Hello again, everyone. My name is Etzer Darout , a senior biotech analyst at Barclays. It's my pleasure to welcome Kura Oncology to our next fireside chat. With me this morning, I have Troy Wilson, President and Chief Executive Officer, and Brian Powl, Chief Commercial Officer. Maybe just to get us started, Troy, if maybe you can just make some introductory remarks for the team, and then we'll go into a Q&A.
Yeah. Thanks, Etzer Darout . Thank you to you and Barclays for inviting us to attend the conference. It's always terrific. So as folks probably know, Kura is now a commercial stage, fully integrated biopharma focused on developing targeted therapies for both liquid tumors and solid tumors. You know, we have sort of three priorities this year that we're gonna talk about in your Q&A. The first is to drive the launch of our marketed product, Komzifti, to majority market share.
The second is we have, I think, the broadest and most aggressive development plan for ziftomenib, which or Komzifti, throughout the treatment continuum, most notably the front line. You know, we have a pipeline of therapies to come that at this point, I think are just a really attractive call option, and we'll move those forward. Company is very well capitalized, and 2026 is gonna be an exciting year.
Great. Maybe just again, given the recent launch of Komzifti, can you just maybe kinda comment on at least what you're observing so far, the feedback that you're getting from KOLs on that sort of initial ramp? We'll obviously ask a little bit more around that.
Sure. Brian, you want to take that?
Yeah. Happy to. Thanks, Etzer Darout, sir, for the question. Komzifti, as we know, was approved back in November of last year. We've had a very successful launch so far. We've really built the messaging and the focus of our discussions with KOLs and prescribers around really four points of differentiation for Komzifti. One, we have built on a strong base of efficacy in the relapsed refractory NPM1 mutant space. The safety profile for Komzifti is viewed by KOLs as differentiated and really meaningful for the physicians and the patients.
Third, the combinability of Komzifti with concomitant medications, the ability not to have to change a lot of your dosing is important. Finally, the simplicity of once daily dosing is also something that's resonated. The feedback we've heard so far has been very positive. KOLs are seeing that there is an opportunity to bring Komzifti into the market, and we believe that we'll be able to achieve that majority market share based on innovation in this space.
Great. As you think about 2026, what do you sort of see as the puts and takes to adoption of Komzifti?
Yeah, I think, you know, it really starts back to the profile. We think that there's opportunity, that this is a market where, you know, the population, patients are coming in, as they progress from their prior line of therapy. We think the opportunity to get patients on Komzifti as a monotherapy really is at that point of decision-making. We see that working for us well so far. In the longer term, we also see the ability, while it's not within our label, a lot of the physicians want to combine with other standard therapies, and within the NPM1 space, patients have other options.
They may be able to get things like venetoclax, azacitidine. If they're co-mutated with FLT3, there's an opportunity for them to get gilteritinib. We're hearing that there may be opportunity to, rather than sequence, a MEK inhibitor after those therapies to potentially combine. That's one of the areas that we see as an opportunity.
Great. Are you observing any friction points, if you will? I guess it would be similar experience to other companies potentially in this space around, you know, standard logistics, you know, prior authorizations, comfort positions, DS monitoring. Anything that you'd wanna highlight?
I would say the one thing I'd like to highlight is we haven't really seen a lot of friction so far. In fact, one of the things that's been quite compelling for us is the rapid uptake from payers to put Komzifti onto their policies has been almost more of an upside surprise. We've had over 80% of private payers have put us on policy in the first 90 days, and that's well ahead of benchmarks. We've seen a lot of open access for Komzifti to go forward. Haven't really seen any major barriers. It's more than just you gotta have the patients that come forward. It's an incident market where patients will, you know, be considered for Komzifti, and that's what we're gonna be working towards with our field teams.
Great. You know, obviously, the longer-term plan is to move into earlier line settings, particularly the frontline AML setting and several MEK inhibitors moving forward in clinical trials to evaluate their drugs in frontline settings. What do you view as key differentiator for you as you're working to execute your plans around KOMET-017, which is your frontline trial?
Yeah, I think it's sort of two pillars, if you will, Etzer. One is the properties of ziftomenib, and the other is the manner in which we're executing on the trials. On the properties of ziftomenib, this goes back to something that Brian was saying. Oftentimes investors or folks, you know, are hearing it's all about efficacy, efficacy.
