In the background, I start off with kind of like, oh, what's an overview for the company? But I kind of feel that everyone knows Kura Oncology, so we don't really need the background per se right now. We can jump in right into the main event, which is kind of the upcoming data at ASH and early 2025, and so maybe just jumping right into it, right? We're expecting about 100 patients' worth of data from the KOMET-007 study evaluating zifto and several combinations. Would love to kind of just, and you've done it in the past, but as we're getting right into the meeting, just kind of level set us with what do you expect to see? What do you consider to be a success from this data set that you'll be revealing to us?
Sure, Ren. So, thanks. And let's use this slide that you've kindly put up to kind of walk people through. So what this shows as we go from left to right is, first of all, the prevalence of menin inhibitor on ziftomenib patients. And what you can see there, we have NPM1 is 30%, KMT2A is 5%, and then we've got that green of other mutations. That actually, Ren, could be more than 50%. I'm just going to sort of jump out and then jump back in. We are currently dosing patients in combination with gilteritinib in the relapsed refractory setting. That's, of course, where gilteritinib is approved. We anticipate dosing patients with quizartinib in the frontline setting. That's where quizartinib is approved. Both of them are FLT3 inhibitors. The FLT3 population is 25%-30% of AML, and about half of those patients overlap with NPM1.
There's a good rationale, Ren, to use menin inhibitors in those FLT3 mutant patients, whether or not they have NPM1. So let's just think sort of holistically as we think throughout the continuum of care. We're trying to treat roughly 50% of all patients. And that's great. That's the opportunity, right? So there's 20,000 incident patients in the U.S. There's 60,000 globally. About half of those patients, I think, are pretty obviously candidates for ziftomenib. The challenge is you've got to get there through multiple trials. And you can see us having laid that out. So we have O7 here, whereas you've indicated we are exploring ziftomenib in combination with both the fit regimen of 7+3, the unfit regimen of venetoclax and azacitidine. Importantly, the fit regimen, the data that you'll see, is in patients with adverse risk. The Ven/Aza is in patients who are relapsed/refractory.
We started in those more difficult patients to make sure that we understood the safety, the tolerability, the combinability. I'm happy to say we're now dosing patients in the expansion arms in both the frontline 7+3 with and without adverse risk and the frontline Ven/Aza populations. You won't see the expansion data at ASH. You'd ask sort of how do we level set. I think if you want these drugs to become blockbusters, you need to think about how do I keep a patient on a menin inhibitor? How do I drive clinical benefit for prolonged periods of time? And just do a quick back-of-the-envelope calculation, right? If you take 3,000 patients, that's 30% of the 10,000 eligible. You treat them. One of our competitors is now launched. So take their price point and then keep those patients on 12 months.
You're going to end up with greater than $1 billion in sales. And then for every six months that you add, you're talking about sort of $500 million in revenue. Those are the variables, Ren, where you're talking about number of addressable patients and then time on therapy. So I would focus people's attention. We're excited to share both sets of data with you, both from the adverse risk fit population and the dose escalation, as well as the Ven/Aza. But for the adverse risk, the benchmark is pretty obvious, right? So it is the 7+3 control arm in the Vyxeos study. Vyxeos was a drug developed by Celator. It's now marketed by Jazz. But just go to the prescribing information to the Vyxeos package insert.
Go to table six, and you'll see that the CR rate in the control is 26%, and the median overall survival is six months. That's the benchmark, right? You can already tell from the abstract, the 200 milligram patients, 100% CR rate. They're all still on therapy. They're all still alive as of a year later. I'm not going to get ahead of the abstract, Ren, but that's kind of how to think about it. This is as hard as it gets in 7+3. So as you go up in dose, 200, 400, 600, I would expect the activity to remain fairly consistent. What will be important is how do we look about duration of response? How do we think about time on therapy? That's really going to help inform the commercial case. With Ven/Aza, it's a much more complicated picture.
It's not to take anything away, but it's relapsed refractory. And as a result, you've got patients who've had prior Ven. You have patients who've had prior menin inhibitors. You have, I think, one to eight lines of prior therapy. What you're really looking for there is safety and tolerability. But the activity, again, I think has been we've been encouraged as we've gone up in dose. The safety review committees, the IDMC and the SMC, have both endorsed, Ren, moving forward at a 600 milligram dose with both 7+3 and Ven/Aza in the expansions. So there'll be a lot of data to share, and there'll be a lot to unpack on the other side of that. But hopefully, that sort of sets the frame.
