Good afternoon, ladies and gentlemen. Welcome to the Kura Oncology Third Quarter 2024 Financial Results Call. At this time, all participants are in a listen-only mode. Later you will have the opportunity to ask questions during the question-and-answer session. [Operator Instructions] Also, today’s call is being recorded. [Operator Instructions] Now at this time, I’ll turn things over to Mr. Pete De Spain, Head of Investor Relations. Please go ahead, sir.

Great. Thank you, Bo. Good afternoon. And welcome to Kura Oncology’s third quarter 2024 conference call. Joining me on the call are Dr. Troy Wilson, our President and Chief Executive Officer; and Tom Doyle, our Senior Vice President of Finance and Accounting; Dr. Mollie Leoni, our Executive Vice President of Clinical Development, is also with us and available to answer questions. Before I turn the call over to Dr. Wilson, I’d like to remind you that today’s call will include forward-looking statements based on current expectations. Such statements represent management’s judgment as of today and may involve risks and uncertainties that could cause actual results to differ materially from expected results. Please refer to Kura’s filings with the SEC, which are available from the SEC or on the Kura Oncology website for information concerning risk factors that could affect the company. With that, I’ll now turn the call over to Troy. Dr. Troy Wilson: Thank you, Pete, and thank you all for joining us. We continue to generate what we believe is a robust clinical data package to support the broad development of our menin inhibitor program, beginning with ziftomenib. We believe ziftomenib is well positioned to transform the treatment of menin-dependent AML so that patients with cancer may lead better, longer lives. Earlier this week, two abstracts reporting preliminary data from our KOMET-007 combination trial of ziftomenib were posted on the website of the American Society of Hematology. As of the June 21 data cutoff, the abstracts continue to support a potential best-in-class safety and tolerability profile for ziftomenib, as well as robust and durable activity in combination with standards-of-care, including venetoclax + azacitidine, as well as cytarabine + daunorubicin, commonly known as 7+3. In the Phase 1a dose escalation portion of the KOMET-007 study, ziftomenib combined with ven/aza was well tolerated and demonstrated promising activity in relapsed/refractory patients. No DLTs or ziftomenib-induced QTc prolongation were reported. On-target differentiation syndrome was observed in 12% of patients, including three of 20 KMT2A rearranged patients and all patients had resolution of DS with appropriate management. Encouraging clinical activity was observed at both 200-milligram and 400-milligram dose levels, including activity in previously venetoclax-exposed NPM1-mutant and KMT2A rearranged patients. Updated results, including data from the 600-milligram cohorts will be reported at ASH. In the AML frontline adverse risk population, we are very encouraged by the safety and tolerability profile, rates of complete response and rates of MRD negativity. Notably, no events of differentiation syndrome were reported at 200 milligrams or 400 milligrams, including among KMT2A rearranged patients, suggesting ziftomenib can be safely combined with induction chemotherapy. We’re particularly encouraged by the fact that in the context of the very challenging 7+3 adverse risk AML patient cohorts, 100% of the 15 NPM1-mutant AML patients and 84% of the 19 KMT2A rearranged patients remained on study as of the data cutoff, one year after study start. Here, again, updated results, including data from the 600-milligram cohorts will be presented at ASH. We look forward to sharing a more mature data set, including data from more than 100 patients with NPM1-mutant or KMT2A rearranged acute myeloid leukemia next month. In the meantime, I’m pleased to report that all four cohorts in the Phase 1a dose escalation portion of KOMET-007 have cleared the highest dose and advanced into the Phase 1b expansion study at 600 milligrams. The Phase 1b expansion study includes multiple combination cohorts, most notably, ziftomenib plus ven/aza in newly diagnosed NPM1-mutant or KMT2A rearranged AML, as well as ziftomenib plus 7+3 in newly diagnosed NPM1-mutant or KMT2A rearranged AML, removing the requirement for patients to have high-risk disease. Each combination cohort is enrolling independently, and we expect to enroll at least 20 patients per cohort. We believe the Phase 1b expansion study will continue to lay the groundwork for helping us to redefine the current standards-of-care for newly diagnosed patients with NPM1-mutant or KMT2A rearranged AML in both the fit and unfit populations. We anticipate sharing preliminary data from the Phase 1b expansion study at a medical meeting in 2025. In addition to KOMET-007, we continue dosing patients in our ongoing KOMET-008 study of ziftomenib in combination with additional standards-of-care, including the FLT3 inhibitor gilteritinib, as well as FLAG-IDA and low-dose cytarabine. Roughly half of all patients with relapsed/refractory NPM1-mutant AML have co-occurring FLT3 mutations, and the prognosis for these patients is poor. Preclinical data for ziftomenib in combination with FLT3 inhibitors has shown strong synergistic effects compared to either single agent alone. When we look across the fit, unfit and FLT3-mutant AML frontline populations, we believe a best-in-class safety and efficacy profile and optimal pharmaceutical properties could enable ziftomenib to become a cornerstone of therapy for patients with acute leukemias. Ultimately, our mission is to develop ziftomenib across the continuum of care for all eligible patients with acute leukemias whose disease is driven by the menin pathway. A critical first step toward that mission is establishing ziftomenib as the best-in-class menin inhibitor for patients with relapsed and refractory NPM1-mutant AML. As a reminder, ziftomenib is the first and only investigational therapy to be granted breakthrough therapy designation for treatment of relapsed and refractory NPM1-mutant AML. NPM1-mutant AML represents approximately 30% of new AML cases annually and is a disease of significant unmet need for which there is no approved targeted therapy. FDA awarded BTD based on data from our KOMET-001 trial, recognizing ziftomenib’s potential as an innovative medicine for patients with this devastating disease. Supporting data from the Phase 1 portion of KOMET-001 were recently featured in a leading clinical oncology journal, The Lancet Oncology. We completed enrollment in the registration-directed portion of KOMET-001 earlier this year, enrolling more than 85 NPM1-mutant patients in fewer than 16 months. We look forward to sharing topline results from this pivotal study next year as we continue to work closely with FDA to expedite development and review of ziftomenib as a monotherapy. Meanwhile, we’ve generated a growing body of preclinical data that supports opportunities for menin inhibitors beyond acute leukemias, including the potential for ziftomenib in the treatment of certain solid tumors. Last month, at the EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Barcelona, we reported preclinical data supporting the combination of ziftomenib and imatinib for the treatment of advanced gastrointestinal stromal tumors or GIST. The combination showed unexpectedly robust and durable antitumor activity in both imatinib-sensitive and imatinib-resistant GIST patient-derived xenograft models, and in all cases, the combination was significantly superior to imatinib monotherapy. Mechanistically, the data revealed a KIT-dependent mechanism with ziftomenib and imatinib combining to sharply reduce KIT expression and/or activity, effectively silencing both the ERK and AKT/mTOR signaling pathways and driving robust cell-cycle arrest and apoptosis. Given that imatinib is well established as the frontline standard-of-care in patients with GIST and generic versions are available, we believe imatinib represents a promising combination partner for ziftomenib. In August, we received FDA clearance of our investigational new drug application for ziftomenib for treatment of advanced GIST. We’re now prepared to initiate a proof-of-concept study evaluating ziftomenib and imatinib in patients with advanced GIST after imatinib failure in the first half of 2025. If successful, the potential opportunity in GIST appears to be agnostic to the mutational status of KIT in GIST, suggesting an opportunity to explore the combination for nearly all patients, including those in the frontline setting. Earlier this year, we reported preclinical data supporting the potential therapeutic utility of menin inhibitors in the treatment of diabetes. We are advancing multiple next-generation menin inhibitor drug candidates targeting diabetes and other metabolic diseases, and we expect to nominate the first of these next-generation development candidates in the first half of 2025. Now let’s quickly turn our attention to our farnesyl transferase inhibitor programs. Despite the success of targeted therapies, a considerable need remains to drive enhanced antitumor activity, while blunting the effects of innate and adaptive resistance. We’re developing our next-generation farnesyl transferase inhibitor, KO-2806, to address this need. 2806 was designed to improve upon the potency, pharmacokinetic and physical chemical properties of earlier FTI drug candidates. We’ve generated a growing body of preclinical and clinical data that demonstrate the potential for KO-2806 as a companion therapeutic to augment the antitumor activities of targeted therapies, including tyrosine kinase inhibitors, KRAS inhibitors and pan-RAS inhibitors. Late last year, we began dosing patients with KO-2806 as a monotherapy in a Phase 1 dose escalation trial that we call FIT-001. FIT-001 uses an innovative design that enabled us to begin dose escalation of KO-2806 in combination cohorts very early in the study while continuing to dose escalating concurrently as a single agent. Earlier this year, we dosed the first patient with KO-2806 in combination with cabozantinib in clear cell renal cell carcinoma. And in August, we dosed the first patient in combination with adagrasib in KRASG12C-mutated non-small cell lung cancer. As a reminder, the study of KO-2806 and adagrasib is supported by a clinical collaboration and supply agreement with Mirati, now a Bristol Myers Squibb Company. If successful, we believe KO-2806 could drive enhanced antitumor activity and become a combination partner to multiple targeted therapies in large solid tumor indications. Meanwhile, we continue to evaluate the combination of tipifarnib with the targeted therapy alpelisib in PIK3CA-dependent head and neck squamous cell carcinoma in a study we call KURRENT-HN. We believe there may be a meaningful opportunity to combine an FTI with a PI3 kinase alpha inhibitor and look forward to presenting preliminary clinical data from the KURRENT-HN trial at a medical meeting in the first half of 2025. With that, I’ll now turn the call over to Tom for a discussion of our financial results.