That's true, but with the differentiated safety, combinability, convenience, you can drive better activity. You can drive better efficacy, whether that's in the relapsed refractory setting or the frontline setting. You can see that from our frontline data. I would put it up against any of our competitors. We're gonna give a data update on the 7+3 frontline phase Ib, and I think, again, you're gonna see that pull through.
That's on the molecule side. On the execution side, a number of years ago, we made a deliberate decision to put the two phase IIIs under a single protocol. We did that because when we went out and we talked to clinical sites in the US and Europe, they said to us, you know, we said, "Look, you're gonna have multiple sponsors. How can we win your love?" What they said was, "Put both trials in one protocol. It's easier, it's simpler to get up and running, it's one IRB, you're standing up, you know, really one trial."
Most importantly, Etzer, any patient who walks in the door can come on one of those two trials. As a result, you know, we are rapidly activating. We're gonna have up to 200 sites globally. We're rapidly activating. We've got many of kind of the premier sites in the U.S., Europe, and Asia Pac, and I think we're just gonna out execute everybody else. We haven't really totaled it, but we've enrolled at this point 350 patients in the phase I studies to date with 30 sites. Now the goal is 1,300, and like the game is on.
Right. Great. You know, in the field of AML patient population, reevaluating combination with 7+3 in both NPM1 and KMT2 patients, I guess, what does the biology tell us about where conviction can lie in either both of those patient populations? I guess ultimately, how could that translate into durable responses and outcomes for those KMT2A patients and NPM1 KMT2A and NPM1 patients?
Yeah. Good question. The biology that you're addressing in frontline is you are trying to get patients to MRD negativity. Why is that so important? You can have 5% leukemic blast counts and be at a CR. If I have 5% leukemic blast counts, you still have full-blown leukemia, right? If you're MRD negative, as measured in bone marrow, which is the accelerated endpoint for the KOMET-017 study, you don't have leukemia down to the limited detection.
There's a very strong meta-analysis that we and the IMPACT Consortium used to convince the agency to allow MRD negativity as an accelerated endpoint, and that's the association between MRD negativity and survival. The biology, as you asked about it, is you use the combination of intensive chemo and ziftomenib to drive the MRD negativity down, and then you use ziftomenib in continuation therapy to maintain those patients ideally in an MRD negative state. You called out the two genotypes.
Let me just spend a moment on each of them. What we're seeing in FTI, much to our surprise, is that the NPM1 patients in general are not going to transplant. The reason for that's pretty simple. If you're MRD negative, CR as an NPM1 patient, transplant's contraindicated. The KMT2A patients are going to transplant because that disease is different, it's more aggressive, it has an eight month EFS versus a 22-month EFS for NPM1. What we are seeing is we're driving patients, KMT2A patients to transplant and then putting them back on ziftomenib on the other side.
Right. Yep. When we think about MRD negativity, we wanna sort of understand the bar for success here.
Yeah.
Can you give us a sense of the expectations around MRD negativity in the control arm?
Yeah. Let's be clear. There is the MRD negativity assessment that the site makes that's typically done in plasma or in blood, and there's the MRD negativity assessment that you're doing that's centrally confirmed. Those numbers are different. The, you know, the site numbers are typically higher. The benchmark for intensive chemotherapy in MRD negativity rates in bone marrow after two cycles for NPM1 is about 45%.
45% of patients are MRD negative after two cycles. Our goal is to demonstrate a rate of MRD negativity using, again, you know, high sensitivity assay in bone marrow that's clinically meaningful above that. That's typically 10%-15%. When we show you the update middle of this year on the intensive chemotherapy combo, look for that rate of MRD negativity that is assessed in bone marrow. The local assessments will always be higher, but the FDA wants to see the central assessment in both the control arm and the active arm.
Great. In the unfit population, maybe also your sense around bar for success when you think about CR and overall survival.
The bar for success in the unfit population, this is the venetoclax azacitidine combination, and we're there. We're only enrolling NPM1. You're in the range of about 60% CR rate in NPM1. Your OS is about 22 months for the NPM1 population. That's what you're in for both of those, either accelerated or full endpoint, those are the benchmarks you're looking to exceed.
