Kura Oncology, Inc. (KURA) Earnings Call Transcript & Summary

Hi, everyone. I'm David Dai. I'm one of the biotech analysts here at UBS. Thank you for joining our inaugural Virtual Oncology Day today. We continue our session with Kura Oncology. It's our great pleasure to have Troy Wilson, President and CEO of Kura Oncology with us. Troy welcome.

Thank you, David, and thanks for the invitation to participate in the inaugural Oncology Day conference.

Excellent, excellent. Great. Always a pleasure speaking with you, Troy. So maybe just for the audience here who are new to the Kura story, could you maybe provide a quick overview of Kura, and then we can dive into some of the latest and greatest over the next 12 months.

Sure. Thanks. I'd be happy to. Maybe let's start with ziftomenib in AML. So we are -- we have our first PDUFA date on November 30, we think we're in a good spot for the FDA approval and getting a label that is competitive in the relapsed/refractory setting for NPM1-mutant AML. We're encouraged by the KOL feedback that highlight the efficacy, the simplicity, the compatibility and the safety of zifto relative to competitors. Our commercial team is in place, and it's ready to go. We've done everything we need to do in terms of hiring, market access, preapproval information exchanges. If we move beyond that initial indication, David, and think about frontline combinations, we are excited to be advancing ziftomenib in combination with the standards of care in the frontline setting. We reported promising data in combination with intensive chemo at EHA. We look forward to reporting similar data with venetoclax and azacitidine later this year, potentially at ASH. We think zifto shows promise as an early intervention in both the intensive and non-intensive setting. Your participants might have seen, we announced this morning the launch of a trial to evaluate quizartinib and 7+3 in combination with ziftomenib this morning. And then building on all of that momentum in the frontline, on Monday of this week, we announced we had initiated registration-enabling trials for ziftomenib in both intensive and non-intensive. So if we look at those settings, intensive, non-intensive and FLT3, we have the potential to impact up to 50% of patients with AML, drive meaningful value. If we move from AML to GIST, we're evaluating ziftomenib in combination with imatinib in patients with advanced GIST, that trial, which we call KOMET-015, is in dose escalation and going well. Our Kyowa Kirin partnership is going well, really bolsters our global development and commercialization of ziftomenib. We're moving aggressively into the frontline, supported by our collaboration with Kyowa Kirin, and we're keen to work with them on the launch and build on the excitement for menin inhibitors. And then finally, our FTI program, we've been making excellent progress there. including with our new FTI, a compound called K0-2806 or darlifarnib. That program is addressing resistance to targeted therapies, enabling deep and more durable responses. And we will have a data update there at ESMO here in just a few short weeks. So hopefully, that -- and then from a cash perspective, we had $630.2 million as of the end of the quarter. We're anticipating receiving substantial milestones in connection with the progress of the ziftomenib program, David, that should leave us in a very strong cash position. So there's a lot going on. We're ready to go, and we're well funded in this environment.

Excellent. Thanks for that overview, Troy. So let's dive into some of the programs you mentioned, many different developments in the space right now. So focus on ziftomenib, especially in the relapsed/refractory AML. The PDUFA will be on November 30, so very soon actually. So we should be expecting potential approval. So could you help us understand some of the key engagement with the FDA so far? Have they performed any site inspections? Have you discussing -- the label discussion so far, what's the latest development on the FDA engagement with zifto ahead of the PDUFA date?

Yes. I mean we haven't really given granular details, David, as we go. What I can tell you is if you look at the FDA guidance, typically, any inspections have to be completed, at least 60 days prior to the PDUFA date. That was yesterday. So you can kind of interpret from that where we might be in terms of your question around inspections and inspection readiness. As far -- we're now late into the review. And our engagement with FDA has been very constructive. The shutdown, notwithstanding the latest drama, we've been impressed by their timeliness, by their engagement through the review process. They continue to be very constructive. We will -- we're looking forward to that November 30 PDUFA, and we will be ready to hit the ground running, if and when we receive approval.

Yes. As you mentioned, given all the things happening at the FDA, have you had any kind of changes in terms of interaction with the FDA so far? Has that just been like things as usual, business as usual? Any updates here?

