Kura Oncology - Earnings Call - Q2 2025

Executive Summary

• Q2 2025 results reflected modest collaboration revenue and increased operating spend as Kura advances toward ziftomenib commercialization: collaboration revenue $15.3M, net loss $66.1M, cash and investments $630.7M as of June 30, 2025.
• FDA accepted the NDA for ziftomenib with Priority Review; PDUFA target action date is November 30, 2025, and U.S. sales force hiring/onboarding is complete, positioning for launch upon potential approval.
• Street expectations were materially higher: Q2 revenue ($15.3M) and EPS (-$0.75) missed consensus ($64.9M and -$0.37) as collaboration revenue proved lower than modeled; management did not provide quarterly revenue guidance, focusing instead on regulatory and clinical milestones. Values retrieved from S&P Global.
• Near‑term catalysts: the PDUFA decision (11/30/25), initiation of two Phase 3 frontline trials (KOMET‑017‑IC/NIC) in 2H 2025, and multiple FTI program data sets at ESMO October 2025; Kura cites up to $375M in additional near‑term milestone potential under the Kyowa Kirin collaboration.

What Went Well and What Went Wrong

What Went Well

• NDA acceptance with Priority Review and defined PDUFA date, with management describing constructive FDA interactions on-track with priority timelines: “We were pleased to announce FDA accepted our NDA… granting priority review with a PDUFA target action date of 11/30/2025” and “interactions have all been collaborative… in alignment with the timeline for a priority review”.
• Commercial readiness: “Hiring and onboarding of U.S. field sales team are now complete,” with pre‑approval information exchanges and distribution/access planning underway.
• Strong clinical narrative supporting launch and expansion: KOMET‑001 achieved CR/CRh of 23% in R/R NPM1‑m AML; favorable safety, combinability, and once‑daily dosing positioned as potential “best‑in‑class” profile; Phase 3 frontline trials on track for 2H 2025 start with dual primary endpoints enabling potential accelerated approval.

What Went Wrong

• Financial results missed Street expectations: Q2 revenue $15.3M vs consensus $64.9M and EPS -$0.75 vs -$0.37; prior quarter also missed, highlighting variability in collaboration revenue recognition timing. Values retrieved from S&P Global.
• Operating spend rose as programs scale toward Phase 3 and commercialization: R&D $62.8M vs $39.7M YoY; G&A $25.2M vs $16.7M YoY; net loss widened to $66.1M vs $50.8M YoY.
• Competitive questions intensifying around menin class dynamics and potential first‑mover advantages; management emphasized differentiation and rapid Phase 3 execution, while analysts probed NCCN guideline timing and competitive positioning.

Transcript

Speaker 3

Thank you for your continued patience. Your meeting will begin shortly. If you need assistance at any time, please press star zero and a member of our team will be happy to help you.

Speaker 0

It Sam.

Speaker 3

Thank you for your continued patience. Your meeting will begin shortly. If you need assistance at any time, please press star zero and a member of our team will be happy to help you. Thank you for your continued patience. Your meeting will begin shortly. If you need assistance at any time, please press star zero and a member of our team will be happy to help you. Please stand by. Your program is about to begin. Hello and welcome everyone. Joining today's second quarter 2025 Kura Oncology Inc. Financial Results Conference Call. At this time, all participants are in a listen only mode. Later, you will have an opportunity to ask questions during the question and answer session. You may register to ask a question at any time by pressing star and one on your telephone keypad. Please note this call is being recorded.

I am standing by should you need any assistance. It is now my pleasure to turn the meeting over to Greg Mann, Senior Vice President of Investor Relations and Corporate Affairs. Please go ahead.

Speaker 0

Thank you.

Speaker 2

Good afternoon and welcome to Kura Oncology's second quarter 2025 conference call. Joining the call today 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, we 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 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.

Speaker 0

Thank you, Greg. Good afternoon, and thank you all for joining us. At Kura, we're committed to transforming outcomes for patients with AML. Today we'll provide updates on our global development progress for our lead program ziftomenib, regulatory status of our New Drug Application, preparations for commercialization with our partners at Kyowa Kirin Co., Ltd., and advances in our pipeline, including menin inhibitors for treatment of GIST and diabetes, as well as farnesyltransferase inhibitors or FTIs for solid tumors. Starting with development, we were thrilled to present positive monotherapy data from the COMET-001 trial at ASCO. Ziftomenib showed promising results in relapsed or refractory NPM1-mutated AML, offering hope for this heavily pretreated population. We're also encouraged by ziftomenib's consistent safety and tolerability profile.

In this setting, we were pleased to announce FDA accepted our NDA for ziftomenib in adults with relapsed or refractory NPM1-mutant AML, granting priority review with a PDUFA target action date of November 30, 2025. We're encouraged by the FDA's engagement and are focused on achieving a successful review outcome by our PDUFA date. In the frontline setting, we reported updated combination data for ziftomenib with intensive chemotherapy in newly diagnosed AML at EHA. These results highlight ziftomenib's potential as an early intervention, offering a meaningful opportunity to improve patient outcomes. Building upon the EHA data as well as emerging data for ziftomenib combined with venetoclax and azacitidine, or VEN-AZA, which we plan to share later this year, we're accelerating development of ziftomenib in frontline AML.

Toward this end, we are in study startup for the two phase 3 frontline trials under the COMET-017 protocol, along with the opportunity to treat KMT2A-rearranged AML patients. These two phase 3 trials could open up the opportunity to impact up to 50% of patients with AML. Mollie will expand on our development activities for ziftomenib later in this call. On pre-commercial activities, we're actively preparing for potential approval by building commercial supply and quality systems, advancing pre-approval inspection readiness for CMC and manufacturing, and recruiting and training our sales force, as well as collaborating with our partner Kyowa Kirin Co., Ltd. on launch planning. Brian will elaborate on our commercial readiness later in the call. Our partnership with Kyowa Kirin Co., Ltd. continues to bolster the global development and commercialization of ziftomenib.

