Kura Oncology Q4 2025 Earnings Call Transcript

Quartr
Provided by Quartr
March 5, 2026

Key Takeaways

  • Positive Sentiment: Komzifti launched after FDA approval and generated $2.1M in late‑2025 revenue, with rapid uptake: ~84% of private payers established coverage within 90 days, a two‑day average prescription‑to‑payer decision via KuraConnect, and some payers implementing step edits that require Komzifti before a competitor.
  • Positive Sentiment: Komzifti is listed in the FDA Orange Book with patent protection through July 2044, which the company says strengthens the long‑term value of the franchise as it expands into frontline and combination settings.
  • Neutral Sentiment: Kura is executing an extensive development plan—pivotal KOMET‑017 (two independently powered frontline trials), multiple combination programs (venetoclax, FLT3 inhibitors), and solid‑tumor efforts including darlifarnib—with multiple data readouts planned in 2026 and a phase‑3 top‑line readout expected in 2028.
  • Negative Sentiment: Commercial launch and expanded development increased costs: Q4 2025 net loss widened to $81M (vs. $19.2M a year earlier), with higher R&D ($64.4M) and SG&A ($39.1M) contributing to the loss.
  • Positive Sentiment: Kura ended 2025 with $667.2M in cash and short‑term investments and expects collaboration revenue and ~<$180M in anticipated milestones to fund its ziftomenib AML program through the first KOMET‑017 phase‑3 results in 2028.
AI Generated. May Contain Errors.
Earnings Conference Call
Kura Oncology Q4 2025
00:00 / 00:00

There are 14 speakers on the call.

Speaker 6

Good day, everyone. My name is Abigail, and I will be your conference operator today. At this time, I would like to welcome you to the Kura Oncology's Q4 and FY 2025 financial results earnings call. All lines have been placed on mute to prevent any background noise. After the speaker's remarks, there will be a question and answer session. If you would like to ask a question during this time, and if you have joined via the webinar, please use the Raise Hand icon, which can be found at the bottom of your webinar application. To allow everybody the opportunity to participate, we ask that you please limit yourself to one question and then re-enter the queue for any follow-ups. At this time, I would like to turn the call over to Pete De Spain, SVP, Investor Relations and Corporate Communications of Kura Oncology. Please go ahead.

Speaker 1

Thank you, Abigail. Good morning and welcome to Kura Oncology's fourth quarter 2025 conference call. Joining the call today are Dr. Troy Wilson, President and Chief Executive Officer, Brian Powell, Chief Commercial Officer, Dr. Mollie Leoni, Chief Medical Officer, and Tom Doyle, Senior Vice President, Finance and Accounting. 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 12

Thank you, Greg. Good morning, everyone. 2025 was a defining year for Kura, marked by FDA approval of Komzifti and initiation of a successful commercial launch. As we enter 2026, our priorities are clear: execute commercially, move aggressively into frontline AML and combinations, and build long-term leadership in menin inhibition while advancing a data-rich pipeline. Komzifti generated $2.1 million in net product revenue in the final weeks of 2025. Although it's early, the launch is off to a strong start. Feedback from physicians, pharmacists, and payers has been consistent. Komzifti delivers meaningful efficacy with differentiated safety, simplicity, and combinability with concomitant medications. In medically complex AML patients, that matters. We believe leadership in relapsed and refractory NPM1 mutant AML will be determined by preference, not by who enters the market first.

Speaker 12

Importantly, Komzifti is now listed in the FDA's Orange Book with patent protection through July 2044. That runway strengthens the long-term value of the franchise, particularly as we expand into frontline AML and combination settings. Our strategy extends well beyond the initial approval. Enrollment is underway in our pivotal KOMET-017 frontline trials, and 2026 will bring important data in both the frontline and relapsed refractory settings. We're positioning ziftomenib as a foundational combination partner in AML, including with FLT3 inhibitors and standard backbone regimens. Across relapsed refractory and frontline AML, we estimate the total U.S. opportunity at approximately $7 billion. Beyond AML, we're advancing a focused solid tumor strategy. Our ziftomenib combination with imatinib in gastrointestinal stromal tumors, or GIST, is progressing in dose escalation, and our next-generation menin programs are advancing.

