Kura Oncology Inc. Q1 2023 Earnings Call

Speaker 2: Good afternoon ladies and gentlemen and welcome to the Q1 2023 Quora Oncology Inc. Earnings Conference Call. At this time, all lines are in a listen-only mode. During the presentation, we will conduct a question and answer session.

Speaker 2: If at any time during this call you require immediate assistance, please press star 0 for the operator. This call is being recorded on Wednesday, May 10, 2023. I would now like to turn the conference over to Pete DeStaine, Senior Vice President of Investor Relations and Communications. Please go ahead.

Speaker 3: I'd like to remind you that today's call will include forward-looking statements based on current expectations. Such statements represent management's judgment as of today and may involve risks and uncertainties that could cause actual results to differ materially from expected results. Please refer to CURUS filings with the SEC which are available from the SEC.

Speaker 3: or on the Cura Oncology website for information concerning risk factors that could affect the company.

Speaker 4: With that, I'll now turn the call over to Troy. Thank you, Pete, and thank you all for joining us.

Speaker 4: Our strong conviction in Zyftomanab and its potential to be the best in class men in inhibitor continue to increase.

Speaker 4: This confidence is supported by one of the highest complete response rates reported for a targeted therapy in the setting of Relapse to Refractory leukemia and is reinforced by the rapid pace of enrollment in our registration directed trial. More on that in just a moment.

Speaker 4: We're also encouraged by the durable remissions in our Phase 1 trial driven primarily by single agent activity of ZIF to menib, and we look forward to sharing an update at the European Humanitology Association Congress next month.

Speaker 4: You've got a glimpse of these data in our recently released abstract, which showed that Zyptometib continues to demonstrate significant clinical activity in patients with heavily pre-treated and co-mutated, relapse the referee, NPM1, MEDEN AMO. As of January 31st, day to cut off...

Speaker 4: 6 of the 20 NPM-1 patients treated at the recommended phase 2 dose achieved complete responses with full count recovery. The abstract showed a median duration of response of 8.2 months with a median follow-up of approximately 8 months.

Speaker 4: Four patients were still ongoing at the time of data cut off.

Speaker 4: Zyftomanib is well tolerated and the on target effect of differentiation syndrome is manageable.

Speaker 4: We are excited by these evolving data and we look forward to reporting updated data as of an early April data cutoff.

Speaker 4: Now, building on the momentum generated by our positive phase 1 data, we announced in February that the first patients were dozed in our phase 2, Registration-directed trial of ZIFTOMENIB in NPM1 mutant relapsed a refractory AML.

Speaker 4: Site activation and enrollment in our Registration Directed Study are outperforming our projections. An indication of the continued enthusiasm surrounding Zyptomeneb among investigators and patients.

Speaker 4: As a reminder, NPM1-NAML accounts for approximately 30% of new AML cases annually and represents a disease of significant unmet need for which no approved targeted therapy exists.

Speaker 4: Once the disease becomes relapsed to refractory, the prognosis for NPM1 mutant AML patients is particularly poor, with an overall survival of approximately six months after initial chemotherapy. therapy.

Speaker 4: NPM1 Mutant AML is further compounded with commutations such as IDH or Flip 3. Notably in our Phase 1 trial for Zyftometib, two-thirds of NPM1 Mutant AML patients who achieved a CR at 600 mg had IDH and or Flip 3 commutations.

Speaker 4: All of whom have failed prior treatment with IDH and or FLIT-3 targeted inhibitors.

Speaker 4: A complete response rate with full count, I'm sorry, a 30% complete response rate with full count recovery after prior failure of these targeted therapies makes the clinical activity of zyptomene at even more striking.

Speaker 4: We're also impressed with the potential precipitum to drive durable remissions as a monotherapy. An additional NPM1 mutant patient who entered the trial with multiple co-mutations, including DNMT3A. Following two prior stem cell transplants achieved a CR with no evidence of minimal residual disease.

Speaker 4: and remains on Zifdomenib for more than 32 cycles as of our January 31st data cutoff. In parallel with our efforts to advance Zifdomenib as a monotherapy, we're preparing to initiate a series of combination studies to significantly broaden the addressable patient population.

Speaker 4: we believe Zifta Menib is uniquely positioned for these combination strategies.

