KURA - NASDAQ

Good afternoon, ladies and gentlemen, and welcome to the Q4 2023 Kura Oncology, Inc. Financial Results Conference Call. At this time, all lines are in listen-only mode. Following the presentation, we will conduct a question-and-answer session. [Operator Instructions] This call is being recorded on Tuesday, February 27, 2024. I would now like to turn the conference over to Pete De Spain, Head of Investor Relations. Please go ahead.

Great, thank you, Eric. Good afternoon and welcome to Kura Oncology's fourth quarter and full-year 2023 conference call. Joining me on the call are Dr. Troy Wilson, our President and CEO and Tom Doyle, our Senior Vice President of Finance and Accounting. Before I turn the call over to Dr. Wilson, I'd like to remind you that today's call will include forward-looking statements based on current expectations. Such statements represent management's judgment as of today and may involve risks and uncertainties that could cause actual results to differ materially from expected results. Please refer to Kura's filings with the SEC, which are available from the SEC or on the Kura Oncology website for information concerning risk factors that could affect the company. With that, I'll now turn the call over to Troy.

Thank you, Pete, and thank you all for joining us. Let's jump right in. Last month we reported preliminary clinical data from the first 20 patients in KOMET-007, a Phase 1 dose escalation trial of our Menin inhibitor,

Thank you, Troy, and good afternoon everyone. I'm happy to provide a brief overview of our financial results for the fourth quarter and full-year 2023. Research and development expenses for the fourth quarter of 2023 were $32.5 million compared to $22.7 million for the fourth quarter of 2022. R&D expenses for the full-year 2023 were $115.2 million compared to $92.8 million for the prior year. The increase in R&D expenses was primarily due to increases in clinical trial costs related to our

Thank you, Tom. Before we jump into the question-and-answer session, let me lay out our anticipated upcoming milestones. For

Thank you. Ladies and gentlemen, we will now begin the question-and-answer session. [Operator Instructions]. Your first question comes from the line of Jonathan Chang with Leerink Partners. Please go ahead.

Hi, guys. Thanks for taking my questions. First question on

Sure, Jonathan. Thanks for the question. So, I'll actually direct folks and there's a revised slide in the corporate deck. If you want to take a look at it, it has the exposure curve by dose on the right side, and on the left side some of the key points Jonathan from the 001 study. Most importantly, from the clinical data we've now generated. The human clinical data, we can say

Got it. Thanks for clarifying. And then just second question with the KOMET-008 study starting. Can you discuss the opportunity for

Sure. So the rationale is maybe just taking a half a step back. When you look at the various combinations of the 007 and the 008 protocols, what our team Mollie Leoni, Stephen Dale and others on the team have endeavored to do is to provide a foundation where physicians can in principle combine

Understood. Thanks for taking the questions.

My pleasure.

Your next question comes from the line of Jason

Perfect. Good afternoon and thank you for taking our questions. I'm curious about 007 as the patients continue to hopefully do well on therapy and potentially approach hematological recovery with longer duration of therapy. What are your expectations in terms of moving them off of therapy? Is the idea maybe to keep them on

Yes. Jason, thanks for the question. So, importantly, when you heard it in the prepared remarks, we don't see any additive myelosuppression. And as a result, we don't have to hold the dosing of

Got it. And then looking at your timelines, thinking about the bigger commercial dynamics here, you're potentially looking at a scenario where you may be a next to market menin inhibitor in the NPM1 space with potentially better efficacy. How are you thinking about launching into this space? I guess what I'm really driving at here is at this stage, do you get the sense that the community, the prescribing community sees the two different menin inhibitors as more distinct versus similar? I mean, what's the feedback been like here?

Yes. So look, we've done a small amount of sort of pre-commercial work with physicians. And what we found is when we profile the

Got it.

You had a follow-up question. Yes, sure.

That was it, but that was the follow-up. Thank you so much for the insights and color.

Our pleasure. Thank you for the questions.

Your next question comes from the line of Li Watsek with Cantor Fitzgerald. Please go ahead.

