stayed on treatment. You're going to be able to see the MRD, which I think is very important, and that will of course still evolve over time. A very important point to look at, which speaks again to safety and combinability, is time to count recoveries. The time it takes for these patients to actually get back to their quote unquote norm where they're not at risk for infections to that extent, where they're not at risk for bleeds. Many drugs, when you combine them, you get compounded myelosuppression. We're very pleased to be able to show you that we do not believe that is the case with ziftomenib therapy. Got it. Okay, very good. I think that's it. Another aspect is you are the first one to report the 7+3 intensive chemo, you know, the combination, while other, you do have the other, you know, menin inhibitor, but they are only in the Veneza combination. Why is that? Why does it matter? Maybe just a correction. We had intensive chemotherapy phase I data at ASH 2024. I think J&J did as well. Oh, J&J. We have announced as part of Comet O17 that we will be doing a randomized phase three in that setting. We have not yet seen, Roger, to your point, we have not seen any other of the sponsors of menin inhibitors yet announce their registrational plans in the intensive chemotherapy setting. That is different than what has happened in the Veneza setting. Yeah, yeah, got it. Okay, the reason that you can move so fast is because you have the phase one data and then also the profile, the safety profile is good enough to do the combination. You know, the phase three design is very, you know, creative and then to be able to combine those two regimens together to do the pivotal. Yeah. Yeah, that's right. Okay, good. Maybe just for the, that's a 7+3, we're going to have some data at the EHA. You also continue to do the expansion for the Veneza. That data will come in a bit later, potentially ASH. What should we expect from there? You know, similar story or any particular points you want us to focus? Similar story, but you know, this will be, we'll show probably the relapsed refractory data, not definitively yet, but we'll make, this will be the first glance at the frontline venetoclax azacitidine data. The patients won't have been on for as long as maybe our phase 1A 7+3 patients, but still you start to see the trend in time to response and time on treatment, the ability to keep these patients on treatment even if they're modifying the backbone durations. Again, time to MRD negativity, time to count recoveries will also be extremely significant. Veneza is, you know, I think every institution uses it their own way because it's so myelosuppressive, they want to use less of it whenever possible. We have designed a study that hopefully allows them to do that for the benefit of the patients and while still getting full coverage of their disease with the menin inhibitor on board. Okay, got it. Okay, and then that's your phase one expansion with that data supporting your plan into the pivotal phase three. As I mentioned earlier, you have pretty creative design for the phase three. You know, the U.S. always asks, you know, with all the FDA change, so you know, the confidence level you still can stick with that accelerator approval potential pathway for your phase three, you know, anything change and based on your interaction with the new FDA? No, we don't expect any changes and we haven't seen any turnover or anything like that in our particular review team. We wouldn't expect like changing perspectives to play any part in it at this point. Yeah, I think the hurdle that we were able to get over or the field has gotten over, Roger, is relating MRD negativity or, you know, in the case of intensive or CR, in the case of non-intensive to, you know, to benefit and to a survival as a surrogate for survival. We do not see that changing, right? I know there has been some discussion around MRD negativity, but that is more in the context of multiple myeloma. The issue was not the adequacy of the surrogate endpoint. It was that you had patients who, you know, have the potential to stay on therapy for 10 years. That is not the case in AML. AML is, you know, patients are in desperate need of these therapies. I think there is a recognition that we need to do all we can to get patients therapy. There will be survival-based endpoints for both of the phase threes that offer the protection to the, you know, to the ultimately to the patient community that there is a survival-based benefit. We do not see any change coming from any of the health authorities. Yeah, got it. Yeah, we're just coming from ASCO, still the pretty clear desire to build the correlation between the MRD negativity to the survival, and then you have all the mounting evidence to support that correlation. I think that may lead to this kind of endpoint design. Yeah, that's correct. Yeah, okay, good. All right, and then you guided it, you will start the trial second half and then between now and then, what's going to supposed to happen before you can start the trial? It's all. Not try to press you, you know, I know it's still on track. Right now it's all about operationalizing. You know, every site has to be contracted with and it has to go through their IRBs, et cetera. That's what we're currently doing. Obviously, the protocol's been final, been with sites and everything's moving along quite well. Yeah, something may not be appreciated, I'll just call it out, Roger, because I think it was a very clever idea by Mollie. We're combining two phase threes under a single protocol. Where