Hey, good morning, everyone. Welcome to our next session with Kura Oncology. My name is Li Watsek, a biotech analyst here at Cantor. I'm very pleased to have the Kura team with us today. Troy, Mollie, and Brian, thank you so much for being here. I know this year is going to be a big year for Kura. You have the PDUFA for ziftomenib coming up, and you have a couple data updates coming in the medical conferences as well. So before we dive into that, I wanna hand it over to Troy to give us some intro remarks.
Sure. Thanks, Li, and thanks for the invitation from you and from the Cantor team here at the healthcare conference. So as you said, I mean, it's an exciting six, 12, 18 months as we look forward. Just at a high level in terms of ... You mentioned the PDUFA, we're in good shape as far as NDA review. Things seem to be going well. We've gotten great feedback from KOLs about the profile of ziftomenib in the relapsed refractory setting. We think we're gonna have a very strong label with efficacy, convenience, simplicity of administration, and safety as kind of the four pillars for zifto in that initial indication. We are in good shape as far as commercial readiness.
Our team is now fully on board, trained. We've done what needs to be done in terms of market access, pre-approval information exchange. Shifting to, you know, the earlier lines and the combos, we're gonna share data. You mentioned medical conference, we think we're gonna share data hopefully at the end of the year for the venetoclax azacitidine in combination with ziftomenib in the front line. We shared positive data with the intensive chemo combination at EHA. This will be the other half at ASH. That sets us up then for the 017 studies. Those, the team has been working really diligently. We've guided to initiation of KOMET-017, the two parallel Phase III studies in the fourth quarter. Team's on track to do that.
As far as GIST is next, combining ziftomenib plus imatinib in patients with advanced GIST. We're currently in dose escalation. That trial's going well. All of that is under the auspices of our collaboration with Kyowa Kirin, which also is going well. We've been working really well together between development and preparation for commercial launch. Shifting to the FTIs, we're actually, as we announced yesterday, we have two investor analyst events, one to discuss the preclinical data ahead of ESMO, the other to discuss clinical data at ESMO and sort of how to think about that. That's potentially a, a, you know, a completely separate, independent value driver for the company. So we'll, we'll, you know, be in a position to talk more about that.
We nominated a development candidate, for menin in diabetes, which we'll talk more about in the fourth quarter, first quarter, and then finally, from a cash perspective, we had $630.7 million in cash as of our last quarterly update. We stand, to receive substantial milestone payments, related to both, development and regulatory milestones. So that should keep us in a very strong cash position as we look to prosecute all these opportunities.
Okay, great. So maybe start with ziftomenib. So obviously, the near-term, you know, milestone is the PDUFA, and you mentioned, you know, the FDA interactions. Maybe just give us a little bit of, you know, insights, given, you know, some changes at the agency. Any outstanding CMC, you know, I guess, steps that you guys have to go through?
Yeah. I... Despite the chaos, we have not been exposed to it. It's remained extraordinarily collaborative. It's been very constructive interactions. All of the timelines have been met or exceeded. So we can't obviously ever comment upon the ultimate outcome or where we'll end up in the review, but at this point in time, we've been very encouraged about the way things have been moving forward, and we anticipate the continued good fortune to interact with them to keep moving forward quickly.
In terms of, you know, CMC, manufacturing, inspections, how did that help?
Yeah, so there's nothing we're worried about thus far. Again, we wouldn't comment on each of the pieces of the review, but so far, so good.
Okay. Now in terms of the pre-launch activities, I wonder if you can maybe just share some of the physician feedback that you may have heard. And then just given there is another menin inhibitor already in the marketplace, maybe help us understand maybe some even the lessons that you can learn from that launch and some of the physician feedback in terms of the differentiation that ziftomenib might have.
Sure. Yeah, so we've had a lot of engagement with KOLs around the pivotal data that we're anticipating to be able to promote on very shortly. The data consistent with what I think Troy was saying earlier, the feedback has been consistently that we have a very strong profile that we believe will be competitive and differentiated in this marketplace. It's really driven on kind of the four key pillars of strong efficacy of driving durable and deep CRs.
