Good afternoon, everyone, and thank you for joining the HC Wainwright 27th Annual Global Investment Conference. My name is Joshua Corson, and I'm an Equity Research Associate. Today, I would like to introduce our presenter, Troy Wilson, who is the CEO of Kura Oncology. The floor is yours.
Terrific. Thank you. Thank you to HC Wainwright for the opportunity to participate in the conference and to present the exciting work that Kura Oncology is doing. Today, I'm going to be making certain forward-looking statements, and I'd just refer you to the SEC's website or to Kura's website for more information about the company. Kura is really now in a strong position building toward long-term growth on three principal pillars. The first is commercial readiness. We are anxiously awaiting our PDUFA target action date of November 30 for our first approval of Ziftomenib in relapsed/refractory NPM1-mutant AML. As we'll talk about, our commercial organization is fully hired, fully trained, and ready to go. We're also approaching initiation of the two Phase 3 registration-enabling studies under the COMET-017 protocol, which will evaluate Ziftomenib in combination with certain standard-of-care therapies in the frontline AML setting.
Menin inhibitors generally, Ziftomenib specifically, we think have the potential to transform the treatment of acute myeloid leukemia, acute leukemias, potentially with a market opportunity greater than $7 billion a year, much of that being driven by the frontline opportunity. Dropping down to the second of the three, behind Ziftomenib in acute leukemia, we have a rich pipeline, notably our Farnesyl transferase inhibitor program. This is a novel mechanism by which we address mechanisms of resistance that are common to large classes of targeted therapies, including tyrosine kinase inhibitors, KRAS inhibitors, PI3K inhibitors. This is a problem that is encountered by all targeted therapies, namely, although patients respond, they often develop innate and adaptive resistance. We have, I think, a very innovative approach to address that.
We're planning on giving an update over a couple of investor analyst calls, one on September 16, one on October 18, where we'll flesh that opportunity out in greater detail. The commercial opportunity is significant. We're looking at potentially a target addressable market of greater than 200,000 patients per year in the U.S. Behind the FTIs, we have other opportunities. We're evaluating Ziftomenib in gastrointestinal stromal tumors. We're also developing a next-generation menin inhibitor for treatment of diabetes and cardiometabolic diseases. Our goal is to build a fully integrated research, development, and commercial company that has multiple products, multiple approvals, and is able to generate billions of dollars a year in U.S. revenue. I think we're well on our way. In terms of being well capitalized, we had $630.7 million in cash on a pro forma basis as of June 30.
We are in a strong position under our collaboration agreement with Kyowa Kirin Co., Ltd. and our partner. We stand to receive significant milestone payments here in the near term, which will keep us in a strong cash position. Assuming we hit those milestones, and we think we will, that puts us in a position where we are fully funded through to frontline commercialization of Ziftomenib, which again is a, we've pegged at potentially $3 billion per year peak sales in the U.S. Exciting things to come. The milestones, this is now on a slide on our website. You can see it's going to be an eventful second half of the year. Our PDUFA action date, initiation of our Phase 3s, we'll have additional data that has been submitted at a major medical meeting in the second half under the KO-2806 Tipifarnib FTI program.
Data coming from multiple Phase 1 trials at the European Society of Medical Oncology meeting in Berlin in October. As I mentioned, we are prosecuting a next-generation menin inhibitor. We've talked about the strength of the company's cash position. We're going to move fairly quickly across the company. Starting with acute leukemia, acute leukemia is, while we've seen advances in other hematologic malignancies, AML has lagged behind. We still see 70% of patients who achieve a complete response actually relapsing within three years. That's the problem we're trying to address is how do we get rid of the disease and how do we keep patients disease-free? You can see the five-year survival is 33%. For certain segments, it's as low as 8%. Really a dismal prognosis. Menin inhibitors offer great hope.
We think we're optimistic that menin inhibitors have a place to work in up to half of all AML patients globally. In the U.S., we're talking about 20,000 patients; globally, in all of AML, I'm sorry, in the U.S., it's 20,000; globally, 60,000. The populations we've identified on this slide are the NPM1-mutant, which is about 30%, the KMT2A rearranged, which is about 5%, and then what we call other mutations. This may include things like FLT3. Collectively, that's about half of the AML population. This is in the U.S. alone, about 10,000 patients. If, as you'll see, we can keep them on therapy for one to two years, that's what's driving that peak sales number. Moving first to the relapsed/refractory trial, this is the trial that set us up for our PDUFA date. I'll just sort of hit the highlights.
