Kura Oncology, Inc. (KURA) Q4 2024 Earnings Report, Transcript and Summary

Good day, everyone, and welcome to today's Q4 2024 Kura Oncology, Inc. Financial Results Conference Call. At this time, all participants are in a listen-only mode. Later, you will have the opportunity to ask questions during the question-and-answer session. [Operator Instructions] Please note this call is being recorded. It is now my pleasure to turn the conference over to Patti Bank, Investor Relations. Please go ahead.

Thank you, Angela. Good afternoon, and welcome to Kura Oncology's fourth quarter and full year 2024 conference call. Joining me on the call are Dr. Troy Wilson, President and Chief Executive Officer; Dr. Mollie Leoni, Chief Medical Officer; Brian Powl, Chief Commercial Officer; and Tom Doyle, Senior Vice President of Finance and Accounting. Before I turn the call over to Dr. Wilson, I'd like to remind you that today's call will include forward-looking statements based on current expectations. Such statements represent management's judgment as of today and may involve risks and uncertainties that could cause actual results to differ materially from expected results. Please refer to Kura's filings with the SEC, which are available from the SEC or on the Kura Oncology website for information concerning risk factors that could affect the company. With that, I'll turn the call over to Troy.

Thank you, Patti, and thank you all for joining us. We're continuing the momentum generated in 2024 as we continue to make meaningful advancements across our pipeline. We're poised to submit our first NDA for ziftomenib. We're preparing to commercialize ziftomenib as a potentially best-in-class menin inhibitor for patients with relapsed and/or refractory NPM1-mutant AML, which serves as a first step to providing clinical benefit to patients across the treatment continuum. And we've delivered unprecedented development and regulatory pathways for ziftomenib in frontline AML. Specifically, we've reached alignment with FDA on potential pathways for accelerated approval in the US in both the intensive and non-intensive frontline settings by allowing the trials to use MRD-negative CR and CR as primary endpoints respectively. We can now report we've also gained alignment with the European Medicines Agency or EMA, on the KOMET-017 protocol. We believe these advancements could meaningfully accelerate the development and commercialization of ziftomenib in frontline AML with top-line results from the MRD-negative CR accelerated endpoint in the intensive chemotherapy setting anticipated in 2028. As we look beyond ziftomenib in AML, we're advancing a strong product candidate pipeline with clinical data updates expected throughout this year. And we're well financed and resourced to create significant value for patients and our stakeholders. So with that, let's turn to specific updates. Starting with our most recent news, earlier this month, we announced positive top-line results from KOMET-001, the Phase 2 registration-directed trial of ziftomenib in patients with relapsed/refractory NPM1-mutant AML. The trial achieved its primary endpoint, consistent with a targeted 20% to 30% CR/CRh rate. The data have been presented -- have been submitted for presentation at ASCO. The benefit risk profile for ziftomenib is highly encouraging and the safety profile was consistent with prior reports. As a reminder, ziftomenib is the first and only investigational drug candidate to be granted Breakthrough Therapy Designation or BTD, for treatment of relapsed/refractory NPM1-mutant AML. Facilitated by the BTD status of ziftomenib, we completed our pre-NDA meeting with FDA and anticipate submitting an NDA next quarter. We believe the combination of safety, tolerability and clinical activity in a once-daily oral medication support a competitive profile in the relapsed/refractory market as well as advanced clinical development in those critical frontline indications. And speaking of the frontline AML indications, I'm going to turn it over to Mollie to review the unmet need in this patient population as well as feedback we've received from regulatory agencies. We're excited to share these updates because we believe the frontline usage of menin inhibitors could be a transformative clinical and commercial opportunity with the US market for menin inhibitors in frontline AML reaching over $7 billion annually. Mollie, over to you.

All right. Thank you, Troy. Our intent with ziftomenib has always been to treat AML patients throughout the continuum of care. And despite advances over the last 20 years, there remains a significant unmet need even in the frontline setting. Specifically, even with approved therapies, up to 70% of patients who achieve a first remission will see their AML return within three years. The five-year survival rate for AML is only 31.9% and is as low as 11.2% for patients older than 65. Given the unmet need, we are addressing the frontline AML population through 2 independent randomized, placebo-controlled Phase 3 trials contained within a single trial protocol we call KOMET-017. On our investor call a few weeks ago, we announced reaching alignment with the FDA on the KOMET-017 trial protocol. We were particularly pleased by FDA's willingness to allow the trial to use MRD-negative CR and CR respectively as primary endpoints for accelerated approval in the IC and non-IC populations. We also stated that we would continue to work with other global health authorities, and we're now pleased to report that we have also gained alignment with EMA on key aspects of the KOMET-017 protocol with both FDA and EMA aligned on the survival-based endpoints, including EFS and the intensive chemotherapy combination to support potential full approval. By combining two trials under a single protocol, we intend to facilitate study start-up and execution and we believe the protocol is more attractive to clinical sites because it provides treatment options to the broadest patient pool. KOMET-017-NIC or non-intensive chemotherapy is a trial that will evaluate ziftomenib with venetoclax and azacitidine in newly diagnosed NPM1-mutant patients unfit to receive intensive chemotherapy. The trial will assess complete response and overall survival as dual primary endpoints to support potential U.S. accelerated and full approvals. KOMET-017-IC or intensive chemotherapy is a trial that will evaluate ziftomenib with intensive chemotherapy or 7+3 in newly diagnosed NPM1-mutant and KMT2A-rearranged AML patients. The trial will assess MRD-negative complete response and event-free survival as dual primary endpoints to support potential US accelerated and full approvals. We believe the best opportunity to achieve long-lasting remission and extend survival for these patients is to achieve MRD negativity with the first attempted treatment. And by utilizing this endpoint in KOMET-017-IC, we are paving the way in the field to establish this new surrogate endpoint. Based upon our current assumptions around the KOMET-017-IC trial, we believe we may have top-line MRD-negative CR results for the intensive frontline trial in 2028. This is notably faster than we expected and well within the time window funded under our collaboration with Kyowa Kirin for the development and commercialization of ziftomenib in AML. We look forward to collaborating with our colleagues at Kyowa Kirin to expedite study start-up timelines and expect to initiate KOMET-017 trials in the second half of 2025. Not only are we now working to develop ziftomenib across the continuum of care in AML, but we are also looking ahead to multiple clinical updates later this year across both our menin inhibitor and FTI programs with the goal of developing innovative therapies for patients in areas of unmet medical need. And with that, I'll turn it back over to Troy.