Thank you, Troy, and good afternoon, everyone. I’m happy to provide a brief overview of our financial results for the third quarter of 2024. Research and development expenses for the third quarter of 2024 were $41.7 million, compared to $29.3 million for the third quarter of 2023. The increase in R&D expenses was primarily due to the increases in clinical trial costs related to our ziftomenib and KO-2806 programs. General and administrative expenses for the third quarter of 2024 were $18.2 million, compared to $13.1 million for the third quarter of 2023. Net loss for the third quarter of 2024 was $54.4 million, compared to a net loss of $38.6 million for the third quarter of 2023. This included non-cash share-based compensation expense of $8.3 million, compared to $7.1 million for the same period in 2023. As of September 30, 2024, we had cash, cash equivalents and short-term investments of $455.3 million, compared to $424 million as of December 31, 2023. We believe that our cash, cash equivalents and short-term investments will be sufficient to fund our current operating plan into 2027. With that, I now turn the call back over to Troy. Dr. Troy Wilson: Thanks, Tom. Before closing, I’d like to thanks -- I would like to take this opportunity to welcome Dr. Michael Vasconcelles to our Board of Directors. Mike is an accomplished biopharmaceutical executive with more than 25 years of oncology drug development experience and industry leadership. His extensive experience in R&D and regulatory affairs, combined with his leadership across both large and emerging companies are invaluable as we advance our menin inhibitor and FTI programs to market while continuing to create value for patients and shareholders. Now before we jump into the question-and-answer session, let me lay out our anticipated upcoming milestones. For our menin-inhibitor program; present updated data from the KOMET-007 trial of ziftomenib in combination with ven/aza and 7+3 at ASH in December 2024; report top line results from the KOMET-001 registration-directed trial of ziftomenib in NPM1-mutant relapsed/refractory AML in early 2025; present preliminary data from the Phase 1b expansion portion of KOMET-007 at a medical meeting in 2025; initiate a proof-of-concept study evaluating ziftomenib and imatinib in patients with advanced GIST in the first half of 2025; and nominate a next-generation menin inhibitor development candidate targeting diabetes in the first half of 2025. For our farnesyl transferase inhibitor programs; identify the maximum tolerated dose for KO-2806 as a monotherapy by the end of this year; initiate one or more expansion cohorts for the combination of KO-2806 and cabozantinib in renal cell carcinoma in the first half of 2025; and present data from the KURRENT-HN trial of tipifarnib in combination with alpelisib in PIK3CA-dependent head and neck squamous cell carcinoma in the first half of 2025. With that, Bo, we’re now ready for questions.