Speaker 4: This belief is driven by several key competitive advantages, including no evidence of drug-induced QTC prolongation, no predicted adverse drug drug interactions, and once daily oral dosing that should enable convenient administration with current standards of care. Our team is working diligently to initiate the comment 007.

Speaker 4: and Comet 008 trials to evaluate Zyftomendiv in combination with current standards of care in earlier lines of therapy and across multiple patient populations, including both NPM1 Mutant and KMT2A Rearranged AML. We've designed these Stage 1 studies to assess safety, tolerability, and anti-luchemic activity of Zyftomendiv.

Speaker 4: in combination with key regimens such as benediclaxin acytidine, the flip-3 inhibitor guilt-ridden ib and the chemotherapy regimen of 7 plus 3.

Speaker 4: Our approach to combinations is to establish, sift a minute as a foundational therapy that can be combined safely with various commonly used regimens and then prioritize those combinations that represent the largest unmet medical need and the greatest potential commercial value.

Speaker 4: namely, Vanetta Clacks and Flip 3 inhibitor containing regiments.

Speaker 4: Notably, up to half of NPM1 mutant AML patients also exhibit commutations in the Flip 3 gene.

Speaker 4: Given the safety profile of ZIF to menib, we believe it may be the ideal men in inhibitor to combine with Flip 3 inhibitors to address this population. A difficult to treat group that represents approximately 15% of AML.

Speaker 4: We also believe that rational combination approaches will help to mitigate differentiation syndrome in the KMT2A rearranged population, as has previously been demonstrated in the development of IDH inhibitors in combination with a deciding.

Speaker 4: We're very excited about the potential for our combination studies to further unlock the value of Zyftom edit for patients with acute leukemias. We've begun site activation in the first of these studies, Comet007, and we're on track to dose first patients this quarter.

Speaker 4: We're very proud of our team's execution, grateful for the continued support of our studies investigators.

Speaker 4: Their enthusiasm coupled with a growing body of clinical data and multiple emerging lines of evidence reinforce our confidence and zip domain as the best in class men in inhibitor. We look forward to sharing more at our upcoming presentation at IHA.

Speaker 4: Now, let's turn our attention to our Farnesyl Transferase Inhibitor Programs.

Speaker 4: FTIs as combination agents to prevent or delay emergency resistance to certain classes of targeted therapy in large solid tumor indications.

Speaker 4: Although targeted therapies have demonstrated meaningful clinical activity across a range of solid tumors, adaptive resistance almost invariably emerges over time, which limits the ability of targeted therapies to drive sustained clinical benefit.

Speaker 4: We have generated a growing body of preclinical and clinical data that support the combination of STIs with multiple classes of targeted therapies, including EGFR inhibitors as well as PI3 kinase inhibitors. In April , we presented encouraging preclinical data at the American Association for Cancer Research annual meeting.

Speaker 4: which supports the potential use of FTIs in combination with two additional distinct classes of targeted therapy. The first of two posters revealed robust synergy between Kippie Farnib and the standard of care anti-angiogenic TKI, exitnib in cell and patient derived.

Speaker 4: xenograph models of clear cell, renal cell carcinoma. The second poster reported regression of multiple models of K-RATS inhibitor resistant, non-small cell lung cancer through the addition of TIPI-FARNIV, either to adegressive or a sort of a sort of torsive therapy. These promising preclinical data illustrate the potential for FTIs.

Speaker 4: to drive enhanced anti-tumor activity, as well as address mechanisms of both innate and adaptive resistance to targeted therapies. In addition, we believe these data strongly support our rationale to combine our next-generation FTI, KO2806, with TKIs in clear-cell renal cell carcinoma, as well as KRAS G12C mutant inhibitors in non-small-cell lung cancer.

Speaker 4: In January , we were pleased to announce FDA clearance of our Investigational New Drug Application for KO-286 for the Treatment of Advanced Solid Tumors, an important next step for this program. Now we intend to evaluate safety, tolerability, and preliminary anti-tumor activity of KO-286

Speaker 4: in a Phase 1 dose escalation study, which we're calling FIT001. We're now in study startup and we look forward to dosing the first patients in FIT001 later this year.

Speaker 4: Concurrent with the dose escalation as monotherapy, we also plan to evaluate KO-28O6 in dose escalation combination cohorts in advanced solid tumors. Meanwhile, we continue to evaluate TIPI-Farnib in combination with the PI-3 kinase alpha inhibitor alpeilicic combination that has potential to address up to half of all patients.

