Good day, everyone. My name is Stefan. I will be your conference operator today. At this time, I'd like to welcome you to the Kura Oncology Investor Call to discuss updated results from the FIT-001 clinical trial evaluating darlifarnib in combination with cabozantinib in renal cell carcinoma. All lines have been placed on mute to prevent any background noise. After the speaker's remarks, there'll be a question and answer session. If you would like to ask a question during this time, if you've joined via the webinar, please use the raised hand icon, which can be found at the bottom of your webinar application. To allow everyone the opportunity to participate, we ask that you please limit yourself to one question and one follow-up question. If time permits at the end of the Q&A session, we invite you to rejoin the queue for additional questions. At this time, I'd like to turn the call over to Troy Wilson, President and Chief Executive Officer of Kura Oncology. Please go ahead, Dr. Wilson. Good morning, everyone. Welcome to Kura Oncology's update. This morning we're going to talk about darlifarnib in renal cell carcinoma, providing a clinical update from the KCRS symposium that was held in Boston. If we could please go to the next slide. In today's presentation, we will be making forward-looking statements. We would refer you to both Kura Oncology's website and the SEC's website for more information about the risks and uncertainties of an investment in Kura Oncology. If we could please go to the next slide. We're delighted today to be joined by Dr. Ayanambakkam. Dr. Ayanambakkam is an Assistant Professor of Hematology -Oncology at the University of Oklahoma Health Sciences Center. He is the presenter at KCRS. He's going to take the opportunity today to walk through the slides a little bit more slowly and a little bit more better detail. In addition, we're also joined, of course, by Dr. Mollie Leoni, Kura's Chief Medical Officer. If we could please go to the next slide. Just before we get into the KCRS data, I just want to step back and recognize this is a really important time at Kura. We now have two major pillars in the company that are driving value for both patients and shareholders. On the left-hand side, with ziftomenib, everything is going extremely well. The launch is going well. The enrollment in the phase III is going extremely well. We're looking toward a number of data updates that will help us to elaborate what we think ziftomenib can do, both as monotherapy and in combination, toward the goal of making it a broadly combinable AML backbone as the therapy for patients throughout the treatment continuum. That's really a great story and one that just continues to move forward. Today, we're going to focus on the right-hand side on the darlifarnib program. The darlifarnib program is exciting because it's really a different way of addressing cancer using small molecule therapy. Darlifarnib is a mechanism-driven, targeted therapy agnostic combination platform. We've shown you data with TKIs. We've shown you data with PI3K inhibitors, with KRAS inhibitors. The way we think about it is darlifarnib is a drug that can enhance the clinical activity of other important targeted therapies, whether they be standards of care such as cabozantinib, or they be investigational agents. Today, we're going to talk about the phase I-A data for cabozantinib in RCC, but just to remind you, the phase I-B is underway. In addition, we are preparing for the phase I-A escalation with daraxonrasib in second-line PDAC. We were excited to see that daraxonrasib's NDA was submitted, and hopefully we'll be looking toward an approval later this year or early 2027. We'll be ready to add darlifarnib to that regimen to see if we can build on the clinical data that we showed you that we were able to do with adagrasib. Thinking more broadly, we're going to focus on what we can do on a go-it-alone basis. Darlifarnib offers a precision combination platform. In that regard, Mollie showed you in our webinar at ASCO, we've started a combination platform study that gives us the ability to evaluate other potential combinations that we think can create value for patients and ultimately for Kura shareholders. If we can go to the next slide, please. The way we think about this very simply is it's about precision combinations, whether it's on the ziftomenib side with things like venetoclax or gilteritinib, or whether it's now on the darlifarnib side with things like cabozantinib and daraxonrasib. We believe that by combining these targeted therapies and by enhancing their clinical activity, we can drive better outcomes for patients. We can go to the next slide, please. Just to remind you, we've now shown you multiple examples where a farnesyl transferase inhibitor can enhance the activity of targeted therapy. Here you can see in the headline, we're three for three. Starting on the left-hand side of the slide, previously at the IKCS symposium earlier this year, we showed you that darlifarnib could enhance the activity of cabozantinib in patients who were TKI exposed and in particular cabo exposed. We showed a 44% objective response rate versus what one might expect from the benchmarks, which is there shown in green, 17%-22%. Today's presentation is going to be different. We're going to shift from the cabo experienced to the cabo naive. We got some questions after the last presentation, and I think you're going to see that the activity continues to be quite encouraging. As we work rightward across the slide, the cabo example in renal cell carcinoma is just one. We've also shown whether it is in PIK3CA mutant head and neck with tipifarnib, or it is in the KRAS G12C mutated solid tumors where we combine darlifarnib and adagrasib. In each case, those blue bars, the activity of the combination, the FTI combination, is better than what one sees with the monotherapy comparator. That's quite encouraging. We have to ask ourselves the question of let's start to put the blocks in place that will support paths toward eventual registration. If we could please go to the next slide. Another way of thinking about this is shown here on slide seven, and this is just going to be an on-ramp to Dr. A's presentation. The way that we believe darlifarnib is working to enhance the activity of these targeted therapies is by blocking Rheb. Rheb is a farnesylated protein. One of Rheb's roles is to determine the localization of mTORC1. By blocking Rheb farnesylation, we prevent mTORC1 from being where it needs to be, and that effectively provides a block on the signaling cascades that are downstream from the MAP kinase pathway on the left and the PI3 kinase pathway on the right. When we add a targeted therapy that inhibits a node higher up in the pathway, whether that be a RAS inhibitor or in this case a VEGF receptor TKI in combination with darlifarnib, we're effectively putting two blocks on the pathway. In the case of cabo, you've got a block at the receptor level, and you've got a block at the mTORC1 level. We think that's a big part of the basis why we're seeing enhanced activity relative to the monotherapy alone. What I'll say is, what we were pleasantly surprised by is that that combination comes with acceptable safety and tolerability. We've seen that now with FTIs, whether we combine them with