Yep, definitely does. You mentioned the 200, the 400, we're going to be seeing 600 milligram doses. And there continues to be this debate, or we get questions regarding dose response, right? And I think you mentioned it just in your previous comments that you expect it all to be roughly around the same area. We would have thought, well, as you increase the dose, maybe you'd get better responses, but how can you get better than 100%?
Correct.
Right? So I guess what I'd love to kind of unpack a little bit is how are you thinking about it? You've already got some of that 400 milligram data in the abstract. It could be just small numbers, but it's a little bit different than what you're seeing at 200. You've already decided that 600 is what you're going to be using moving forward. How did you make this decision? And how should we be thinking about these dose responses that we're seeing?
Yeah, so great question, Ren. Let me be really clear to you and the audience. There is no inverse dose response, right? I understand why people might ask that. Dose escalation studies, this study is not intended to sort out the activity of one dose versus another in the escalation. Those cohorts are not powered to do that. Certainly in the Ven/Aza context, the cohorts are not sufficiently homogeneous to even assess that. Again, we and others, I think, are seeing a difference whether patients have been pretreated with Ven or not. That alone, Ren, will throw off that kind of analysis, right, when you're talking about sort of six to eight patient cohorts. In fact, there is a dose response, but it's interesting on safety and tolerability.
People might scratch their head and say, "Well, how's that?" Remember that the toxicities that AML patients, or I should say the safety events that they typically encounter are infections, transfusions. That is what gets them in trouble. As the safety monitoring committee and the IDMC saw, interestingly, Ren, and this is particularly easy to see in the frontline Ven/Aza setting, the safety gets better as you go up in dose. You say, "Well, why is that?" It means the counts are recovering more quickly. So as a result, patients have fewer transfusions. They have fewer infections. So the overall safety picture looks better as you go up in dose. Because these regimens are already pretty active, Ren, to your point, you can't do better than 100%. I think what you want to see is a high level of activity as your dose is escalating.
Then if you can give 600, give 600. What I will say to you is look to the ASH data, both the frontline and the relapsed/refractory 7+3 Ven/Aza for evidence as to why we say that. But these committees, which are the investigators themselves, have looked at the totality of the data, not just what's in the abstract, and have clearly said 600 is the right dose. There's no inverse dose-response as it pertains to clinical activity.
Got it. Got it. Well, we're probably a week away now from seeing all that data, so we're looking forward to it, and I won't belabor the combination data. Let's talk a little bit about KOMET-001. This is the near-term kind of opportunity data in the first quarter of 2025. You've set expectations before, but now we have an approval of a competitor drug out on the market. Kind of would love to get your thoughts based on the label of the competitor as well as what you're hoping to show, let's say, in the first quarter of 2025.
Yeah. So we've guided that we'll release top-line results in early 2025. I don't think, Ren, I've ever varied in answering this question. And that is you're looking for 20%-30% CR/CRh. You're looking for a median duration of response of four to six months. Anything in that window, FDA has indicated is likely approvable. And you've seen that with the competitor approval. Look, ideally, beyond the upper end of that range, I've said to people very clearly, don't expect the 35% CR/CRh rate that was seen in the phase one. You're going out to many more sites. You're going out to generally different and in some cases sicker patients, but you're looking for 20%-30% CR/CRh. I think, Ren, as with many targeted therapies, you're going to see we see this with the other competitors as well, right?
The activity is kind of looking like it's in that band, particularly as you go out to larger numbers of patients. What's interesting, and I'm just going to allude to the second part of your question or address the second part of your question, is the safety and tolerability. I'm going to give a caveat. In the relapsed refractory setting, there is a very high tolerance among physicians for DDIs, for AEs because these patients are in such, there's such a high unmet need, particularly among the KMT2A rearranged patients. I congratulate our colleagues and our competitors who got that approval. That is what patients need, right? Hooray for them that they did it. Interestingly, between that and then the top-line NPM1 data that came out, you're now seeing evidence of grade 4 NPM1, sorry, grade 4 QT prolongation. You're seeing now higher rates of DS.
