Kura Oncology, Inc. ($KURA)

Good day, everyone. My name is Jenny, and I will be your conference operator today. At this time, I would like to welcome you to Kura Oncology's 2026 IKCS Investor event. [Operator Instructions] 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.

Thank you, Jenny. Hello, everyone. Today, we're delighted to share with you some updates that were presented at the international kidney cancer center [indiscernible] over the next couple of days, [indiscernible]. This relates to our -- the ongoing study evaluating darlifarnib and cabozantinib in patients with kidney cancer. . If we can go to the next slide, please. In today's presentation, we're going to be making forward-looking statements I would refer you both to our filings and our website or SEC filings on our website for more information about Kura Oncology and the risks and uncertainties of an investment at this time. I'm joined on today's call by 2 participants. Dr. [indiscernible] is Assistant Professor of Hematology Oncology and Medical Director of the Gene Urinary Medical Oncology Research at Oklahoma Health Sciences Center. And also joining us today is Dr. [indiscernible] Kura's Chief Medical Officer. Both of them are going to be presenting slides through this presentation. This is an incredibly exciting and dynamic time at Kura. We are squarely focused on the launch of our first commercial product, KOMZIFTI, which was approved just last year in relapsed/refractory [indiscernible] mutant AML. We're looking forward to giving an update on how the launch is going at our earnings call next month. We're also broadening out the opportunity with ziftomenib or KOMZIFTI as it's known commercially to be able to treat up to 50% of AML patients. What we're here to talk about today is one of our pipeline programs. And we have a thesis at cure that cancer is best treated in combination. And we'll talk more about that today. But as you'll see with both our [indiscernible] inhibitors and our [indiscernible] transferase inhibitors we're advancing innovative therapies that I think have the potential to combine with other agents to really drive better outcomes for people with cancer. If we can please go to the next slide. So we call these precision combinations. And if we can go to the next slide. On the left-hand side, you can see the combinations that we're undertaking with ziftomenib. Many of these are familiar to you. We're, of course, evaluating ziftomenib in acute myeloid leukemia, both in the relapsed refractory and in the newly diagnosed setting. Now importantly, we'll be giving an update on the intensive chemotherapy combination in newly diagnosed patients middle of this year. we're looking toward a publication with the nonintensive chemotherapy combination to be published a little bit later this year. And then finally, we'll give an update on the [indiscernible] combination, specifically with gilteritinib in the relapsed/refractory setting. Our view is and always has been, while [indiscernible] inhibitors offer tremendous promise, we want to move them forward and move them into combination as quickly as we can. Continuing that theme, we've got ziftomenib in GIST. And we're looking forward potentially to an update next year for that program. On the right-hand side, if we can go to the next slide, we're going to focus today on our pipeline program, darlifarnib, which is just now beginning to come into its own. And specifically, as you know, we're evaluating darlifarnib in 2 contexts. Today, we're going to talk about the data combining darlifarnib with cabozantinib, which of course, is an anti-VEGF receptor inhibitor. A little bit later this year, we're looking forward to sharing with you the darlifarnib data in combination with adagrasib, which, of course, is a KRAS G12C mutant specific inhibitor, and there will be showing you data in lung, colorectal and pancreatic cancer. This idea of precision combinations is not new, but we think it's really the right way to go. If cancers use a number of different mechanisms to be able to grow and evade and metastasize everything from genomic instability, inducing angiogenesis, avoiding immune destruction. And our view is -- and our focus is to develop therapeutic agents that can combine with other therapies. If we go to the next slide, that's in fact, what we've seen in renal cell carcinoma, the evolution of treatments in kidney cancer. And Dr. A is going to speak to this as he goes through the data slides. But initially, the first approvals were with classical immunotherapy, then we saw a wave of tyrosine kinase inhibitors as well as mTOR inhibitors. Now increasingly, we're seeing doublets and triplets. And that's, in fact, where we anticipate darlifarnib will go ultimately is in combination, but we think it's important to demonstrate the mechanism of action and validate that as well as to get a sense of what is the safety, tolerability and activity as we think forward. [indiscernible] will be able to speak to this as she goes through our strategy building on this initial data. So if we go to the next slide, darlifarnib, as all of you know, is our next-generation [indiscernible] transferase inhibitor. We've been working on furnical transfers really since the inception of the company. Darlifarnib is as good as it gets as far as the furnace transfer inhibitor is concerned, extremely potent has great safety and tolerability. We took everything we knew about tipifarnib, and we optimized it. And we're really delighted. We did share some data, some early data from the Phase Ia study late last year. This is now an update of that data and ideally will provide yet another update here in kidney cancer a bit later this year. If we go to the next slide, these are the last couple of slides before I turn it over to Dr. A, what's the rationale here? Well, we know that cabozantinib and other tyrosine kinase inhibitor therapies block various signaling pathways. And in particular, they blocked VEGF receptor, but they also block PDG RF, they block other targets as well. TKIs are -- have become a mainstay of treatment in kidney cancer. They're used throughout the treatment continuum. The challenge is once patients once TKI therapy fails a patient the treatment either with the same TKI or another TKI or really any subsequent treatment is reduced. So there's a significant need to be able to either drive deeper, better responses or ideally to resensitize patients to treatment with these TKIs. If we go to the next slide, that's really where darlofarnib comes in. So darlifarnib acts in this context in renal cell carcinoma by blocking a protein called REV. REV is RAS homolog expressed in brain and the significance of REV is that rev controls the transport of TORC1. [indiscernible] is 1 of the 2 tour complexes that sit at the bottom of the MAP finance pathway. And when you defarnesylatEP can no longer get TORC1 to where it needs to be. So what that does effectively is it provides a second complementary blog on the signaling pathway. And each of the targets that these TKIs are targeting are signaling through these signal pathways. So one has the ability if we can go to the next slide. Once we introduced the combination, for example, of cabozantinib in darlifarnib, one can see you're blocking at the receptor level, you're also blocking down much further in the pathway. And the consequence, as we've seen both preclinically and clinically, is you get less angiogenesis and tumor death. We validated this. We have presentations available on our website and that have been put in the published literature on the mechanism of action and preclinical data with various combinations. I think it's important to generalize these results. What we're going to show you today is the specific combination of cabozantinib and darlifarnib. But what we've seen at least preclinically, is that these results are generalizable to any tyrosine kinase inhibitor. And as we talked about, we've been quite encouraged by the safety, the tolerability and the clinical activity that you're about to see. If we go to the next slide, I'm going to turn it over to Dr. A to walk us through the slides. These slides were presented by Dr. Sagaria, in a poster presentation at IPCS, but Dr. A is kind enough to present the slides and put them in the appropriate context. Dr. A, I'll turn it over to you.