TKIs, with RAS inhibitors, or with PI3 kinase alpha inhibitors. We can actually dose these FTIs and maintain the dose of the targeted therapy. We're able to provide a better block on the pathway and hopefully that leads to better outcomes for our patients. We could go to the next slide. With that, I'm going to turn it over to Dr. A and let him take you through the slides that were presented at the IKCS symposium. Dr. A? Good morning. Thank you for letting us present the data again. My name is Adanma. I'm one of the GM at Oncs and honored to present as part of the FIT-001 study group and the results of the FIT-001 study. Next slide, please. Here are my disclosures. Next slide, please. We all are aware about the role of mTORC1 in renal cell carcinoma, especially in tumor growth and angiogenesis, and the limitations we've had with prior attempts at blocking the mTORC1 pathway. Darlifarnib is a potent next-generation farnesyl transferase inhibitor that blocks Rheb farnesylation, which directly results in selective mTORC1 inhibition without the mTORC2 inhibition, and thus sparing some selective toxicity. At IKCS earlier this year, we had talked about data about the safety and efficacy of darlifarnib in combination with cabozantinib, where it had demonstrated an objective response rate of 44% with an impressive disease control rate of 94%. Next slide, please. The FIT-001 study is a phase I dose escalation, dose expansion study that's evaluating the combination of darlifarnib and cabozantinib in the locally advanced and metastatic RCC that has been refractory to prior lines of treatment, including immunotherapy. Multiple dose levels of darlifarnib and cabozantinib have been evaluated. For the purpose of this discussion, we're talking about the safety data about all patients with RCC in this study, but also focusing on the efficacy data on cabozantinib-naive clear cell RCC patients. Of note, the cabozantinib 60 mg and darlifarnib 8 mg and 5 mg cohorts were limited to just cabozantinib-naive patients in comparison to others which had a mixed bag of both cabozantinib refractory and naive patients. Next slide, please. Baseline characteristics of our study as of May of 2026, we had about 72 patients enrolled in the study, predominantly clear cell in 80% of these patients. Important to note that these patients were heavily pretreated, with about 50% of these patients having had more than two prior lines of treatment. Of note, at least 67% of these patients had a prior IO+ TKI combination, 38% had prior cabozantinib at any line, and 17% had a prior HIF-2 alpha inhibitor. Next slide, please. When we look at the safety and the tolerability data, it is an extension of what we had previously seen at the IKCS, where the combination seems to be safe, tolerable, with very acceptable side effect profiles. As we would expect, we did see some side effects that we all are aware of in terms of the TKI era, especially cabozantinib-induced diarrhea, nausea, stomatitis, and hand-foot syndrome. Important to note, they were predominantly less than Grade 3, and significant Grade 3 or higher events with TKIs were not significantly different from what we have seen previously. Of note, we did have treatment-emergent adverse events of any grade in 90% related to darlifarnib and 96% related to cabozantinib. Grade 3 or higher were 58% and 57%, with 76% in the overall group. Important to note that serious treatment-emergent adverse events were minimal, less than 20% in both groups. Of note, the most significant difference in treatment-emergent adverse event was neutropenia of any grade at 47% and Grade 3 of 38%. Most of this neutropenia was initially during the initial DLT period, where growth factor support was not allowed during this process. Next slide, please. When we come to the antitumor activity, we want to limit our analysis to just the cabozantinib-naive patient population. Here it is important to note that in this cabo-naive cohort, about 47% of these patients had a prior TKI, including lenvatinib or axitinib. We had encouraging antitumor activity, with objective responses ranging from 33%-50%. Of note, the darlifarnib 5 milligram cohort + 60 mg of cabozantinib had an objective response rate of 50%. Disease control rate was acceptable, with 83%-100% among all groups. Clinical benefit rate was above 70% in that target group of 5 mg of darlifarnib + 60 mg of cabozantinib and 58% in the group that had darlifarnib at 8 mg and cabozantinib at 60 mg. Next slide, please. Here is our waterfall plot that's looking at the objective response rates at various dose levels of darlifarnib and cabozantinib. What's important to highlight over here is that even at the lower dose levels of darlifarnib at 3 mg, 5 mg, and 8 mg, we had some significant responses, and also in both the cabozantinib 40 mg and 60-mg cohort in this cabo-naive population. Next slide, please. What is also important to understand was that the benefits that we had seen with these objective response rates were durable, and they were evaluated across all the combination dose levels. Median progression-free survival was 13 months in these cabo-naive clear cell RCC patients, with six-month PFS probability at 74% and nine-month PFS probability at 60%. Next slide, please. Here is a swimmers plot that's telling us about the durability of these responses, but also important to note that more than half of these patients currently are on treatment at the time for their data cutoff. Hopefully our progression-free survival continues to increase. We also should note that most of these AEs that we had seen, the Grade 3 neutropenias was manageable with dose modifications, including dose reductions and dose interruptions. It tells us that despite these AE profiles, this is a safe, tolerable profile that we're able to manage without significant adverse events. Next slide, please. We'd like to highlight a couple of examples of patient scenarios, this is patient scenario number one, which includes a 66-year-old male with clear cell RCC diagnosed in 2023 who had double immune checkpoint inhibitors with nivolumab and ipilimumab as his frontline response, who started darlifarnib at 5 mg and 60 mg in January 2025. As of data cutoff at May 2026, he continues to have a response and is ongoing on treatment. As you can see, pretty early on in the disease course at week 8, he had a partial response. What is impressive is that this partial response continues to be maintained at week 48, we see ongoing reduction in his tumor lesions even at week 24, which is impressive. Next slide, please. Not only is darlifarnib effective in the TKI-naive patient population where we know cabozantinib is a good drug to use. Importantly, it is also effective in a patient cohort that has had TKI prior exposure as well. Here is an example of a patient who's had prior axitinib+ nivolumab as his frontline treatment when he was diagnosed with RCC in 2022, had a partial response and then discontinued due to radiographic progression. He started darlifarnib at the lower dose at 3 mg and cabozantinib 60 mg in October 2025, again, was able to see a partial response at week eight through week 24 and ongoing disease response at week 24 as well from a 33% tumor shrinkage to a 54% tumor shrinkage. Next slide, please. In conclusion, with long-term follow-up, this combination