Improvement in terms of the safety profile is a strong safety profile, where you'll see minimal requirements for monitoring for things like potentially with QTc prolongation or other side effects that can hinder longer-term administration and treatment for patients. The convenience of a once-daily oral medication resonated a lot with physicians as we've spoken to, because it also has an impact on their patients. They have a lot of different medications they need to monitor, and having a once-daily treatment is really beneficial. Then the fourth is around the combinability. For the first indication with concomitant meds, there's a you know, ziftomenib has the ability to combine with a lot of the other therapies that patients may be on.
And then as you look towards the future, where a lot of physicians are excited about combinations, we anticipate that will be a long-term differentiator as well. Speaking about the launch, I think, of one of our competitors in the space, I think, you know, what we're excited to see here is that, you know, there's an appetite and a demand, I think, for the menin class. It validates that these are therapies that physicians and patients are excited to be able to try and work out. And so we're happy to see those early successes. We anticipate that as we get into the market, there's some market learnings we'll be building in, of course, in terms of engagement with the location of where patients are.
Our teams are already in a lot of the space. We'll be ready to launch very quickly upon our approval, and we really, you know, don't think that there's going to be a big difference in terms of timing of approvals between the two products. In terms of being, you know, if they're launched at the same time or one month apart from each other, I don't think that'll have a big impact on the dynamics of the launch.
Okay. I mean, to your point, Brian, just given, you know, two drugs are going to be approved in, you know, within maybe a month difference, so when we think about the dynamic of you know, new patients versus switches, should we just assume initial bolus of patients should all be sort of new patients for the menin class?
Yeah, I think that's reasonable, and I would just, you know, point that most of the patients we understand of the competitor right now are patients who have the KMT2A rearrangement. And it's unlikely that we'll see a patient switch from one therapy to another there, particularly because the indications will be different. It's mostly going to be, I think, the new patient starts that we'd be monitoring and try to see where the patients come through into the practices offices. And we're expecting that they'll make the decision based on, you know, the profile that they see as the right opportunity. We think that we will be competitive in that space there for new patients.
Okay. So I guess in the later-line setting, MRD, obviously we have, you know, some targeted therapies approved. So when we talk about this issue of, you know, co-mutations with IDH1 and, you know, FLT3, do you get any sense, you know, from physicians of their approach to, you know, sequencing combinations with, you know, menin inhibitors?
Sure. I mean, I think that, you know, the learning so far from KMT2A is difficult to really see because there's not a lot of co-mutations there. So we're trying to base it on an understanding of how the physicians are treating. I think that the patients who have a FLT3 co-mutation with an NPM1 will be the ones where they, you know, have a long... you know, some significant experience treating with the FLT3 inhibitors. For us, I think as a monotherapy, we'll be talking through around the sequencing and try to identify when the right time for a patient to receive ziftomenib.
Mollie can maybe speak to actually some of the, our, you know, kind of our broader plans as well, which gets to, actually combining these agents because we think that the profile of ziftomenib allows, physicians to combine with FLT3 inhibitors instead of worrying as much about sequencing. So Mollie...
No, that, that's exactly right. Monotherapy approval is a huge next step, but it's only the first next step. And now getting data in these combinations, these important combinations, will really take the next stage. And we will be presenting our combination with gilteritinib next year. We've been enrolling that trial now, and it's about time that the data will be ready that we can share it. So it's really our ability to combine with these FLT3 inhibitors that'll probably be very important for physicians, and getting that data out there, very important.
Okay, to your point, Mollie, so I get it, that you guys are trying to get more, you know, data in, you know, combinations, maybe with FLT3. I think that's probably the most relevant co-mutation for menin. I guess, what you know, what physicians want to see to start to use, you know, menin in combinations? Do you just need to see some, you know, publications, not necessarily you have to run, you know, pivotal, you know, study? You know, you talked about some NCI guidance, maybe talk to us about the strategy there.
Yeah, I think that's exactly right. They're gonna wanna see robust data that reassures them that, one, it's safe to approach that way, and two, that it's worth any additional risks that could potentially come by combining the two drugs. So you're gonna wanna see you know a good increase in efficacy. I think the CR rate that's published in the label, at least for gilteritinib, is in the teens. So obviously there's room for improvement there, and there's reason to believe that these two could potentially be synergistic together, and we've actually published that preclinical data in the past showing just that. So it'll be good to see the actual clinical data next year.