Thank you. Good morning, everyone. My name is Adam [indiscernible]. I'm a geo medical oncologist at the University of Oklahoma. And on behalf of the FitOn team, I'm happy to present the data and give you a perspective on how things are moving along in this trial. Next slide, please. Briefly discloses all pertaining to research or consulting and advisory roles. Next slide, please. So the FIT trial is a Phase Ib dose escalation dose expansion study, and that evaluated both darlifarnib monotherapy and darlifarnib/monotherapy plus cabozantinib. . Now the darlifarnib in monotherapy, the dose escalation cohort who was not in [indiscernible] cell carcinoma, it was in predominantly RAS-mutated tumors. And what we found was that it was efficacious drug and also safe and the recommended dose for expansion was around 8 to 10 milligrams. We moved on to the dose escalation trial. And in this was when we combined it with cabozantinib and evaluated cell carcinoma patients. So this is the portion of the study that we're talking about today. And in order to evaluate the safety, we started off at a lower dose of cabozantinib at 40 milligrams, which is a lot more tolerable, but not as efficacious as the recommended dose, which is cabozanitinib at 6 milligrams. So the study started at darlifarnib at 3 milligrams escalated to 5 8 in addition to cabozantinib 40 milligram. And when that was considered safe and we did not meet our DLP, moved ahead to the second part of the study, which looked at the ideal dose of cabozantinib, which is 60 milligrams in combination again with escalating doses of darlifarnib between 5 and 8. Currently, the study has moved on to the expansion phase, where cabozantinib at 60 milligrams is being evaluated with darlifarnib at 5 and 8 milligrams. Next slide, please. In the dose escalation, our patients were a mixture of patients who are cabozantinib naive and cabozantinib assistant. But for this talk and the poster that's being presented by Dr. [indiscernible] at IKCS, it was focused on those patients who had been cabo exposed. All these patients had prior line of cabozantinib or some TKI during the course. About 67% of patients had exposures to other TKIs apart from cabozantinib and almost 56% or half of these patients had cabozantinib as their immediate prior line of therapy and all had progressed on cabozantinib. So about 26%, what we would consider cabozantinib refractory. Total sample size is around 18, a small population, but still an important population to evaluate pretty evenly distributed from all the different cohorts. But important to highlight that a predominant portion of this study includes patients about 15 of the 18 patients had cabozantinib at 40 milligrams, not at 60 milligrams. Next slide, please. Overall, the safety profile was pretty consistent and tolerable. And for the safety profile, we look at the whole dose escalation patients are just the cabozantinib had a refractory patients. Here, what we found was that darlifarnib was a pretty tolerable and safe regimen. Now if you look at any great TRAs, the most common ones were neutropenia fatigue in that area, but for the Grade 3 or more TRAs from darlifarnib, neutropenia and anemia were by far the most common. Now it's important to understand that while neutropenia has increased, it is an expected event from [indiscernible] transplant inhibition and it is also something that's easier to manage. So in comparison to the other side effects from cabozatinib which are discussed elsewhere in the poster, what we are showing here is that darlifinab did not add to the toxicity profile of cabozantinib and neutropenia, anemia and thrombocytopenia, while our TRAs are usually asymptomatic to the patient's perspective. So it did not lead to any significant deterioration in quality of life, which is very important in this patient population. Next slide, please. Overall, darlifarnib was well tolerated. There were obviously some dose reductions, predominantly due to cytopenias, predominantly neutropenia. There were introductions in about 60% of patients, but most of them were able to continue on it. 13% had to dose reduce the darlifarnib. A good portion we're able to go back without any discontinuation in the -- on dose reduction in the darlifarnib. Overall, the number of patients who needed discontinuation of darlifarnib was around 6 patients, so 470, so a pretty good number. In comparison, cabozantinib needed dose reduction in about 26%, cabozantinib needed to be interrupted in about 70% and to put it into context, other trials that have looked at cabozantinib like the recent [indiscernible] trial or the CONTACT-03 trial that cabozantinib as the control arm had about dose interruption about 90% to 100% of these patients. And we know cabozantinib that number longer duration is toxic and can have some As. So within that context, I think this is pretty reassuring in terms of the tolerability of darlifarnib and how we are able to manage the AEs that arise from it. Next slide, please. The clinical activity is pretty encouraging. What we noticed was that in these 16 patients, about 15 of them had disease control rates, so a disease control rate of [indiscernible] 94%. But what was even more promising is that the objective response rate in this population was around 4%. So to put it in perspective, these are patients who had prior line of cabozantinib about 60%, 56% to be precise and cabozantinib as the immediate prior line and had progressed on cabozantinib. And even among those patients, we had a good amount of response 4 out of these 7 responders, who at cabozantinib as immediate prior line of treatment had an objective response rate on this study. So in that context, pretty promising objective response rate of 44%. Next slide, please. What is even more interesting is that the objective responses that were seen on the study seems to be seen along multiple doses of the darlifarnib. You can see that darlifarnib by 3 milligrams also have significant partial responses and darlifarnib at 5 and 8 also follow. Now what's also