Thanks, Mollie. Turning now to other opportunities for ziftomenib. We remain on track to initiate the KOMET-015 trial in the first half of 2025, which will evaluate the combination of ziftomenib and imatinib in patients with advanced gastrointestinal stromal tumors or GIST. This will be the first expansion of a menin inhibitor into solid tumors for us and it's supported by extensive preclinical data. The combination of ziftomenib and imatinib shows robust and durable antitumor activity in both imatinib-sensitive and imatinib-resistant GIST preclinical models, representing the full GIST treatment continuum. Until now, all therapeutic approaches to treating GIST have been through targeted KIT inhibition via tyrosine kinase inhibitors or TKIs. Menin inhibitors offer the potential to shift the treatment paradigm and ziftomenib may delay the onset of resistance to the frontline standard of care imatinib or overcome such resistance in patients pre-treated with imatinib, a drug to which 60% of patients develop resistance within two years. Because of the unique mechanism of action and the demonstrated synergy between ziftomenib and imatinib, this preclinical data has been described by our clinical collaborators as potentially transformative. Given the unmet need and the continued significant interest in novel therapeutic approaches to GIST, we're working hard to initiate the KOMET-015 study, which we believe will begin in the first half of 2025. And we believe ziftomenib's market potential in GIST may represent an additional $1 billion peak sales opportunity. Now while much of the focus externally is rightfully on our ziftomenib program in AML, our team has also been hard at work on our farnesyl transferase inhibitor programs. Despite multiple advances, innate and adaptive resistance remains a challenge for many classes of targeted therapies in cancer. We've learned a lot from our growing body of clinical and preclinical data, demonstrating the potential of tipifarnib and KO-2806 as companion therapeutic agents to augment the antitumor activities of various targeted therapies and to overcome resistance in combination. We're making good progress in our FIT-001 trial, evaluating our next-generation farnesyl transferase inhibitor, KO-2806, and the dose escalation portion of our KURRENT-HN trial is now complete. We look forward to presenting the first clinical data for KO-2806 as a monotherapy and in combination as well as clinical data from the KURRENT-HN trial. If successful, we believe KO-2806 and other farnesyl transferase inhibitor drug candidates could drive enhanced antitumor activity and become combination partners to multiple targeted therapies in large solid tumor indications. All of this work is made possible through the support of our shareholders as well as the global strategic collaboration we announced in November with our partner, Kyowa Kirin, to develop and commercialize ziftomenib, funding the expansive AML development program through frontline U.S. commercialization. Our financial health was strengthened by our team reaching alignment with FDA on potential paths to accelerated approval in the large frontline AML indications. Under our partnership with Kyowa Kirin, we're now well capitalized and resourced to prepare for NDA submission of ziftomenib to continue our preparation for commercialization and to expand and accelerate our ziftomenib development program. With that, I'll turn the call over to Tom Doyle for a discussion of our financial results. Tom?

Thank you, Troy, and good afternoon, everyone. I'm happy to provide a brief overview of our financial results for the fourth quarter of 2024. Collaboration revenue from our Kyowa Kirin partnership for the fourth quarter of 2024 was $53.9 million compared to none for the fourth quarter of 2023. Research and development expenses for the fourth quarter of 2024 were $52.3 million compared to $32.5 million for the fourth quarter of 2023. General and administrative expenses for the fourth quarter of 2024 were $24.1 million compared to $14.2 million for the fourth quarter of 2023. Net loss for the fourth quarter of 2024 was $19.2 million compared to a net loss of $42.8 million for the fourth quarter of 2023. This includes non-cash share-based compensation expense of $8.6 million compared to $7.2 million for the same period in 2023. As of December 31, 2024, Kura had cash, cash equivalents and short-term investments of $727.4 million, including the upfront payment of $330 million from Kyowa Kirin compared to $424 million as of December 31, 2023. We believe that our cash, cash equivalents and short-term investments as of December 31, 2024 will be sufficient to fund our current operating plan into 2027 and combined with payments anticipated to be received under our collaboration agreement with Kyowa Kirin should support our ziftomenib AML program through commercialization in the frontline combination setting. With that, I’ll now turn the call back over to Troy.