You're seeing now deaths on study. You're seeing, again, DDIs and needing to alter the dosing paradigm. I think zifto, as having good or better efficacy and significantly improved safety and tolerability, will be very competitive in that relapsed refractory setting. What you're going to see, Ren, is that combination of clinical activity, safety and tolerability, absence of DDIs, absence of these AEs, like, again, our competitor requires weekly ECGs and then monthly ECGs. Try doing that in the frontline setting, right? If you're going out 12 months, 18 months, and you've got other options, and not just Kura, right? There are other competitors steaming along as well.
I think safety and tolerability. I keep saying this, safety and tolerability becomes important because that's what governs, can you push the dose in combination with standard of care and can you keep patients on therapy without dose reductions, without dose interruptions for long periods of time. That's what's going to maximize clinical benefit, Ren. It's also going to maximize the commercial story.
We heard something very similar. We had just spoken with Dr. Medeiros from Stanford as one of our KOL calls just as part of the summit. And it's very interesting. He talked exactly like what you were saying. Because you and I have talked before in the past, he said, "Look, in the second line, maybe people aren't as worried about QTc prolongation." He kind of actually said that if another drug comes in that does not have QTc prolongation, that has, at least from a physician's perspective, it has significant room to grow and even supplant the first-to-market mover advantage. So it'll be really nice to see how it all comes together. One quick question on the safety aspect. We saw differentiation syndrome as a black box label with the competitor. Do you think this is something that is likely to be a class effect?
Like every menin inhibitor will have it?
Yeah, Ren, I would go so far as to say if you're not seeing episodes of differentiation syndrome, you probably don't have a menin inhibitor, right? That is the mechanism of action. And so long as, so just so folks understand, in the relapsed refractory setting, these patients are often hospitalized. If you're hospitalized, that's grade three. That's per se grade three. What you're looking for is can it be readily managed? Can you continue to treat through it? Does it cause any sort of discontinuation or interruption? We're out now at a point, Ren, as a monotherapy in the NPM1 setting and in combination, we're seeing, I think, very acceptable levels of DS.
To your specific question, I would anticipate, I mean, look, I'm not going to speak for the agency, but I would not be surprised if each of the menin inhibitors got that kind of black box language for DS because it is something that physicians need to be aware of. And it's no different than the FLT3 inhibitors have seen this. So it's something that the community, the physician community, is very much learning how to work through.
Got it. One final question just regarding ASH. I assume that there'll be an analyst event or some sort of public disclosure and discussion with KOLs. Is that correct?
Yeah. In fact, I think our press release came out this morning. We are going to do a virtual event. It is bright and early 5:00 A.M. Monday morning. We should have two of the investigators from the 007 study to walk you through both the relapsed refractory data with Ven/Aza and the frontline data with 7+ 3. So we're going to get an early start on the day. But at that point, Ren, we'll have the benefit of all of the oral presentations having been done on Saturday and then our Ven/Aza poster presentation on Sunday.
Excellent. Looking forward to it. So I'd be remiss if we didn't talk about what I thought was an amazing deal that was done with you guys several weeks ago, right? You announced a global partnership. I'd love for us to maybe discuss a little bit about how you think about maximizing the value of ziftomenib for patients, especially in context with this partnership and why you could have done this after the KOMET-001 data. There are different times you can do it. Why do it now?
Yeah, sure. And let me speak about it, and then we can go to the specific terms, Ren, or that's fine. We can go there now. So our overriding goal is to maximize the value of ziftomenib for both patients and shareholders. And I think we've taken a conservative view. The market opportunity in the relapsed refractory setting is probably several hundred million dollars. And that's just driven by time on therapy. It's just that simple. Those patients are unfortunately so sick. That's why the median duration of response, you're shooting for kind of four to six months. That's going to have a commensurate impact on the commercial case. The frontline opportunity we believe could be multibillion.
And that's where I say to you, if you're treating 10,000 patients per year in the U.S. and 30,000 globally, at these kinds of price points, you can build a model fairly quickly that gets you into the blockbuster range. The advantages of monotherapy, the strategic partners are not particularly focused on monotherapy. And the reason is just, look, it's relapsed refractory. It's a relatively more modest opportunity. But the advantages of an approval are high unmet need. We're the only menin inhibitor that has BTD in the NPM1 mutant subset. There's the chance to set pricing. That's important. And then, of course, the opportunity to give patients commercial access. But if you look at the opportunity in the relapsed refractory versus the frontline, you're talking about something that could be like 10 to 1, 10 to 1 in favor of the frontline.