Thank you, Dr. Wilson. [Operator Instructions] We go first this afternoon to Li Watsek at Cantor. Li, please go ahead.

Hi. Hey, guys. Congrats on the progress and thank you for taking my questions. Troy, I guess, how are you thinking about the potential of using MRD negativity as part of the frontline endpoints and then for the MRD data -- negativity data that was just presented in your ASH abstract, is there any difference in the methodology used by you versus your peers? Dr. Troy Wilson: Yeah. Great question, Li. I’ll give you my answer, and then I’ll ask Mollie to comment if she will -- if she can. So for everybody’s benefit, I mean, the base case scenario for these frontline studies is that you’re using survival as the endpoint. There may be an opportunity to use MRD negativity as a surrogate endpoint in an accelerated design, but I wouldn’t consider that the base case. I think although there’s good evidence to support it, that’s not yet sort of a path that has been given the green light by the health authorities. It is something that we intend on discussing with them here in the relatively near future. So I think, Li, we’ll be able to come back to you and others on this call probably early next year with an update on the regulatory strategy, the trial design and endpoints. We’re certainly going to try to reach for that. I don’t know if we’ll be successful. I think we can make a strong case, but we’re using survival as the base case and MRD negative -- negativity, excuse me, as the upside case. I’ll let Mollie add her thoughts to that, and Mollie, if you could also maybe comment to Li’s question on how our methodology may differ from others. Dr. Mollie Leoni: Sure. So Troy is exactly right. While we know that we’ll be able to use a survival endpoint in each of the frontline indications we wish to pursue, MRD negativity is a clear and obvious new way to be looking at the benefit for these patients. We’ve seen it in other studies as they’re pursuing their indications turn out to be an excellent surrogate. So we do think there’s a good argument to be made with the health authorities to use it as part of the study, but how we can use it and to what extent it would be able to be allowed to be used as an endpoint is very much up for discussion and nothing we are able to confirm or deny at this point because we have yet to have those discussions. With regards to our MRD data and our abstracts, you’ll notice we were more quiet about it in the relapsed/refractory setting due to the fact that it’s -- we get less samples in that setting and they’re of a much more varied type of methodology used to assess them, as you might imagine. So what our plan to do is to actually do a central analysis of those samples so that we can actually give a uniform answer to what our MRD negativity looks like in these particular patients. Frontline setting, we did provide the local test results. They are done more consistently because they’re used to make standard of care decisions with regards to transplant, et cetera. So we did provide those site-based tests, but we do plan also on running those centrally so that we can give a much more uniform result on the MRD negativity.

Okay. And then for the 6 mg data that you’ll present at ASH, I just wonder if you can give us a sense of number of patients, follow-up and what types of data that we might see? Dr. Troy Wilson: Yeah. Li, so we’ve said we’re anticipating showing data on more than 100 patients at this point. That will -- I think you can see by the abstract, we’re kind of halfway there. You’ll see additional patients at the different dose levels. We’re planning on really updating every patient on the study as of their status with respect to response, as well as duration of any clinical benefit. In terms of what to expect, given that the activity is pretty robust at 200 milligrams and 400 milligrams, we’re expecting to see sort of pretty consistent activity. We get asked a lot, do we expect a dose response? Not clear if one expects a dose response with these high levels of activity. But something that you’ll see is we actually do see interestingly a dose response with respect to safety and tolerability, i.e., as you go higher in dose, the safety and tolerability actually improves, which might seem counterintuitive, but that helps to support, as you know, we’ve moved forward now into the expansion cohorts at 600 milligrams across all the cohorts and that’s partly driven by activity. It’s also a significant component of safety and tolerability. So you’ll see that -- you will see sort of that, it will actually be, I think, a meaningful update even relative to what you see in the abstracts.