Thank you, Tom. Before we jump into the question-and-answer session, let me just quickly lay out our anticipated upcoming milestones. We expect 2025 to be a robust year of research, development and pre-commercial activity for the company with several expected data read-outs across multiple programs. Notably, we look forward to potentially providing updates across our pipeline at every major medical meeting this year. For ziftomenib, we expect to submit an NDA in relapsed/refractory NPM1-mutant AML in Q2, present top-line data for KOMET-001 for presentation in Q2, present preliminary clinical data from the KOMET-007 Phase 1b expansion cohort evaluating ziftomenib with intensive chemotherapy at a medical meeting in Q2, initiate the KOMET-015 trial evaluating ziftomenib and imatinib in patients with advanced GIST in the first half, initiate two independent Phase 3 registration-enabling trials in frontline intensive and non-intensive AML in the second half, present preliminary clinical data from the KOMET-007 Phase 1b expansion cohort evaluating ziftomenib with venetoclax and azacitidine at a medical meeting in the second half, and nominate a next-generation menin inhibitor development candidate for use in diabetes in mid-2025. For our farnesyl transferase inhibitor programs, we expect the following milestones. Initiate one or more expansion cohorts of KO-2806 and cabozantinib in patients with advanced renal cell carcinoma in the first half; present data from the Phase 1 monotherapy dose escalation of KO-2806 in patients with RAS mutations in the second half, present data from the Phase 1 trial evaluating KO-2806 and cabozantinib in patients with renal cell carcinoma in the second half, and finally, present data from the dose escalation portion of the KURRENT-HN trial evaluating tipifarnib and alpelisib in PIK3CA-dependent head and neck squamous cell carcinoma in the second half. And with that, Angela, we're now ready for questions.

[Operator Instructions] We'll go first to Li Watsek with Cantor Fitzgerald. Please go ahead.

Hey, everyone. Thank you very much for taking my questions. Troy, you guided to the Phase 3 top-line in frontline intensive AML setting in 2028. Just curious what assumptions went into that guidance? And anything you can share on the trial size, that plan or enrollment timeline?

Yeah, Li, thanks for the question. We thought it was important because we've been getting questions from both analysts and investors to give people some idea of the timeline, particularly now that we've gained alignment with both FDA and EMA, but specifically with FDA on pathways to accelerated approval in the US. And we feel comfortable, we think we're being conservative, but we feel comfortable saying that we think we can have top-line results for that accelerated approval endpoint in 2028. We'll give you more detail on the trial size, the powering, et cetera, as we get a little bit closer to the trials actually going live and being posted on clintrials.gov. And that's being driven both by -- we're just doing some further refinement and we're in the process of study start-up. But that is meaningfully faster than what we were projecting for prior to our engagement with the health authorities. And obviously, it positions us well in the context of the funding received under the Kyowa Kirin collaboration. I would say look forward a little later this year for more updates, Li, not only on the intensive trial that you're asking about, but the non-intensive trial as well, the sizes, the powering and then how do we get to both the potential for accelerated and then the survival-based endpoints. I hope that's helpful.

Yeah, understood. And then just wondering what the remaining items that you may need to work through before the NDA submission. Any notable feedback from the pre-NDA meeting?

No. I mean, that's -- thank you for the question. I don't know if at the time we made that announcement a few weeks ago, if that -- if people sort of read over that. We were deliberate actually in not saying anything until after we've had the pre-NDA meeting. And the team -- Mollie and the team did a phenomenal job of again gaining alignment with the agency on all the aspects of the submission. Clearly, the clinical data is always the long pole in the tent, and that's what is driving the timing of the submission at this point. But given that we have BTD and given that we've had pretty constructive engagements not only on the monotherapy, but now in the combination setting with FDA, we feel like we're in good shape. And again, we're guiding to a second quarter submission. The team is doing everything in its power to accelerate those timelines. But so far, I think we have everything we need and we've gotten very -- it's been a very constructive series of interactions with the agency. Angela, should we go on to the next question?

We'll go next to Jonathan Chang with Leerink Partners. Please go ahead.

Hi, this is Yen-Der Li on for Jonathan Chang. Thanks for taking my question. So the first question I have is that when we look at the commercial opportunities for ziftomenib, I guess, the most important variable is the treatment duration. Could you share the reason behind your confidence that frontline AML patients will be able to stay on the treatment for more than a year? Thank you.

Yeah. Let me actually -- Yen-Der, thank you for the question. I'm actually going to do this in two parts. Maybe Mollie can speak to how we've informed the duration of treatment from our experience with KOMET-007. And then I'll ask -- after she answers, I'll ask Brian to comment on how does that translate into our assumptions around the commercial potential in the frontline. Mollie, if you would?

Sure. As Troy alluded to, the 007 trial has been highly informative to how we handle designing and our expectations for the 017 trial and for use in the frontline in general. I think initially, we thought that, especially with the intensive chemo setting, the use would be some induction, some consolidation, then the patient will go off to transplant and potentially some proportion would come back after transplant, post consolidation maintenance. What we're seeing is incredibly different, especially for the NPM1 patients that make up such a large majority of the patient population. These patients are coming on doing induction, consolidation and post-continuation consolidation immediately with few trips to transplant, except for the KMT2As who get to transplant whenever possible and then almost universally either have returned or intend to return to post-consolidation, post-transplant maintenance. Similarly, with the ven/aza, we have patients that are staying on for very prolonged periods of time on treatment in the frontline even when -- or if the backbone drops away or is decreased in intensity or used a little bit differently from when it's used prior to gaining control of disease. So we're seeing good prolonged use in each of these that was probably more significant than what we initially thought. But with that, Brian, I'll turn it over to you to how you see that translating.

