I would now like to hand the call over to Troy Wilson, CEO. Please go ahead. Thank you very much, and welcome everyone to our Farnesyl Transferase Preclinical Program Review. I'm Troy Wilson, Kura's President and CEO, and it's a pleasure to have all of you with us today. We could go to the next slide. In connection with today's presentation, we're going to be making certain forward-looking statements. We would refer you either to the SEC's website or to the Kura Oncology website for more information about Kura Oncology and about the risks and uncertainties in an investment in Kura. If we could go to the next slide, please, slide three. Joining me today on today's call are Francis Burrows, Kura's Chief Scientific Officer, and Mollie Leoni, Kura's Chief Medical Officer. As you'll see, I'm going to give a few introductory remarks, and then I'm going to turn it over to Francis to walk you through a lot of the preclinical data. He'll then turn it over to Mollie to connect that to the clinical trials and what you might expect at the upcoming ESMO presentation in October. Next slide, please. It's an exciting time at Kura. We are really, we think, well-positioned to build on the success with Ziftomenib and to develop a robust pipeline of targeted therapies for the treatment of cancer. Ziftomenib has really been much of the focus at Kura over the last couple of years, and we continue to be both very excited and very well prepared. We are currently under review with the FDA for our first potential approval in NPM1-mutant relapsed/refractory AML. We think ultimately that, you know, if successful in both the relapsed/refractory and the frontline settings, the menin inhibitor class could be a $5 billion- $10 billion class. We think we could take meaningful share of that. Our commercial team has been hired, is trained, is out in the field engaging with physicians, and we're very grateful to the collaboration with Kyowa Kirin, who have been our partners both in the development and commercialization of Ziftomenib. We look forward to positively impacting the lives of patients worldwide. Today, we're going to actually now talk about something that has been years in the making, and that's our Farnesyl Transferase inhibitor program, which is in the center of slide four. As I think you'll see, FTIs really represent a compelling therapeutic target in their ability to address innate and adaptive resistance to multiple large classes of targeted therapies. Today, we're going to walk you through the preclinical data. This is chapter one, if you will. Chapter two will be from ESMO, where we'll share with you the first preliminary clinical results. As you'll see, the breadth of potential indications is vast and includes head and neck, lung, colorectal, breast, as well as endometrial and neuroendocrine. We're very excited to bring both the preclinical and the clinical data to you. This is really the next installment in our pipeline, but even behind that, we have additional therapeutic opportunities. These are familiar to many of you. We're progressing Ziftomenib in combination with Imatinib for treatment of patients with advanced gastrointestinal stromal tumors. That study is currently in dose escalation. Hopefully, we'll be in a position to share data with you next year. We've also, just in the last quarter, nominated our first development candidate, menin inhibitor, for the treatment of diabetes and other cardiometabolic indications. We'll have more to say about the development plans, the timelines, and what to expect in a future call. Next slide. As I mentioned, today we're going to focus really on the Farnesyl Transferase inhibitor program and, in particular, the rationale for how do we use FTIs in combination with other targeted therapies to overcome drug resistance. Next slide, please. The industry has really been incredibly productive and successful with developing small molecule targeted therapies against a range of different targets. Many of those therapies are successful. They're able to drive tumor regressions, but they're not the whole story. Unfortunately, despite the fact that they may show monotherapy activity in the clinic, they're often insufficient as monotherapy to really give patients the full benefit. As such, there's really a premium on developing rational combinations, for example, the combination of KRAS inhibitors with EGFR inhibitors. This is a longstanding problem with targeted therapies, and it really motivates a need to identify and develop companion therapeutics that can address innate and adaptive resistance. Next slide. What we have at Kura is the Farnesyl Transferase inhibitor program. We are the pioneers. We've been working on this target for a number of years, and today we'll talk to you about, in particular, one of the farnesylated targets, a protein called Rheb, and its relationship to a central target, namely the mechanistic target of rapamycin. TOR, you'll hear TOR and specifically TORC1 through Francis's slides, is a central actor in both the MAP kinase and the PI3 kinase pathways. What we'll show you is that simultaneous inhibition of Rheb and mTOR through de-farnesylation of Rheb has the potential to address resistance, again, to multiple large classes of targeted therapies. Please, if we can go to the next slide. That's really shown here on slide eight. You can see the canonical signaling diagram. This is the signal transduction pathway, KRAS on the left, PI3 kinase alpha pathway on the right. This is, of course, an oversimplification of the pathway, but it makes an important point, namely, these pathways work in concert to drive cell signaling, and they are relevant to these three large classes of targeted therapies: RAS inhibitors on the left, VEGF receptor tyrosine kinase inhibitors at the top, and PI3 kinase alpha inhibitors on the far right-hand side. As you'll see, 2806 blocks farnesylation of Rheb and, in so doing, blocks the activity of TORC1. Francis is going to show you the preclinical data and help set the stage for the translation into the clinic. We go to the next slide. Today's presentation is primarily going to focus on several examples. We show you here this is not an exhaustive list, but, of course, these are therapeutic targets where there's tremendous interest, tremendous activity. The point we want to make to you with this preclinical data, as you'll see, is if you're seeing good activity with, for example, adagrasib, it's our view, at least preclinically, that should read through very positively to the entire class, both mutant selective and Pan-RAS inhibitors. Similarly, in the case of the VEGF receptor TKIs and the PI3 kinase alpha inhibitors, although we won't show you every combination, we think there's good reason to believe that if you're seeing additivity or