Global conference. My name is Roger Song, one of the senior analysts covering SMID-cap biotech. It's my pleasure to welcome Kura CEO, Troy Wilson, to join me for the first session. Thanks for the invitation, Roger. Thank you to you and the Jefferies team for putting on a great meeting. Awesome. Great. Maybe before we dive into your exciting pipeline and the all the kind of upcoming catalyst, can you give us some intro remark in terms of recent updates from the field, from yourself, and then what's the kind of opening remark you wanna give us? Sure. So Kura is a precision oncology company. Two major pillars to the business. The first and foremost is our menin inhibitors, ziftomenib. We are now at a point where we've completed enrollment in our first registrational study. We've just received breakthrough therapy designation. You know, we are beginning to put the package together for the NDA submission. On that, I'm sure we're gonna touch on that in the questions to come. We are also enrolling in a couple of different studies evaluating ziftomenib with various standards of care. The goal for this agent and this class of agents is that you would use them for approximately anywhere from 35%-50% of AML throughout the treatment continuum, from first diagnosis all the way through to maintenance. We've been very encouraged by the safety, tolerability, and activity data that we've seen. And you know, that in and of itself would be a lot. You're gonna see us, Roger, move into solid tumors. We'll talk a bit about that here in the second half of the year. We also will have our first presentation in a couple of weeks at the American Diabetes Association meeting, where we'll talk about non-clinical data for ziftomenib in diabetes. So really, a lot to offer there. The other program, of course, is our farnesyltransferase inhibitor program. There we have two molecules, tipifarnib and 2806. They are both moving forward in combination studies in solid tumor indications. And the goal with that program, as with ziftomenib, is, you know, how do you make other targeted therapies that much better? By blunting innate or adaptive resistance. I think, you know, we'll have more to say about that, probably in 2025. From a, from an organizational perspective, we're well capitalized. You know, we had $527 million in cash, which takes us to early 2027. And it's. We're glad we do because there's a lot to do, a lot of value to create for patients and for shareholders. Awesome. That's a very, very, very informative overview here. All right, maybe we start, stay on the ziftomenib, which I probably is the major driver of the current value and a lot of the investors' focus. Understanding you are just crossed the enrollment in May, last month. Mm-hmm. Last month, yeah. Yep. for the monotherapy at the pivotal for NPM1 mutated AML. I think in the guidance, you say you will potentially have the data in 1Q next year- Yep. early next year. Yep. So what will be, what will trigger that, top line analysis, and what should we expect to see from that data? Because, you know, your competitor is talking, you know, when they release the top line, they give us some, like, hyp- null hypothesis. Yep. Say, "Okay, we'll file for NDA for the trial or for the program, and then we'll do the same thing. Sure, yeah. So, so just to maybe amplify on a couple of the points that you've raised. So that, that trial, which we call KOMET-001, as you said, it's a registration-enabling study for relapsed/refractory AML patients with NPM1 mutations. In terms of kinda how to think about the data, you wanna see 20%-30% rate of CR/CRh. You wanna see a median duration of response of 4-6 months. We've never really deviated from that. That's what's needed for approvability. You know, I think the fact that we recently received breakthrough therapy designation from the agency in that indication, I think speaks well for the potential of the program. The timing, you, you've said it correctly. I think we would expect top-line data in early 2025. That's driven, Roger, it's just it's mathematical. So it's six months from the last patient enrolled, the 85th patient, plus a sufficient amount of time to clean the data, that when we come to you with that top-line data, we can stand behind it. And for those who aren't familiar, by data cleaning, we mean we go to the site, and we actually verify, you know, each of the laboratory values or other values and make sure that the data is really, quote, unquote, "clean." All companies go through that. It's a standard part of clinical trial practice. That timing, given that we completed it just a couple of weeks ago, we completed enrollment a couple of weeks ago, means we're looking at a top-line release, probably in early 2025. Awesome. Great. Just to confirm, you, once you had the top-line data, how should we think about the potential NDA filing afterwards, and what else you need to complete before you can file NDA? Yes, great question. So in terms of the NDA submission, this is where breakthrough therapy designation really helps, and we had said that. When it matters is from the time you complete enrollment until the submission, because the advantages of it are, you know, you get priority within the FDA, you get a dedicated review, experienced review team, and the agency is willing to work with you by various mechanisms and various capacities to accelerate the process. Because you know, the therapy, the breakthrough therapy, represents a substantial improvement over the standard of care. With that backdrop, Roger, we're gonna do