Good day and thank you for standing by. Welcome to the Kura Oncology discussion of FTI clinical data at the ESMO 2025 congress. At this time, all participants are on the listen-only mode. After the speaker's presentation, there will be a question-a nd- answer session. To ask a question during the session, you will need to press star one one on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star one one again. Please be advised that today's conference is being recorded. I would now like to turn the conference over to your first speaker, to Troy Wilson, President and CEO of Kura Oncology. Please go ahead. Thank you, Dulum. Good morning, good afternoon, good evening, everyone. As Dulum mentioned, I'm Troy Wilson, Kura Oncology's President and Chief Executive Officer, and it's a pleasure to have us here with you today to review our farnesyltransferase inhibitor program and, in particular, our clinical updates from ESMO 2025. This is the second in a two-part series. The first part was a discussion of the preclinical data and rationale, which was presented on September 16, last month. For those interested, that webcast and those slides are available on the Kura Oncology website. If we could please go to the next slide. In today's presentation, we're going to be making certain forward-looking statements. I would refer you to either our website or to the SEC's website for more information about the risks of an investment in Kura Oncology. If we could go to the next slide, please. Slide three, today's agenda. We're going to be reviewing each of the three data sets that are shown here. First, we'll discuss the KO-2806 monotherapy data in advanced HRAS-mutant solid tumors. Then we'll talk about the combination data of FTIs and TKIs in renal cell carcinoma. Finally, we'll conclude with a discussion of the combination of FTIs and PI3Kα inhibitors in PIK3CA-mutant head and neck. We expect that the prepared remarks should take about 30 minutes or so. There should be plenty of time for a Q&A session at the end. If we could go to the next slide, slide four. The participants in today's call, in addition to me, include Dr. Mollie Leoni, Kura's Chief Medical Officer, and then we're very pleased to have with us Dr. Glenn Hanna. Dr. Hanna is Director of the Center for Cancer Therapeutic Innovation. He's a medical oncologist with a specialty in head and neck at the Dana-Farber Cancer Institute. He's also an Associate Professor of Medicine at Harvard Medical School. Dr. Hanna has been an investigator both with Tipifarnib and KO-2806, and he'll be presenting the data on the HRAS-mutant solid tumors as well as the PIK3CA-mutant head and neck data. If we could go to slide number five, please. In our call on September 16, last month, we introduced to you for the first time KO-2806 in the context of preclinical data. Now we're going to follow that up with the clinical data. Notably, with KO-2806, we took all of the lessons of Tipifarnib as well as the other FTIs. We tried to improve everything that we could. As you'll see, darlifarnib is an extremely potent, well-behaved molecule. We have efficacious doses that are in the single-digit milligrams with anticipated daily dosing, excellent drug-like properties. Of course, this is a novel chemical entity, a new chemical entity, excuse me, and so it has an appropriate patent estate. We're hoping it really forms a foundation for which we can now advance this concept of using FTIs as a companion therapy to various targeted therapies. As an introduction, let's talk a little bit about the data that gave us confidence, really, that darlifarnib was giving us what we expected and what we wanted to see. With that, if we can go to slide six, I'm going to turn it over to Dr. Hanna. Glenn? Thank you, Troy. As stated, I think the first step is to talk about darlifarnib or KO-2806 as monotherapy in advanced HRAS-mutant solid tumors. This data is being presented in the poster session at ESMO this weekend. On behalf of my co-authors, it's a pleasure, and my colleagues here, to present the data to you. Next. KO-2806, or DARLI, the mechanism of action for monotherapy is described here. Just a reminder that in post-translational biology, we know that prenylation is an important process whereby different carbon chains, like little strings, are attached to the ends of proteins and flag them for localization to the surface of the cell. This is a key process, right? The signaling process requires farnesylation. This is just based on the number of carbons that are added to the end of a molecule to localize it. This can be important in oncogenic and cancer signaling. We know that HRAS and Rheb depend solely on farnesylation. There are other forms of prenylation, like geranylgeranylation. Don't get mixed up with these names. It just implies the number of carbon chains that are added, whether it's 10 or 13, like a little tail to the end of proteins. This has important implications for how these are handled and how cell communications occur. Importantly, HRAS and Rheb, as we said, solely focus on this farnesylation function, whereas other RAS isoforms, which are a little bit different, are using a different carbon attachment mechanism and enzymatic process for their cleavage. This offers an opportunity to target HRAS-mutant tumors. We know from the Tipifarnib experience that they're sensitive to these FTIs. Tipifarnib has very well demonstrated encouraging clinical activity in patients with HRAS-mutant tumors. Darlifarnib, as we heard from Troy, is a next-generation, hopefully best-in-class optimized version of farnesyltransferase inhibition that offers enhanced potency. It has optimized pharmacokinetic properties. Importantly, it's a small molecule with even single-agent activity