important to understand is that most of these patients were on cabozantinib 40-milligram as depicted by those [indiscernible] and very few patients as in the solid bars were patients who had cabozantinib at 60 milligrams. Why this is important is that we know cabozantinib 60 milligrams has the better objective response rate than the 40 milligram. And it's interesting to see that this combination in the cabozantinib pretreated or cabozantinib refractory population still has considerable responses at the lower dose of cabozantinib at 40 milligrams, which is also the more easier to tolerate dose of the cabozantinib. Next slide, please. Duration of response is still evolving. We don't have a long-term follow-up as of yet, but it's important to note that many of these patients continue to respond. We have a follow-up of around 50, 56 weeks for the longest patient in this cohort. The responses do seem to be durable, but we will need to wait to see how durable these responses are in the long term. But what we are seeing is there a slow evolution of disease that goes from stable disease to partial response, some people with partial response pretty earlier on in the disease course. And what we have not identified is a long duration of stable disease before we see a response. At most patients had a partial response by the 8- to 10-week mark around the first couple of scans. But important to note that so far, the responses do seem to be durable, but long follow-up is required. Next slide, please. We'll highlight a couple of different patient vignettes for us to put this in perspective. This is an 80-year-old patient with [indiscernible] RCC diagnosed in 2022. Starts frontline treatment with nivolumab and cabozantinib with a best objective response of stable disease was on this treatment from around 2023 to 2025. initial study treatment was on June of 2025. So about 3 years after he was a nivolumab and cabozantinib. Get started on cabozantinib 40 milligrams and darlifarnib at 8 milligrams. And at week 8, he did have a partial response. We had 36% reduction at 8 weeks, and these responses seem to be durable and his last scan at 16 weeks shows a partial response with a [indiscernible] score 32%. So patient continues to remain on treatment, and this highlights that despite progression on cabozantinib as prior line of treatment, patients continue to respond at the lower dose of cabozantinib without significant side effects. Next slide, please. This, I think, is a little bit more relevant to the ongoing discussion. And here, again, another -- a younger patient, 53-year old female diagnosed in 2021, get started on frontline immune checkpoint inhibition doublets with nivolumab and cabozantinib progresses to nivolumab and cabozantinib, and this was done before we knew that IO beyond progression is not meaningful. And importantly, this patient AXA had HIF inhibition with Belzutifan, the FDA [indiscernible] inhibitor and she subsequently started study treatment in October 2024. What's important is that in this heavily pretreated patient population, prior IO doublet, prior cabozantinib and [indiscernible] hit inhibition. The darlifarnib at the lower dose of 3 milligrams and the cabozantinib at a lower dose of 40 milligrams, cost the PR about 38% reduction at week 8 and continues to evolve with a 53% reduction at week 48, indicating an ongoing response to this heavily pretreated population. So pretty promising responses, pretty good safe profile that as is got us excited about this normal combination. Next slide, please. This is a little bit exploratory. We always thought not to make cross-trial comparisons. But in oncology, we always end up making cross-trial comparisons, and this is one such scenario. Not to highlight the superiority of any such regimen, but to highlight the tolerability and the safety profile of these different regimens. There has been Phase II trials looking at lenvatinib abrolymas showing that they had better outcomes. There was a recent Len/cabo trial that was presented at ESMO last year that looked at lenabrolymus in a randomized manner. And importantly, the control arm on that trial was cabozantinib in a cabozantinib naive patient population. In that trial, what they did show is that cabozatinib injective response rate in a naive patient population was around 40%, and it was inferior to the superior objective response rate of lenvatinib relevance. So making big jumps. It's interesting to see that the combination has an objective response rate of 44% in a capital refractory population compared to cabozantinib monotherapy of 40% and odd responses in the naive population. But what's important to understand is that the safety profile seems to be a lot more tolerable. I would want to focus your attention on the second column, which is lenvatinib plus [indiscernible] and [indiscernible] inhibition combination doublet with PKI and the diluted combination to look at the different safety profiles. And what we are not seeing here is an increasing toxicity profile from the combination. We are definitely not seeing a significant amount of pneumonitis, apology and other side effects that we see with [indiscernible]. And so as demonstrated in the preclinical rationale, the selective mTORC1 modulation via the red pathway does seem to avoid set in side effects that we don't want while still retaining the efficacy that we want. Next slide, please. So overall, I think it is a very good combination that has a proven safety and tolerability profile. We will need to wait for a longer follow-up evaluate the durability of the responses, but it's important to highlight that even in this heavily pretreated population in this population of patients who are cabozatinib refractory. We had an impressive objective response rate of 44% with a disease control rate of about 94%. The study is now actively enrolling in the expansion phase, which is looking at capital-accretive patients in combination, and we're excited to see how the study will fit in the evolving landscape of RCC. Next slide, please.

