Good day, everyone. My name is Megan, and I will be your conference operator today. At this time, I would like to welcome you to the Kura Oncology investor call to discuss recent clinical data and the company's updated development strategy for darlifarnib. All lines have been placed on mute to prevent any background noise. After the speaker's remarks, there will be a question and answer session. If you would like to ask a question during this time and you have joined via the webinar, please use the Raise 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 would like to turn the call over to Troy Wilson, President and Chief Executive Officer of Kura Oncology. Please go ahead, Dr. Wilson. Thank you, Megan. Welcome, everyone. It's a pleasure to come to you today and share the darlifarnib clinical results from ASCO, as well as our strategy and next steps for the program. If we can go to the next slide. In today's presentation, we're going to be making forward-looking statements. We would refer you to our website and to the SEC's website for more information about Kura Oncology and risks and uncertainties relating to an investment in the company. Next slide, please. Today's participants include Dr. David Hong from MD Anderson Cancer Center, we're delighted to have him here today, as well as my colleagues, Dr. Mollie Leoni, our Chief Medical Officer, and Dr. Francis Burrows, our Chief Scientific Officer. Next slide. This is an exciting time for Kura Oncology. In addition to the substantial momentum that we're making with our ziftomenib program, both in the commercial marketplace as well as in the clinic, we're now in a position where darlifarnib is moving into a position that's quite exciting. That's really the purpose of today's session is to share with you the data, some translational data, and thoughts around strategies and next steps. Next slide, please. At Kura, one of our key focus for the company is on a concept we call precision combinations, and that is the idea that patients will do better, drive better outcomes, through use in combinations. If we can please go to slide 6. Oh, sorry. If we can go forward to the next slide, please. One more, please. Thank you. Here, some of the challenges of developing an effective companion therapeutic to enhance clinical activity. This is really the opportunity and the challenge with darlifarnib. This is not a new concept. People have been trying to develop combination therapies, particularly against targets on the MAP kinase and PI3 kinase pathways, for quite some time. Some of the requirements are, of course, that the targets have to be drugable. They have to be selective. Often, these combinations are limited by toxicity. We've seen this with various combinations. Sometimes those toxicities prohibit actually being able to reach doses where you can drive maximum activity. Similarly, there are pharmacokinetic or pharmacodynamic interactions that can limit dosing. We go to the next slide, please. That's what we think we've addressed here with darlifarnib. We have a companion therapeutic. We've now demonstrated in multiple settings that we're going to walk through today the ability to combine and the ability to suppress this pathway signaling and enhance activity. With that, we think there's really a significant opportunity for patients and potentially for Kura shareholders. Next slide. Darlifarnib is our next-generation farnesyl transferase inhibitor. As many of you know, we've been working on this program for a number of years. This compound is really as optimized as one could be. Importantly, not to take anything away from others, we're not working on another tyrosine kinase inhibitor, another KRAS inhibitor. We're developing an approach with darlifarnib where we think we can enhance the clinical activity across multiple targeted therapies and multiple settings. In that, we think FTIs represent a mechanism-driven, targeted therapy-agnostic combination platform approach. It's quite different, we think complementary, and really positions us quite favorably relative to these rapidly evolving landscapes. Next slide, please. Here, this pathway diagram, really several key points. First of all, we've shown you now three different examples where darlifarnib is able to enhance the activity of a targeted therapy. Working from left to right, we have adagrasib, which the data will show you today. A few weeks ago, we showed you the combination data with cabozantinib, and last year we showed you combination data of tipifarnib plus alpelisib. In each case, we've been able to see an enhancement of clinical activity. The common mechanism of action here is blocking Rheb farnesylation. Rheb is responsible for the localization of mTORC1. By darlifarnib blocking the farnesyl transferase, that's able to attenuate pathway signaling, the MAP kinase pathway signaling, and PI3 kinase signaling. This gives us opportunities both within each of these classes. As you'll see, we think this approach can apply to adagrasib as well as other KRAS inhibitors. It gives us opportunities to go it alone. It also gives us opportunities to