Good morning and welcome to TD Cowen's 6th Annual Oncology Innovation Summit: Insights for ASCO and EHA. This year's conference includes 27 virtual fireside chats with many of the companies that will have notable presentations at ASCO and EHA this year. We hope you find the sessions useful as you prepare for the meetings. This is Phil Nadeau, one of TD Cowen's biotech analysts, and I'm happy to host the first session with Kura Oncology's President and CEO, Troy Wilson, and CMO, Mollie Leoni. Kura will have very notable presentations at both ASCO and EHA, including the results from ziftomenib's pivotal trial in NPM1 mutant AML. With that, Troy, I thought I'd hand it to you. Can you give us a brief state of the company overview, biggest strengths, biggest challenges, and what does Kura need to do to create shareholder value over the next year? Yeah, Phil, thanks to you and TD Cowen for the invitation to participate. There's a lot going on at ASCO and EHA, both with Kura and the oncology segment generally. For us, we have sort of three buckets for the menin inhibitor program. You've already mentioned we're looking forward to sharing our top line data, or I should say our full data for the KOMET-001 registrational study at ASCO. Turning to EHA, we'll give an update on the KOMET-007 intensive chemotherapy phase I-A, phase I-B. That's relevant because that's a direct lead-in to the KOMET-017 study, which is two parallel phase III studies in both intensive and non-intensive. We'll cover all of that. We've also, as you know, a month or so ago began dosing patients in KOMET-015, which is our phase I study combining ziftomenib with imatinib in patients with advanced GIST. Beyond those menin inhibitor programs, Phil, we have an update on our farnesyl transferase inhibitor programs, both Tipifarnib and KO-2806. They're in the second half of the year, hopefully at ESMO. We will give another update with additional data for the ziftomenib combinations, likely in both the relapsed refractory and the frontline setting, rounding out the year at ASH. We're in a strong position. These are tough markets, Phil, but Kura is well capitalized. We have just over $700 million as of the last quarterly update. We have up to $375 million in near-term milestones coming in. We can stay focused, put our heads down, and keep generating value. I think the thing one has to do is just keep a steady hand and just try to push through these very difficult markets for the biotech sector. I think we've got good programs, good data, great team, great partnership. I think we're well positioned. Maybe turning to ASCO first, as you noted, the full data from the KOMET-001 trial will be at the meeting. Some of the top line results were actually in the abstract that was released last week. Can you provide the highlights of the data in the abstract and which measures are most important in defining ziftomenib efficacy and safety? Yeah, so the headline number, of course, Phil, is the CR/CRh rate, which is 23%. We provided a median duration of response. As we look forward to the ASCO presentation, and I'm sure Molly can speak more to this, you'll get additional granularity on that data around things like MRD negativity, survival, all the attributes. We're really pleased. We think this is an approvable product. We think it's very competitive from both a clinical activity and a safety and tolerability perspective with the competition, and look forward to sharing that data. I think a key concern among investors of just about the menin inhibitor class is the competition in the space. How would you position ziftomenib pivotal data compared to what we've seen from other pivotal trials, as well as the earlier stage data from Johnson & Johnson and Sumitomo? Yeah, it's a good question. I think it's important to sort of run your own race here and don't worry too much about the competition. We now have two successful monotherapy registrational studies, Phil, one for us and one for our competitor Syndax. I think what that says is this is a real drug class, right? This is likely to make a difference for patients with AML. The reality is the way in which these drugs are going to be used is in combination and in earlier lines of therapy. We really view these initial registrations as getting out there into the market, familiarizing both physicians and patients. What I would point people to is increasingly look at that combination data, whether it's in the relapse refractory setting or in the frontline setting, because that's where I think you're going to begin to see programs distinguished from one another. Importantly, as I think you'll see, the challenges of ziftomenib as a monotherapy, Phil, the biggest challenge actually is just educating physicians to be patient and keep patients on the drug, give the drug time to work. As you go into combinations, that problem melts away because, of course, you have the combinations helping to keep the counts under control. We're going to give you a couple of meaningful updates, actually several meaningful updates this year. The first at EHA in the intensive setting, the second hopefully around ASH in the non-intensive setting. Then, as I mentioned, some additional updates in the relapse refractory setting. If our number, Phil, is in that frontline population, this is a $5 billion-$10 billion market. You take 10,000 patients times the price point, times 18-24 months of therapy. If that's true, there's room for two or even three competitors. We are charging ahead to try to get there as quickly as we possibly can. You mentioned the NDA for ziftomenib. Which results will be central