What is your view on sequencing menin inhibitors, just given there are some resistant issues?
Is that something that you think in practice physicians might wanna do?
Absolutely. As a physician myself, it makes sense to me to try to preserve as many therapies as you can for potentially later lines. We know that one of our competitors has a very high rate of MEN1 resistance mutations. So that's a gatekeeper mutation that then, you know, obviously makes the drug less effective. But they've seen about 40%, 50% of patients that they administer the drug to ultimately develop a MEN1 mutation. We see it in far less patients. I think it'll become a lesser problem as we're moving into combinations. You won't see as many issues arising from MEN1 mutations, but still, in this relapsed/refractory monotherapy setting, it's something that definitely needs to be considered.
One would think that you'd want to sequence something first that is less likely to knock out an entire therapeutic class, for these patients to subsequently pursue. So using ziftomenib first, with very low likelihood of MEN1 mutations developing, would make sense, that you preserve the class should these patients become relapse-refractory, should these patients require additional therapies, and save for later the drugs that would potentially cause them to be much harder to use, a menin inhibitor overall in a patient population.
Is that something you also, you know, heard from physicians that you've spoken with, that maybe ziftomenib is the better menin to be used upfront?
I don't know if you've had conversations about this. It's something that I've talked to investigators about, and they certainly are on the same page. We want to publish the data to really reassure folks that what we're saying is true about the low rate of these resistance mutations, and we will be doing that in the not-too-distant future. I don't know if you've heard-
Yeah. I mean, I would just add that there's tremendous enthusiasm in the AML community around treating with menin inhibitors. And I think that the best example I think we can share is the rapid enrollment of KOMET-007 in the frontline settings show how excited and eager physicians are to put their patients on ziftomenib combinations upfront. I mean, we've been able to enroll over 100 patients within a year in just a handful of sites, and I think that really shows how quickly they wanna test the potential of ziftomenib. And we're hoping as you know, Mollie and the team start the KOMET-017 studies, that that will continue with a broader footprint.
Okay, so you also have a partner here, Kyowa Kirin. Just wondering how you guys are collaborating in terms of pre-approval, pre-launch activities?
Yeah. You wanna take that?
Sure. So from a partnership perspective with Kyowa Kirin, we've had... As you know, the partnership that we signed last year is a co-development, co-promotion deal. We are the lead party in the U.S. for commercialization. We're booking sales. We're the ones who are, you know, holding the NDA. There's a lot of benefits within that. We've had a very strong collaboration with them on the commercial side of things as well, so, we're building... You know, most of the team is, well, now that it's all built out, is going to be partnering very closely with Kyowa Kirin. They'll have some of their field force in the hemonc space is gonna be also promoting ziftomenib.
But we'll probably have a larger share of that overall promotional voice, but they'll be supporting us along the way. And they have a number of capabilities that we're building from, such as some of their analytics and omni-channel capability that will help us to get to reach more patients and be able to you know, kind of follow to get to the right physicians and the right targets at the right time.
Okay, so maybe we can switch to the frontline combo. So my understanding is you guys going to share some frontline Aza-Ven, you know, combination data later this year. Will be helpful to maybe set the expectations for investors in terms of the types of data that we're gonna see, and then what would define, you know, the bar, the benchmark, given some of the, you know, competitors already have data out there?
Yeah. I think although a lot of good data is being generated, VIALE-A, which is the trial that established venetoclax and azacitidine as a very good combination for these more frail patients, is still our best source of data. But I would start from there saying that what you wanna do is augment what they have shown from an efficacy perspective with VIALE-A, without bringing any cumulative toxicities to it.