Speaker 4: with recurrent and metastatic HNSTC. We're encouraged by the preliminary activity observed in our ongoing current HN trial, including a durable partial response in a patient with PIC3CA mutated squamous cell carcinoma of the tonsil. We're also very pleased by our ability to combine TIPI-PARNIB with another targeted therapy, in this case, alpelisib,

Speaker 4: with no dose limiting toxicities reported to date. We remain on track to determine the optimal biologically active dose in mid-2023.

Speaker 4: We continue to unlock the potential therapeutic and commercial value of pharnasal transprase inhibition. The challenging, but we believe, increasingly substantial opportunity that has potential to address large solid tumor indications such as renal cell carcinoma as well as cancers of the lung and four rectal system.

Speaker 4: As with our Men in Inhibitor Program, we believe FTI programs have potential to create significant value for patients, healthcare providers, and our shareholders. We're confident we have the leadership, experience, and operational and financial resources to realize that value. With that, I'll now turn the call over to Tom Doyle for a discussion of our financial project. I'll be seeing now. I'll be seeing now.

Speaker 5: 20.9 million for the first quarter of 2022.

Speaker 5: The increase in R&D expenses was primarily due to increases in clinical trial cost related to our SIFT Omenib and KO-2806 programs.

Speaker 5: offset by decreases in clinical trial costs related to our TIPI FARINET program.

Speaker 5: General and administrative expenses for the first quarter of 2023 were $11.4 million compared to $11.9 million for the first quarter of 2022.

Speaker 5: Net loss for the first quarter of 2023 was 34.1 million compared to a net loss of 32.5 million for the first quarter of 2022.

Speaker 5: This included non-touch, sure-based compensation expense of 6.8 million compared to 6.7 million for the same period in 2022.

Speaker 5: As of March 31st, 2023, we have cash, cash equivalents and short-term investments of 405.9 million compared to 438 million as of December 31st, 2022.

Speaker 5: We believe that our cash equivalents and short-term investments will be sufficient to fund our current operating plan into the fourth quarter of 2025.

Speaker 4: With that, I now turn the call back over to Troy. Thank you, Tom. Before we jump into the question and answer session, let me lay out our anticipated milestones for the remainder of this year. Brazil Domenade, dose the first patients in the Comet 007 combination trial in first half. Present updated data from our Phase I trial in NPM1 Mutant AML at IHA in June .

Speaker 4: second half of 2023. Without operator we're now ready for questions.

Speaker 2: Thank you ladies and gentlemen. Should you have a question, please press the star followed by the one on your touch-drawn phone. If you'd like to which drive a question, please press the star followed by the two. One moment please for your first question.

Speaker 2: Your first question comes from Jonathan Chang from SVB Securities. Please go ahead.

Speaker 5: Hi guys, thanks for taking my questions. First question, can you help set expectations for the upcoming IHA ZIFTO Minute update and discuss the importance of achieving a good duration of response?

Speaker 4: Sure, Jonathan. And thanks for the questions. So as you saw from the abstract, which was released, the abstract is focused on the the NPM1 Mutant AML patients.

Speaker 4: treated at 600 milligrams, which of course is the FDA's accepted recommended phase two dose. The abstract, Jonathan, was as of, as I said, a January 31st data cutoff. We're going to bring forward all of the clinical data on those patients and report it as of an early April cutoff at EHA.

Speaker 4: And as we said in the prepared remarks, you know, we're seeing now multiple converging lines of evidence that suggest to us that Zifdomenib is potentially the best menin inhibitor in acute leukemias. And we very much look forward to sharing that data with you and others at EHOP. And in terms of your...

Speaker 4: So first things first, as we said consistently, what we understand is that for FDA approval, as a monotherapy, you're looking at a 20 to 30% CRCH rate as well as a median duration of response of 4 to 6 months. I don't think we've got...

Speaker 4: So if you're driving a duration of response that's in that same time frame, that's clinically meaningful.

Speaker 4: And nothing has changed in our understanding of that. Those being, you know, the registrational bars. In terms of what's important clinically, I would draw your attention to a couple of things. The first is that we are driving CRs with full-count recovery. This, you know, again, not CRIs or even CRHs, but really the full-count recovery.