Yes. So I mean, I can only comment on our specific interactions. We're working with the hematology oncology group within the oncology division. I think, David, that, that group has been relatively insulated from a lot of the change and the drama that's gone on. The reviewers that we have on the ziftomenib NDA are the same folks with whom we've been interacting on the various combination studies, the front-line registrational studies. So there's been a good continuity of experience and we've not experienced any disruptions to this point.

Got it. Okay. That's really helpful. And then so on the label discussion so far, we saw that FDA would ask for their own or perform their own adjudication of complete response assessment for AML. So can you just help us understand what are some of the differences between your assessment versus FDA's assessment? And do you think this might lead to some differences in terms of CR, CRh rates?

Yes. I mean -- so it is true. I mean, it's not just the efficacy data, right? The FDA goes in and performs its own analysis on everything you give them. So safety, PK exposure, drug-drug interactions, efficacy, they really do an independent review, David. I can't comment on the specifics of where I think we'll end up. But that's well known, right? So we were prepared for that. That's part of the information requests and answers that go back and forth between sponsors and the agency. We'll look forward to sharing the label with you again, if and when. We're optimistic. I just want to caveat it that it's never over until it's over. But hopefully, you'll see an approval here shortly, and then we can talk specifically to the label.

On that front, I'm just curious, is there any difference in terms of the CR assessment between the FDA's adjudication versus yours?

There shouldn't be. No, because we're using the same guidance, the guidance that they've put forward. But the -- let's see where everything ends up in terms of the label.

Where could difference come from, though? I mean we did see a difference between your competitor, right, their assessment versus FDA label seems to be a little bit off. What do you think that could be?

I don't know. We'd have to ask them. I don't actually -- it's hard enough, David, to have visibility into your own engagement with the agency. I'd be speculating if I talked about anybody else's. I think ours is going to be, again, very strong, very competitive in terms of safety, combinability, convenience and efficacy. And at the end of the day, I mean, let's step back and look at the bigger picture, right? This -- for both us and any potential competitor, this is your first approval. If you really want to maximize the value for patients, you need to get into combinations, you need to get to the frontline as fast as possible. We are now, I think, in a position to get ahead of everybody else in those frontline settings. The 017 study, I know maybe we'll talk about it in a subsequent question, but that is designed to really begin to outpace the competition and get us potentially to registrational data sets in the frontline. You'll also see us publishing additional data on combinations of ziftomenib with various standards of care in the relapsed/refractory setting. So that's -- it's less, I think, about the little differences in the labels between the two drugs and more about how do you capture that very significant opportunity throughout the continuum of care in AML.

Got it. Yes. That's helpful. And so then ahead of the PDUFA date, you mentioned that you're currently preparing the launch activities, especially getting market access, hiring commercial team. Maybe just tell a little more -- provide a little more granular detail around what things you're doing right now to make sure that it's going to be off to a good start once its -- launch will be off to a good start once it's approved in November.

Yes. So we're doing this in the context of the collaboration. November of last year, about a year ago, we signed this collaboration with Kyowa Kirin to develop and commercialize ziftomenib globally. The funding that's coming, really helps to support this broad development strategy. We and Kyowa Kirin are working together to commercialize ziftomenib in the U.S., which will hopefully be the first approval. Importantly, under that collaboration, Kura leads global development, Kura leads U.S. commercial strategy and Kura books all U.S. sales. We have -- David, as you said, we have -- we call them now oncology account managers, in the old days, we used to call them sales reps. We have the sales organization, marketing, market access and medical affairs, all in place. We have the agreements in place with the specialty pharmacies, the specialty distributors will be ready to go. The way we're going to do it, David, is our sales organization and Kyowa Kirin's will actually sit on top of each other. So rather than trying to divide up territories, what we're going to do is call on more sites in a given territory and call on them more frequently. Our organization will look very similar probably to our competitors. But on top of that, we'll have a similarly sized organization from Kyowa Kirin where they are allocating at least 30% of their time to promoting ziftomenib in this initial indication. That should give us, David, the ability to work from the Tier 1 sites all the way down into the stack, to get out to as many sites, both in the academic and the community, as possible. And we're going to compete -- I definitely don't think the NPM1 relapsed/refractory market is a winner take all. We're going to be competing very aggressively for every patient out there and looking to get share of voice with ziftomenib. Our medical affairs team will be educating physicians, nurses, study teams on the opportunities to combine ziftomenib with other standards of care, both in the relapsed/refractory and eventually in the frontline setting. So that's how we're going to handle it.