Sure. Thank you, Mollie. And based on the assumptions that we are observing -- or what we've observed in the trial, like Mollie said, we do think there's a tremendous potential that menin inhibitors could transform the treatment of AML with patients being able to get on therapy, stay on therapy for a long period of time. When you think about our opportunities with -- and as we've stated that we think this could be -- as Troy said, it could be a $7 billion potential market. If you're able to get patients to receive menin inhibitor for 18 to 24 months, and there could be potential for longer than that, but if you think between that 18 to 24 months in the FIT intensive chemo population and then 18 months plus within the non-intensive, that gives you a significant duration that we think really could reflect that transformative potential and really kind of align with what we've seen in some other markets like multiple myeloma where long duration of treatments with IMiDs have really transformed the market and also the outcomes for patients.

Got it. Thanks for the comprehensive answer. And I have also a follow-up question related to that. So for the KOMET-017 intensive combination study, if I recall correctly, the patient will include both transplant and non-transplant chemo as consolidation options. And is there a concern about the imbalance of consolidation treatment received in each arm? And do you have any like protocol to mitigate such concern? Thank you.

Yeah, Yen-Der. Let me let Mollie speak to that. Mollie, do you want to take a shot at Yen-Der's question?

Sure. Well, starting with the KMT2A patients, we really don't think there will be an imbalance. The intent is always to get them to transplant. So it's likely that all that can will get to transplant. With regards to the NPM1-mutants, it may be that some of the patients do better, hopefully, they do better in the active arm and so are less requiring of transplant. So we've built in multitudes of sensitivity analyses to be able to account for that. But ultimately, we've built the trial, sized the trial, powered the trial, taking that into account and weighing in the effects that the KMT2A patient population would have on the overall population and being able to assess the effects of transplant or no transplant in the active versus placebo arms, if that's helpful.

Yeah, that's helpful. Thank you so much.

Thank you, Yen-Der.

We'll go next to Jason Zemansky with Bank of America. Please go ahead.

Good afternoon. Thank you so much for taking our question and congrats on the progress. I was curious, as you look to the additional dose expansion data from the 007 study, what in your view would be encouraging from the 7+3 combo as you start to expand into the non-adverse risk group? Specifically in terms of MRD negativity, what gives you -- what would give you confidence that addition of zifto would ultimately give you a survival benefit?

Yeah. Jason, thanks for the question. I'm going to ask Mollie to speak to it. But, Mollie, maybe you can take a minute and help folks understand how we think about the MRD negativity and sort of what the standard is as you answer Jason's question.

Absolutely. So what we understand, obviously, we're part of a consortium of a large amount of pharmaceutical companies that are really looking into this MRD negativity for this patient population. And we have access, therefore, to both published and unpublished data from those other pharmaceutical companies as well as from some of the key opinion leaders that are really advancing the MRD as an endpoint in AML. So we understand that a good outcome for these patients with the current treatments available would be to see about a 40% to 45% MRD negativity in the bone marrow. And that's for the better performing patients, so your NPM1s, for instance. So we would expect that any incremental increase in that would be due to the influence of having a targeted agent in the mix as well and maybe getting into the 50s and 60% MRD negativity rate would be encouraging for translation into the overall survival as well. So that's the way we're thinking about our data as we continue to look at these patients enrolling. Obviously, you've seen the patients do very well from a response perspective. So I wouldn't expect to see much difference in that. They're going to continue to do well. But it's -- as you're pointing to, the MRD that is what we're looking at to make sure we're headed in the right direction.

Got it. Makes sense. And maybe just a quick follow-up here. I noticed the other mutations bucket, about 10% to 15% of the population. Curious, what does it take to get there to that group of individuals? And what gives you confidence, I guess, that a menin will be active in these subtypes?

Yeah, I'll take that, Jason, and then Mollie can add her comments. We have seen what we call off-target activity, not only with the SETD2/RUNX1 patient, but we've seen other patients as well who appear to be receiving clinical benefit from ziftomenib in the monotherapy studies. One of the obvious areas there, of course, is FLT3. And of course, there's an improved standard of care in the intensive setting. There's actually a couple of them less so in the non-intensive setting. But if one were to look at KMT2A, NPM1 and then FLT3, that gives you approximately half of the eligible AML patients. We have a study ongoing with gilteritinib in the relapsed/refractory setting that is supporting the notion that one can combine a menin inhibitor and a FLT3 inhibitor with appropriate safety and tolerability. Clearly, if you want to go into the frontline, you need to go with an approved agent. There are a couple, midostaurin and quizartinib. We've guided that we anticipate starting -- hopefully, I should say, potentially a frontline combination study of ziftomenib plus quizartinib. And again, we're optimistic that we can go straight into the frontline because now we have adequate safety of ziftomenib, both as a monotherapy and in combination. So that would likely then give -- it would require us to go beyond what we're doing with the KOMET-017 trials. But as I think we mentioned when we talked more about the deal with Kyowa Kirin, the collaboration is structured and we are actually funded to run multiple global Phase 3 trials and one could potentially be an upcoming FLT3 trial. So there are a lot of priorities at Kura at the moment. Clearly, the NDA submission, the pre-commercial activities, KOMET-017, but FLT3 is very much on the team's mind and something that I think you'll see us move toward here in the second half.

Got it. Appreciate the feedback. Thanks.

Sure.

We'll go next to Peter Lawson with Barclays. Please go ahead.

Hey, thanks, Troy. I wonder if you could just kind of talk a few minutes just around where you stand for diabetes and the nomination of the candidate and kind of where that fits in your priorities and how you're thinking whether it's type 1, type 2 or particular stage of the disease? Thanks so much.

