Annual healthcare conference. I'm Phil Nadeau, one of the Biotech Analysts here at Cowen, and it's my pleasure to moderate a fireside chat with Kura Oncology. We have with us today Troy Wilson, President and CEO, Brian Powl, Chief Commercial Officer, and Mollie Leoni, Chief Medical Officer. T, maybe I'll toss it to you to begin. Could you give us a brief state of the company overview, biggest strengths, biggest challenges, and what does Kura need to achieve to drive outperformance over the next year?
Sure. Phil, thanks to you and TD Cowen for the invitation and the opportunity to participate. This is always such a good conference. 2026 is gonna be an important year for us. We are now, you know, 12 weeks into the launch of Komzifti, our first commercial product, in NPM1-mutated AML. You're gonna look to see us drive strong quarter-over-quarter growth and establish market leadership in that initial indication. I think we have the broadest and most aggressive development plan behind that. We have two phase III trials that are Kura-sponsored underway in intensive and non-intensive frontline AML. You're gonna see us combining with two of the three marketed FLT3 inhibitors. I think you're gonna see us make a push there.
One really needs to do that to realize the full value of menin inhibitors in AML. We have a number of important data sets that are coming this year that I think we'll speak to in follow-up questions. Below AML, we're pursuing solid tumors, starting with ziftomenib and imatinib in GIST. That's in dose escalation. That's early, but I think we're encouraged so far. Below that, we're gonna show you again, two or three clinical data sets from darlifarnib, our farnesyl transferase inhibitor. Look for an update of darlifarnib plus Cabozantinib in renal cell carcinoma and darlifarnib plus adagrasib in KRAS G12C mutated solid tumors, sort of around the middle of the year. Finally, on the discovery platform, we have a menin inhibitor in solid tumors, distinct from ziftomenib.
As we've said, we're pursuing menin inhibitors for diabetes and cardiometabolic disease. You're gonna see us do something creative, I think, to advance the latter of those two. Company's in a strong cash position. We're actually doing earnings tomorrow morning at 8:00 A.M. Eastern, we'll give you the cash numbers then. What I can tell you is we're financed through our top-line results in frontline AML and the ability to move all of that forward, maintain ownership and strategic optionality. I think it's gonna be a big year.
Let's start with commercial and Komzifti's launch. For those less familiar, can you briefly review the data that got Komzifti approved and the indication that it's being launched in?
Mollie?
Sure. Just to remind, we are now approved in the relapsed refractory NPM1 mutant AML space. We did that through our KOMET-001 registrational trial. If you look at the label, you will see that we have solid efficacy with over 21% of our patients being able to achieve a Complete Response or a Complete Response with partial hematologic recovery in this relapsed refractory setting, which is unusual considering most of these patients can expect about a single-digit Complete Response rate. That response was durable, with about five months of median duration of overall response. I think the important things are what you don't see in there. You don't see any clinically meaningful CYP3A4 inhibitor interactions, which make dosing much more simplistic, and make safety much more simplistic.
You don't see an increase in cytopenias with the administration of ziftomenib, which we do watch some competitors struggle with. You don't see dosing complications. You do not have to change the dose if you're administering, let's say, with an azole, and are able to continue on with a single dose. Overall, the efficacy and safety are very strong in the label.
Appreciate it's early days in the launch. What is the feedback you're getting so far from clinicians as you roll out Komzifti?
Brian.
Do you wanna?
Yeah. As you said, it has been, you know, first few weeks of launch, and now we're hitting about 12 weeks. We've been very impressed with the feedback we've heard from clinicians so far. We've been outlining, and as Mollie outlined some of the data, we really think that we Komzifti is gonna be able to establish differentiation in this space and ultimately become the leader in the relapsed refractory NPM1 mutant menin class, based on four key areas. We think the efficacy, the safety, differentiation, the compatibility with other agents, and the ability to not have to worry about too much dose modification, as well as the simplicity of once-daily dosing are differentiating factors for Komzifti. The feedback we've heard from physicians since the launch has been really kind of mirroring that back to us.
We had a very successful ASH where we talked to a lot of physicians about the new approval. We're starting to see a lot of prescriptions coming through from that point. I would say importantly that the physicians have given us this. You know, we have physicians who've had a lot of experience with Komzifti. There's others who've had less experience but are learning and are starting to use Komzifti. There's other stakeholders that have also I think really the pillars have resonated. One of those is with pharmacists, so the academic pharmacists that are working closely with the centers.