Yes. I think that's sort of my next question, which is your competitor will launch their drug in the NPM1 setting a month before, right? So -- and they've already seen some off-label use in NPM1 anecdotally. So I'm curious just in terms of your strategy to kind of gain market share while you're a little bit later to the market, but your safety or your ability to combine with others might be able to offset that lateness to the game. So help us understand the overall commercial strategy there?

Yes. And I would say this, even if we were a few weeks ahead of them in terms of our PDUFA dates, I don't think a few weeks makes any difference, David, in this setting. And the reason it is, unfortunately, in relapsed/refractory AML, there's not a large body of patients that are sitting around waiting for therapy. If you don't treat them within a matter of a few days to weeks, they're going to expire from the disease. So it's not like there's a big pent-up pool of patients that somebody is going to capture in a few short weeks. You said it exactly right. And that is you started in the labeled indication of NPM1-mutant AML, there's as much competition, David, between the menin inhibitors as well as with other standards of care like gilteritinib, venetoclax. Half of the NPM1 population is FLT3 mutant in the relapsed/refractory setting. That's why I'm putting such a strong emphasis on the upcoming data that you'll see next year of ziftomenib combination with gilteritinib. You need to get to combinations as quickly as possible. That also allows you, David, to get to earlier lines of therapy. Ideally, you'd like to get these patients when they're second line because obviously, there are more of them, and they do better on therapy when you treat them earlier. If you have to wait until third, fourth or later lines, then it's harder to help these patients with their disease. So you're going to see us competing very aggressively, both on the ground with our oncology account managers and again, we -- part of the reason we did the partnership with Kyowa Kirin is it gives us the operational and the financial firepower to be able to do the broadest, deepest development strategy of any menin inhibitor out there. And between intensive, non-intensive FLT3, there really isn't any standard of care we're not currently combining with. So all of that data is going to be out there. And the physicians will tell you, they want to use these drugs in combination, they want to use them earlier in lines of therapy. The first few quarters, we're both going to kind of find our rhythm, David. Again, I think it's good to have options for patients. And eventually, you're going to see all these drugs trying to move into combination and into earlier lines. That's very much part of our near-term and then longer-term strategy to really become the market leader.

So you're saying that with combination with zifto -- or with combining 7+3 or ven-aza right now, is it possible to move into off-label use in frontline setting?

So I have to answer this very carefully, right? Because you always -- we will only be able to promote within the four corners of our label. That is clear, right? So the oncology account managers will speak to the label. Medical affairs, the physicians, if you ask them, how do they want to use menin inhibitors. They will tell you, well, we want to use them in combination. We have to be very careful how we walk that line, and we will. I mean other companies do this all the time. I would expect, David, there will be some off-label use, particularly in combination. We are going to show you data at ASH, hopefully this year of ziftomenib with venetoclax and azacitidine, both in the frontline setting and in the relapsed/refractory setting. And part of the reason for us doing that is we've heard very clearly from the physicians you need to show data of zifto in combination with ven-aza because that's how we'd like to use it. And let us -- whether it's through the NCCN guidelines or other mechanisms, let us work with you to make other physicians aware of the potential of using these drugs in combination. I think we'll be able to do it all. We are going to keep our oncology account managers very focused on promoting on-label. And then with this ever-expanding data set, and we're talking now, David, about hundreds of patients being treated with ziftomenib in these various combinations. That's going to provide a good body of data, body of evidence to help both support the ongoing registrational studies and to give physicians comfort that they can safely combine these agents together and potentially drive better activity.

Okay. One last question just on zifto in elapsed/refractory NPM1. So you just published the KOMET-001 data in Journal of Clinical Oncology last week. So then that also gives you a fast track to potentially include zifto in NPM1 in NCCN guidelines. So any thoughts around potential time line as to when this will be included in NCCN guideline?