Speaker 12

Darlifarnib, our farnesyl transferase inhibitor, is designed to address resistance mechanisms across multiple oncogenic pathways. Its combination flexibility, including with cabozantinib, KRAS inhibitors, and PI3K inhibitors, gives it potential to impact more than 200,000 patients annually in the US. We expect multiple clinical updates this year. In short, we're executing commercially, expanding development of ziftomenib across the AML treatment continuum, and advancing a pipeline with meaningful catalysts in 2026. With that, I'll turn it over to Brian.

Speaker 1

Thank you, Troy. Good morning. Our commercial objectives for Komzifti are straightforward: establish clear differentiation in the menin inhibitor class, deliver strong quarter-over-quarter growth, and achieve leading class share in relapse refractory NPM1 mutant AML. The early launch is exceeding expectations. I could not be happier with the execution of our world-class team who have been laser-focused on delivering a strong launch. Prescription trends are strong, and the qualitative feedback has been consistent and encouraging. Physicians, both academic and community-based, consistently cite Komzifti's clinical activity and ease of use. Once-daily dosing and lack of required azole dose adjustments are meaningful advantages in real-world AML practice. Institutional pharmacists firmly echo this. In complex patients on multiple medications, safety and predictability drive confidence. We also hear clearly that the safety profile matters. Komzifti carries a single boxed warning for differentiation syndrome compared to multiple boxed warnings for a competitor.

Speaker 1

That difference is resonating. Importantly, Komzifti was added to the NCCN guidelines as a Category 2A recommendation within a week of Kura's submission. That rapid decision reflects enthusiasm and strong alignment among clinical thought leaders. Operational execution has been strong. Komzifti was shipped within days of approval. Our experienced sales force brings an average of more than 20 years of industry experience and deep hematology expertise. The team was trained and fully deployed and in partnership with Kyowa Kirin, is targeting more than 4,000 hematology professionals. Our message is simple. NPM1 mutations are now actionable, and Komzifti offers a differentiated profile. Access has been a major strength and highlights a powerful leading indicator early in the launch. We engage payers covering approximately 90% of insured lives prior to approval.

Speaker 1

Within 90 days, approximately 84% of private payers had established coverage aligned with the label and without additional restrictions. That speed of coverage surpasses both industry benchmarks and our internal expectations. We're also thrilled to report that certain blue plans are now requiring patients to go on Komzifti before allowing coverage for the other approved menin inhibitor. It's our understanding that their decision to implement this step edit was based on the efficacy, safety, and predictable price per patient. Step editing is uncommon in oncology. We view this as a meaningful independent validation of Komzifti's profile and competitive advantage as the class evolves. Komzifti is distributed through a focused network of specialty distributors and pharmacies. Through KuraConnect, the average time for prescription-to-payer decision is two days. Patients are getting rapid access.

Speaker 1

We estimate the initial U.S. market for NPM1-mutated relapse refractory AML at approximately $350 million-$400 million annually. This is our starting point. On top of our enthusiasm about our early launch, we strongly believe that long-term leadership across the AML continuum will be determined by breadth, by who can combine effectively with venetoclax, 7+3, and FLT3 inhibitors and take the lead in frontline disease. Komzifti's profile, particularly its safety, combinability, and simplicity, position us to maximize the efficacy benefit across settings and drive class leadership. In the near term, we'll remain focused on quarter-over-quarter growth, net revenue, and new patient starts. Over time, we anticipate providing additional metrics to track progress. I'll now turn it over to Mollie to discuss our pipeline.

Speaker 5

Thank you, Brian. FDA approval in relapse refractory NPM1 mutant AML was a major milestone. It's just the beginning. We are building a durable, expanding franchise backed by the most comprehensive development strategy. Our goal is clear: Make ziftomenib a foundational therapy across AML. We are executing the most comprehensive development strategy in the category. We expect to deliver multiple updates this year across key programs at major medical meetings, supported by an expanding publication plan. Relapse rates in AML remain high, up to 70% within three years. We believe deeper and more durable outcomes require moving effective therapies earlier in treatment. This drives our first-to-frontline strategy. We are rapidly advancing our registrational KOMET-017 program in newly diagnosed AML, which will recruit patients at approximately 200 global sites.

