Hello, everyone. Thanks for joining us. My name is Jonathan Chang. I'm part of the Leerink Partners Equity Research Team. It's my pleasure to host the management team of Kura Oncology. We have with us today CEO Troy Wilson, CMO Mollie Leoni, and Chief Commercial Officer Brian Powl. Thank you guys very much for joining us.
Thank you.
Thank you.
Would you like to take a few minutes to briefly introduce the company?
Sure. Happy to, Jonathan, and thanks to you and Leerink, for inviting us to attend the conference. Kura Oncology is now a fully integrated commercial stage precision oncology company. The lead program is ziftomenib, or KOMZIFTI is the commercial name, which is our menin inhibitor now approved in relapsed refractory NPM1 mutant AML.
I would say we have the most ambitious, probably most aggressive development plan behind it, with an intention of, trying to move ziftomenib throughout the continuum of care in various combinations, which I'm sure we'll touch on. The big driver there are the frontline opportunities, which are well underway with the KOMET-017 studies. If we drop down below that, we are also evaluating ziftomenib in solid tumors. Initially we're in a dose escalation of ziftomenib and imatinib in gastrointestinal stromal tumors.
We have a next generation menin inhibitor behind it, that's gonna go into other solid tumors, and that's a discovery stage program. Shifting from our menin inhibitors in oncology to our farnesyltransferase inhibitor program, we have a new, FTI, darlifarnib, and we're gonna be coming out with data there in both renal cell carcinoma and KRAS G12C mutated solid tumors.
That's an interesting opportunity because it addresses a major resistance mechanism to multiple classes of targeted therapies in large solid tumors. This is a big year for us. It's a year of commercial execution. It's a year of development execution. It's four or five clinical data sets on either the ziftomenib or the darlifarnib side. We continue to be in a strong cash position and able to drive the business forward and create value for patients and shareholders.
Great. Thanks for the introduction. Let's start off with the early KOMZIFTI launch experience. How has that been going?
Yeah, sure. Yeah, thanks for that, Jonathan. Yeah, we're very pleased with the progress of the launch so far. As you know, KOMZIFTI was approved in mid-November of last year. We rapidly were able to get product out into the market within about a week's time. The team had deployed had a lot of very successful metrics that we met in that first several weeks. Last week's earnings, we shared the first few weeks of revenue, about $2.1 million. But I think coming from that, we've seen some very good successes around our commercial execution.
Physicians have given us very strong feedback that mirrors back what we've been saying that KOMZIFTI is a differentiated menin inhibitor based on kind of four key pillars that we've outlined, the efficacy, the safety, the compatibility of combining with other agents, as well as the simplicity in once daily dosing. These four areas really, I think, have outlined where we see potential for KOMZIFTI to grow and build into that NPM1 space. A couple other things we've said that there's been some early wins is around the rapidity of our market access coverage.
We've had in the first three months since our launch, we've seen over 84% of plans have put KOMZIFTI on their policies. Some of those have even incorporated a step edit favoring KOMZIFTI over the competitors. We've seen a lot of good early signs, and we're encouraged of where we're going forward. Our plans for the year is to generate quarter-on-quarter growth and ultimately become, based on that profile, the menin inhibitor of choice in the relapsed refractory NPM1 mutant setting.
Got it. I think you guys first touched on that step editing on the recent earnings call. Could you just double-click on that and give some more color around what you're seeing?
Yeah, absolutely. As I said, our market access team was very successful in getting very quick coverage across a lot of the payers. Other than the time to get up to speed, the focus has been to get parity access. We've received some, you know, through some of the engagements and what we've learned, there is a particular consulting company called IPD Analytics that does assessments of new products to support payers in their decision-making to put on policies.
They released an assessment of the relapsed refractory NPM1 mutant space with a recommendation that based on the pillars I discussed, as well as the potential pricing differentiation for patients of the competitor's highest dose, really shows that at an annualized cost, KOMZIFTI should be preferred. They recommended that payers consider a step edit to get patients to get KOMZIFTI before they would get revumenib. We've started to see a few plans started to implement that coming forward. We see that as an early indicator and a strong indicator that we have a good momentum for us to become the market leader in the space.