synergy with one, it's reasonable to think about how do you translate that across the entire class. That's why FTIs are potentially so impactful as this mechanism. With that, I'll turn it to the next slide, slide 10, and I'm going to turn it over to my colleague, Dr. Francis Burrows, to introduce to you KO-2806 and to walk you through the preclinical data. Thank you, Troy. At Kura's inception in 2014, we in-licensed the J&J Farnesyl Transferase inhibitor tipifarnib with a view to developing it in HRAS mutant head and neck cancer. It was appealing because it had shown clinical activity, and its safety profile was very well characterized, and it duly performed very well in the clinic, delivering excellent antitumor activity in HRAS mutant head and neck patients and combining quite well in various trials with challenging drugs such as alpelisib. On the downside, the pill burden was high, with patients receiving 1.2 g per day due to its extensive first-pass metabolism. There's little doubt in my mind that tipifarnib was the best in its class, but since that class graduated some time ago, its IP protection is now limited. Using tipifarnib as a solid platform, we evolved a next-gen FTI, recently dubbed darlifarnib, optimized for use in combination regimens. This drug is significantly more potent than tipifarnib in mice and demonstrated good combinability with a laundry list of PI3K, RAS inhibitors, and TKIs in vivo. darlifarnib is administered q.d. at substantially lower doses than tipifarnib due to its reduced clearance and optimized metabolism and also, of course, has extended protection as a new chemical entity. Initial clinical testing of darlifarnib in the FIT-001 trial is in progress, and today we'll summarize the preclinical data supporting the use of the new FTI in combination with several classes of targeted therapies in solid tumor models. Our first example is renal cell carcinoma, where TKIs that inhibit VEGF receptor signaling are a prominent therapeutic class. As you see the pathway diagram coming back here, in this case, it's playing out in the tumor endothelial cells where the anti-angiogenic activity of TKIs such as axitinib, lenvatinib, or cabozantinib is limited by mTOR activation. FTI co-therapy silences mTOR, deepening the anti-angiogenic effect of the TKI, and this, of course, is the real Achilles heel of RCC. Indeed, the mTOR pathway is hyperactivated in RCC, and several mTOR inhibitors of the rapalog class are approved in the indication, although uptake has been poor due to tolerability issues with high rates of dose reductions and discontinuations associated with high-grade AEs being frequently reported. FTIs silence mTOR signaling by displacement of the farnesylation-dependent mTOR co-activator Rheb from lysosomal membranes, preventing correct mTOR localization. mTOR does all of its business from the lysosomal membrane. If it cannot insert into there, it is essentially switched off, and this is how FTIs shut down the mTORC1 node. Anti-angiogenesis is a key component of all therapeutic strategies in clear cell RCC, with VEGF pathway TKIs and HIF2 inhibitors validating the particular dependence of this tumor type on its neovasculature. I'll spare you the blot showing that cabo only partially inhibits VEGF-dependent mTORC1 signaling in tumor endothelium, but sufficient to say that the KO-2806 finishes a job which really puts the brakes on angiogenesis. As you can see in the IHC here, while both cabo and 2806 monotherapies do reduce vascular density, the combination of the two agents is synergistic in this particular PDX model. Indeed, we saw similar effects with the first-line anti-angiogenic TKIs. As expected, given the angiogenesis dependence of RCC, the improvement offered by addition of KO-2806 to TKI monotherapy was both class-wide and highly consistent. As you see on the left, in the TKI-resistant VHL wild-type Caki-1 model, addition of 2806 made all three TKIs highly effective. These composite waterfalls can be a little hard to look at sometimes, but essentially, the gray here is showing you the TKI monotherapy activity. You can see the tumors are progressively growing, whereas the orange captures the combo activity where all of the waterfalls fall below the line, indicating everyone was experiencing regressions. That was also seen in the wider panel of RCC models, where we see that the FTI enhanced the activity of cabo in both resistant models towards the left of that chart or more sensitive models, irrespective, importantly, of the VHL genotype. Anti-angiogenic TKIs are prominent components of early-line regimens for metastatic RCC, so we wondered whether prior exposure to VEGF pathway-directed therapy would render mTOR-driven resistance irrelevant. In animals bearing RCC tumors that were progressing on first-line TKI therapy, switching to cabozantinib did indeed slow tumor growth, but switching to the cabo-FTI combo induced consistent regressions, even in animals progressing on cabo monotherapy. Summarizing what we've seen in RCC models, we see a composite effect of inhibiting both VEGF receptor signaling and the adaptive mTOR signaling that comes up in response to that, improves and lengthens the anti-angiogenic activity, and that this is effective with both first and second-line tyrosine kinase inhibitors and is active even in tumors that are progressing on the first-line therapy. Although our RCC program is the most advanced with KO-2806, the first place where we found a role for FTI-dependent mTOR activation in drug resistance was actually in the context of PI3K inhibition. PI3K α, or PIK3CA, is one of the most commonly mutated genes in solid cancers, prevalent in several large indications, including breast, colorectal, bladder, and endometrial cancers. PI3K inhibitors, as if you look back at the pathway diagram there, unsurprisingly, effectively block the right-hand side of the pathway, but collateral signaling through the MAP kinase pathway reactivates mTOR and undermines their effectiveness. FTIs blunt this resistance pathway by blocking farnesylation of Rheb, leading to more effective reduction of mTORC1 signaling, while importantly sparing mTORC2. This is quite significant clinically because blockade of mTORC2 can cause insulin resistance and type 2 diabetes, can lead to increased susceptibility to infection, and have significant lung complications, particularly pneumonitis. Building on the clinical activity we achieved with tipifarnib in HRAS mutant head and neck squamous cell carcinoma, we sought to extend the clinical benefit of farnesyl transferase inhibition to the larger population of PIK3CA mutant head and neck cancer patients by combining tipifarnib with alpelisib, an approved PI3Kα inhibitor. In preclinical models, we saw that the alpelisib rapidly induced