Kura Oncology - Earnings Call - Q1 2025

Executive Summary

• Kura submitted its first NDA for ziftomenib in R/R NPM1-mutant AML on March 31, requested Priority Review, and expects FDA’s acceptance decision in Q2 2025; ASCO/EHA podium/encore presentations are scheduled, supporting near‑term visibility on clinical data.
• Q1 results: collaboration revenue $14.1M, net loss $(57.4)M, EPS $(0.66); pro forma cash $703.2M including a $45M NDA submission milestone earned under the Kyowa Kirin collaboration; runway into 2027 maintained.
• Versus S&P Global consensus, Q1 revenue and EPS missed as collaboration revenue recognized ($14.1M) lagged Street expectations despite milestone earning; Street had modeled higher collaboration revenue recognition in the quarter (see Estimates Context).
• Key catalysts likely to drive stock: FDA acceptance/PDUFA setting with potential Priority Review, ASCO/EHA data (KOMET‑001 monotherapy; KOMET‑007 7+3 combo), and Phase 3 KOMET‑017 trial initiations in 2H25.

What Went Well and What Went Wrong

• What Went Well

  • Regulatory execution: “we achieved a significant milestone with the submission of our first NDA for ziftomenib,” with Priority Review requested and no observed FDA disruptions; BTD status supports review resourcing.
  • Clinical momentum: KOMET‑001 monotherapy accepted for ASCO oral; KOMET‑007 7+3 frontline data accepted for EHA oral; robust enrollment across combo studies.
  • Balance sheet strength: Pro forma cash $703.2M including a $45M milestone; management reiterated runway into 2027 and ability (with collaboration funding) to support frontline commercialization.

• What Went Wrong

  • Miss vs estimates: Q1 collaboration revenue ($14.1M) and EPS (−$0.66) missed S&P consensus as Street expected higher collaboration revenue recognition; net loss widened y/y despite collaboration revenue.
  • OpEx step-up: R&D rose to $56.0M (from $36.3M y/y) and G&A to $22.8M (from $18.2M y/y) as Kura scaled development and pre-commercial efforts.
  • Sequential cash decline: Cash and equivalents fell to $658.2M from $727.4M at year‑end (though pro forma cash including the earned milestone was $703.2M).

Transcript

Operator (participant)

Please stand by. Your program is about to begin. If you need assistance during your conference today, please press star zero. Good day, everyone, and welcome to today's First Quarter, 2025, Kura Oncology Financial Results Conference Call. At this time, all participants are in a listen-only mode. Later, you will have the opportunity to ask questions during the question-and-answer session. You may register to ask a question at any time by pressing star one on your telephone keypad. You may withdraw yourself from the queue by pressing star two. Please note this call may be recorded, and I will be standing by if you should need any assistance. It is now my pleasure to turn the conference over to Apoorva Chaloori. Please go ahead.

Apoorva Chaloori (Senior Associate)

Thank you, Operator. Good afternoon and welcome to Kura Oncology's First Quarter, 2025, Conference Call. Joining me on the call are Dr. Troy Wilson, President and Chief Executive Officer; Dr. Mollie Leoni, Chief Medical Officer; Brian Powl, Chief Commercial Officer; and Tom Doyle, Senior Vice President of Finance and Accounting. Before I turn the call over to Dr. Wilson, I'd like to remind you that today's call will include forward-looking statements based on current expectations. Such statements represent management's judgment as of today and may involve risks and uncertainties that could cause actual results to differ materially from expected results. Please refer to Kura's filings with the SEC, which are available from the SEC or on the Kura Oncology website for information concerning risk factors that could affect the company. With that, I'll turn the call over to Troy.

Troy Wilson (President and CEO)

Thank you, Apoorva. Good afternoon, and thank you all for joining us. Over the past quarter, we've made substantial progress executing against our pipeline. We've achieved important clinical and regulatory milestones, which have clinically and financially de-risked our preparations to commercialize ziftomenib in acute myeloid leukemia, or AML, including the recent NDA submission for ziftomenib as a monotherapy in relapsed or refractory NPM1-mutant AML. The ziftomenib monotherapy phase two registrational data were accepted for oral presentation at the 2025 ASCO Annual Meeting, which will be the first of multiple clinical data updates we anticipate presenting at major oncology medical meetings throughout this year. Earlier this week, we announced the first patients with advanced gastrointestinal stromal tumors, or GIST, after an imatinib failure were dosed with the combination of ziftomenib and imatinib.

Our FTI program continues to advance, and we expect to share preliminary clinical data from multiple phase one cohorts later this year, evidencing the potential of FTIs as combination therapies. As we continue to build Kura into a fully integrated organization, we're pleased to announce the appointment of Samir Vattompadam to our leadership team as Senior Vice President, Global Program Leadership. Samir joins Kura with more than 20 years of experience in the biotech and pharmaceutical industry, including extensive leadership of global program teams, which have driven the development and commercialization of 16 novel medicines and indications across 13 diseases, primarily in oncology and hematology. As adjusted for the $45 million milestone payment under our collaboration agreement with Kyowa Kirin, upon receipt by FDA of the NDA submission for ziftomenib, Kura had, on a pro forma basis, $703.2 million in cash, cash equivalents, and short-term investments as of March 31, 2025.