Understood. Can you talk about the type of metrics that you're tracking, and what could we hear from you guys in the coming quarters?
Sure. Coming up, of course, we're gonna be talking about some standards, you know, our net revenue. We'll get to new patient starts, and we'll give you a better sense in terms of the number of accounts that we're covering and the number of lives covered over time. As you know, you can't really present on things like duration of treatment until you have some time in the market. So we'll start to present that. Overall total prescriptions, TRx, things like that coming forward, and then we'll ultimately also plan to share our expectations in terms of the share of the class of the menin inhibitors as well.
I see. Later this year?
Later this year. Yeah. Not right away, but that some of those will be over time.
Understood. How are you thinking about the size of the relapsed refractory market? Maybe we'll start there, and then you can help us compare it to how you see it growing, once you start getting into the front line opportunity.
Yeah. We've shared this in the past. We believe that the total market for the relapsed refractory NPM1 mutant space is approximately $350 million-$400 million per year. That's based on number of patients that are about 30% of patients are NPM1 mutated. We think there's overall about 6,000 patients per year in the relapsed refractory setting, so you get 1/3 of that. We assume that patients with NPM1 would get about six months of therapy, which gets you to that TAM. Our expectation is that we'd, as we said, we would get to the majority share of that, so our goal is to get to think about that share.
This is also the assumption of that is that this isn't a monotherapy, which is what our approved indication is. We do understand and of course expect there may be physicians who make the choice to prescribe in combination, which would be outside of our label. We'll provide data to help, you know, support their decision-making, but that may also have an impact on that overall TAM depending on how many patients are in combination, which may lead to longer durations of treatment.
In the front line, Jonathan, just the second part of your question, our estimate on the TAM is probably 20 times larger than the relapsed refractory, and that's driven by two things. As Brian said, you go from, if you assume you can treat all menin-dependent patients, that's about half of the incidence population per year. Let's call it 10,000. Rather than the six months duration of treatment, we're thinking it's 18 months or longer. Those two factors working together, a larger incidence population and a, you know, 3x or 4x the duration of treatment is what drives the much larger numbers in the front line.
Understood. Can you talk about the path to getting to that front-line market? What is the strategy there?
Yeah. I mean, I'll let Mollie speak to it. Our strategy has been either with Kura-sponsored studies or in collaboration with either investigator-sponsored or cooperative group studies to combine ziftomenib with every, you know, commonly used regimen. But Mollie, maybe you can speak to the KOMET-007 study.
Yeah. That's exactly right. Even in our attempt to get to the front line, we're going very broad. What we did was actually take two studies and combine them into one protocol so that any patient that has a menin-dependent disease, a menin-dependent AML, has a place to go in a study. Right now we have the sites are coming up and getting running for KOMET-017, and they will be enrolling either into the non-intensive chemotherapy or the intensive chemotherapy side, depending on what's appropriate for the patient.
It's really helped us kind of get a good bit of sites that are gonna participate with us, at least 200 that have signed up. It has made it so we've really had the choice sites in US, Europe, and Asia-Pacific. We are generating data that should be first shared in 2028, and we'll be able to share the top-line results from the CR MRD-negative endpoint for accelerated approval for the intensive chemotherapy option.
Understood. I believe you've guided that you have three different combination datasets for ziftomenib this year. That's the KOMET-007, 7+3 combination in newly diagnosed AML in the first half. There's the Ven/Aza combination data in relapsed refractory NPM1 in the first half, and also the preliminary KOMET-008 gilteritinib combination in the relapsed refractory NPM1 mutant FLT3 mutant AML in the second half. Take your time for this question, but can you help set expectations for these combination datasets?
For the 7+3 , it's really an update from what we showed you about a year ago, and it's what gets us excited about this combination. In the beginning, everyone wanted to combine with Ven/Aza because they assumed patients come onto Ven/Aza and the additional targeted agent and just stay on that until they progress.
Whereas on 7+3 , they do two cycles, and they go to transplant. That's just not the case. Our KOMET-007 data very well demonstrates that. These patients come on, they receive drug through induction consolidation and then through post-consolidation maintenance, and these patients are staying on for years. That's what you're going to see, this prolonged time on drug without me being able to tell you a median OS, without me being able to tell you a median DOR, which is excellent for the patients.