Yes, Peter, I appreciate the question. That wasn't expected, but is welcome. So a couple of comments. Going for everybody's benefit, we put out data at the American Diabetes Association meeting last summer. That data shows four things, four hallmarks, glucose lowering, insulin -- stimulation of insulin production, insulin sensitization and selective expansion of pancreatic beta islet cells. All the -- to our knowledge, all of the existing antidiabetics do various of three of those four. We haven't yet had an agent that selectively expands pancreatic beta islet cells. And that's really kind of the holy grail. The work that we did preclinically is with ziftomenib. We wouldn't take ziftomenib forward into diabetes for safety reasons, pricing reasons, IRA reasons. That's why we've been very clear from the get-go. If you're going to go into diabetes, you go with a different molecule. And Peter, we have been carpet bombing the chemical space in menin for now going on three years. So we have molecules that have different PK profiles, different tissue distributions. We really feel like one can actually ask that question in the right way with chemical -- with drug candidates. To your specific question, in our internal work, our work with investigators and KOLs and our work with certain, shall we say, strategic partners that know diabetes well, there really is an interest in exploring both type 1 and type 2. We wouldn't put restrictions on those populations today based on what we know. It appears that if one has some reservoir of pancreatic beta islet cells, there's probably good applicability. What we want to be clear about is, there is potentially a lot of value here to be created for patients, first and foremost, but also for Kura's shareholders, but we have to do that in the right way. We are a specialty oncology company. We know what we know. If you see us work in diabetes, we could do some initial -- we can do the preclinical work, maybe some initial clinical work, but we recognize you pretty quickly need to get that into the hands of a company that is going to be invested from the get-go at running the large global Phase 3s that would be required to test those hypotheses. So there are a lot of creative ways one can do that. The good news is we have the chemical matter. I think we have as good -- due to Francis Burrows, who is not on the call with us today, our CSO, we have as good an understanding as anyone about menin inhibitors in diabetes. At the moment, the nearest term milestone is nomination of a development candidate. We're going to take our time because the demands on the therapeutic index are quite different than oncology and you want to have the right molecule, the right drug-like properties and the right therapeutic window. And we want to have a molecule, Peter, that has the potential to go the distance. Does that answer your question?

Yeah, that's great. Thank you. I guess there was a breadcrumb in there for me, just kind of what's the right route forward so you kind of capture the potential upside of something like diabetes yet not dilute yourself?

What's the right -- say that again, Peter, what's the right what?

What's the right strategy there? Is it like a JV partnership? How should we think about so you kind of capture upside yet you don't lose your focus around oncology?

Yeah. So yeah, understood. I mean, a few things there. I think you want to make -- you want a flexible structure that allows you to cleanly separate the biology, and importantly, the IP, the oncology from the non-oncology. Ideally, you want to make certain that the value is captured for Kura shareholders. This could be the first novel mechanism of action in diabetes since GLP-1. But I don't think we're under illusions that Kura shareholders are looking for royalties a decade out from now. So we want to be thoughtful about how we do it. You would ideally, Peter, look for -- look to a structure that really allows you to go very fast, may allow you to take more than one molecule forward and ideally allows you to monetize that IP in a way that you could again either extend runway or do other creative things, stock buybacks, et cetera. So fortunately, this -- we're not inventing the wheel here. There's lots of wheels that have been demonstrated to work. But you'll see -- those are sort of the themes that we're looking at. And the good news is this is essentially a call option on the story. I think it's scientifically and clinically really interesting. It is not as high a priority as what we need to do in AML in this year and everyone at Kura knows that. But we would be -- we wouldn't be doing our best for patients if we didn't find a way to get this into the hands of the clinicians and let them really test the hypothesis.

Great, thanks so much. Thanks for letting me deviate the conversation away from [payment] (ph). Thanks, Troy.

Sure.

We'll go next to Phil Nadeau with TD Cowen. Please go ahead.

This is [Daniel Rodriguez] (ph) for Phil. Thanks for taking our questions. I will start with -- I have two questions. First one is on the competitive landscape. Now that we have -- that you have at hand the results from KOMET-001 and we had updated data from several other menin inhibitors that were presented at ASH, how do you think or expect zifto to be differentiated from the others or how do you see the competitive landscape ultimately playing out?

Yeah. Thanks for the question. I mean that's a big question, but we'll try to be maybe brief and hit the high points. If we go back to -- so there's an opportunity to do the very best you can for relapsed and refractory patients with NPM1-mutant leukemia. That's what we're targeting with zifto. And we think we're going to be very competitive in that space. As you heard Mollie say, and I think Brian echoed, when you talk to the physicians who treat these patients day in and day out, they will say to you, you need to treat early and you need to treat in combination. And ideally, you keep these patients in remission for as long as you can. What zifto is allowing the physicians to do is to keep these patients on therapy. Regardless of whether the backbone is intact or the backbone has fallen away, these patients are staying on ziftomenib for prolonged periods of time in our 007 study, as Mollie said, in both the intensive with 7+3 and the non-intensive with ven/aza. The ven/aza may fall away, but they're remaining on ziftomenib. And in the case of NPM1, many of them are not going to transplant. Why is that? It's because, of course, the compound has meaningful clinical activity, but it also has a safety, tolerability and convenience factor that allows for once-a-day daily dosing with very good tolerability. We've been touting this from the get-go and continue to believe that as you look toward those large frontline indications, combinability is going to be key. That is what is going to give patients the best chance to stay on therapy for prolonged periods of time. We have no QT prolongation, no myelosuppression, once-daily dosing, no clinically meaningful drug-drug interactions. It's a very easy drug to use. For folks who may be listening, I would refer you to when we did our investor event after the ASH presentations, the commentary that Dr. Zaidan gave around his experience with intensive chemotherapy patients. That's really how we see ziftomenib being differentiated from the competition.