Hi. Good afternoon. Congrats on the progress. Maybe just a couple of follow-up questions from me. Just wondering if you can clarify the plan for data disclosure for 007 study around midyear. Other than RP2D dose selection, would you be sharing data at higher doses? And also can you comment on if you have started to dose patients at 600 mg?

Yes. So thanks, Li, for the questions. Let me take them in reverse order. So as of today, no, we haven't started yet dosing patients at 600 mg. I think you can hear from us, we're encouraged thus far by what we're seeing. And as you know from the monotherapy, there's nothing that we've seen that really gives us cause for concern, but one still has to run the experiment. In terms of what data one might expect, so obviously going back to the January update which feels like a lifetime ago, but was just about a month ago. At that point we had 20 patients that we -- for which we shared data, and we were focused on safety, tolerability, combinability, and then some early signs of activity. The next logical update ideally you said it in your question I think it's right is around the RP2D. Are we able to dose escalate? What does that look like from again safety, tolerability, combinability? Is there any difference or are we simply giving more

Okay. And then maybe a follow-up question. Troy, you mentioned about enrollment speed here. I mean, given the very strong data from 007 study last month, I guess, what is your expectation for the enrollment rate for the 008? And also in terms of clinical sites, what's the degree of overlap between these two studies?

Yes. Good question. So again, I appreciate it's a two part question. Let me take the second part first, because it's a little easier. At this point, there's sort of minimal overlap between 007 and 008. We're trying not to create situations where sites are competing although the trial that they go on to is largely driven by the line of therapy. So the front line patients obviously have front line options. For 007, once we reach the RP2D, for example, for Ven/Aza, we'll do the expansion validation in the front line, right? So that will be self-limiting. The -- I think it's early. Li, we've just really gotten going. We're sort of taking the first tentative steps on 008. We'll have a better sense of how that's going as the weeks and months continue. 007 is going very robustly and as this 001, I think we have every expectation 008 will as well. We particularly expect to see interest in Gilteritinib. The investigators fondly refer to this study as the FLT3 study. I think they're excited to see this combination and we're excited to get going on this study and begin to get some experience. So look forward to an enrollment update on 008 again the next time we have the microphone or a little later in the year.

Thank you very much.

Sure.

Your next question comes from the line of Peter Lawson with Barclays. Please go ahead.

Great. Thank you so much. Thanks for the updates. I had a quick question on KOMET-007 combo. Just why

Yes, so actually the opposite, Peter. So I don't know if you heard the answer to the question that Jonathan asked, but there's a new slide in our corporate presentation that I would direct everybody to that says as clearly as we can say it,

Perfect. Thank you so much. Thanks for clarifying that. And then just on the expansion cohort, that's really interesting. So patients without NPM1 came to 2A. Are there particular mutations you're targeting or is that kind of all-comers approach? Just curious on how you're kind of focused?

Yes. So thanks for the question. So to clarify for everyone in the prepared remarks, we announced that we've dosed the first patient in an addition to 001. It's not part of the registrational study, but it's part of the one protocol that is looking to dose

Got you. Perfect. Thanks so much. Really appreciate it.

Yes. Pleasure.

Your next question comes from the line of Justin

Hi, thanks for taking the questions and congrats on the progress. So Troy, you mentioned interrogating Menin in other indications outside of acute leukemias. You mentioned, some solid tumor and, non-oncology indications. So will that be with

Yes, Justin. Really good question. So let's tease those two parts apart. We really view

Great. Looking forward to it. Thanks for taking the questions.

Sure. Thank you.

Your next question comes from the line of Reni Benjamin with Citizens JMP. Please go ahead.