We'll give you some landmark on that. Thankfully, I can't tell you more than that because it's going well for them. For the relapsed refractory Ven/Aza, that's going to be a publication, and that is really going to help physicians that choose to use this in combination understand how to use it in combination safely for both NPM1 and KMT2A rearranged patients.
Generally, in the relapsed refractory setting, Ven/Aza is certainly used. Most of the data has been generated up front in the front line, but once the patients become relapsed refractory, it is a common choice to go right to that. I usually see, you know, modest response rates as you would expect in a relapsed refractory population, maybe 30%-40%.
What we found in our data, and we have presented this previously, is that patients, especially those patients that had not previously seen venetoclax, and venetoclax is known to kind of change the response dynamics for these patients as time goes on. What we saw was more about a 70%-80% response rate.
This is the type of data that'll be published in larger form so that people can have a choice of how they use this and to get away from maybe sequencing Ven/Aza, then a menin inhibitor and put them all together to give these patients a better shot. Then for gilteritinib, which we'll be presenting, that's also in the relapsed refractory setting. I think the gilteritinib label has about a 19% complete response rate, so looking to improve upon that.
First and foremost, looking for the actual ability to combine. We've watched competitors have a very big problem with that, with dose-limiting toxicities at every dose level tested. First and foremost, can we combine with one? Yes. We're gonna show you the dose escalation and expansion. Are we looking stronger than either drug alone? I think that people will be happily surprised.
What are the considerations around combinability with gilteritinib?
At least for one of our competitors, because gilteritinib also has a QT prolongation signal, when combining, they were having a hard time controlling the QT, and there was problematic QT at every dose level tested. Thankfully, we don't have the same risk of QT prolongation and thus, we were able to combine successfully.
Understood. Can you discuss the Kyowa Kirin partnership and how is that going? Can you discuss some of the, you know, potential upcoming milestones that we see?
Yeah. It's going well. Just to refresh everyone's memory, we're in a global partnership with Kyowa Kirin for the development and commercialization of ziftomenib initially in AML. Kyowa Kirin also has an option to opt in to GIST if we move that forward. We may come back to that in a subsequent question. We book U.S. sales, control U.S. commercial strategy and global development. It's been a very strong partnership. They're very, very motivated to maximize the value of ziftomenib, and we're working really well together. I think we have a similar goal of get it out as broadly as we possibly can and go as fast as we can.
Understood. Just in terms of potential upcoming milestones.
Oh, sorry. Yeah.
How should we be thinking about that?
Sorry, Jonathan. I neglected that. We've guided to $180 million in additional milestones. Those are tied to execution in the phase IIIs. I wouldn't anticipate those until probably early 2027. That combined with the cash on hand takes us through, as Mollie indicated, the initial top-line results for the MRD-negative CR endpoint, accelerated endpoint in the first of the phase IIIs, for ziftomenib.
Got it. You know, we will. You said we should revisit this, of course. How are we thinking about opportunities for ziftomenib beyond AML?
You wanna speak to GIST?
Yeah. Right now we are enrolling a GIST study, gastrointestinal stromal tumor study. That is using imatinib, which is the frontline favorite of physicians and patients in combination with ziftomenib. What we find is that these tumors are heavily addicted to KIT, and so that's why, of course, they have KIT inhibitors as the main line of treatment.
However, that's not the only way that these cells, these cancer cells get their KIT. They get it transcriptionally as well. By menin is actually the pathway that unlocks the transcription that allows additional KIT to be produced for these cells to keep regenerating and surviving. By cutting it off at two different points with the KIT inhibitor and with the menin inhibitor, you really starve these cells.
We are looking at these patients in the relapsed metastatic setting, which means they've already seen and failed imatinib at some point in their treatment history, and they're coming onto our trial, and we're seeing if we can put them back into a response or give them a good stable disease, which is also a very good outcome for these patients. As we finish the dose escalation, then we'll move into a dose expansion. What's interesting is that we have a lot of optionality there.
As we watch more data come out in this particular space, and very good data for patients, we have the optionality to maybe go for a relapsed metastatic setting, maybe a second or third line, or even into the front line, which actually the FDA thought was a good idea when we first started presenting the data to them.