Accounting for the $45 million milestone payment, we stand to receive an additional $375 million in near-term anticipated milestones. This strong cash position provides sufficient capital to fund our ziftomenib AML program to commercialization in the frontline setting, as well as advance our pipeline to multiple value inflection points. With that overview, let's now dive in, starting with ziftomenib. On March 31, we submitted our new drug application, or NDA, for ziftomenib, our once-daily oral investigational menin inhibitor. As a reminder, ziftomenib is the first and only investigational therapy to be granted Breakthrough Therapy Designation for treatment of relapsed or refractory NPM1-mutant AML. There are no FDA-approved therapies targeting NPM1-mutant AML, which represents approximately 30% of new AML cases annually and is a disease of significant unmet need. Priority review was requested, which, if granted, would provide a target FDA review period of six months from NDA acceptance.

FDA has been a collaborative and supportive partner, and although it's early days in our review cycle, we've not experienced any disruptions or delays due to the changes underway at Health and Human Services or FDA. We look forward to continuing to work closely with the agency throughout the review process and are optimistic about the potential for ziftomenib to impact patients with relapsed refractory NPM1-mutant AML. With that introduction, I'd like to turn it over to Mollie to walk through updates to our development pipeline and programs. Mollie.

Mollie Leoni (CMO)

Thank you, Troy. First, let's start with our ziftomenib development program. Earlier this year, we announced KOMET-001, our phase two registration-directed trial of ziftomenib in patients with relapsed refractory NPM1-mutant AML, had achieved its primary CR/CRh endpoint, and we are pleased the data will be shared in an oral presentation at the upcoming 2025 ASCO Annual Meeting in Chicago. The benefit-risk profile for ziftomenib in this patient population is highly encouraging, and the safety profile remains consistent with data shared previously. We believe the combination of favorable safety and tolerability profile and clinical activity in this once-daily oral medication support a competitive profile in the relapsed refractory setting, as well as clinical development in the critical frontline indications. Our plan is to socialize the data among scientific and medical communities in the U.S.

and Europe between the oral presentation at ASCO, as well as an encore presentation of the data at the 2025 EHA Congress, ahead of potential marketing approval. Moving to the combinations, we continue to see robust enrollment in both the KOMET-007 and KOMET-008 studies, which are evaluating ziftomenib in combination with various standards of care. We are pleased to announce the preliminary clinical data from the phase 1b expansion cohort evaluating the combination of ziftomenib with intensive chemotherapy in the frontline setting has been accepted for an oral presentation at EHA, and we anticipate presenting preliminary clinical data from the KOMET-007 phase 1b expansion cohort evaluating ziftomenib in combination with venetoclax and azacitidine in the frontline setting in the second half of the year.

These will be important updates as they will help inform the safety, tolerability, and potential clinical activity of the triplet combinations and directly inform the design and conduct of the phase three frontline trials under the KOMET-017 protocol. In addition, we announced last quarter we had reached alignment with FDA and EMA for the design and conduct of this trial. Notably, we also announced we had broken new ground to use MRD-negative CR and CR, respectively, as primary endpoints for accelerated approval in the United States in the intensive and non-intensive chemotherapy frontline trials, respectively. As a reminder, the global protocol comprises two independent, randomized, double-blind, placebo-controlled phase three trials to evaluate ziftomenib in combination with both intensive and non-intensive combination regimens in patients with newly diagnosed NPM1-mutant and KMT2A-rearranged AML.

We have received feedback from institutions, investigators, and their study teams that the design of KOMET-017 with two independent phase three trials under a single protocol is very attractive to clinical sites because it simplifies trial startup and conduct and provides a single option to nearly all of their eligible frontline patients. KOMET-017 is now in study startup, and we remain on track to initiate the studies in the second half of this year. Turning our attention to solid tumors, earlier this week, we announced the first patients dosed in our phase one KOMET-015 trial to evaluate the safety, tolerability, and preliminary tumor and anti-tumor activity in ziftomenib in combination with imatinib in adults with GIST who are currently on or have previously been treated with imatinib therapy.

Approximately 4,000-6,000 new cases of GIST are diagnosed each year in the U.S., and advanced GIST patients have limited treatment options. The current frontline standard of care regimen in these advanced patients is imatinib, which targets KIT inhibition. The challenge is most patients eventually develop resistance to imatinib due to the development of secondary KIT mutations. TKIs such as sunitinib target an imatinib-resistant genotype and are approved in later lines. The response rates and long-term outcomes are modest, so new therapeutic options are needed. Ziftomenib offers potential to shift the treatment paradigm in GIST. Although we could certainly pursue development in advanced GIST patients who have failed imatinib treatment, this novel mechanism of action potentially permits ziftomenib to prevent resistance to imatinib in the frontline setting, an approach which builds on the strengths of imatinib itself and is not addressed with current therapies.