that really helps us is at this point in terms of operationalizing the trial. There's contracting, there's budgeting, there's IRB or ethics review. We don't have to do that twice for two phase threes. We're doing it a single time and you now have a protocol where, with a fairly narrow exception, almost any patient who presents at the clinic is eligible to come on the O17 protocol. We have a lot of operational synergy and that's what allows us to be competitive and we think move more quickly than our competitors in the field in the front line setting. Maybe just how big a deal you can combine them, you know, in a relatively in parallel session to be able to get a label pretty broad in the first line. And then based on your feedback from the investigator or advisor, say, okay, if I get that label, how I will, you know, use the drug, you know, more or less than people with a narrower label. Are you talking about in the combination? Yeah, combination. Intensive versus non-intensive. Yeah, I mean, keep in mind the labels will come in waves. So, you know, should everything go as planned, the initial accelerated approval will be for NPM1 mutants. And then we'll add on the overall, the full approval with all patients. And similarly for Veneza, it'll be initially the CR approval with full approval coming after that. The label is just one piece of data that treaters have when they're using. And they are always looking to revolutionize the way they're treating their patients. So they are always wanting to do new ISTs, which we have a lot of those going on so that they can try out new combinations or maybe some of their pet combinations that they think are good. So the label will be wonderful, but will they always stick to it? No, they're going to treat the way they think is best for their patients. Yeah, I was going to say that goes back, Roger, to where we're stressing safety, tolerability, convenience, once-a-day dosing. These physicians are very sophisticated. Treatment patterns vary by institution. Many of them use venetoclax, but we've done two things. Again, Mollie spearheaded this. One is we have a broad foundation of both Kura-sponsored and investigator-sponsored studies with ziftomenib in different combinations. Including intensive chemo, Veneza, but also things like FLAG-IDA, low-dose azacitidine, gilteritinib to give, we'll eventually publish that data. That'll give clinicians experience with how to use ziftomenib safely. This growing body of safety and tolerability data gives them the flexibility to use the drug as they see fit. Ultimately, that's what they're licensed to do and that's what we want to enable them to do. To Mollie's point, it's less about, yes, the breadth of the label is really our ability to promote, but this growing body, and we've made, as you can tell, a considerable investment in development. We think that's really going to position ziftomenib to be best in class. Got it. Understanding your intensive chemo cohort or study, you do have the maintenance therapy component. That part is likely coming along with the accelerated approval or that's maybe later on? That'll be along with the full approval because it'll come after they've finished consolidation and the accelerated approval endpoint is measured prior to consolidation. It will, it is designed to be in the label once for the final result. Absolutely. Okay, got it. All right, let's talk about the market opportunity. I think you give us some good assumption for the future first line AML and then maybe talk about the overall market and then how ziftomenib will play into the future market. In the front line setting? Yeah, in the front line setting. Sure. I think the way we look at this is that, you know, there are approximately 20,000 patients diagnosed with AML a year. We think about half of those patients may be eligible to receive a menin inhibitor, either if it's, you know, in these combinations that have KMT2A, NPM1 mutations or FLT3. If you think that, if you split those patients, somewhere roughly half of each, half of the patients may go on to intensive therapy, the other half may go to non-intensive. The intensive therapy patients, we see there may be an opportunity for patients to receive ziftomenib for, you know, 12-18 months within that. On the non-intensive, it may be, maybe say 12-18 months. With those, you know, kind of putting those together with the premium pricing, you may get it within AML that could lead you to a between, you know, $5 billion-$10 billion market in that space. We think that with our profile and as the, you know, in the studies that Mollie's been kicking off and we hope to get forward to get an approval, we could easily capture half of that. It is a, you know, $3 billion potentially or more. You know, the confidence I think that we have and we'll hope to continue to see with the data is that the tolerability of being able to put patients on therapy and keep them on is really where you can see a transformation of AML into a market where you could have billion-dollar products. That's great. Okay. All right, so I understand you have this lead indication as the AML, but ziftomenib or menin inhibitor potentially can do more, right? The bigger, even bigger market opportunity is the solid tumor. I know you are doing the GIST and then some other combination as well. Tell us about the, you know, the cancer expansion on the cancer side and then also maybe on the non-cancer side for the whole menin franchise. Yeah, so we initiated earlier this year the COMEDO-15 study, which is the combination of ziftomenib and