Hey, great. Thanks, everyone, for continuing to join us on this Stifel Targeted Oncology Forum. I'm really happy to do the next fireside here with Troy Wilson, President, CEO of Kura Oncology. Troy, always great to see you. Let's just kick off with a brief intro to the company, and particularly where you are now after an exciting data update to start the year this previous January. Yeah, Brad, thank you for the, thank you for the introduction, and thank you for the invitation to be, to be part of this, this program. So we're at an interesting and exciting time at Kura. Two sides to the business, as we've talked about. Our menin inhibitor is making great strides. This is ziftomenib. We are closing in on the completion of enrollment in the first, registration-enabling study, which we, we hope if, if successful, will support an application for marketing approval. We're also aggressively recruiting the combination cohorts that will support advancement into earlier stage trials. And, we gave it, to your, to your point, we gave an exciting update on that, the end of January. We'll look forward to giving another update here, a bit later in the year. We've also started an IST that will support advancement into the maintenance setting. And then finally, you'll see us make a move into the first of what we hope are perhaps multiple solid tumor indications with menin inhibitors, and we'll talk more about that in the second half of the year. But we think, you know, this, all of the exciting work that's been done in acute leukemias is really, is really perhaps chapters one and two of the menin story, and hopefully multiple chapters to come. The other side of the house are our farnesyltransferase inhibitor programs. I'll focus on KO-2806 chemical entity, brand new FTI. We began dosing patients in November of last year, in a trial that we call FIT-001. We announced not that long ago that in addition to the monotherapy escalation, we had begun dosing patients in combination with cabozantinib in clear cell renal cell carcinoma. We've also guided that, I think within the next month or two, you should see us begin dosing patients in combination with adagrasib in KRAS G12C non-small cell lung cancer. Why should people care? The potential for FTIs to be a preferred combination agent for, let's just say, KRAS tumors, is significant. If you look at the preclinical data that we've put out, you know, the FTI doesn't care what the mutation is, it doesn't care what the tumor type is. It works with multiple KRAS inhibitors in multiple settings. That gives it a real advantage in an area where there's clear activity, there's huge unmet need, 30%-35% of all human cancers, and yet people are still asking, "How can we do more for patients?" The fact that we have 5,000 patients' worth of experience with tipifarnib tells us exactly sort of what we're looking to dial in, what the safety and tolerability is, and how we think about moving aggressively into those combinations. So to your point, Brad, the rest of this year, on into 2025, I think it's an exciting setup, both in the menin space and in the FTI space. Yeah. Let's start with your, your combo update. As we think about this moving forward down the line into large, pivotal studies where patients will receive these drugs for quite some time, hopefully, what did you demonstrate in that early update that gives you confidence in, in the properties of ziftomenib in that setting? Great question. So it's early days, right? The data that we showed was ziftomenib at a 200 milligram dose in combination with venetoclax and azacitidine in patients with relapsed refractory AML, NPM1 mutant and KMT2A rearranged AML, and then in combination with the chemotherapy regimen of 7+3 in frontline patients with adverse risk. Again, those two genotypes. You always start with safety. Safety, tolerability was excellent. No new signals, no, no safety signals above and beyond, you know, what one would expect from the backbones. Importantly, no, no instances of differentiation syndrome. That was a question, a literal, I think, overhang on the stock is, could we, could we mitigate the differentiation syndrome that had been seen with ziftomenib as a monotherapy? I think that's an unequivocal yes. Will that continue as we dose escalate? You know, I would say stay tuned. I think there's reason for optimism. And then the activity. The activity, look, these, you know, these, these regimens are active on their own, but, you began to see some suggestions, Brad, of daylight between what we might expect of the regimen and what we might expect from the triplet combinations in both cases, particularly in the case of 7+3, we had a 100% CR rate. In the case of, you know, the venetoclax and azacitidine, a high level of activity, particularly in patients who were not menin experienced, but who had, in many cases, had previous exposure to venetoclax. I think that's a significant opportunity, and it's something that you see with both of the two agents, the ability to drive