to the filing? Is it the pivotal phase II data, or is the combination of the phase I, phase II data what's going to be reviewed by the FDA? Yeah, let me ask Mollie if she can answer that for you, Phil. It's a good question. Sure. Really, the FDA has the ability to review any and all data that they would like to. They have been provided with both the phase II and the phase I- B2 combined. Obviously, the phase II will be the pivotal data reviewed, but the phase I- B will probably be supportive, could be combined in a label. The big things that they're going to be looking at are, of course, response rate and really evidence of safety. Lack of myelosuppression, lack of big risks that would outweigh the benefits of monotherapy. As well, one of the factors to look at is transfusion independence and maintenance of transfusion independence. That's why we think that's an important topic to cover. On the safety profile, it seemed like in the pivotal phase II data, the rate of differentiation syndrome was very manageable, was quite low. Do you think that's because physicians have become better at managing the risk, given that we've seen it for multiple members of the class? I think the differentiation syndrome guidance we put in place, I like to say it's no longer just manageable, it's managed. These physicians have learned how to identify it early. They know when to be looking for certain signs and symptoms, and then they're able to intervene at the appropriate time. I think it's been a learning about ziftomenib, because I think each of the menin inhibitors shows differentiation syndrome at different points and in different ways. Great. Maybe turning to EHA, you referenced the data from KOMET-007. Can you briefly summarize the data that were in the EHA abstract? Oh, would you like to do it? We were presenting the data. This is our frontline intensive chemotherapy trial with 7+3, with the addition of ziftomenib in both the NPM1 mutants and the KMT2A rearranged patients. We've gone through the dose escalation portion, and we have decided on, with the FDA's input, of course, the recommended phase II dose of ziftomenib, which is 600 mg. What we'll be showing at EHA is the 600 mg treated patients. We will take them both from the escalation and from the expansion phase that we've done so that you get a nice large patient pool. Separately showing the NPM1 and the KMT2A, you're going to see response rates. You're going to see that the durability is really quite impressive for these patients, especially the KMT2A patients. You'll see how the duration of response is progressing. I wouldn't say that you should expect to see a median yet, thank goodness, which is a good sign for patients, similarly with survival. You will get to see overall how these patients' courses are evolving. Can you remind us what you'd expect for intensive chemotherapy on its own in this patient population? What's sort of the benchmark for CR as well as duration of response? Yeah, so it varies for either of the types, and it's varied depending on what sources you use, but you'd expect anywhere from a 50-75% CR rate in this patient population in general. When you break it down by subtypes, in the NPM1 mutant, you probably expect higher within the 70-85% range. Within the KMT2A, they probably respond well, but then they relapse quickly, so probably closer to the 70% range and then a quick relapse. By the first year that patients have been on therapy for NPM1 mutants, even the "good" AML to have, more than half will have either been relapsed or refractory by that point. You want to look and see if these patients are actually able to maintain their responses for prolonged periods of time. It's still early in the study relatively for these patients and their courses, so it'll just be giving you a general trend in that direction. KMT2As, you expect to be relapsed refractory by six months, seven months. Again, watching their course as they've evolved over time will be important for folks. Yeah. Phil, it's not about response rate, it's about durability, right? You expect the backbone to drive high response rates. As you look across the competitors in the class, you should be looking at the swim lanes and looking for durability, as Molly said. What would you consider to be good durability versus disappointing in your mind? Where do you need to be? I'm hoping that we barely even know the answer to that question by the time we hit EHA, because we're just still going and going and going. I'd really like to have it so that we beat that one-year mark of the 50% relapse refractory rate and have these patients still in a response and seeking the treatment they want, be it transplant or avoiding transplant. Obviously, a key question for any combination regimen is whether there's overlapping toxicities. Have you seen anything concerning in the initial data? The easy answer is no, we have not. We actually, one of the biggest things that I think every combination is concerned with is count recoveries, how quickly, because these backbones are tough and they really wipe out a patient's bone marrow. We wanted to make sure, FDA wanted to make sure, investigators wanted to make sure that ziftomenib wasn't prolonging any of those time to count recoveries. That is also a very important point to look at, but also the biggest source of overlapping toxicities that you could have. I am satisfied that we are not seeing it. It has been a very good journey to be part of. Great. Maybe moving on to the other part of KOMET-007 in combination with venetoclax. There was some data reported at ASH 2024. Can you summarize that data