Healthcare conference in very toasty, Las Vegas. My name is Jason Zemansky. I'm one of the senior, small-cap analysts here at BofA, and I'm very pleased to have with us on stage Kura, Troy Wilson, CEO, and Brian Powl. Thank you so much for joining us.
Thank you, Jason.
Thank you.
Maybe to start broadly for those less familiar with the Kura story, could you please provide a brief overview of ziftomenib and darlifarnib?
Sure. Yeah. On the, on the one side you have ziftomenib and, or commercial name KOMZIFTI. We have approval in the, relapsed refractory NPM1 mutant setting. Our goal is to be the market leader and drive sustainable quarter-over-quarter growth there. We have a, I think the largest, most comprehensive phase III development program in both the intensive and non-intensive frontline settings. We'll be giving a data update on that here in a few weeks. We have extensive studies looking at different combinations to really be able to advance the standard of care and get ziftomenib throughout the treatment continuum in AML. We're also studying ziftomenib in gastrointestinal stromal tumors, or GIST. We're making good progress in dose escalation.
Probably not looking at a data update until next year, but definitely some potential there, as well as investigating other solid tumors. Shifting to the darlifarnib side, darlifarnib is really trying to address the problem of innate or acquired resistance to targeted therapies. We have a data coming out at ASCO looking at darlifarnib in combination with adagrasib, the KRAS G12C inhibitor that's approved. That will be the third installment of an FTI plus targeted therapy. The first being in PIK3CA mutant head and neck, the second being in renal cell carcinoma. That's a really interesting opportunity. You know, FTIs potentially combine with and can enhance targeted therapies in kidney cancer, breast, lung, colorectal, and pancreatic. There's quite a significant opportunity.
We're gonna have a poster presentation on 30th May a nd an investor event, 3rd June to really give a strategy update on that program. So each of those two programs, Jason, I think drives value for cancer patients. I'll just remind everybody, the ziftomenib AML program is in a partnership with Kyowa Kirin and fully funded through to initial top-line results. That gives us, you know, a significant running room and really the ability to maximize both ziftomenib and darlifarnib for patients.
Thanks, Troy. Let's focus initially on ziftomenib. You framed sort of the key driver here in the market as physician preference. I'm curious, you know, what has initial feedback been like from prescribers and treatment centers on ziftomenib?
Sure. Brian, you wanna take that?
Sure. Yeah, thanks. We announced in our first quarter earnings just yesterday, which I think is a good proxy for how physicians are responding. Yesterday we reported USD 5.8 million in net revenue for the first full quarter of launch. This equates to coming from 85 new patient starts. Of the patients in this population, of the NPM1 mutated population, that equates to about 40% of the new patient starts among the menin inhibitor class. That's a great start for us. I think what that shows is the profile of KOMZIFTI is competitive. Physicians see it as a compelling choice for them.
Of those patients, 1 more stat just to share with you, of those patients that started, about 40% of those were actually treated in combination, which is off-label outside of our approved indication, but based on physician choice, were used in combination with either Venclexta or in combination with the FLT3 inhibitor, gilteritinib.
You know, you flagged the administration profile as being a major source of differentiation and its combinability as well, which you sort of alluded to in the previous answer here. Any sense that these are starting to resonate? Is it something else you think that's getting physicians excited?
I think what this has shown us is that physicians are getting excited and they have a choice, right? I think, before we came to the market, there was one choice available for the for a menin inhibitor, you're starting to see uptake in a lot of centers, both those who are experienced with KOMZIFTI, in ziftomenib in our trials, but also those who are experienced with other menin inhibitors. It's really the profile, the balance of the efficacy, the safety, combinability, and the convenience of once-daily dosing in a very complex patient population puts KOMZIFTI in a potentially favorable position that we think will help us get to leading the market share coming out of that first year.
You mentioned a good point, is that a lot of your prescribers participated in the clinical studies. In terms of how do you reach new prescribers, and I think from a maybe broader perspective, you know, what about the community prescribers that maybe are less familiar with some of the more nuanced profiles of both assets?
Sure. I think that in the treatment of relapsed refractory AML, largely the treatment is happening in the academic centers, right? It's probably 85%-90% of those patients are gonna be treated. With these are sick patients, they tend to go to those academic centers. The decisions that are being made are really more focused right now at the academic centers. These are kind of those large tertiary centers.