The dosing of the first patients marks a significant milestone to develop a new combination treatment to potentially improve outcomes and address a meaningful unmet need for GIST patients. We look forward to sharing clinical updates as it becomes appropriate. Moving from our ziftomenib development programs to our FTI development programs, we continue to make significant progress in the FIT-001 trial, evaluating our next-generation farnesyl transferase inhibitor KO-2806 as both monotherapy and, importantly, in combination. Our approach is a revolutionary one, where FTIs are used in combination with targeted therapies to either blunt or overcome resistance and potentially drive deeper and more durable responses, reshaping the FTI story. We expect to share combination data for KO-2806 plus cabozantinib in renal cell carcinoma in the second half of 2025.

We also anticipate sharing data from the phase one monotherapy dose escalation of KO-2806 in patients with RAS mutations in the second half of 2025. We are pleased to report the momentum continues in the FIT-001 trial, and we expect to initiate one or more expansion cohorts of KO-2806 and cabozantinib in patients with advanced renal cell carcinoma in the second half of 2025. We also continue to evaluate the combination of KO-2806 and adagrasib in patients with KRAS G12C mutant solid tumors. Finally, we are pleased to share that the current HN phase one trial that was evaluating tipifarnib in combination with alpelisib in patients with recurrent or metastatic PIK3CA-dependent head and neck squamous cell carcinoma is now close to enrollment. We anticipate sharing clinical data later this year and are evaluating the next steps for that combination and the program.

With that, I will turn it back over to Troy.

Troy Wilson (President and CEO)

Thank you, Mollie. Regarding the dynamic macro landscape in which we're now operating, we continue to monitor developments and remain vigilant to the rapidly evolving situation, and we're prepared to adapt as needed. At this time, we believe the impact from tariffs would be negligible, and additionally, all of our intellectual property is domiciled in the United States. Importantly, in this challenging market, our strategic partnership with Kyowa Kirin provides us with greater development, commercial and operational resources, as well as increased financial stability. Our partnership and cash resources enable our team to stay focused and execute on our pre-commercial and launch preparation efforts, as well as our efforts to create a clinically meaningful impact in other areas such as GIST, renal cell carcinoma, and other solid tumors. I'll now turn it over to Tom to provide the first quarter financial highlights. Tom?

Tom Doyle (SVP of Finance and Accounting)

Thank you, Troy, and good afternoon, everyone. Collaboration revenue from our Kyowa Kirin partnership for the first quarter of 2025 was $14.1 million, compared to no revenue in the first quarter of 2024. Research and development expenses for the first quarter of 2025 were $56 million, compared to $36.3 million for the first quarter of 2024. General and administrative expenses for the first quarter of 2025 were $22.8 million, compared to $18.2 million for the same period in 2024. Net loss for the first quarter of 2025 was $57.4 million, compared to a net loss of $49.5 million for the first quarter of 2024. This included non-cash share-based compensation expense of $7.8 million, compared to $8.5 million for the same period in 2024. As of March 31, 2025, Kura Oncology had cash, cash equivalents, and short-term investments of $658.2 million, compared to $727.4 million as of December 31, 2024.

As adjusted for the $45 million NDA submission milestone payment under our collaboration agreement with Kyowa Kirin, Kura had, on a pro forma basis, $703.2 million in cash, cash equivalents, and short-term investments as of March 31, 2025. Based on our current operating plans, we believe that our cash, cash equivalents, and short-term investments as of the end of the first quarter will be sufficient to fund our current operating expenses into 2027. If we include anticipated collaboration funding and milestones under the Kyowa agreement, Kura's financial resources should support advancement of our ziftomenib AML program through commercialization in the frontline combination setting. With that, I'll turn the call back over to Troy.

Troy Wilson (President and CEO)

Thank you, Tom. Before we jump into the question and answer session, let me lay out our anticipated upcoming milestones. For ziftomenib and our menin inhibitor programs, we look forward to presenting full data for KOMET-001 in Q2 2025 in an oral presentation at ASCO and an encore presentation at EHA, present preliminary clinical data from the KOMET-007 phase 1b expansion cohort evaluating ziftomenib with intensive chemotherapy, or 7+3, in the frontline setting at EHA, presenting preliminary clinical data from the KOMET-007 phase 1b expansion cohort evaluating ziftomenib with venetoclax and azacitidine in the frontline setting at a medical meeting in the second half of 2025, initiating KOMET-017, two independent phase 3 registration-enabling trials in frontline intensive and non-intensive AML in the second half of 2025, and nominating a development candidate for a next-generation menin inhibitor program in diabetes in mid-2025.