Got it. Thank you. Dr. Troy Wilson: Sure.

Thank you. We go next now to Jonathan Chang at Leerink Partners.

Hi, guys. Thank you for taking the questions. As we’re starting to see longer-term data for zifto and other menin inhibitors in the space, how has that impacted your thinking on what the opportunity could be for the class? And what do you see as the key factors determining how long patients can stay on treatment and benefit? Thank you. Dr. Troy Wilson: Yeah. Jonathan, thanks for that question. That’s actually -- while I appreciate that there are a significant number of folks that sort of want to get into the scrum of comparing one relapsed/refractory data set against another, one of the big take-home messages from our abstract is something I think you’re alluding to, which is the -- what’s beginning to emerge in the frontline setting. So just for everybody’s benefit, if you go and you read the abstract for the frontline 7+3, you’ll notice as of the data cutoff in June, 15 out of 15 NPM1-mutant patients and 16 out of 19 KMT2A rearranged patients remained on study -- on therapy as of the data cutoff. And for some of those patients, that study had been going at that point for a year. So what we’ve said consistently, Jonathan, is there is clearly a significant unmet need in the relapsed/refractory population. Those patients are in dire need of options. But as one thinks about the commercial opportunity, clearly, if we can intercept patients early in their treatment journey and provide clinical benefit, whether that is in the form of continuation therapy, i.e., they get a response, they stay on ziftomenib, don’t necessarily go to transplant or in the alternative, they get a response, they go to transplant and then they go back on zifto in a post-transplant maintenance. That’s what we’re seeing, we think, beginning to emerge in the 7+3 adverse risk frontline population. The fact that you have 90%-plus of the patients, again, as of the data cutoff, staying on study, that’s not even survival, right? That’s on study. That’s significant. I think that the way I’ve always thought about it is adverse risk 7+3 is about as hard as it gets in the frontline setting. We’re hopeful that, that trend continues now that we’re in the expansion cohorts for the frontline 7+3 without adverse risk, i.e., all comers as well as the frontline ven/aza. If we can take these frontline patients, keep them on -- in a response and keep them on therapy for a year, 18 months, potentially even longer, that’s where you really begin to see significantly inflecting the disease and that’s what, in our thinking and our models, really helps drive the commercial case. And I think we’re excited to share with you the update for both the relapsed/refractory and the frontline, but that frontline picture is beginning to come into focus and I think it looks pretty attractive relative to the competition.

Understood. Thanks for taking the questions. Dr. Troy Wilson: Thank you.

We’ll go next now to Jason Zemansky at Bank of America.

Good evening. Congratulations on the progress and thanks so much for taking our questions. Regarding the combination updates at ASH, what should we be thinking in terms of benchmarking a win here? Is safety still the focus or do you expect the data at that point to be mature enough to gain key insights into efficacy? And then a follow-up. Dr. Troy Wilson: Yeah. So let’s start with that, Jason. And Mollie, maybe you want to take Jason’s question in terms of how we think about benchmarking, maybe we can start with the relapsed/refractory and then we can talk a little bit about the frontline and sort of what the benchmarks would be. Dr. Mollie Leoni: Sure. Realistically, in the relapsed/refractory setting, these patients have, for the most part, failed venetoclax. And as we know, that’s an extremely poor prognostic factor for doing well on any therapy. For KMT2A, you should probably set the bar at less than 10%. Potential response rate for NPM1 is slightly higher, but the data tends to suggest that overall, the survival would only be 2.4 months or so in these particular subsets of patients. So that helps see how bleak the situation is. And so we think any improvement, obviously, over that would be very significant. But as you point out, really, the goal is safety and tolerability with a Phase 1 dose escalation. And the fact that we’ve been able to safely escalate through the 600-milligram dose without DLTs, and as Troy referred, to see not only the ability to escalate safely, but to see improved safety as we escalate is an extremely strong sign that we’re getting good activity as we increase in doses. Troy, is there anything you would add? Dr. Troy Wilson: No. Not to that, Mollie. But maybe you could help set expectations for frontline and how we think about that in the adverse risk… Dr. Mollie Leoni: Okay. Dr. Troy Wilson: … population. Dr. Mollie Leoni: Absolutely. So our best comparison for the frontline is the Vyxeos control arm, which put the response rate at about for -- a composite response rate at about 60%. So that would be your CR, your complete response, your complete response with partial hematologic recovery and your complete response with incomplete hematologic recovery. So about 60% there and an overall survival of about six months. So again, in these adverse risk patients, not a good setting to see. But again, we’re seeing excellent ability to be able to escalate the dose these patients are staying on for very significant periods of time. As Troy alluded to, very few have come off study even in our 200-milligram cohort, which has been going on for well over a year. So far, I think we’re seeing signs that make us encouraged to keep moving forward.