everything we can to go as fast as we can. The clinical data, I can tell you, is the long pole in the tent. We are doing, as you can imagine, CMC, we're doing companion diagnostics, we're doing the safety data, the statistics. All of that is coming along. We are, we interact with the agency on a pretty regular basis, across all of our programs, and we'll do everything we can. We haven't given yet guidance on the timing for the NDA submission, but, we do think we can be very competitive with, with at least one of our competitors, who we know is, is also, recently completed enrollment of its own trial in NPM1 mutant. We were just a few weeks behind in terms of enrollment, and with BTD, we're gonna do everything we can to, to catch up and possibly to overtake them. Yeah, good. That's very consistent with what you have been saying. Okay, good. So that's a monotherapy. Yep. I think, for investor benefit, it is the starting point- Yep. and then when the standalone for AML trial or AML kind of a pipeline, the indication is supposed to move into the combination very much kind of echoed by a lot of physicians we have been talking. So where are you with the combination kind of a regimen, understanding you already in, you know, released the initial data from- Yep your lower dose cohort, and then you are moving forward towards the RP2D. So when we're gonna see the next update from your combination KOMET-007? Sure. So great question. So, KOMET-007 is a trial that is evaluating ziftomenib in combination with two approved standards of care, 7+3 chemotherapy in fit patients, and venetoclax and azacitidine in unfit patients. We enroll, so the trial is designed with an enrollment phase, and it's 4 distinct genetic cohorts. We're enrolling NPM1-mutant and KMT2A-rearranged AML patients separately as separate escalations in each of the 7+3 and ven/aza. So think of it as 4 parallel escalation cohorts. We remain in 600 with 3 of the 4 cohorts, and the fourth cohort, which is KMT2A 7+3, is still enrolling at the 400 mg cohort. I think that's primarily because it's just a smaller population. It's, you know, approximately 5% of AML. NPM1 is 30% of AML, so it's just a numbers game. It is enrolling very quickly. In terms of data, we will not have anything yet on 007 at EHA. We did submit an abstract that was accepted. We subsequently withdrew it, and the reason was the trial's enrolling so quickly, we find ourselves kind of in this place where we're neither here nor there. So we would if we were to show you data, it would be kind of intermediate through the 400 milligrams while we're now enrolling at 600. Your very next question would be, "Oh, that's great. How does the 600 look?" We've heard from our shareholders that they would prefer we give them fewer, more substantive updates. So although there will not be anything at EHA, there will most certainly be something at ASH, and I'll talk a little bit more about the design in a second. Mm-hmm. But I think, Roger, there may also be something intermediate between now and ASH. And the reason I say that is, I talked about the dose escalation design. That's really intended to establish what is the identified recommended phase 2 dose for ziftomenib in each of those populations with those standards of care. Once we identify the recommended phase 2 dose, you will see us do up to 7 expansion cohorts, and that is venetoclax and azacitidine in frontline patients, 7+3 in frontline patients now without adverse risk- Mm-hmm ... venetoclax and azacitidine in relapsed refractory patients, and interestingly, venetoclax and ziftomenib in relapsed refractory NPM1 alone. Mm. The reason for that is there's a question as to whether the doublet is sufficient, and you don't actually need the triplet in the NPM1 population. That's 7 expansions. Those, of course, are where the ultimate pivotal trials will go, the frontline pivotals. We don't need to go back to the agency, to FDA. Once we identify a recommended phase 2 dose from this Phase 1a portion, we then talk with the safety monitoring committee, which has the ability to, with us, then select or identify the RP2D for each combination, if you will. And you should see that happen here, you know, in the second half of the year, and then we're on into the expansion phase. Lot of patients, enrollment's been very robust, a lot of data coming. We continue to be very encouraged by the safety, the tolerability, our ability to combine with standards of care, emerging clinical activity. It's, you know, the final thing I'll say is, of course, we are beginning now to prepare at risk for frontline trial or trials. We don't have to have that data complete before we begin to design and begin to think about operationalizing frontline trials. You certainly need the data before you actually move to phase 3, but we've seen enough to date that we can tell you we are preparing for a trial or trials. I'll be more specific about mono or plural a bit later in the year, but I would say so far it's, you know, it's all green lights. ... Awesome. Okay, so a couple things to clarify. One is you don't have the KOMET-007 update at EHA. Correct. I think it's a placeholder. Yep. But you don't have the abstract, and now it's kind of a withdrawn. Yep. And then you say for sure will be ASH kind of update, but before that, may or may not have the update. Yep. How should we think about, because you also say you try to identify the RP2D by midyear? Yep. -or around midyear. Yep. How should we think about the data release versus your RP2D announcement or, decision? Yeah. What would