activity in patients who perhaps had previously experienced venetoclax. If that continues, that really underscores, you know, one of the major advantages of menin inhibitors as a novel therapeutic class. If you can drive better activity with Ven, given the strong interest in that as a regimen, I think that really speaks to what you can do initially in the relapsed refractory setting, ultimately in the frontline setting. Yeah. And now you mentioned to stay tuned with how DS will evolve with a larger sample, but I guess if we think about that potentially coming back, what is an acceptable rate of DS t hat makes these combinations feasible in the future? Yeah, the data that our competitors showed was, you know, 30% all grade, I think single digit, grade three and above, and nobody blinked, as far as I could tell. I would say that's acceptable. If you can do better than that, that's great. You certainly want, Brad, just qualitatively, is that the DS is well managed. You don't have to take the patients off of therapy. You can treat them with steroids and just let them ride through while they stay on the menin inhibitor. Qualitatively, that's what you're looking to do. Remember that these are AML patients, so the fact that something is grade two or grade three, if a patient has DS, they, you know, they're often hospitalized. As soon as they're hospitalized, they're grade three, but if they get, you know, 24 hours of steroids, and then they're in good shape, I think the docs are very comfortable with that. What we saw as monotherapy is that we saw no difference between a 200 mg dose and a 600 mg dose. In other words, you don't see a higher incidence of DS as a monotherapy as you dose escalate. You would hope to see that as well. As you're dose escalating from 200 to 400 and hopefully above, in combo, you should continue to see DS being well managed, well mitigated. I would say, you know, we were very excited that the number was 0. It doesn't need to be 0. It just needs to be, you know, it needs to be low. It needs to be low and very well managed, and I think, you know, I think, there's reason for optimism there. Yeah. And now what is the current status of the combo dose escalation? How much work is there left to do? 'Cause I think, key for investors is when you hope to be dosing at 600 mg, your RP2D for monotherapy with Venetaza in frontline patients. Yeah, yeah, yeah. So the way you've set that up, so just to remind everyone, we have four cohorts that are escalating in parallel. For each regimen of venetoclax and azacitidine, the 7+3, we've separated the NPM1 mutant and the KMT2A rearranged patients out, and that's really to make sure that we can characterize the safety adequately for both genotypes. If the safety looks identical, you'd really argue to collapse those cohorts back together, just for the efficiency of running the trial, but you go, you know. The reason we did it is to make sure you could really dose enough patients that you could understand the safety and tolerability profile. I'm pleased to say, Brad, we now have one of the four at 600. We have the other three at 400, and, you know, we have an earnings call coming up. Hopefully, at that point, we'll be able to give a you know, another perhaps, you know, more fulsome update on where we are, but people should take away we continue to make, you know, really good progress. In terms of the second part of your question, again, for the audience's benefit, the trial is structured in such a way that we're dosing relapsed refractory patients with Venetaza, patients who have adverse risk with 7+3. Once we've identified the RP2D, and we use that term, you know, very, very deliberately, then our safety monitoring committee can give us the green light to essentially flip the switch, and we go frontline, Venetaza, and we go to all patients in 7+3, i.e., patients who are not just adverse risk. I think if you can tell from the pace of enrollment, we're on track, right? We're, we're making good progress. These are generally 6-patient cohorts for each of the, the combination arms, so I'm hopeful. I think we've put a goal out there, Brad, of identifying the RP2D by midyear and commencing enrollment of those validation cohorts, the result of which will then validate that RP2D and give us a basis then for a discussion with the agency. Do we have enough data to support dose and schedule for an ultimate registration-enabling trial? I think we're, you know, we're right where we wanna be. Yeah. Great to hear 1600 mg cohort has started, Troy. Yep, it's exciting. Now, last quarter, on the earnings call, you also disclosed that ziftomenib is not a clinically meaningful CYP3A4 substrate or inhibitor, and that's important as we think about, can it impact venetoclax exposure levels, which has a pretty narrow therapeutic index? What preclinical and clinical work went into supporting that statement? Yeah, great question, and I'm gonna go back and just for the benefit of the audience, just underline what you said. So it's