Got it. How should we be thinking about timelines, for the efforts in GIST?
We haven't really guided yet, but I think next year I'll be able to show you our dose escalation patterns.
Got it. How about for opportunities for menin inhibition beyond oncology?
Just before we leave oncology, it's like Disneyland. Before we leave oncology, we do have a program for a next generation menin inhibitor in solid tumors in combination. It's in the discovery portion of the pipeline. Look for more information about that later this year. On the non-oncology side, we are advancing a development candidate, another menin inhibitor.
Each of our menin inhibitors, Jonathan, are chemically and patentably distinct from one another. We're taking a menin inhibitor forward in diabetes and cardiometabolic disease with a specific focus on type 1 diabetes as an initial proof of concept. Look for us to advance that in a creative way, to bring additional resources in and actually be able to move that forward. That diabetes program would likely enter the clinic in the first half of next year.
Understood. Let's switch over to the farnesyltransferase inhibitor darlifarnib. How do you see the opportunity for this program?
Yeah, I mean, I'll let Mollie speak to kinda how to think about the data, but at the kind of the broadest, we're going after a mechanism. We're using a farnesyltransferase inhibitor to attack a mechanism of resistance that's common to tyrosine kinase inhibitors, PI3K-alpha inhibitors, and KRAS inhibitors, and that is through reactivation of the mTORC1 pathway.
There's a protein called RHEB that is uniquely farnesylated. RHEB controls mTORC1. So effectively, what you have with an FTI is a mTORC1 inhibitor, a very potent, very well-tolerated mTORC1 inhibitor, and it is an ideal mechanism to take those tumors that perhaps are no longer responding to the targeted therapy and put them back into response. Mollie, maybe you wanna talk a little bit about how we're applying it and what to look for in 2026.
We've previously shown data with cabozantinib plus darlifarnib in renal cell carcinoma patients. We plan to show you an additional update of that this year. This time we'll be able to show you more dose levels. We were able to successfully give it with both a lower dose of cabo at 40 milligrams and full dose of cabo at 60 milligrams. Again, what's fascinating to look forward to is that these patients are all going to have already seen a TKI, usually cabo in a previous line of therapy. Are we able to then get them into a response, thus proving the mechanism. If we plug that mTORC1 hole that these cancer cells can keep going.
We have patients that we'll be able to show you that came directly from cabo onto our trial and how they did in their response. You don't expect to see more than maybe teens levels of response in patients that have already seen cabo previously, so that gives you a benchmark to look at as you're thinking through these things.
I think most importantly, we announced that we're now enrolling, so that'll be the dose escalation data we present, but we're now enrolling in the dose expansion portion, and this is designed to really just confirm that this mechanism does what we said it does. First and foremost, it's going to incorporate the Project Optimus rules, so we're gonna really be refining the dose.
We'll have two dose levels the patients can be randomized to, but the third is just cabo monotherapy arm to get a real baseline of what these patients look like in this particular line of therapy after the IO, what should we expect to see. Then for those patients that do not respond or that relapse, they can cross over into one of the darlifarnib arms. Again, if we're able to rescue responses or induce responses in those patients, we've really accomplished something and demonstrated the mechanism.
Got it. I guess just given all the different potential combinations and tumor types where you could evaluate darlifarnib with this mechanism, how are you thinking about where to prioritize your efforts and what places make sense for this?
We wanna be able to do two things. One is to have a strong kinda go it alone strategy. Mollie mentioned cabozantinib combinations, you know. That continues to be very strong in the second line. Even with an evolving landscape, we don't think TKIs are going away. Importantly, I may have stressed this, right? If we can enhance cabo, we can enhance Lenvima or any other TKI.
If we can enhance adagrasib, we can enhance sotorasib or divarasib or, you know, any of the KRAS inhibitors, whether they're MEK selective or pan. To your question, in parallel with our go it alone strategy, and by go it alone, it means, you know, ideally you can get to the market needing only capital, investment capital.
We're also, now that we have a clinical data set that says it's safe, it's well-tolerated, it's combinable, it's interesting, we're in a number of different discussions and looking to find call them collaborators. I don't think we're looking at the moment to do a strategic partnership, so clinical collaborators to combine darlifarnib and enhance the activity of their drug candidate or drug or their program.
