Kura Oncology at Stifel Forum: Strategic Moves in Targeted Therapies

On Tuesday, 08 April 2025, Kura Oncology (NASDAQ: KURA) participated in the Stifel 2025 Virtual Targeted Oncology Forum, where CEO Troy Wilson outlined the company's strategic advancements. The discussion centered on the promising prospects of Ziftomenib, a treatment for relapsed refractory NPM1 mutant AML, amidst robust financial backing. However, the competitive landscape poses challenges for Kura's market capture ambitions.

Key Takeaways

• Kura Oncology has submitted an NDA for Ziftomenib, aiming for priority review.
• The company holds a strong cash position of $700 million, with expected milestone payments of $240 million in 2025.
• Kura aims to capture $3 billion in peak sales from the menin class, estimated at $7 billion annually.
• Upcoming Phase III trials will explore Ziftomenib in combination therapies.
• The company is ramping up pre-commercial activities for a competitive product launch.

Financial Results

• Kura Oncology reported a cash reserve of approximately $700 million.
• Expected milestone payments of up to $240 million this year will bolster financial stability.
• This financial strength supports ongoing clinical programs and reduces associated risks.

Operational Updates

• NDA Submission: Kura has submitted a New Drug Application for Ziftomenib, seeking priority review and benefiting from breakthrough therapy and fast track designations. The PDUFA date is anticipated in Q2.
• Phase III Trials: Two trials under the COMET-seventeen protocol are starting, evaluating Ziftomenib with intensive chemotherapy and with venetoclax and azacitidine. The COMET 15 study, focusing on Ziftomenib and benematinib in GIST patients, will begin in the first half of the year.
• Commercial Readiness: The company is enhancing pre-commercial activities for Ziftomenib's launch, preparing for competition.

Future Outlook

• Data Updates: Kura plans to release data updates on KO-2806 and tipifarnib in the latter half of the year, with potential presentations at ESMO, EHA, and ASH.
• Trial Timelines: The initiation of the Phase III COMET-seventeen intensive chemotherapy trial is expected in late 2025, with top-line results anticipated in 2028.
• Market Potential: Kura estimates peak sales for the menin class at $7 billion annually, targeting $3 billion for Ziftomenib, with treatment durations of about 18 months in various settings.

Q&A Highlights

• Regulatory Interactions: Troy Wilson noted consistent interactions with regulatory teams, unaffected by changes at HHS and FDA.
• Combination Strategies: Kura is exploring combinations such as a FLT3 quadruplet with chemo for frontline FLT3 mutation patients and Ziftomenib with gilteritinib for relapsed refractory NPM1 mutant AML.
• MRD Negativity as Endpoint: The company is part of the Impact Consortium, advocating for measurable residual disease as a surrogate endpoint for survival in AML.

For more detailed insights, readers are encouraged to refer to the full transcript below.

Full transcript - Stifel 2025 Virtual Targeted Oncology Forum:

Brad Cannino, Host, Stifel: Great. Thanks everyone for attending us at the Stifel Virtual Oncology event. Really happy to do the next fireside chat, with CURA Oncology. My name is Brad Cannino. I'm hosting Troy Wilson, president and CEO of CURA.

And let's maybe start off with the state of the business and priorities for the rest of the year. Troy?

Troy Wilson, President and CEO, CURA Oncology: Sure. Brad, thank you to you and Stifel for inviting us to participate in the conference. In terms of the state of the business and the priorities, as you saw this morning, we announced, we've submitted our, new drug application for Zifdomenib in relapsed refractory NPM1 mutant AML. So now we're going to be doing everything we can to support the agency's review, and we'll have more updates, on that as the year progresses. In connection with that, we are increasing our pre commercial activities to support the launch of ZIFTOMENIB in that indication.

Looking beyond the initial, opportunity in relapsed refractory leukemia, we're now in the process of study startup for the two Phase III trials, under the COMET-seventeen protocol That is Zifdomenib in combination with intensive chemotherapy, and with venetoclax and azacitidine. We provided some important regulatory updates, on that earlier this year. We should be initiating the COMET 15 study, which is evaluating the combination of ZIFTOMEN and benematinib in GIST patients. We've guided to the first half of the year. And then, we're looking to initiate one or more expansion cohorts for our farnesyltransferase inhibitor KO-two thousand eight hundred and six in combination with cabozantinib.