collaborate with others. It's quite an extensive menu, and this is why we wanted to give you the strategy update to help you understand our proposal for a platform study, which will really help us to evaluate these different combinations efficiently. Next slide, please. The opportunity for patients is really quite significant. Just working our way around the circle here at the top, you have the indications that are relevant for the tyrosine kinase inhibitors, kidney cancer, as well as neuroendocrine tumors. We have, of course, the PI3 kinase alpha mutant tumors in the lower right. Then really what'll be the focus of today's presentation, the KRAS mutant tumors, pancreatic, colorectal, and non-small cell lung. These are significant numbers. We have now, as you'll see a little later in the presentation, clinical proof of concept data in a number of these indications. Kura won't be able to prosecute all of these on our own. We will, however, be able to advance some of them on our own, and we think to work with others, to really be able to do what's best for patients. Next slide, please. With that, I'm going to turn it over to Dr. David Hong and let him walk you through the data that was presented this weekend at ASCO. Dr. Hong? Hey, guys. I don't know who's on the other line, but I'm sure I've met many of you talking about KRAS in general. I'm going to walk you through the combination that we've now started looking at with adagrasib. I'm very familiar with adagrasib. I helped lead a number of other combinations with adagrasib. Next slide, please. This was a poster presentation that we presented this ASCO. Next slide, please. Yeah. Okay. Really three dose levels, from 3, 5, and 8. We really didn't feel like 8 was going to be able to be advanced further, but I think you'll see from the data on 3 and 5 that those doses also show some significant activity. Next slide, please. This is the overall demographic profile of the patients. There were 15 patients at the 3 milligram of darlifarnib and at 15. As you know, adagrasib was set at 400, which is the standard care dosing. Pretty much even distribution here. Most patients with good ECOG and really three tumor types that we're looking at, non-small cell lung, PDAC, and colorectal. You can see the distribution. Next slide, please. Typical of most phase I trials, these patients had lots and lots of prior therapy. As you can see here, the majority of these patients had two or more. Many of them had prior, either sotorasib or adagrasib, which is now the standard care in non-small cell lung to some extent, and also colorectal. Also had other investigational agents such as daraxonrasib and divarasib, albeit smaller numbers. Next slide, please. You can see here the distribution of tumor types, PDAC, non-small cell lung, and colorectal. Some of you may know KRAS G12C PDAC is a much harder subset of patients to identify. It's probably less than 5% of all PDAC. You can see here that the majority of patients who had prior G12C were non-small cell and colorectal, which as you know, there are two drugs approved in both areas. The majority of these patients got either sotorasib or adagrasib. Next slide, please. These are the adverse events. Pretty much when you compare that to adagrasib, especially the diarrhea, nausea, really no significant add-on toxicities. Clearly, there's no rash as we see with daraxonrasib. The overall neutropenia anemia that usually is probably associated with darlifarnib, we rarely see that with adagrasib. Looks like pretty much no significant synergistic toxicities noted here. Next slide, please. This is what is really, really interesting. There's still small numbers. I'm going to be honest with you. If you look at these numbers, look at the number of patients, particularly in the pancreatic subset. As you recall, both adagrasib and sotorasib, the response rates are in the, for sotorasib, because I ran that trial, is in the low 20s, and adagrasib may be low 30s. This is like it's 60-some% with darlifarnib here in the pancreatic setting. Every one of these patients are having some kind of tumor shrinkage. That is significant. You don't know until you obviously add another maybe 10, 15 patients here. I don't think that's something that you can dismiss. That's what was really intriguing about this combination. Next slide, please. Again, you can see here, especially in the pancreatic subset, these are not just one-and-done responses. They are ongoing. It tells me that this may definitely be something that plays out in not only in responses, but also PFS and possibly overall survival. Next slide, please. You can see the spider plot again, looks good. Next slide, please. Overall, again, 67% response in pancreatic. Now, small cell lung, albeit the overall subset is 50, but in the naive was also 67. If you recall, adagrasib was probably in the high 30s, mid-40s subset. There is something going on here. Especially with care, also colorectal cancer, you're seeing a 29% response rate. Remember, with sotorasib, it's literally in the single digits. With adagrasib may be a little bit higher, like 11%, 12%. The fact that it's 29% could tell you that there is something there. I really think that with the colorectal subset, I think you would see significant increase in response if we would add an EGFR inhibitor, which as many of you know is one of the reasons that single agent RAS inhibitors don't seem to respond. There's something about blocking [RET and RO] that definitely adds, if not additivity, maybe even synergy. Next slide, please. This is an example of just a really nice response. 