downregulation of mTOR activation close to baseline, but this did not persist, and quite rapidly, we saw a rebound that was complete within 24 hours. By contrast, when KO-2806 was added to the mix, mTOR activity was suppressed throughout the dosing interval, and this translated into a significant improvement in tumor activity in this PIK3CA mutant head and neck squamous cell carcinoma CDX model. As you see on the right, the alpelisib monotherapy gave a mixed response with some progression and some regression, whereas all animals treated with the combo exhibited deep regressions. We subsequently expanded this to a panel of a dozen or so CDX and PDX models with similar results, and this formed the basis of our current HN trial, combining tipifarnib and alpelisib in PIK3CA mutant head and neck cancer, upon which we will report at the forthcoming ESMO meeting. As far as KO-2806 is concerned, we're digging into the role of mTOR-dependent resistance across the range of tumor types with prevalent PIK3CA mutations. It's early days, but so far, the pattern that we saw in the RCC model seems to be maintained in that addition of KO-2806 enhances the antitumor activity of both of the mutant selective next-gen PI3K inhibitors tested and displayed this property across the full activity range of both PI3K inhibitors, slowing or stopping tumor growth and inducing regressions in more sensitive models, including, as shown on the right, some encouraging preliminary activity in breast, bladder, and cervical models. How about RAS inhibitors? Just to remind you, the reason why RAS is so important in cancer is because it's the only non-RTK that drives both MAP kinase and PI3 kinase pathway signaling, but its control of the MAP kinase pathway is stronger. The rationale for using 2806 as a partner for RAS inhibitors, therefore, mirrors the issue for PI3K inhibitors. In this case, RAS inhibition takes out the MAP kinase pathway very nicely, but residual PI3K pathway activation drives mTOR-mediated resistance. Once again, RAS inhibitor monotherapy fails to persistently block mTOR signaling, but the combination is effective across the class. For example, as shown on the right, while adagrasib only partially blocks mTOR activity with full rebound observed, the combo flatlines it for days. The RMC Pan-RAS inhibitor does a better job, but the activity still decays and can still be rescued with KO-2806. KRAS inhibitor development has been focused on non-small cell lung cancer and colorectal cancer with mutant selective inhibitors, with KRAS G12C and G12D, and Pan-RAS on inhibitors such as the RMC compound. Darlifarnib enhances the activity of both classes of RAS inhibitors across their full activity range in both lung and colorectal xenografts. In the lung cancer panel shown on the left, for instance, KO-2806 improved responses to adagrasib in refractory models by slowing tumor growth and deepened regressions in sensitive models, but most excitingly, also converted some tumors from resistant to sensitive. We also saw this with MRTX1133, the G12D inhibitor in colorectal models, and with the RMC Pan-RAS inhibitor in the colorectal panel also. I'm sure you all appreciate that KRAS inhibitor development is a highly active field, and it's likely that many patients accruing to our trials will have had prior exposure to one or more drugs in the class. We modeled switching to the combo after failure on KRAS inhibitor monotherapy. In this lung cancer model, KRAS monotherapy was temporarily effective, and switching within class didn't help, as you see on the upper right, going from sotorasib to adagrasib. Switching from adagrasib to the Pan-RAS inhibitor provided some benefit, but by contrast, the FTI-RAS inhibitor combo induced regressions in all cases. To model the KRAS inhibitor naive situation, we also looked at the upfront combination, and either with adagrasib or RMC, as you can see here, the upfront combinations did not disappoint. In a KRAS G12D mutant CRC model, mutant selective and Pan-RAS inhibitors are highly effective for 3-4 weeks, inducing nice regressions, but then they consistently fail. In this case, switching from mutant selective to Pan-RAS inhibition does not slow tumor growth, perhaps due to the PIK3CA co-mutation in this particular model. Once again, combination with KO-2806 drives long-lasting regressions in all of the animals. As before, combination treatment was rapidly active and maintained deeper regressions in KRAS inhibitor naive animals. The big take-homes from the KRAS models are that the FTI enhances activity of all the classes of RAS inhibitors across their full activity range in both tumor types we looked at, and the darlifarnib combination therapy can deliver regressions in animals bearing tumors that have failed RAS inhibitor monotherapy. In conclusion then, from the preclinical session, we've shown you, I hope, that FTIs address a resistance pathway common to many targeted therapies across a range of large indications, and that the targeting of this innate and adaptive resistance via FTIs in combination with highly active targeted therapies has demonstrated the potential to drive deep responses in preclinical models. FTIs have been successfully combined in the preclinical setting with multiple drug classes, including PI3Kα inhibitors, KRAS inhibitors, and anti-angiogenic tyrosine kinase inhibitors. KO-2806, or darlifarnib, is our next-generation FTI optimized for combination approaches with improved pharmaceutical properties. Hopefully, we've convinced you that these preclinical data robustly support combination therapy using darlifarnib to address resistance and provide more durable activity. With that, I'm going to hand you over to our CMO, Mollie Leoni, to briefly preview the upcoming clinical data reveal at ESMO. Thank you, Francis. If we move to slide 39, I think the question, of course, now turns to the clinic and the ability to help patients, and we are excited to show you the monotherapy. The focus will be on safety and tolerability, as well as the therapeutic window for clinically active doses. Tipifarnib is, of course, a very well-understood molecule that we can use to inform our expectations for 2806, or darlifarnib, which is the improved FTI with potential for broad application. Importantly, we will be presenting data with FTIs in combinations with standard-of-care agents. Please take note of the data surrounding safety and tolerability, as well as combinability with these standard-of-care agents. Based on the preclinical data, we hope that these combinations will drive deeper and more durable responses and that we may even be able to resensitize patients who have previously progressed on one of these standard-of-care agents. We are looking to develop the clinical program so that the data can support