of darlifarnib and cabozantinib has demonstrated durable and encouraging antitumor activity in both the cabozantinib-naive and the cabozantinib-exposed patients. In this study, we've shown an objective response rate of 33%-50% in the cabozantinib-naive population with a median progression-free survival of 13 months. This combination was well-tolerated with a safety profile that was manageable, with dose modifications including interruptions and reductions in both the cabozantinib and darlifarnib. Neutropenia was successfully managed, and in the ongoing phase I-B expansion phase, we do recognize this and allow G-CSF support to avoid dose modifications for the darlifarnib if feasible. These data support the continued development of darlifarnib in this space, along with a combination cabozantinib and VEGF TKI. Currently, the FIT-001 phase I-B portion of the study is enrolling. Next slide, please. In the expansion phase, we are testing two dose levels of darlifarnib at 5 mg and 8 mg. The study is randomized in a 1:1:1 fashion to either darlifarnib 5 + cabo 60 versus darlifarnib at 8 mg + cabo 60 versus cabozantinib 60 mg monotherapy. Given the efficacy of darlifarnib combinations in a prior cabo-exposed population, we do allow those patients who enroll on the cabozantinib monotherapy population or cohort to be enrolled in a subsequent cohort of combination darlifarnib and cabozantinib. Next slide, please. With this, I'll hand it over to Dr. Leoni for further comment. Thank you. Thank you, Dr. A. I would say the basis for our excitement is clear as we move through those patient outcomes. Thank you very much for presenting them. To the next slide, please. When looking at our renal cell carcinoma program, what you have seen is a new mechanism of action that can help reshape the RCC landscape. We have shown you that darlifarnib can safely and tolerably enhance the clinical activity of cabozantinib. Because of the impressive results thus far, we are currently in dose optimization, as described by Dr. A., in our phase I-B trial, where we randomized to the 5 or 8 milligram darli dose and to a mono cabo dose that allows crossover upon progression. This will be the basis for future registrational trials. We plan to share these data with you in the second half of 2027. These data easily support initial registration into the second or third-line advanced RCC space. Future combinations that could be explored in our platform trial design that is currently being developed are of interest to bring this combination to patients even earlier in their treatment journey and provide improved outcomes. If we go to the next slide. Important to remember, our combination data significantly outperformed what you would expect of cabo as a monotherapy in second-line, as showed on this slide. More importantly, the combination showed these improvements in a safe and tolerable manner. This new mechanism not only holds the ability to enhance activity of the TKI, but also to overcome prior resistance. A new TKI partner that can enhance activity for these patients is a valuable addition to the treatment landscape. Moving to the next slide. The next question is, of course, now what? What is the registrational path? As we allow our data to mature and as the shifting landscape of RCC therapy evolves, there is a clear path to market in the third line plus RCC, as is evidenced by our data versus the current third line benchmarks shown here. We could bring a new mechanism of action to this space of high unmet need that has a differentiated profile, including improved PFS. As our data mature and the landscape becomes clear, we will, of course, be looking to move into earlier lines through even broader combinations. This new mechanism of action that can broadly enhance TKI effectiveness is an important addition for patients and prescribers, we look forward to sharing more data with you next year. With that, I will hand it over to Troy. Thank you, Mollie. If we could please go to the next slide. I think with today's presentation from KCRS, in combination with the data that we showed you from ASCO and a little bit earlier this year, the data that we showed you from IKCS, you can see why we're so encouraged about the opportunity with darlifarnib. Darlifarnib is a drug candidate that has the potential to improve the clinical activity of many other targeted therapies. Here we've shown you we have both preclinical and, in now many cases, clinical data, evidencing that we can drive better outcomes for patients potentially by doing rational combinations with darlifarnib, whether that be in the KRAS space on the left-hand side or potentially TKIs in the upper right or PI3 kinase inhibitors. Really a very large number of potential patients we could benefit. We say this isn't another KRAS inhibitor. This isn't another TKI. It's a drug that can not only make one member of the class better, could potentially make multiple members of these classes better. With that, if we could go to the next slide 28. In the specific context of kidney cancer, what we've shown you today is we think there's certainly a meaningful opportunity in third line plus. There may be an opportunity as well in second line plus. We haven't made the decision yet as to exactly what the design of the registration-enabling trial will look like. Because of the improvements in therapy for these renal cell carcinoma patients, we're now seeing more patients in the third line plus setting. That's a quite significant opportunity at $2 billion a year. In the second line setting, potentially looking at a total market opportunity of up to $6 billion a year. One of the reasons that we started with cabozantinib, of course, is as we look at the TKI landscape, cabozantinib remains the market leader. What we're hearing from physicians is there's a desire to improve on those outcomes, whether it be in the cabo-naïve or the cabo-experienced population. We'll provide more information. As Mollie indicated, we're looking toward full enrollment in the phase I-B, and we'll continue to elaborate where we're going to take darlifarnib. If we just focus initially in the addressable market for RCC, we think the future for darlifarnib is quite bright. We go to the next slide, please. I just want to recap where we started, which is it's an exciting time at Kura. Ziftomenib continues to gain momentum as the market leader in relapsed/refractory NPM1-mutant AML patients. We really see a path to where we will have market leadership throughout the treatment continuum, not only in NPM1-mutant but as well in other mutations. We're looking forward to providing additional data for you later this year. On the darlifarnib side, this program continues now to pick up momentum. The phase I-B study is underway with cabozantinib. We'll be starting the phase I-A with daroxadrosib early next year. I think you're going to see us look to be selective and provide additional opportunities to provide value creation for patients, better outcomes, and potentially for our shareholders. The company remains in a very strong cash position, with $580 million in cash, as well as $180 million in anticipated collaboration payments coming in the relatively near term from our partners at Kyowa Kirin. If we could go to the next slide. That concludes the prepared remarks, we're happy to turn