5th line treatment. Somebody who's had cisplat gemcitabine Durva, went on to see 2nd line docetaxel and then got sotorasib. Progressed, got 3rd line cisplat pemetrexed, then got venetoclax, and then went on darlifarnib and adagrasib and had this amazing response. Next slide, please. Again, against, albeit small numbers, but I do think that there is something, a definite signal here in all three, given and particularly PDAC. I've not seen a combination where you're seeing things like that to date. Next slide, please. Let me give you the reason I've been interested in this combination. My first trial, by the way, ever was tipifarnib many years ago. At that time, we didn't have NGS. I tried putting patients with a KRAS hotspot, and they weren't responding. Many years afterwards, Kura picked this up and realized that in patients with HRAS, we could induce responses. In addition to this, which I think is really important, there have been several really prominent investigators, including Channing Der, who's a good friend of mine, one of the godfathers of RAS, who had argued to you that the next reiteration of RAS is really combinations. What they've seen is that there are certain key molecules downstream that may significantly combine. AXL, ERK, MYC, and Rheb and mTOR. Right now, there's not a good real clean AXL inhibitor. There are not really good MYC inhibitors. The ERK inhibitors have been tried in the past, but they were just too toxic. The fact that this thing appears to have a strong signal really validates that preclinical data that Channing Der and others have generated. Next slide. I think that's the end of my presentation. Thank you, Dr. Hong. Francis? Thanks, Troy. Hello, everybody. I'm here today to give you a little bit of the highlights of our translational work with darolutinib in combination with RAS inhibitors. This work was recently published in Cancer Research. I'm just going to touch on a few of the highlights here. Here's the pathway diagram again, as Troy showed you. The reason why RAS is such a big dog in oncology is that it drives signaling down both the MAP kinase and the PI3K/Akt pathways. Its control of MAP kinase is much stronger than on the other side. The Rheb-mTOR node is downstream of both of those. What I hope you can appreciate from these charts here is that in all three major RAS-driven solid tumor types, RAS inhibitor monotherapy fails to either completely suppress mTORC1 activity, as you see here with adagrasib in the non-small cell lung cancer model. If we move on to a better RAS inhibitor, darlifarnib in either CRC or PDAC. In this case, you do get a nice suppression, but it does not last. Under continuous exposure conditions, we see a pretty robust bounce back of the mTORC1 activity. In all three cases, this can be rescued by combining the RAS inhibitor with the darlifarnib to suppress mTORC activity over a longer period of time. Next slide. When we started this work, it was probably about four years ago now, there was only a few RAS inhibitors in the clinic. The first few G12C and other selective compounds. Now clearly there is a really growing field here. We've looked at all three of these classes, mutant-selective G12C or G12D, or pan-RAS or pan-KRAS. With all classes, we're able to get robust enhancement through blockade of the Rheb/mTOR node. We think that this is going to be a broadly applicable combination approach. Next slide. As I mentioned, the early work was all in non-small cell lung cancer, G12C mutant, and we modeled that in combination with adagrasib or divarasib, another similar RAS inhibitor. What I hope you can appreciate from this is that irrespective of how active the RAS monotherapy was on its own, we were able to enhance it. On the left-hand side of the chart, you see models that were pretty refractory, but you throw in the darlifarnib on top of that, and we can at least slow tumor growth. On the right-hand side, you see models where you get regressions on the monotherapy, but we can deepen those regressions and extend their duration. Most excitingly, perhaps, in the middle there, you see a number of moderately responsive models, which when we add in the darlifarnib, we can move from progressive disease to some pretty deep regressions. We think that we shouldn't need to do any kind of patient selection to take these trials forward. On the right, there's some data with darlifarnib in a CRC panel. This is a slightly more challenging tumor type for RAS inhibitors, and the darlifarnib is only able to generate, at best, a tumor stasis on its own. We see across the range of activities that by adding in the