For our farnesyl transferase inhibitor programs, we expect the following milestones: initiate one or more expansion cohorts of KO-2806 and cabozantinib in patients with advanced renal cell carcinoma in the second half of 2025, present data from the FIT-001 phase one trial evaluating KO-2806 and cabozantinib in patients with renal cell carcinoma in the second half of 2025, present data from the FIT-001 phase one monotherapy dose escalation of KO-2806 in patients with RAS mutations in the second half of 2025, and finally, to present data from the current HN trial evaluating tipifarnib and alpelisib in PIK3CA mutant head and neck squamous cell carcinoma in the second half of 2025. With that, Jess, we're now ready for questions.

Operator (participant)

Thank you, sir. At this time, if you would like to ask a question, please press star one on your telephone keypad. You may remove yourself from the queue at any time by pressing star two. Once again, that is star one to ask a question. We will move first to Li Watsek with Cantor Fitzgerald.

Hi, team. This is Dan on for Li. Congrats on the progress and the milestone payments. Can you maybe set the expectations for the combo data coming later this year, especially the A's of N cohort? What do you need to show us to be competitive? It looks like some of your competitors have kicked off a phase three trial here. Just update us a little bit as well. What you're thinking about in terms of initiating the frontline trial. Thanks.

Troy Wilson (President and CEO)

Yeah, thanks, Dan, for the questions. Just to recap, what are we looking for from the A's of N cohort and then really timing of initiation of that trial relative to the competition? Mollie, would you like to take Dan's questions?

Mollie Leoni (CMO)

Sure. As I'll remind you, we're always looking for, especially in these preliminary data presentations, safety as our first, second, and third priorities. The ability to safely combine our ziftomenib with the venetoclax in the frontline is what we really want to establish. Obviously, now being able to finally see the data in these frontline patients, we'll be able to see some additional characteristics about time on treatment and overall patients' responses to therapy. We look forward to being able to show you the combineability of ziftomenib with these agents that can be difficult to combine with if there was to be any added toxicity or any adverse events on combination.

Troy Wilson (President and CEO)

Dan, with respect to your question around timing, we remain on track to start the study in the second half of 2025.

Okay. Thank you.

Sure.

Operator (participant)

We'll go to Jonathan Chang with Leerink Partners.

Jonathan Chang (Analyst)

Hi guys. Thanks for taking my questions. First question, can you discuss how the changes at the regulatory agency have impacted or not the potential approval process and timelines for ziftomenib?

Troy Wilson (President and CEO)

Yeah, they.

Jonathan Chang (Analyst)

The second question.

Troy Wilson (President and CEO)

Yeah, go ahead, Jonathan.

Jonathan Chang (Analyst)

Sure, go ahead.

Troy Wilson (President and CEO)

The second part. No, no, go ahead.

Jonathan Chang (Analyst)

Oh, the second question, can you help set expectations for the upcoming ASCO presentation of the KOMET-001 results? How should we be thinking about what will be in the abstract versus the full presentation? Thank you.

Troy Wilson (President and CEO)

Yeah, thanks, Jonathan. Thanks for that. As for any changes underway at FDA, as we said in the prepared remarks, we're not seeing any impact at all. The agency has been responsive, collaborative, productive. We're not seeing any effects at all. We requested priority review. We'll be able to give guidance. We would expect to receive notification from FDA on whether the application's been accepted for review and the PDUFA date here in the second quarter, and we can communicate that at that time. At this point, it's business as usual. I'll just add, Jonathan, recall that we have breakthrough therapy designation in NPM1-mutant AML.

As we said at the time, this is when that designation matters because agents that have breakthrough therapy designation generally get a higher priority and more resources within FDA because, of course, they are directed at significant unmet needs and needs for which there's no available therapy. Whether or not that's playing into the fact that we're not seeing any impact at all, I can't say, but I think we feel today pretty good about where we are with FDA. With respect to the second part of your question about the monotherapy data, again, we've answered this question I think many times. The CR/CRh rate will be between 20-30%. We'll also look at time on treatment, safety, and tolerability, all the key considerations. You'll see much of that articulated in the abstract.

The ASCO presentation will have a more fulsome data set, of course, because you can go much beyond the abstract. The timing of those two, they'll be as of the same data cutoff, but of course, the oral presentation will have more data, of course, relative to the abstract.

Jonathan Chang (Analyst)

Got it. Thanks for taking my questions.

Troy Wilson (President and CEO)

Sure. Happy to.

Operator (participant)

We'll go next to Salim Syed with Mizuho.

Salim Syed (Analyst)

Great. Thanks for the question and the commentary today, Troy and team. I guess one just for your upcoming expected launch in the NPM1 setting. A lot of people, I think, are thinking here that at least in terms of CR/CRh rates here, that these two menin inhibitor molecules seem more or less the same. Just curious what your updated market share work is sort of telling you, Troy, how these are going to sort of get used if and when they're both on the market in the relapsed/refractory setting.