We're aligned on advancing both relapsed/refractory and frontline programs, and we value our shared commitment to bringing ziftomenib to patients. Beyond menin inhibitors, we're making strong progress with our fully owned next-generation farnesyltransferase inhibitor KO-2806. We're excited to announce three clinical abstracts from our FTI program have been accepted for presentation at the 2025 ESMO Congress. Mollie will share more of the details on the upcoming presentations a bit later. We're also thrilled to welcome Greg Mann to our leadership team as our Senior Vice President, Investor Relations and Corporate Affairs. Greg brings an extensive biotechnology and pharmaceutical experience with a proven track record of strategic communications and investor engagement, fostering strong relationships with analysts, investors, and key stakeholders. As of June 30, 2025, Kura Oncology had $630.7 million in cash, cash equivalents, and short-term investments. Under our Kyowa Kirin Co., Ltd.

collaboration, we stand to receive up to $375 million in additional near-term milestones, including significant milestones tied to initiation of our phase 3 frontline trials as well as first commercial sale of ziftomenib in the relapsed/refractory setting. As our data continues to demonstrate, we believe ziftomenib represents a potential best-in-class menin inhibitor for AML and GIST, and with our current cash reserves and anticipated milestones, we're well funded to become the market leader, continue to advance our ziftomenib AML program through to commercialization in a frontline setting, and drive our pipeline to multiple value inflection points. With that overview, let's dive in. Starting with ziftomenib. I'll turn it over to Mollie to highlight our development activities.

Speaker 4

Mollie, thank you, Troy. Let's begin with highlights from our ziftomenib development program at ASCO 2025. Dr. Eunice Wang of Roswell Park presented data from the COMET-001 trial evaluating ziftomenib monotherapy in 92 heavily pretreated relapsed/refractory patients with NPM1-mutated AML. The trial achieved the CR/CRh rate of 23%, surpassing historical controls with consistent activity across prespecified subgroups, including those with prior transplant, prior venetoclax, those with numerous prior therapies, and those with FLT3 or IDH comutations. At the time of the data cut, 63% of responders were MRD negative. Ziftomenib's consistent safety and tolerability profile, including effective management of differentiation syndrome, low rate of myelosuppression, lack of clinically significant QTc prolongation, and absence of drug-drug interactions, underscore its favorable benefit-risk profile for patients with relapsed/refractory NPM1-mutated AML. We're progressing through regulatory milestones for our NDA submission, including information requests and pre-approval inspections in line with timelines for priority review.

As Troy noted, our interactions with FDA remain collaborative and constructive. Ziftomenib's favorable safety profile supports its broad use in combinations in both the relapsed/refractory and frontline settings. COMET-007 and COMET-008 are evaluating ziftomenib in combination with various standards of care in patients with both newly diagnosed and heavily pretreated disease. At the 2025 EHA Congress, Dr. Harry Erba of Duke University presented phase 1a/1b data from the COMET-007 trial, testing ziftomenib at a 600 milligram once daily dose plus intensive chemotherapy in newly diagnosed NPM1-mutated and KMT2A-rearranged AML. Despite available therapies, it's important to remember that up to 70% of AML patients relapse within three years, highlighting a substantial unmet need, and only a third are alive at the five-year mark. COMET-007 data were highly encouraging, with rates of complete remission and MRD negativity across the 7+3 cohorts and a safety profile consistent with previous reports.

The safety profile observed with ziftomenib in combination with intensive chemotherapy was actually similar to what is expected in patients treated with 7+3 alone. Ziftomenib's continuous daily dosing was maintained through count recovery and consolidation therapy as well as maintenance without delaying neutrophil or platelet recovery or causing any additional myelosuppression. A single case of grade 3 differentiation syndrome in a patient with KMT2A-rearranged AML was successfully managed. Composite complete remission rates were 93% for patients with NPM1-mutated and 89% for KMT2A-rearranged AML. Complete remission rates were 84% and 74%, respectively. At the time of this data cut, 96% of NPM1-mutated and 88% of KMT2A-rearranged patients remained alive and on study with a median follow-up of 25 and 16 weeks, respectively. MRD negativity was achieved in 68% of NPM1-mutated and 83% of KMT2A-rearranged patients with a composite CR at medians of 4.7 and 4.1 weeks, respectively.

We anticipate presenting preliminary clinical data from the COMET-007 trial evaluating ziftomenib at 600 milligram dose with venetoclax and azacitidine in both newly diagnosed and relapsed/refractory AML patients in the second half of this year, potentially at ASH. Last quarter we broke new ground aligning with FDA and EMA on the COMET-017 protocol, which comprises two independent randomized double-blind placebo-controlled phase 3 trials. The first is COMET-017 IC, which is ziftomenib with intensive chemotherapy, and the second is COMET-017 NIC, ziftomenib with venetoclax and azacitidine or non-intensive chemotherapy. FDA alignment on the use of MRD-negative CR and CR as dual primary endpoints for accelerated approval in both trials could substantially shorten development timelines. The single protocol design streamlines trial startup and is attractive to clinical sites because it accommodates nearly all eligible frontline patients.