development across multiple solid tumors. These first presentations will be supportive of an FTI's ability to augment the effects of PI3Kα inhibitors, as well as TKI. In coming months, we will also share the KRAS inhibitor combination data. Moving to slide 40, to get more into the details, our monotherapy 2806 dose escalation trial will be presented by Glenn Hanna of Dana-Farber. The objectives of this trial are to evaluate safety and tolerability and to determine the monotherapy RP2D, as well as the therapeutic window for 2806, which involves both safety and efficacy findings. This dose escalation has been done in patients with RAS mutant tumors. We know from our work with tipifarnib that of these, HRAS tumors are uniquely sensitive to FTIs, which allows determination of clinical activity. Moving to slide 41, our second abstract describes the combination of 2806 with cabozantinib in patients with renal cell carcinoma and will be presented by Dr. [Ayanna McBaugh] of the University of Oklahoma Health Sciences Center. In this trial, we have evaluated the safety and tolerability of the combination with a goal of identifying the recommended phase II dose. This will be based upon both safety and efficacy findings. This trial has been conducted in patients in their second and later lines of therapy, including patients who have previously received cabo-based therapy, thus giving a method beyond even ORR rates in assessing clinical activity. It should be noted that in this particular stage of therapy, cabo alone would be expected to have around a 25% response rate, and 2806 monotherapy would be expected to have no effect on disease. Moving finally to slide 42, our third abstract will describe the results of dose escalation trial with tipifarnib in combination with alpelisib in patients with PIK3CA mutant head and neck squamous cell carcinoma. We will be presenting data around the safety of the combination that, along with evidence of efficacy, can support selection of the optimal biologically active dose. This is a trial in recurrent and/or metastatic PIK3CA mutant head and neck squamous cell carcinoma patients. In this population, alpelisib monotherapy would be expected to result in stable disease as best response, whereas tipifarnib monotherapy would not be expected to demonstrate any effect on the disease. We look forward to sharing these data with you, and with that, I will turn it back to Troy. Thank you, Mollie. We can go to the next slide, please, and actually the slide after that. I want to just touch on the opportunity and then the upcoming milestones. As we look across the tyrosine kinase inhibitors, the KRAS inhibitors, and the PI3Kα inhibitors, the unmet need is clear, as Francis showed you. These drugs as monotherapy are effective at shrinking tumors, but we have an opportunity really to make good drugs that much better, and as such, there's a significant epi-population and a significant commercial opportunity. By our estimates, as we look across just a range of potential applications where we would combine FTIs with other targeted therapies, we're looking at a patient population in excess of 200,000 annual patients per year in just the U.S. alone. Clearly, we're going to need help in terms of prosecuting this, and we look forward to talking with you about both our development strategies as well as our business development strategies about how we might bring the most benefit to patients and the most value to our shareholders. If we go to the next slide, as both Francis and Mollie mentioned to you, we're looking forward to giving you a data update at ESMO. That's just one of a number of anticipated milestones here between now and the end of the year. Of course, with our NDA under review, we are optimistic that we're on a good track to approval of Ziftomenib, and we're looking forward to commercial launch in the NPM1-mutant relapsed/refractory AML setting. We're looking forward to starting the KOMET-017 phase III studies, where the team is making great progress. We expect to show you additional data from the combinations with venetoclax and azacitidine in both the frontline setting as well as the relapsed/refractory setting, and then, of course, we're looking forward to elaborating more about our development plans for our FTIs as well as our next-gen menin inhibitors. If we can go to the next slide, please. We do all of this from a very strong financial position. We're fortunate, as of our last quarterly update, we had $630.7 million in cash and cash equivalents. We anticipate receiving substantial milestone payments between now and the end of the year. As we've told you in the past, we are looking toward anticipated near-term milestone payments of a total of $375 million. Although we haven't been specific, we would expect, again, substantial milestone payments, which should keep us in a very strong cash position. If we go to slide 47, again, we'll invite you. This is the first chapter now of the FTI story. Hopefully, this gives you some important context in which you can review and evaluate our upcoming clinical data, and we look forward to having the second installment in this series, actually from ESMO on Saturday, October 16th. There will be a link to the webcast available on our website, and we'll be coming to you direct from ESMO. With that, if we can go to the next slide, that concludes our prepared remarks, and Latif, we're happy to open it up now to questions. Yes, sir. As a reminder, to ask a question, you will need to press star one one on your telephone. To remove yourself from the queue, you may press star one one again. Please stand by while we compile the Q&A roster. Our first question of Li Watsek of Cantor. Please go ahead, Li. Good afternoon. This is [Daniel Brunner] on for Li. Thank you so much for the update today, and thank you so much for taking our question. We're just curious to learn a little bit more about the expectation going into the ESMO update. How many patients should we be expecting? Can you tell us a little bit more about the type of data that you will be sharing? Should we be expecting confirmed versus unconfirmed responses? You've set a pretty benchmark for ORR historically in the 20% - 30% range. Where do you think you would have to land to be competitive with, for example, HIF2α combinations that have historically shown 31% - 45% of ORR? Yeah, Daniel, thank you for the questions. Mollie, would you like to take Daniel's questions in turn? Yeah, sure. In the written abstracts, and it may change as we get to the actual presented abstracts with new data cuts, you should be expecting to see anywhere from 11 -3 5 patients in each of these data presentations that we'll have, and we'll show you all of the usual types of information, the response rates, which will be