that has the ability to improve outcomes. You can see on the cartoon at the right, by blocking this important process in HRAS and Rheb, we disrupt the downstream signaling cascade that allows cancers to grow through the MEK/ERK pathway. FIT-001 is a monotherapy study design that looks at first-in-human multicenter open-label usage of KO-2806, or darlifarnib, alone, but also in combination, as we'll hear soon, in a number of advanced solid tumor types where preclinical data is supportive. KO-2806 monotherapy was conducted in RAS-altered solid tumors. We included HRAS-mutant and highly amplified. Generally, cutoffs around 6- 12 are used, but that can be a point of discussion. HRAS overexpression in head and neck squamous cell carcinoma was permitted. In non-small cell and colorectal, we did allow other RAS isoforms, like NRAS and KRAS, primarily because it's never perfect in science or in biology. There is farnesyltransferase use in some of the other RAS isoforms. It's just not preferential. There was a rationale in the dose escalation to get data quickly and to expose patients with KRAS and NRAS to the darlifarnib compound. This was administered orally, once daily on days 1 through 7 and 15 to 21 in a 28-day cycle. On-off dosing, one week on, one week off. This data cutoff that we'll share is as of August 15. You can see the dose levels on the right, starting at 3 mg daily dosing up to 15 mg as an estimated sort of cap point. We'll walk through that in the dose escalation. We did anticipate monotherapy activity based on the Tipifarnib experience and the potency of this molecule. Here are the baseline characteristics and demographics of the population. From left to right, showing you monotherapy dosing, 3 mg sequentially all the way to 15 mg. No need to read the entire slide. As a clinician, this is balanced for what we would expect in this population. We see a proportion of men and women. The median age is on par. There is a larger proportion of white patients, and that's typical for the epidemiology of the disease we see with head and neck mucosal disease, as well as an important point about the primary tumor opportunity here. You can see head and neck was an important enrolling tumor, as well as salivary gland and thyroid. We also had some colorectal patients, GI with pancreas represented. I think the other important point is prior lines of therapy. These patients were heavily pretreated, and that's impressive when you start thinking about monotherapy activity for a novel agent, with some patients between 30% and even 60% in dose levels with more than three lines of treatment. Of course, HRAS alteration is highlighted at the bottom across each of the dose ranges as well. Importantly, we see that KO-2806 demonstrates encouraging safety and tolerability. This is on brand with what we experience in the clinic with the Tipifarnib population. This is really a clean molecule. I think the point I would make here as a drug developer and someone who leads a portfolio of more than 60 oncology drugs in development in solid tumor oncology, this is one of the easiest drugs to dose in clinic. You have very predictable and manageable cytopenias. You can see there rates of treatment expected AEs in terms of neutropenia and anemia and even thrombocytopenia. Most importantly, at the bottom in the blue chunk is the grade three or greater treatment emergent AEs. You're noticing that in the dose range of interest, the sort of optimal range between 3 and 8 mg, we're seeing manageable and modest rates of neutropenia, anemia, and minimal thrombocytopenia. These other points of interest, like fatigue, mild nausea, this is impressive for what you'd expect from contemporary small molecule inhibitors, which are plagued with a lot more issues related to rash, dosing disruptions, and GI toxicity. Again, it's a pleasure to work with this class of drug like it was with Tipifarnib. We were happy to see an encouraging safety profile for darlifarnib. In terms of monotherapy activity in patients with HRAS-mutant solid tumors, this is an important slide showing you that there's a number of tumor types represented. This is a tumor-agnostic and molecularly selected compound for HRAS-altered patients across a number of different HRAS mutants and hotspots. We saw, for example, stable disease with tumor regression and even partial responses with maximum tumor regression in hard-to-treat tumor types across the 5 and 8 mg dosing range. As we heard, much lower doses, a more narrow but importantly focused therapeutic index where there's potency at low dosing. We even see a hint of durability at that 5 mg with patients staying on beyond 20 months in some cases at data cutoff. This was very encouraging, right? I think as a drug developer, we want to see excellent tolerability. Now we're demonstrating in a molecularly selected population monotherapy activity. That's exactly what we expected with darlifarnib. Here's just a clinical case example showing deep and durable response. One of the comments we often get is, oh, you're just shrinking tiny tumors down to smaller size. Not in this case. You can see examples of upwards of 4.5 mm of disease decreasing by a large percentage in this case. In this case, it's a salivary gland cancer, heavily pretreated, excuse me, heavily resected and radiated patient with upfront surgery who had a very difficult-to-treat disease that has no standard-of-care options. With this molecularly targeted agent, had a confirmed PR exceeding 60% and continues on treatment at week 80, well over a year. This is actually one of my patients. She's thrilled to have gone on to this study and remains, I can say, even to this day, still in response and doing very, very well. That's really important, right? A lot