Got it. That’s helpful. And maybe to circle back on your comments on tolerability and safety. The team has been guiding away from a zero percent DS rate, which makes sense. But I’m curious, is there a level that you think would be especially encouraging in both the 7+3 and ven/aza settings and is there a ceiling here as well? Dr. Troy Wilson: Go ahead, Mollie. Dr. Mollie Leoni: We… Dr. Troy Wilson: You take that? Dr. Mollie Leoni: Sure. Yeah. We traditionally thought that as long as it was easily controllable, easily addressed, 20% or less DS rate is extremely tolerable. What I always like to remind people is that, for the grading of differentiation syndrome, Grade 3 simply means that a patient was hospitalized for the event and in these patients, they’re extremely fragile and tend to have fevers of unknown significance and other symptoms that might need urgent intervention, they’re hospitalized all the time. So a Grade 3 DS is not necessarily associated with extremely severe symptoms. And what we’re seeing is Grades 2 and 3 DS that are very easily controlled, and what’s different from the monotherapy is it doesn’t even appear that we need to interrupt drug to be able to control them, steroids and supportive care do seem to be sufficient. So just to summarize, a reasonable severity level, probably about 20% and with the ability to treat easily and quickly get these patients continued on therapy is where we would set the bar.

Great. Good color. Dr. Troy Wilson: I’ll just add to that. Yeah. Jason, I’ll just add to that. You’ll expect to see, when we give the full data, the DS rate drop to single-digit percentages. So I think we’re encouraged. We’ve seen it primarily, as Mollie indicated in the KMT2 rearranged in the relapsed/refractory setting, seems to be well managed with these combinations.

Very helpful guys. Thanks so much. Dr. Troy Wilson: My pleasure. Thank you.

We’ll go next now to Roger Song at Jefferies.

Great. Congrats for all the progress and taking all the question. Maybe one question related to the -- again, back to the potential pivotal plan, understanding you’re discussing with the FDA right now. Just curious about the timing for the pivotal study initiation versus your expansion data release. Do you need to see more dose-dependent efficacy at the higher dose or RP2D dose 600-milligram versus the others or the current dose exposure or the total package sufficient for you to move into the pivotal once you finalize the design? Thank you. Dr. Troy Wilson: Yeah. Roger, thanks for the question. We already have those trials designed and are preparing to engage the health authorities in discussion. So if that helps address your question. As Mollie indicated, both the clinical activity and the safety and tolerability support that 600 milligrams is going to represent the dose that we recommend to FDA and other global health authorities as the dose in combination. The health -- in addition to the dose selection, as Mollie indicated in an answer to one of the previous questions, we’ll talk about endpoints. The powering, the design, I mean, that’s really up to us, but the endpoints are a critical question and we’ll want to have a robust discussion there. We’re currently thinking that we’ll kick off those studies middle of next year. We believe there’s an opportunity to combine ziftomenib in both 7+3 and ven/aza, and so we’ve designed trials for each of those two settings. Something that I think has been an interesting surprise to us is, before we had dosed a patient, I don’t think we really appreciated the opportunity in the frontline 7+3. We sort of naively assumed patients would enter that cohort. They would go through two or three cycles, go to transplant and then we might or might not get them back. That’s really not what we’re seeing and you don’t necessarily see it in the abstract, but you’ll see it in the more fulsome data set. Patients are -- as Mollie indicated, they’re staying on therapy for prolonged periods of time. Many of them are not going to transplant and we’ll -- obviously, you need to see the data to understand this. But what that’s led us to is an appreciation that whereas we may have thought that venetoclax and azacitidine was the much larger commercial opportunity, it is meaningful. There’s no question and we’ll pursue that. But 7+3 plus zifto appears to be nearly equally important. And we can see that in terms of enrollment. We can also see that just in terms of the clinical benefit profile that’s beginning to emerge. So we’re rolling all of that in, think about regulatory discussions in the early part of next year with a goal towards starting a combination study or studies middle of next year. Hopefully, that helps answer your question.

Excellent. That’s very helpful. And similar in terms of the time line regarding your -- the monotherapy NPM1, the data continue to be early 2025 and how should we think about the NDA filing for that monotherapy? Thank you. Dr. Troy Wilson: Yeah. Another -- thank you for that question. So, yes, once the data has been collected and cleaned and locked, we’ll be in a position to provide the topline results. Within some period of time, measured by a few months, we’ll be ready to submit that NDA to the agency. We would be looking for ideally, if all goes well with the submission and review, for an approval in the second half of next year. We’ll be in a better position, Roger, to guide on that more specific timing next year when we’re a little bit closer, but that should give you a rough idea of how to think about it.

Excellent. That’s very helpful. Thank you. thank you, Troy. Dr. Troy Wilson: Sure.

We’ll go next now to Charles Zhu at LifeSci Capital.

Good afternoon, guys. Thanks for taking the questions and congrats on the progress. A couple from us. First, could you remind us what proportion of patients are, quote, adverse risk? And if you’re including this a broader population beyond adverse risk in your Phase 1b expansion cohorts, how should we be thinking about enrollment speed there? Thank you. Dr. Troy Wilson: Sure, Charles. Thanks for the questions. Mollie, can you speak to that, sort of how we think about adverse risk versus the broader population and then what, if anything -- I don’t know, what, if anything, we can say about enrollment? Dr. Mollie Leoni: Sure. So the way we’ve defined adverse risk is older patients that may also have a complex cytogenetic or be treatment-related AML. So that is how we define adverse risk and realistically it does comprise a fair amount of patients. I don’t know exact numbers, but my estimate would be about 30%. And with regards to how that affects enrollment being able to open it up, I can tell you that our enrollment in the 1a, where we did have the adverse risk, was extraordinarily brisk. As you can see with the fact that we’re able to now share 105 patients’ worth of data after just over a year. It is now just as brisk, if not more so, as we move into the Phase 1b. So we are very encouraged by the excitement of the investigators and the desire of the patients to participate in our trials.