mostly confirmed, and if one is not confirmed, we will document it as such, especially if it is simply just one that needs the next scan to be confirmed. We'll show you as much durability as we can. I think the waterfalls will ultimately be enormously informative for you to see that even when these patients are not hitting the mark for a partial response just yet, they're certainly on their way. As you said, right now, I think the landmark is probably the HIF2α inhibitors. That's the latest and greatest, and we see those producing numbers in small studies, of course, between 31% and 46%. We would want to have our combination to be competitive to fall within that same kind of range. If I may ask on safety as a follow-up, where do you see the potential for a combination of KO-2806 and cabozantinib to differentiate on safety from the cabo plus HIF2α inhibitor combination? Yeah, so that's, you know, actually, there's such different molecules. Obviously, with the HIF2α inhibitors, you have the hypoxic issues and the anemia. We, of course, would not expect to have that. We would expect that the farnesyl transferase inhibitors will continue to have, as their most common adverse event, neutropenia, and same for the combination as a whole. It is something that you can really anticipate and identify early and treat and hope actually prevent as well, as we will be looking into in coming trials. I do think that there will be a safety differentiation between the two combinations. Great. Thank you so much for answering our questions. Thank you, Daniel. Thank you. Our next question comes from the line of Jonathan Chang of Leerink Partners. Please go ahead, Jonathan. Hi guys, thanks for taking my questions. First question, given the breadth of the potential opportunities with darlifarnib, how are you thinking about a future clinical development strategy and potential business development opportunities? Second question, how important is it or not to demonstrate single-agent activity in the clinic with darlifarnib, given the mechanism of the drug and the combination development strategy? Thank you. Sure. Yeah, Jonathan, thanks for the two questions. I think I'll take the first question, and I'll invite Mollie to take the second question around monotherapy activity. With respect to your question around the clinical development and the business development strategy, that's a blessing here. Obviously, we could go in multiple different directions in parallel. I think what's appealing to us about cabozantinib is we have the potential, you know, Daniel in his previous question related the data to the HIF2α inhibitors. They are, as Mollie said, the latest and greatest thing in RCC, but of course, cabo goes much beyond that recently with an approval in neuroendocrine tumors. One of the ways we think about it is, as you look to a day when cabo is generic with $2.5 billion in global sales worldwide, could you actually improve on its activity with a combination with 2806 in RCC, in neuroendocrine, and elsewhere? We think that's a very strong standalone story for Kura. There are obviously opportunities to enhance the activity of KRAS and PI3Kα inhibitors. Our view there is we'd like to continue. We have a productive relationship with BMS on the combination with adagrasib. We would look forward to potentially enabling other combinations as well and really say, what value can 2806 add? Is it in a mutant context? Is it in a combo context? Is it in breast with PI3Kα, perhaps colorectal with KRAS? Give us some time. As you know, with this data updated at ESMO, we're not only using it to disclose it to the investor and analyst community, but it's also helping to support ongoing discussions about potential clinical collaborations. There will be more to say about that. I think it's early days. At the moment, we're quite encouraged that we could take it in different directions, and it really becomes a very important strategic asset. On the question of the importance of the monotherapy activity, Mollie, maybe you can speak to Jonathan's second question. Absolutely. Single-agent activity is very important in a drug that you're developing for use as a single agent. We are actually not currently pursuing that track, though we do know that HRAS mutant tumors, regardless of location, so head and neck, salivary, thyroid, etc., are uniquely sensitive to FTI inhibition. Having that knowledge from so many years of tipifarnib data allows us to really be able to evaluate the dosing required to be establishing an appropriate monotherapy and range of doses for our combination program. What we're doing is something nice and new and interesting in keeping with true targeted therapies, and we're developing almost the companion molecule to these other targeted therapies that already have so much good monotherapy activity on their own. We're developing a method for them to maintain and even deepen the activity that they already have. Monotherapy, the understanding of where we should see monotherapy for 2806 was helpful in determining a dose range, but I do not think that activity overall is what will drive our combination approaches. Understood. Thanks for taking the questions. Thank you, Jonathan. Thank you. Our next question comes from the line of Roger Song of Jefferies. Please go ahead, Roger. Great. Thanks for the presentation and taking all questions. My question may be a little bit more specific following the previous question related to the partnership strategy. It seems, Troy, you are alluding you are thinking about clinical collaboration, and then maybe just, you know, seems that can be multiple kind of fronts with different partners for the next clinical development. First of all, is that true? Also, you have a different pathway to do the combination, and then will you start to prioritize certain combinations and indications to do the clinical development, or you want to do that, you know, still kind of pursue all fronts before you make the decision for which indication to prioritize? Thank you. Yeah, Roger, thank you for the question. The answer really, you know, you've asked sort of two important parts of the question. It's early days. We're going to show you phase 1-A data from three of the four trials. As Mollie may have indicated, we think we'll be in a position to show you data from the KRAS cohort next year. They're all moving along quite nicely. The RCC cohort is probably the most advanced with respect to 2806. We've been watching, you know, there's different strategies, Roger. We've seen, for example, a company like Olema take an approach where they're doing combinations with a couple of major players in a space. SpringWorks is another example. I think we would be, you know, we are going to prioritize what is best for patients and what is