FTI, we can enhance the activity and get some pretty decent regressions in some models. Next slide. As we've been talking about, the reason we're all here is that RAS inhibitor clinical development has really taken off. Even when we started this work, we anticipated that we were going to be accruing a lot of patients to our trials who had already seen a RAS inhibitor before. We thought we would model that, and it worked out quite well. As you can see here, this is a non-small cell lung cancer model, which does respond for a while to either adagrasib with a stasis or darlifarnib with regressions. It only lasts for a few weeks and then the tumors start to progress. If we add darlifarnib at this moment, next, we can recover tumor control and induce deep regressions in these relaxing tumors. Indeed, next one, it doesn't look that different from if we did the combination up front. That's giving us, or gave us at that time, some optimism that we're perhaps not going to see huge differences in the types of responses in patients who were KRAS-inhibitor naive versus those who were experienced at receiving that class of drugs. I think our clinical data has confirmed that. We see a similar situation in the colorectal model on the next slide. In this case, we've compared, this is a G12D mutant, we look at the Mirati G12D-selective compound, MRTX1133, and also darlifarnib on the right. Both of these do very nicely. They induce good regressions for a solid month, but at that time, the tumor control dissipates and the tumors start to grow again. If we add darlifarnib at that time, we can recover the regressions and, one more, please. You can see that the outcomes are not that different from the upfront combo. What we concluded from this work, on the next slide, is that we could see enhancement of activity of all the classes of RAS inhibitors we've looked at. We've looked at a total of seven or eight now in various models. We see that whether they work well or less well, in a decent panel of preclinical CDX and PDX models, the combination is able to induce regressions even in these preclinical models where there has been previous exposure and progression on either mutant-selective or pan-RAS inhibitor monotherapy. We feel that this preclinical data supports evaluating darlifarnib with both pan-RAS and mutant-selective inhibitors, and as such, DALI represents a mechanism-driven, RAS inhibitor-agnostic combination platform with potentially very broad applicability. Thank you. What have we seen thus far? We have seen preclinical data that has translated to clinical data across a combination partners and indications. We have seen a mechanism-driven, targeted therapy-agnostic combination platform. Next slide. Across three different combination partners and five different tumor types so far, we have shown you that the combination consistently outperforms what you would expect with backbone therapy. Let me emphasize, we would not expect daralfernib to have more than minimal to no monotherapy activity in these settings. What does that mean? It means that daralfernib is able to augment the activity of these targeted agents. Based upon the preclinical data, we know that this mechanism can augment more than cabo in renal cell carcinoma, more than alpelisib in PIK3CA mutant head and neck, more than pancreatic, non-small cell, and colorectal in combination with adagrasib. This truly is a mechanism-driven, targeted therapy-agnostic combination platform. We can consistently make good therapies better for patients. Next slide. The number of patients that could potentially benefit is extraordinary, likely with more to come. One therapy that can improve outcomes across PDAC, CRC, non-small cell lung cancer, breast cancer, head and neck cancer, neuroendocrine tumors, and renal cell carcinoma so far. Next slide. How do we get this drug to patients? What are the next steps? For renal cell carcinoma, we are currently enrolling our phase I-B that is evaluating daralfernib in combination with one of the commercially available VEGF TKIs, namely cabozantinib. We anticipate having these data that confirm the recommended phase II dose, as well as continue to support the overall hypothesis in 2027. We are also preparing for a registrational path with the same combination that would at least allow for a third-line registration and likely second-line plus that can be initiated in 2028. From there, we can expand to the front line. daralfernib is easily combinable, making triplet regimens the likely and best next step for patients. Wherever the TKI can go, be it in combination with HIF-2α or IO therapy, daralfernib can follow and augment the activity. Next slide. With regards to KRAS-driven tumors, we are currently operationalizing our platform trial that will allow evaluation of daralfernib in combination with any pan-KRAS, pan-RAS, or KRAS mutant selective agent. Our first cohort in the trial will be a combination with [deruxtecan] or cetuximab pancreatic cancer, anticipated to initiate in early 2027. From there, we will continue to build on this mechanism-driven, targeted therapy-agnostic