of drugs are plagued by the inability to dose consistently, the inability to demonstrate that resistance is not developing. This is proving on-brand mechanism, good tolerance, and durability. That's what we want to see with novel agents. Here's another example of a deep and early response in a fourth-line patient. That patient had come out as a first-line or early patient with HRAS targeting. We're talking about someone who's already had chemoimmunotherapy with advanced head and neck cancer, has already had EGFR modulation, and now in the fourth line, look at this. This is locoregional disease. It's been radiated. It's hypoxic, fibrotic. This drug is breaking through and causing locoregional regression from 6.8 - 2.7 mm. That is drug activity. That is monotherapy impressive activity with a nice 60% response rate in this case, which is excellent. In summary, darlifarnib has demonstrated a manageable safety profile, no new safety signals, excellent tolerability with a Q-day or once-daily dosing schedule in weeks on and off alternating. We see encouraging monotherapy activity observed at multiple dose levels in that 3 - 8 mg range in HRAS-mutant solid tumors, which span a number of different hard-to-treat cancer types, as well as some more common tumor types like head and neck cancers and mucosal disease. We see on-target activity through that broad therapeutic range. These data definitely further support evaluation of this compound and make it an optimal partner for a number of different small molecules. I want to remind people that what's been very challenging with many small molecule inhibitors is that the time when you start combining, you get dose-limiting toxicity. I'll point you to examples of CDK4/6 combinations. You name it, with MEK and ATR inhibitors, all of these new glamorous drugs, it's very, very difficult to envision combination and tolerance. This drug is delivering on that account. It's really exciting to see this drug move forward. Mollie is going to talk to us a little bit about some of the emerging data in RCC with Cabozantinib. Yes, thank you so much. If we want to go to the next slide. I'm really happy to share our Cabo combination data that were actually shared earlier today at ESMO. I might like to add, received the Best Poster Award in the session. We're very proud of our FTI, KO-2806, in combination with Cabozantinib and renal cell carcinoma. Our data today was presented by one affectionately known as Dr. A. As we and others have been emphasizing, an overactive mTOR pathway signaling drives cell growth, proliferation, and survival in RCC tumors. Rapalogs block this pathway and are FDA approved in RCC, but have seen limited use because of tolerability issues, as Dr. Hanna was just quoting. As seen on the right, Cabozantinib offers clinical benefit to these RCC patients, where you see around a 25%- 28% expected ORR in this particular line of therapy and stable disease approaching 60%. However, this is limited activity, and we see reduced activity with subsequent TKIs, which underscores the need to optimize these VEGF-targeted therapies. KO-2806 inhibits farnesylation of Rheb, which uniquely inactivates mTORC1. Additionally, KO-2806 enhances Cabozantinib antiangiogenic activity in both endothelial cells and pericytes in RCC xenografts. Thus, we tested this combination in RCC patients. Next slide. This is our FIT-001 trial. In addition to the monotherapy that was just described by Dr. Hanna, we are evaluating combinations as well. It is a first-in-human, phase I, open-label trial studying KO-2806, both alone and in combination in advanced solid tumors. The KO-2806 plus Cabozantinib combination, we enrolled specifically patients with renal cell carcinoma, either clear cell or non-clear cell. For the dosing, the KO-2806 was dosed at 3, 5, or 8 mg once a day in one week on, one week off, plus the continuous dose of Cabozantinib. We We started at 40 mg, and we're soon able to escalate to 60 mg. This is also given every day in 28-day cycles. Just as a reminder, this is data as of the 15th of August data cut. We've enrolled over 50, close to 60 patients as of this data cut. As you can see, clear cell was, and there's similarly with the baseline demographics here, there's nothing of great surprise with the types, ages, or performance status of patients that were enrolled into this. I'm just going to draw your attention to a few things. As you can see, clear cell was the majority of patients that were enrolled. The initial portion of the study was well dominated by patients that were prior Cabozantinib exposed. That's your 40 mg patient population, while earlier line patients dominated the 60 mg cohort. Please note that the 3 mg plus 60 is still enrolling, which is why you're seeing lower patient numbers in that particular cohort at this time. Next slide. The combination has been well tolerated to date. No apparent overlapping toxicities have been seen. We really see the safety profiles of each individual agent as if given alone. Next slide. As a reminder, in this patient setting, we would expect to see maybe a 25%- 28% response rate with Cabozantinib as a monotherapy. We'd expect a 0% response rate for KO-2806 alone. We first filled the 40 mg cohorts, and at that dose, saw encouraging activities with consistently a 33% response rate overall and activity even in prior Cabozantinib failures. Of the patients that had cleared efficacy evaluation period at the 60 mg, preliminary data is demonstrating about a 50% response rate in the 5 mg combination. Again, those patients were enrolled first. The 3 mg and 8 mg are currently maturing data and were not sufficiently mature at the time of this data cut to share. We look forward to sharing them in the future. Next slide We