Yes. I'm glad you asked. So in order to be included in the guidelines, David, a drug has to first be approved. So we will -- if and when, ziftomenib is approved on or around its PDUFA date, you'll see us immediately turn around and submit to NCCN. Now that we have that JCO paper out there, but a condition precedent is the drug has to first be approved before it can be included in the guidelines. For subsequent conclusions, David, we'll be ready to go. But those will be very close in time. The NDA approval and the submission to NCCN, expect that those are going to happen contemporaneously. The NCCN committee meets, my understanding is about every 6 months or on an ad hoc basis. And we'll do whatever we have to do to support them as they review the data. The timing of that, David, that I can't forecast yet.

Got it. Okay. It makes sense, Troy. So let's switch gears and talk about the frontline opportunity here, which is a big focus, right, especially focusing on the KOMET-017 trial in frontline AML. One thing we noticed a couple of days ago was that you just initiated -- or first person was dosed into this trial, I believe, or enrolled into this trial. And so the one thing we're just wondering is, Troy, can you provide some additional kind of color around like when are you going to be providing details around this trial, enrollment targets, powering assumptions, any kind of planning term analysis?

Yes. Let's -- so there's a lot in that question. So as you said, I mean, we announced the first patients into KOMET-017. Just for everybody's benefit, this is two parallel Phase III trials, one in intensive, one in non-intensive, each with their own co-primary or dual primary endpoints. So in intensive, you have a potential for accelerated approval off of an MRD-negative CR endpoint with a survival-based endpoint of event-free survival. For venetoclax and azacitidine, it's the CR endpoint with an OS survival-based endpoint. All in, David, it's about 1,200 patients, more toward the intensive trial because that's a three-arm trial, designed to try and get a continuation label for ziftomenib. So think of it as maybe 700 in that trial and about 500-ish in the ven-aza trial. There really, David, isn't an interim to your question there. There is the potential for an accelerated review. We did that in consultation with FDA. What's triggering the timing of that, and we've guided that we think the first top line result for an accelerated endpoint could come in 2028. We haven't yet been more specific about where in 2028. But that, David, is driven by enrollment. That's the MRD-negative CR accelerated endpoint in the intensive trial. In our mind, that's half the market, van-aza is the other half. But the reason that's in 2028 is FDA guidance requires that you have the trial very nearly enrolled. But at the time at which you would unblind it essentially on an accelerated endpoint. So that's what's driving the timing of these accelerated reviews. It's enrollment. It's not events. In terms of putting the two trials together, why we think we're so well positioned, it really streamlines it with the sites. They have one -- a single budget, a single trial agreement, a single either IRB or ethics board review. The sites have said to us, this is what would make us prioritize your trial over any competitor. And I think we'll very quickly catch up and overtake our competition. We've seen the number of patients that have been enrolled in our competitors' trial. And I would expect that we will overcome that and out-enroll them relatively quickly. And just look at the number of patients we've enrolled in the 007 trial, the Phase I trials, David, more than 100 in both intensive and non-intensive to this point with just a handful of sites. In 017, it's going to be nearly 200 sites globally. So I think it will go -- it will go quite quickly.

Got it. And what are some of the initial feedback from the physicians so far on using zifto in frontline setting. Maybe you can share some of the feedback, especially in those open sites on the enrollment for frontline.

Yes. I mean -- again, this is -- one has to take a holistic view of this, David. We talk about like what are the oncology account managers going to do, right? Your earlier questions about how do you sell in that initial setting. We are going to be at nearly every major medical center in the U.S. and most of Europe. I mean 200 sites globally. We -- if you ask the physicians, we are the most attractive trial because it's a one-stop shop. They can do almost any patient who walks in the door in their clinic. They can put them into 017. The reason we did that, David, we made a very deliberate decision, if that site is already working with zifto, whether it's a frontline trial or a relapsed/refractory trial for 007 or 008, they're going to have familiarity with it. They're going -- these physicians all talk to each other. They're going to want to recommend it to their patients in a commercial setting. We've gotten very, very positive, very strong feedback, both for the 7+3 data, which we've shared with you. We'll give you an update likely next year on 7+3. As well as ven-aza, which you haven't yet seen kind of the frontline data. You'll be seeing that at ASH. The docs are -- what the drug is doing is it's you're not really going to increase CR rate in the intensive setting, you're going to increase MRD negativity. That's what we're seeing, right? We're seeing great durability, patients staying on, not needing to go to transplant. With ven-aza, you do have the prospect of actually meaningfully increasing the CR rate. And that's what we expect to see, David. And we're looking forward to sharing that data with you and with your audience hopefully at ASH, if those submissions are accepted.