Troy Wilson (President and CEO)

Yeah, Salim, it's a good question. Let me comment, and then I'd actually ask Brian to maybe add his thoughts. Obviously, let's have that conversation, I think. I understand why you're asking the question. We keep emphasizing safety, tolerability, clinical activity. It is the whole package. It's important as a monotherapy. It becomes increasingly important as one goes into combination. We have, of course, done internal demand studies. I don't think we've ever made that public, but we do believe that ziftomenib will be very competitive in the relapsed/refractory setting. We're obviously seeing very strong enrollment in the combo settings, which I think, again, speaks to its ability to treat more patients and ideally get them to better outcomes overall. Brian, anything you'd add?

Brian Powl (CCO)

I think you answered that. Thank you, Troy. I think you answered that pretty well. I would just maybe add, as you said, we've been doing our demand studies, trying to get a better understanding of where we see the potential profile differences between agents that come forward. I think that what we're seeing is that this will be a competitive space as we expect it, but that we have very good confidence, I think, in the strength of our profile that we will be able to be competitive in that monotherapy launch, and we're going to put the resources behind to support that as well.

Troy Wilson (President and CEO)

Yeah. Salim, to that point, this is one of the advantages of our partnership. We know we're going to be competing for patients, right? It's an area of high unmet need. It will, we think, be a competitive dynamic, but we're planning, and we'll provide greater color on this as we get later in the year. Brian and his team are working very thoughtfully with our colleagues at Kyowa Kirin, and we expect to bring the resources and the focus to bear on competing for every single patient. We're doing that ideally in the relapsed/refractory setting, but also ultimately, we are optimistic that you're going to see use of these menin inhibitors in earlier lines of therapy and in combination. There is a lot of education to be done.

Salim Syed (Analyst)

Okay. Perfect. Thanks so much.

Troy Wilson (President and CEO)

Of course.

Operator (participant)

We'll move next to Jason Zemansky with Bank of America.

Hey, team. This is Cameron on for Jason. Congrats on the updates, and thanks so much for taking our question. Connecting the dots from some of your earlier comments, as you look to additional combination data from 007 at EHA, starting with the FIT population, what, in your view, would constitute a win from the 7+3 combo, specifically on response rates in KMT2A and NPM1? How does that change now that we should see data in non-adverse risk patients? As we start to get additional insights into MRD negativity, what would drive confidence here and a potential pathway to accelerate approval for zifto ultimately?

Troy Wilson (President and CEO)

Yeah, that's really good questions, Cameron. Let me ask Mollie if she can speak to those.

Mollie Leoni (CMO)

Sure. As we've shown our frontline FIT data in the past, we're obviously seeing really high rates of response, even in the adverse risk patient. It would be hard to improve upon the 100% response rates we were seeing, nor did we expect to maintain that perfection. Throughout the literature, what we've seen is that in these patient populations, you expect to see anywhere from a 60-90% CRc rate. Maintaining and not interfering with the efficacy of the backbone and hopefully augmenting it, of course, is the goal. How do you augment an ORR rate that's that impressive? You don't exactly target the ORR rate. As you referenced, we're looking at other signs as well. Usually, most of these patients will become relapse refractory within a year.

You're going to see data on patients that are approaching a year's worth of therapy so that you can get an idea of maybe the durability of these patients' responses to this combination of therapy. Obviously, we will be showing MRD data as well. However, I'm not sure if we will be able to show a centralized version at the time of the presentation. It'll still be a mix of both bone marrow and peripheral blood, which will make interpretation slightly more difficult. Of course, in bone marrow, you expect maybe 40% of patients to achieve MRD negativity. That should be an anchoring point for looking at the data.

Great. Thank you.

Troy Wilson (President and CEO)

Thanks, Cameron.

Operator (participant)

We'll go next to Charles Zhu with LifeSci Capital.

Charles Zhu (Analyst)

Hey, everyone. Thanks for taking the question. I'll start off by saying congratulations on submitting your NDA in NPM1 AML. Interesting timeline relative to your competitor's sNDA, even though they hit top line months before you did. Anyways, onto the question. I'll ask one actually on farnesyl transferase inhibitors regarding KO-2806. How do you envision the longer term in combination development with VEGF TKIs in RCC? Just given the movement in that space with next-gen VEGF TKIs, HIF2 alphas, as well as checkpoint inhibitors, and how do you see KO-2806 fitting into that as it shapes out longer term? Thank you.

Troy Wilson (President and CEO)

Yeah, Charles, thanks for the question. Mollie, do you want to answer Charles' question about how we see 2806 fitting into the evolving RCC landscape?

Mollie Leoni (CMO)

Of course. I mean, as you point out, there are thankfully new therapies coming into this area of high unmet need, but none of them are going to be curative. Until there is actually a cure, there is always going to be the need for additional therapies. We see the combination of 2806 with cabo to be highly synergistic with the way physicians are currently comfortable treating. They will be able to make use of a drug they are comfortable with, that they have seen high rates of response with. Hopefully, with the addition of 2806, they will see deeper, longer, and higher rates of response for these patients. We see a very big potential for 2806 to really augment the current treatment paradigms.