important, you know, when you're talking about properties of drug candidates in human populations, there's a lot of heterogeneity, right? The FDA doesn't ask for absolutes, so I'm not gonna sit here and tell you there is zero interaction. That, that's probably a bit of a bridge too far, but this is per the FDA guidance. There is no, you know, this agent, ziftomenib, is neither a clinically meaningful substrate nor a clinically meaningful inhibitor, and what that means, the upshot of what that means is, we don't have to adjust the dose of ziftomenib in the presence of agents such as azoles, which may inhibit 3A4. That would be a substrate. We don't have to do that, and we don't have to adjust the dose of venetoclax due to any interaction of ziftomenib with CYP3A4, which would, again, ziftomenib is not a meaningful CYP3A4 inhibitor. That is, Brad, both preclinical data done in appropriate in vitro studies, you know, some amount of modeling, and then clinical data as well from the ongoing both the monotherapy studies and these combination studies. And, you know, we always start more conservative, and you rule things out, but at this point, we can comfortably say both of those statements are true. It's neither a clinically meaningful substrate or a clinically meaningful inhibitor. I don't really see that changing, and I think that's partly, Brad, why you see enrollment going so quickly. So i f you think about the escalation trial just in 007 across the 4 cohorts, if all we do is enroll 6 patients at each dose, that's 72 patients. We started dosing in July. Think about how fast we're going relative to the registration-enabling studies in monotherapy. I think that speaks to how easy ziftomenib, ziftomenib is to use in these combinations. I will also tell you, Brad, we are beginning to do the work just to complete the modules that will support the NDA submission. As part of that, you engage with the agency. We've had, you know, clin pharm discussions, we've had other discussions. We're very comfortable. We were very deliberate about putting those 2 statements in our corporate presentation, and it's, it, it is supported by the data that will go in the NDA submission. Yeah. Okay. Now, how might additional combo data updates unfold for you in 2024? You've traditionally had a presence at EHA. Would that be a target for you this year? Are corporate updates now the route for Kura? At this point, this is a little bit of a. It's gonna be a bit of a non-answer. I hope the audience doesn't find this too unsatisfying. But what we think, what we've heard from investors, both, current and prospective, is they would appreciate fewer, more substantive updates, rather than us slicing the salami. You know, this is 200, this is 400. You can tell by based on where we are, there's no real prospect of showing 600 milligram data at EHA. There's just physically not enough time to move those patients through. I'm not gonna take off the table that we would have an EHA presentation because, you know, although the abstract deadline has passed, the late breaker is still open. We're t his is obviously an open-label study, so we're watching carefully. But to your point, and you asked the question a couple questions ago, really what people wanna know is, what's your identified RP2D, and then what does safety, tolerability, and activity look like at that dose, right? In both the relapsed, refractory, and the frontline populations. I think that's sort of what we have to be shooting for. It could very well, Brad, be a combination of a corporate update and ASH. We may have something to say at EHA. I think, you know, why would we show something at EHA? The docs really wanna talk about the drug. They view menin inhibitors, the entire class, as practice changing. I think they're very excited by the data that they're seeing. They don't always wanna operate according to the corporate investor calendar—you know, calendar. We have to make sure we manage our physician constituents and our investor constituents, and so when we know for sure what we're doing, we'll communicate it. But that's to hopefully give some people some transparency around our thinking. Everything's going well. I think hopefully by the end of the year, folks will have all of the answers they're looking for, and it's all directionally, it's all going in the right direction. Yeah. Helpful and reasonable. You mentioned some of the important elements of the next update, but how important is response durability in these initial cohorts for your next combo update that you give? Yeah, it's important. I mean, just again, you know, I always, I will start here, right? Safety and tolerability, you wanna make sure that that continues. I think we're feeling optimistic, but, you know, there's, that's not a substitute for running the experiment. I think we wanna see kinetics of count recovery. This is an interesting topic that's come up. We do not have to hold ziftomenib to allow counts to recover. You say, "Well, why does that matter?" It matters