be before you can move into the expansion cohort? Yeah, it's a great question. So, there's a few questions kind of tucked in there. Yep. Mm-hmm. The identification of the RP2D will be predominantly based on safety and tolerability. We're not gonna wait for these cohorts and say, "Okay, which is more efficacious?" We have enough data from the monotherapy trial. As long as there isn't something really unexpected, that as you dose escalate, the efficacy falls off a cliff, you know, the data all says between 200, 400, and 600, go with the highest dose you can, and that will be determined by safety and tolerability. So we will find a Reg FD manner, Roger, in which to communicate that we've identified the RP2D and commenced enrollment into the expansion cohorts. It's really a question of the data from the escalation, the emerging data from the expansion, and at what point is it appropriate to kinda tell that story. And I would say stay tuned on that. That's why, you know, there are more than 70 patients in the escalation across the seven expansion cohorts. That's another 140. If you go 20 patients in each, there's a lot of data coming. And I would also say, you know, we're beginning to take some of the limitations off. We started, at request of FDA, in patients with adverse risk in frontline 7+3 and in the relapsed refractory setting. Once we get to the identified RP2D, we can go into the target populations, and that's really, I think, where you want the focus to be, but you're gonna continue to see that trend. Final thing I'll say is if we go back to the January update, the reason we gave that update at that time was there was an overhang on the program. There was a question of is Kura going to be able to mitigate differentiation syndrome and get the drug to work effectively in the KMT2A population? And we made a commitment late last year that we would show that data in the first approximately 20 patients. That's what we did. You saw, I would say, outstanding safety, outstanding tolerability, you know, no evidence of DS. And I said, you know, there may be some DS, but the DS is in our view, largely a solved problem. And I think efficacy or clinical activity that was better than maybe what people were expecting. What you'd like to see as you escalate is that the activity continues, that it's not worse at the higher doses, and it's certainly not worse than standard of care. So, you know, enrollment's going rapidly, and we'll have, I think, a lot more to say here in the second half of the year. Got it. But just wanna confirm the second half of the year, the data will be mostly focused on the dose escalation, or you will, since you identified the RP2D midyear, so you will start to do the expansion, we will expect to see some data from expansion as well? It's – I appreciate the question. It's a little hard to say yet 'cause we haven't dosed any patients in the expansion. Mm-hmm. My expectation is the expansions will go even faster in the frontline venetoclax than now. Yep. But, you know, that's my expectation. Let's get that going, and then I think we'll be able to guide you as to exactly, you know, what to expect and when. You know, we take advantage of clinical meetings when we can. We think if there's an important update, and here, obviously, everybody's trying to understand if ziftomenib is, in fact, best in class. I think it continues, you know, to trend that direction. We'll do our best to put the data together that you and the other analysts and the shareholders are looking for. Okay, good. Look forward to that. And then that's just one of the combination regimen- Yep. and also you're enrolling the other one, and which is very important because that's the FLT3 Yep ... which your competitor potentially will have been challenging enrolling. Yep. So, tell us about that regimen, and then you just started, and when we're gonna start to see the data? Sure. So again, good question. So the combination that you're referring to is ziftomenib plus. It—this is in the KOMET-008 protocol, and there are three cohorts there, gilteritinib, FLAG-IDA, and low-dose Ara-C. Gilteritinib is of high interest, that combination, and it's of high interest for a couple of different reasons. It's very popular among physicians. It's very efficacious for FLT3 mutant patients, and the non-clinical data that we and our competitors have generated with menin inhibitors and FLT3 inhibitors is some of the strongest non-clinical data that's been put out to date. In the animal models, the combination of a menin inhibitor and a FLT3 inhibitor is effectively curative. The other thing is the population size. So NPM1 is approximately 30% of AML. FLT3 is about 25%-30% of AML, and they are approximately half overlapping. So half of your NPM1 mutant patients also are co-mutated in FLT3. If you had an option of an all-oral targeted regimen to drive durable responses, that should be very attractive, given the non-clinical and clinical data we have to date. As far as I know, you know, we're right now the only menin inhibitor that's dosing with a FLT3 inhibitor. It's early days. You know, we wanna get some experience. I will say to you, we deliberately didn't open a lot of sites initially with 008. So we have 001, 007, and 008. We've talked about each of them. I think we came in ahead of schedule with 001 in terms of enrollment. Had we not had 007, we would have come in even sooner. Mm. The reason is, of course, we have NPM1 patients enrolling in both trials. I will tell you one thing, if you give physicians an option of a menin monotherapy