and what does that initial data suggest about the combinability of ziftomenib and the standard of care in the unfit population? What we presented last year was from the dose escalation portion of the trial, the phase I-A in both the NPM1 and the KMT2A. That was in the relapsed refractory patient population as well. Once we reached the 600 milligram dose and confirmed both internally and with the FDA that 600 milligrams does appear to be the proper dose, we opened up an expansion phase in this frontline patient population, continued the relapsed refractory, but also opened the frontline population. This will be people's first glimpses at that frontline data. Relapsed refractory data tends to be hard to interpret because these patients have had so many different things in their past and they're at such different points in their treatment journeys. This frontline data is what we're very excited to be able to share with you guys finally now. You can see how the combination of ziftomenib plus venetoclax really could potentially transform the field. What will differ from the ASH presentation in the update we get in the second half of the year? Is it specifically we'll get the frontline data or are there other elements that we'll see as well? You'll get the frontline data. It'll be your first peek at the frontline data. You should also be getting an update on the relapse refractory data. Yeah. Sorry, Phil, just to jump in, they are obviously, these are unfit patients. The goal is not always to get them to transplant. You are looking at, can you keep them on a menin inhibitor as monotherapy? Essentially, as Molly said in the intensive setting, can you keep them in a durable response? Right? That is what you are going to be looking for. Recall, our focus in the frontline is really around the NPM1 because in our experience, most of the KMT2A frontline patients go to the intensive chemotherapy because that is their best chance for a cure. The frontline focus will be around NPM1, as Molly said. We will also give you an update. Now we have experience at 600 milligrams in the relapsed refractory setting, and you will likely get an update on that as well. Great. Maybe moving on to the pivotal study in December, you announced the design of the 017 trial. Can you describe the highlights of that design? Go ahead, Molly. Sure. Under the umbrella of a single trial, we are actually performing two pivotal trials, one in the intensive setting with 7+3 and one in the non-intensive setting with venetoclax. In the intensive setting, we'll be enrolling both KMT2A and NPM1 mutant patients. And we'll be doing it in a fashion that allows the physician and whoever's reviewing the data to understand where ziftomenib makes the biggest impact. We'll be looking at it in induction, we'll be looking at it in consolidation, and we'll be looking at it in post-consolidation, whatever that consolidation may have been, whether it be chemo or whether it be transplant. It'll be a three-arm study in order to really isolate the effects of ziftomenib, randomized, blinded, placebo-controlled, all the works. Similarly, with the VEN/AZA, as Troy mentioned, we have seen that the KMT2A patients do not enroll in VEN/AZA in the frontline any further. It's very rare that they are part of the frontline VEN/AZA. They're younger. They're seeking different outcomes. That is why we're going to focus on the NPM1 mutant patients. Again, it'll be double blind, randomized. These both studies were designed with the potential for accelerated approval in mind. The 7+3 has an accelerated approval endpoint of MRD negative CR that hopefully we would be able to get a readout of that in 2028, as we've previously shared. For VEN/AZA, similarly, the accelerated endpoint would be the CR rate. We haven't really discussed exactly when we should be seeing that, but as the study gets underway and we see the operational characteristics, we'll be able to give some more color. The use of CR and MRD negative CR as regulatory endpoints is novel. It seems very likely to accelerate development. Can you discuss the key discussion points with regulatory agencies that enabled using those endpoints as primary for accelerated approval? Yeah. Thankfully, the regulators, they're scientists, they're physicians, they see the data, they've read the papers, they see all the trends towards CR, MRD negativity really being more predictive of a more durable response. They have become more open to it. When we take additional data to them, showing them our interpretation of MRD negativity in our data, as well as those additional resources that have already been published, they're open to discussing what points they need to see in order to really believe that they can correlate MRD negativity with overall survival. They do have a checklist that's been developed of all the data points that they want to see at the time of submission that'll really help validate. They were satisfied that we were able to provide those based upon the plans that we have in place. I think they're rooting for this to work because they really would like to make development less than the timelines that it currently operates under with many, many years to time devoted to getting to the right answer. I don't think you've disclosed the powering of this study for either the primary and part of the accelerated approval endpoints. Could you disclose those if you have and remind us what they are if you have disclosed them? If not, when do you think we will be able to know the powering? We'll probably disclose that, Phil, as Molly said, a little later in this year as we get closer to