Kura Oncology, Inc. (KURA) Earnings Call Transcript & Summary

My name is Peter Lawson. I'm one of the biotech analysts at Barclays. I have the pleasure of covering Kura Oncology. Up on stage with me, I've got Troy Wilson, President and CEO, and also Mollie Leoni, the CMO.

The questions we have been asking today have just been kind of some macro questions around whether you think there's any impact on the supply chain with tariffs and any worries or learnings from COVID as we think about the new environment that we're in.

Sure. First of all, thank you, Peter and Barclays, for the invitation to participate in the conference. With respect to the macro, during COVID and actually during the BIOSECURE debate, we actually took a long look at our supply chain and made some adjustments. So, we at Kura specifically aren't experiencing or anticipating any kind of disruptions or slowdowns from either tariffs or any of the kind of macro features as well as there are some questions just around federal head count and the agency, the FDA, we're also not expecting anything there. But we're being vigilant, and we'll be prepared in the event that happens.

Have there been any changes in the rate of communication and any levels of confusion there?

No, not that we've seen. It's been pretty much just business as usual. We've not seen any difference at all.

I know you're funding your own trials, but are there any kind of knock-on effects that we should be thinking around for NIH budgetary funding and if that trickles through to clinical trial sites?

I think that's a longer-term issue. The trial sites, back to your question around COVID, a lot of the trial sites are still recovering from the bolus of trials that went through during COVID. Unfortunately, a lot of those clinical sites have lost staff due to the sponsors, who are recruiting good people out of the clinical sites. So that's a constant kind of work in progress. We haven't, again, seen anything immediate from any of the NIH cuts. That will probably be a longer-term issue for the sector.

And maybe before we dive into the Q&A around the various aspects, but if there's any state of the union or any initial lead-ins you want to prepare or talk through around catalysts that we should be thinking through over the next 6 to 12 months?

Sure. Yes. So as we look out 6 to 12 months beginning with ziftomenib, we're expecting to submit an NDA next quarter. Hopefully, that would lead to a review this year and, potentially, commercialization either late this year or early next year. That's in the monotherapy setting. In the combination setting, we will initiate the 2 Phase III randomized trials in the fit and unfit segments later this year. We're guided to the second half. I think we'll talk a little bit about the timing there, but that's really a big push into the front line. You'll see us continue, Peter, to innovate in the AML space. You'll see us starting the trial in GIST with ziftomenib and imatinib. We're quite excited about that. And then you'll see us release data for the FTI program here in the second half, potentially at ESMO. And that will, I think, hopefully start to get people to pay attention to the FTI programs. So if you look back, I mean, we are, particularly in these challenging times, extremely well-capitalized, financially de-risked, I think, scientifically and regulatory de-risked. And at this point now, we're looking at how we can make a big difference for patients, whether it be in AML, in GIST, or in solid tumors. We're hoping to have clinical data at every major medical meeting this year and on into next year. So, it's going to be a good year. It's tough out there in the markets, but we're in the enviable position of being able to keep our heads down and just execute.

And then just specifically around the COMET-1, and you've got the 2Q top-line data. Where do we see that data? Is that kind of an ASCO thing, abstract? How much do we see?

Yes, potentially at ASCO; that's where we've submitted it. The abstract release, I think, is in late May. The titles come out a little earlier than that. We're hopeful. It is a positive pivotal trial. So we're hopeful that it gets a proper venue.

What should we expect to be seen in terms of CR/CRh rates and response rates in that data set?

Yes. So we've consistently guided the trial was designed to deliver between a 20% and 30% CR/CRh rate. I think we've never once wavered from that. It is within that range, and I think we've said it's not on the boundary. So in terms of the safety, tolerability, clinical activity, we think it's going to be very competitive with what's already out there. We look forward to sharing that data initially in the abstract and then hopefully in an oral presentation, potentially, as I said, at ASCO.

How should we think about patients who are pretreated with venetoclax? Does that have any impact on the results, and/or does that matter?

So I can't really speak to the second half of the question of whether it matters. The first half of the question is whether the rate of venetoclax pretreatment is consistent with what we saw in Phase Ib. And so that will be one of the things. If we look at the forest plot, I think that will be one of the things that we can talk about when we have the data. It's actually a really interesting data set, and we're looking forward to sharing it with you.

And remind us of the number of patients you expect to see. And then also, I guess, on the side effect profile, is it differentiation syndrome that we hone in on? Or are there other components that we should be thinking about?