Speaker 5

The program includes 2 independently powered trials, intensive and non-intensive chemotherapies, each designed to support potential U.S. accelerated approval and full approval. Data from the phase 1 KOMET-007 trial support this strategy. In newly diagnosed patients treated with 7+3 or venetoclax plus ziftomenib, we observed high CR rates and deep MRD negativity. Importantly, the addition of ziftomenib did not meaningfully delay platelet or neutrophil count recovery in either combination. We expect to present updated intensive chemotherapy data from KOMET-007 in the first half of 2026. In parallel, we are preparing a manuscript detailing ziftomenib in combination with venetoclax in the relapse refractory NPM1 mutant AML setting. Data presented last December showed encouraging safety, tolerability, and clinical activity in this population. The combination was generally well-tolerated without additive toxicity and meaningfully improved overall response rate, composite CR rate, and overall survival relative to ziftomenib alone.

Speaker 5

We view this as an important component of our strategy, and we believe it has the potential to significantly improve outcomes in patients with relapse refractory NPM1 mutant AML. FLT3 co-mutations present another significant opportunity and one we are well ahead of competitors. We are evaluating ziftomenib in combination with Gilteritinib in the relapse refractory setting and with Quizartinib in the frontline setting. If we can demonstrate the ability to combine ziftomenib safely with FLT3 inhibitors, we believe that will be a key differentiator. Outside AML, KOMET-015 is evaluating ziftomenib and cabozantinib in patients with advanced GIST. Dose escalation continues without dose-limiting toxicities in a broad range of doses. We remain very encouraged and plan to provide an update when appropriate. Turning to darlifarnib, we are advancing this FTI in combinations to address resistance biology across solid tumors.

Speaker 5

We announced today the initiation of the phase 1B dose expansion of FIT-001 with cabozantinib in advanced renal cell carcinoma. The phase 1B portion comprises a randomization into 3 arms in line with Project Optimus, including 1 cabozantinib monotherapy arm. This third arm provides a control benchmark and enables us to evaluate the combination in patients who are not responding to or just beginning to fail cabozantinib therapy. phase 1A dose escalation data from FIT-001 showed encouraging safety and tolerability as well as antitumor activity, including in patients previously treated with cabozantinib. Updated data will be presented in the second half of this year.

Speaker 5

We also plan to present preliminary data from our phase 1A study evaluating darlifarnib with Adagrasib in patients with KRAS G12C-mutated lung, colorectal, and pancreatic cancers in the first half of 2026. Finally, our MEK inhibitor programs continue to advance, including preclinical work in solid tumors as well as diabetes and cardiometabolic indications. In summary, we are working to move ziftomenib earlier in the AML treatment paradigm, expanding our combination strategies, and advancing a second growth pillar with the FTI platform with multiple catalysts this year. With that, I'll turn it over to Tom for a financial update.

Speaker 11

Thank you, Molly. I'm happy to provide a brief overview of our financial results for the fourth quarter of 2025. As we pre-announced in January, our net product revenue from Komzifti sales was $2.1 million compared to none for the fourth quarter of 2024. The first commercial sale triggered a $135 million milestone payment under our collaboration agreement with Kyowa Kirin. Collaboration revenue from our Kyowa Kirin partnership was $15.2 million compared to $53.9 million for the same period in 2024. Research and development expenses were $64.4 million compared to $52.3 million for the fourth quarter of 2024. The increase was driven by ziftomenib combination trials, including the start of enrollment in our KOMET-017 trial in 2025.

Speaker 11

Sales, general, and administrative expenses were $39.1 million compared to $24.1 million for the fourth quarter of 2024. The increase was driven by the commercial launch of Komzifti. Net loss for the fourth quarter of 2025 was $81 million compared to a net loss of $19.2 million for the fourth quarter of 2024. This includes non-cash share-based compensation expense of $11.3 million compared to $8.6 million for the same period in 2024. As of December 31st, 2025, Kura had cash equivalents, and short-term investments of $667.2 million compared to $727.4 million as of December 31st, 2024.