Looking forward to providing an update on those studies both for twenty eight zero six and tipifarnib in the second half of the year potentially at ESMO. So that's and and then from a cash perspective, obviously, we we remain in a very strong cash position. We had, you know, approximately 700,000,000 in cash. I think I've I've said previously, we stand to receive up to 240,000,000 in milestones under our collaboration this year. So that gives us, you know, the resources and the stability, the derisking that we need to be able to prosecute these different programs, across the business.

Brad Cannino, Host, Stifel: Great. And let me add my congratulations on today's announcement. It's great to see such an expedited submission for being for Zithrombin. Now what is the process from here, and what regulatory capital is can you leverage for Libutin?

Troy Wilson, President and CEO, CURA Oncology: Yeah. So we have we've submitted the NDA. Obviously, you know, we have breakthrough therapy designation for NPM1 mutant AML. We also have fast track designation. We're going to be seeking priority review.

I get this question often. We've seen no impact from the changes underway at HHS and FDA. It may be that the hematology oncology section of of the oncology division is more insulated. But, you know, we see the same people, whether it is the guidance, that that we obtained from them on the frontline studies or, you know, members leadership members of the review team. We're gonna be working with them, Brad, to first of all, we'll be awaiting, you know, formal formal receipt for review from FDA and in connection with that a PDUFA date.

I would expect that that will be in q two. And at that point, we'll we'll obviously disclose that. Once that happens, we'll be doing everything we can to support the agency and its review of the application. So I think it's you know, we'll we'll continue to take advantage. All the track has been laid between the BTD, the Fast Track.

Now it's really a matter of how quickly can we, respond to requests for information and and get the agency the information that it needs.

Brad Cannino, Host, Stifel: Now you released the top line result with the NPM1 relapsedrefractory setting was successful as a monotherapy for zyptomet and COMMENT-one. How should investors think about the profile? Because obviously we have not seen the data yet. Mean, those are forthcoming at a medical meeting.

Troy Wilson, President and CEO, CURA Oncology: Yeah. Yeah. So as we said at the time, I'll

Troy Wilson, President and CEO, CURA Oncology: say it again. The benefit risk profile for ZIFTO is highly encouraging. The safety and tolerability were consistent with prior reports. I think of this in stages, Brad. You know, I'm charged to look beyond the initial launch.

So I think we're going to be very competitive in the NPM one setting. We'll let you know, we're hopeful that we will have the the data to present, you know, at a major upcoming medical meeting here. We'll we'll obviously update you on that when when we're able. I think we'll be very competitive in the relapsed refractory setting. We're also looking to share data from the ongoing COMET seven study, which is now evaluating ZiftoMetib in combination with intensive chemotherapy and venetoclax and azacitidine in newly diagnosed patients in the frontline setting.

And, again, we're guiding to, the intensive chemotherapy combination data potentially at EHA, the, venetoclax azacitidine data potentially at ASH. The reason that that's significant, Brad, is you would expect even with a monotherapy approval that some physicians are going to be using these agents in combination. That's really how they're intended to be used, whether that's in the relapsedrefractory setting or ultimately in the frontline setting. And so I think the overall profile, will be as important as that monotherapy profile. And I think we're gonna, you know, stand tall on both counts.

Looking forward to, again, multiple data updates throughout the year.

Brad Cannino, Host, Stifel: And how will you and your partner approach commercial strategy? And will that change depending on if ZYPTO is the first or second MET inhibitor approved in the NPM1 setting?

Troy Wilson, President and CEO, CURA Oncology: Yeah. I mean, as I've said, so we're going to do everything we can to work with the FDA to support its review timelines. The initiation of our pre commercial readiness activities have put us on a strong path to commercialization and we'll prepare well for a competitive launch. We're assuming, Brad. I think it's safe to assume, you know, we're gonna be even with the competition or even a little bit behind.