They understand how difficult it is to manage relapsed refractory AML patients, and they've been impressed with the simplicity, the compatibility, of Komzifti. The other is payers. We'll talk a little bit as we get to our earnings tomorrow about the success we've had there, but we've seen a lot of payers have shared with us the differentiation between the two menin inhibitors is real for us.
You are reporting earnings tomorrow morning, but you have pre-announced $2.1 million in sales already, or you've pre-announced $2.1 million in revenue. What other metrics should we expect on the call tomorrow? You suggest maybe we'll get some payer data. Anything in terms of the scripts or patients on therapy?
Yeah. At this point it is, as we said, the revenue is gonna be one thing we'll cover. It is a little early to start to give too much detail around new scripts, and, you know, particularly around repeat scripts, things like that. What we're gonna be sharing is more of kind of some of the leading indicators that we see as potential success for the launch for us.
Great. FactSet reports consensus for 2026 Komzifti sales is $48 million, at least as of a couple weeks ago. Does that estimate seem reasonable to Kura? What could drive upside or, and what are the risks?
It's my mic. It worked. Okay, thanks. I didn't realize. Yeah. You know, We haven't been giving any guidance yet on our revenue targets for 2026. I think that what we have shared before, and we've been consistent on, is giving the overview of the expected TAM for this market. We think that the relapse refractory NPM1 mutant market is approximately about a $350 million-$400 million TAM. We expect that, as we've said, Troy mentioned, we'll be driving quarter-on-quarter growth, and we expect to become the leader in this MET inhibitor class over time. That will lead to, you know, a share of that overall TAM.
It's a little early for us to identify at what point we'll be able to reach that TAM, you know, over time, but we do think we're seeing the right signs that we're putting ourselves in a good position to build that market leadership.
How important is the European market to Komzifti, and can you remind us where you are in the regulatory process?
Yeah, sure. Our goal has always been to seek regulatory approval in the EU with the combination data. That gives you the survival data that you need in order and the comparator arm that you need for very solid regulatory approvals in that region as well as payer reimbursement.
Great. Maybe actually now turning to development. you are in the phase III KOMET-017 trial, that's been enrolling since September 2025. For those less familiar, can you outline the design of that study and provide an update?
I can. This trial was designed with essentially two trials in under one protocol. We have it so that patients can enroll into either an intensive chemotherapy 7+3, or the non-intensive chemotherapy option, Venetoclax plus Azacitidine, depending on, you know, what is more appropriate for their treatment. By doing that in one protocol, you're able to get sites up and running much more quickly. Sites are only going to take on one trial that covers a single patient population. The fact that we are able to be that trial that actually covers all menin-independent AMLs walking into a physician's office is extraordinarily powerful. Because we've done that, we have had a lot of site engagement. Sites are very interested in participating.
As we've announced previously, we will be activating 200 sites plus in the U.S., EU, and Asia. Because of our design, we have actually kind of cornered the market, especially in the U.S., edging out a lot of our competitors, so that they are having to go to some separate markets and such as China and India, where the standard of care is slightly different, and so it'll be a different patient population that they're dealing with in a lot of ways. We're doing this obviously as a company-sponsored trial so that we really have control over the data, over the enrollment, over the design of the trial. It's a very robust trial.
We are looking at Venclexta for accelerated approval and for full approval, so endpoints so that we'll be able to get earlier into the 7+3, very importantly, it's designed so that not only do you look to see if the addition of ziftomenib is important in the induction and consolidation phases of treatment, but to see if it also contributes to the post-consolidation phase, which would be post-consolidation with chemo or with transplant. We're opening up that entire portion of the patient population as well through this design.
Have you disclosed how many sites are up and running today?
We have not, but I can tell you that it is a large proportion of the sites that we plan on ultimately enrolling, and that every day, it's more. It's going very well in that regard.
In the unfit patients, as you mentioned, the primary endpoint for accelerated approval is CR rate. What have you said about the powering of the study for that CR endpoint? If you aren't willing to disclose the powering, what level of CR would support a accelerated approval?
Sure. No, we haven't shared the powering, specifically, but if you're looking at Venclexta in this frontline patient population, you'd expect about a 60% complete response rate. There's ample room for improvement. We would look to get into, you know, 10%-15% improvement over that to also then be able to demonstrate a good improvement in survival, 'cause you do expect the CR rate to translate into a survival improvement as well.
In terms of the fit patients where you have MRD negative CR, I guess similar question, what would you expect from standard of care, and what would be a meaningful benefit?