I think from our objective to reach those patients, we have our current sales force, which is out in the field engaging with those physicians, but we also have our partner, Kyowa Kirin, who has their field force also spending a percentage of their time also raising awareness and focusing. It allows us to get breadth and depth to educate on the differentiation, and that's what we're starting to see already kind of in this first full quarter of launch, strong uptake. We expect to extend that to even more centers as the launch progresses this year.
Yeah. I might, Jason, I might just add to that. We were actually pleasantly surprised by the extent of combination use, spontaneous combination use, as Brian Powl mentioned. A lot of these academic, you know, physicians are very sophisticated, and they're really experimentalists. Almost every patient history is different. They're, you know, they're up on the literature. They're talking to one another all the time. I think it speaks to KOMZIFTI or ziftomenib's profile that they can combine it. They can It's once a day. You know, it has very benign safety and tolerability profile.
That's allowing them to do, to really find the best solution for each patient. This is very much in the relapsed refractory setting, kind of a bespoke treatment that the physician does for each of his or her patients. KOMZIFTI, although we're not promoting that, we're really promoting the monotherapy, it gives them that flexibility and that ability to find just the right solution. I think it's giving us this, you know, real momentum and real potential to continue to not only take market share, but ultimately grow the market in this relapsed refractory NPM1 setting.
We, you know, sometimes we talk about leading indicators of how well a launch is going. Is the combination percentage, is that kind of what you would point to as being something investors should focus on? Or is there another sort of indicator that would help indicate that, you know, everything is resonating and the trajectory is, you know, inflecting well?
I would say the two things that would count for that to kind of show some of that lead to those leading indicators, one is the new patient starts. The number of new patient starts are much more rapid than even we expected. We knew we would be able to come out strong, but 40% of those new patient starts in the first full quarter is a strong start.
Couple that with the combination use of physicians choosing to use KOMZIFTI in combination, those two also will lead to potentially it's finding the right patient to be treated potentially in the earlier lines of therapy rather than salvage lines of therapy, and they potentially may get a longer benefit because they're earlier in their treatment course. In combination, there may be a benefit that the physician sees to add, you know, KOMZIFTI and then potentially treat longer and get a better benefit for those patients.
You might also add the access and the payer preferences. I think those are also good leading indicators.
Yeah.
If you want.
Yeah. Yeah, to add to that point, we did also share that we have over 93% of covered lives are now on policy and on plan for our payers. We've largely in that first, you know, quarter and a half, essentially, since we got our approval, have very good coverage that is at parity. We do have a number of plans, I think we have 10 plans that have actually put favorable positioning of KOMZIFTI, either step edits or tiered formularies where they prefer KOMZIFTI over other therapies in this space. It equates to about 12 million lives right now.
Lots of good leading indicators.
Absolutely. Given how relatively small the patient population is and the level of high unmet need, you know, how quickly do you think it will take for menins to re-reach that peak penetration in the relapsed refractory setting? Then, you know, could we potentially see KOMZIFTI taking measurable share of the, you know, what you call, what you've estimated as a $300 million to $400 million market opportunity?
Yes. I think that the, as we've shared before, as you said, it's a $350 million to $400 million market, we think, in that relapsed refractory NPM1 mutated setting. The market dynamics for those patients is that there are several options already available to them, Venclexta, FLT3, if they're co-mutated, other therapies that we need to be able to penetrate in. What we're trying to do is build out, grow the market for menin inhibitors and show that menins are the preferred treatment of choice for those patients, but also then ultimately become the market leader in this space. We feel confident that it may be a slower growth in areas where there's no options available for those patients, but ultimately, we think we'll be able to get to become that leading class share in the menin class by the end of the year.
In terms of making, Ziftomenib, foundational across all of AML, I mean, you've talked about a very comprehensive first-line, development program moving forward, but, you know, there's certainly more menins coming up the pipeline. You know, what does it take, and what does sort of the timelines look like?
Yeah. There are, you know, there are three or four menin inhibitors, Jason Zemansky, that are in active clinical development. I would say us, J&J and Syndax, you know, we're all in registrational studies of some sort. There's a, you know, the Sumitomo Pharma compound is quite a ways back. They have a dose in KMT2A. They don't yet have a dose in NPM1. One of the challenges for subsequent drug developers in AML is, as you see triplets getting approved, and that's why we're sprinting as fast as we can to the frontline, you know, the next company coming along has to run its investigational triplet against an approved triplet.