Charles Zhu (Analyst)

Got it. Great. Thank you.

Troy Wilson (President and CEO)

Thanks, Charles.

Operator (participant)

We'll go next to Ellen Horste with TD Cowen.

Ellen Horste (Analyst)

Great. Thank you for taking the question. Congrats on the NDA. Super exciting. A couple of questions. What is Kura Oncology's strategy to capture the share of the NPM1 market and overcome ziftomenib's second-to-market position? What points of differentiation do you think will resonate most with investors?

Troy Wilson (President and CEO)

Yeah. Maybe I can take issue just with the thesis of the question. It's not obvious to us at the moment that we'll be second-to-market. We've disclosed that we submitted our NDA in March, admittedly end of March. Let's call it end of Q1. We've requested priority review, and we have breakthrough therapy designation. Just as you are, we're waiting to see kind of where our competitors are in terms of their submission timelines and regulatory review. I think under any scenario, it's going to be very, very close. That's just our operating hypothesis. If you go back not that long ago, I was hearing from people that we were a year behind or two years behind. Kudos to our development and regulatory teams for closing that gap. Unfortunately, there isn't a large prevalent population of relapse refractory NPM1 mutant patients.

We wish there were, but that actually speaks to the significant unmet medical need. These patients progress and unfortunately pass away within days or weeks if you do not get them on therapy. I think where you are going to end up is a competitive dynamic where physicians have choices, and choice is always good for patients. As Brian said in his prepared remarks to the earlier question, we are going to mount a significant, we lead commercial strategy, and we and Kyowa Kirin are working together. We are going to be fighting for every patient, and we are going to be looking both to promote within the relapsed refractory setting and then to educate about the potential for menin inhibitors in earlier lines of therapy and in combination.

That's why you see a comprehensive approach to us moving ziftomenib to what we believe will be first-in-class and best-in-class throughout the treatment continuum. This is the first step. It's an important step, and we're feeling pretty good about it.

Ellen Horste (Analyst)

Thank you, Troy. That's helpful.

Troy Wilson (President and CEO)

Yeah. Pleasure.

Operator (participant)

Once again, it was Star One if you would like to ask a question. We will move next to Peter Lawson with Barclays.

Peter Lawson (Analyst)

Hey, thanks for taking my questions. Troy, just on the GIST side of things, what patient segments do you think are going to be more responsive to the combination and the particular subgroups you are going to be focused on, whether it's the imatinib refractory or naive?

Troy Wilson (President and CEO)

Peter, that's actually one of the beauties of this program, but I'll let Mollie fill in the details. That's a great question, and it actually, I think you've put your finger on sort of what is potentially so transformational about this MOA. Mollie?

Mollie Leoni (CMO)

Yeah, that's exactly what I was thinking, Troy, is that's what makes this approach so revolutionary and potentially transformative is that it will be mutationally agnostic. We do not have to worry about picking the appropriate combination partner for each line of therapy, using it with imatinib, whether the patient is currently on imatinib or has already failed imatinib and has had additional previous lines of therapy. The combination should still work. With ziftomenib, as with the way it affects the KIT transcription, and the imatinib affects the KIT stability. Overall, these highly KIT-dependent cells are then deprived of what they need to continue being oncogenic from two different mechanisms. As I said, that should be independent of what the KIT mutation is.

We would, of course, start to show ourselves that it works in a second-line plus setting, but we hope to move into the frontline setting as well because we really think we could be a superb adjunct to imatinib therapy, which physicians are already so comfortable with and which patients tolerate so well.

Peter Lawson (Analyst)

How do you think that kind of plays out? Does that play out in ORR or PFS? What are the goals, I think, or the go-forward decisions around those? I know it's early, but around ORR and PFS?

Mollie Leoni (CMO)

Yeah. As we look at our preclinical data, we think it'll be a combination of both. We think that we'll see it's very rare you see a complete response in a GIST patient. We're hoping to see potentially deeper responses, longer-lasting responses. Again, if we see a response in a patient where imatinib has now failed or is starting to fail and we can save that response, that's also a very clear sign that this potential mechanism truly is synergistic and is what these patients need.

Peter Lawson (Analyst)

Gotcha. Thank you so much.

Troy Wilson (President and CEO)

Peter, I just want to pick up on something that Mollie said, and this is in response to your question as well as Charles' question. What you see as you look across our portfolio is we're taking these targeted therapies and ideally layering them onto standard of care that is either generic or will be generic by the time we get to market. Chemotherapy in AML, potentially cabozantinib in RCC, imatinib in GIST, that if we can take opportunities where the market is very well understood, it's physicians' first choice, and we can make a claim that we can actually do better for your patients, and you have the ability to drive premium pricing as well because you're not layering on top of another novel therapy, we see that as a really compelling opportunity across both liquid tumors and solid tumors.