This is a novel endpoint that we're pursuing. This is CR MRD negativity in the bone marrow. If you look at what you would expect the backbone to provide alone after two cycles of intensive chemotherapy, be that induction, two induction cycles or an induction consolidation, you would expect to see about a 45% MRD negativity rate in the bone marrow of these patients. Again, we'd be looking to take that up, 10%-15% for a clinically meaningful improvement that should then also translate to a survival improvement.
You referenced the three-arm design for the intensive chemotherapy portion of the study. Ziftomenib during induction and consolidation versus induction, consolidation, and maintenance. What do you hope to achieve with that design? What's the rationale between that three-arm design?
Yeah. Ultimately, I think in the beginning, everyone thought that Venetoclax was the right combination to go to. It's where the patients stay on until they progress, et cetera. We very early in our KOMET-007 trial, which has led us to our KOMET-017 trial, our phase I trial, saw that patients are not just coming off after induction and consolidation. They actually want to stay on for prolonged periods of time, and physicians actually have faith that this will really increase the efficacy of this potential combination. we wanted to design a trial with the regulators that would enable us to get a label that actually included post-consolidation maintenance. Again, post-consolidation does also include post-transplant maintenance.
The reason we did that is as long as there's no real increase in safety issues and there's at least a modest increase in benefit, which we think there'll be more than a modest increase, we would be able to get that label for these patients, that they're able to stay on for, you know, two to three years of treatment.
You've guided to the initial data from the study, in 2028. How confident are you that you can hit that timeline?
Extraordinarily confident. I think we've proven over the years that our teams can really execute. If you look at KOMET-007 again, the precursor, we enrolled hundreds of patients in a very short period of time and always beat our own expectations. I don't lose sleep.
How does Kura size the market opportunity in the front line, and how is that broken down between fit and unfit patients?
I'm jinxed. Yeah. Within the frontline market, we essentially at a high level assume that it's 55%, 45% split between the 55% IC and 45% non-intensive. We think that there are, you know, approximately the incidence of AML around 20,000 patients a year. When you think that as, you know, with NPM1, FLT3, KMT2A population, that reaches up to approximately 50% of AML patients. Our assumption is that those patients at the non-intensive are probably able to achieve or receive therapy for 12-18 months, and then for the intensive, it could be 18-24 months.
We think that ultimately comes out to approximately a $7 billion TAM for those patients, so.
We jumped right into the trial design and commercial. Maybe taking a step back on the data that you've generated in phase II to support phase III development. Last year, you presented results in both the fit and unfit patients. For those less familiar, can you review those results?
Sure. We presented the fit patients. 7+3 data for your NPM1 and your KMT2A, what we saw is 90%-100% complete response, CRC rate, essentially. It was at 100%, you know, we said we couldn't stay there forever. We're still hovering around the high 90s for complete response rate. You saw high 60s-70% MRD negativity rate. It's slightly different in the way it was measured because it was blood, and it was local testing. That is an update you should look forward to this year. We'll update on the longevity of these responders as well as the MRD negativity rate run centrally, which will be extraordinarily helpful in evaluating.
Also with the Venetoclax frontline, we showed good improvements over that 60% that I said that you should be looking to benchmark us at. What we've found with this phase I is that the KMT2A patients do not go to Venetoclax. That is why we designed our frontline Venetoclax to have just the NPM1 mutants within it, and have put the KMT2As where they do best, which 7+3 plus ziftomenib arm. We did not, we did not think that it was appropriate to include them in our frontline plans. You'll also see a publication coming out from us this year on the relapsed refractory Venetoclax, where we see a very significant improvement for these patients with the addition of ziftomenib to the backbone of Venetoclax.
Can you discuss the development in combination, particularly Quizartinib, is one combo regimen that you are looking at. What's the rationale behind doing a study in combination with Quizartinib? What's the design, and when could we see data?
Yeah. Ultimately, NPM1 mutants, half of them have a FLT3 mutation. There's already very well-established treatment for those patients with targeted agents targeting that FLT3 mutation. If you can't be part of that, you're gonna lose half of your NPM1 mutants. We, as a company, are very far ahead of competition in the fact that we can actually target FLT3 mutations. Not only are we doing a Quizartinib combination, that is a quadruplet of 7+3 plus ziftomenib plus Quizartinib in the front line, that we are currently in dose escalation for, we haven't guided to when we'll be able to release the data for, we expect that it will be in the not too distant future.
We are also doing a combination in the relapse refractory setting in Gilteritinib, kind of hedging our bets 'cause as Gilteritinib is gonna read out in the frontline soon as well. The winner, you know, we will obviously be moving that into our frontline, and we will be developing in our frontline. If you've seen the data for our competitor in the relapsed refractory setting in combination with Gilteritinib, you've seen that they are unable to combine, that they have dose-limiting toxicities at every dose level tested. We are going to be presenting Gilteritinib data towards the end of this year. You will be seeing both escalation and expansion, which should tell you that we were very successfully able to combine and without safety limitations.