It's always good to be paranoid. We are preparing to, you know, have a have a very meaningful commercial presence between us and our partners at KewaCuren. And we'll be competing for share of voice and looking to win over as many patients as we can. I think we'll be ready when the time comes.

Brad Cannino, Host, Stifel: What are your insights from Syndax's recommended about the potential sales opportunity in relapsedrefractory AML for MENN inhibitors as we've seen that launch?

Troy Wilson, President and CEO, CURA Oncology: Yeah. So the preliminary insights say there's a growing awareness of menin inhibitors in the relapsedrefractory AML setting. Because of the specialty pharmacies that our competitor is using, you don't really have visibility into what's going on there. You can see certain aspects but not others. We do believe and we hear from our feedback, physicians are looking for products, which they believe offer the best benefit risk for their patients.

I think we're going to see again, that's part of why it's helpful to have multiple sponsors working in the space, the initial relapsed refractory data, then the combination data, other combinations that will feed you're looking for awareness. You're looking for both the class and of Zifdomenib in particular. The fact, Brad, that we're targeting again, potentially ASCO, potentially EHA, potentially ASH, we're looking to get that data out to the physician and patient communities. And, you know, that's going to be our job for the next, several years, again, in partnership with Kewacure. And I think we're well set up to do it.

Brad Cannino, Host, Stifel: Now you mentioned, moving to combinations and the priority there as well. Remind us what was the combination profile that you think ZYPTOMETY demonstrated in the phase one dose escalation data for those combos that we saw at ASH last year?

Troy Wilson, President and CEO, CURA Oncology: Yeah. So let's start with

Troy Wilson, President and CEO, CURA Oncology: the intensive chemotherapy side. There we saw from the interim analysis of the phase one portion, we saw one hundred percent CR rate in the NPM one mutant setting, an eighty three percent CR rate in the KMT two a rearranged first line adverse risk setting. We had a hundred percent of the NPM1 patients and I think ninety six percent of the KMT2A patients alive as of the data cutoff with a median follow-up of thirty one and I think nineteen weeks respectively. That bodes well. We'd also, Brad, seen and this was a surprise from what we were expecting the KMT2A patients for the most part go on to transplant and then in our experience back on to cystomenib.

The NPM1 patients, many of them are electing to delay transplant or forego transplant in favor of staying on ZYPTOMENIB as continuation therapy. And that's a compelling benefit risk opportunity for them. They avoid the complexities, the comorbidities of transplant. They're just taking Zifto as a once a day oral pill. It's also, you know, important for investors and and our business from the commercial standpoint.

As you look toward a data update middle of the year, look really to durability, Brad. That's going to be the question, right? That's what's ultimately going to drive the commercial case here is, are we able to keep these patients in response for prolonged periods of time? Shifting to the venetoclax and azacitidine setting, what we saw there again, we were asked, we were FDA requested that we do the dose escalation in the relapsed refractory setting primarily because your goal there is safety and tolerability. We didn't see any issues as far as combinability.

We were able to continue to dose escalate. As you look to a data update, again, probably now in the second half of the year potentially at ASH, I would look now to the expansion cohort, which will be the newly diagnosed patients. There again, now in the Venaza, of course, patients don't typically go to transplant. If they did, they'd go to intensive chemo. So what you're looking there is can you keep patients in response?

Can you deepen the responses? And I would say we're encouraged by the data that we're seeing. We would not be, accelerating development of the 17 Phase 3s were we not seeing very promising data from the seven expansion cohorts. So those I think will be two pretty meaningful updates middle of the year and end of the year for intensive and non intensive respectively.

Brad Cannino, Host, Stifel: So you covered the difference in the patient baseline characteristics from the dose escalation which we've seen to the dose expansion which we will see this year. Do you see the expansion cohort data as a way to reiterate the profile you've already shown or is there going to be a new focus or additional data points for investors to focus on?

Troy Wilson, President and CEO, CURA Oncology: I think new data points. Right? So so for durability, the the commercial case here that that folks are trying to wrap their head around is how large is the frontline opportunity. And and I I'm pretty simple. Right?