best for our shareholders. Clinical collaborations are a relatively easy way to get engaged, ensure that there's a strong basis for safety, tolerability, combinability. If people obviously want to be more exclusive, that's a conversation that one can have down the road. You put yourself in a position. The attraction to this is, and those of you who've spent time with us know, the attraction here is, you know, I was intimately involved in the inception of the KRAS inhibitors. It's been remarkable how much progress that field has made. They all still have the same issue, which is the innate and adaptive resistance that Francis alluded to in his slides. The extent to which we can help anyone or ones of them, we're happy to do that. To the second half of your question, it's probably a little too early, Roger, to say we're going to focus down in a particular area. We are very mindful that we need to be able to chart a path where we can create value for our shareholders on a standalone basis. If a partnership or something more strategic creates more value, that's great, but you need to be able to articulate your ability to get to the market, drive value for patients and for shareholders really in partnership with investors, and we think we'll be there. You can see us thinking about cabo, but again, as Francis's data has shown you, you would expect if you're seeing good data with cabo, you're going to see good data with any TKI in RCC. We're going to be very open. We're going to be very data-driven. I think it's exciting. We obviously, Roger, can't do everything. You'll see us focus in those areas where we can drive value as a standalone company and then look to supplement that creatively in other indications where we could drive more value for patients and then, you know, add to future global revenue. Excellent. Thank you. Thank you. Thank you. Our next question comes from the line of Jason Zemansky of Bank of America Securities. Please go ahead. Your line is open, Jason. Hi, this is Jackie on for Jason. Thanks for taking our question. Maybe just at a high level, can you speak to where exactly tipifarnib fell short despite encouraging preclinical data, and how 2806 bridges that gap enough to give you confidence about moving forward? I guess ultimately, what's the lesson learned here? Yeah, that's a really good question, Jackie. Thank you for asking it. I would say, you know, the only limitation, as Francis articulated, there are, I was going to say the only, but there are actually several limitations of tipifarnib. It was best in class at its time. The issues for patients are a high pill burden and a high sort of drug burden, needing 600 mg BID. The dose of 2806 will be substantially less than that, and we anticipate, you know, an oral daily schedule. Importantly, Jackie, it's the question of composition of matter IP. We certainly could chart a course where you could take either tipifarnib forward or potentially, you know, we'll talk about the combination of tipifarnib plus alpelisib. When you're talking about a commercial opportunity of, you know, a couple of hundred thousand patients, you really want to make sure you've made the appropriate investment on a global basis in composition of matter IP, and that's what we have with 2806. We have been working this space now for a number of years. I think we are the pioneers. This is as good as it gets as far as an FTI is concerned, and it has the drug-like properties. It has the combinability. We describe it as very well-behaved. We could put it into a clinical collaboration, make it available to a third party, and feel confident they could use it without having to jump through a lot of hoops or a lot of safety concerns. Importantly, Jackie, you can consider doing global development across multiple indications with an extended IP estate. Just to highlight for everyone, when Congress passed the big beautiful bill by fixing the orphan provision of the Inflation Reduction Act, probably the greatest beneficiaries of that were targeted oncology companies because previously you were going to be limited by a single orphan indication. Now, so long as you stay within orphan indications, which most, even the large oncology tumor types are, you can get the benefit of actually being able to do development in potentially renal cell carcinoma and KRAS-driven tumors and yet still remain in a very competitive position. We are, Jackie, probably multiple years ahead of any potential competitor with an asset that should be attractive to, you know, a number of potential partners and allow us to create value, as I said, across multiple different indications. Great. Thank you so much. Our pleasure. Thank you. Our next question comes from the line of Charles Zhu of LifeSci Capital. Your line is open, Charles. Hello. Thank you for doing this and for taking our questions. We had a couple more regarding benchmarks. How many of your RCC patients might have seen prior cabozantinib in some form, whether it's mono or in combination with a PD-1? If you do expect such patients on your study, how much efficacy would one expect from cabozantinib rechallenge in later line RCC? The second one that I have is, because you are prioritizing combinations and staying on RCC, how should we think about 40 mg versus 60 mg cabozantinib? Thank you. Charles, thanks for those questions. Mollie, would you like to take Charles's questions? Sure. What's interesting, and I think you'll see in the presentation, is that we started off with a high number of cabo previously treated patients because it was a first-in-human study, and they were tending to put their most heavily pretreated. Towards the end of our dose escalation, you'll see that pattern changed remarkably. I think you're going to have a good opportunity to get a sense of what cabo could do in that particular instance, and obviously, it is hard to tell what a benchmark is for that. There's not much published in there. You'd obviously expect it to be less than the 25% that we described earlier, but exactly what it would be is difficult to say. The interesting points will be when you see a patient come off of cabo and then go on to the combination and see if you get a return of sensitivity to cabo or the first time experiencing sensitivity to cabozantinib. With respect to 40 mg versus 60 mg, this is where we ended up having a nice problem to have. We started off testing in the 40 mg c abozantinib range because we figured we would be seeing these patients that have previously seen cabo, and in general, if it is reused, it is reused at a lower dose for tolerability reasons. We did an escalation in 40 mg plus various dose levels of 2806 and realized that it really was tolerated well enough to be able to go to 60 mg. We also dose escalated through 60 mg. We'll