We have not talked much about the pipeline. There has just been so much focus on zifto, but that is the theme that you are beginning to see come together. We will have much more to talk about this in the second half of the year and on into next year.

Peter Lawson (Analyst)

Perfect. Thank you so much.

Troy Wilson (President and CEO)

Sure.

Operator (participant)

We'll go next to David Daiwith UBS.

David Dai (Analyst)

Great. Thanks for taking my questions. I also want to add my congratulations to a great quarter. Just focusing on phase three, KOMET-017 trial, what are some of the gating steps before you're able to initiate the trial in the second half? More specifically around that, how are the site activations going? What are some early receptions from trial investigators on the ziftomenib's profile that could really accelerate your initiation in that trial?

Troy Wilson (President and CEO)

Yeah. David, thanks for the question. Maybe I'll take the first half, and then I'll ask Mollie to speak to what we're hearing from sites and investigators. We've said we're in study startup. There's a lot that has to happen for a global phase three, contracting, budgeting, as you say, site initiation. We haven't been more granular on our guidance beyond saying it's second half. The team is doing everything it can to pull those timelines in. As I like to say, first patient in matters. Last patient in arguably matters more. Our team, I think, increasingly has shown an ability to execute at a very high level: development, regulatory, clinical operations, hopefully soon to be commercial. We'll give you more color around these trials as we get into the second half of the year.

In terms of what we're hearing about ziftomenib in the context of O17, let me ask Mollie if she can speak to some of what she and her team are hearing from investigators.

Mollie Leoni (CMO)

Sure. I mean, really, we have such a good preview of 017 from our 007 trial that it gives us a real good insight into how both the treaters and the patients are feeling. One of the things we hear most often is that they don't realize they're taking another medication. They feel the same or better than they did on the backbone therapies. We don't really see that there's going to be much opposition to including the addition of ziftomenib within these backbone therapies as well. There's a lot of excitement. We get contacted directly from people that want to participate. I think as we share more data from the 007 trial, the excitement will only build. It's all been very positive so far.

David Dai (Analyst)

Great. Thank you so much.

Troy Wilson (President and CEO)

Thanks, David.

Operator (participant)

We'll move next to Jeet Mukherjee with BTIG.

Jeet Mukherjee (Analyst)

Great. Thank you for taking the question, and congrats again on the NDA submission. My first question was, we do hear anecdotal off-label use of other currently approved menin inhibitors in relapsed refractory NPM1 patients. My question was, what do you think is perhaps needed to pull clinicians who are perhaps familiar and comfortable with one agent over to zifto following a potential approval? Thanks.

Troy Wilson (President and CEO)

Yeah, Jeet, thanks for the question. Let me ask Brian if he can speak to it.

Brian Powl (CCO)

Yeah. Thanks, Jeet. I've heard and we've seen reports around some of the competitor agents having some off-label usage of NPM1. I think to what Troy's point earlier is, is that we anticipate there may be some experimentation and use of other therapies in this setting, which I think demonstrates the very high unmet need in this space. To the point that Troy made earlier, we don't anticipate that there is a large pool of patients that are just waiting for a therapy to be available. If there are patients that are currently being prescribed another menin inhibitor, we think that there will still be patients as we move forward to approval that will still be available for us.

I think our objectives and goals will be able to appropriately communicate the risk-benefit profile of our therapy relative to other competitors so that we can understand and give physicians the information they need that what we understand and we think may be a favorable profile relative to others. I am glad that physicians are excited about the introduction of menin inhibition and the treatments. On the other hand, I think that gives us a good position for us as we prepare for a launch to kind of be ready to go out there and get every patient possible to put on the ziftomenib.

Jeet Mukherjee (Analyst)

Great. Thanks. Maybe just a quick follow-up with all that's going on in the FTI franchise between RCC, RAS mutations, and head and neck as well. Just are you looking to advance all these indications in parallel, or what will it take to make you have a go, no-go decision with all these indications?

Yeah.

Thanks.

Troy Wilson (President and CEO)

Yeah, Jeet, that's actually a very, very good question and very forward-looking. Thank you. This goes back to a comment that I made earlier after Peter's question. I think it's important that biopharma companies of our size have a compelling sort of standalone proposition that one can finance and execute on independently. If you can add on to that and drive increasing uptake and revenue, that's great. What does that mean? We think we'll be in a position if the data supports moving forward into RCC. Admittedly, it's early days. We haven't shown you any clinical data. You've seen, I think, pretty compelling preclinical data, clinical data coming in the second half of the year. If there's an opportunity, we could arguably do that alone because by the time we reach the market, the partner compound, in this case, cabozantinib, would be likely generic.