Great. You know, you've highlighted a couple of updates from other ziftomenib studies, KOMET-007. We'll get an update in the first half of 2026, 2028 in the second half-
Yeah
... of 2026. Maybe starting with the 007 update, where you presented some data at ASH. Maybe help us to understand what additional data we would get in the first half of this year. Then again, what should investors be focused on as those datasets are rolled out?
Yeah. Thanks. There's actually three updates. Maybe I can just-
Yep
....clarify. We're going to present a publication that was really a continuation of the data you mentioned at ASH. That's venetoclax azacitidine ziftomenib in the relapsed refractory NPM1 setting. The significance there, particularly when you put ziftomenib on top of Ven/Aza, your ORR goes to almost 80%. To Brian's point, you know, that's not gonna be within the label, but what we heard very clearly from clinicians, "Get this data out." Like, we wanna be educated.
The physicians wanna use these drugs in combination. You'll see that probably around midyear. We don't control publication timing. That's. That'll be a peer-reviewed publication. There will be a frontline update. What I would look for there is the sort of the median patient had been on the phase Ib frontline study last year for about five or six months. This is now a year later.
That means your median patient will have been on almost 18 months. The significance of that is if you know, thinking about the frontline opportunity, if you can. You know, you have 10,000 patients. If you can keep them on therapy for 18 months, that is a $10 billion market. Investors should be paying attention to that. You're still gonna wanna see, you know, a positive phase III, but these phase Ib's are so large and robust, they'll go a long way to de-risking it. The last dataset is the one you mentioned that is the ziftomenib gilteritinib combo in relapsed refractory NPM1 FLT3 co-mutated patients. I'll just remind folks, that's half of your NPM1 population in every line of therapy.
We have already said we were successfully able to dose escalate and get into an expansion with no DLTs. You're gonna see that data back to the point that Brian was making. Right now, there's. You know, what we hear is physicians will sequence FLT3 NPM1 co-mutated patients through gilteritinib and then give them a menin inhibitor because gilteritinib has a survival advantage. It's went through a randomized trial. If you can give them data that says, "Don't do that. Actually give the two on together, you'll drive a better outcome," that, we think that will be very informative. Look for that data around the end of the year.
What sort of data will kind of help us inform us, if you will, on sort of whether or not these patients are seeing a better outcome-
Yeah
...with the combination?
The CR rate for gilteritinib in that setting is less than 20%. The CR rate for ziftomenib is 21%. The CR rate for our competitor is, I think, 23%. You wanna see a CR rate that is meaningfully better than those numbers and good durability. If you see that, I think you're in good shape. I'll also remind you, Etzer, that we're also evaluating quizartinib plus ziftomenib in the frontline setting. That study is still in dose escalation. To date, we've had no trouble at all combining with either of the two marketed FLT3 inhibitors.
Great. KOMET-001 study ongoing in just-
Yeah
Maybe if you can just comment on that study and perhaps where you are in dose escalation.
What you're referring to is the study to assess imatinib plus ziftomenib in recurrent metastatic GIST. These are patients who have failed imatinib. The significance here is, menin controls the transcription of KIT. By combining a menin inhibitor and a KIT inhibitor, you're attacking KIT from two different directions. You're blocking the catalytic activity, and you're blocking the transcriptional activity. What we've seen preclinically is we can resensitize KIT failures to almost any KIT inhibitor. If we're successful, this is the first novel MOA in GIST since the advent of KIT inhibitors.
Right? Gleevec, like, 25 years ago. That's a big deal. I think we all appreciate from Cogent, from GSK, how big that GIST market could be. We're currently in dose escalation. I think we're encouraged by what we're seeing. We're at doses that now that are higher than the AML doses, and it's going well. I think, Etzer, you're probably looking at a data update next year. We wanna have enough data that we can come forward and really have a conversation about where we go from there.
Maybe we can spend the last few minutes on tipifarnib.
Yep.
A couple of programs there, KRAS G12C mutant solid tumors, RCC. Maybe just first, on the KRAS mutant program, you know, how much data, again, could we see across the different KRAS mutant types? We can have some follow-up questions on that.
Yeah. We are in that study combining adagrasib, the KRAS G12C mutant selective inhibitor, and tipifarnib. We're evaluating it in patients with non-small cell lung, colorectal, and pancreatic cancer. Many of those patients have actually already seen a KRAS inhibitor. You're gonna see, Etzer, well, actually, this is just the escalation. You'll see 30-40 patients.