Got it. Great. Thanks for that. And regarding your ASH abstract, one clarifying question here. Is there a response deepening effect that we could be seeing at the lower 200-milligram dose given that it has longer follow-up versus the 400 milligrams and granted these are very small end, but how should we be thinking about what appears to be a numerically inverse dose response between 200 milligrams and 400 milligrams in combination? Thank you. Dr. Troy Wilson: Mollie, do you want to take that? Dr. Mollie Leoni: Yeah I think -- sure. I think there’s a combination of reasons. I think the biggest one is, exactly as you point out, small numbers. And within those small numbers, when I look at the demographic details, there’s varying baseline characteristics as well that can complicate the interpretation. So you’ll have different ECOG medians for different dose levels, different numbers of priors for different dose levels. So ultimately, it really does become the totality of evidence that helps us determine what the correct dose to carry forward should be. And I should clarify that we have both the safety monitoring committee and an independent data monitoring committee that have been involved consistently throughout the study, not only in helping to decide when and if we should dose escalate, but also helping to decide what the totality of data tells us about the right dose for these patients. And ultimately, both of those committees agreed that it is 600 milligrams that should be taken into the expansion cohort based upon not just the response rates, taking into account the baseline characteristics, especially the safety and tolerability, the count improvements, the speed to response, a myriad of different data pieces. So, we -- while it could appear to be an inverse dose response, we don’t think that is actually the reality of this particular study.

Perfect. Great. Makes sense. If you could humor, maybe just one last one from me. Regarding the on target menin resistance mutations, we’ve heard a few things from some third parties out there, but could you clarify the assay that you used relative to one of your peers/competitors assays when they reported their 38.7% rate of mutations and how similar or different are the sensitivities of those assays and what does that mean with the rate of emergent menin resistance on zifto? Thank you. Dr. Mollie Leoni: So I think you’re referring to the difference between digital droplet PCR and RT-PCR that we used. We also use different sources, DNA versus RNA, for examining that data. However, the patients that we looked at for mutations would have been detectable at even a less sensitive assay. So we didn’t need digital droplet PCR in order to determine if these mutations were there. So we do think that our data is highly reliable and that we’re able to compare to these other data. And remember, they were using the digital droplet PCR to determine if these were present at baseline rather than things that developed over time. In addition, we’ve obviously continued to do our work on this topic, and we have continued to confirm through more and more sensitive analyses that our findings are extraordinarily consistent with what we presented at EHA.

Excellent. Thank you very much for taking my questions and congrats again. Dr. Troy Wilson: Thanks, Charles.

Thank you. We go next now to Phil Nadeau at TD Cowen.

Good afternoon. Thanks for taking our questions as well. We were intrigued by your comments about safety improving for zifto as the doses increase. Is there a mechanistic rationale as to why safety should improve with increased exposure? Dr. Troy Wilson: Yeah. Phil, there is actually and I’ll let Mollie give you more color. Dr. Mollie Leoni: Yeah. It’s actually a little bit more obvious than you’d even think. We are seeing faster count recoveries with increased dose. Obviously, faster count recoveries mean these patients have less time to be susceptible to infections, have less time to be susceptible to bleeds, have less need for transfusions. So there does seem to be a very good basis for why we are seeing the improved safety at increased dose.

That is very helpful. And then second question on the next-generation menin inhibitors. I think you mentioned specifically that you will nominate a candidate for diabetes in the first half of 2025. Are there efforts underway to identify next-generation menin inhibitors to advance in heme malignancies as well? Dr. Troy Wilson: Yeah. Good question, Phil. There could be. I mean we have molecules. It’s -- you always think your baby is the most beautiful, right? It’s hard to imagine improving on zifto. The one thing you might say is, could we actually develop a molecule that was active against all the known gatekeeper mutations. We have such molecules. It’s not obvious to us now that we’re in combinations. And as Mollie said, we continue to see very, very low rates of induction of gatekeeper mutations that, that’s an advantage. So at the moment, I would say we have the molecules. We’re holding them and really putting the bets on zifto going into combinations initially in the front line as well as doing work, for example, with the FLT3 inhibitors. We are, however, looking at menin inhibitors potentially for other solid tumors. And we put out what I think is some very nice preclinical data combining ziftomenib with imatinib in GIST. We’re doing the work to determine, is that an isolated example or are there other solid tumor applications. And if there are, you want the optionality of having a distinct next-generation menin inhibitor for those solid tumor applications. As we continue to do more work, Phil, we’ll begin to fill that picture in probably next year.

That’s helpful. Thank you for taking our questions. Dr. Troy Wilson: My pleasure.

We go next now to Peter Lawson at Barclays.