Very interesting actually. And on the CR rate, MRD-negative CR for accelerated endpoint or accelerated approval, surrogate endpoints. I'm curious, any kind of updates on the level of CR -- MRD-negative CR will be considered meaningful for the FDA and also for the clinicians?

Yes. So one has to be careful about where are you assessing MRD. And we're doing it in bone marrow. We're doing it at the end of the second cycle. The -- for 7+3, David, the standard is about 45% MRD negativity among the CRs, just for 7+3. If you look at what we've published at EHA, you're seeing sort of 60% to 70%, and that number is evolving. It's actually getting higher as time goes on. It needs to be clinically meaningful, David. That's usually 15% above kind of baseline, we think we're well within that range. The other thing that we've shown is in the Phase I trial, those numbers are assessed at the site level, but we've done the work now to test the concordance with a central review because that's the way you're going to show the -- demonstrate to the regulators that you've actually achieved the goal. And we're seeing very good concordance between the central review and the site review. So again, that data is going to evolve over time. But I think you're -- and you say, David, is it working? Well, these patients are staying on without having to go to transplant, right? That's the problem with intensive chemo. You have very high CR rates, but also very high recurrence. 60% of patients recur, and then they're relapsed/refractory and they go rapidly downhill. If we're able to keep them on zifto, they can delay or perhaps even avoid going to a transplant, that tells you clinically you're having the effect that you desire, you're keeping that disease at bay. So I think that's going to be a very good story over the next year or 2 as we're now running the 017 study on top of it in a registrational context.

Great. That's really helpful, Troy. So a couple of minutes left. Just wanted to focus on -- switch gears and focus on the FTI program, especially the most near-term update will be at ESMO, right, for darlifarnib. And so I'm curious, for darlifarnib, you're going to be showing some data in RCC. Maybe just help us understand some expectations heading into this data set, and what should we be looking for, for this data set here?

Yes. So big -- to help people understand big picture, an FTI has the potential to take good drugs and make them better by addressing innate and adaptive resistance, TKIs, PI3 kinase inhibitors, KRAS inhibitors. You focused in on RCC. I think that's appropriate. We're going to show you a combination data with cabozantinib at 2 different doses of cabo, 40 milligrams, 60 milligrams. The 40-milligram dose, David in combination are going to be heavily pretreated patients, many who have already seen cabo. The 60-milligram will be largely cabo naive. We did that because actually, we were able to combine much better than we ever expected. We can combine at a full dose of cabo with a full dose of 2806. The way to think about it, David, is cabo monotherapy gives you a response rate of 25% to 28%. With the HIF2 alpha inhibitors, we've seen 31% to maybe 45%. And you're going to see combo data. You want to see activity of the combo in that range. You also, David, want to see examples where we can take a patient who is progressing on cabo and actually put them back into a response. If we could show you that with good safety and tolerability, we think we have a very competitive play. The difference from this and HIF2 alpha is, we can go anywhere cabo can go. So we can go, for example, to neuroendocrine, we can go to other tumor types as well as KRAS and PI3 kinase. If we're right, the FTIs have a total addressable market of greater than 200,000 patients in the U.S. It will be a very significant drug. And I think a nice complement to what we've been talking about with zifto.

Great. This is really, really helpful, Troy. We're at the top of the hour, and I think we'd just wrap up here. I really, really appreciate you taking the time to speak with us, and hopefully, you all have a good time here at our Virtual Oncology Day.

Thanks very much again, David, for the opportunity to participate and thank you for all the questions.

Great. Thank you so much, Troy. Have a good one.

You too.