show you the data, but I think that this way we have data generated at both dose levels, and there's going to be a convincing argument, in my opinion, for which one will make more sense, the 40 mg versus 60 mg. Understood. Thank you. Thank you, Charles. Thank you. Our next question comes from the line of Phil Nadeau of TD Cowen. Please go ahead, Phil. Good afternoon. Thanks for doing the session. Very helpful. Two questions from us. First, kind of a broader question on the concept of benchmarks. I think one of the challenges that we've seen over the years for companies who are developing an add-on therapy to an active agent in a combination regimen without demonstrating single-agent activity is the challenge is understanding when the add-on therapy is truly adding efficacy to the already active agent. Maybe epacadostat from Incyte is the poster child for this, where it looked effective in phase II, and obviously the phase III readout, and it seemed like it was adding nothing. Can you talk a little bit about how Kura is going to avoid that pitfall? How are you, as a management team, going to build confidence from the data that's produced in the early stage smaller studies that you are seeing truly additive efficacy in the clinic that's sufficiently robust to warrant further development, particularly into a pivotal study? That's the first question. Second, just a theoretical one, the data showing the ability of the mechanism to overcome resistance is really intriguing. We're curious whether resistance that's generated, maybe not through single agent, but combination regimens, whether it's a VEGF in combination with chemo, for example, is that mechanism any different? Do you have data that shows the ability of FTIs to overcome that type of resistance? Thank you. Yeah, Phil, thanks for the questions. Maybe I'll comment initially on the first question, and then I'll ask Mollie to add her thoughts, and then Francis can take your question on the, you know, if we'd expect different resistance from other combinations. You're absolutely right, in terms of one needs to, how do you convince yourself that you're seeing additive or synergistic activity? Mollie gave an important clue, and let's talk about, you know, are we hitting a target? Are we hitting Rheb, and are we hitting it hard enough to make a difference? Importantly, one of the reasons we want to show you the current head and neck data is, of course, alpelisib, you would expect stable disease. Tipifarnib, you would expect no responses. To the extent that you are seeing durable responses, that's a good indicator that you're hitting the target and it's on mechanism, and that's relevant to head and neck. If you translate then to RCC, the onus is going to be on us to make the case first to us and then ultimately to you and to physicians that we're really seeing additive activity, and that's where I think, let us show you the clinical data, and we are very much keeping that in mind, right? These are all active agents that we're combining with, but I think importantly, from the preclinical data, you can see consistent activity across these, a common mechanism across these vastly different tumors and histologies. Mollie, is there anything you'd add in terms of how we think about demonstrating the additive or synergistic activity? These are the questions that we ask every day because we also want to be positive that there is a there there. We believe that we have plans in place. This is our first in-human dose escalation, so it'll give you some information, but not a complete picture. We will build to get that complete picture over time. I think one of the biggest things you'll be able to look to right now that'll be reassuring is the increased efficacy over what you'd consider cabo to be as a monotherapy, as described, and again, the cabo rescues. I think it's fascinating if you're able to see a patient who previously had failed cabo and now they are having a good response on it. Stay tuned is my overall message. Yeah. Phil, if I can ask Francis, maybe a comment on your second question about resistance arising from combinations. Yeah, sure. Thanks, Troy. I think it's hard to predict what we're going to see from combinations that we have yet to look at, even in the lab, but what we do know is that if there is an anti-angiogenic TKI in the mix, so to speak, its activity will most certainly be limited by mTORC1 reactivation downstream of the suppression of mitogenic signaling in the endothelial cells. We're confident that if there is a TKI on board, then we are definitely going to make that better. We have also shown that exposure to a prior TKI either the same one or a different one, doesn't sort of spend that pathway, if you like, so it's still there. Although we've not modeled this yet in the animals, we also have every reason to believe that prior IO will not sort of use the mTORC pathway up. It will still be there and ready to drive resistance in second and third line. Great. Thank you, Phil. That's very helpful. Thank you. Yeah, we probably have time for a couple more questions. I know we're getting close. Thank you. Yes, sir. Our next question comes from the line of Peter Lawson of Barclays. Your line is open, Peter. Great. Thank you so much. Just a couple of other follow-ups on the upcoming ESMO data. Firstly, on the monotherapy data, what tumor types will we see, and will that help point us towards which indications and combinations you'd be thinking about? I wonder if you could just talk about beyond the ESMO, what other data sets we should expect to see for 28 doses. Thank you. Sure. Mollie, do you want to take the question of what histologies we're running the monotherapy cohort in and kind of how to think about it? Absolutely. The monotherapy, again, first-in-human monotherapy dose escalation trial, we focused on RAS mutant tumors. They could be of any type of variety, but it's RAS mutant in general, and obviously a lot of our investigators that were already in the know and previously associated with Kura understood that HRAS would have the best chance of having a response, and those are the patients that tended to be brought on most often by the investigators that were familiar with the HRAS patients. You're going to see a smattering of different types of indications, and I wouldn't use that as an indicator of what combination therapies we're going to head towards. This was really to show you that, one, 2806 is an FTI, like we promised. Two, what the safety looks like. Three, what the therapeutic window looks like where you're still seeing good safety and seeing some form of efficacy, and that efficacy that I speak of is really largely driven by the HRAS mutant patients that have been enrolled. That's the way to think of the monotherapy. Yeah, Peter. In terms of your second question, as we said, we think we'll be in a position to share the KRAS data with you. We are evaluating the combination of adagrasib and darlifarnib in lung, colorectal, and pancreatic KRAS G12C mutant patients. This is obviously a phase I, and so it's a pretty heterogeneous population, but we're looking forward to an opportunity to share that data. There may also be an opportunity to share further data on the RCC cohort with you. We're going to be at a point where we expect to move into an expansion, given, as Mollie described it, the high-class problem that we found we could dose with both 40 mg and 60 mg of darlifarnib with cabozantinib. The timing of initiating the expansion has been pushed out a little, but it should be a, you know, you should get some robust data updates in the 2026 timeframe. Gotcha. Thank you. That's full dose cabozantinib? It was ESMO. We did both, exactly. 