Got it.
It's a meaningful data set.
Yeah. When you think about the sort of with the KRAS space.
Yes.
There's always been a lot of focus around PDAC-
Yep.
...is there a particular histology that, you know, you think could be more meaningful than others? Or just maybe where sort of the benchmarks lie and what be able to sort of come ahead of those benchmarks?
Our goal is, you know, maybe just to frame the problem. It's a common problem in both RCC and KRAS. Resistance is the problem, right? Even with all of the successes that we've seen, it's not like we're curing patients, right? Half of them respond. Of those half, you know, most of them eventually relapse. What you're doing with tipifarnib is you're blocking a major resistance mechanism. To your question, what we'd like to show with this data is we're bringing forward a novel mechanism of action that is broadly combinable, and whether you have a mutant selective, a pan-selective, you're gonna wanna combine with tipifarnib. What are people doing right now?
They're combining with Cetuximab, right? They're going back 20, 30 years, because they're trying to overcome resistance. That's really gonna be the focus. You'll see us articulate a development plan. Is it pancreatic? Is it colorectal? You know, doublets or triplets. Look for us to do that a little later. At this point, I think we wanna get everybody saying, "Yeah, that's obviously an MOA I would want to combine with these KRAS inhibitors.
Right. I think, and to your point around sort of, you know, KRAS cancers and then the inevitable escape mechanisms that develop, right, to be able to keep patients on longer, durability matters.
Yes.
I guess, is there another data set later on that could be more telling in terms of whether or not you're seeing the durability associated with being able to stop that resistance mechanism, or could we get that type of update at this first time?
I mean, the hope is whether we're talking about RCC or KRAS, what you're looking for is if a patient's had adagrasib and progressed, a physician wouldn't normally think to put the patient back on adagrasib, right? Same thing with cabozantinib. If we can show you examples of patients where we've been able to put the patient back into response, the only thing we've done is to add tipifarnib, that's pretty interesting in terms of overcoming the resistance mechanism. Part of the reason, you know, we're just now much more mature and disciplined. Part of the reason we've waited to show this data is you wanna give your responses time to confirm. You wanna have enough durability data that you can say something meaningful.
It's still a phase Ia, but we're also using that data in confidential conversations with a number of the players in the KRAS and RCC space because everybody has the same problem, right? Just to go to RCC for a second, you know, there's a view that we're gonna see a triplet of HIF-2 alpha TKI IO go to frontline. If a patient fails that, you've just exhausted the three mechanisms in RCC. What do you do, right? We're hearing a lot of enthusiasm. If we can introduce a new mechanism of action that resensitizes patients to one or more of those MOAs, that's a big deal. The second line opportunity is gonna look different and is gonna continue to be quite significant in RCC. Lots of exciting data to come in the early program.
Great. With the combinations, particularly with KRAS, I think the question around safety always comes up, just given sort of the KRAS historically being-
Yeah.
...a problematic-
Yeah.
...molecule to combine with. Maybe you're thinking around, like, what sorts of safety signals should we be looking out for? What's problematic? What is reasonable to us so from a manageable safety perspective?
I can say this, right? You know, folks who have followed this story for a while have heard me say this. I always talk about safety and tolerability for 'cause if you can't combine. You can't drive efficacy. The fact, Etzer, that we can combine at a full dose with cabo, alpelisib, and adagrasib, full dose of each of them, full dose of tipifarnib, kinda tells you everything you need to know.
The only AEs we see are on mechanism myelosuppression, which you're not gonna address in a dose escalation 'cause you wanna see the tox, but you just give, you know, supportive care, you give G-CSF, for example, for the neutropenia, and you can address that quite meaningfully. The beautiful thing about FTIs is, this is why I keep pushing this mechanism, we have 5,000 patients worth of data.
Right? The safety profile is as good as it gets. It's better than Cetuximab, for example. No disrespect, right? I think people will be very pleasantly surprised. We hear from the clinicians in the RCC study. They remark at how well tolerated the cabo tipifarnib combo is relative to other things they've seen. I think that's gonna allow us to drive, you know, interesting activity.
Great. We're up on our time. Troy, Brian, thank you so much for your participation, and thank you to our listeners, and we'll be back shortly with our next session.
Thanks, Etzer.
Thank you.