COMET-017 is now in study startup and on track for initiation in the second half of this year. Turning our attention to ziftomenib in combination with imatinib for patients with advanced gastrointestinal stromal tumors or GIST, approximately 4,000 to 6,000 new cases of GIST are diagnosed each year in the United States, and advanced GIST patients have limited treatment options. Imatinib, the current frontline standard of care for advanced GIST, targets KIT via tyrosine kinase inhibition, but resistance often develops due to secondary KIT mutations. The COMET-015 trial will be combining a dose escalation to evaluate the safety, tolerability, and preliminary anti-tumor activity of ziftomenib in combination with imatinib in adults with gastrointestinal stromal tumors (GIST) who are currently on or have previously been treated with imatinib. We're advancing in dose escalation and we will share clinical data updates as it becomes appropriate.

Progress also continues in our next-generation menin inhibitor program for diabetes. We see strategic potential to expand menin inhibition to diabetes and cardiometabolic disease. We've nominated a next-generation development candidate for diabetes and will share development plans and timelines in a future update. Moving now from menin to our FTI development programs, our FIT-001 trial evaluating our next-generation farnesyltransferase inhibitor KO-2806 is progressing significantly. Our innovative approach combines FTIs with targeted therapies to overcome resistance and enhance response durability, reshaping the FTI story and expanding the use of these combinations. As Troy mentioned, three clinical abstracts from our FTI program were accepted for presentation at the 2025 ESMO Congress covering KO-2806 with cabozantinib in renal cell carcinomas, KO-2806 monotherapy in advanced RAS mutant solid tumors, and tipifarnib and alpelisib in patients with PIK3CA mutant head and neck squamous cell carcinoma.

We'll plan to host a virtual event in concordance with the ESMO Congress in October to discuss the emerging clinical data and we'll share more details ahead of that conference. We're also evaluating KO-2806 and adagrasib in patients with KRAS G12C mutant solid tumors and are already encouraged by the data being generated in dose escalation. We will look to share data from this combination likely next year, and with that I'll turn it over to Brian to discuss our commercial readiness activities.

Speaker 1

Thank you, Mollie. With the ziftomenib PDUFA date of November 30th well in sight, our pre-commercial activities continue at a brisk pace. We're confident Kura's commercial organization will be fully prepared for launch ahead of potential approval. As Mollie noted, the COMET-001 and COMET-007 clinical data were well received by the clinical community. We're encouraged by positive feedback from the KOLs highlighting four key aspects of ziftomenib in the relapsed/refractory setting. First is efficacy: strong CR rates, CRh rates, and durable responses in heavily pretreated patients, with overall survival among responders exceeding the KOLs' expectations. Second, simplicity. The once-daily dosing facilitates adoption and integrates seamlessly into patient care, benefiting both providers and patients. Third, compatibility. No clinically meaningful drug-drug interactions with CYP3A4 inhibitors enable combination with antifungals or other concomitant medications. Fourth, safety.

The low rates of QTc prolongation eliminate the need for burdensome weekly cardiac monitoring and alleviate concerns of combining with other agents known to prolong QT. This KOL feedback reinforces ziftomenib's potentially best-in-class profile in the relapsed/refractory space and their enthusiasm for its use in combination with frontline standard of care therapy in patients with newly diagnosed AML. On commercial readiness, our team is focused on raising awareness about menin inhibition in NPM1-mutated AML, ensuring access, and upon approval, communicating ziftomenib's best-in-class potential to accelerate adoption and build trust with patients and providers. Our Medical Affairs and Market Access teams are fully staffed to engage thought leaders, payers, and group purchasing organizations, or GPOs. We're executing educational initiatives on disease awareness and menin inhibition in NPM1-mutant AML alongside ongoing pre-approval information exchanges with key stakeholders, including payers, GPOs, and other market decision makers.

We've recently onboarded our sales team, selected through a rigorous nationwide screening process. The group has deep experience in hematology/oncology, with over 21 years average experience in sales and over 7 years average experience in hematology. As they deploy, they will work alongside the experienced Kyowa Kirin U.S.-based field team as the lead party. In the U.S. we are building capabilities across commercial functions while working collaboratively with Kyowa Kirin Co., Ltd. on field operations, account planning, training materials, and team building. Our market access, trade, and distribution team has identified patient support needs and is designing programs to help eligible patients navigate their treatment journey. Finally, we are implementing a focused distribution network to maximize efficient access at oncology centers and enhance provider satisfaction and drive early uptake to ensure a rapid launch of ziftomenib upon FDA approval.

Together with Kyowa Kirin Co., Ltd., we are confident in our commercial readiness and ability to deliver ziftomenib to eligible patients at launch. The relapsed/refractory AML population is our initial market entry and a critical step toward building a successful commercial product. Ziftomenib's potential best-in-class profile in NPM1-mutated AML gives us confidence in capturing robust market share in this high unmet need population. We estimate the total addressable market for NPM1-mutated relapsed/refractory AML is between $350 million to $400 million annually, driven by a patient population that can reach up to 30% of relapsed/refractory AML patients who could benefit from an average of 6 months of treatment. Ziftomenib's efficacy, safety, tolerability, and convenience position it for market leadership share in this setting. Our launch planning for the NPM1-mutated relapsed/refractory AML market lays the groundwork for the substantial opportunity we see in the frontline AML space for transformative impact.

A therapy must deliver deep, durable responses to the maximum number of patients with a tolerable profile for extended use. Ziftomenib's data, unhindered by complex dosing, excessive myelosuppression, or burdensome monitoring, support its potential best-in-class profile. Of the 22,000 newly diagnosed AML cases in the U.S., we believe menin inhibitors can reach 50% of patients where the KMT2A pathway is a driver of their disease. This includes both NPM1-mutated and KMT2A-rearranged. Our comprehensive development plan is designed to address multiple populations where patients may benefit from ziftomenib for 12 to 24 months or more, leading to a total addressable U.S. market potential of over $7 billion per year. I will now turn it over to Tom to provide the second quarter financial highlights.