because if for any reason you have to hold these drugs, you give the disease a chance to come back. And so we wanna make sure we pay attention to that. You would expect menin inhibitors to actually stimulate count recovery, but, you know, they're stimulating differentiation of progenitor cells, so you'll look for an update there. And then, you know, there's this interesting dynamic. In the NPM1 population, in our experience, less often they go to transplant, so you're looking for how long can you keep them in a response and what's the quality of that response to the extent that they go to transplant? Our trial is designed now, 001, 007, 008, that patients can go back on drug after transplant. You know, we're working through that now. That there is a willingness of physicians to do exactly that, but, you know, physicians want the latitude to say, "I, you know, the patient and I decide. Do they go to transplant and then back on the drug? Do they stay on the drug? Maybe this is their second transplant or their third." I think duration is part of it. I think quality and depth of the response is part of it. I think another thing, Brad, that we saw was, do we continue to see activity in patients who've had prior venetoclax exposure, right? What do we see in the front line? You should expect, I think, pretty strong data in untreated patients. That's what we've seen with our competitor. I think, you know, we have an expectation of a pretty high bar there. But, and then the final one, and one that will lag a bit, is MRD negativity. We do get questions around that. There you wanna be careful because the sites often use assays that are maybe 10 to the -3. The regulators wanna see assays that are 10 to the -5, 10 to the -6. So you wanna make sure that you're assessing MRD negativity using an assay that could ultimately support, you know, inclusion in a regulatory submission. Particularly, and I, I really don't wanna get ahead of the agency here, but there may be a big step forward in myeloma, based on the, the most recent ODAC. You would love to see that kind of, you know, that kind of philosophy applied to AML. I think it's early days, but, but hopefully, you know, there's a willingness to look at MRD as a supported endpoint or even an accelerated endpoint, CR— MRD negative CR, for example, as an accelerated endpoint. That would dramatically improve the time to value creation for both patients and, you know, these companies working on menin inhibitors. Agree. Maybe moving backwards in time to the relapsed/refractory NPM1 AML monotherapy, you've maintained your enrollment guidance for the pivotal single-arm cohort from mid 2024. How has progress gone, and how are you specifically defining mid 2024 now that we're getting close to it? Yeah, so, so we've never wavered, right? We've never varied from mid-2024. We're right where we wanna be. Mid-2024, I mean, for investors, and the way we think about, you know, when we say mid is sort of May to maybe July, late July or early August. Obviously, we're doing everything we can to go as fast as we can. We are— I will be honest with you, if you give physicians an opportunity to use the combos versus the mono, they'll use the combos. And you only need to look at the combo data from both us and, and Syndax and say, "Wow, that's as good as the monotherapy is, the combos, I think, are even better." You wanna be very thoughtful in how you roll your studies out so that you don't create internal competition at sites and siphon patients away. And I, you know, kudos to my, my clin ops colleagues. They've done an exceptional job with 001, 007. This is why 008 is taking. You know, we're booting it up a little bit more slowly because ideally, you want 001 to complete, 007 to move to expansion, and then all the relapsed/refractory patients go to 008. You know, there's as much art as science. To your specific question, I think we're right on track for midyear. We're doing everything we can. We are keeping an eye on the competition, but we're not obsessed about it, right? We're gonna run our own race. I think we're putting together a high-quality data package. We're gonna go as fast as we can to get to market because there's a big bolus of patients who need these drugs. Yeah. I think regardless if it's May or August, you will have data pretty soon after your closest competitor, and I think the question is: Do you believe it's important to demonstrate clear cross-trial monotherapy efficacy superiority in this setting, or what else might lead to a preference for ziftomenib in that setting? Yeah, I think t here's a very strong enthusiasm to use ziftomenib in NPM1 mutant patients. Based on the phase 1b data, based on physicians' experience with the ongoing registrational trial, I think what folks should look at is the combos are actually. So to the extent folks were concerned that we would be out of the KMT2A market, we're certainly not seeing that in the enrollment in the combo studies. And, you know, these, we will not be able to promote