Unfortunately for Astellas, we saw just recently, just a, you know, few weeks ago, they did not have a successful trial when they ran the triplet of gilteritinib 7+3 versus midostaurin 7+3. That was a 700 and something patient trial, not enough to, you know, ultimately deliver the survival-based endpoint. I think you're gonna find the AML development limiting. There are other options for menin inhibitors, you know, in solid tumors, potentially in diabetes. We may see, you know, later entrants going elsewhere. You know, our goal is to be the market leader throughout the treatment continuum in AML. We've been, you know, we were there first, we were in menin first, continue to, you know, drive leadership not only in AML, but in solid tumors, diabetes, and elsewhere.
Got it. Let's talk about some of the specific catalysts near term.
Sure.
The KOMET-007 study, we'll see first half of 2026. It's the update in intensive chemotherapy. You know, how would you frame the outcome and what should investors be looking for?
Right. We just yesterday announced the abstract was published for that study. For everybody's benefit, this is ziftomenib plus intensive chemotherapy in both NPM1 mutant and KMT2A rearranged patients. This is a data update from the KOMET-007 study that we've had ongoing. The last update we gave was at EHA 2025, we're now a year on from that. It also forms the basis for the KOMET-017 registrational study that's being run in the same populations. What are you looking for? You're looking for high rates of CR. You're looking for high rates of MRD negativity. You're looking for extended durability. Each of those will be important. You can see from the abstract, you know, the CR rate for NPM1 I think is 96%. The MRD negativity is 80%.
The, the median patient has been on something like 17 months. You know, fortunately for the NPM1 population, there we don't yet have a duration of response, so I think that bodes well. It's. The study is ongoing. One of the interesting learnings, Jason, from intensive chemotherapy is, we believed, and, you know, I think the dogma was before any of us had started, that in the intensive setting, you know, you'd maybe get patients on a menin inhibitor for one or two cycles, and you'd lose them to transplant. Interestingly, when you look at the KOMET-007 data, that's not what you're seeing in the NPM1 patients. You do see the KMT2A patients going to transplant, because that's really where what they need to do.
If an NPM1 mutant patient has an MRD negative CR, transplant is contraindicated. The mortality risk doesn't outweigh the clinical benefit. As a result, you have these patients, and you look at the swim lanes, and they're all just on ziftomenib, you know, cycle after cycle. That's important from, you know, really improving the standard of care. It's also important from a commercial perspective. 18 months of therapy is, you know, if you take the incident patient population of 11,000 patients, that's a $10 billion opportunity.
Now, we'd look to take just a portion of that, but I think we're starting to see the difference between ziftomenib and all, everything that's come before is these patients can stay on for 18, you know, cycles or longer. We've not seen that with chemo, with venetoclax, with other targeted therapies due to tolerability concerns. Everything you asked Brian about those attributes, combinability, convenience, cost, safety, those become even more important as we're thinking about the frontline population in that continuation therapy setting.
Great. Let's extend this a little bit further. You have the KOMET-008 update coming up.
Yep.
You know, how much of a driver can this be just given how common you see a FLT3 mutation with a menin mutation?
Yeah. FLT3 is 1/3 of AML, and it's 1/2 of NPM1, the patient population. They're co-mutations. There are three FLT3 inhibitors out there. We're actually working with two of them. We have the KOMET-008 study ongoing with gilteritinib in the relapsed refractory setting and a study with quizartinib in the frontline setting. In preclinical models, Jason, that combination is curative. I think, you know, the update that you referred to, the KOMET-008 update, we're expecting at the end of the year at a major medical meeting.
That will be important because, you know, if you can improve on both a FLT3 inhibitor and a menin inhibitor as monotherapy by putting them together, you know, nearly 1/2 of your NPM1 mutant patients are gonna have that genotype. In terms of both creating a solution that's best for them and giving physicians choice and then market leadership, we're well ahead of the competition on pioneering these combinations with FLT3 inhibitors. I think that'll be a meaningful update.
Got it. You referenced the KOMET-017 programs as these are the frontline settings. Can you give us your expectations on enrollment timelines? What's the status look like, especially now that, as you mentioned earlier, we have multiple menin inhibitors advancing?