So what I mean by that is, let's improve upon the OS, which would be around 14.7 months. Let's significantly improve upon that OS. Let's significantly improve upon the cycle one MRD negativity, just 'cause it's a good data point to look at, which would be about 25% in most of these patients. Let's significantly improve upon the complete response rate with full count recoveries, which usually hovers in the 30%-40% range in the VIALE-A. But let's do it all while we're maintaining these patients' abilities to recover their counts. These patients with Venetoclax and Azacitidine alone should be recovering their counts in about five to seven weeks. You'd hope not to run over that. You'd hope to even make that better. It's really just improving upon these outcomes they have seen, while not worsening the safety profiles of these relatively toxic backbone therapies.
Okay. And then in terms of the Phase III enrollment, obviously, you guys have a very efficient, you know, protocol, basically building two trials into, you know, one master protocol. So I think just from the patient enrollment perspective, maybe that has some advantage relative to the competitors. So they're already, I believe, starting their trials as well. But I wonder if you can share any, you know, insights into how that's actually translating into, you know, patient enrollment, given we have, you know, three pretty large Phase III frontline trials are underway. So there's always a concern whether you have to compete for patients?
Yeah, and the competition we welcome because it is really better for patients to give them an optionality so that wherever they're going, they should hopefully have some access to a study that would be of use to them. But the competition is also what we were prepared for and what we kind of decided to really embrace as we were designing the trial, 'cause we have such good relationships with ziftomenib investigators and a lot of the KOLs in general, and we're continuing to expand those relationships. So we discussed with them, "What would make this more compelling, more interesting, easier for you to bring on?" And that's how this study design came about, where it's essentially something for both...
For any patient that walks into their office with an NPM1 or a KMT2A mutation, they don't have to try to decide what trial to put them in. They have a single trial that they can start screening procedures for. These large institutions, they do not take on trials that compete with each other. So everybody's gonna take on, you know, a Ven/Aza here from J&J, Ven/Aza there from revimenib. But if they have the optionality to take on something that has the Ven/Aza and the 7+3 all in one, they're gonna take it.
As Troy referenced earlier, we have an extraordinary amount of sites that are going to be participating, both in the U.S. and abroad, and it's because they're so excited about the ease with which they can enroll patients and the operational ease of being able to get these studies up and running. It's, you know, one round of contracting, one round of budget negotiations. It really does simplify the process, and I think that's why we've been so successful in competing for the sites and getting the sites.
Just to add to that,
Yeah
Yes, it matters when you start. It matters when you finish. At one time, you know, we were perceived as two years behind the competition in the relapsed refractory setting. At worst, we're a month behind now. I think we have the potential to overtake the competition with, as Mollie described, because we have so many U.S. and European sites where, you know, we are now the preferred trials, so although we may be a few months later in terms of starting, I think we'll make up for that in terms of execution.
Yes. And just to highlight, the others have only started in the Ven/Aza, w e're going to start at both at once. So right there, you start taking a lead.
Okay. That's a great point. Maybe switching to KO-2806, so that's your next-gen FTI, and I understand you guys are gonna have some data at ESMO, and I thought that could be a pretty, you know, interesting and exciting update, other than, you know, the MEK inhibitors. So I wonder if you can maybe just give us a little preview in terms of what we expect to see and why you're so excited about this.
Yeah. Maybe I'll start with that, Li. So we've been working on FTIs, you know, for quite a number of years. What we're excited to show you is the data from three of the four studies. KO-2806 is a monotherapy, KO-2806 plus cabozantinib in renal cell carcinoma, tipifarnib plus alpelisib in PIK3CA mutant head and neck. We'll save the KRAS data for next year. That's KO-2806 plus adagrasib in KRAS G12C mutant solid tumors. We wanna show you that this is really the preferred way or a very attractive way of addressing a problem that vexes a lot of targeted therapies, and that is resistance.
With an FTI, we can block the activity of a central node, TOR, target of rapamycin, specifically TORC1, TOR complex 1, and that is a central mechanism of resistance across these various classes. So, you know, this is early days. These are phase 1 trials, so you're gonna be looking at, you know, safety, tolerability, combinability, some evidence of clinical activity. But the opportunity is significant, as you say, and that is a mechanism that is now applicable to three large classes of targeted therapies: TKIs, PI3-kinase alpha inhibitors, and KRAS inhibitors. It has a, you know, potentially a very large TAM.