That's not true for, that may be true for, for example, PI3 kinase alpha inhibitors or KRAS inhibitors. There, you're more likely going to need to partner with either a large company or a small company to find the path forward. I would put that in the bucket of, Jeet, of nice to have. I don't think you want to have your company's strategy necessarily dependent on a partner. I think you want to have that as optional and a really high commitment from both parties. What you're seeing, again, we're in a great place with Kyowa Kirin and AML. I think we'll look forward in the future to sharing data in GIST with you. We'll talk about FTIs. We are trying to identify those product opportunities, i.e., the combinations, which Kura can take forward on its own or in the case of zifto with Kyowa Kirin.

That's at a high level, Jeet, how we'll think about prioritizing it. Below that, you ask, what are the best agents? Who are the partners? How do we think about working together? It will be very much starting with what is best for Kura, for our patients, and for our shareholders.

Operator (participant)

We will be looking to George Farmer with Scotiabank.

George Farmer (Analyst)

Hi. Thanks for taking my questions. Troy, given that you do have BTD with zifto and NPM1 disease, shouldn't you have a good feel about whether you can get priority review by now? Also, do you think you'll need that FDA will want to convene an ODAC meeting? Also, regarding the co-primary endpoint in your phase threes of MRD negativity and CR/CH, do you need to hit both of those in order for a win, or can you just hit one or the other? Thanks.

Troy Wilson (President and CEO)

Yeah, George. I'll take the first two questions, and I'll let Mollie take the endpoint questions. We can't look. We've said we're feeling good. There've been no disruptions. The agency's been responsive. I think at this point, we've said as much as we can say. Next stop is hopefully the dossier's accepted for review, and we're assigned a PDUFA date. We'll communicate that when it happens. Your second question was, forgive me.

George Farmer (Analyst)

Oh, ODAC.

Troy Wilson (President and CEO)

Oh, the ODAC. I think it would be unusual. I don't think we're expecting an ODAC here, given this is a palliative setting, given that the agency's expressed a willingness to grant full approval for agents in relapsed refractory AML, and given, George, quite frankly, that the safety and tolerability profile, to Mollie's point, really, I think is very strong in the case of ziftomenib. You would never say never, but I don't think we're anticipating an ODAC. Mollie, do you want to—I don't know if you want to add anything, Mollie, to my first two answers, but could you speak to George's questions about the endpoints on the phase threes?

Mollie Leoni (CMO)

Sure. No, I mean, I think your first two answers are spot on. We'll find out about priority review when they formally accept the dossier. As for the co-primaries, what I want to correct is they're not actually co-primary endpoints. They're dual primary endpoints. Even if you, for some reason, did not win on your accelerated endpoint, so your CR or your MRD-negative CR, you could still win in the overall trial with the survival-based endpoint, that being the EFS or the OS. You can hit both or just the overall survival endpoint and still have a win.

George Farmer (Analyst)

Okay. Thank you.

Troy Wilson (President and CEO)

Yeah. Thanks, George.

Operator (participant)

We'll go next to Roger Song with Jefferies.

Roger Song (Analyst)

Great. Thanks for the update and the technical questions. The first is a clarification. Maybe Troy, I'm not sure I missed that. You said the ASCO abstract and the presentation will be the same data cut. Can you just confirm that? It also relates to your 017, the first-line combination pivotal. How should we think about the enrollment given you will soon have approved the drug, and you already have approved the drug, and then soon ziftomenib will be approved in the RNR setting? How should we think about the pivotal first-line enrollment timeline? Thank you.

Troy Wilson (President and CEO)

Yeah. Yeah, Roger. Thank you for the questions. Yeah, the abstract and the presentation will have the same data cut. As I said, the full presentation is a more expansive tour through the data. As far as your second question, Roger, around the dynamic between a potentially approved ziftomenib product and the frontline trial, there really should not be—let me put it this way. There should not be a drag on enrollment in the frontline trials because obviously that is a patient population for which no menin inhibitor is approved. As Mollie indicated in her answers to a couple of questions, we continue to see very robust enrollment in both the intensive and non-intensive setting. I think maybe the reciprocal question of, will there be an impact of the frontline studies on the relapsed refractory setting, I do not think we know the answer to that.

We'll be watching for that, but I think it's too early to say at this point whether there'll have any impact of frontline development on the availability of patients in the commercial setting in the relapse refractory, excuse me, in the relapse refractory setting.

Roger Song (Analyst)

Yep. That's fair. Thank you.

Troy Wilson (President and CEO)

Thank you.

Operator (participant)

It appears that we have no further questions at this time. I will now turn the program back over to Troy Wilson for any additional or closing remarks.

Troy Wilson (President and CEO)

Thank you, Jess. Thank you all once again for joining our call today. We'll be participating at several medical and investor conferences over the next couple of months, including ASCO and EHA. Look forward to seeing many of you there. We also plan to host a virtual investor event following our oral presentation at ASCO. Look for more details in the coming weeks. In the meantime, if you have any additional questions, please feel free to reach out. Thank you, and have a good afternoon and a good evening, everyone.

Operator (participant)

Thank you, sir. This does conclude today's program. We thank you for your participation. You may disconnect at any time.