What you want is a fit where we agree if there's strong data, we move forward aggressively, you know, to the market. The opportunity is the challenge. There's, by our calculations, 200,000 incident patients that we could attack with darlifarnib. Obviously, we can't do everything, but that opportunity is 20 times bigger than even the ziftomenib frontline opportunity. If we can start to chip away at that and, you know, we now have some competition. We've just seen-
Our first competitor on the FTI side. We think it's gonna be what you see in the KRAS space, for example, folks are going to combinations using cetuximab, for example, right, to deal with resistance and drive better durability. Combinations in RCC, right? It's all about now doublets and triplets. Darlifarnib is going to be an ideal combination agent in these different tumor types. There's a lot to do, a lot of value to create for patients.
Got it. Tell us about the competitive landscape?
Yeah, it's.
For darlifarnib.
I had said to the team, "You know, as soon as you show clinical data, expect that you're gonna see one to three companies in China," and we've now seen our first. You know, they're actually pursuing a covalent approach, a covalent FTI. Personally, because we also pursued covalent, we think that's probably not ideal. Imitation is the sincerest form of flattery. You're doing something interesting.
Yeah.
Let's see. You know, I think more working it into the way people think about how do we deal with resistance, how do we enhance outcomes for patients, I think that's a good thing. We welcome the competition.
Understood. We're expecting a couple data sets with darlifarnib both in combination with KRAS G12C, and also an update on the cabo combination RCC. Can you help sort of provide any additional color into those readouts, how we should be thinking about those?
Yeah. As I was describing for the RCC, you're gonna see, you know, more patients. You're gonna see about a year's worth more data. You'll really get an idea of the doses we're selecting to move forward into dose optimization. All around, that should be a very encouraging update, especially in these patients that have already seen cabo and other TKIs.
With the KRAS inhibitor, you're going to see our first time being able to show our adagrasib data in combination with darlifarnib, and again, the types of patients that are enrolled in these types of studies are patients that have, in general, already seen a KRAS inhibitor, even adagrasib in the past.
Being able to induce responses of any kind in these patients that are, you know, heavily pre-treated is impressive, especially if you're able to rescue a prior darlifarnib, prior adagrasib failure. I would be looking for those data and these very hard to treat patient populations, 'cause I'll remind you, it's non-small cell lung cancer, it's pancreatic cancer, and it's colorectal cancer where you really don't expect good outcomes once these patients are in the recurrent metastatic setting.
Got it. Remind us sort of your cash position. I think you mentioned you're running-
Yeah.
...about the milestones.
I think we announced $667 million, if I'm not mistaken, last week. That plus the $180 million that we have line of sight to takes us through that initial phase III MRD negative top-line result in the frontline setting and allows us to pursue not only this expansive development and commercial plan for ziftomenib, but darlifarnib, the next generation menin inhibitor. I mean, we're building a pipeline of targeted therapies around these two, we think, very important targets of menin and farnesyltransferase, so a lot that we can do. We're in a strong cash position.
Got it. Just last question from me. What are the catalysts and milestones for the year that we can look forward to?
Yeah. I think we've touched on it, but maybe I'll just sort of go through the year. As Mollie said, you're gonna see a publication on ziftomenib plus Ven/Aza in the relapsed refractory setting. You're gonna see the combination of ziftomenib plus 7 + 3 likely in the middle of the year. That's an update from EHA. Toward the second half of the year, you'll see ziftomenib plus gilteritinib in the relapsed refractory setting. Moving over to darlifarnib, you'll see the RCC data that Mollie mentioned, the KRAS G12C data. As Brian spoke to, you're gonna see us, I think, continue to post quarter-over-quarter growth in KOMZIFTI sales.
Hopefully by the end of the year, or very early next year, it's clear that we've taken market leadership in NPM1 mutant relapsed refractory AML. We think that speaks to our potential to take leadership throughout the treatment continuum and in the class. We wanna be the leaders on menin and the leaders in farnesyltransferase. If we can do that, then it's gonna be a very good year.
Great. Thank you very much for taking the time.
My pleasure.
Thank you.
Thank you.
Thank you, Jonathan.