Speaker 4: your question around duration. And I don't want to get in front of the abstract or kind of under the four corners. I'll tell you this. We have been very pleasantly surprised by the ability of Zipto-Menib to drive durable responses as a monotherapy, i.e. without needing to go to either to transplant or to other therapies.

Speaker 4: We see quite a different sort of mutational profile from what has been reported for other agents. And I think that's going to be important not only in the Relapse for Fractory setting, but it will become even more important as we roll forward into combinations.

Speaker 4: So we'll look forward, as I said, to sharing all of this both at EHA, Jonathan, and very likely at an associated investor events alongside.

Speaker 6: Understood. And second question, can you provide any more granularity and what you mean by the phase 2 NPM1 study enrollment outperforming projections?

Speaker 4: Yeah, I'm happy to. So I'll just remind everyone that last year we reported that we had enrolled 14 patients in our Phase 1B study in approximately three months. So I'll just remind everyone that last year we reported that we had enrolled 14 patients in our Phase 2B study in approximately three months.

Speaker 4: And here's where we are today. So our total goal for this trial is 62 clinical sites in the US and Europe . We're now open Jonathan in a majority of those sites. And we've seen site activation in both the US and Europe that has exceeded our expectations.

Speaker 4: And the only thing we can attribute that to is the excitement of the investigators, the sites, the patients for getting their hands on Zip Domina. And the only thing we can attribute that to is the excitement of the investigators for getting their hands on Zip Domina.

Speaker 4: As you know, an obvious competitor of ours has extended its timelines for recruitment of NPM1. We're not ready yet Jonathan to pull timelines in. What I can tell you is the investigators on the Phase 1B study, as well as the new investigators, has picked up exactly where they left on. Off.

Speaker 4: So, and side activation is always a leading indicator, but we've seen both side activation and now enrollment that it's exceeded are already, you know, pretty aggressive, pretty aggressive goals. So I think we're seeing just a continuation of the excitement, the enthusiasm from the Phase 1-B, and I think it positions us very well not only to come forward with potentially

Speaker 7: Great. Thanks for the update and taking our question. Maybe just follow up your earlier comments related to the best in class. Profile particularly in the emerging resistance data.

Speaker 7: on the manning inhibitor. So maybe just tell us a little bit more about this, how the the matter but well differentiated in this kind of resistant mechanism and why I think it's better see what we did. Thank you.

Speaker 4: Sure, Roger. Thank you for those two questions. So let's start with kind of what we see and then we can talk about the implications for what it means. First, what we see. One of our competitors, you know, was reported that they're seeing the emergence of resistance mutations at roughly 30 to 40% of patients.

Speaker 4: But to this point, having analyzed quite a number of patient samples, I can tell you we've seen three examples of resistance mutations.

Speaker 4: Two of them were patients who presented with the 3-27 methionine mutation as soon as they presented to the study, having failed RevuMentib. So do we see them? Yes, we do. What's interesting is we don't seem to see them nearly at the same frequency as perhaps our competitors do. Through

Speaker 4: Now, what's the implication of that? Well, as we know from, you know, pick EGFR, pick any other small molecule oncology target, right, the emergence of resistance mutations typically means, you know, the therapy is becoming less effective. And what I think this is going to mean, Roger, I should say...

Speaker 4: can get away with resistance mutations, now you've lost that therapeutic activity. So I think it sets up very nicely. There are a number of both biochemical and drug-like properties that we think are contributing. But it's very clear, Roger, that these compounds have very different profiles. And again, as I said to Jonathan, look forward to sharing much more of this data. And I'll see you next time.

Speaker 7: add an around e-ha. Excellent. Thank you. Yeah, so in the end we'll be on to the tipi phone app or your FKI franchise. Since you're planning to announce the biologically optimized data, the R así file app we want to design So we're going on to .gl within the event RDelft.

Speaker 7: So what will be the next step for that program and also how that will play into your 28 or 6 overall FTI franchise? Thank you. Yeah, thank you Roger for that question as well. So...

Speaker 4: So, stepping back just for a second, you know, a number of our analysts and shareholders have been with us for a number of years, and they know, you know, this is a program that we've been very passionate about. I don't think, Roger, that it's an overstatement to say that STIs may turn out to be one of the ideal combination agents for targeted therapy.