It's it's number of eligible patients times price point times duration of therapy. The number of eligible patients for the class is approximately half of all of the, you know, the incident population each year, about 10,000 patients. The price point's been established by one of our competitors. So now the the variable you're looking for is is duration of therapy. And that I think, Brad, is what you're looking for from both of those frontline studies, both the seven plus three and the Venaza.

You're going to see a higher response rate in both settings. But the response rates I mean, intensive chemo is has a pretty high response rate to begin with. Venaza is, you know, more modest. You can improve upon it. We what we're seeing is you can improve meaningfully on both of those.

And importantly, we think, you know, extend the durability and give patients a a a more, long lasting clinical benefit. That's the new data from both of those cohorts that you're going to look for. I think the safety profile, Brad, should be fairly consistent. We've not seen, you know, DS. We're not seeing QT.

We're not seeing any DDIs or any challenges with combinations. That's why those cohorts are enrolling so quickly. So it'll be about magnitude of clinical activity, depth of response in terms of response rate, depth of response, and then duration of response. That's what you should look for in those newly diagnosed patients in the expansion cohorts.

Brad Cannino, Host, Stifel: And what level of durability maturity do you expect to have in the data?

Troy Wilson, President and CEO, CURA Oncology: So for seven plus three, we'll show the 600 milligram patients from the escalation as well as the patients from the one b expansion. We're gonna zero in on on, you know, the RP two d. We'll show all of those patients as of the data cut. For Venaza, obviously, the focus will be on the newly diagnosed population because that's the population of interest. That's what informs o 17.

And and importantly, we made a, you know, a shift from relapsed refractory in the escalation to newly diagnosed in the frontline. So that that is likely. I mean, it's still early days. That's you know, we've guided to second half of the year. But you're likely to to to see a focus on the newly diagnosed patients in the Venaza cohort, here in the second half of twenty five.

Brad Cannino, Host, Stifel: Yeah. And for these durability metrics, what do you think are the right benchmarks to consider as we think about these upcoming combo data?

Troy Wilson, President and CEO, CURA Oncology: Yeah. So let's start with VENESA to begin with. So from Vialy A with VENESA, overall we saw a CR rate and CR is the key. Right? That is the the the the endpoint.

You saw a CR rate of of less than 40%. Now the CR rate for NPM one mutant would be you'd expect that to be slightly higher. Maybe it's in the 50% range after four cycles. For for KMT two a, it's probably a little lower. For seven plus three, the data shows us CR rates for NPM one in the eighty to ninety percent range.

However, there you need to look at the rate and the timing of relapse. So you have, again, if you look at the at the literature, forty seven percent of the NPM one patients relapse. Of those, sixty percent relapse in the first year, eighty percent relapse within two years. And that's the Bertoli, if you go to to blood in 02/2018, the Bertoli reference. That that's really your benchmark, Brad.

The KMT two a patients in the intensive setting, you'd expect to have a CR rate closer to fifty percent to sixty percent with more frequent relapses. So it's going to be important to look at the evolving times on therapy in those patient populations. But each of those, Brad, gives us opportunities to demonstrate a clinically meaningful benefit in terms of MRD negative CR for intensive, CR for non intensive, and ultimately the survival based endpoints.

Brad Cannino, Host, Stifel: Now looking forward to your registrational studies combos, for the chemo combo you've proposed a trial design of leverage MRD negativity for accelerated approval. That would be a first for AML. The question is what key questions have you answered to the FDA that will allow this endpoint to finally be used in AML after we have seen it be utilized in ALL and hopefully soon in myeloma?

Troy Wilson, President and CEO, CURA Oncology: Yeah. It's a good question. So the key question, of course, is the adequacy of measurable residual disease as a surrogate endpoint for survival. We have been a a member of the what's called the Impact Consortium, starts with an m, Impact, which was founded in 02/2018, and it was founded among Janssen, Genentech, Novartis, Celgene, I think, AbbVie Amgen, Cronos. We we petitioned and became a member.