You're doing a number of other combination studies in the relapsed refractory space. What's the rationale for having combo regimens in relapsed refractory, and can you discuss those trials?
Yeah, sure. AML is not a monotherapy disease. We're still kind of head-held from a regulatory standpoint in developing a lot of our drugs in the oncology space as a monotherapy first. I think that's gonna fall to the wayside because these patients really need the combination approach. What we want to do, I always called it my data buffet. I wanted to develop data in all of the biggest combinations that are used for these patients. Not only are we in the 7+3, in the Ven/Aza, both frontline and relapsed refractory, we also have combinations, as I said, with Gilteritinib, we have combinations with FLAG-Ida, we have combinations with low-dose Cytarabine.
These are to enable physicians as we disclose the data, which we will be doing more and more over the coming years, have options to understand how to safely use this drug. That's been what's been most positive coming out of all this is that it does combine safely with all these agents. You can use it with all these agents. It can become part of the backbone of therapy. We plan to release it so that physicians are able to get away from the monotherapy use, as they've told us that's really not what they plan to do either. Now they will have optionality as to how to treat these patients.
What's Kura's assessment of the competitive landscape? You referenced the other marketed menin, but there's also a couple in development, one from Sumitomo, one from J&J, where we saw data last year. How does Kura perceive the overall landscape?
I can give my opinion and then if others would like to jump in. I think J&J is always your unknown. They don't always share too much. I think that they're obviously behind, which does make their development a little more difficult because I plan to take every patient in the front line so that they are unable to actually enroll them in a relapsed refractory registrational trial. That's, you know, just my plans. I do think that they'll make it to market, and I obviously think they'll be a player in that, in that realm. Sumitomo, they don't even have a dose yet for one of their subtypes. I think they showed good data. I think they showed small numbers of patients. I don't think we really know what's gonna happen with their drug yet.
Again, they are much further behind, and it's gonna get harder and harder as we start to saturate this frontline market for them to be able to run appropriate studies in the relapsed refractory setting to get registration.
Moving to zifto in GIST. What's the design of that trial and the rationale for conducting it?
GIST is a disease that is currently treated with lots of KIT inhibitors, that there's really no innovation beyond KIT inhibitors, which is great. It does work. You know, these patients mutate, and then they have to move to a different KIT inhibitor. Once you pass imatinib, which is the first one, the safety really becomes an issue. What we saw is that if you combine a KIT inhibitor with a menin inhibitor, you are kind of double-heading that KIT over reliance pathway. These patients' tumors, the tumors need KIT, they love KIT, they're addicted to KIT. We're able to cut it off then through the KIT inhibitor and then cut it off transcriptionally using a menin inhibitor. That's the rationale for doing this.
Right now the study is designed to be a dose escalation, then a dose, tweaking it to make sure we comply with Project Optimus, and then going into possibly the relapsed refractory. FDA actually encouraged us to consider that frontline imatinib indication. We have been successfully able to combine these drugs so far. Again, look forward to being able to share that data.
What will be the size and scope of the data update when we get it?
Oh, I think it's premature to say, because we don't know how many doses we'll escalate through. I can tell you that we've been very able to escalate and that we actually have gone beyond what we would do with AML. It'll be a sizable patient pool.
One more question on the menins before moving to the FTIs. You've suggested that there's a next gen candidate that could move forward in diabetes. Any update on that program and when we could see an IND?
We are in the process of doing the IND-enabling work now. Phil, I think you'd look for an IND in the first half of 2027.
Great.
We're specifically targeting Class I initially, because the consensus among the KOLs and others is if it works in Class I, it'll work in Class II. It just seems like a cleaner experiment.
Great. Turning to FTIs and darlifarnib, there was an update at ESMO. Can you, for those less familiar, remind us of what darlifarnib is and the data that were presented?
Darlifarnib is our next generation farnesyltransferase inhibitor. It is the son of Tipi, the daughter of Tipi, I think.
Mm-hmm.
It's just a better version of an FTI, a farnesyltransferase inhibitor that you've probably heard of many times over the years. Essentially, what we've discovered is that this is a drug that can make good drugs even better. It is able to help selectively, through Rheb, inhibit the mTOR 1 pathway. It is less toxic than other drugs that hit more broadly at mTOR 1 and 2. That pathway plays a big part in a lot of tumors, both innate and adaptive resistance. If we go in with these good drugs like TKIs, like PIK3A, PIK3CAs, like KRAS inhibitors, and add this in, you're going to be able to address that innate and adaptive resistance right up front.