Hey, thanks for taking the questions guys and congratulations on the progress. Maybe just two questions for me, Troy. One, in the prior data that you guys had already reported from 007, you talked about 10 patients who had already received prior [indiscernible] and you were still seeing a 40% ORR. And I don't know if this was asked before or not, but does this suggest that then could potentially be taken out of that regimen and a less toxic, call it,

Right. Okay. So several questions packed in there, Ren. Maybe taking your second question, second set of questions first. So the yes, you will by design cannibalize those later lines if you're successful. Our goal, I think the goal of everyone in this field is to prevent the need for use in the relapsed refractory setting by treating patients in the upfront setting. Our goal is treat patients early in lines of therapy where the benefit, the clinical benefit is potentially much greater. Will that come at the expense of the relapsed refractory? It will. But ultimately, that's better for patients, offers them a better clinical benefit and is arguably a more compelling commercial case. The combinations that we're doing, we really are wanting to make -- wanting to generate safety data to give physicians freedom of choice. For example, there are fewer drugs approved in Europe than in the U.S. The LDAC combination might be very attractive in Europe. Dr. Mollie Leoni, who's the Clinical Lead and our EVP of Clinical Development for Kura has said, it doesn't really matter how you get patients to a response. If you can get them there with a "softer response", that's better. You don't have to use a hard chemo. Your goal is to get them to response and LDAC might be an attractive way to do that. You heard me answer the question on FLT3. That's another option. Not so much driven by BD considerations, although I will say to you, we recognize to fully maximize the value of Menin inhibition in these various indications, I think we've said this before, at some point we would likely need to engage a partner in some sort of strategic relationship because that's just what it's going to take to generate multibillion dollar sales numbers in a multiplayer market. With respect to your specific questions on the 007 study in Ven/Aza, I guess a couple of clarifications. So the significance of seeing responses in patients who are Venetoclax failures is, these are single arm dose escalation studies. I mean, you're really kind of squinting at times to say what's clinical activity, but it's pretty well established for patients who failed then, they don't respond to then retreatment. That I think most physicians will agree with that. That is a disease of high unmet need. How is that happening? Is it that we're blocking a driver mutation like an NPM1 or a KMT2A? Are we blocking MCL1? Are we interacting with BCL2 to re-sensitize the tumor. We're still figuring that out. What does appear to be clear is that menin inhibitors plus ven are better than ven alone. That seems clear. To your question, I don't think you would go menin aza. I think you might go Venetoclax menin inhibitor, and do the doublet. You may not need the aza. And as we've talked about in the past, we will do that experiment when the time is right. We'll actually ask the question, do we need the triplet of Ven/Aza menin or can the -- will the doublet suffice? And that's something you just have to figure out empirically. But going back to 007, and again, I'll acknowledge our colleagues at Syndax, we've both seen activity in Venetoclax failures. And I think that's highly encouraging of the clinical benefit that these menin inhibitors can provide.

Great. Thanks for taking the questions.

Sure.

Your next question comes from the line of Brad Canino with Stifel. Please go ahead.

Hey, good afternoon. Troy, how important does response durability become at your next combo data update?

I mean it's important, Brad. It's always important. But I would say I cautioned people at the time with the 200 milligram dose. We're looking at an immature data cut in a dose-escalation study. So I'd be careful not to over interpret. Ideally, you should be seeing a direction of travel that is better than the monotherapy, right. Will the data be mature enough? Hard to say. We're still I mean, obviously, we haven't dosed a patient yet at 600 milligrams. So if we were to disclose in the next several months, we'll be limited in terms of what we can say about durability. I do think it's important. We have every reason to believe as we go into combinations, as we go earlier, durability will improve. There isn't anything that's suggesting, there's nothing we're seeing we're seeing from others that would suggest that that wouldn't be the case. I wouldn't have an undue reliance on that one data point. What I would be looking for Brad is, can we combine effectively at 600 milligrams with those standards of care? Because if you go back to the monotherapy, that's the optimal dose from a monotherapy perspective, it maximizes exposure after that it plateaus. It should be no different in the combos. That's the critical datapoint to look for. The durability will come in time, and I think we're cautiously optimistic it will inform in the right direction.

Okay. And then another question. We talk a lot about potential best-in-class drug properties on this call and in others. But as we move towards more substantial Ven/Aza triplet data from both you and other menin inhibitors that are being developed. How do you expect potential differentiation might emerge in those clinical data reported in the Phase 1, 2 studies?