All right. Thank you, Dr. A. And with that, I want to discuss the company's next steps. So these data are spectacular, and we have to ask ourselves what's next. We are currently in our dose refining Phase Ib. It is a randomized trial enrolling into 2 different dartly doses, the 5 and 8-milligram as well as a cabo monotherapy arm where pod progression patients can then roll over onto the darla combination. These patients will have [indiscernible] but be cabo naive and with no more than 3 priors. Endpoints will include response rate, durability and of course, safety. Going to the next slide. These data encourage us to move forward exploring second line plus and demonstrate a novel mechanism to add to the RCC armamentarium. We are currently enrolling into this randomized Phase Ib and expect to be able to share data next year. We are excited to be exploring option for the IO refractory patient population. There are limited options for patients that have progressed on IO HIF-2 alpha combinations and adding Darley to these combination backbones provides new options for patients. We recognize that the field is appropriately moving to combination approaches in the advanced setting. As HIF2 alpha continue to move towards the front line, we believe Daly combinations offer a potentially new way to address disease after failure of HIF-2 alpha. We believe that darlifarnib and cabozantinib have the potential as a combination to establish a new standard in IO refractory second-line plus clear cell renal cell carcinoma. And with that, I will turn it over to Troy.

Thanks, Molly. We'll go to the next slide. So as Molly said, we're really pleased with this data. This is just the first multiple data updates on our precision combinations. You can see them laid out here. It's going to be an eventful year. And from our perspective, we're just -- we couldn't be happier. We have a strong launch. We have outstanding execution on the Phase IIIs, and we have a lot of upcoming clinical data of these precision combinations that will help us figure out how do we position them in order to achieve the best outcomes for patients. In particular, I'll draw your attention to -- this is the kidney cancer side of the darlifarnib story. We expect to present to you the KRAS side of the story here before too long in the context of an upcoming major medical meeting. So with that, we can go to the next slide. We're happy at this point, Jenny, to turn it over and open it up for questions and answers.