Yes. So the number of patients, we overenrolled in the pivotal registrational study. I think it's 92 or something like that. Is that right? In terms of the safety and tolerability profile, yes, I mean, the big questions for the class are the presence or absence of drug-drug interactions, QT prolongation, myelosuppression, and differentiation syndrome. Those are the 4 things you watch. Because that's what's going to impact your ability to combine with other agents. I think you'll see that we score very highly on all 4 of those metrics. And Mollie is going to speak to it, I know in your next set of questions, but I think the safety and tolerability of ziftomenib on a once-daily schedule is part of what has allowed us to combine so effectively with the standards of care and is what is driving enrollment to be so robust. It's very, very easy to work with. Differentiation syndrome, Peter, as you know, really wasn't much of an issue in the NPM1 segment as a monotherapy, and it really becomes well-managed, well mitigated in combination.

And then, are you on track for the BLA submission?

We are, yes, and we are for the NDA.

What are the gating factors that we should be thinking about?

The team thought we were like whipping. It's really down to the team doing the work to put the application together. It's 90-plus percent of the way there. You're just finishing it off. There's a lot of QA and QC that goes into it, but it's in very good shape. We're on track to hit that second quarter, and the team will hit it.

But it's not kind of last minute 2Q, you're thinking.

No, I don't think it's less. We try now to give ourselves some room to breathe, some room to maneuver. So we're in good shape; the team has done a phenomenal job. And then COMET-07, so the fit population, 7 plus 3. And for that data set, when should we expect that? 2Q? And kind of what do you want us to hone in on that data set?

Sure. So, yes, Q2, as Troy said, we're submitting to as many major conferences as we can with our data. So you're going to want to hone in again on the safety, tolerability, and combinability. That's the biggest thing. That's where drugs win or lose their combinability. And then, of course, just to continue to see the positive trends we set in the data, we've already shared previously at ASH a continuation of really good efficacy and safety in these patients.

And for that combinability and what we should hone in on, are there particular segments of that safety profile that we should be focused around?

For the 7+ 3, the patients continue on with our drug as a monotherapy for significant periods of time in addition to using it in combination with the backbone therapies. However, you'll notice that patients don't require dose reductions or dose interruptions, et cetera, to handle adverse events when they continue on as a monotherapy. That will be a very important piece to hone in on.

For the 7+ 3 alone, what's the best bar that we should be thinking about?

I was thinking about this. It's a 70-year-old treatment, so there are so many references out there. But usually, the ranges are between 50% to 80% for a complete response rate in these patients. NPM1 is probably higher, probably closer to that 80%, and KMT2A a little bit lower just because they have a harder time with all treatments in general.

And what's a good bar for success when you add on top of something that's already getting kind of 80%? Or do we think about it in terms of durability, et cetera?

Yes, that's exactly right. At this point, with adding targeted therapies on top of these really good backbones, it's like, for instance, with the quizartinib trial, they didn't see a significant increase in the complete response rate. They saw a significant increase in durability and overall survival. And it's looking for markers of that increase in the durability and the overall survival that are extremely important because it is hard to make an improvement upon an enormous CR rate in the backbone. So that's why this MRD-negative CR endpoint becomes so important because it likely is one of the best markers to be looking at for that increase in durability and increase in overall survival.

And then I guess moving on to the unfit population, the ven/aza. What should we be thinking about for the ven/aza arm? And what's the appropriate bar for ven/aza, and where do you want that to go? And again, around durability, how should we be thinking about that?

Yes. So the VIALE-A study, which is still the premier source of information, puts the CR rate at about 38% for these patients. Obviously, people are used to seeing the mixed CRC rate, where it gets you closer to 60%, but the FDA is only focused on CR. So you'd want to see about 40% with the ven/aza backbone alone. So we do look to improve upon that 40% in the front line.

Do we get any other doses with the updates? Do we get higher dose levels with --

So when we share this data, you're going to be seeing for the first time the frontline ven/aza data because we did our dose escalation in the relapsed/refractory setting. So you'll be seeing the ven/aza at the 600-milligram dose level. And so again, safety and combinability are the first, second, and third things you should be looking at because if you can't combine it well, if you have to keep reducing the venetoclax or interrupting the ziftomenib, it would be a problem. But luckily, these are not things we are seeing because it is so easily combined.

So here's no worry that physicians in the real-world setting will end up dose-reducing one of these components, whether it's --

I think that's actually the goal. I think physicians would love to be able to back off on the venetoclax dosing at least the amount of dosing per month because we see that in the real world. It is very toxic, and these patients have a hard time with that and with infections and with bleeds and everything else. So if we have a drug that can help get these patients into a response, help maintain them in their response, and you can lessen that backbone therapy, you're actually making a huge improvement for these patients. As we shared in the previous update, we got an agreement with the FDA to formalize a dose reduction for the venetoclax backbone in our pivotal trial so that we do not have to adhere to label dosing and can go to a lower dosing over the course of the trial.