Speaker 11

Our $667.2 million balance at the end of 2025 reflects fourth quarter 2025 receipts of $195 million for the first commercial sale of Komzifti and KOMET-017 enrollment milestone payments. Kura is providing guidance for collaboration revenue, which reflects non-cash-based accounting recognition of performance obligations under our collaboration agreement with Kyowa Kirin. We expect this to be $45 million-$55 million in 2026, $90 million-$110 million in 2027, and $90 million-$110 million in 2028. Current cash equivalents, and short-term investments as of December 31, 2025, together with anticipated milestones of $180 million under our collaboration agreement with Kyowa Kirin, are expected to fund our ziftomenib AML program through the first top-line phase 3 results from KOMET-017 anticipated in 2028.

Speaker 11

With that, I turn the call back over to Troy.

Speaker 12

Thank you, Tom. Kura enters 2026 with strong momentum. We have a launched product which is performing well. We have the broadest frontline AML development strategy underway. We have multiple data readouts ahead. We have a second platform advancing in solid tumors. Our priorities are clear: accelerate uptake of Komzifti in relapsed refractory NPM1 mutant AML, deliver strong quarter-over-quarter product revenue growth, advance and execute on our first-to-frontline strategy, generate and publish combination data which guides treatment decisions, and deliver clinical updates across our FTI platform. 2026 will be a year of execution, expansion, and data. We're building a durable franchise in AML and a broader oncology pipeline with both breadth and depth. Everything is moving forward commercially, clinically, and operationally. We're focused on converting that momentum into long-term value for patients and shareholders. With that, Abigail, we'll conclude and open the call for questions.

Speaker 6

We will now move to our question and answer session. If you've joined via the webinar, please use the Raise Hand icon, which can be found at the bottom of your webinar application. When you are called on, please unmute your line and ask your question. Our first question comes from Li Watsek with Cantor Fitzgerald. Li, please unmute your line and ask your question.

Speaker 4

Hey, good morning. Congrats on the progress. Maybe a commercial question for Brian. You made a very interesting comment about step editing that some payers may require to use Komzifti before the competitor product. I just wonder if you can, you know, give us a little bit more information about that. What percentage of payers have implemented this step through policy? Any specific sort of feedback you can share from payers regarding this edit?

Speaker 12

Thanks, Li, for the question. I'm gonna just to remind everyone, we're gonna try to limit the 1 question per analyst so that we can get through everyone. Brian, I'll let you. You know, there's 2 or 3 questions tucked in there. I'll sort of let you.

Speaker 5

Sure

Speaker 12

... you know, speak to them.

Speaker 5

All right. Thanks. Thanks, Li, for the question. Yeah. As we shared in the remarks, I think-

Speaker 1

We think that this news of a step edit and required from some payers that's just come forward is a powerful leading indicator that supports kind of our overall assertion about Komzifti being differentiated. You know, I will say that our team, the market access team has done a phenomenal job securing access and working with payers so broadly to get this access so early. What I can kind of share around the step edit, and as you know, what the recommendation from some of these payers is that a patient would be recommended to receive Komzifti before receiving any other menin inhibitor.

Speaker 1

Our understanding is the basis of that is built on a report from a group called IPD Analytics. It's a independent consulting firm who is influential to many payers. Their recent reports of the relapsed refractory market in evaluating Komzifti recommended this step edit for adult patients with relapsed refractory NPM1 mutant AML. We know that there are some payers that have started to implement that, as I shared. The biggest driver from what we can understand from this from the consulting summary from IPD is that really, you know, the four pillars we talked about around the differentiation of Komzifti stood out, particularly because of the predictability of the cost. If you look at the...