[Operator Instructions] Our first question comes from Charles Zhou with Life Sky Capital.

Congrats on the data. Recognizing that these data are from about 4.5 months ago, and not that many patients were valuable at 60-milligram cabo combinations. Could you talk about the decision to expand at some of these 60-milligram cabo combinations. Maybe what you've seen. And is there a potential to see enrichment in response rates as you treat patients with these higher doses and potentially introduce prophylactic GCSF.

Yes, Peter, thanks for the question. I'm going to ask Molly to speak. You have a couple of subparts in there, but Mollie can take the question.

Yes. I just want to remind you that what we're showing you here are the patients that have already seen cabozatinib therapy. So it is not the full data set. And by the time we got to the 60-milligram portion of that dose escalation, we were not enrolling patients that had seen cabo previously. So that's why you see less data at the a 60-milligram combination doses. But while we present the updated Phase Ib data a little bit later this year, you'll see the full patient profile. So you'll see all the patients that were treated, and we'll be clear to you why we think that the 60-milligram dose with either 5 or 8 milligrams of darla makes the most sense. With regards to your safety-related question, now that we're done with the dose limiting toxicity portion of the trial, meaning we're done with kind of the initial dose finding and safety portion, we'll be able to do prophylactic treatment. So we will be able to use GCSF or give a transfusion, et cetera, in order to mitigate these events. So I expect patients to be able to stay on at least as long, if not longer, and again, continue to have an easier time on treatment because we'll be able to use prophylaxis.

Our next question comes from Jonathan Chang with Leerink Partners.

Maybe for Dr. [indiscernible]. Where do you envision darlifarnib fitting into the RCC treatment landscape? And how has that changed with HIF-2-alpha inhibitors? .