are definitely encouraged by the overall activity we're seeing. Here, the 40 mg Cabo patients are the hash-marked patients, and those with prior Cabo exposure are marked with stars. Our non-clear cell patients are also included in this particular figure. As you can see, there are consistent decreases in tumor size across doses and subtypes, which is highly encouraging. It appears as we've gone up in the Cabo dose, we are seeing increased efficacy. Obviously, we are still evaluating those patients in these combination settings. Next slide. Just to highlight a patient's experience, this is a 61-year-old male with clear cell. Previous treatment included pembrolizumab in the adjuvant setting, and the patient came on trial in stage IV disease. After eight weeks, the patient had experienced a partial response that actually deepened by week 16, and this patient remains on trial as of this data cut. Next slide. We've previously shown you preclinical data on RCC xenografts that were non-responsive to monotherapy TKIs, but that were then responsive to the combination. The results support a potential sensitization to Cabo therapy with the use of this combination. If we move to the next slide, we are actually also seeing this on study in our patients. This is a 53-year-old with clear cell renal cell carcinoma with two prior lines of therapy, the most recent of which included Cabo. This patient enrolled at our Cabo 40 mg + 3 mg, the lowest dose of KO-2806, and the patient quickly obtained a partial response that has been very durable. In fact, this patient is almost going on a year since the time of data cut, again, after just having failed Cabozantinib therapy in their most immediate prior line. Next slide. What messages should you take away? KO-2806 and Cabozantinib have a manageable safety profile, which is the most important, and that's across dose levels tested for both drugs, as we were able to explore multiple dosing levels of both drugs. The antitumor activity of KO-2806 and Cabo in combination was observed across all doses, including among patients with prior Cabo exposure. We were seeing an ORR of 33%- 50% in clear cell. If they had had prior Cabo, we saw 17%- 50% responses, and a disease control rate was extremely high, as one would expect, but maybe even a little bit increased over Cabo alone, around 80%- 100% in the clear cell renal cell carcinoma. The activity of KO-2806 and Cabo combinations really does support the hypothesis that KO-2806 is able to enhance this antiangiogenic activity of Cabozantinib and supports our further development in this space. With that, I will pass it back to Dr. Hanna. Yeah, so we're going to go a little back and talk about farnesyltransferase inhibition with Tipifarnib because the program from the current trial predates the enrollment of the dose escalation and experience with darlifarnib. This was a combination study, as we'll talk about, with a PI3K-alpha selective inhibitor in head and neck cancer. Really, dual-targeted oral small molecule inhibition or targeted therapy in head and neck. This is the current trial in head and neck, tipifarnib and alpelisib in recurrent metastatic head and neck squamous cell cancer. This was a phase I study. Just to remind us that the FTI mechanism of action, we talked about this, really targets that HRAS and Rheb farnesyltransferase interaction and flagging proteins, or carbon chains, I should say, on proteins for localization. What we learn, and as all of you know, is that mechanisms of resistance are significant. One pathway that's upregulated or altered in a co-adaptive mechanism is the PI3K/mTOR/AKT pathway. A number of preclinical experiments and data from different tumor types has shown that blocking one of these pathways can lead to analogous upregulation or sort of adaptive upregulation of the alternative pathway. We see this a lot in oncology as we understood resistance mechanisms. The preclinical data supported that we would want to use farnesyltransferase inhibition to suppress that upregulation of MAPK pathway signaling and mTOR feedback reactivation. This was really strong preclinical rationale for combining these two small molecule targeting agents. That was the basis of the current head and neck study design, which tested both Tipifarnib in combination with alpelisib in PI3K altered or PIK3CA altered mutated or amplified recurrent metastatic head and neck patients. As it should be familiar, we used Tipifarnib in its typical schedule on days 1 through 7 and 15- 21 with weekly on-off dosing. Alpelisib, however, based on the label and experience from breast cancer, was once daily dosing. Together, this was given in monthly cycles. I have to say the BLRM mechanism to understand safety and tolerability was an important part and an elegant part of this design where we incrementally adjusted the dose stepwise for each of the agents using an algorithm based on safety events observed at the prior dose level. This allowed us to understand the contribution of safety and potentially efficacy at different dose levels to combine these drugs safely. Additional patients were enrolled in the candidate optimally biologically active dose. You can see here we started at tipifarnib 600 mg total dosing daily. Remember, Tipifarnib is a twice-daily medication, so that would be 300 twice daily plus 200 of alpelisib. You can see we escalated based on safety and efficacy observation to land on two potential dose levels, dose level 2, where we enrolled 16, and dose level 4, 17 patients. You can see we achieved doses of 1,200 mg per day, or 600 BID, if you will, of Tipifarnib and alpelisib at the 250 mg daily dose. In terms of safety and tolerability, this was one of the main focuses of this phase I trial, again demonstrating