Speaker 2

Tom, thank you, Brian, and good afternoon, everyone. Collaboration revenue from our Kyowa Kirin Co., Ltd. partnership for the second quarter of 2025 was $15.3 million compared to no revenue for the second quarter of 2024. Research and development expenses for the second quarter of 2025 were $62.8 million compared to $39.7 million for the second quarter of 2024, driven by spending on our ziftomenib combination clinical trials. General and administrative expenses for the second quarter of 2025 were $25.2 million compared to $16.7 million for the second quarter of 2024. This increase was predominantly due to pre-commercial activities. Net loss for the second quarter of 2025 was $66.1 million compared to a net loss of $50.8 million for the second quarter of 2024. This included non-cash share-based compensation expense of $6.9 million compared to $8.4 million for the same period in 2024.

As of June 30, 2025, Kura Oncology had cash, cash equivalents, and short-term investments of $630.7 million compared to $727.4 million as of December 31, 2024. Based on our current plans, we believe that our cash, cash equivalents, and short-term investments as of June 30 will be sufficient to fund our current operating expenses into 2027. If we include anticipated collaboration funding and milestones under our Kyowa Kirin Co., Ltd. agreement, Kura Oncology's financial resources should support advancement of our ziftomenib AML program into commercialization in the frontline combination setting. I'll now turn the call back over to Troy for final comments.

Speaker 0

Troy, thank you, Tom. Before we jump into the question and answer session, let me just lay out our anticipated upcoming milestones for ziftomenib in our menin inhibitor programs. We look forward to continued engagement with FDA reviewers as we approach our PDUFA target action date of November 30 for ziftomenib as monotherapy for patients with relapsed/refractory NPM1-mutated AML, initiating COMET-017, our two independent phase 3 registration-enabling trials in frontline intensive and non-intensive AML in the second half of 2025, and presenting preliminary clinical data from the COMET-007 Phase 1b expansion cohort evaluating ziftomenib with venetoclax and azacitidine at a medical meeting in the second half of 2025. For our farnesyltransferase inhibitor programs, we expect the following milestones. We 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 plan to have a strong presence at the 2025 ESMO Congress this October with three presentations: data from the FIT-001 Phase 1 monotherapy dose escalation of KO-2806 in patients with RAS mutations, data from the FIT-001 Phase 1 trial evaluating KO-2806 and cabozantinib in patients with renal cell carcinoma, and finally, data from the current HN trial evaluating tipifarnib and dalpelisib in PIK3CA-mutant head and neck squamous cell carcinoma. As Mollie mentioned, we expect to host a virtual event around the time of the ESMO Congress in October to discuss the clinical data for our FTI programs. More details and a save-the-date to come with that. Brittany, we're now ready for questions.

Speaker 3

Thank you. If you'd like to ask a question, press Star one on your keypad. To leave the queue at any time, press Star two. Once again, that is Star and one to ask a question. Our first question comes from Jonathan Chang with Learning Partners. Please go ahead. Your line is now open.

Speaker 0

Hi guys. Thanks for taking the questions. First, can you give us some color on how the regulatory interactions on ziftomenib have progressed as we look towards the PDUFA date later this year? Second question, how are you thinking about the scope of the farnesyltransferase inhibitor opportunity between the possible combinations and tumor types? What do you see as an area or areas that Kura can move forward with alone, and which do you see as areas better suited for a potential partner? Thank you.

Speaker 4

Jonathan.

Speaker 0

Thanks for the questions. Let's take them in turn. With respect to any additional color on the regulatory interactions, Mollie, would you like to comment to the extent that we can.

Speaker 4

Yeah, sure. As Troy's alluding to, we're currently under our active NDA review, and we can't really provide detail about every evolving interaction with the FDA. The interactions have all been collaborative, they've been very constructive, a lot of back and forth, and everything we've seen to date is in alignment with the timeline for a priority review with a net approval of November 30th. We're very encouraged by the way things have progressed thus far.

Speaker 0

Yeah, thanks, Mollie. Jonathan, on your second question, maybe I'll take a crack at it. Then again I'll ask Mollie to add her comments. As she said, I think in her prepared remarks, what I think you're going to see is really a reshaping of the FTI story. We're showing you data not only with KO-2806 as a monotherapy, but in two of the three possible opportunities. Renal cell carcinoma, where there's obviously been a lot of activity with HIF and TKIs, as well as PI3 kinase alpha, where again we've seen work from Scorpion, from Relay, and really a lot of interesting opportunity. The third one, where hopefully we'll have something to share next year, is of course in the KRAS space. We've put out a lot of preclinical data that's available on our website.

You'll see us set the context and I think help analysts and investors set expectations as we get closer to ESMO. Suffice it to say, with each of these areas, RCC, PI3 kinase and KRAS, they all have the common problem of innate and adaptive resistance. That's what we're looking to address and we're looking to share further data with you. Mollie, anything you'd add to that?

Speaker 4

No, that was a good segue. I was actually going to comment that not only does this reshape the FTI field, it also reshapes these other targeted agents. As we look to prevent or prolong these patients' ability to respond to these drugs, there's no reason to think that the results from one particular combination wouldn't be generalizable to similar drugs in the same class. We're very excited to see where this leads.

Speaker 0

Understood. Thanks for taking the questions. Thank you, Jonathan.

Speaker 3

Thank you. We'll go next to Lee Watsik with Cancer Fitzgerald, please.

Speaker 2

Go ahead.

Speaker 3

Your line is now open. Hey guys.