Yes. Thanks for the question. I think it's an important question, and it's something that's very promising from a treating kidney cancer dog because now we have a lot of options. But I think the landscape is evolving, and it's evolving really quickly. And we're going to change how we do stuff over the next few years. We have seen in the [indiscernible] 022 trial that looked at adjuvant therapy with inhibition, pembrolizumab plus [indiscernible]. We noted that are frontline trials looking at I-O combination with HIF-2 inhibition. There's also a triplet approach, IO plus TKI plus 2 inhibitors in the frontline setting. Triplet therapy in frontline kidney cancer has been an elusive strategy. We've -- this is not the first time we've tried it, but we've not had success before. Maybe things will change, and we will move on to combination therapies. But as of now, I would argue that there is a combination therapy that's recommended in the frontline setting. And 2 important trials have looked at combination therapy against the best TKI second line that we had, which is cabozantinib, which are [indiscernible] 011 and also the [indiscernible] trial. The len/cabo look at lenvatinib [indiscernible] versus cabozantinib. The other trial, lenvatinib [indiscernible] looked at cabozantinib as the control arm. In both of the trials, objective responses with cabozantinib median PFS was around 10 months odd. The CONTACT-03 trial which had cabozantinib in the control arm, all these 3 trials at cabozantinib at 60 milligrams, so they're very strong control arms. And all of them objective response to 40%, PFS of 10 months, showing that a combination approach is probably better. But as more people start using pembrolizumab in lenvatinib upfront maybe with another HIF-2-alpha depending on how that other trial pans out. And as people start using lenvatinib, [indiscernible] more it makes the question of what other options there are. We know that the [indiscernible] pathway is an important pathway to inhibit an important pathway that adds to mechanical resistance. So I see this as being a doublet strategy for second line and above, whether we see -- whether this combination is sequenced before [indiscernible] abatable defend depends on if the patient has had his inhibition before or not. And it will be interesting to see. But this is probably in subsequent or in sequence with the combination with HIF2-alpha.

Our next question comes from Ed Sadara with Barclays.

And congrats on the data. Just given what we've seen here from an efficacy safety standpoint, maybe your view around the mechanism translating into sort of the KRAS update on both efficacy and safety. If you could comment on that.

Mollie, do you want to take that? .

Sure. I mean, for us, just as well as our PIK3CA data that we've presented last year, now I believe it was. This is showing that the mechanism is what we say it is. This inhibiting the ability of REV to activate MTOR is really shutting down that additional pathway that cancer uses to evade treatment with targeted therapies, including KRAS inhibition. So I think you should take away from this that mechanism of action we have yet once again, shown you evidence of its activity in this particular combination in PIK3CA and we'll be moving forward into that KRAS inhibitor, where we think that you'll take away the same message that this works. This is an appropriate combination partner to help get rid of some of the acquired or the acquired resistance mechanisms that these cancers use to abate?

Our next question comes from Daniel Bronder with Cantor Fitzgerald.

This is Daniel Bronder on for Lee Watsa. Could you elaborate on the 10 patients of the 18 that you had noticed had disease progression on prior carbo. And what were the reasons the other patients discontinued carbo and whether or not you see responses across the whole spectrum of prior cabo exposure?

So just in answering the last part of your question first, yes, we see responses across the continuum of how and when and where they've received cabozatinib previously. So for the patients that Especially in the 40-milligram group, they either came off for progressive disease or potentially intolerance. And that makes sense with why they would want to come back along on a 40-milligram combination because that's usually how they reexpose these patients to cabo after they've previously seen it. But I think the most important piece to recognize is that of the 7 responders, all of them had, had progressive disease on their cabo. And 4 of those 7 had come directly on to our trial from cabo therapy, so [indiscernible] a cabo failure. And we're able to have the responses rescued from use of darla as well. and their best response on their prior cabo was only stable disease. So we were able to actually not only get them out of a progression, but move them into a response using a combination where the monotherapy was not able to even get them into a response originally.

Our next question comes from Erik Lavington with Mizuho Securities.

Erik, on for Salim. Congrats on the progress recognizing it's really early days yet. Just curious about the dosing of darlifarnib. If you have an interest or capacity in protocol to look at dosage above 8 milligrams, your thoughts on that.

Sure. So we did a monotherapy dose escalation in addition to these combination dose escalations of the cabo 1 of which you're seeing right now. in the monotherapy dose escalation, as we've previously described, 10 milligrams appear to be really the maximally tolerated dose. But you have a very wide therapeutic window with anywhere from 3 to 10 in producing efficacy in expected patient populations and being safe enough to keep patients on. So we would be able to increase the dosing between that 3 and 10 milligrams in any combination that we're looking at, that's probably the escalation pattern we would look at. But here, we felt that the 8 milligrams offered the appropriate safety and and efficacy and really moving to 10 milligrams would have only increased the toxicity. And so that's why we're moving forward with the 5 and 8.