combination platform and move towards a registrational path in second-line plus KRAS-driven tumors, and ultimately to the front line as we look to improve patient outcomes. Next slide. Exploring these combinations and indications through a platform study allows us to evaluate outcomes in parallel rather than sequentially, and overall demonstrate the broad applicability of this mTORC1 inhibition. The design is flexible, and both approved and investigational therapies can be evaluated, making way for the ability to collaborate with multiple partners. If new and interesting possibilities become available, they can be evaluated in the same trial. Each combination and indication can be individually evaluated for milestones that will result in a graduation to the next phase of development. As I said, darlifarnib and PDAC will be among the first combinations evaluated. Colorectal cancer, possibly in combination with EGFR inhibitors as well, and other indications are subsequent opportunities that need to be explored. This trial will allow us to demonstrate the vast applicability of this mechanism to enhancing the targeted therapies already available, and I look forward to being able to share these data as we progress. With that, I'll turn it back to Troy. Thank you, Mollie. We can go to the next slide, please. As Mollie mentioned, our initial focus is going to be in 3rd line plus kidney, the potential to go earlier, as well as 3rd line plus PDAC. These are significant opportunities. We talk about ziftomenib as being a multi-billion dollar opportunity in AML. These large solid tumors, there's just unfortunately so many patients who are in need. We really see this as a meaningful opportunity for the company and for shareholders. We've also prioritized, as Mollie mentioned, combinations with agents that are either available in standard of care in the case of cabozantinib, or that everyone anticipates will very shortly be the standard of care in the case of divarasib and PDAC. We are open to additional combinations as the science and the development plans and the interest from potential collaborators guide us. Next slide, please. Just to summarize it again, a whole set of milestones for ziftomenib. We really are going to be the market leader in not only relapsed/refractory NPM1 mutant AML, but we think we've got the opportunity to dominate the front-line setting. Now with darlifarnib, we have a completely separate, wholly-owned asset where there's going to be a lot going on. There's been a lot of inbound interest. Everyone wants to be involved. Everyone wants to do the best for patients. I think everybody recognizes the need for these precision combinations, and we think we're in a very good spot. If we can go to the next slide. We're happy to, at this point, end the prepared remarks and open it up for questions. Before we do, I will just say, Dr. Hong was very generous to share his time with us. He has a hard stop at the top of the hour. We would ask you, if you have questions for him, to please prioritize those. We'll get to as many questions as we can. Again, we'd limit each of you to one question and one follow-up so that we can get as many analyst questions answered as possible. With that, Megan, we're happy to open it up to Q&A. Thank you. We'll 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 on the bottom of your webinar application. When you're called on, please unmute your line and ask your question. We'll now pause a moment to assemble the queue. Again, we ask that you please limit yourself to one question and one follow-up. You're welcome to reenter the queue if we have more time. Thank you. Our first question will come from Li Watsek with Cantor Fitzgerald. Please go ahead. Oh, hey, guys. Thank you so much for taking my question. I guess for pancreatic cancer, how should we think about the translatability of the G12C data that you're seeing to the G12V and D and other RAS isoforms? Francis, do you want to give that a short answer? Sure. Yes. As I said, we see the same kind of patterns with all of the different classes of RAS inhibitors. The pan-RAS are more active than the mutant selective in most models, and that it will be in part because of resistance mediated by the wild-type RAS. Nonetheless, even with [diraxant], which is an awesome compound, it takes a lot to get a standing O at ASCO, and that's a truly great compound. Even with that compound, it is able to suppress the mTOR pathway, but you need 10 times as much drug to achieve that as you do to suppress the MAP kinase pathway. Our goal is to combine with the FTI and enable us to get at those more resistant cells. One thing we all know about PDAC is that it has the fibrotic TME, which retards drug access and really has made PDAC a drug graveyard for decades now. We feel that in order to get most efficient and as efficient as it needs to be, suppression of the pathway throughout these pancreatic tumors, you are going to need a combination like this. Thanks, Francis. I can comment. Yeah, Dr. Hong, please. History often does not repeat, but it rhymes. I'm serious. If you look at