What we presented was our renal cell carcinoma data, and that was our Cabozantinib in combination with our darlifarnib data. What it showed you is that not only do we see really good responses in patients that have never seen cabo before, but you also see really good responses in patients that have. That really, for us, proves the mechanism that we are able to resensitize these patients by fixing the pathway that, inhibiting the pathway that was allowing these patients to, and their cancer to kind of slip through and slip by. We'll also be showing you later this year an update on those data, and we will be showing you an update, well, the first look at our KRAS inhibitor data, which is in combination with adagrasib, in both PDAC, non-small cell lung, and colorectal.
In the RCC group in particular, what's the bar to moving forward? What do you want to see to be confident this is a program that should be developed further?
You know, the golden child right now is HIF-2αs coming out. We wanna be competitive with that, and right now they see. They just released some additional data, but, you know, the benchmark that we're looking at is around a 31% to 40%, 47% response rate that they are able to generate in these patients. We would wanna be able to at least be competitive with that. HIF-2αs are obviously not curing the cancer, so there's always gonna be additional options needed. We think HIF-2αs will move more towards the frontline as well, so the second line especially is gonna be wide open. If we're able to show this impressive activity again in combination with TKIs, we think that's extremely important. We also think it's important that we're not just a one-trick pony.
We're not just stuck with RCC. We'll be able to do other tumors as well, like neuroendocrine tumors. Anywhere cabozantinib can go, we can go essentially and make the drug better.
What about on the KRAS side? Which tumor types in particular are you excited about and what is the bar for moving forward?
I'm excited about all of them. I feel that we're treating tumors that are incredibly difficult. The relapse refractory colorectal, you know, these patients expect stable disease at best. Being able to improve upon that in this setting is extraordinarily important. We're also looking at pancreatic. I don't think anyone has a good feeling in their stomach when they think about pancreatic because it is so difficult to treat. That is another one we're very excited to share the data with. Non-small cell lung cancer. Big field, very complicated field, but it also has a lot of area for improvement, and so we will also be sharing the data in that combination.
Just to add to that, Phil, to build on something Mollie said, you're seeing folks go and combine with things like Cetuximab, right, in order to drive better activity, durability, address resistance. There's really a paucity of agents that you can combine with, to Mollie's point. This is unique in that it's potentially applicable to all of those different tumor types and allows you potentially to drive better activity, better durability with. We'll show you the clinical data hopefully midyear, but with, you know, better tolerability relative to some other options that are out there. It's a big. The challenge with the darlifarnib program is sort of the breadth of the opportunity, the number of places you can go. We obviously have to choose carefully. We have to choose partner drugs carefully. I think we'll come forward in 2026.
You know, why is this an important year? This will be the clinical data that I think validates Mollie's comment around inhibiting TORC1. Looking at RCC, looking at KRAS, we've previously shown some PI3K data with tipifarnib. I think this will help reinforce that, the validity of the mechanism of action. Great. Maybe to finish up with a couple corporate questions. First on business development, you've obviously built a great clinical organization, great commercial organization. What's the desire of Kura to bring in an asset from outside? Is there any? We are, I mean, we're always looking. I think at this point, for us to bring something in, we'd have to not do something. You know, we have a lot of things we want to do.
We are actively, Mollie's indicated it, I mean, the beauty of where we are is we're talking to a lot of different folks, whether it is FLT3, whether it is combinations with darlifarnib, whether it is, you know, working in GIST, working in diabetes, we're in touch with a lot of the strategic players in the industry, that's good validation of what we're doing. Look for us to continue to do clinical collaborations, right, to help get our pipeline candidates into these combinations. We may consider some other options either. You know, I don't think we're looking right now to do another big strategic partnership, we can be thoughtful about how we build out the portfolio.
Last question, appreciating that you're gonna report earnings in the morning and we'll get an update, can you remind us of your most recent cash balance and cash burn guidance?
Yeah, we'll end, you know, with about a little bit more than $650 million, and then we have a line of sight to $180 million in additional milestones that are tied to the phase IIIs, to the enrollment. With that, because we obviously give it with and without the $180 in milestones, we will have cash through the first top-line results, as Mollie mentioned, in that intensive frontline combination with ziftomenib at 7+3. We think that's an important value inflection point.
That's assuming everything keeps going full blast and we don't do business development or any sort of financing. We're in a strong position.
Great. With that, we're out of time.