Yes. Erik, just to add to Molly's comments, I mentioned that darlifarnib is a next-generation FTI, and that really is kind of on 3 axes. One is significantly greater potency relative to tipifarnib. Tipifarnib was dosed at 600 milligrams twice a day and one really needed to be at that dose in order to see activity in HRS mutant solid tumors. As Molly indicated, here, we have obviously a much more potent compound beginning with activity at 3 milligrams, but we also interestingly have this window between 3 and 10, probably 3 and 8 million where we can balance safety, tolerability and activity. So it gives us a lot more flexibility, and it's also once-daily dosing versus the twice daily dosing of tipifarnib. It really is an ideal set of properties for these precision combinations, whether it's cabozantinib, [indiscernible] as you'll see, or other TKIs and [indiscernible] inhibitors in the future. .

Our next question comes from Jason Zemansky from Bank of America Securities. our next question comes from Roger Song with Jefferies.

Congrats on the data updates. So curious on the treatment durations. We still have a couple of patients on therapy. How are we interpreting durability at this stage?

Yes, it's a great question. It's still early, but you saw that there's patients that have been on even in this subset of the Phase I that we're showing you for getting close to a year. So an evolving story with the patients still [indiscernible]. And I think that it will be nice for you to get a broader picture when we show you the additional Phase Ib data in coming weeks, where you'll be able to see even more patients, even more patient stories and even more of the durability story testing. .

Our next question comes from Roger Song with Jefferies. Apologies that is Jason Zemansky with Bank of America.

Congrats on the progress. Maybe just a quick follow-up to Molly regarding the mechanism, but appreciating RCC is just one indication of a broader strategy. Has the data set changed your outlook about which indications to pursue next? Are there any read-throughs to other solid tumors here that make them more attractive indications?

So what it does reassure me is that we can do this with any of the compounds that we can really more than just indication, it's really the combination partner. So anywhere cabo can go, we can go anywhere lend book can go, we can go. And then I would generalize that also to the KRAS inhibitors and the PIK3CA inhibitors. So that's really your landscape, wherever those particular compounds can go, we can make them better. And that's why we'll continue to evaluate potential options and pick the right one to get this to patients as quickly as we can. .

Yes. And Jason, just to add to to Molly's comments, again, you should be seeing the KRAS data, hopefully here before too long. I think at that after we show you that, we may be in a better position to talk about the balance between going fast and getting to registration versus going broad. Nothing -- if anything, this data reinforces that there's a significant opportunity here in solid tumors. We are actively working through what's the right development strategy for Kura, both alone and in collaboration with others. And we'll be in a position kind of as the year goes on, I think to speak more to that.

[Operator Instructions] Our next question comes from Phil Nadeau with TD Cowen.

Congrats on the data. We want to follow up on the activity in the refractory patients. So it seems like based on our math, approximately 4 to 10 patients who are refractory to cabo had a response. That's a very similar response rate to the roughly who [indiscernible] refractory to cabo. Is that analysis correct that you're relatively seeing the same efficacy across those 2 populations? And if so, I guess our question is, for the next trial, you're looking at cabo naive patients, why not continuing capital refractory given the pretty strong efficacy there? .

No. What we do think is that this combination gets the cabo exposed up to what you'd expect to see with cabo monotherapy in the naive patient population. I think that actually more of the patients were refractory than maybe your calculations are taking into account, like I said, of the 7 responders, all of them were refractory to cabo at the time of coming onto trial. And as for our Phase Ib trial, it's part of the reason we're doing the cabo monotherapy arm is one, to establish a good baseline in this patient population that has this ever-evolving landscape. So we want to see what our patients look like now today with HIF2 [indiscernible] IO, et cetera. But having that rollover potential really allows us to continue to demonstrate the mechanism of being able to save or induce responses in patients that progress on the monotherapy. So we'll still be able to see additional data in that regard. But just to get the clear signal, we wanted to make it so that we had cabo-naive patients.

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, Jenny, and thank you to everyone who participated in the call today. We will look forward to our -- the next time we talk to, I think, will be our earnings call in early May. I look forward to that. If in the meantime, you have any questions, feel free to reach out either to Greg or me, and we appreciate it. We hope everyone enjoys the Friday and the weekend. And with that, we'll adjourn the call. Thanks very much. .