Speaker 4: People have looked at SHP2, they've looked at SOSS. You know, people have been trying to drug both the MAP kinase and the PI3 kinase pathway for at least the past couple of decades.

Speaker 4: And you might ask, why did nobody discover this sooner? By the time most of the FDI programs were discontinued, that was right at the dawn when a lot of these targeted therapies were discovered. And it wasn't really until our team began doing first preclinical and then clinical work on the combinations.

Speaker 4: that we really began to see the opportunity. When we started, we naively said, you know, we need to go after farnesylated oncoproteins, H-RAS being the most obvious and perhaps the only. What we've learned is actually when you stress the cell with EGFR inhibitors, K-RAS inhibitors, TKIs.

Speaker 4: the cell responds in a very organized, highly choreographed way, and it exposes farnesylated proteins, such as REB, and those become ideal targets for drug synergy. And I think it's that, Roger, that's driving the biology that you see in the two posters at AACR. Just incredible synergy both in the context of RCC and KRAS mutant inhibitors.

Speaker 4: So, to your question now, because I think that's important background. I think the most immediate takeaway from our Alpelisib combo is we can actually take these two drugs, I think, to their full dose with no dose limiting toxicities. I think most investors, in fact,

Speaker 4: Even many people at Cura would not have expected that would have been the case. But that bodes extremely well for combining 2806 with these various targeted therapies. If you can combine with alpelicid, that sets a pretty high bar. For that program specifically, Roger, we're going to do two things. The first thing is, I mean, we know we have adequate safety and tolerability.

Speaker 4: The question is, is the clinical activity sufficient to support continued development of Tipeee Farm of Endalpelisib, or do we perhaps prioritize K-RAS driven tumors RCC as potential next steps, next investments? The good news is I think we're going to have options, we're going to have choices. The team is is uh...

Speaker 4: doing a lot of work to get 2806 into those targeted combinations as quickly as possible. It's really not about the monotherapy, it's how quickly can you get into the combos, how quickly can we see if we can replicate that preclinical data. So that's the data that we're expecting Roger and the way that we're going to the lenses that we're

Speaker 8: Sure

Speaker 2: Your next question comes from Peter Lawson from Barclays. Please go ahead.

Speaker 9: Hey, good afternoon. This is Alex on for Peter. Thanks for taking our questions. Just just given the comments on the pace of site activation and enrollment in the pivotal study, any color you could provide around, you know, when enrollment could complete in that.

Speaker 4: in that study? Yes, Alex, thanks for the question. So we've guided that, maybe taking a step back, the phase 2 study is designed to enroll a total of 85 relapsed refractory NPM1 mutant patients. The reason it's 85 is

Speaker 4: We felt that that was an appropriate safety database to support a best in class men and inhibitor. Typically, the FDA wants to see about 100 patients at your recommended Phase 2 dose just from a safety perspective. Obviously, from an efficacy perspective, you probably don't need 85 patients.

Speaker 4: And within the context of those numbers and that trial design, Alex, we've guided that full enrollment of the 85 is probably middle of next year, but given that we are, given that our initial site activation and enrollment is exceeding our expectations, although we're not yet ready, Alex, to pull the timelines in, I can tell you...

Speaker 4: a report on the Car rijab protected On the item

Speaker 9: Great, thanks. That's very helpful. And then just a second question on EHI. Now the focus is on NPM1, but should we expect any updated data from the MLLR patients you've treated so far? Thank you.

Speaker 4: Yeah, Alex, thanks for the question. At this point, I'll just refer you back to the abstract. Again, I don't want to get ahead of the abstract or get under the four corners. We'll focus at this point on giving you an update on what's laid out in the abstract. As I mentioned,

Speaker 4: We're intending to provide an investor event in connection with EHA. And as I've said, we're seeing multiple lines of evidence, really, that are supporting ZYFTOMENIV, as being a best-in-class inhibitor in acute leukemias. We'll look forward to sharing that data with you and the rest of the folks on this call at that time.

Speaker 1: Thank you.

Speaker 10: Your next question is from Brad Cunino from CIFOL. Please go ahead. Hi, thanks. A strategic zip-domendan question from me, Troy. You've been open in the past about the requirement for a global pharma partner to capitalize in the valuable frontline AML setting.