the important power of an FTI for combinatorial potential given its very predictable and well-tolerated safety profile. Even with alpelisib, a drug that has evidence of some hyperglycemia, some maculopapular rash, and some electrolyte disturbances and lipase elevation, we were able to safely get up to 250 mg daily and maintain tipifarnib at the 1,200 mg total daily dose in dose level 4. This was very encouraging from an investigator standpoint, again resonating the point that combinatorial opportunity has high potential with the FTIs that Kura Oncology is developing. Moving forward to activity, we saw encouraging antitumor activity for this combination in patients with alterations or hotspot mutations in PIK3CA. This is showing you the objective response rate. What was most impressive is when we were in the optimal dose range of interest, particularly at dose level 4, where safety was not much greater, we saw at the 1,200 and 250 respective dosing of these drugs, almost a 50% response rate. That's pretty impressive. Keeping in mind these patients have already been treated with platinum. They've already failed immunotherapy. In many cases, we were allowing patients in later lines, as I showed you with the darlifarnib experience. We have good safety and at an optimal biologic dose, we have a very encouraging ORR. In a prior study, just a reminder that alpelisib monotherapy has been explored in PI3K altered patients. We're talking about response rates approaching 0%. This is impressive activity proving our hypothesis. Median duration of the objective response, I do want to point out, those numbers are impressive, the high end reaching 20 months in some cases. Again, we're seeing that durability, patients staying on for long periods of time, and very nice disease control rates, particularly at that dose level 4 in complement to our response rates around 47%. Tipifarnib enhances the activity of alpelisib in preclinical models that I believe you've seen before. It's important to show that Tipifarnib does inhibit mTOR signaling rebound that's observed with alpelisib when dosed alone and that that combination does allow for deep regression. We saw that in CDX models but are now demonstrating that in patients. Next slide. This is just an example of a deep response in a patient treated with the combination. You can see their imaging on the left. This was a 36-year-old HPV positive, never smoker. I do want to point out that PI3K alterations are common in HPV positive patients, which is the majority of patients we're seeing in practice these days in some instances, given the trends in smoking and the epidemic of HPV. It's about a 30% rate of hotspot alterations in this pathway. This patient was pretreated with immunotherapy, a novel vaccine, and had an R88Q mutation, which is generally sensitive to PI3K, and had an 80%+ reduction at four weeks. That's rapid disease control in distant metastatic disease with durability exceeding a year, exactly what you want to see in a dual-targeted therapy combo. These deep responses, here's another example. Again, tough to treat locoregional disease, heavily pretreated with radiation. We said this is a hypoxic and fibrotic environment. This combination is doing a nice job to overcome resistance of platinum and immunotherapy in this 75-year-old patient with PI3K mutated head and neck cancer. This was a rapid regression. This was one of my patients who was immediately able to avoid a feeding tube and get back to swallowing with minimal dysphagia once they were able to start the combination. This was an impressive response in a difficult-to-treat tumor location for head and neck. Putting this together in the Tipifarnib alpelisib experience for PI3K mutant patients with head and neck cancer, we see, I would say, very nice tolerability and a very manageable safety profile where many combinatorial pairs have failed in the past because of overlapping tox. We see robust antitumor activity, fast regression, heavily pretreated patients, and nice deep responses with evidence of durability, as shown at that 250 mg daily alpelisib dose and in dose level 4, 1,200 mg daily or 600 mg BID of tipifarnib. These data really do support that the mechanism has been addressed in this adaptive resistance scenario and really speaks to the power of this drug in combinatorial states going forward. We are very happy to see this data and happy to share it. I think the next steps going forward is probably where we will focus before opening it up to questions. Sure. Obviously, we're very encouraged by all of these data that we have seen thus far. Our next steps for the darlifarnib, the name for KO-2806, is to obviously complete the escalation of our combination in renal cell carcinoma, so our Cabozantinib combination. We're going to be conducting a phase I study for KO-2806 plus Cabozantinib and using that combo to determine our optimal biologically active dose and select our recommended phase II dose. We will be completing dose escalation for the KO-2806 plus Adagrasib in KRAS G12C-mutant patients that either have non-small cell lung cancer, colorectal cancer, or pancreatic cancer. We plan to develop data generation options for darlifarnib plus a PI3Kα inhibitor as well in the future in solid tumors. We're also looking to be able to share additional data, hopefully next year. That'll be updated data, of course, for the renal cell carcinoma, the Cabozantinib arm, but also the preliminary data, which we're also very excited about for the KO-2806 plus Adagrasib. With that, I'd like to pass it back to Troy. Thanks, Mollie. If we can just go to the next slide, the large potential opportunity. As you've heard, one of the pleasant surprises is that the FTIs combine well with each of these