versus a combo, a triplet, they will choose the triplet. Mm-hmm. We would all do that. This is not rocket science. So, for that reason, we made a very deliberate decision to not open 008 too quickly so that we could get 001 across the line, get it heading toward an NDA. Now, 007 is moving in the right direction, and 008, you're gonna see ramping up. Mm. I would not expect, Roger, data on 008 until probably 2025- Mm-hmm. realistically. We just, you know, we need to get some experience. It will be, of course, all three cohorts, but there's a real primacy on figuring out the path with FLT3 because there's an option for FLT3 NPM1 double mutant, FLT3 alone, and if you followed the data with the other FLT3 inhibitor, quizartinib, from Daiichi Sankyo, that's showing some intriguing activity in the FLT3 wild type. Mm-hmm. Again, the combination of a menin inhibitor and a FLT3 inhibitor has some real attraction from a therapeutic potential, so there's a lot to do there, and we're happy to sort of take that space. Excellent. Great. And then, so you give us some kinda teaser around the outside of AML, right? Particularly on the solid tumor and ADA- Yep. - this, diabetes. So how should we think about that opportunity, and then what's, how you're gonna prioritize your pipeline in terms of the ziftomenib versus maybe other, you know, other, you know, menin inhibitor, pipeline? Yep, yep. So I would say I've gotten asked this question a couple of times. I would say the major outstanding question now for investors on menin is, what's the commercial case, right? What's the, what's the addressable population? How do we think about durability and time on therapy? I would make the argument to you that a menin inhibitor in AML looks like the early days of IMiDs, and anti-CD38 in myeloma. You have the potential to transform the disease. And I think there's enough clinical data now that we can check a lot of the other boxes. We have taken our time. We've been sitting on this first set of solid tumor data for about a year and a half. We did not, you know. Investors will appreciate this. We wanted to wait until we had completion of enrollment and BTD before we rolled out solid tumors and diabetes, because otherwise people go, "Uh-oh, are they pivoting?" No, we're not pivoting. We're actually building, we're expanding the franchise. So you'll see the first solid tumor opportunity. It's a combination play. Mm-hmm. If there's a significant prevalent population, it could be as large as AML, as all of AML. When we do experiments, we not only do Zifto, we do all of the competitor compounds as well, and Zifto has three advantages as far as solid tumors. It's highly tissue penetrant, it has a long half-life, and it's a menin degrader. Mm. That makes it ideal for oncologic applications. So you're gonna see both an IND submission and the non-clinical data later this year. It's time now to begin to further broaden the TAM. Diabetes, we'd said late last year, we're doing the non-clinical work. If we have something to say, we'll come back and say it. Clearly, we have something to say, right? Yep. So we have an e-poster presentation. We have done an exhaustive non-clinical set of experiments of menin, and for those of you who don't have access, the title of the abstract, I think, is "Ziftomenib Induces Insulin Production and Restores Insulin Sensitivity. Mm. So it actually does both in rodent models of type 2 diabetes. This is a data set worth paying attention to. What are we gonna do with it? We've talked about the fact that we have a next generation menin inhibitor program. Our goal would be, if we can inform through clinical studies with ziftomenib, the development of a next gen menin inhibitor—'cause you don't, in our view, you don't wanna take ziftomenib into diabetes as a commercial product. There's a lot of reasons not to do that. However, just as we believe ziftomenib is best in class in cancer, we think we can deliver a best-in-class menin inhibitor in diabetes and metabolic disease. Ideally, we would have a clinical study that would help inform the selection of one or more next-generation candidates. Our chemistry team can dial in or out the PK. They can dial in or out the menin degradation. They can dial in or out the tumor penetrance. We'd like to be able to use both non-clinical and clinical data to set that up. Will we ultimately commercialize a diabetes drug? I doubt it. I think we will remain pure oncology, but can we create and then monetize value for shareholders? You know, I would say, you know, stay tuned for the ADA presentation, and then we're happy to talk to people about it. It's a good data set. People will enjoy it. Excellent. Troy, I've known you for a couple of years, covering you. Every time Tipi and the FTI, always like a last minute kind of a thing. I will see when you're gonna change maybe next year. So maybe last a minute- Yep. How much you wanna share with us about the tipifarnib and FTI franchise, and how should we think about the next update? Yeah, we know we'll arrive, Roger, when that's your first question. I would say it's again gonna be all about combinations. How do you make good drugs better? Between Tipifarnib and 2806, we have two FTIs. Just as we're very thoughtfully de-risking menin, we're very thoughtfully de-risking FTIs. If we can avoid the innate and adaptive resistance that arises to targeted therapies like KRAS inhibitors and TKIs, you've got something really special that's complementary to and orthogonal to what a lot of other people are doing. Probably with everything-