beyond a monotherapy relapsed/refractory NPM1 label, but these docs use these drugs how they, how they think they should use them. Docs use gilteritinib all over the place, right? It's approved. They're very, you know, they feel very strongly about it. I think the emerging data, Brad, both in monotherapy and in combo with both regimens, and then remember, we're doing a gilteritinib cohort, we're doing low-dose Ara-C, we're gonna do FLAG-Ida. I think it's going to make ziftomenib the agent of choice with whatever regimen a physician wants to use. That's what we're shooting for. Durability, depth of response, that'll, those will take care of themselves. You wanna make it as easy as possible, no drug-drug interactions, minimal monitoring, and by, you know, by the time we launch, those combo studies should all be completed and the data available to physicians. And then, you know, we see the docs continually use the term transformational for menin inhibitors, not just Zifto, but the class generally. I think you're gonna see that in terms of uptake. Troy, how has your thinking evolved on menin inhibition for diabetes? So we said late last year that we were going to let the data be our guide, and we've continued to do that. We haven't yet guided to a specific update. We are doing work behind the scenes. I would say, stay tuned, let us complete the work. And I will say, you know, long term, were you to develop a menin inhibitor in diabetes and metabolic disease, our view is you would wanna use a different compound. There are safety reasons, there are regulatory reasons, there are commercial reasons. But you can use, you know, your first-generation compound, ziftomenib, if you will, as a proof of concept. We're doing the work. I am, you know, I think I'll probably leave it at that. It's if it's an opportunity, and we're looking at the other of our competitors and following their progress, you know, that's a—t here are perhaps other than obesity and maybe Alzheimer's disease, there are few diseases with as large an unmet need as Type 2 and Type 1 diabetes. So, but as always, Brad, whether it's liquid tumors, solid tumors, diabetes, we're gonna come first forward to you with data and let that data guide those next steps. Okay. Now, on the FDA program, to close out, unfortunately, we won't have time to go into the weeds of this, but you've suggested a strategy of multiple different combinations with TKIs, and TKI combinations aren't always the easiest. What have you learned from the initial combination data you generated with your older generation drug with alpelisib, which is probably one of the toughest drugs on its own? Yeah, I love the way you framed the question. Ultimately, what has been done in almost all combinations, just to restate what you've said, people have tried to combine inhibitors of the MAP kinase pathway, inhibitors of the PI3 kinase pathway, and by and large, those have all crashed and burned, with the exception of probably RAF/MEK. Now, the mutant-selective KRAS inhibitors may give some flexibility. Here's the interesting thing. If you look, we're very deliberate. I'm very deliberate about the language that we choose. When we talk about current HN, we say, "It's generally safe and well-tolerated. We're doing dose optimization at different doses." You don't do that unless you have adequate safety, tolerability, and evidence of clinical activity. We know the response rate in PIK3CA mutant head and neck for alpelisib alone is zero or close to zero. So the fact that we're seeing activity, to your point, with an agent that is, you know, has rash, has hyperglycemia, I think is encouraging. You know, we've been able to go very fast with 2806 because we were able to argue to the FDA, "Look, we have 5,000 patients' worth of data with tipifarnib. This is an NCE, but it's an NCE, if you will, in quotes." That's allowed us to go very quickly. You're basically looking for no new tox. Yes, you're gonna see some myelosuppression, 'cause that's part of the mechanism, but ideally, you're seeing no surprises. Ideally, you're seeing activity if you dose HRAS mutant patients. And then, again, if you can get to ranges where we already are with alpelisib, whether it's cabozantinib, whether it's a KRAS inhibitor, our preclinical data suggests you can do pretty, pretty great things. And I like the idea of going into that space with an agent that's agnostic, that maybe doesn't— you know, can work with multiple different players. Because that's—y ou really wanna leverage the power of precision oncology, but then go after much larger populations. And I'll you know, people hear me say this, I think FTIs may be the preferred combination agent in this setting. We'll let the data, we'll let the data show, but it's so far so good. Yep. Bold statement. I look forward to seeing some of the data, Troy. Yeah. Thanks so much for joining us. We're out of time. Again, thanks, everyone, for listening in. Always great to hear the latest from you, Troy. Our pleasure. Thank you, Brad.