Yes. So it's going to take the form in a couple of different ways. So there's a -- I would say, does one need to hold the menin inhibitor to allow counts to recover? That's question number one. And when you get out into the real world in a broader population? If you have to hold the menin inhibitor, that potentially gives the disease a chance to escape. The second is, one of our competitors presented data in a post-transplant maintenance study, and you can look at the rate of dose reduction or interruption or discontinuation due to AEs. And with several menin inhibitors we're seeing a high rate of Thrombocytopenia that is not on mechanism. That's something else. We don't see that a couple of the other compounds don't see that, but that is a characteristic of some menin inhibitors. So I think, Brad, it's going to go kind of both directions. Number one, can you keep constant pressure and constant exposure? Number two, can you really saturate all the sites in the body on a sustained basis? I would argue to you that if you can bathe a patient in a menin inhibitor, essentially indefinitely with no talks, that's probably the best thing you can do to delay recurrence. I think that's a good setup for

Very helpful. Thank you.

Sure. Thanks.

Your next question comes from the line of Eva Privitera with TD Cowen. Please go ahead.

Hi, good afternoon. Thank you for taking our questions. So with escalation going really well in 007 and the RP2D expected mid-year, when could

Yes. Eva, thanks. You saving the best questions for last. So in terms of timing for development, it's a little bit early. We recognize again it's a competitive landscape. I think realistically, you probably wouldn't dose a patient in a pivotal until early next year. But you can imagine, we're already putting the designs together on the basis of the data we've generated thus far, right? Based on what we're seeing in the 007 study, I think we're highly encouraged. It's a matter of dropping the data in to support it. A big part of that is the lead time to actually engage with global health authorities. You could potentially have the study up and running by the end of the year, but it would be very aggressive to dose the patient. I dare say it would be impossible to dose a patient, just because these things take time, right? And we do need to do the expansion to make sure that we validate the dose. As for your question about MRD, probably not an endpoint at this point. I think there are a number of parties that are working as part of a consortium to try to help the field move in that direction. It's not likely to be an endpoint, but it is likely to be supportive. We do think that there's likely to be an integrated design where you'd go with an accelerated endpoint, probably based on response, and then a full end point based on survival. And the agency has been pretty clear that's what they're looking for. Project FrontRunner, they want to see that as a first approval, but the themes of Project FrontRunner carry through to designs. How can we do a seamless design? And that's very much what we'll be looking at here in the various combinations.

Thank you. That's helpful. And a quick follow-up on an earlier question about additional genetic subtypes, where you're pursuing other activity. Does this patient selection algorithm enrich for the HOX/MEIS transcriptional pathway?

It -- so there is an association, Eva. I think we remain unconvinced that if you use HOX/MEIS expression as your selection algorithm that that's going to work. What we're doing instead is mutations, which are a proxy for that. What's clear is, this is a central node, right? This biology is fundamental to leukemia. It's wired into MCL1 to BCL2 to FLT3 to IDH. I don't think we fully understand all the wiring. So, we're going to do our best and see if we can enrich for a signal. And I think we're particularly optimistic of what might be possible when you then go and layer that on top of say example, Venetoclax or FLT3 or something that might give you an extra on. Back in the 1a, 1b days, people kind of shrugged. Everybody wants to see a CR, right? But actually blast count reduction, sustained disease stabilization in this setting is really clinically meaningful. And it's telling you like spend more time here, look here, it's giving you a little neon sign. So that's what we're doing. And we'll see where it goes. But, it's associated with HOX/MEIS, but it's not -- it's just an association. It's not going to be a direct correlation. I hope that helps.

That helps a lot. Thank you.

Sure.

I would now like to turn the call back over to Troy Wilson for closing remarks. Please go ahead.

Thank you, Eric, and thank you all once again for joining our call today. We'll be participating in several investor conferences over the next couple of weeks, and we look forward to seeing many of you there. In the meantime, if you have any additional questions, please feel free to reach out to Pete, to Tom, or to me. Thank you again and have a good evening everyone.