the BRAF story, right? BRAF plus cetuximab in colorectal, that translated into what Scott presented like the fifth time, the BREAKWATER study, right? It's translated into G12C with cetuximab. Likewise, I think what's going to happen is you're seeing in pancreatic, possibly in also colorectal and non-small cell lung, this combination, which in C, it's less of a leap than even RAF to KRAS, that you're going to likely have the same kind of mechanism in DEV, whatever, pan-RAS, whatever. I think that's just the reality of the situation. I am a big fan of Mark Twight. Thank you. Megan, next question. Our next question will come from Jason Zemansky with Bank of America. Your line is open. Please go ahead. Good afternoon. Thank you so much for taking our question. Congrats on the great data. Maybe a quick one for Dr. Hong. Obviously, the efficacy looks pretty potent. Just curious about the safety dynamics. Do you think the thrombocytopenia is going to be an issue at all, and are there ways to mitigate it, especially as you explore some of those higher doses? Yeah. No, I'm not worried about thrombocytopenia. We don't get worried about thrombocytopenia until patients' platelets get below 10K. Most of these patients, and with darlifarnib, the vast majority of the time, we would just hold it for a couple of days and bring the patient back, and it would come back. Thrombocytopenia is not an issue. Neutropenia, as you know, we have ways to mitigate that. Even now, Nplate is actually approved in patients with low platelets. It's not a quality of life issue, right? You have a platelet of 50,000, people are not worried about nausea, vomiting, or anything like that. I'm not too worried. The good thing is that there's really no overlap with daraxonrasib. There are some small percentage of these patients who get cytopenias, but the vast majority don't. I don't see where we're going to have troubles combining these drugs. The overlap in toxicity at all is very minimal, maybe some GI, but even then, I think it's going to be manageable. Great. Thanks for the color. Our next question will come from Charles Zhu with LifeSci Capital. Please go ahead. I know Charles. Charles, please unmute your line and ask your question. Not a problem. We can come back to Charles. The next question will be Jonathan Chang from Leerink Partners. Please unmute your line and ask your question. Hi, guys. Thanks for taking my question. What settings in pancreatic cancer are you expecting to evaluate the darlifarnib plus diraxant RAS combination in? Thank you. Mollie, do you want to take that? Sure. We're initially going to start in the 2nd-line plus area. Obviously, easiest to always see the signal in that relapsed, recurrent setting. As our plan shows you with the potential for the platform trial, if we see what we expect to see, we can have it graduate to the next level towards a registrational program, and then obviously start branching out further into earlier line of therapy. Understood. Thank you. Thanks, Jonathan. Next question, we will check on Charles Zhu with LifeSci Capital. Please unmute your line and ask your question. Charles Zhu, if you could unmute your line and ask your question, please. Charles is having a problem with his mic. Not a problem. We will move on to the next question. Eric [inaudible] with Mizuho, your line is open. Please go ahead. Hi. Thanks for the presentation, and thanks for taking our question. Very curious about your thoughts on rationale and biology. If darlifarnib is kind of in your upfront, right, data, it kind of looks like you are getting breakout mutations, I'm just curious if there's some underlying biology that might explain that, if you have data on the mutation landscape through time, to explain that or to tease that out. Wouldn't that kind of point to bringing darlifarnib in as early as possible, to prevent RAS mutations? Thanks. Eric, maybe I can take that question. There's a lot going on in these pathways and in these tumor types. I think we have to balance the biology that you're seeing with the ability to run the study. At the moment, we're talking about phase I dose escalation and then potentially expansions. We'll start there. Our goal would be to move as quickly as the data supports to earlier lines. We really think of this as a potent means of attenuating pathway signaling, as Francis mentioned, through both MAP kinase and PI3 kinase. The tumor's always going to be looking for other ways to get around it, but I think Dr. Hong said it nicely. This is a very potent way of adding two inhibitors at the top of the pathway. We do see patients that their disease is failing therapy. We'll move as quickly as we can. Your next question will come from Phil Nadeau with TD Cowen. Your line is open. Please go ahead. Good afternoon. Congrats on the data. Thanks for taking our questions. Just two follow-up from us. First you said second line in pancreatic cancer. What do you define as second line? Is that post-chemo, or will you allow patients to have had adagrasib monotherapy experience before? That's first. Second, in terms of the adagrasib dosing, you