You can certainly read the slide, but we think we have a very strong safety and tolerability profile, very strong clinical activity, particularly deep and durable responses in heavily pretreated patients. The data supports combining Ziftomenib both with concomitant medications like Azoles, as well as with other standards of care as we move into the combination setting. This is the only menin inhibitor that has this constellation of properties: safety, convenience, simplicity of administration, and strong efficacy. We're looking forward to, we've been working very closely with the FDA. We're looking forward to our target action date of November 30th. As I mentioned to you, these are the headlines from what we hear back from KOLs. It all starts with efficacy here on the left. That's most important.
The once-a-day oral dosing is very important, the not needing to do cardiac monitoring, the combinability, the absence of drug-drug interactions, and then a really differentiated safety profile. This not only distinguishes Ziftomenib in this initial indication of relapsed/refractory NPM1-mutant AML, it puts us in good stead as we move into the combinations. We've guided that the commercial opportunity in the relapsed/refractory setting is on the order, just coming to the far right of the slide, of $350 to $400 million per year in the U.S. We get there by, you know, we're talking about a couple of thousand patients who we hope will stay on therapy for approximately six to eight months. We're happy if the numbers ended up to be larger, but this would represent a significant advance for this NPM1-mutant population, which to date has no approved targeted therapy.
Moving from that initial trial, the COMET-017 protocol, you can see we are evaluating Ziftomenib across a whole range of opportunities. Our goal is twofold. AML physicians have their favorite therapies. They like to combine things. This is a disease where you want to treat earlier, you want to treat in combination. Our goal has been to evaluate Ziftomenib with as many standards of care as possible. Now, we're only going to pursue registration-enabling trials where it makes economic sense for our shareholders. That's why you'll see the COMET-017, intensive and non-intensive. Those are going to be the first two Phase 3 trials. This is data that was presented at the European Hematology Association meeting here on slide 13. I want to draw your attention to a couple of things. This is Phase 1 data from what we call the COMET-07 trial.
This is essentially the same patient population as 017. A couple of things should jump out at you, several things. The first is all of the red dots. Those are all complete responses. That's what you want to get these patients to, right, is to a complete response. Importantly, notice the blue bars are when the patients are on Ziftomenib. There's no discontinuations. There's no dose interruptions. The longest patients up at the top are out almost a year. This is why we tell you we're optimistic that we'll be able to treat patients in this setting. The backbone, the chemotherapy backbone, falls away in week one. Everything beyond that from day eight onward is all Ziftomenib as a monotherapy. This is what drives our enthusiasm about moving Ziftomenib into the frontline population. This data was at EHA.
You will see an analogous data set, again, hopefully at a major medical meeting end of the year in combination with venetoclax and azacitidine. The final thing is look how few patients are actually going to transplant. Generally, the view is like, isn't transplant a good thing? It is for patients where that's the best option. Transplant comes with a one in five chance of mortality. Even if it's successful, significant clinical comorbidities. You're on lifelong immunosuppressants. You may have graft versus host disease. With Ziftomenib, what we're seeing is patients are able to delay or possibly even avoid transplant and just remain in their response. This is really unexpected and I think a remarkable opportunity if it holds up in the Phase 3 to really inflect how we think about frontline AML. The conclusions, I've given you most of the headlines already.
Very good safety, minimal dose-limiting toxicities, no drug-drug interactions, and just incredibly compelling activity. Notably, median overall survival was not reached for the populations and very high rates of MRD negativity. Coming off of that 007 trial and the accompanying 007 trial in the non-intensive setting, I mentioned to you we are setting up the two halves of the COMET-017 protocol. You see them here. These are placebo-controlled, randomized-based global Phase 3 trials. FDA has given us a pathway to accelerated approval in both settings. This operates, it's not strictly Project Front Runner, but this operates under the FDA's rubric of design a single trial that gives you the potential for an accelerated endpoint as well as a survival-based endpoint. You'll see that in both of those. Importantly, on the right-hand side of this slide here, slide 15, the CR-MRD negativity endpoint is a novel endpoint.
It's one where we've said publicly we think we would have top-line results in 2028. That is a really exciting inflection point. In contrast, this is now the commercial opportunity in the frontline setting. Whereas the opportunity in the relapsed/refractory setting was 350 to 400, which admittedly we think is conservative, here we think comfortably for the class, the opportunity is greater than $7 billion a year. The way you get there is take 10,000 patients, take analog pricing, and keep them on therapy for 12 to 24 months. What's the difference? The difference is you've never seen a therapy in AML where you can keep patients on therapy for 12 to 24 months. That's the breakthrough. Keep them in their response, make it a chronic therapy, really a potential for a significant commercial opportunity. We're delighted to be partnering with Kyowa Kirin Co., Ltd.