Speaker 1

Based on their assessment, the annual WAC for Komzifti in this setting is about just under $600,000 a year. With our competitor menin inhibitor, because of the different dosing, schemas and SKUs that come forward, it comes out to almost $1 million a year. I think that's where we see, they're driving the difference when you also add in the safety profile, the combinability and the predictability of that. I can't really give you know, an overview of how many plans. There are a handful, and we can't predict how many other plans may do this in the future, but it's encouraging for us as we look to become the class leader here in the NPM1 space.

Speaker 6

Thank you.

Speaker 1

Thanks.

Speaker 6

Your next question comes with Roger Song from Jefferies. Please unmute your line and ask your question.

Speaker 9

Excellent. Congrats for the update and then the very encouraging early launch signal. The step edit is certainly very interesting. Maybe just given the access is very rapid and broad, can you comment on the patient demand side versus the revenue generation? If anything you can comment on the trend for the rest of the year, that would be helpful. Thank you.

Speaker 1

Yeah. Thanks, Roger. Happy to do that. You know, we're not gonna be giving you guidance specifically on the trend. What we can tell you is that the launch has, as I said, been off to a very strong start. We are seeing patient demand. You know, the feedback we've heard from physicians has echoed back the differentiation pillars that we've talked about. Payers, physicians, and pharmacists have all kind of given us similar feedback. What we anticipate and, you know, as we get into our next quarters, we'll start to see a little bit more data we'll be able to share around, you know, new patient starts and things.

Speaker 1

I can tell you that the demand has been strong and that we've been pleased with the direction that the launch has gone so far.

Speaker 9

Excellent. Thank you.

Speaker 6

Our next question comes from Jonathan Chang with Leerink Partners. Jonathan, you may now unmute and ask your question.

Operator

Good morning. This is Albert Agustin on for Jonathan Chang. Thanks for taking my questions, and congratulations on all your progress. My question is: What do you see as the biggest hurdle now for Komzifti to gain market share in 2026? Now, is it just prescribers inertia or something else? Thanks.

Speaker 1

Yeah, sure. Sure. Thanks, Albert, for that. Yeah, I mean, I think that what we anticipate with the NPM1 market, this is a market that is really gonna be driven on new patients coming forward and kind of incident patients as they're diagnosed into the or progress into the second, third, fourth line setting. It really will come down for us as to getting those patients into our queue. One of the I think one element of this market that's a bit unpredictable for us, as you as you well know, is that, you know, we're approved in a monotherapy setting, and that's where our teams are gonna be promoting. We've heard a lot from physicians that they're looking to use menin inhibitors and Komzifti in combination.

Speaker 1

That will be one of the questions for us to understand, is how that uptake comes out in the combination setting. That will be something we'll be able to see coming forward in the future. You know, we don't see. You know, the payer hurdles have been, you know, really nonexistent. We're really pleased with how quickly our uptake has been getting on policies. We don't really see any major hurdles other than just getting those incident patients onto therapy.

Speaker 12

Yeah, Albert, this is Troy. I might just add a comment or two to Brian's, to Brian's response. This is why we've laid out, you know, in our, in our milestones for 2026 the significance of the publication in relapsed refractory NPM1 mutant AML with venetoclax that Molly mentioned, as well as the combination with gilteritinib. You know, as Brian mentioned, this is a very different market than KMT2A. We're obviously gonna have the sales team promoting on label with monotherapy, but what's clear, and I think will continue to be clear is the ability to combine, the ability to drive better outcomes for patients is ultimately going to, you know, be of great value. It...

Speaker 12

What we see, it's why we feel confident that, you know, we're gonna take leadership not only of the NPM1 mutant class, but ultimately, you know, of the much larger opportunity. It's going to be about combinations and those attributes that Brian mentioned that were highlighted in the IPD Analytics report, those become ever more important as you move into combinations. You know, just to make an example, you know, we're well ahead of the competition in terms of combining with FLT3 inhibitors. As you know, that's half of the NPM1 population. It's an important part of our leadership strategy.

Speaker 7

Thank you.

Speaker 6

Your next question comes from Salim Syed with Mizuho Securities. Please unmute and ask your question.