40 mg in the cabo-exposed or experienced and 60 mg in the naive. Gotcha. Okay, thank you so much. Great. I think we have time for maybe one more question before we wrap. I want to be respectful of people's time. Thank you. Our next question comes from the line of Salim Syed of Mizuho. Please go ahead, Selene. Great. Thanks for the presentation, guys. Troy, maybe just one high-level one and then a couple on the actual presentation. High-level, Troy, just menin versus FTI here, because you're sort of thinking about the long-term value contribution for the company long-term here. Just please give us your view here. How much of you think, I mean, it sounds like you're pretty excited about these FTIs. Just how are you sort of thinking about value contribution as a respect to menin longer term here? Yeah. Go ahead, and then I'll just ask my data questions, move forward to Mollie or Francis. Yeah. Yeah. Yeah. Salim, the way we think about it is, you know, our goal with ziftomenib is to treat up to 50% of all AML patients across the treatment continuum. If we're right, you know, we've guided that's $3 billion in peak sales in the U.S. I don't think that's unreasonable based on the data that we and others are showing. We will be moving very shortly into a combination with [prezardinib]. We may be in a position to share with you next year data on the gilteritinib combo, which would open up FLT3. That would give us, if we could hit KMT2A and NPM1 and FLT3, that's half of AML. Obviously, those trials have to work, but that's a huge driver. We're not spending any time today on GIST. If GIST works, that's a blockbuster right there. It's the same story, different lead characters. You're going to have a imatinib plus Ziftomenib. Stay tuned for an update on the GIST story likely in 2026. Here, Salim, let's just focus, you know, for the sake of the argument on RCC and NET. There again, I think you've got a pathway to a blockbuster. Our goal is to build a pipeline of robust targeted therapies that are driving, you know, value for patients and potentially billions of dollars in peak sales just in the U.S. If we can continue to do that, and we're doing it in a highly de-risked way, you know, we think we can attain, you know, the aspirations of some of the legacy companies that have come before us, many of which are not here anymore, but that's what we'd like to do. You're asking us, you know, which of our children do we love the most? At the moment, I think, you know, they're all beautiful. They're at different ages, but the attraction is there's a lot of value inside of Kura, and we're well capitalized at least into 2026. Our AML business is funded, you know, through to frontline commercialization. If we find ourselves in a position where we need to now make additional investments to bulk out the pipeline, that's a high-class place to be. Okay. What are your data questions? Yeah, quickly on slide 17, was there anything in particular about the, on the right-hand side of the slide, the RCC models where you didn't see a negative change in tumor volume, but the 315 and 097 models? Just remind us what the theoretical talks here is with these FTIs as we approach more data. Thank you. Yeah. Selene, can you restate your question on slide 17? What, you Asked about specific data. Oh, yeah. Oh, yeah. Sorry. It looks like the pink bars here weren't in the negative Tier. I mean, look, the data, the bars all look consistent with negative change in two, if I'm reading this correctly, but not in the two most left pink bars, the 351 and 097. I don't know if there were something particular about those models where the data looks inconsistent with the rest. Yeah, no, there's nothing I could really put my finger on there, I'm afraid. As I mentioned, some of the models in here are VHL mutants, some are wild types, some are CDX, some are PDX. There are very varying growth rates between them. I don't think we have done or have the potential to do a big enough mouse population study to really get a grip on potential biomarkers, which is, I guess, where you're going for patient selection. We feel going forward that we can take all comers and it's not really come up, but we have non-clear cell RCC patients in this trial as well. It really is a very broad-based approach. Right now, we feel like we should just go for it and see what we can achieve. Yeah. On the toxicity, as Mollie said, you're expecting, you know, anemia, thrombocytopenia, and neutropenia. Importantly, that's manageable as a monotherapy and it hasn't precluded, as Francis mentioned in the case of tipifarnib, combinations with erlotinib, alpelisib, chemo. That is actually something we sort of skipped over. That's actually one of the most important attributes of this program. So many companion therapeutics have died because of toxicity. Because when you shut down MAP kinase and PI3 kinase pathway signaling, not surprisingly, you're going to induce toxicity. Here, we're able to do it by inhibiting TORC1 in a very, in a surgical way. I think that's critically important. You'll see that in much more color when we show the clinical data with you. It is that question of combinability and long-term safety and tolerability in combos that is one of the central questions. We look forward to sharing that data. Okay, perfect. Thanks so much for taking the questions. Our pleasure. Apologies to those of you whose questions we couldn't get to. We do have some one-on-ones scheduled after this. We appreciate your time and hope this has been helpful. Please tune in to the second chapter of this, where we'll be coming to you after the presentation of the RCC data at ESMO. We'll pick up the thread and continue the discussion. We wish you all a good afternoon and a good evening. Thank you again for your time. This concludes today's conference call. Thank you for participating. You may now disconnect.