Now, as you'll begin to see from the data that we present at ASH, I think J&J is presenting data at ASH in the frontline combinations that could be a very meaningful opportunity provided you can A, drive a survival advantage and B, keep patients on therapy. So pay attention to those two things as you see the data. Now, we had a lot of people stand up and applaud. We had, as you could tell from the stock reaction, people from whom I will not be getting holiday cards. And I'm not trying to make light of that. It's just, it wasn't. It was viewed negatively by a number of shareholders who I think were disappointed, A, by the prospect of near-term M&A, and B, like, what does the timing mean? And let me just address that, Ren, head on. So I went back and looked.
Every major first-in-class HemOnc asset has been developed in partnership. I cannot think of one that hasn't. Perhaps the audience has one, but I can't think of one. This is first-in-class, right? Starting with Rituxan, which was IDEC and Genentech, Imbruvica, Pharmacyclics, and Janssen, people forget venetoclax was developed by Genentech and AbbVie. Either one of them could have done it independently. They came together to do it. You have Carvykti with Legend. You have Darzalex with Genmab and Janssen. That, I think, Ren, speaks to the challenges of frontline development in HemOnc. You can see back from the slide before. We don't have to go to it. You're talking about fit, unfit, FLT3, and post-transplant maintenance. If you really want to maximize the value, you've got to do all four of those. All four are randomized global phase threes.
I operate that there's going to be at least one large pharma competitor out there. And that competitor, of the deals I just mentioned with frontline first approvals, they're on three of them, I think. So they understand a good thing. And they've said that. They've said, "We see the opportunity in frontline and in post-transplant maintenance." Let's go back to the deal term for a second, Ren, if we can. So importantly, this is for ziftomenib alone. And it's going to be leukemia, GIST, and then any other solid tumor we would do with zifto, but at the moment, we're focused on leukemia and GIST. We think those could both be billion-dollar-plus opportunities. We received $330 million upon closing. People got a little bit wrapped around the axle with the near-term milestones. Let me just say this.
The model was Pharmacyclics, Janssen, where if you go back and you look at that, they very carefully titrated the milestones to the development spend. So we sat down with the global development plan across four trials and said, "How do we make sure the milestones line up in such a way that Kura always has multiple years of cash and is able to sort of fully fund its portion of this development and commercialization?" And that's why, in our view, that's $750 million, which if we just execute is reasonably well assured. There will be additional milestones beyond that, but that allows you to get all the way through O17, which is fit and unfit, and either PTM or FLT3. Post-transplant maintenance will probably be the next trial to lock in, and then FLT3 will be the fourth.
Importantly, Ren, what we retained was we're the lead commercial party. We run global development, and importantly, we book global sales. If we're able to achieve our goal, and for the first time, you've seen us put now in the press release and in our corporate presentation, we think this could be up to $3 billion a year in the frontline, more if you consider the ex-U.S. markets. If we're booking all those global sales, yes, it might take M&A off the table in the near term, but in the longer term, pharma is looking for top and bottom line growth, the ability to control development, to control commercialization, to book all of U.S. sales. Those are strategically valuable rights that we retained. You can count on one hand, Ren, the number of deals that look like this.
We, of course, went and talked to a number of other parties, and they said, "Wow, that is an amazing deal. Congratulations." If you, Kura, were willing to give up the booking of sales or willing to give up leading commercial, we could do something similar, but that isn't the right thing for Kura shareholders. So what this does, Ren, importantly, is it funds the development of this program through to commercialization in the frontline. Now, hear me clearly. Not commercialization next year, commercialization in 2028, 2029 when we're in those frontline indications. Our entire ziftomenib development program is funded. And importantly, investors and others will get to see these continual data updates. So you're going to see the data at ASH. I'm hopeful perhaps we'll give you another data update at EHA middle of next year and then again at ASH.