Got it. Thank you. That's very helpful. And on the earlier pipeline, 015 on GIST, you have mentioned the potential to delay the onset of resistance in that population. So as we look forward to the clinical data in the future, do we -- is it more relevant for us to be looking at the duration of the response aside from ORR or how should we be looking at the data once it's ready to come out?

Yeah, that's a good question. And, Mollie, let me ask you if you can speak to that and I'll just summarize the question. What are we looking for in terms of a clinical evidence of activity in the 015 study combining ziftomenib with imatinib? What are we looking to do clinically?

Yeah. So I think there's several different things we could see and each would be very positive and very confirming of what we think the combination could do. For those patients that are on imatinib and starting to fail, hopefully, we're able to save that response and get that patient back into a response. Patients that are on imatinib, and this is something we will be exploring at certain points, but after we finish most of the dose escalation, seeing if you can deepen the response to imatinib. Most of the patients that respond to imatinib do so only partially. You rarely see a complete response. So getting patients into a complete response would also be obviously of great importance. And then finally, as you referred to, the durability. So having a good duration of that response, a good progression-free survival, prolonging the usual two years TIL resistance that these patients are able to stay on drug with their imatinib backbone. So those are the three areas that I'm looking to, deepening of the responses, saving responses once they've been lost with imatinib and then maintaining the responses to imatinib for prolonged periods of time.

Thank you. And thanks for taking our questions.

Pleasure.

We'll go next to Brad Canino with Stifel. Please go ahead.

Hi, this is Dara Azar on for Brad. Thanks for taking our questions. First, on the frontline development, do you expect EMA to have an entirely different opinion than the FDA on MRD negativity as a regulatory endpoint? And maybe tell us more on how you expect to conduct 017 trial to support a global approval? And I do have a different question after this.

Okay. Yeah, those are two good questions. Mollie, would you like to take those?

Sure. So I do think that there's the potential for EMA and FDA to be at slightly different points in where they would be accepting of MRD negativity, although both regions recognize that MRD negativity is clearly a very significant piece of getting these patients into a successful remission. I think what you're kind of drawing attention to is are we going to do things differently between the regions? And the answer is yes. The accelerated approval endpoints were always intended to be for the United States, whereas we intended the survival-based endpoints to support the approvals in the EU. Does that help?

Yeah. Helpful commentary. Now switching over to relapsed and refractory, will the data cut and patient denominators match between your upcoming medical meeting presentation, I suppose, first would be ASCO abstract and the NDA submission?

Yeah. Mollie, do you want to take that?

Yeah. So we will not be adding patients to the denominator. We submitted to the FDA the full patient pool. We submitted to ASCO the full patient pool. So you would see the same group of patients, same patient population in both.

Thanks for the questions.

We'll go next to Charles Zhu with LifeSci Capital. Please go ahead.

Hey, guys. Good evening and thank you for taking the questions. Maybe one outside of AML. So maybe one program where, frankly, lots of folks have been paying very little attention to, farnesyl transferase's KO-2806. I mean, like, what would you say you need to deliver here in the second half of 2025 in order to gain more conviction on this asset and also to gain more conviction from the investment community on these, especially not only in context with the assets themselves, but also in context of some of the emerging competitive landscapes in areas like RAS or renal cell carcinoma? Thank you.

Yeah, Charles, thanks for the question. I mean, very simply, you're looking to do something that people have been trying to do for a long time, I think, largely without success. And that is how do you develop a companion target to some of these big oncogenes. People have looked at SHP2, they've looked at SOS1 in the case of KRAS. People have tried to combine inhibitors of the MAP kinase pathway and the PI3 kinase pathway largely without success. But we know, and you see it in every single study, you get responses in if you're lucky, half the patients, the other half don't respond and many of the responders actually eventually relapse due in many cases to mechanism-based resistance. So to your question, what are we looking to do? You're looking to show that you can combine a farnesyl transferase inhibitor with these other targeted therapies with acceptable safety and tolerability. You can't skip over that because that's what kills most combinations. You can have the best preclinical data in mice. And if the patients can't tolerate it, you're not going anywhere. So that's first and foremost. The second is you're looking for evidence of activity initially, and these are Phase 1 studies, right, dose escalation studies. You're looking for evidence of clinical activity that is unanticipated, unexpected. So I mentioned to you in the case of both tipifarnib and alpelisib in PI3 kinase mutant head and neck, alpelisib delivers at best stable disease. Tipifarnib is inactive. So what are you seeing when you combine those two in that population? In the case of RCC, the one that you mentioned, are you seeing activity either after the appropriate standards of care, and in particular, in combination with cabozantinib. What are you looking for? If you see clinical activity in patients who have failed the existing therapy and then you -- and this is what Mollie was alluding to with GIST. Patients who -- you give them the drug, they begin to progress, then you give them your novel agent and the drug again and you restore the response, that's -- and you have good tolerability that's telling you keep going, right? You've got an encouraging signal. I think the thing that has us encouraged continuing to move forward is we're evaluating 2806 and tipifarnib really as a sort of a test case in TKIs, in PI3 kinase alpha and in KRAS-driven tumors. Each of those are big potential blockbuster opportunities. If we're able to deliver this, that's -- I think that could really be a significant contribution to patients. We have the ability to take our time. 2806, we're confident is a very good drug. And we look forward to sharing data with you and the community in the second half of the year, hopefully, at a major medical meeting.