mentioned 400 milligrams is what's moving forward. We're under the impression that in some indications, 600 milligrams BID is standard. What's the rationale for using 400 milligrams? Thanks. Mollie, do you want to take those two? As we get the trial started, we will be looking kind of at an all-comer patient population in that recurrent metastatic setting. It'll be a second-line plus trial for the dose escalation where, yes, we would consider them having failed frontline chemo to define them as now being eligible for trial. In those initial dose escalation cohorts, we would also allow prior adagrasib exposure, just as we've done in pretty much all of our other trials. We really do think it proves the point and proves the mechanism to be able to save those responses. With regards to adagrasib, there's a lot of debate right now as to what the appropriate dose is, and BMS is actually performing studies in both 400 milligrams and 600 milligrams in order to satisfy some regulatory requirements. A great deal of their combinations right now are at the 400 milligram dose, and it does seem to still be a very effective dose for these patients. Dr. Hong, did you have any additional comments on that? Yeah. Daraxonrasib is a very good drug. I led the phase I on that thing. It's not a cure. I don't know about you, but if you're a pancreatic cancer patient in the second line after chemo, which it won't be approved for a while, if it does get approved, which I think it will, you want something better. If I was a pancreatic cancer patient who finished FOLFIRINOX and somebody said, "Hey, I have daraxonrasib plus a new drug that's going to make this better," heck, I'd enroll. I don't think that we'll have trouble finding patients, if that's your question. That's very helpful. Thank you. Thanks, Phil. Your next question will come from Charles Zhu with LifeSci Capital. Please unmute your line and ask your question. Hi, this is Peter on for Charles. Just wondering, how do you feel that FTI plus daraxonrasib could be positioned against daraxonrasib plus KRAS mutant selective inhibitors? Thanks. Mollie, do you want to take that or Dr. Hong? I don't know that they're mutually exclusive. I think we need to do everything we can. Yeah, I agree. Right now, for example, probably the one that's most ahead right now is zoldonrasib. I think Revolution Medicines is trying to position zoldonrasib plus Dexon in the frontline setting, right? They've already announced that they're doing that trial, and we'll see how it goes. I think ultimately pancreatic cancer, five years from now is going to be treated like non-small cell lung. You're going to have KRAS, but you may have KRAS plus MTAP loss. People are going to try to position themselves for that. If you talk with any pancreatic doc, and you saw that in the PRO with daraxonrasib, they don't like chemotherapy, and they don't want to give chemotherapy. So if this darlifarnib plus whatever looks amazing in the second line, I definitely think it's going to have a likelihood that it could position itself in the frontline. You could have possibly, you could combine this with zoldonrasib. Ideally, they can't obviously combine Dex. I'm not sure. Maybe they'll come out with some data that I haven't seen, they can't combine daraxonrasib with EGFR. Right now, at some point in colorectal, they're going to try to combine Zoldon plus EGFR. What if this thing augments that, holy cow, you could also combine it with that. There's just so many different reiterations as to how it's going to pan out. I think in the pancreatic space, everybody's going to try to push chemo out of the picture at some point, and this could be one of those situations where you either have a G12D inhibitor or the pan-RAS inhibitor, whatever, in the frontline setting. Thank you. Peter, just to add on to Dr. Hong's comments, this is part of the motivation for the platform study. We're getting approached, as you can imagine, by folks with all manner of targeted therapy looking to do combinations. We're not going to be able to do it all. We'd like to do the ones that make the most sense for patients, and ideally not have regimens competing with each other. There's a clear opportunity, we think, in pancreatic to test this combo. Dr. Hong's alluding to it. There are combinations in colorectal that we look to pursue. Stay tuned throughout this year and early next year. I think we'll have much more to say about that. I have to go, guys. Thank you. Thank you, Dr. Hong. We appreciate your time. All right. I'm just going to say I'm excited. I'm very excited to do this combo, okay? Please support them so I can do this combo. Thank you. Bye. We appreciate your time. Thanks, Dr. Hong. Thanks, Dr. Hong and Troy. We can keep going with questions, thank you. Just a reminder, if you've joined via the webinar, please use the Raise Hand icon to ask a question. Your next question will come from Ren Benjamin with Citizens JMP. Please unmute your line and ask your question. Hey, guys. Thanks for taking the questions and congrats on the progress. I guess since Dr. Hong is gone, Troy, maybe