targeted agents. While we're not showing you the combination today with Adagrasib, we are encouraged there again by the ability to combine darlifarnib with a KRAS G12C inhibitor. Importantly, as we showed you with the preclinical data, if this mechanism works with one drug candidate, it likely works with the entire class. That is both an opportunity and a challenge. The way that we think about darlifarnib and FTIs in general is they're making good drugs better. They're driving better outcomes for patients. That's what's giving us this large total addressable market here of greater than 200,000 patients across all potential indications. There's a lot that we can do. We have to have a thoughtful development strategy. We have to have a thoughtful collaboration and business development strategy. We'll have much more to say in the months ahead. With that, we'll conclude the prepared remarks. We're preparing to open it up to questions. I will say, based on the feedback that we got from our last presentation, we're going to do this one a little bit differently. We have a long queue of people who want to ask questions. I would ask those who want to ask a question to please just ask one question. We're going to try to get through everyone. If there's time, please feel free to get back in the queue. You can ask additional questions. We want to make sure that everyone gets an opportunity to ask a question. With that, Dulum, we're happy to turn it over to you for the Q&A session. Thank you, sir. As a reminder, to ask a question at this time, please press star one one on your telephone. To withdraw your question, please press star one one again. We ask that you please limit your questions to no more than one. Please feel free to go back into the queue. If time permits, we'll be happy to take your follow-up questions at that time. Please stand by while we compile the Q&A roster. I share our first question. It comes from the line of Jonathan Chang. Please go ahead from LeeRink Partners. Hi, guys. Thanks for taking my question. On the Cabozantinib combination data, can you give us a sense of what the duration of response and/or time on treatment metrics look like? Is there anything you can comment on there? Is it still too early? Thank you. Mollie, would you like to take that? Sure. Thankfully, it's still a little bit too early, especially because I think we're going to be seeing the selected dose come out of your 60 mg cohorts, so Cabo cohorts. I'd say stay tuned. We're not disappointed thus far. We've had patients stay on for significant periods of time. It's still time for some—let the data mature. Like I said, we'll present more next year. Thank you. I share our next question in the queue. It comes from the line of Charles Zhu from LifeSci Capital. Please go ahead. Hi, this is Peter Green on for Charles. Congrats on the data. Just a question on patients treated with Cabozantinib and darlifarnib. Any color on whether those 4 of 12 responders that had had prior best response of stable disease, whether they stopped Cabozantinib due to progressive disease or for some other reason, like toxicity? Of those 12, did any of them have progressive disease? I guess how many on Cabozantinib? Thanks. Mollie? Yeah, sure. Their best response tended to be stable disease, and they would come off usually for progression prior to coming on to our treatment. As we said with that one patient, their best response had been stable disease, and then they were losing control when they came on to the combination. I can't give you the details on every single patient with prior Cabozantinib. We saw some stable disease, and we saw at least two partial responses that looked very good thus far. I think let's look towards these individual cases and the data we plan to develop even more in the future. We certainly are seeing, like I said, anywhere from 17%- 50% response rate in prior treated Cabozantinib patients that are receiving the combination. The other point I would just make about that is you'll notice we were able to go up to 60 mg of Cabozantinib in combination. If patients had come off for safety issues, we wouldn't be getting to 60 mg. To Mollie's point, it was a progression issue, not a safety issue. Thank you. I share our next question in the queue. It comes from the line of Reni Benjamin from Citizens Bank. Please go ahead. Hey, thanks, guys, for taking the questions. Congratulations on the combination data. I guess my one question, and maybe it's for Dr. Hanna, is you know how do you view these combo results when compared to, let's say, the HIF2 alpha plus Cabozantinib combinations? Any sort of color would be great. Thanks. I think the HIF2 alpha story is still evolving. Certainly, there's a difference in toxicity profile. I do think seeing combinatorial potential around even that window that Mollie shared was 33%- 50%. That's impressive. From my understanding of the emerging data with HIF2 alpha inhibitors, we're not necessarily seeing anything outside that ballpark. This would be equal or better. Yeah, just to add to that, the HIF2 alphas are focused, obviously, at least currently, on developing in renal. We do have a firm belief that wherever Cabo goes, we can go as a combination. We think that there is broader opportunity as well. Thank you. I share our next question. It comes from the line of Salim Said from Mizuho. Please go ahead. Hi, this is Eric on for Selim. Congrats on the data, and thanks for taking our question. Just eyeballing the waterfall plot on the Cabozantinib plus KO-2806, it looks like the prior Cabozantinib experience are kind of leaning towards lower responses. Just wanted to see if there's any color on that, how we should be thinking about that. Thanks. Yeah, I think it's tough for