I'll remind you, Kirin was one of the first partners way back when biotech started. They were actually Amgen's partner and continue to be today. They've been a terrific partner. We have a co-development, co-commercialization partnership. Importantly, Kura leads global development. We lead U.S. commercial strategy. We book all U.S. sales. The collaboration is structured in such a way that milestones are paid to Kura as we incur R&D expenses. That allows Kura to remain in a very strong cash position to be able to prosecute our pipeline. Moving out of AML into now a couple of the pipeline opportunities, talk about menin inhibition in GIST. GIST is a tumor type where despite multiple approved therapies, there remains a significant unmet need. These are tumors typically in the GI tract. These are stromal tumors. You have about 4,000 to 6,000 patients.
Typically, these patients do not experience responses beyond the frontline. This is a disease that just sort of chronically continues. You're not able to drive responses, although we've seen approvals here in the frontline, second line, third line, and fourth line. Notice how the response rates decay as you go. Initially, with imatinib, you get very high responses, but then the responses decay as you get into second and later therapies. What we're looking to do with Ziftomenib is to, and this preclinically works with all the, these are called KIT inhibitors, all the KIT inhibitors and almost all the menin inhibitors, you see very potent synergy. There is an opportunity to take a generic drug like imatinib, which physicians love, and say, how can we address the innate and adaptive resistance? I'm not showing you any of the preclinical data. It's on our website.
This trial is actively enrolling in phase one. We would look to share data with you next year. If we're right, this tumor type is conservatively a $500 million to $1 billion in peak sales in the U.S. You can see how we get there. Again, it's all about can we keep patients on therapy, in this case, Ziftomenib plus imatinib, and actually keep them in response. That's what we're looking to do. Finally, KO-2806, this is our FTI program, which I'll touch on in the last few minutes. This again is going to be the focus of the upcoming first preclinical and then clinical investor analyst events that we do in September and October. The goal here, this is a bit of a busy slide, but I want to draw your attention right to the bottom here, what's called MTORC1. This is half of the target of rapamycin complex.
What we can tell you is there's been lots of drug development at the top of the pathway. You can see the three drugs that we're combining with in our ongoing trials with our Farnesyl transferase inhibitor programs: adagrasib, which is a KRAS inhibitor, cabozantinib, which is a TKI, and alpelisib, which is a PI3 kinase alpha inhibitor. What do they all have in common? This is like playing whack-a-mole, right? If you shut down a node on the pathway, what does the pathway do? It tries to get around it. It either mutates or upregulates. A significant fraction of that upregulation goes through TORC1. It so happens, and you can see on the right-hand side, Farnesyl transferase inhibitors are very good at blocking farnesylation of a protein called Rheb. Rheb, in turn, controls TORC.
The beauty of this, and I'll just take your eye down to the waterfall plot, this is in renal cell carcinoma where you would expect to see synergy. In fact, you do. The tumor volume is on the Y axis. Higher is worse, right? Higher are larger tumors. The vehicle control is in gray. The FTI on its own, not that potent. Cabozantinib, which is the current approved standard of care in the second line, gives you a mix of responses. Each of these is individual mice. Some of the mice respond, others don't. When you look at the combination in both cases, you see significant additivity. When we move on now from RCC to KRAS-driven tumors, qualitatively, you see the same thing. You see the vehicle.
FTIs on their own are not the right therapy, but they are exquisitely good at dealing with the innate and adaptive resistance that arises to these targeted therapies. I'll draw your attention on the far right-hand side in green. This is effectively the waterfall plot, the space-filling version of the tumor growth slide on the left-hand side. Notice the potent synergy in the combination. A similar one here just depends on when you add it. If you add it to the model right at the beginning, you get much more active combination. We are now evaluating two different Farnesyl transferase inhibitors, first generation and second generation. The second generation is here in the FIT-001 trial. At ESMO, we're going to show you phase one data from three of the cohorts. KO-2806 is monotherapy where you're looking for activity in HRAS mutant solid tumors.
You're going to see phase one data in combination with Cabozantinib. You're looking to do better than Cabozantinib as a monotherapy. Cabo has typically 25% to 28% response rate. You're looking at a combination in another cohort of Tipifarnib plus Alpelisib. That's significant because that's in PIK3CA mutant head and neck. PIK3CA is PI3 kinase mutant head and neck. Alpelisib gives you at best stable disease. Tipifarnib gives you no activity. If you're seeing responses that are deep and durable with the combination of the two, just taking you back here for a second to this slide, what we're looking to show you is are we seeing in patients a recapitulation of what you're seeing there with the deep synergy on the right-hand side of the slide. We look forward to sharing that data with you.
Again, I appreciate the chance from HC Wainwright to give you an update on the Kura story, and I'm happy to take any questions.
I'll go to the last of the meet-out. I don't have any questions. No one wants to ask any questions now, feel free to find management over the next three days of the conference, and we'll be happy to talk with you. Thank you.
Great. Thanks, everyone.