Speaker 4

Congrats on the progress. Maybe a little curious about your thoughts on the menin class launch so far. Looks like even in KMT2A patients, the market opportunity could be quite sizable. Any rate through to your own launch of ziftomenib and then in terms of phase 3 trial starts in the second half this year. Wondering if you can elaborate a little bit more in terms of the progress that you made since last quarter and then your confidence that you could still potentially be first in class in the frontline.

Speaker 0

Yeah, Lee, thanks. Thanks for the questions again. Let's take them in turn. Brian, could you address Lee's first couple of questions, which is our impression of the KMT2A-rearranged relapsed/refractory market opportunity and some of the results we've seen from some of our competitors and perhaps any read through to our own, you know, our own thinking or our own program.

Speaker 1

Thanks, Troy, and thanks, Lee, for the question. Yeah, I think we've obviously been watching closely, as you have, on understanding the first launch in the KMT2A space of the menin class. I think our first impression is that it's great news for patients that there is a new class of therapies available that could help to target a broader range of patients with a high unmet need. The KMT2A population, as we know, is a smaller population in incidence relative to the NPM1-mutated population. I think we're encouraged to see the preliminary uptake in activity of our competitor. When we think about what that means as we read it through into ziftomenib, first, we understand that this will be a competitive space.

We feel pretty confident, as we mentioned in our prepared remarks, that ziftomenib has the properties that we believe have the potential of being best in class as their profile across both the efficacy, the safety, the combinability of the drug and also the convenience. We think that as we bring our, or hopefully get to our FDA approval, our commercial, our medical and market access teams will be able to quickly begin communicating and be able to be competitive in this space where we see a very high unmet need for this population who are in need of new therapies.

Speaker 0

Thanks, Brian and Mollie, for you, maybe on the second question, I'm just going to restate it. Looking at the phase 3 starts here in the second half of the year for COMET-017. Can we elaborate on the progress since the last quarter and what gives us confidence we will be potentially first and best in class in those combinations?

Speaker 4

Yeah, I mean, I think I'd like to remind just what the 007 data has taught us. It taught us how much need there is for this patient population, how quickly these patients enroll, how much these sites want dedicated trials to treat these types of AML. With COMET-017, we have put both trials under a single protocol. What does that do? That makes it easier for every single site, every IRB, all of your contracting resources to go through one contracting process and not laboriously go through multiple stages or multiple negotiations and not have to choose one trial over another. Choosing one trial gives. Choosing our COMET-017 trial gives you access to two trials in one. We hear enormous amounts of excitement coming from all of our sites that have kind of put their hands up to participate. We continue to make a lot of progress.

It does take time to get a study started. We have to work out all of the contracts and everything else, as you know. It's going quickly. I have no doubt that we will start that trial the second half of this year and I have no doubt that the enrollment will be really impressive and will get us to that 2028 additional high level data that we've been talking about all along. Keep in mind, this really does allow any patient with a KMT2A or NPM1 mutation, well, almost any patient with those mutations, to have a place to go in their frontline treatment setting. I think that the potential patient population that we will be able to address is going to be enormous. I look forward to very robust enrollment and a broad patient base to be able to treat in this particular COMET-017 trial.

Speaker 0

Thank you, Mollie. Thanks, Lee, for the questions.

Speaker 3

Thank you. We'll take our next question from Roger Song with Jefferies. Please go ahead. Your line is open.

Speaker 0

Great. Thank you for the progress and thanks for taking questions. Seeing your upcoming milestone, you talk about the RCC expansion cohort. Since you already made a decision, if that's the case, what's the criteria for the expansion cohort, and then what will be the next step in time for SEC, HCC, and then KRAS and the program? The second question relates to the regulatory interaction. Given all the changes within FDA, have you had any recent interaction with the FDA regarding your phase 3 CBD design and understanding? You're about to start, but any last minute kind of feedback you're getting from the FDA. Thank you. Roger, if we may, Mollie is going to answer both of those questions. Mollie, maybe we can take them in reverse order. Let's start with the first one, which is any recent interactions with the agency on the phase 3 designs for COMET-017.

Speaker 4

Thank you for that. It's the usual interactions, just making sure we're all in agreement on even the nitty gritty. Overall, it was agreed to back months ago what the design would be, and now it's really just operationalizing. There hasn't been any additional concern or additives by people coming or going from the FDA. It all is holding pretty steady for us. Yeah.

Speaker 0

Maybe just to build on that, Roger, on Mollie's comment, this is nothing new in oncology, right? When the agency gives you the pathway to accelerated approval, whether that's monotherapy or in combo, the condition is always that you come back with the data. I think maybe what's different here is there's a recognition in AML that it may not be or it isn't in the best interest of patients to wait around for survival endpoints in some cases. There is a real willingness on the part of the FDA to consider accelerated approvals or pathways to accelerated approval. That's what Mollie and her team were so, so skilled in, in coordinating with the FDA. Everything is on track from our perspective. Mollie, on the first question, it's probably a little early, but Roger asked, you know, what's our decision making process for RCC for KRAS?

You want to speak a little bit to that? I know it's early in where we are.

Speaker 4

Yeah, it's early. I'll focus on RCC because that's probably the easier story to explain at this point. We're going through our dose escalation, of course, and we had our go/no-go criteria that we established prior to starting the study. I'll say that we've not really shared publicly our go/no-go criteria, but we had no problems in meeting that. Currently, when we talk about our expansion cohort, it's really with the thought of correctly fulfilling Project Optimus and giving them the data that they want. We will expand out to at least two doses and look to see which dose is best tolerated and most efficacious at the same time. At that time, obviously, we will look for convincing data that you're seeing more than just a Cabo monotherapy activity, which these patients that have already failed Cabo shouldn't be that hard to demonstrate.

Similarly, with Adagrasib, as we keep on with the dose escalation, we'll probably proceed in a very similar fashion.