And we will, as we announced yesterday, we're gonna do an analyst investor event on the 16th of September to walk you through the scientific rationale and the preclinical data, and then we'll do a second investor analyst event from ESMO, where we'll actually walk you through the clinical data and connect the dots.
There's also a significant amount of the preclinical data on our website, so people could start looking there to understand really the pathways we're attempting to address.
Okay. I guess, you know, in RCCs in particular, I think that's a very interesting, you know, indication, and you guys are gonna have some combo data there. So I wonder if you can, you know, share, you know, your views on the space. We're seeing some new agents move in there. HIF-2 has shown some pretty strong results, even I think with the cabozantinib as well. So I guess, what's the bar that you guys have to beat? I know it's still early, right? I mean, we may have seen. We may be able to see some indications of clinical activity, I assume over time we're gonna, you know, accumulate more data, so what's the bar for success?
Yeah, and as you're referencing, this is going to be Phase I data. This is gonna be dose escalation data, so it'll only be evolving, and be able to show you more over time. But really when we look for what should cabo be doing alone in this setting, that's where your starting point is. And if you look at CANTATA and some real-world evidence, you would expect to see about a 25%-28% response rate in this particular patient population. So improving upon that would obviously show that our thoughts on the synergistic interaction of these two molecules, the FTI and the cabozantinib, is working. We recognize HIF-2alpha has become the latest shiny thing in RCC, and everyone's watching that, and we're seeing there, what?
31%-45% response rates, so we know that that's a good ballpark to be shooting for, and we would hope to do it with improved safety. Obviously, these are not benign drugs, so being able to give patients a different safety profile option is very important, but it's also important to remember that we're not just looking at RCC. HIF-2alpha is going to be RCC-focused. Our plans are going to expand well beyond that. I always say we can go wherever Cabozantinib goes or a similar drug, so neuroendocrine tumors, I wouldn't be surprised if you saw us start discussing soon, and just other various opportunities to help synergize with TKIs in general.
Do you wanna set while you're on it, do you wanna set expectations for the head and neck? 'Cause I think that's important as well.
Yeah, the head and neck we're also very excited for, and just as a reminder, that's in PIK3CA mutant head and neck patients. When Alpelisib has been investigated in these patients previously, they've only really shown a best result of stable disease. FTIs, farnesyltransferase inhibitors, should show no efficacy in this particular patient population. So seeing if we put the combination together and seeing any responses would be very supportive of our theories about the interacting pathways that need to be suppressed in order to get activity for these patients and actually move this field forward. But it again, that'll be mechanistic support for what we're saying about PI 3-kinase, KRAS, and TKI potentials.
Okay. So, Troy, you mentioned in the beginning there is, you know, optionality for, you know, ziftomenib and, you know, menin in general, in GIST, in, you know, diabetes. Maybe talk a little bit about the opportunities there and how do you prioritize?
Yeah. So, so obviously we're gonna do everything we can to expand the reach of Ziftomenib in acute leukemia. We're looking forward to the data evolving in GIST. Beyond AML and GIST, we would look to use probably another menin inhibitor. We have now a next-gen menin inhibitor, which we've nominated for use in diabetes. You'll see us develop that. I think we're gonna try to do a creative development and financing approach, not use our balance sheet, which, you know, is really focused on oncology, but try to find a creative way to create value there for patients and shareholders. You would then look for, Li, kind of a third-generation menin inhibitor for additional oncology applications. Our team, you know, I think we can continue to lead the discovery and development of menin inhibitors. I think menin has, you know, additional surprises yet to share with us.
We're looking forward to that. And maybe, you know, just looking to, you know, 2026, what will be the top two or three priorities for Kura that you hope to deliver, you know, the value to investors?
Yeah. I mean, between now and then, I think you're looking at, you know, approval and launch of ziftomenib. You're looking at additional data in the combinations, the start of the KOMET-017 study. We've talked about GIST. We've talked about data with KO-2806 KRAS, potentially more data in RCC with KO-2806, elaboration around other applications of menin in diabetes, and then just, you know, continued evolution to a fully integrated research, development, and commercial company. It's gonna be an exciting, you know, next couple of years.
Yeah, many top priorities. Many priorities.
Thank you so much, guys.
Thank you.