Speaker 10

Great. thanks so much, guys. Congrats on the progress. just one from us on the 50%, that you noted here, Troy, you know, the market feedback suggests you get up to 50% of AML patients here, for targeting. Just what is the assumptions that you put in front of these doctors when you're kind of doing your market feedback work? Is it just based on the existing data or is there something that you're still planning to sort of get to that, you know, leading, you know, the leading share, I think, as you put it.

Speaker 12

Yeah.

Speaker 10

Like-

Speaker 12

Yeah.

Speaker 10

... earlier?

Speaker 12

Salim, I take from your question you're referring to the relapsed refractories segment. Is that where-

Speaker 10

Correct. Correct.

Speaker 12

your question was pointed?

Speaker 10

Yes. Correct.

Speaker 12

Yeah. Yeah.

Speaker 10

Yeah, just the market feedback.

Speaker 12

Maybe I'll ask Brian. Yeah, I'll ask Brian to speak to that. Thanks for the clarification. Brian?

Speaker 5

Yeah. No, absolutely. You know, we've gotten feedback. You know, both from physicians, but we do physician market research as well. It's interesting, we've had, you know, we basically provide the profiles of the products. It's blinded. We don't ask them which company. They don't know who's asking the questions. Of those we found that have had familiarity with the menin class, the profile that we've outlined seem to has come back to be the preferred profile, both across efficacy, safety, the, you know, the simplicity, combinability, compatibility of working with other agents. That's the feedback we've heard.

Speaker 5

Gives us the confidence that as we build into this market, we'll have an opportunity to become that market leader and take the lead share in the menin class.

Speaker 12

Yeah. I'll just add to that.

Speaker 5

Okay

Speaker 12

Salim, I'll just add to that. I mean, at this point we're not, you know, we're not really talking about FLT3 in terms of doing the market research. This is really focused on the monotherapy. you know, one of the differences between this market and the KMT2A market is obviously if you have a FLT3 mutation, gilteritinib has a survival advantage. it's reasonable to assume a menin inhibitor is gonna be sequenced after gilt. If you can demonstrate, as Mollie indicated, that you can safely combine and that that's beneficial to the patient, that's gonna ultimately drive kind of a next leg within that relapsed refractory segment. We're not really yet there with the physicians, 'cause we obviously have to do that with data, that's what gives us the encouragement.

Speaker 12

Today it's monotherapy, tomorrow it's the combination with venetoclax, you know, the day or two after tomorrow, it's the FLT3 combination. It just builds, you know, one after the other.

Speaker 10

Got it. Super helpful. Thanks so much, guys.

Speaker 12

Sure.

Speaker 6

Your next question comes from Reni Benjamin with JMP Securities. Please unmute and ask your question.

Speaker 8

Hey, good morning, guys. Thanks for taking the questions and congratulations on the early launch and hopefully this going well for 2026. You know, Molly talked a little bit about the combination of quizartinib and gilteritinib and the FLT3, you know, opportunity. Can you talk a little bit about, you know, what you're hoping to see in your FLT3 data and how important is kind of maximizing the FLT3 opportunity when we're thinking about, you know, the potential $7 billion TAM for ziftomenib? Thanks.

Speaker 5

Thanks for that question. The most important thing you can see when you look at our combination data is gonna be safety. Safety indicating that you actually can combine. Obviously after that, looking to improve upon the agents in isolation. As I said, we'll be presenting our relapsed refractory Gilteritinib data towards the end of the year. We will be presenting both the dose escalation and the expansion, which should tell you that we were able to combine the drugs successfully and safely for these patients. With the frontline, we are in the process of dose escalation with Quizartinib in combination with ziftomenib plus 7+3. Again, that continues to advance.

Speaker 5

Overall, we expect to be able to show you not just the fact that we can combine, but that we can improve upon the outcomes of these drugs in isolation.

Speaker 1

Ren, just to build on the, on Mollie's comments, you know, we've seen commentary recently from Astellas that have identified gilteritinib as 1 of their blockbusters, 1 of the 5 sort of emerging blockbusters. They have a frontline trial that was conducted with Hovon that is expected to read out any day now. As we said, FLT3 is 1/3 of all of AML patients. I, it's hard to imagine you can have a market leadership strategy without including FLT3. That's why we're combining with both quizartinib and gilteritinib. You will see us over the next quarter or 2 move more aggressively into the FLT3 frontline setting, 'cause that.