Speaker 0

Thank you, Mollie. Thanks, Greg, for the questions. Thank you.

Speaker 3

We'll take our next question from Jason Zymanski with Bank of America. Your line is now open.

Speaker 0

Great. Good afternoon. Thanks for taking our questions and congrats on the progress. Maybe a high-level question for you, Troy, now that the die has been cast regarding timeline, so to speak, can.

Speaker 2

You speak to some of the puts.

Speaker 0

any takes regarding the commercial dynamics in the relapsed/refractory NPM1-mutated setting? You know, how much is your competitor's first-to-market advantage and current inroads?

Speaker 1

As a hurdle?

Speaker 0

I mean, ultimately, how quickly do you think you can overcome any residual or at least initial physician inertia here and then maybe secondarily, what are your expectations regarding the evolution of NCCN guidelines for the class, whether they include ziftomenib specifically or sort of just reference the larger menin inhibitor class. Thanks. Yeah, Jason, thanks for the questions. Let me maybe just make a couple of overarching comments and then I'm going to ask Brian to speak to your question. I think if I were to distill your question down, it's really like what's the meaning of a first mover advantage, right? What does that mean here? What I'd say is everything we're seeing I think is good for patients. We've seen strong interest and strong uptake in menin inhibitors, as you've heard us say.

Ziftomenib is potentially best in class, I think not only in NPM1-mutated AML, but increasingly, as you'll see in combination. We think it's going to be very competitive in the KMT2A-rearranged subset and we're looking forward to giving physicians and patients options for therapy. These patients are in desperate need. I'll let Brian speak really to the feedback that we've heard from KOLs and sort of the positioning and then we'll come back to your question on NCCN and when he's done with that, Brian, could you maybe build on my comments?

Speaker 1

Sure. Thanks, Troy. Thanks, Jason, for the great question. I think as Troy said, we've been working towards building that first presence and first approval in this market. As you said, we're happy that patients may have a number of options available for them. Our team has been working for the last two years to begin this preparation. We've actually, from a medical perspective, been engaging with KOLs with our MSL team over the last two years or more. Our market access team has been out in the field and engaging with payers through pre-approval information exchanges over the last year, and we're really building a strong reputation among those teams.

A lot of that's actually built, I would say, at Kura Oncology based on the strong reputation that Dr. Mollie Leoni and her team have built in executing on these clinical trials and how quickly they've been able to enroll patients and really partner strongly with a number of the U.S. physicians. I think that there will be, of course, we recognize there will be some competition coming forward between potentially two approved agents in the space. We're confident in the profile that ziftomenib has, that we'd be able to rapidly engage with physicians upon approval. Our sales teams will begin some profiling once they finish their training in the short time frame between now and as they get closer to the approval, so they could start to introduce and engage on Kura's behalf as we get closer to our approval.

We think that we're doing all the right things that a company like Kura needs to do. While there may be some initial awareness from some of the competitors, we think that the need is substantially high and the enthusiasm we've heard around ziftomenib continues to be high, that we'll be in a good position once we get that approval.

Speaker 0

Thanks, Brian. Brian, do you want to just add to that and address Jason's second question, which is around how do we think about the evolution of the NCCN guidelines? Is it, you know, menin as a class? Is it ziftomenib specific, any color you want to give?

Speaker 1

Yeah, absolutely. I mean, I would say at the highest level, Jason, since we only have external visibility to what the NCCN AML committee does, we can't really comment as to when they will be addressing the NPM1-mutated population. Our intent within our team is as soon as our data are published and we have our approval, we'll be submitting the application to NCCN for consideration on the guidelines as soon as possible. It's one of those key early launch metrics that we'll be putting towards to get ziftomenib on those guidelines. Mollie, would you want to add anything else to that?

Speaker 4

Yeah, I thought the question about whether they would list out individual drugs or menin as a class is an interesting one. I mean, obviously we don't know, but as we are the only two companies that will really have strong data packages already produced, I would think, at least for the foreseeable future, it would be named menin inhibitors in the guidelines rather than just a class.

Speaker 0

Got it. Thanks so much for the good color. Appreciate it. Thanks, Jason.

Speaker 3

Thank you. We'll take our next question from Ellen Horst with TD Cowen, please. Go ahead. Your line is open. Hi, guys.

Speaker 4

Congrats on such an exciting quarter and thanks for taking the question. I'm just wondering what you think are the biggest potential risks to the pivotal program timelines, if there's anything that could potentially push initial data out past 2028, and then is there any risk to running combined studies with both the KMT2A population and the NPM1 population? Thanks.

Speaker 0

Yeah, thanks, Ellen, for the questions. Mollie, you want to speak to that? Risks to timelines sort of getting extended or risks to running the blended populations?

Speaker 4

Yeah, I mean, obviously we can't predict the future, and if something really unexpected happens, obviously it could push out the readout dates. We're very, very conservative, and we only released that 2028 date when we felt very confident in our ability to meet it. With regards to mixing of the populations, again, I will go back to our COMET-007 trial. It has taught us so much. We understand what these patients now look like in these settings to a great extent with very robust data sets. The mixing of the populations doesn't frighten us, and we've obviously approached it from many different scenarios to make sure that this was the appropriate way for us to proceed as a company. COMET-007 really was the best building block for this big trial.

Speaker 0

Thanks, Mollie. Thank you, Ellen, for the questions.

Speaker 3

Thank you. We'll take our next question from Peter Lawson with Barclays. Please go ahead. Your line is open.

Speaker 0

Great. Thank you so much.

Speaker 1

I joined late, so I apologize if.

Speaker 0

The question's already been asked just around.