Speaker 10: So as I look at it now, you're in a position where you have NPM1 data evolving positively. You've got this pivotal trial progress that's ahead of schedule as you state, and you're moving to dose optimize the combos as quickly as possible. Ahead of you, you've got competitor pivotal data and combo safety data in second half 23.

Now, I look at your cash burn guide. That would suggest even with all the plan trial additions that you have laid out in your press release, you expect the cash burn to cap at about a 50 percent increase from the current level of this past quarter as I look through 2025. So as you think about the evolution of all of these pieces, how are you currently weighing the ideal time for such a transaction? Thank you. Yeah. Yeah.

Brought out I appreciate the thoughtfulness with which you laid out the question so

I can tell you that the discussions that we've had with sophisticated parties that do research, development, and commercialization of products in HEM have reinforced the idea that we have a best in class compound. And not only are they drawn to the clinical activity, but very much some of the other properties that we've continued to highlight.

the lack of of of of QT, the lack of drug drug interactions, you know, the oral ones today dosing, the ability to not have to very dose as you're changing SIP, you know, nasal regimens or others is very appealing. In particular, you'll hear us in our prepared remarks stressing the opportunity with the Flip 3 inhibitors.

That's fully half of NPM-1, and you want to hit that head-on as early as you possibly can because you have a real potential to drive durable responses in those NPM-1 FLT3 patients. All of that, Brad, is saying the team is doing everything you've said and even more behind the scenes.

with every other approved agent as well as emerging agents and clearly you know at some point you need global scale to be able to do that but we also very much you know we prioritize patients we also prioritize our shareholders and so we want to make sure that anything we do

It ensures that our shareholders are appropriately rewarded. I can't be a lot more specific than that, obviously, but I can tell you, those of you who know me know I have a history on both the business side and the science side, and I would say there's a lot of excitement about ZYFTOMED-IB kind of across the continuum. And as we have more to say, we'll give updates throughout the year. Thank you.

Thanks, Fred. Thank you, Brad. Your next question comes from Lee Watsack from Kentar, Fitzsimmons, Fitzgerald. I'm sorry, please go ahead.

Hey, thank you for taking our questions. I guess for the deal or that you just shared with us, just wondering if you could put this thing to perspective for us, relative to your competitor. And the second, in terms of the combinations, you mentioned that you could put this thing to perspective for us, relative to your competitor.

Yeah... So...

Yeah, in terms of excitement. So, yeah, very good question. So your first question is,

I'm sorry, can you tell me your first question again?

Yeah, duration of response, maybe just, you know, share your perspective relative to your competitor. Yeah, okay, thank you. I wanted to make sure I answered the question you're asking. So, um,

If you'll indulge me, if you look at the phase 1B study, right, this is what we're updating. I just want to underscore something for everyone. We're reporting data on 20 patients, 20 NPM-1 mutant patients at our recommended phase 2 dose. And that's nearly, you know, between a third—between 25 percent and a third of the way to a registrational study, just in terms of pure patient numbers. So…

that because you want to make sure you're comparing apples to apples. The competitor is three patients, right, two of whom went to transplant almost immediately. And so I'll highlight that to you, Lee. I'm not going to give you an exact number. I'm going to wait for Iha to do that, but what you'll see is the duration of response being driven by ZiftoMinute.

As you saw from the abstract, we have had a couple of patients who, who, for, luckily for them, gone on to transplant with, with, with good results. But it's clear both the, the efficacy, the potency of ZIFTO, the ability to drive full count recovery and the ability to avoid these resistance mutations were driving very good durability.

And I think Lee, it's that entire package that is what is driving the excitement among investigators. So to your other question of, do we think that's going to pull through to the combos? Yeah, very much. Again, our combo strategy is...

We believe Zyftomanid has the potential to be a cornerstone of therapy for acute leukemia. And, you know, our goal is to transform AML the way, for example, I think it might sound cliché, but the way Gleevec transforms CML, right, turned it from a...

from a devastating disease into kind of a chronic condition. Men and inhibitors may be the first thing to come along in AML that have the potential to do that. And we've seen similar levels of excitement and enthusiasm among investigators who are jostling to either get into the O-7, the O-08 study or both.