imatinib in patients with advanced GIST. That we think is the first example, Roger, of we may see multiple examples where a menin inhibitor plays an important role in combination. You don't expect a menin inhibitor to really have meaningful activity in solid tumors as a monotherapy, but what you're doing is you're targeting epigenetic control of other oncogenes. In the case of GIST, as it turns out, GIST tumor cells require KIT overexpression. That overexpression is regulated by menin. By blocking the menin interaction in combination with a KIT inhibitor, you're attacking the tumor cell from two different directions. You're blocking the catalytic activity of KIT and you're downregulating the epigenetic expression. GIST tumor cells are oncogene addicted to KIT. When you do that, you can actually push those tumor cells over into apoptosis. We see activity of ziftomenib with all KIT inhibitors in sort of every line. This is preclinically. We're now evaluating that in the clinic. It's early days. It's in, you know, it's in dose escalation. The significance of that is imatinib is the, you know, the approved standard of care. It's well accepted. It's well liked in front line GIST, but 60% of patients develop resistance to imatinib. If we could deepen the responses, if we could make those responses more durable, you could imagine now you're using ziftomenib right from the beginning on top of imatinib. You could go, you know, two years, potentially three years. That opportunity could be as significant as either the intensive or non-intensive AML setting. We haven't guided yet to data from GIST. We're still early in dose escalation, but the preclinical data is stunning and the GIST KOLs are excited to have a new mechanism of action. We met many of them at ASCO and they're just thrilled. Beyond that, there are other opportunities. One that is quite public is the combination of a menin inhibitor and a CAT6A inhibitor in breast cancer. Breast is a, you know, it's a very dynamic field. I think you have to be careful, but it's another example where menin on its own, maybe not enough, but when you get into the context of synergy with another therapeutic target, it becomes quite significant. We will likely pursue GIST with ziftomenib. Anything else, Roger, we would do in either solid tumors, diabetes, or other indications, we would probably do with a next-generation menin inhibitor distinct from ziftomenib. Got it. Okay, very good. Couple more minutes and then you do have another side of the pipeline, which is the FTI franchise and KO-2806. Tell us what's the status of that, when we potentially can see some data that can potentially be even, if not bigger and bigger at the menin side. Yeah, yeah, thanks for mentioning that. The opportunity, it's interesting that the FTI inhibitors are conceptually similar to the menin inhibitor, right? Neither of those are an oncogene. They are proteins that regulate other genes or other proteins. In the case of an FTI, you are blocking farnesyltransferase. This is a post-translational modification on other proteins. Think of it as it's important for drug resistance. Whether you look at KRAS inhibitors, PI3 kinase inhibitors, tyrosine kinase inhibitors preclinically, you know, we see pretty consistent activity, but inevitably most of those patients develop resistance and unfortunately go on to pass away from their disease. It turns out they all have a common vulnerability and that is a choke point in the target of rapamycin, mTOR. mTOR is regulated by a protein called Rheb. Rheb is RAS homolog enriched in brain. Rheb is a uniquely farnesylated protein. What we see is we, in preclinically, again, we can give an FTI, FNT inhibitor, whether it's Tipifarnib or our new compound 2806, with these targeted therapies and rescue them in some cases, in the cases of resistance or drive deeper and more durable responses. It is an interesting opportunity, Roger, to your point in that, you know, this has for a long time been a, you know, an area of high interest. How can we find a target that is combinable with other solid tumor targets to drive better clinical benefit for patients? Later this year in the second half, we're going to show you, I think it's four different, no, three different cohorts. We'll show you Tipifarnib plus Alpelisib in PIK3CA mutant head and neck cancer. We'll show you two cohorts, a monotherapy of KO-2806 and a combination of KO-2806, which is our second-gen FTI plus cabozantinib in renal cell carcinoma. There's a lot of development going on there. We look forward to sharing that data, you know, again, in the second half of the year, potentially at ESMO. Excellent. All right, just last couple seconds for the cash because you do have a significant cash to support the whole AML program and then with the partner with KK. Yeah, so we had $703 million in cash as of the end of the last quarter. We have, I think we're eligible for an additional $375 million in near-term milestones under our collaboration with Kyowa Kirin. We've guided, Roger, that we should be fully funded through in the AML program through to front line commercialization. We won't be able to do late-stage development, for example, in the FTIs, but if the data, you know, justifies doing that, I think, you know, there will be a lot of value for patients and for shareholders. Between AML, GIST, the FTI program, diabetes, there's a lot of value drivers over the next, you know, six to 24 months. Excellent. Great. Thank you for the team being there with us this afternoon. Thank you everyone for listening. Thank you. Thank you.