Speaker 1

we haven't really yet broken it out, but that will be, you know, it's a major driver in that $7 billion TAM, ultimately, as you look across all lines of therapy.

Speaker 11

Perfect. Thanks very much, guys.

Speaker 6

Your next question comes from Charles Zhu with LifeSci Capital. Please unmute and ask your question.

Speaker 2

Good morning, everyone. Thanks for taking our questions and congrats on all the progress. I'll ask one on a slightly different topic regarding FTIs. We had a lot of updates from the recent ASCO GU conference, particularly in renal cell carcinoma and some of the emerging and approved HIF-2 alpha inhibitors in that space. Maybe could you help contextualize your upcoming second half data for darli plus cabo, not only within the current standard of care, but also amongst the potential emerging standard of care as well. Thank you.

Speaker 5

Sure. Yeah, we're following that data very closely as well, and it's looking very good for patients. In fact, I think as you're referring to, it's looking so good that it probably will end up moving up in line of therapy for these patients. We, as we announced, have just started our phase 1B, which is a randomized phase 1B, so that we can both contend with Project Optimus, but also set some baseline data for ourselves with cabozantinib in this particular line of therapy. We will be able to also see if patients that are randomized to the cabo monotherapy can cross over and successfully either gain or regain responses, when you combine it with darolutamide, which I think is an important demonstration of our mechanism of action.

Speaker 5

We do think that our data as progressed as they are, and we have, you know, we have limited follow-up time compared to some of these other studies, are still competitive with a lot of these data that are being presented, and we look forward to sharing that updated information with you. What we do think is, again, that these good outcomes for patients with HIF-2 alphas will move them earlier in lines of therapy. You'll see them in the frontline, and ultimately it can open a rather big vacuous space in the second line, that we could then jump right into with this cabo darolutamide combination.

Speaker 2

Got it. Thanks.

Speaker 6

Your next question comes from Jason Szymanski with Vieve. Please unmute and ask your question.

Speaker 1

Good morning. Thanks so much for taking our question and congrats on the progress. Brian, I was hoping you could share some of the early feedback from your prescribers that are new to Komzifti, maybe that haven't been associated with any of your clinical programs or at least minimally associated. We recognize this is a small community and it's early days, but maybe for those especially have participated in a trial associated with your rival or don't have a large AML population, how has the product profile resonated? Thanks. Thanks for that question, Jason.

Speaker 1

I'd speak to it, you know, both from physicians we've heard from, but I'd also point to pharmacists, like the pharmacists that are, you know, have maybe not been involved so much with treating the patients outside of the trials. The feedback that we've heard has really, you know, they recognize that there are, you know, there's multiple MEK inhibitors available. The efficacy we've heard has, seems to be, you know, table stakes essentially. I think both products have similar efficacy. What really does outline is, you know, the questions around how to manage QT, understanding what monitoring for QT prolongation means versus...

Speaker 1

It's the not just having to monitor, but to understand the potential implication of a higher risk of cardiac issues has come back from us, as well as, I mean, even the simplicity of treating patients once a day without having to do a lot of, you know, dose modifications based on the complexity of other therapies they have. We've heard that. I mean, I think what we know is that, of course, a lot of probably early scripts are gonna be those for people who've had a lot of experience with us, but we have received, you know, feedback from physicians who are new to the menin class, and we've been spending our time educating them around Komzifti. We're.

Speaker 1

Yeah, as we said, it's early days, but we're pleased with what we're hearing so far, and it seems to be consistent, from what we've heard from those who do have experience.

Speaker 6

As a reminder, if you wish to ask a question, please use the raise hand button, which can be found at the bottom of your Zoom screen. Our next question comes from Etzer Darout with Barclays. Please unmute and ask your question.