Yeah, happy to. We made a deliberate decision a number of years ago to combine the 2 phase III studies into one protocol, and that is the KOMET-017. We call it the one-stop shop. As a result, it's easier for sites. They activate one protocol. Any patient that presents at their clinic has a space in either the intensive or non-intensive study. It's one budget, it's one sort of stand-up, and we're essentially standing up 2 phase III at the same time. Enrollment has been brisk. I think we've demonstrated with 007 and 008 that, you know, the 007 update that we talked about is nearly 100 patients in the relapsed refractory setting, enrollment is going very well. We're well ahead of the competition by one year, maybe two, in the intensive chemotherapy setting.
I'm not aware that our competitors have yet started their trials or started enrollment. In the non-intensive, the venetoclax combo, everybody's working together. By combining the two studies together, Jason, we were able to attract many of the leading sites in Europe, in the U.S., and in Asia-Pac. That does two things, right? These are many of the leading practitioners in AML. They're also our customer base, and part of this is winning hearts and minds. If they're having good experience in the 017 studies, you know, we know that's gonna read through into the commercial landscape. We're taking kind of a whole holistic approach that very much commercial and development working in partnership.
Great. You mentioned earlier there's opportunities outside of AML, just being one of them, diabetes, there's cardiometabolic indications as well. Why does a menin make sense in this population?
Menin is an epigenetic modifier, right? Menin acts by regulating gene expression of other downstream genes. In AML, these are genes involved in either in differentiation or in leukemogenesis. In GIST, menin regulates KIT expression. You have a KIT inhibitor that, you know, blocks catalytic activity, and you have a menin inhibitor that blocks KIT transcription. In diabetes, menin regulates the CDKs in pancreatic beta islet cells. It actually, by blocking menin, you take the brakes off the CDKs, and you get selective proliferation of pancreatic beta islet cells. It's context dependent, but it also gives you It's sort of the Swiss Army knife of therapeutic targets.
You have discussed a potential $7 billion opportunity for the menins. I mean, what are some of your key assumptions here and, you know, timelines in terms of getting to that potential?
Yeah. Very simply, in the U.S., you have, we think 50% of AML patients are going to be eligible for menin therapy, and very simply, that's FLT3, NPM1, and KMT2A. There are likely additional mutations as well, but let's just keep it simple. That's 50% of all of AML. There's 22,000 patients a year diagnosed with AML. Let's 10,000 patients to make the math easy. If you could keep those patients on therapy for 12 months, you're talking, you know, about $5 billion. If you can keep them on for, you know, a year and a half, as I said, it's $10 billion. I think we're being conservative and saying, you know, you're going to get a stacking year-over-year, but $7 billion peak sales for the class seems very reasonable.
How do you get there? You need, of course, you know, to get the patients on drugs and then to keep them on for many cycles. That's why I think the 007 update from EHA will be so illustrative because that's as close to both the phase III study and the real-world population of what one would expect as you're gonna get at this stage. All indications are, Jason, I mean, what you'd like is to delay the onset of disease recurrence. The drugs are very good at eliminating the leukemia. The problem is the leukemia comes back. In, for example, in the intensive chemotherapy setting, 60% of patients recur within two to three years.
That's what you're trying to prevent. By having a therapy on board with the patient that's very well tolerated, you could prevent that recurrence. You know, you can delay the time to transplant. Have we seen this before? Yeah, in myeloma. Right? This is exactly these, the multi-drug regimens that both allowed to get disease remission and then to extend that. We've seen dramatic transformation of the landscape in myeloma. The hope is this is the beginning of the same thing in AML.
Got it. Well, let's shift gears to darlifarnib. Obviously, the FTI class has been a focus of development for some time. Why do you think agents like tipifarnib fell short, and I guess where's the confidence that darli can deliver?
We needed, you know, three things, for FTIs to work. You needed an understanding of how to use them. Because they're not like a kinase inhibitor. They block farnesylation of different therapeutic targets. You need an understanding of the biology. You need next-generation sequencing to be able to find patients. Jason Zemansky, most importantly, you need the other targeted therapies. An FTI on its own is really not effective at driving responses except in something like HRAS mutant tumors. That was really chapter one with, or maybe chapter two, with tipifarnib in HRAS mutant solid tumors.