it over now for a Q&A session. We will now move to our question and answer session. If you've joined via the webinar, please use the raise hand icon, which can be found at the bottom of your webinar application. When you're called upon, please unmute your line and ask your question. We ask that you please limit yourself to one question and one follow-up question. You're welcome to reenter the queue for any additional questions. Our first question will come from Charles Zhu with LifeSci Capital. Please unmute your line and go ahead. Good morning, everyone, thank you for putting out your data and for hosting this event. Two questions from me. One, could you perhaps elaborate a bit more on the specific prior treatment history for your patients here? Where I'm getting at is that you talk about how many patients have had prior TKI, including cabo. Can you also talk about how many patients may have had prior lenvatinib, given some of the existing clinical data out there that strongly suggests that cabo has possibly wildly different outcomes depending on if patients have seen prior IO, axitinib or lenvatinib sort of so forth. Thanks. My second question, of course, is how would you position or contextualize your data relative to some of the TKI +HIF-2 alpha as well as lenvatinib+ everolimus data out there. Thank you. Great, Charles. Thanks for the questions. Let me ask the first one, though. Your first question is on the prior treatment history. Dr. A or Mollie, do one or both of you want to take Charles's first question? Yeah, sure I can. For the overall patient cohort, we have about 72 patients that were enrolled in this study. In that group, about 67% of them had prior TKI, and that was TKI at any line, including front-line IO plus TKI. If you factor in the patients who've had just cabozantinib, that's around 38% of these patients. The analysis has been split into two parts. The first analysis that was presented at IKCS earlier this year was patients who had prior cabozantinib, and the efficacy that was presented recently or just now was efficacy in patients who were cabo-naive. In this cabo-naive population, 47% of these patients had prior TKI, including lenvatinib, but obviously not all lenvatinib. I don't have the exact breakdown on how many it was lenvatinib, but there's a sizable portion here that was exposed to TKI, including lenvatinib. We do not have a lot of patients on lenvatinib+ belzutifan, if that's the direct question, because it is a regimen that's been recently approved. Interestingly, we do have patient snippets of those who have been on lenvatinib+ belzutifan, and also belzutifan monotherapy. About 18% of patients on this trial have had prior belzutifan exposure too, and we've seen the response. Now, it's interesting to look at the recent cabo-len trial that looked at cabozantinib versus lenvatinib everolimus, where lenvatinib everolimus seems to be doing better. Everolimus is also a harder drug to tolerate, and that probably is coming from both mTOR one and mTOR two inhibition, whereas darlifarnib with a selective mTOR one inhibition does not seem to have that same efficacy, same toxicity profile with the same efficacy being retained. We did not see the same side effects that we see with everolimus, as in worsening stomatitis or any of the significant pneumonitis or diarrhea or rash that we had seen with everolimus with darlifarnib. It seems to be a better, more tolerable drug. Again, with limited data thus far, we will need to see what the future data holds. Mollie, did you want to take Charles's second question, which is how do we think about positioning this relative to TKI, HIF-2 alpha or, Charles, I think you called out specifically lenvatinib, everolimus, as Dr. A was saying. Mollie, you want to comment? Sure. Well, first I want to remind that this isn't just a cabozantinib combination. This particular darlifarnib activity can be seen in any TKI combination. We think that yes, we can enhance the activity of cabo, but we can also enhance the activity of lenvatinib, axitinib, any of the others. Where do we see ourselves being positioned? We see a definite third line play. However, I think as we watch the field settle down a little bit with all the HIF-2 alpha data that's coming out and the kind of tinkering of different combinations being added together, we can see an earlier play as well. I also foresee us going into more of these broader combinations. We are starting a platform trial, which will allow us to evaluate even broader combinations and earlier combinations in these patients. We look forward to sharing that data with you. Ultimately, this is a new mechanism of action we're introducing into this space. We really look forward to being able to bring it as early and as broadly as we possibly can. Excellent. Thank you very much for taking our questions. Thank you. Thanks, Charles. Our next question will come from Li Watsek with Cantor Fitzgerald. Please unmute your line and go ahead. Hey, good morning. Thanks for the update. I just wanted to follow up on the second-line development strategy versus the HIF-2, just given this combination now set a new benchmark in second line, and we're seeing some of the next-gen HIF-2 that seems to deliver even longer PFS benefit. Maybe Dr. A can comment on this as well. Just given the data you've seen s o far, where do you think darlifarnib+cabozantinib can fit in the second and third-line RCC? Then how are you thinking about potentially combining with or perhaps sequencing after the HIF-2 alpha class for your initial target patient population? Mollie, you want to start? Then maybe you could turn it over to Dr. A. Yeah. As we said, the field really is changing a lot. HIF-2 alphas will bring a lot of efficacy for these patients, we're excited for that. We're introducing a brand-new mechanism that can then help to even augment the activity that's being seen with these HIF-2 alpha combinations. Really anywhere you're seeing a TKI brought into a line of therapy, we can easily be the partner for that TKI, bringing even more efficacy, preventing resistance, et cetera, in that combination. I foresee us starting the easy access into the third line, then obviously broadening out into the second line and ultimately going with an IO combination in the front line. Again, reminding you that we have started a platform trial that will enable us to really explore all of these things in parallel rather than in sequence. Dr. A, I'd love to throw it over to you. Yeah. I think it's definitely exciting. I think it's good to have all these options from an oncologist standpoint and also a patient standpoint. I think there are a few caveats to remember here. We know that belzutifan is now approved in the adjuvant setting, so that means that many patients are going to be getting belzutifan, and they're going to be belzutifan exposed. We also know that there's a subgroup of patients who don't tolerate belzutifan, either due to significant anemia or hypoxia, and we as a community are trying to figure out how to manage that. It is promising that in patients who are responding well to belzutifan, there do seem to be durable responses. When we come to the frontline setting, a significant portion of these patients are either going to have pembrolizumab and lenvatinib combinations upfront, and if they've had