you to really be able to interpret because in addition to these patients being prior Cabozantinib pretreated, they're much more heavily pretreated if you look at the baseline characteristics for these patients as well. They've been through additional lines, and we're still seeing at least some tumor regression in these patients. You have to wonder, is it a function of having prior Cabozantinib exposure? Is it a function of having their disease hit in so many different ways by multiple different lines of therapy? Tough to interpret at this point. We hope to gain additional data so that we can answer that question a little bit more clearly. That will be part of our plans for our next phases of development. Thank you. I share our next question. It comes from the line of Li Watsek from Cantor Fitzgerald. Please go ahead. Hey, guys. Thanks for taking our questions. Very interesting data. I wonder if you can just comment on neutropenia, whether you have seen any febrile neutropenia, and whether this impacts the dose intensity of Cabozantinib? Maybe just more information on the dose modifications in the trial. Mollie? I would say I do recall, I mean, I can just speak to this more broadly. If there is the element of anemia that's a little more focused generally in the FTI mechanism and then some concern that neutropenia may play in as well, from my recollection of the RCC data, we didn't see any synergistic concerns around cytopenias or cytotoxicity issues that cause dosing problems. I'll again turn to the point that we've been able to escalate to the 60 mg dose of Cabozantinib in combination with DARLI, which speaks to the fact that neutropenia hasn't been a significant issue. We haven't had to turn to growth factor support or long periods of dose interruption. I can at least say that from the combo. Yeah, and I fully agree. We've seen limited dose reductions in the Cabozantinib. I do not think we've actually seen dose reductions in this particular combination in the KO-2806 as of yet. Overall, I'd say you're really just seeing non-cumulative tox. Thank you. I share our next question in the queue. It comes from the line of Phil Nadeau from TD Cowen. Please go ahead. Good afternoon. Thanks for taking our question. Congrats from us also on the data. Can you discuss in a bit more detail the design of the phase Ib of KO-2806 in Cabozantinib? In particular, what Cabozantinib patients will you be recruiting to the study? Will they be mostly Cabozantinib-naive, Cabozantinib-experienced, or a mix of the two? Thanks. Mollie, you want to take that? Sure. We haven't really released the details yet. Suffice it to say, this is going to be a very robust phase I study so that it allows us to not only select the dose that we think is probably best for this combination, but also to evaluate even more some of these potentials to resensitize patients to Cabozantinib. We're going to more than likely focus on the 60 mg Cabozantinib dose, which means that we're going to see fewer patients or no patients that have seen prior Cabozantinib in their treatment paradigm. We'll be getting more data out on that as the time comes closer. Thank you. I share our next question. It comes from the line of Jason Zemansky from Bank of America. Please go ahead. Good afternoon. Congrats on the data, and thanks so much for taking our question. I just wanted to hone back to the waterfall plot for the KO-2806 Cabozantinib combination. I appreciate it's still somewhat early, but it looks like the majority of responses here are from the 5 mg dose. Appreciating it's still dose escalating here, I'm curious, does that sort of imply that there's a saturation point on what you can get from a farnesyltransferase inhibitor in this case? Do you think if you could increase the dose meaningfully, you could see more responses? Thanks. Mollie, you want to take that? We certainly see a linear dose response curve for the PK. We're still evaluating. Like I said, the 8 mg, especially at the 60 + 60, is still ongoing. Let's give it a little more time for these data to mature so we can really understand what the 60 mg efficacy looks like. We understand what the 60 mg safety looks like. It doesn't look prohibitive for the dosing of these patients. Let's see what the efficacy turns out as we continue to fill these cohorts. Thank you. I share our next question. It comes from the line of Roger Song from Jefferies. Please go ahead. Great. Congrats for the data. Thank you for taking our question. Maybe just a clarification. In terms of the 60 mg Cabo combo cohort, since you are interviewing more Cabo-naive patients, I think, Mollie, you mentioned earlier, if you pick the 60 mg, you're more than likely going to focus on the Cabo-naive patients. I just want to confirm that moving forward for the phase IB and then the future development, you were focusing on the Cabo-naive patients. Thank you. Absolutely. We obviously haven't absolutely finalized the protocol, but yes, you're correct that we would probably be focusing on the Cabo-naive, so earlier stage patients, Cabo-naive patients. Thank you. I share our next question. It comes from the line of Peter Lawson from Barclays. Please go ahead. Great. Thanks so much for taking our questions and congrats on all the data. On the dose-response relationship for the combination with Cabozantinib, do you kind of interpret that as a flat kind of curve? Is this just still a reflection of limited sample size? Peter, I think your question relates to the 40 mg Cabozantinib with different doses of KO-2806, if I'm understanding correctly. Right. Thank you. The parallels are around 33%. I mean, I'll just say it's too small an N, I think, to draw any kind of conclusion. Interestingly, each of those dose cohorts is better than