Great. Thank you.

Sure.

We'll go next to David Dai with UBS. Please go ahead.

Great. Thanks for taking my questions. Two from me actually. One is just on the relapsed/refractory pivotal data readout at ASCO. You mentioned that it will be a later data cut. So could you maybe just help us understand how do you think the later data cut could change the CR/CRh rate? And then on that, do you -- can you just talk a little more about the baseline characteristics of the patients that we'll potentially see? Would you expect the patients to have similar prior venetoclax treatment?

Yeah, David, let me just correct you on something you said because we may have misstated it or you may have misheard it. It's not a later data cut. What we said was it's the same -- it's effectively the same data cut the agency is seeing. We're not trying to slice and dice it. And as Mollie said, we're not going to be looking to add patients to the denominator or the numerator. So it will be the same data cut that is going in as part of the NDA submission. On the baseline characteristics, Mollie, could you answer David's question to the extent that we can?

Yeah, sure. Expect to see similar patient characteristics to what we saw in the Phase 1. Again, patients are heavily pre-treated. Most have seen venetoclax, many have had prior transplants. It's really largely a very similar patient population to the one for whose data we've already presented.

That's really helpful. And then just on the frontline KOMET-017 trial, how should we think about the contribution of Kyowa Kirin on the clinical trial? And do you think they could potentially have them help out with some of the clinical trial development to expedite the clinical trial development?

Mollie, do you want to speak to that?

Yeah. I mean, that's absolutely the hope. They're very good partners to have. They have a good presence in areas we don't like the EU, like Japan. So they will be very good partners on the ground helping to get sites up and running. Of course, they are also good standing boards for our particular strategies, especially in some of the regions they're most familiar with. So we expect them to be -- well, to continue to be very big help on both design and study start-up.

All right. Thank you so much.

Thanks, David.

We'll go next to Justin Zelin with BTIG. Please go ahead.

Thanks for taking our question. Maybe just a follow-up on Charles' earlier question. I also find the FTIs quite interesting and also important given that you have wholly owned economics on the programs and are the only companies developing the programs. Troy, you mentioned the combination approach with KRAS, which I find quite compelling. Can you talk to whether you have preclinical data with a pan-KRAS inhibitor? And just how you kind of view that landscape on the combination potential with the pan-KRAS inhibitors or the KRAS variants?

Yeah. Justin, thanks for the question. We do have non-clinical data with both mutant selective and pan-RAS inhibitors. You do see potentially synergistic activity with both. It depends interestingly on the cellular and the organ context. So for example, you see better synergy in colorectal than you do in pancreatic. That's not terribly surprising. Even though we think of both of them as being RAS-driven, it does appear that colorectal is probably more multigenic. And one of the things we're looking to do, Justin, I mean, when we started this combination, we went with adagrasib, because frankly, it was one of only two commercially available KRAS inhibitors with a well-understood safety and tolerability profile. We are eager for the KRAS field to catch up to us. There are opportunities to combine with G12D, G12V, pan-RAS. And we are -- that's an opportunity. It's also a challenge of how do you think about doing what's best for patients, while at the same time, threading the needle to get to the market and ideally take the largest segment of the market. So we are in discussions with a number of different folks. I would say, we've been encouraged thus far by the combinability of farnesyl transferase inhibitors with these other agents. That -- and when -- back in the day, before we started dosing with tipifarnib and alpelisib, people had said, what are you most worried about? And I would say to them, it's the tolerability. You don't -- that is what most of the time does these combinations in. 2806 has shown itself to be very well tolerated in combination. Now it really comes down to what kind of clinical activity are we seeing and how do we think about that forward development strategy. And what you're seeing -- what you will see us do, Justin, is likely move multiple FTIs forward to give ourselves optionality in light of competitive dynamics, pricing, IRA, et cetera, because as I said, each of those tumor types could be an entire program onto itself and we want to think carefully about how we do that. We've made a very sustained investment in farnesyl transferase. I think we're ahead of everyone else. It starts to get interesting here in the second half as we start to show clinical data. I would encourage anybody who is interested, we've got a ton of preclinical data available on our website. As I said, we will look to do some sort of event probably ahead of the clinical data with the analysts and the investor community to help educate folks on how do you think about FTIs, what's the scientific rationale, what's the current landscape, how should you think about the clinical data. Look for us to do that in the second half. We want to get on the other side of the KOMET-001 data, on the other side of the 007 data, but that's -- it's something to look forward to in the second half.

Thanks, Troy. And maybe just quickly, how should we think about business development activities from Kura, either in-licensing or out-licensing throughout the rest of the remainder of this year and into next?

In-licensing, I mean, we get pinged probably several times a week. We have yet to pull the trigger on anything. We have a very high bar to bringing anything in given everything we have going on. Our goal would be to deliver a blockbuster in AML, a blockbuster in GIST and a blockbuster in one of those FTI indications. I think if we could do that, we don't need to add anything else, to be quite frank, and we're funded to do that. But there are a couple of interesting opportunities. In terms of out-licensing, at the moment, our focus is really clinical collaborations. How can we generate clinical data that will help inform the development path. You'll see that we've prioritized drugs that are either -- that are ideally standard of care and generic or generic in the foreseeable future because it gives you and anyone in the future maximum optionality. But when we start to think about KRAS, PI3 kinase, those are going to be novel agents and you need to find people that have a shared vision of what you might do together. So I don't know about BD as much as clinical collaborations. Justin, with one footnote, and that would be back to Peter's question around diabetes, I think we have to think carefully about what we do there. And I would say, stay tuned.