lenvatinib combinations upfront, they're not going to be eligible for lenvatinib plus belzutifan. We also know that the frontline registrational trial, which has a preliminary result out that it's not positive when they've combined lenvatinib and belzutifan, is interesting. That combination of TKI plus HIF-2 alpha is important, relevant, it doesn't seem to have breached the frontline space as of yet. Maybe there's another combination that we need to look at for the holy grail of a triplet therapy in the frontline setting. Maybe FTI is one opportunity there that's definitely worth evaluating. I think this space is wide open in terms of what we are going to do in the second line or the third line. In patients who have not seen lenvatinib belzutifan, we know that that's a good combination. It works. It has a good PFS and OS benefit. Not OS, pending OS benefit. In those patients post lenvatinib belzutifan, what we use in the third-line setting is important, and tivozanib or axitinib in single agents have really not had great responses. Maybe the goal is to move from a synergistic combination approach in the frontline to a combination approach in the second line and maybe third line. Darlifarnib in combination with, like Mollie and Troy pointed out, any TKI is probably a good option post belzutifan exposure, whether that's belzutifan monotherapy or belzutifan pembrolizumab or lenvatinib belzutifan. We do have some patient snippets who have responded to it despite being on lenvatinib belzutifan before. I do personally have that experience as well on this trial. We'll need to wait for more mature data to be confident that all patients post lenvatinib belzutifan will respond to this combination. This is a new mechanism of action, there's no reason to believe that they won't, and we have not seen any signals that tell us that they won't. Whether this is sequenced before or after that combination approach is yet to be decided by the company, but also will be informed by the data that we generated this expansion phase. Before we go to the next question, I might just add one more comment, Li, to your question and for everyone on the line. We have here go-it-alone strategies with both cabozantinib and daraxonrasib in PDAC. One of the reasons we articulated the platform study is, just as Mollie Leoni said, we're anticipating additional combinations. We can't speak to specific discussions, but I would look forward to that in the months to come. That may provide us with even more options to be able to move darlifarnib forward, whether that is as a doublet, as a triplet, I would say stay tuned. What is clear, as Mollie Leoni said, is this combination we think really is compelling in the third line. We look at it relative to the comparators, pretty clear that would be a place we could go. We'd love to move it even earlier. Second line, we just want to make sure we do the right combination, and as Dr. A said, there's a number of things we can be looking at. Look for us to clarify that. Part of that will come from our own data. Part of that will come from the potential for additional combinations. I just wanted to add that thought. We can go on to the next question. Thank you very much. Our next question will come from the line of Roger Song with Jefferies. Please unmute your line and go ahead. Hey, team. This is Nabil on for Roger. Congrats on the data, and thanks for taking our question. Just maybe one quick one on the neutropenia management. As mentioned, after DLT period, the supportive care became permitted. I was just curious what% of patients require any growth factor support, dose interruptions, and reductions. Were there any cases of febrile neutropenia or infection or any discontinuation due to neutropenia? Thank you. Dr. A, do you want to take that? Yeah, I can take it. I think this is something that we are learning as we go, because we don't usually see neutropenia as a significant AE for RCC treatment. In the initial phases of this trial, during the DLT period, G-CSF was not allowed, these patients had to have dose interruptions of their darlifarnib and cabozantinib. As we have treated more patients, we know this is a darlifarnib-related effect. Most of our patients have been managed with just dose interruptions, with re-challenge at the same dose or at a lower dose, and they've tolerated it well. It seems to be an effect that happens early on. Patients either get neutropenia upfront, and if they do, their darlifarnib dose is modified, or they never get neutropenia. It's not a cumulative toxicity that we're seeing, but it's a signal that happens early on. Even despite these dose reductions, we've seen ongoing responses. For example, there is a patient of mine who had a Grade 4 neutropenia, neutropenic fever, was admitted with sepsis in the hospital and hence had to hold darlifarnib. He was re-challenged with darlifarnib at a lower dose, and currently he's on that darlifarnib combination for more than a year now. Dose reductions seem to be effective, as we've moved on into the expansion phase, we realized that toxicity. Now patients are allowed to have G-CSF support. If we're seeing neutropenia pop in, we are supplementing them with G-CSF, and we've been able to avoid dose modifications or dose reductions. It does seem to be one of those easier-to-manage side effects. About 38% of patients had Grade 3 or higher neutropenia, but neutropenia, fortunately, is not very symptomatic. Yes, there have been cases of neutropenic fever. I think this is something that we are recognizing. With G-CSF support, it doesn't seem to be a major hindrance to treatment at this point. Thank you. Our next question will come from Salim Syed with Mizuho. Please unmute your line and go ahead. Great. Congrats on the data, guys. Just another one from us on the potential second-line strategy here. Troy, you spoke about maybe even doing some sort of doublet. I know the initial commentary here was maybe going towards triplet. Just curious what the thoughts are from yourself or Mollie or Dr. A here on cabozantinib plus darli, just given that caz is already doing 15 months, meeting PFS as a monotherapy in the ARC-20 study, and we'll get obviously some more data for that prior to ESMO. What are your thoughts here on a doublet cabozantinib plus darlifarnib for second line? Is that an option? I'm happy to take that and maybe ask Mollie to comment. Salim, it's a good question. Because HIF-2 alpha doesn't work through the MAP kinase pathway, you wouldn't necessarily expect additivity or synergy in a combination with darli. Were you to do the triplet, with a TKI, HIF-2 alpha, and darli, that could be quite interesting. Just mechanistically, we wouldn't necessarily expect darli to enhance the activity of HIF-2 alpha the way that we're seeing it enhance the activity of both cabo clinically and multiple TKIs pre-clinically. Mollie, you want to comment? Yeah, absolutely. I agree with you. The cabozantinib data is impressive, but it's impressive as long as you're not the patient that is progressing after 13-15 months. Until there's a cure, we have to keep augmenting these combinations and getting patients into deeper remissions or overall remissions. Agree with Troy. This is a TKI combination. Darlifarnib is a TKI drug. Bringing that TKI new mechanism into other combinations is extremely