what you would expect from even Cabozantinib monotherapy. As Mollie said, we're not probably going to spend a lot of time optimizing at a 40 mg dose. I think it's encouraging. Mollie, you should add your thoughts. No, that's exactly right. We're not going to spend too much time optimizing the 40 mg. When we refer to that 25%- 28% response rate of Cabozantinib monotherapy, we're referring to the 60 mg dose. The fact that we're seeing these 33% in previous Cabozantinib failures implies that things are certainly going in a better direction than one would expect for either therapy alone. I still think it's small numbers, but we will continue to update the data. Yeah, maybe I'll just add before we prompt the next question. One of the things that gives us confidence, again, as we look across these different tumor types is, you know, this goes back to the way that Dr. Hanna laid it out. Is TORC1 pathway reactivation the key mechanism of action? As you look at both the RCC data and the PIK3CA mutant data, and of course, you're not seeing the KRAS data, but hopefully, you will next year, that's what gives us confidence that we're onto something significant here, that we've known that TORC1 is a validated clinical target. This may just be a much better way to inhibit its activity. I will say before we take the last question, if anyone else would like to ask another question, please get back in the queue. We have time for just a few more questions. Dulum, over to you for the next question or two. Thank you, sir. As a reminder, if you have a question at this time, please press star one one on your telephone. Thank you. I share our next question in the queue. It comes from the line of David Dai from UBS. Please go ahead. Great. Hey, thanks for taking my questions and congrats on the data. For the Cabo combo, we did see pretty good safety with no overlapping toxicity. We did see slightly higher levels of diarrhea at 60 mg Cabo dose. Maybe a question for Dr. Hanna. From a clinician's point of view, what do you think about the rate of diarrhea in this combo? How do you typically manage them? Yeah, I mean, I think as Mollie or Dr. Leoni alluded, we're not seeing an uptick in these types of side effects. It's on par with what you would expect. We don't generally see a lot of GI toxicity by partnering with darlifarnib. Whatever we are seeing in the RCC cohort at 60, which is small numbers at present, is going to be from the Cabo alone, just given its mechanism of action. Because these drugs have been around for some time, these are generally manageable and predictable side effects. You would give someone Imodium or Lomotil, encourage them to take magnesium and hydrate. I can't say that having seen the data that I've been to date, that there's been any concern that there's enhanced GI tox. That has not been my observation. Just to keep in mind, a lot of the data you're seeing is from the dose-limiting toxicity period where you don't necessarily prophylactically treat for a lot of these things that we would be able to treat for in quote unquote normal life or in later lines of our development program. I think that there's a lot of room for improvement in how we approach pretreating and prophylactically treating these patients once we're through this particular phase. Thank you. I share our next question in the queue. It comes from the line of Jonathan Chang from LeeRink Partners. Please go ahead. Hi, guys. Thanks for taking the follow-up. Maybe for Dr. Hanna, how would you compare your experience with darlifarnib versus tipifarnib? I know it's not apples to apples here given the differences in the settings. It would be great to hear your thoughts here. Thank you. Yeah, there's, you know, I think I highlighted in the earlier presentation of the escalation monotherapy data that they're both very well-tolerated molecules. I think the properties that were outlined by Troy initially and then the preclinical work and now in patient dosing exhibit that very nice activity level at a broad therapeutic range, but at low dosing levels and allows for a more predictable PK profile and PD that give us a once-daily dosing option. I think that's very important. Another point to make is that in our experience with salivary gland cancer, where we're seeing some patients, as I showed you, with durable and impressive partial response rates, I actually put together the tipifarnib salivary cancer population data a number of years ago. We weren't actually seeing, I think there was only one short-lived PR in that cohort. We're seeing more evidence of anti-tumor activity in comparable diseases with the darlifarnib sort of more modern FTI. I think for that reason, it's starting to become appealing as sort of a preferred agent, not just a me too. Thank you. I'm showing no further questions in the queue at this time. This concludes our Q&A. At this time, I would like to hand the conference back over to Troy Wilson, President and CEO, for closing remarks. Thank you, Dulum. I want to thank in particular Dr. Hanna for being generous with his time and his experience. He's been an incredibly valued partner from the very first days of our FTI program. We're at an exciting inflection point. I want to thank all of you for your attention and your questions. Glad we were able to get at least one question from everyone. We will be available for follow-up if people would like. You can contact Greg or me. We'll look forward to talking to you next time, at least at our next earnings call, which is for early November. We appreciate it. We hope everyone has a very productive and successful ESMO. With that, we'll conclude the call. Thanks very much. Thank you. This concludes today's conference call. Thank you for participating. You may now.