Our goal though, Lee, is to try to give as many sites around, you know, in both the US and Europe , the opportunity to work with Ziftomentin. So that enthusiasm where people actually, you know, use it with their own patients, that that continues to build. That's what's, I think, driving those exceeded expectations.

and we fully expect that to pull through into the compost. Great, thanks. Ladies and gentlemen, as a reminder, should you have a question, please press the star followed by the one.

Thanks for taking our questions. A follow-up perhaps on the last question. In terms of those earlier lines of therapy and the combination regimens, when we've discussed the opportunity for men inhibitors with our consultants in the earlier lines, some have questioned what trial design would be necessary to support approval and use. Do you have any thoughts on what a registration trial would look like for an early line?

combat regimen? In particular, what endpoints do you think would be meaningful and likely to be hit? Yeah, Phil, it's a good question. And I don't want to get ahead of the team on this. It is very much an active topic of discussion. I don't think we've said much publicly about what registrational studies would look like in the front line.

you know, clearly you're going to need to have a—I think it's unlikely you can rely on MRD negativity. You may be able to go on the basis of response rate with survival, but as for specific parameters, it's obviously going to, you know, depend on the specific combination and the line of therapy. I will tell you, you know, we're—

We've highlighted trying to do two things simultaneously. Provide a data set so that physicians can use ZYFTOM-NEP with whatever regimen they want to use, whether it be Venetoclax, chemotherapy, other targeted therapies. That's our first goal. Our second goal is to go where there's the greatest unmet need and the greatest commercial opportunity.

a little bit more experience in phase one and build up that data set. And then as we've started to lock it down with the investigators and the KOLs, we can communicate it. But it's very topical for our team internally.

Got it. That's fair enough. And then second question is, we're wondering whether you have any new visibility on the potential competitors, obviously not the competitors that are coming from the public companies, but investors have an eye out for those potential competitors, the menin inhibitors, either at Big Pharma or foreign pharma. Any visibility on when the first data from any of those programs could be announced or are you running into any of them as a new

We're not, you know, we're careful not to put our investigators in a position where we ask them for data because for obvious reasons we wouldn't want them to share data on our programs. But we've been impressed, Phil, to this point. As I said...

by the pace of site activation and the pace of enrollment in the NPM-1 setting. And I think that's as much of a biomarker as we probably have. And I'll go even a step further and say my prediction as we go into KMT-2a, you're going to see the activity pick up significantly based on what we've seen with NPM-1. And I'm cautiously optimistic that we're going to see a

Great. And last question from us, one that we get from investors. We're curious to hear your thoughts on it. Any...

Does care have any desire to go into diabetes? Yeah, it's a good question. So I would say the following. We are doing work, we're doing preclinical work with not only Zifto-Menib, but next generation menin inhibitors that are reversible, and we're doing them in diabetes models.

And we're doing that to try to feel sort of be very data driven. I think the data that you're referring to, it's provocative, but it's very incomplete. I can tell you this, if there's a connection there, and there's a biological rationale for why one would use a men in inhibitor and diabetes.

The question is really, you know, the effect size, the safety, etc. I would tell you this. We believe Ziftominib is the best in class menin inhibitor in acute leukemia. If you want to go into whether it's diabetes or solid tumor indications, both from a safety perspective and from the perspective of the IRA, you want to take a different chemotype. You want to take a different compound forward.

And I believe, based on the work that our chemistry group has done, we'll have a best-in-class reversible inhibitor to take into diabetes. But let us do the work and really validate that as a meaningful opportunity, because as you know, it's a completely different development paradigm. Yep, that makes a lot of sense to us. Thanks again for taking our questions.

I believe based on the work that our chemistry group has done, we'll have a best-in-class reversible inhibitor to take into diabetes. But let us do the work and really validate that as a meaningful opportunity. Because as you know, it's a completely different development paradigm. Yep, that makes a lot of sense to us. Thanks again for taking our questions. Our pleasure.

There are no further questions at this time. I will turn the call over to Troy Wilson, President and CEO for closing remarks. Thank you, Julie, and thank you all once again for joining our call today. We'll be participating in the JMP Life Sciences Conference next week in New York and look forward to seeing a number of you there. In the meantime, if you have any additional questions, of course, please feel free to contact Pete,

Thank you again and have a good evening, everyone. Ladies and gentlemen, this concludes your conference call for today. We thank you for joining and you may now disconnect your lines.