Speaker 13

Hi, good morning. This is Gustav on for Etzer. Thank you for taking our question. I'd like to ask about, KOMET-008, guided to showing data in combination with Gilteritinib in the second half of this year. Could you remind us where you stand with regards to the combination of ziftomenib with FLAG-IDA and with the low-dose cytarabine? Thank you.

Speaker 1

Sure. No, as you said, we've been guiding to release the gilteritinib data because in large part we think that is very informative to physicians in how to treat the relapse refractory NPM1 mutants co-mutated with FLT3 as well. Also within that study are our FLAG-IDA combination, which sees mostly second-line patients, and our LDAC combination, which allows for an easy combination with ziftomenib that gives time for this differentiating agent to really take effect while keeping disease control at simultaneously. We haven't guided to when we'll be releasing that data, but I do think that We'll do it pieces at a time to keep the information coming and also be writing a publication. Again, we haven't guided as to when those additional cohorts will be shared.

Speaker 6

Your next question comes from Phil Nadeau with TD Cowen. Please unmute your line and ask your question.

Speaker 7

Morning, thanks for taking our question, and it was great to see the team this week in Boston. We have one commercial question. I think you suggested that the relapse refractory NPM1 market's about $300 million-$400 million in revenue. We're curious to hear how quickly you think the menin class can penetrate the market. Seems like the value proposition is pretty clear today, but we're wondering if there's any gating like combo therapy data in particular that could be necessary to fully penetrate the opportunity. Thank you.

Speaker 1

Great. Thanks, Phil, thanks again for seeing you. Good to see you yesterday. yeah, As we've said, you know, this TAM of $350 million-$400 million is kind of representing that relapse refractory space. we think as because of the dynamics of the NPM1 population where physicians have previously had choices for their patients to either get venetoclax or a FLT3 inhibitor for those who are co-mutated, we anticipated early on there'll probably be more of the relapse or, you know, kind of the relapse refractory in the third or fourth line setting. Combinations will help to drive that into the second line, where you'd be able to see, you know, the more patients get therapy and benefit earlier.

Speaker 1

Our expectation is that there'll be a lot of, you know, as we said, there's a lot of use likely in the, as a monotherapy, but the physicians are very excited about using in combination. It's not something we can promote on actively, but we will educate based on publications around the, like the venetoclax publication that we plan to publish in the, with based on KOMET-007. What we anticipate is that there will be, you know, a ramp up based on incident patients coming forward, probably starting more in the, in the third, fourth line. We will see, and we are starting to see the, you know, those second line patients as well.

Speaker 1

We'll need a little bit of time to really get an understanding as to how those, how Komzifti's being used in combination relative to monotherapy.

Speaker 6

Your next question comes from David Dai with UBS. Please unmute and ask your question.

Speaker 3

Great. Thanks for taking my questions and watch on the quarter. Just, you know, one question on the duration of therapy. Understand it's just the early innings, but any thoughts on duration of therapy for Komzifti so far? As you are thinking about combination with venetoclax or Gilteritinib, how do you think the duration of therapy could evolve over time?

Speaker 1

Great. thanks, David, for that question. you know, obviously, we're sharing 5 weeks of data. We can't really give you a lot of detail around duration of therapy at this point. Our expectation is that patients will be able to get therapy for up to You know, we take an average of 6 months. Our label suggests that patients are treated for up to 6 months to maximize the depth of their response. For those patients who do get a response, we've seen duration of therapy of 5 months or duration of response of 5 months, and oftentimes it takes 3 months or so for them to get that response, to achieve the deep response. We think that we'll get to. We're not seeing any signs yet because it's too early to see.

Speaker 1

We are seeing repeat pre- prescriptions, but we're, it's too early to talk through any duration right now. To your question around FLT3 inhibitors, I think that any combination is expected to give a longer duration of treatment than you would expect as a monotherapy.

Speaker 6

There are no more questions at this time. I'd now like to turn the call over to Troy Wilson for closing remarks.

Speaker 1

Thank you, Abigail. Thanks everyone for joining the call today. Thanks for all the questions. We will see many of you next week in Miami, at the various events and conferences. If you have any additional questions, please reach out to Greg or me. We wish all of you a good morning and a good rest of the day. Thanks again.

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