Great. Thanks. Just as we think about expectations for kind of prior then treated patients in the pivotal study, how should we think about that versus what we saw in the Phase 1 data that was published? Dr. Troy Wilson: Yeah. Mollie, do you want to speak to Peter’s question? Dr. Mollie Leoni: Sure. Obviously, the published data was on a very small data set and we’ll continue to analyze the monotherapy data as we put out our Phase 2 data set as well and probably gain a better picture as to exactly what these patients look like post-venetoclax failure and if we’re able to resensitize and get these patients back, able to respond to therapies. In the combination setting, we are -- we will be presenting more data on that as we get to ASH. We do think that there is still the good potential for patients to respond post-venetoclax failure. Again, is that due to our ability to resensitize these patients to venetoclax? Is it a synergistic effect between the two molecules? We don’t know. It’s too early. But we’ll continue to analyze the data. All I can say is we continue to be encouraged.

Perfect. Thanks. That’s really interesting. On the 7+3 adverse risk patients, what would the duration of response? How could that differ between, do you think, the NPM1 versus the KMT2A patients? Dr. Troy Wilson: Yeah. Mollie, do you want to take that question as well? Dr. Mollie Leoni: What’s nice is that the answer to this question is, we don’t know yet, because all of these patients are realistically still ongoing therapy. So, thankfully, we haven’t reached our median duration of response for these groups and we hope that it continues on that way and so that this question continues to be difficult to answer.

Okay. There’s no kind of fundamental difference, do you think, between the NPM1 and KMT2A patients? Dr. Mollie Leoni: I do. I think KMT2A are much harder to permanently control. They have just a much more aggressive monocytic disease that is so invasive. But I think that’s where a molecule like ziftomenib becomes so important because our drug is able to actually accumulate in tissues as well and find some of these areas where the KMT2A rearranged cells have been able to already invade at the time of diagnosis even in the front line. So, yes, definitely a fundamental difference in the level of aggression between the two, but we hope that menin inhibitors at least become the great equalizer for them.

Perfect. Thanks so much. Thanks for taking the questions. Dr. Troy Wilson: Thanks, Peter.

We go next now to Justin Zelin of BTIG.

Hey. Thanks for taking the question and congrats on the progress. Maybe following up on an earlier question about resistance mutations. Would you look to do that analysis in your combination and earlier line studies? And just expectations there if you think that it might differ in those settings? Dr. Troy Wilson: Mollie, do you want to take that? Dr. Mollie Leoni: I mean -- yeah. Obviously, in frontline settings, we don’t expect to see at least a baseline existence of these resistance mutations, although they could very well be in your relapsed/refractory setting after exposure to other menin inhibitors. But with regards to a differential ability to develop these mutations, once you get into combination, your risks are going to decrease enormously. It’s the monotherapy that’s really the big risk for developing these types of mutations because you’re just not hitting it hard enough, fast enough and you’re giving it time, just like with bacteria to grow out resistant colonies. So I think that you’re just going to see a decrease overall in these mutations becoming an issue for patients that are able to have successful outcomes on the combinations.

Great. That’s makes sense to me. Thanks for taking our question.

And we’ll go next now to Brad Canino at Stifel.

Hi. Thanks for the question. Just one for me. I am wondering, given we’ve seen one of the peer menin companies initiate a frontline trial in collaboration with one of the European cooperative groups. Just what’s your current thinking about employing a similar strategy? How do you think about the pros and cons of using such a collaboration versus, say, doing a full company-sponsored one? Thank you. Dr. Troy Wilson: Yeah. Thanks, Brad, for the question. So cooperative groups play a really important role in the ecosystem. They do some terrific work. In our view, and you can see this reflected in the development plan, we are establishing data packages for safety, tolerability, combinability, clinical activity across a range of different combinations. Much of the focus, obviously, in the run-up to ASH, is around 7+3 and ven/aza. But hopefully, next year, we’ll talk more about 008, which is gilteritinib, LDAC, FLAG-IDA. And so to the extent that for some of these perhaps either smaller opportunities or populations where it’s more difficult to identify these patients for treatment, those are ideal for cooperative groups and I think you really want to take full advantage. And in that context, you probably know we have a collaboration with LLS’ pedal in the pediatric indications because they’re huge unmet need, difficult to find those patients. It’s not a huge commercial opportunity, but it is unquestionably one of the most important things you can do and we are very happy to be collaborating with LLS. The downside to a cooperative group study is it’s their design, it’s their time line, they dictate data release, they dictate how the -- how you interpret that data, any amendments you make to the study. I don’t think you’re going to see us using cooperative group studies for either our 7+3 or ven/aza trials because that’s where 90% of the value is, to be honest, right? We all know this. The big money here is, get patients on study right at the get-go and ideally keep them on 12 months, 18 months, perhaps, even 24 months. So you’re going to see us, Brad, do Kura-sponsored studies, but we’ll continue to work and have studies planned for cooperative groups where those smaller indications may be appropriate. We’ll do a mix of both.

Thank you. Dr. Troy Wilson: Sure.

We’ll go next now to David Dai at UBS.