Speaker 2

About your FDA dialogue, how that's proceeding.

Speaker 0

If it's changed in frequency or any emphasis has changed around that, the second question would be around importance.

Speaker 2

Of the AML maintenance setting.

Speaker 0

Do you think you have the ability to kind of capture that market as well? Peter, Mollie, can you just maybe summarize the FDA dialogue or Peter?

Speaker 4

Sure. You know, we're under active review. We are regularly interacting as you would expect, being on a priority review timeline. We really haven't seen any change in the quality, the quantity, or the frequency of interactions with the agency. Things have been progressing as expected.

Speaker 0

Mollie, maybe you can take the second question around how one thinks about maintenance, and then Brian, I'll probably ask you to come to build on that from a commercial perspective. Mollie, do you want to start?

Speaker 4

Yeah. Obviously, in our COMET-001 trial, we're not pursuing a maintenance indication, but as we've heard, there are folks that would expect some use in that setting already. COMET-007 has taught us, again, taught us a lot. While most of our NPM1-mutated patients don't need to go to transplant in that frontline setting, the ones that do have in general come back onto a maintenance protocol. The KMT2A-rearranged especially are very apt to come back to trial. I think the maintenance indication that has been built into the COMET-017 design is going to be extremely valuable in appropriately capturing that patient population.

Speaker 0

Brian, is there anything you'd like to add on Peter's question around maintenance?

Speaker 1

Thanks, Troy. Maybe just to add on that, I think that the way we view it from a commercial perspective, a lot of the post transplant maintenance or extended non post transplant, that would likely be something we would observe or expect to see in the newly diagnosed setting. As COMET-017 builds out, we think that gives us an opportunity for significant durations of treatment in both the IC and the non-IC setting that could lead to anywhere from 12 to 24 months of continuous therapy for patients in the relapsed/refractory space. Based on what we've seen in the market so far, you know, KMT2A-rearranged, there may be more patients who would go to transplant relative to the older population of NPM1-mutated patients in the relapsed/refractory setting.

We're observing and we'll be following to see, but we expect that to be a lower rate of transplant for those relapsed/refractory NPM1-mutated patients. We'll be tracking that and try to understand, and our goal of course will be to get patients on therapy and to stay on therapy for a longer period of time.

Speaker 0

Thanks, Brian. Thanks, Greg, for the questions.

Speaker 3

Thank you. We'll take our next question from Charles Zhu with LifeSci Capital. Please go ahead. Your line is open.

Speaker 0

Hi, this is Peter on for Charles, a couple of questions from my end. First of all, for the KO-2806 data in RCC at ESMO this fall, just wondering if you could provide some color on patient baselines, how heavily pretreated, rates of prior Cabozantinib exposure. Second question, as you're looking down the nose.

Speaker 1

Of approval in relapsed/refractory NPM1-mutated for.

Speaker 0

Ziftomenib, just wondering what your plans are, if any, for additional data disclosures in that setting, for example at ASH.

Speaker 1

Or in a journal release.

Speaker 0

Thanks and congrats on all the progress. Thanks, Peter. Mollie, do you want to take those questions? I mean we don't want to go into too much detail, but any additional color we can give on RCC, that's.

Speaker 4

Exactly what I would say is I don't want to preempt the abstracts, but they will be sharing all of that data with you. You can expect, you know, a typical phase 1 patient population where initially it could be your most heavily pretreated, and then as investigators feel more comfortable, you come further and further in line. You'll see a variety of patients at baseline.

Speaker 0

Great. Mollie, what about Peter's second question about any additional disclosures on the monotherapy? Could the COMET-001 study for people look forward to additional data disclosures?

Speaker 4

That was what I was getting at. Yeah, you should expect a publication within the coming months.

Speaker 0

Thanks, Peter. Thanks so much. Thanks. Yeah, our pleasure.

Speaker 3

Thank you. We'll take our next question from Salaam Saeein with Mzizzo. Please go ahead. Your line is now open.

Speaker 0

Hi, thanks for taking our question. This is Eric on for Sandim. I just wanted to get your thoughts on potential launch ramp as you get into unexp refractory NPM1-mutated given what that you know, we've seen with the KMT2A launch here recently, and you know, given that there was no really good reason to expect any warehousing of patients with KMT2A-rearranged in a relapsed/refractory. Might there be a bit with the NPM1-mutated population? Thanks. Yeah, thanks Eric. Brian, you want to address Eric's question about any launch dynamics?

Speaker 1

Eric, thanks for that question. I think that we're, I don't think we're ready to disclose what our expected launch ramp up will be. What I can tell you is the focus that we've been working towards right now is to immediately get product available for patients, get access from with our payers, and build on the work the team has been working on so far, really communicating around the areas where we see ziftomenib as differentiated as I've said before, around our robust efficacy, the safety and tolerability, the convenience, and the ability to have a kind of simplicity of dosing without some significant additional monitoring challenges as some of the competition may have. Our expectation, your second question around whether or not you would expect to see a bolus. We haven't actually, we don't expect to see a large bolus.

This is not a patient population where patients are waiting for a new therapy to come forward. Unfortunately, because of this very high unmet need, these are going to be elderly relapsed/refractory patients that have probably been significantly pretreated and may not have the expected, you know, the expected life expectancy in this space is pretty short unfortunately. I think there's less of a dynamic of a pool of patients we think that have already been kind of taken up by other therapies by the time we get to approval. I hope that helps with some clarity.

Speaker 4

Yeah.