And that consortium used or its goal is really to establish MRD as a surrogate endpoint for overall survival in the treatment of AML. EMPACT, that consortium, worked with the academic community to conduct a meta analysis to assess the association of MRD with overall survival. And as part of our briefing book for the phase threes for the Commodose seventeen intensive chemotherapy trial, we shared both published and unpublished data from EMPACT with FDA as part of our briefing book. In fact, you know, FDA asked us, you know, how are you how are you in the in the dialogue, how are you going to, you know, to to demonstrate the the connection? And we said, well, we're a member of the Impact Consortium.

And they were like, oh, okay. Yeah. You know, that that gave them a lot of confidence, because it's a multi sponsor effort. And and then finally, Brad, and importantly, the o 17 intensive chemotherapy trial includes both MRD negative CR and event free survival. So there's a built in safeguard for patients.

You're not gonna maintain the benefit of accelerated approval unless you can also demonstrate a survival based benefit, longer term.

Brad Cannino, Host, Stifel: Now if MRD negativity is used for accelerated approval, how should investors think about the timeline for a Phase III from start to potential registration?

Troy Wilson, President and CEO, CURA Oncology: Yes. Good question. So we've guided that we anticipate initiating the Phase III COMET-seventeen intensive chemotherapy trial in the second half of twenty twenty five. I think that's likely to be probably in the fourth quarter. We've also guided we would expect top line results in 2028.

We haven't been more specific than to say 2028 because our crystal balls are a little bit cloudy. But that will be important, Brad, when you look at the number of patients who have been enrolled in the expansion cohorts to date and you get a sense of the pace of enrollment. I think that'll give us confidence. And and that's that's what we're using to benchmark the enrollment and ultimately the trial timelines. The rate limiting step, not surprisingly, is actually site activation in these phase threes.

Once the sites are up and running, enrollment goes relatively quickly. But you have sort of a sigmoidal curve of site activation. I think you could see data, you know, in 2028. And we're gonna do everything we can to make that earlier in 2028, but we feel we feel good that we can deliver data in 2028.

Brad Cannino, Host, Stifel: Yeah. And now sticking with the chemo combo for FIT patients, what do you expect around transplant utilization in this trial? And how will ZIFTOMENUM maintenance be employed or not?

Troy Wilson, President and CEO, CURA Oncology: Yes. So as I it's a

Troy Wilson, President and CEO, CURA Oncology: good question. As I mentioned, I think in an answer to a previous question, we anticipate most of the newly diagnosed KMT2A rearranged AML patients go to transplant. That is their best hope for a cure. Our experience thus far has been many of the newly diagnosed NPM one patients who are MRD negative, and this is MRD negative as measured by the sites, which uses a different assay than what we'll use in the trial. We're going to do a central review using bone marrow.

Many of those patients who were MRD negative will stay on ZIFTOMENENB in continuation therapy and not go to transplant. The data suggests that patients who were MRD negative transplant has a negative benefit risk. Importantly, and this is a, I think a coup for Molly Leone, our CMO and our development team and regulatory team. The trial is designed, Brad, as a three arm trial to assess the impact of ZiftoMenib both in the induction and consolidation portion as well as the impact of ziftamenib post induction consolidation. So you get to look at both in that three arm study, and the statistics are based on the NPM one, mutant population.

So that's how that's how we expect it's going to be used.

Brad Cannino, Host, Stifel: What is the status of potentially working towards a FLT3 quadruplet with chemo to address the other frontline FIT patients who have the co occurring FLT3 mutation?

Troy Wilson, President and CEO, CURA Oncology: Yeah. This is the challenge and the opportunity with AML is just just as you're getting the triplets going, people start talking about the quads. And and that's that's really the best benefit for patients. So we have generated encouraging preliminary data thus far combining ceftobenib with gilteritinib in relapsed refractory NPM one mutant AML. Remember that the co mutations with KMT two a are are so infrequent, it it doesn't really make sense to have a separate cohort.