important. We are going to show through our platform trial that we are able to combine with these. We will start to do something eventually where we show that we can be combined with the HIF-2 alpha along with the TKI, can be combined with IO along with the TKI. It's really a story where we want to continue to augment the efficacy of these various combination products. Okay, got it. Thank you. Salim, just to build on that, one more thought. Dr. A can comment on this as well. Interestingly, we've seen activity even at the starting dose of darlifarnib and lower doses of cabo. People may remember, if you look at the data, we initially dose escalated at 40 mg of cabo, and that was on the recommendation at that time that that was the combination dose. We advanced through that, you saw the combination was well-tolerated, so we then went to the 60 mg dose. You still see meaningful activity at those lower doses of both darli and cabo. That could help to make a TKI regimen better tolerated, and help to drive sustained activity. Dr. A, I don't know if you want to add anything to the thoughts or to Salim's question. No, I think it's a very valid point of when we have successful drugs, we're always looking at how to improve their efficacy by being synergistic. We've tried this in RCC for quite some time, and it's that elusive frontline triplet option that we still haven't established, like ICONIC, COSMIC, all those trials looking at IO doublets and TKIs have not broken through. We now have this upcoming result that will probably be reported by Dr. Chowdhury maybe at ESMO, where the combination of pembrolizumab and cabozantinib plus a HIF-2 alpha did not seem to make a difference in the frontline compared to a very strong pembrolizumab and cabozantinib. Whether our hypothesis that a triplet is better than a doublet is always going to be true is a question that remains to be answered, and it would be nice to test out all these newer mechanisms of actions like darlifarnib. I think the toxicity profile is uniquely different. We do not see any overlapping toxicity with darlifarnib and HIF-2 alpha inhibition. Maybe anemia could be one example, but anemia is multifactorial, and I don't think that's an on-target side effect of darlifarnib. It's more the neutropenia with darlifarnib that we've seen. Theoretically, darlifarnib and any HIF-2 alpha could be combined without synergistic toxicity, but we have to look at what the synergistic efficacy of both of them are, and I would be surprised if there is any synergy. Again, not knowing what the data is just from a hypothesis standpoint, like Troy pointed out. It is a tolerable drug. It does not seem to be super hard to tolerate, or we've not had to have dose reductions with cabozantinib pretty upfront. We've been able to treat these patients with cabozantinib at 60 mg. cabozantinib is not an easy drug to tolerate, and many patients do have dose reductions. When this trial first went from the cabo-40 to the cabo-60, I was one of those patient advocates who thought that this would be a harder regimen to tolerate. I'm happy to announce that I've been wrong about it, and most patients who's tolerating the cabo-60 have not had significant toxicities from what we would normally see. I do think that this is an easy drug to tolerate, but we have to be careful when we are adding them on without data, and that's where the BAY platform trial is going to be important, where you have these small snippets of information and how you move this darlifarnib drug combination in this wide-open space of RCC where there's no other drug that's inhibiting the farnesyl transferase mechanism is important. Got it. Thank you so much. Thank you. Our next question will come from Asthika Goonewardene with Leerink Partners. Please unmute your line and ask your question. Hey, guys. Thanks for taking my question. Maybe one for Dr. A here, please. Dr. A, among the 47% of the cabo-naive patients who had seen prior VEGF TKI, could you tell us a bit about what proportion had discontinued prior TKI, either due to best response progressive disease or due to subsequent treatment resistance? I'm just wondering, how does that inform your view on how darlu resensitizes patients versus if the patient had originally discontinued therapy due to toxicity? I have a quick follow-up. Yeah. I don't have the exact numbers for you as to how many patients had stopped due to a side effect of a TKI versus progression, but the protocol doesn't include patients or specify whether patients should have had progression of disease prior to enrollment. They don't allow patients who've just been on a break to go back on the cabo. I personally have enrolled quite a bit to this trial, and I do have my own share of patients who've been on cabozantinib and progressed and then gone on this study and then have had a response. There are specific patient examples that I can cite where patients have been on cabozantinib 40 mg a year or two into treatment with progression of disease that have gone on this trial combination and have responded. There are also patients who have gone from an IO doublet to go. Most of the patients, about 67%, if I remember right, had an IO TKI approach at some point during the course of the treatment. Not all of them just immediately prior, but there is a good portion of patients who had a prior TKI as their immediate prior line before they came to the cabozantinib and darlifarnib drug. There does seem to be some ongoing sensitivity despite cabo. What I, from a physician standpoint, think is the more important or relevant data point here is not the efficacy signals that we're seeing in the cabozantinib-naive population, but the efficacy signals that we saw in the cabozantinib-exposed population that was presented at IKCS earlier this year in Paris. In that group of cabozantinib-exposed patients, objective response rates were above 40%, disease control rates were about 90%. This is a drug combination that works, and in that cohort, a majority of them, more than 50%, I don't know the exact numbers, we can look at it and get it back if it's not listed in the publication. A majority of those patients added TKI as their prior line of therapy before they came on the cabo and the darlifarnib. There does seem to be some efficacy signal here telling us that there is some resensitization happening to the TKI. Whether that's all just resensitization to the TKI or whether there is a synergistic efficacy of the FTI inhibition is something that we don't know. We also know that FTI monotherapy really hasn't moved the needle too much. I do think it's the combination, and I'm assuming that there's some resensitization to the TKI regimen that's happening, but we don't have that answer yet. Got it. Thanks. That's encouraging. It's good to hear that you're able to manage the neutropenia now in patients by giving G-CSF. I'm just wondering if you can talk to us a little bit about the number of patients who you managed this way following the dose escalation work. What proportion of them did you avoid dosing down darli? Or were you able to even avoid dosing down darli completely by giving G-CSF? It's important to understand that the dose expansion phase is in its initial enrollment period. It hasn't been one or two years since the dose expansion started, right, compared to