Hi. This is Ihan [ph] on for David. Thank you so much for taking our question and congrats on the quarter. So I guess our first question is kind of like for the pivotal data, ziftomenib pivotal data, in relapsed or refractory NPM1-mutated AML in early 2025. So just curious if you could set some expectations on the clinical meaningful efficacy, as well as duration bar. And the second one, I think for your ASH abstract for the ziftomenib plus aza cohort, so we saw there were around like 25% patients who actually have prior menin inhibitor. So just curious if we are going to see the efficacy profile from these set of patients at the presentation? Yeah, I think it’s just like related to potentially like higher activity against some mutation resistance to the patients? Thank you. Dr. Troy Wilson: Sure. Thanks, Ihan, for the question. So with respect to the monotherapy pivotal data, I think even before we ever dosed a patient, we’ve always given the same guidance, which is the regulatory bar in our view, the bar to approval is, 20% to 30% CR/CRh and four months to six months median duration of response. I don’t think I’ve ever varied from when I’ve been asked that question. Certainly, to this point, nothing has changed. Now that is the bar that the agency uses to consider approvability. As Mollie has already indicated to you, there are a lot of other factors, and some of those have been spoken to by competitors of ours. So CRC rate, overall response rate, things such as that as well as safety and tolerability, it all factors in. But that’s how we’re continuing to think about the monotherapy data. As far as data on activity in patients who have experienced prior menin inhibitors, yes, there will be some additional data in the materials that are presented at ASH that -- in the relapsed/refractory setting, it’s part of the story. It is, as Mollie indicated, still kind of an evolving part of the story, because these patients are -- because the patient population is so heterogeneous, i.e., ECOG status, lines of therapy, what they’ve seen previously. I don’t think we yet fully have the rules of the road, but we are encouraged to see activity in patients who have progressed on prior menin inhibitors and learning what if anything can we do to increase that when we treat them with ziftomenib.

That’s awesome. Thank you so much. Dr. Troy Wilson: Sure.

And we’ll go next now to George Farmer at Scotiabank.

Hi. Good evening. This is Koli [ph] on for George. Can you hear me okay? Dr. Troy Wilson: We can.

Okay. Great. Curious about your diabetes program and how this next-gen menin inhibitor, that we’re going to get more information on next year is going to be different from ziftomenib and from this other competitor molecule from which we expect some critical Phase 2 data by year-end? And I guess they’ll be setting the benchmark for the potential of menin inhibition in diabetes and what you’ll need to see from your own program eventually down the road. So in what ways are you hoping to be similar or differentiate from that other program? And then I have a follow-up. Dr. Troy Wilson: Yeah. Okay. Yeah. Great question. So in our hands and when we do these experiments away from AML, whether it’s GIST, whether it’s diabetes, folks should understand we evaluate not only ziftomenib, but competitor compounds, as well as next-generation compounds in our portfolio. So we try to get a holistic picture. And for example, in GIST, zifto is uniquely active in GIST and we think in part due to its tissue penetrance. In diabetes, it also seems to be extremely active. Francis Burrows, who is not with us on the call, who is our Senior Vice President of Translational Research, he characterizes zifto as it hits menin as hard as you can hit it. It provides very potent knockdown. It’s a menin degrader, which is a property that is shared by some of the other compounds, not all. We’re not -- I think we can actually say, we probably don’t have to hit menin quite as hard as one hits it with leukemia in order to drive the sort of pharmacology that you’re seeing in the diabetes models that we showed at the ADA meeting in June. As we think about the properties of a next-gen compound, most important is safety. safety and tolerability. In the type 2 setting, honestly, these patients are not that sick, right? They are -- we’re not talking about leukemia patients. We’re talking about diabetic patients. That’s not to take anything away, but the hurdle for safety and tolerability is much higher. So you’re going to see us put a real emphasis on not only activity in the appropriate animal models, but really trying to create as large a therapeutic window as we can. The other interesting thing, and we’ve benchmarked this against other compounds that you may be aware of. What we see with zifto is, when you add zifto, it takes several weeks for the activity to kick in. When you remove zifto, it takes several weeks for the activity to decay. Does that make sense? Yes, it does because this is an epigenetic mechanism. With certain other competitor compounds, you do not see that. As soon as you remove the competitor compounds, the pharmacology goes away almost immediately, suggesting that maybe that’s not acting entirely via menin and so we’re going to want to make sure we understand that as well. The final thing I’ll say is there are very sophisticated parties out there that know this space and we are not shy about consulting them on what they would want to see as far as preclinical and clinical data that would ultimately allow you to do the right sort of diabetes study. So we’ll have much more to talk about that. Again, looking forward to nominating probably the first compound, maybe of a couple, in diabetes first half of next year, and then happy to walk people through that data as it continues to evolve. And you said you had a follow-up.

Yeah. Yeah. Thank you. Very helpful color there. Does your current cash runway estimate include this early clinical work -- early Phase 1 work in diabetes as you enter the clinic? Dr. Troy Wilson: Yeah. Let me ask Tom actually if he can speak to that question.

Thank you. It does. Our cash runway does include the menin next-generation work in diabetes.

Great. Thank you so much.

And it appears Dr. Wilson, we have no further questions today. I’d like to turn the conference back to you, sir, for any closing comments. Dr. Troy Wilson: Thank you, Bo, and thank you all once again for joining our call today. We’ll be participating across the pond at the Jefferies London Healthcare Conference in a couple of weeks and look forward to seeing many of you there. In the meantime, if you have any additional questions, please feel free to contact Pete, Tom or me. Thank you all again and have a good evening, everyone.

Thank you, Dr. Wilson. Again, ladies and gentlemen, that will conclude the Kura Oncology third quarter financial results call. Again, thanks so much for joining us and we wish you all a great evening. Good-bye.