We are anticipating initiating a combination of Zifdomenib and Quasartanib in newly diagnosed NPM1 mutant FLT3 mutant patients in the second half of this year. We continue to think that the FLT three mutant population represents a significant opportunity for menin inhibitors. I think, Brad, to your question, we need to we have some work to do just to understand how how broad you want the aperture on FLT three mutants to be. But, certainly, you know, I think we're optimistic that there's a there's a path to combination and and a and a pretty meaningful opportunity to drive benefit for patients. Again, if if you're able to prolong them in response and delay transplant as well as a a meaningful commercial opportunity.

Brad Cannino, Host, Stifel: Moving to the Benazza combo and strategy there, you mentioned the endpoint focus on complete response. Yep. One of the questions I have for this study, though, in phase three is what level of dose management should we expect for venetoclax specifically in the triplet? Yeah. We know that causes cytopenias.

Will the FDA allow for reduction in VEN to control cytopenias before they require a reduction in the investigational MEN inhibitor?

Troy Wilson, President and CEO, CURA Oncology: Yeah. It's it's a really good question. And and here again, I have to tip my hat to to Molly Leone and and and our our development and regulatory teams. So you're you're absolute so so first of all, let's talk about kind of what do you expect. The rate for CR in Venaza is lower.

It's typically about fifty to sixty percent, which is what enables it to be a CR for accelerated approval. You don't need to go to MRD negative CR. You actually have enough of a margin that you should be able to show a clinical benefit by dosing with the triplet, including a menin inhibitor. The survival based endpoint, of course, is overall survival. Relatively few patients go to transplant.

To your question about dose management, we continue to not see any drug drug interactions between Zifdomenib and any of the standards of care. We don't have to hold or reduce Zifdomenib to manage cytopenias. And we were encouraged, and we shared this as part of our feedback from our meeting with FDA. We were encouraged that the FDA permitted reduction of Venaza after two cycles, consistent with real world experience, Brad. That's typically when you start to see those cytopenias begin to impact, you know, patient well-being.

And the f and, you know, kudos to my team and and credit to the FDA, that FDA recognizes that and actually allows us to, if you will, adopt real world usage of Venaza in the trial. And that will of course be in both the Zivtomenib arm and in the control arm. So it should be better for the patients. It should lead to a better result.

Brad Cannino, Host, Stifel: Then what type of treatment durations would you expect in the frontline unfit population? And I guess there's always the question of how you think about the relative size of a market potential for the frontline fit versus the frontline unfit?

Troy Wilson, President and CEO, CURA Oncology: Yeah. So so what we what we've guided to is that we expect, eighteen plus months in the frontline intensive chemotherapy setting, and approximately eighteen months in a frontline non intensive setting. And and the difference is, of course, the the non intensive, the patients are generally older, they're not as fit. That's what's driving that. It's not it's not the therapy.

At present, based on our experience, Brad, we're guiding that we think peak sales for the menin class are probably about 7,000,000,000 a year. Peak sales for Zifdomenib, we think we can probably take 3,000,000,000 of that 7,000,000,000. How you split between intensive and non intensive, it could be $60.40 VENESA to intensive, it could be $50.50. What we're seeing interestingly is the KMT2A frontline patients all go to intensive chemotherapy. They're generally younger.

They're going to go to transplant. You're going to try to get them to a cure. The NPM1s interestingly, if if if they don't have to go to transplant and you can drive a durable response, intensive chemo becomes a lot more attractive to them if they can stay on ZYFTTO as an oral agent. So that's why I say to you, you know, let's call it roughly fifty fifty. It might it might sway a little bit one direction or the other.

Brad Cannino, Host, Stifel: Okay. Well, great, Troy. Unfortunately, we're out of time. I wanna congratulate you again on the progress with with the NDA. And I

Troy Wilson, President and CEO, CURA Oncology: guess as

Brad Cannino, Host, Stifel: we're sitting here in this macro environment, it's a great time to be a well capitalized company. So kudos for executing the deal with your Japanese pharma partner. Thanks for joining us. Thanks everyone for listening in. I hope you have a great day.

Troy Wilson, President and CEO, CURA Oncology: Thank you, Brad.

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