What you're looking for is what does that landmark data look like in the frontline settings, right? Are we seeing patients stay on 12 months, 18 months? How do we think about that? That's going to help both de-risk the ultimate phase 3s and also to help support the commercial case. We're thrilled to be working with KK. They have a dedicated expertise in HemOnc. They have boots on the ground in terms of clinical operations and regulatory in both Europe and Asia. We're going to have a larger and I think more muscular commercial sales force in the U.S. to try to capture that market in the relapsed refractory setting. I think long term, Ren, this will ultimately prove out to be a great thing for Kura shareholders.
Again, I'll remind you, go back and look at the stock chart that Pharmacyclics did with Janssen the day they announced the deal and then three and a half years later. And that's just fully funded execution. If we're right and we can keep proving this out, we have the potential, Ren, I think, to create a blockbuster in AML and potentially in GIST, and we're now fully funded all the way through development and commercial. So it's a unique deal. I think it's great. I understand the stock reaction. And for those whose investment thesis was near-term M&A, I can understand why they're disappointed. We are developing a product. We are building a company here. We're going to do what's in the best interest of patients.
And I think hopefully here in the not too distant future, people will look back and say, "I understand why they did that." And Kura's goal is to be first to market in that frontline, in that all-important frontline setting. And if you can put a patient, Ren, on in the frontline setting and imagine they're now on 12 months, 18 months, or longer, then and only then are they going to switch to another menin inhibitor. So that's the prize that everybody has to keep their eyes on.
Thank you very much for that summary. I appreciate that. One quick question before we just talk quickly about the pipeline in the last couple of minutes we have. What's the filing strategy for kind of ex-US? How are you thinking?
Yeah. So I don't want to get ahead of our partner. There is the potential based on regulatory precedent to file in Japan based on a monotherapy approval from the 001 study. In general, Ren, in Europe, with rare exceptions, there are exceptions, but in general, single-arm trials that are on the basis of response rate typically both are a challenge for the European regulators, but more importantly, Ren, they're a challenge for the payers. So even if you can get approval, if you look at it, you're very unlikely to get reimbursement on a country-by-country basis. And that's what folks need to understand is that you actually have to get to the frontline setting before you really get a meaningful ex-US component out of this. We operate in a world where the FDA allows accelerated approval and full reimbursement, but that is not worldwide.
So we're going to go as aggressively as we can, Ren, but I think there are some regulatory and commercial realities ex-US that you want to work through. And again, we are expecting to have a regulatory update early next year on our KOMET-0017 study, which is frontline, fit, and unfit. And it's not our base case. I think it's a best case, but there may be the potential for an accelerated approval in the context of the fit population. We'll have more to say about that early next year, but that could really expedite both the development and commercialization ex-US.
Got it.
To that point, Ren, that takes you back to that 7+ 3 data that I keep pointing everybody at. That's instructive. This is the first time we've really given anybody a meaningful update. That's instructive on a lot of different levels.
Gotcha. We have a growing pipeline. We talked about the majority of it. Maybe in 30 seconds, Troy, just the remainder of the pipeline. You have plenty of cash. You have a wealth of resources now. Where do the rest of them kind of fit in?
Yeah. So you'll see us dosing patients with ziftomenib and imatinib and GIST. If that works, that again could be a very significant commercial opportunity. We have a second- and third-gen menin inhibitors for other solid tumors and for diabetes. And then we have our FTI program. Each of those, Ren, are fully funded now to some sort of critical near-term clinical inflection points. We're excited to be developing the pipeline, but we're not going to take our eye off the ball with zifto. We really can be, I think, both first and best in class in the frontline. But from the standpoint of building out now some commercial opportunities in solid tumors, I think there's some really interesting opportunities there.
Yeah, and that pretty much brings us to the milestones, a lot of which you just covered right now. I think the biggest thing I want to highlight to investors is, of course, the $785 million pro forma cash position that we think is quite impressive, especially given the enterprise value where the company trades right now.
Yeah. And the $420 million in near-term milestones, Ren, will help to offset any burn in the next couple of years. So we're in a strong cash position. We're going to stay in a strong cash position. And we're very much in a show-me time, and we're looking forward to showing.
I'll look forward to seeing the data this coming ASH and then kind of early 2025, so wishing you the best.
Thank you. Appreciate spending time with you and your audience.
Thank you.