Got it, some more partnerships rather than [indiscernible]. Okay, got it, thanks so much, Troy. Thanks for taking our questions.

Our pleasure. Thank you.

We'll go next to George Farmer with Scotiabank. Please go ahead.

Hi, good afternoon. Thanks for taking my questions. A couple from me. Troy, you and Mollie indicated on your last call that we would be seeing a slightly later data cut at the medical meeting versus what you would be submitting to the agency. And now you're saying it's going to be the same cut. I was -- perhaps you could elaborate on why that shift. And then also in your conversations with the agency agreeing to this MRD endpoint, that seems to be very different than how the agency has approached other hematologic indications like multiple myeloma, where they called a committee to talk about this. Can you talk about your interactions with the agency? And do you think this is something that we could see with other programs beyond Kura's? Thanks.

Yeah. Maybe on the first question, I mean, there's -- we're talking about a ton of data here, right? So there's what's in the abstract, there's what's at -- hopefully, at ASCO, potentially at ASCO and then there's what's going to the FDA. Those are slightly different, but they're all contemporaneous. And to Mollie's point, I don't think they're going to move the numbers around significantly, which is what people are really getting to. The numbers that you see in the abstract and at the -- ultimately, the poster or the oral presentation should be consistent with what we see -- with what we will be submitting to FDA for review. So to the extent that we -- no intention to create any confusion there. It's just you're talking about ever larger sort of data packages, if you will. On the engagement with the agency around MRD negativity and how that might differ from myeloma, I think again, our work with the IMPACT Consortium is instructive. But I'll let Mollie speak to that because she's really been spearheading that, George. Mollie, do you want to take George's question?

Sure. No, as we've said, we are working with a consortium of other pharmaceutical companies that are really working to gather the data that's on FDA's checklist for establishing the relationship between MRD-negative CR and overall survival. Ultimately, as we've said before, we don't need any more data right now to get our trial started. But obviously, to confirm the endpoint and to analyze the data, we'll have to be submitting a larger data package. It's hard to know in three years or less, more than likely, if -- when we start submitting these data packages that the FDA will be looking at in advance of our data to start to establish MRD-negative CR as a surrogate endpoint if they'll be calling a committee or not. They seem to be very accepting of the fact that their own internal expertise suggests that it is, in fact, a good surrogate endpoint once we get their data packages together. And so we will see how that plays out over the coming years. But we expect them to do a lot more work in the area. We're going to help support them doing the work. And all of this work is just expected to be submitted at the time we submit our own data supporting the accelerated endpoint.

Okay, great.

Yeah, George, I was going to just add to that. This is not unprecedented. Kronos a couple of years ago reported that it had alignment with the FDA on developing its SYK inhibitor in NPM1-mutant frontline AML as well. So as Mollie indicated, our interactions have been -- there's a willingness to create a pathway for accelerated approval. Obviously, we have to run the trial and show up with the data, but there's a willingness to consider that and that builds on, as you indicated, myeloma and some of the other areas where we've seen that endpoint become widely accepted. Just wanted to add that point.

Yeah. That's very helpful. And when do you think you would capture the EFS endpoint from the study?

Yeah. We haven't guided, so we've been careful. We're still working through putting those dates down. We want to make certain that when we put dates out, we can stand behind them. All of these endpoints are driven by, number one, enrollment assumptions and then other assumptions around time on therapy and survival and whatnot. Give us a bit more time. We'll come back again with more details on the trial design, more details on the timing of the endpoints later this year as we get closer to study start-up.

Okay. Great. Thanks very much, Troy.

Our pleasure. Thanks, George.

Our last question comes from Salim Syed with Mizuho. Please go ahead.

Hi, this is Eric on for Salim. Just another divergence from AML real quick, if you don't mind. One with the whirlwind of changes at FDA, staffing cuts, just wondering if you've come across anything in your engagement with FDA recently that has given you any cause to update your expectations on how quickly they're able to come back to you, their share of timelines, whether things might be picking up or slowing down due to anything that's going on from the FDA's side at this point? Thanks.

Sure. In our immediate interactions with the agency, they have been just incredibly professional, timely, cooperative. We're not getting any indication. They are such good partners. We're lucky as an industry to have such a good regulator. We are -- you are going to see us be conservative on our timing and our guidance. I don't think we'll be guiding to things coming in ahead of schedule because you just never know in this environment, right? And we have no idea what's going on internally at the agency. So we're just going to do everything we can to give them the data that they need to be able to evaluate not only ziftomenib in the monotherapy, but as we have the frontline studies, the GIST studies, the FTI studies and then hope for the best. I don't think people should necessarily be guiding to more aggressive timelines, but we're not getting any indication yet that there have been major disruptions at the FDA. And I think that's -- let's hope that that continues.

All right. Very helpful. Thank you.

Sure.

This does conclude today's question and answer period. I will now turn the call back over to Dr. Wilson for closing comments.

Thank you, Angela, and thank you all once again for joining our call today. We'll be participating in the Cowen, the Leerink and the Barclays investor conferences in Boston and Miami over the next couple of weeks and we look forward to seeing many of you there. In the meantime, if you have any additional questions, you know how to reach us, please reach out. And thank you once again and have a good evening, everyone.

This does conclude today's program. Thank you for your participation. You may disconnect at any time.