What Francis Burrows, Shivani Malik, and our translational team figured out is if you can assault a tumor with a targeted therapy, a TKI, a KRAS inhibitor, you can actually make that tumor cell then dependent on an FTI. The FTI is working by blocking a protein called Rheb, Ras homolog enriched in brain. Rheb localizes a protein called mTORC1 or a complex called mTORC1. mTORC1 sits right at the bottom of the MAP kinase and the PI3 kinase pathways. Everything I've just mentioned, TKIs, PI3 kinase inhibitors, KRAS inhibitors, they all ultimately signal through those pathways. It's like turning the stopcock at the bottom of the, you know, of the cascade. You get a very effective block. The question is now, can you safely combine? We've shown twice you can. You'll see the adagrasib data here shortly.
Can you enhance the activity? This is just to be clear with everybody, this is not a new problem, right? People have been trying to find companion therapeutics since I've been in this industry. We've tried, you know, AKT, we tried MEK, we tried SOS1, we've tried SHP2. Nothing's really worked. FTIs may actually be the solution. I think the data that you're gonna see at ASCO will be very illustrative of what we can do in KRAS-driven tumors.
Got it. Why does it make sense to start in RCC? I mean, you've shown promising preclinical efficacy in tumors like NSCLC, colorectal, HNSCC.
Yeah. This is where you have to take the science, and you have to overlay it with the business realities. One needs to be able to have a clear path to get to the market where you have only one investigational agent. I mean, you can do novel combinations, from a development perspective, those are much more difficult, right? How do you show the contribution of individual components? As an alternative, if you go on the back of cabozantinib is the accepted standard of care in second-line renal cell carcinoma. It continues to grow market share. It has other applications. You know, that's well established. You build on that, you have to show what can darlifarnib do to add to cabo. It's just simpler from a development, regulatory, and commercial perspective.
You could do a similar thing. You know, there will be a KRAS inhibitor here approved relatively shortly, we think, in pancreatic. Going on the back of that just greatly simplifies your development and regulatory as well as your commercial strategy. You can start to get more creative if you want. You can add other novel agents. I think you need to, Jason Zemansky, have your base case and then your upside cases. That's, that's where we translate the research and the early development to how do we think about, you know, being good fiduciaries and making choices. Ultimately, FTIs can go a lot of places.
You have to prioritize. We'll talk more about this strategy at our investor analyst event on 3 June . That'll be after the ASCO data is presented. We're gonna have a very well-known KOL in the KRAS space, and we'll, you know, we'll explain kind of the background. We'll go through the clinical data with adagrasib, and then we'll talk about the next steps and what's the development and commercial strategy going forward. I think that'll the KOL will be able to add valuable perspective on why a companion therapeutic, why an FTI, why darlifarnib.
Got it. Well, you reported some fairly encouraging numbers last month at IKCS ORRs of 44%, DORs of 94%. You know, obviously, it's still early, but where does that translate in terms of overall benefit in these later line settings? You know, is there a compelling enough case you think where you can move not only second line, but first?
I think so. I think at this point, Jason Zemansky, we feel confident we have a play in third line based on the data we have today. I'll just remind everybody, we are conducting a phase I-B study in combination with darlifarnib in combination with cabozantinib. We're investigating a five and 8 mg dose of darali with a 60 mg dose of cabo. We're doing a third arm of cabo monotherapy, where patients who progress on cabo can then roll over into the combination. We can further test this hypothesis that we can rescue them by adding darlifarnib. Based on what we have today, the KOLs are telling us we've got a clear shot in third line. You'd like to obviously go earlier.
We need to get we need to finish the phase I-B and understand, is a second line strategy the doublet on top of cabo, or do we consider a triplet? Let's, you know, we'll hold that thought. The tolerability, what we hear from the physicians, and I think you saw it in the data, darlifarnib's extremely well-tolerated. The only real AE we see is neutropenia. We didn't make any effort to try to mitigate that in the dose escalation because you want to see toxicity. Now in the phase I-B, we allow the physicians to use G-CSF, so that, you know, that will be mitigated. I think there is an opportunity to combine in the front line.
Something we hear from physicians is, as they're considering these combinations of IO, TKI, and HIF-2 alpha, if a patient's disease progresses on those three, what else are you going to give them? You going to give them some subset of that? Not ideally. The physicians are really attracted to the idea of a novel mechanism of action coming into renal cell carcinoma. Now we have to sort of figure out what's the development plan year one, three, five, and onward. You'll see us elaborate that throughout the rest of this year.
Well, wonderful. Exciting year. Thank you so much, Troy and Brian.
Thank you, Jason.
Thank you.