you can answer this. You talked about how darlifarnib is broadly applicable through a variety of these indications and combinations. How important is it to have additional combination agents on top of the KRAS inhibitors? Maybe just as a follow-up, I think Dr. Hong had mentioned EGFR on top of KRAS. I'd love to kind of get your thoughts as to how you're thinking about it. As a follow-up, I probably missed it in the poster, but how many patients remain on treatment, and kind of what's the median duration of response? Any comments on resensitization of patients who are refractory to KRAS monotherapy? Thanks. Mollie, do you want to take that second question first, and then I can address Ren's sort of broader question? A good amount of the patients still remain on treatment as of the time of this data cut. Almost all of the pancreatic, all but one, are still on treatment. 37% of patients overall are on treatment. They're doing very well. Not just deep responses, but actually durable responses. We are seeing, these are small numbers, my statistician would kill me if I gave you true median duration of responses, because they're so unstable to actually estimate. For non-small cell, we have seen about at eight months. PDAC is still evolving in four months. These are still evolving numbers, but they're already starting to exceed what we would expect from the background therapy alone. Stay tuned. We'll discuss more as we get more data. Yeah, Ren, to your first question, there's no accident that that second box in the platform study is darlifarnib plus compound A in colorectal. There's a clear need. I think we all recognize it's likely to be a triplet. One of the advantages you have with darlifarnib is it combines nicely with EGFR inhibitors. There was a trial run with tipifarnib and Tarceva, for example, was run in the wrong patient population, but there was good safety and tolerability. Part of this is we're juggling kind of what we can do internally with the folks who are approaching us, but colorectal is of high interest, both for MEK selective inhibitors and for pan-RAS inhibitors. We'd like to find a way to move darlifarnib further along in that area for sure. Thanks for taking the questions. Sure. Your next question will come from Daniel Brims with Lake Street. Your line is open. Please go ahead. Thanks. Thanks for taking the question. Just curious what you saw or didn't see in the eight mg dose that you decided not to push that forward? Thanks. Sure. Mollie, do you want to take that? Yeah, sure. Obviously, every protocol has its defined toxicity limits. While we didn't see any drug-drug interaction between the two molecules, as we got into the higher doses, we did start to see some overlap of the neutropenia, and that was simply we reached a level that we didn't think the benefit outweighed the risk enough to keep pushing it forward. Overall, it wasn't any different safety profile. It was just we felt that three and five were the more tolerable options and still efficacious. Thank you. Yeah. Dan, as a reminder to everyone, you don't mitigate toxicities in a phase I-A dose escalation. The whole goal is actually to understand the tolerability profile. As Dr. Hong indicated, many of these are clinical values, and they can be mitigated as we go forward, but for the dose escalation, that wasn't possible. As Mollie said, the benefit risk didn't justify going forward at eight, but either three or five, as you can see, are very active. The only one tolerability or toxicity that I think we have to watch for is neutropenia. We've now been able to combine FTIs with cabozantinib, with alpelisib. Previously, J&J combined with both chemo and a couple of targeted therapies. There's a very broad combinability. You do have to watch for neutropenia. All right. Thank you. There are no more questions at this time. I'd now like to turn the call over to Troy Wilson for closing remarks. Thank you, Megan. Thanks, everyone, for joining the call today. We're at a really exciting inflection point with this daralfernib program. Apologies that we couldn't corral Dr. Hong for longer. He had patient obligations, which obviously have to take priority. You can hear from his comments the enthusiasm around both the daralfernib combination and other combinations. He's been a tireless advocate for this program. Sounds like a number of you have relations with him and would invite you to engage with him as you will. We will come back to you in about a week with another update back on our ziftomenib program and the frontline AML results out of EHA. That will be one to pay attention to. Those results, I think, are very encouraging for the potential for ziftomenib to drive clinical benefit in a frontline setting. Mollie will walk you through what that data means for the ongoing intensive chemotherapy arm in the KOMET-017 study. We'll look forward to talking to you again then. If anyone has additional questions, you can reach out to me or Greg, and we're happy to get back to you. We appreciate your time. We appreciate your interest. With that, we'll conclude the call. Thanks, everyone.