the dose escalation, which has been a while. I don't know the exact numbers again, but most patients, like my patients on the trial, we have not had to dose reduce on the darlifarnib due to neutropenia. There have been other scenarios where cabozantinib has been dose reduced, but so far on the expansion phase, I've not gone down on the dose of the darlifarnib. I've just been able to use G-CSF. For example, I had previously talked about a patient who had these Grade 4 neutropenias, hospitalization, and then went on a re-challenge with a dose reduction of the darlifarnib. In that patient, we did empirically add G-CSF along with the dose reduction, and he's been tolerating it well now for about nine or 10 months since CD challenged, and we've not had to dose reduce further. It does seem to be an all or none phenomenon where some patients get it, some patients don't. In those patients who get it, we've been able to get away without dose modifications as of yet, but it's pretty early, and I don't know how these are going to change. Because if you look at the cabozantinib naive population, median PFS was around 15 months. I think that as patients stay on the darlifarnib longer, we might encounter some of these neutropenias. It's also encouraging to know that there's no cumulative toxicity, as in, as the longer they stay on the darlifarnib, it's not like the neutropenia gets worse. Thanks for taking my question. I wanted to add a little bit to that, is that very rarely do we see a darlifarnib dose reduction rather than a darlifarnib dose interruption. The darlifarnib dose interruptions are really what is sufficient to allow the neutropenia to recover. Got it. Thanks for taking my question, guys. Thanks, Asthika. Thank you. Our next question will come from Jason Zemansky with Bank of America. Please unmute your line and go ahead. Good morning. Congrats on the great progress and thanks for taking our question. Maybe to connect some of the dots in recognizing this is somewhat speculative at this point, based on what you've seen thus far from Darly's emerging profile, where do you think the ideal setting in RCC is for the FTI? Given how entrenched and fragmented the first and second-line markets are, is there potential to leapfrog some of the emerging novel regimens by simply adding on to one of the more established combinations? Thanks. Dr. A, do you want to share some of the questions or comments you've maybe got from your colleagues at the IKCS about their thoughts, of how to use this? If they could, setting aside Kura's designs, maybe speak to a little bit of the commentary you received in the theater. I think, it's along the lines of what we expect and anticipate. We're seeing data that tells us that this combination is doing better than what we would with just cabozantinib monotherapy. cabozantinib was that gold standard second-line treatment. We've also had multiple trials beat it, whether it was the lenvatinib trial or the lenvatinib trial, which had cabozantinib as the competitor. Dr. Chowdhury, who chaired the KCRS meeting in Boston and who is the person who introduced cabozantinib and so on. His comment specifically was, "Well, this seems to be doing better than cabozantinib. Why are you not doing a frontline trial with that?" I personally, we as physicians, do think that this is a regimen that's worth exploring in the frontline space, right? Adding it on to an existing regimen seems like the best strategy, whether that's pembro and vucanib or nivo cabo or pembro axitinib. Obviously, we know the response rates are better for pembro and vucanib than nivo cabo. Maybe that's a scenario that we need to think about. We've had discussions before internally in our meetings as to, we're curious to see what Kura is going to do with this drug, too. I do think it's going to be very easy to enroll patients in the frontline setting to this, too. For example, I as a phase I physician will have no qualms against offering this to a patient in the naive setting. I do believe that it needs to be combined with a TKI because I think there's some synergy like we have seen. I don't believe that it has to be cabozantinib. I do think it can be any TKI, whether it's cabo, whether it's lenvatinib, whether it's Sutent. We don't know what the efficacy signals of each of them are. Assuming that the basket trial that they're talking about shows that it's safe and effective with all these combination approaches, I think a drug like darlifarnib could be one of those drugs that can combine with any upfront treatment strategy without marrying into a specific frontline treatment. It doesn't need to be tied in with lenvatinib or tied in with cabozantinib. It can be IO TKI plus darlifarnib. That's the way I would design a trial if I were given all the resources I want to do. Again, easier said than done. Like everyone else, we're eager to see what Kura will do to this combination. Great. Thanks for the color. Thank you. As a reminder, if you have joined via the webinar, please use the raised hand icon, which can be found at the bottom of your webinar application to ask a question. When called upon, please unmute your line and ask your question. Our next question will come from Phil Nadeau with TD Cowen. Please unmute your line and ask your question. Good morning. Thanks for taking our questions. Two follow-ups from us. First, in terms of the baseline characteristics of the patient in this study, any notable differences between these patients and the precedent cabozantinib second-line trials that you highlighted on the comparison slide? Anything that would bias the patients, either more likely or less likely to respond to cabo? That's first. Then second, in terms of the pivotal study, the first pivotal, I guess, what exactly are you debating? Is it just the patient population that could be enrolled as well as the dose in third-line, but you're committed to going forward with a cabo combo? Or is there a scenario where you actually wait for the results from your platform study and perhaps move a different combo forward into the first pivotal? Thank you. Yeah. Thanks, Phil, for the questions. Mollie, do you want to speak to Phil's question about the baseline characteristics relative to the comparator trials that we highlighted? Absolutely. We attempted to show you the closest apples to apples comparisons that we could for what you'd expect cabo to do in a second-line setting. However, really, our patients were really in a third-line plus. That's your biggest difference between the groups is that we actually are showing you patients that are somewhat less pretreated. Really, our results then are even more outstanding, in my opinion, compared to what we would expect to see with these patients that are receiving cabo alone. Phil, maybe I can take your second question. We're deliberately sort of not yet articulating that registration-enabling design. As in any case, what are we weighing off? We're weighing off the unmet need. We're weighing off the commercial opportunity, the competitive landscape, cost, and time. As Mollie indicated, we've gone in a relatively short period of time from FTIs being either, I'll be harsh, irrelevant or a HIF-2 alpha inhibitor, to something that could broadly combine with TKIs in RCC and I think could really positively impact the evolving KRAS