Speaker 0

Eric, just to build on Brian's comments, another thing you'll look forward to is, as Mollie indicated, we're going to give an update on the combinations of ziftomenib with venetoclax. We're also looking at combinations with other standards of care, including gilteritinib. All of that data is coming, will be promoting on label. We're looking really to publish as much data as possible to help inform physicians and patients. Those four pillars that Brian hit on, I think that's really ultimately going to allow ziftomenib to potentially become the market leader: the efficacy, the safety, the compatibility, and the convenience. We're excited to get out there and offer more options to patients. It's going to be an exciting next few quarters. All right, thank you. Kay. Yes, thank you.

Speaker 3

Thank you. We'll take our next question from BTIG. Please go ahead. Your line is now open.

Speaker 4

Great.

Speaker 0

Thank you for taking my question. Just to follow up on maybe your comments previously, just any sense from your investigators about their willingness to use ziftomenib off label, frontline or perhaps in the relapsed/refractory setting in combination, pending potential approval. My second question was, can you provide any commentary on the % site overlap you have with your approved competitor, at least among your current clinical trials? Thank you. Yeah. Great. Let's tease those two questions apart. Mollie, do you want to speak to the feedback from. We've heard from KOLs on a, on a. I think your question was sort of a willingness to combine. A willingness to combine ziftomenib with other standards of care.

Speaker 4

Yeah. I mean, what we hear is ultimately they're going to do what's best for the patient. If they have a safe way to administer our drug in combination that they feel would be more beneficial to the patient, then they would. With regards to in the frontline, they have the option of putting them on our trial. I'm hoping that they will do that so that we can fill up just as quickly as we plan to. Yes, we do hear not just our investigators, but other KOLs discuss liking to have the information available to be able to safely use drugs in combination. Oh, and regarding the sites.

Speaker 0

Yeah, the site overlap.

Speaker 4

That's all right. For COMET-001, the monotherapy study, it was very few, you know, a handful, probably mostly in the U.S. With COMET-017, you can expect that number to drop precipitously because sites don't have the capability of conducting multiple phase 3 studies in the same or similar indication.

Speaker 0

Yeah, just to build on that. I mean that's part of why we designed COMET-017 the way that we did, because it's really a one stop shop for these clinical sites. We're really looking to build relationships with many of the leading centers all over the world, and if they can treat nearly all eligible patients in the frontline with one trial, they've shown us that that's what they're going to do. To Lee's earlier question, we're not overly concerned. It's not really first patient in, it's going to be last patient in and who gets the data. I think we're very well positioned to compete on that. Appreciate your questions.

Speaker 3

Thank you. We'll take our next question from David Day with UBS. Please go ahead. Your line is now open.

Speaker 0

Hi, this is Eric Masona asking for David Dye. Thanks for asking. Taking our questions about the commercial ready. Could you share some more details about how Kura Oncology's existing commercial sales force could help expedite the commercial execution? How many salespeople do you think will be needed for a successful launch? Just a quick follow up on that. J and J just initiated a phase 3 trial for Bleximenet in frontline AML. How are you planning to catch up or potentially leapfrog? Yeah, thanks Eric for the two questions, let's start with the commercial readiness question and the relationship with Kyowa Kirin and Brian. Do you want to address Eric's question?

Speaker 1

Sure. Thank you, Eric, for that question. Yeah. Our team, our commercial team, as I mentioned, has been fully built out. Our sales organization will share, probably as we get up to launch, a bit more details of the size of that field force and how they'll be working with Kyowa Kirin Co., Ltd. What I can say is that our team is building out based on the target physicians that we've outlined for the acute myeloid leukemia (AML) space. We'll have national coverage with Kura field representatives, and they'll partner very closely with the national team that Kyowa Kirin Co., Ltd. already has in the field. You may know that they have a product that they're currently promoting in the lymphoma space, which has a pretty significant overlap at an account level with the AML population.

What we're working on is their team will have a portion of their effort focused on ziftomenib. The rest of their effort will be focused on their other product. For ziftomenib, they will be partnering very closely with our team to essentially give a broader depth and breadth of our ability to reach physicians than we would if we were to be alone. We think this is going to be a significant advantage for ziftomenib as we launch because we'll have a field force that is maybe broader, more dedicated to extend to more physicians, to have more frequent interactions and contacts, so that we'll be able to communicate our messages and support patients who are in the community who may need to or have the potential to get ziftomenib. As we're working towards that launch, we'll be able to provide a little bit more detail.

I can tell you that the teams have been working very well together. They're going through their training to be ensured that as we get to our launch, they'll be ready to go and start to communicate, both from the Kura side as well as our partners at Kyowa Kirin Co., Ltd.

Speaker 0

Thanks, Brian and Eric. I'll take your second question around the timelines for Janssen. Everyone knows Janssen's a formidable development organization. I think, though, the answer is kind of in your question. Right. You mentioned the two phase 3 trials. To our knowledge, they've only initiated the one CAMELOT study in the frontline venetoclax setting. As Mollie indicated, we've just seen overwhelming enthusiasm and enrollment in both COMET-007 and enthusiasm for COMET-017. I think we'll be very well positioned to compete with them in terms of enrollment globally. You'll see us initiate those trials here shortly in the second half. We're looking forward to it. Thanks for the questions.

Speaker 3

Thank you. At this time, this concludes our question and answer session. I will now turn the meeting back over to Dr. Troy Wilson.

Speaker 0

Thank you, Brittany. Thank you all once again for joining the call today. We'll be participating in several investor conferences over the next couple of weeks, couple of months, as well as the ESMO Congress in Berlin. As Mollie mentioned, we're planning to hold a virtual investor event to discuss our presentations of clinical data from our FTI program. In the meantime, if you have any additional questions, please feel free to reach out. Thank you all again and have a good evening, everyone.

Speaker 3

This brings us to the end of today's meeting. We appreciate your time and participation. You may now disconnect. Thank you.