those trials actually initiating. They'll go live on ClinicalTrials.gov and we'll be able to speak to them. Not quite yet. You've guided to the MRD negative CR data available in 2028. That seems like an aggressive timeline. What gives you confidence that you can hit it? The robust enrollment we've been experiencing throughout the trials. Uh-oh. Mollie Leoni, I'll pick it up. Phil, the robust enrollment that we've been experiencing in the 007 intensive chemotherapy trial. Site excitement. Oh. Sorry. Good. As well as the site excitement because you can't really conduct the trial of it and want to part of it globally for something this large. We know how many sites will likely participate. We know the enrollment we expect. We do think 2028 is a very reasonable guesstimate. Also, again, it's an accelerated endpoint. We've timed it so that it's something that is reliably easily measured in these patients at an earlier time point rather than a survival endpoint. What other additional registrational trials are being considered? Are there perhaps trials in the maintenance setting or in combination with FLT3s? Both. Short answer, Phil, both. We have to be data-driven. I think, again, you'll see as you see the EHA data and then hopefully the data, if we're able to present it at ASH, one needs to consider carefully what a maintenance trial looks like. One of the takeaways from EHA may be the large number of patients who are just remaining on ziftomenib as monotherapy without going to transplant. As you mentioned, there's clearly an unmet need among FLT3 mutant patients. We have a combination with gilteritinib underway in the 008 trial in the relapsed refractory setting. We intend to evaluate the combination with quizartinib in the frontline setting. Depending on the outcome of those, we can make a data-driven decision on how best to prosecute the frontline FLT3 mutant population. When could we see additional data from the 008 trial? Is that likely in the second half of this year? It's not going to be the second half of this year. I think the second half will focus on 007. 008, not everything can be a priority at the same time. The 008 cohorts still, which are FLAG-IDA, LDAC, and gilteritinib, are all still moving methodically through dose escalation. Let's give those a little bit of time before we share that data with you. None of those, Phil, are likely to be registrational. Molly's strategy has been to do combinations of ziftomenib with all the appropriate standards of care, get that data out there, reassure physicians of the safety, tolerability, combinability. There isn't as much of a rush to really get those into a registrational setting. The focus is, as you correctly put, 007 and 017. Maybe last question on menin inhibitors before moving to the FTIs briefly at the end. You've announced the intention to pursue a menin inhibitor in solid tumors. What's the status of that program and when could we see the initial data? I think we can split that into two pieces, Phil. The first opportunity is ziftomenib plus imatinib in GIST. That's the KOMET-015 study. That study is now enrolling in dose escalation. We haven't guided yet on timing for data. It's enrolling well, but let's get some experience with it before we guide on data. Beyond that, there are additional opportunities in other solid tumors. We think it's likely we would use a different menin inhibitor beyond ziftomenib for those opportunities. One of them you can see is the KAT6A plus menin in combination. That looks interesting. There are other opportunities as well. Great. Maybe moving on to the FTIs. Can you give a brief summary of the status of the FTI programs and when we could see data next? Yeah. The thing that people should be looking for is, and this has been quite a journey for us. I think the killer application for FTIs is in combination with other targeted therapies. As it turns out, whether it's a TKI in renal cell, a KRAS G12C inhibitor, a PI3 kinase alpha inhibitor, when you treat tumors with those molecules, the tumors, you either get innate or adaptive resistance. That resistance runs through a common mechanism that involves a farnesylated target called Rheb, RAS homolog enriched in brain. What you're looking for from this update, Phil, is, again, safety, safety, safety. Can you safely combine with these different classes? Can we show you data that says the combination of an FTI plus that targeted therapy is meaningfully better than the targeted therapy alone? That's the bar that we're setting. We're going to provide updates on the current trial, which is Tipifarnib plus Alpelisib, as well as the FIT trial, which is the monotherapy escalation for KO-2806, as well as the combination with Cabozantinib in renal cell carcinoma. Look for that in the second half of the year, potentially at ESMO. Great. Maybe last question to wrap it up. Question we're getting about all companies. Can you remind us where Kura Oncology's manufacturing, its IP is domiciled, and any potential impact on pharmaceutical tariffs? IP is based in the U.S., domiciled in the U.S. The tariff impact, Phil, is de minimis. It's a small molecule, fortunately. And we've actually strengthened the supply chain. We do have certain segments that are in China. We also have segments that are in India and then some of the final production is done in Canada and the U.S. We think we're well protected from any of this extra turbulence. Great. With that, I think we're out of time. So thanks so much for a very interesting update and congratulations on the data. ASCO and EHA. We look forward to the full presentations. Thank you. Thank you.