space. We want to make sure that when we do this, we're doing it with all the available information. There are a number of combinations we can take forward. We want to make sure we think about and carefully consider the overall development plan. We won't be able to do everything, so we have to be selective. You do hear us wanting to move DARLi as quickly as we can earlier in the treatment setting. We also want to ensure that we give it the very best shot to get that first registration. Just look for us to provide more clarity either later this year or early next year. To your question about dose, the great thing is either five or eight, both look to be pretty good. I think we're in a good spot as far as that's concerned. For Project Optimus, we do need to make sure that we do the right experiment, right? The FDA is looking for the proper Project Optimus design, and that's what the phase I-B does. We'll be able to, I think again, later this year or early next year, articulate a registration-enabling design. I hope that helps. Yes. Thank you. Thank you. Our next question will come from Reni Benjamin with Citizens. Please unmute your line and ask your question. Great. Thanks for taking the questions and congrats on the data. Maybe just two for us. Are there any patterns that are starting to develop of the patients you think are most likely to benefit from this combination? In this study, are there any biomarker analyses that you guys are conducting that might help in identifying those patients? Just as a follow-up, maybe for Dr. A, looking ahead, is there any additional data from the ongoing randomized phase I-B study that would be most important for you as a practicing physician, or is that really more for the company and you'd be more interested in really the registrational pivotal study path? Thanks. Sure. Thanks, Reni, for the questions. Mollie, do you want to take the question about biomarkers and- Sure patients most likely to benefit? Sure. It's a great question. It's early. Let us continue on with our phase I-B work. We'll have a good pool of more homogenous patients that will be able to help us potentially answer that question more. Again, these are some questions that occasionally don't get answered for a very long time. We hope to be able to gain more information from that to help guide, maybe it's earlier line patients, maybe it's patients that haven't seen other TKIs, maybe it is patients that have. Let us continue to generate that data, and then we'll share it with you. Dr. A, for you, anything in particular you're looking for from the phase I-B to Reni's second question, or are you really excited to, and Reni, I'm reframing your question, excited to sort of move into that next combination or pivotal design? I think we're all excited to see where this drug goes. We've had experience with it. It's been an easy drug to manage in clinic, and patients have stayed on it for a long time. Two things that we are all waiting to see is, one, durability of response. In the KCRS presentation where we had a PFS of 13 months, about 50% of these patients are still on treatment. We know that we don't have long-term follow-up yet, and hopefully we can see a better PFS and a longer durability. Like six-month PFS was around 74%, nine-month was around 60%, if I remember right. It does seem to be durable when we're seeing these responses, and that's what the long follow-up will show. The second thing that's going to be important is that this phase I-B expansion will be randomized, it's randomizing to cabozantinib monotherapy at 60 mg, which we all know is a good drug. That will tell us what the combination is doing in terms of incremental benefit, and the randomization is also stratified based on a prior TKI exposure. Instead of looking at it by saying, "This cohort of patients had this or that," I think we'll have prospective randomized data, which is always stronger. We all hope and believe that this will be something that's promising, and how you combine it or take it forward in the next line setting is going to be important. I am not of a firm belief that it has to be cabo. I think it can be any TKI, and probably a multi-kinase inhibitor is the one that Kura should target. Now, whether that's cabo-like, len-like, or any of the other agents that are being investigated in this field is up for debate, and it opens up the opportunities in the basket trial. I'm optimistic that the trial will be relevant and significant, and that the addition of the cabo to the darlifarnib, whether it's at five or eight, will have some meaningful improvement in outcomes. Hopefully by that time this data is out, the basket trial data is out, which tells us the safety of combining it with everything else, and then Kura will have a good headache of trying to figure out which trial combination they need to take forward with. It'll be interesting times. Great. Thanks for taking the questions. Thank you. Our last question will come from David Dai with UBS. Please unmute your line and ask your question. Great. Thanks for squeezing me in. Just a quick one. Thinking about the potential other combinations in addition to cabo and RAS inhibitors, maybe wondering if you can tease some of the potential combination strategies or interesting MOAs you're currently evaluating. David. Thanks. A good question to end on, actually. This will be my concluding comments. We'd like to benefit as many patients as we can in RCC. As Dr. A mentioned, there's a rationale to combine with any of the TKI-containing regimens. It would be great if we could do something akin to what we're doing in AML with ziftomenib, where, as you look toward the end of the year, you're going to see combinations with venetoclax and azacitidine, with FLT3 inhibitors, with other regimens, like LDAC. Would be great to do that in the RCC space. In the K RAS space, we've committed to moving forward with adagrasib, because obviously that's the second-line standard of care. Interestingly, a number of these companies are now pivoting and going to frontline. These are other RAS companies. We're not doing that. We actually think we can build upon the strong data with daraxonrasib and potentially make it even better. That puts us in an attractive place, I think, in this evolving KRAS landscape. There again, we can combine with the mutant selective inhibitors, we can combine with the pan inhibitors, and we can likely do it in each of the major tumor types. This is going to require a meaningful development spend, but I think the opportunity. There hasn't been a molecule like an FTI before, one that actually can work well in a solid tumor space like RCC, that as we indicated, is a $6 billion market opportunity in the second line, and then the RAS space, which is just on fire. It's an exciting time. It's a high-class problem that we have to make these development decisions, but look for us to articulate that through the rest of the year. With that, I know we're a few minutes over. I want to thank everyone for your listening to us and participating. I particularly want to thank Dr. A for being so generous with his time, both at KCRS and in this webinar. We will be releasing earnings here within the next couple of weeks, and look forward to talking to you all then. Until then, happy Monday and enjoy the rest of your day. Thanks very much