Housing would be proceeding as you think about the ven/aza versus the 7+3 combination. Is there any kind of delta between the 2? Is there anything to read between the lines?

They are both keeping the team extraordinarily busy. The enrollment rate is extraordinarily robust. It does appear that 7+ 3 is still the treatment of choice for the majority of these patients. But still, the enrollment is incredibly quick for both patient populations, the ven/aza and the 7+3.

Is there any reason to believe menin is going to combine or generate better results with 7+3 versus ven/aza?

Certainly not combined better. There's theoretically always been that assumption that maybe there's some synergy with venetoclax. But the populations are so different that you're not going to be able to compare head-to-head to 7+3 and the venetoclax patient populations, but they both do very, very well on treatment, and it's a very robust effect.

What's the read-through from these studies to the frontline study? And you mentioned the frontline data with ven/aza 600 milligrams. Are there other read-throughs we should be thinking about triangulating between this data set and future data sets?

It's really taught us a lot. I think, as you've seen with others developing in this space, it was the belief that it was venetoclax and azacitidine that was the preferred combination partner. Our data, our experience, and our investigators and KOLs have shown us that, that is not necessarily true that it really is both the 7+3 and the ven/aza that are extremely important to developing this molecule. That's one of the biggest read-throughs we've had from our trial in general. And secondly, it's the ability to get these patients on, get them into a response, and maintain them, at least for the NPM1s in that response, without necessarily having to go to transplant. And these patients are doing overall, especially the NPM1s, extremely well not having to go to transplant. And if you can avoid that toxicity, it's huge for this population as a whole.

And then, thinking about 017, what are the timelines for initiation for that pivotal study?

So, as we shared, we've obviously already had our regulatory interactions, and we hope to be fully operationalized and enrolling by the end of the year.

What are the gating factors there?

I was saying to Troy at one point, my team is going to kill me if we do not stop pressing them to do everything very quickly, all at once. But it's really just operationalizing. It takes time to get the sites up. It takes time to get the contracting done. That's where we are now. We're in those bureaucratic hangups rather than any scientific jiggering or anything from our end. It's really just actually getting through the red tape.

We're in the process of studying startups. And for big global trials like this, that can take a while, the contracting, the budgeting, just the blocking and tackling that has to happen for sites to open and a study to begin.

And that's why we did it as 2 studies in 1 because now we only have to do it once rather than twice for ven/aza and 7+3.

It's a clever design. And just the rationale for the partner, Kyowa Kirin, what do they add to that process? Do they slow it down? Do they speed it up?

Yes, they've been very addictive. They definitely don't slow it down in any way. I mean the first, I think, is obviously financials. So you commented on the trials, it's a clever design. You're doing 2 Phase III studies under a single protocol. There are some significant operational synergies that I don't know we could have done alone with just the capital markets as our partner. That would have been challenging, particularly given that we haven't shown frontline ven/aza data yet. So we're starting Phase III when you and the market haven't yet seen the ven/aza data. Obviously, Kyowa Kirin has the FDA have. So that's part of it. In terms of operationalizing it, Kyowa Kirin has people on the ground in territories where we just have no hope. So Europe, Asia, these are going to be global studies. And sometimes it's helpful to have someone there who can go and just physically walk around the site and help keep things lubricated and keep things moving along. We are, of course, driving global development. We're driving commercial strategy, but Kyowa Kirin, we're being very thoughtful with them about how we can work together to help move things forward. And then the final thing, Peter, is there are 2 additional opportunities that are under the collaboration in AML. One is in the frontline FLT3 population. One is in the post-transplant maintenance population. Remember that those are also included under the collaboration; you'll see us take those on in due course. So it really gives us the ability to compete effectively in all of the relevant segments of the frontline population.

And the MRD-negative CR, that's changed the field, and I guess, what drove that? Are all the new trials in the frontline, do you think going to be MRD-negative CRs?

Yes. You have to realize we've been thinking about this for 4 years and preparing for the idea of this for 4 years. So the fact that it's actually come to fruition is a testament to the team and its preparation. Yes, I think it will help change the field. I think it will help get at least 4 patients treated more quickly. And it's something that our KOLs are extremely excited about. I get texts regularly congratulating us and thanking us for helping to pioneer this.

And then, how should we think about interim analysis? When would you want there is that built in?

So we had previously shared that we expect the data for the accelerated approval, which would be the MRD-negative CR in 2028.

And the expectations of the control arms, whether it's for the MRD-negative CR rates or event-free survivals.

Sure. So again, we're looking in the bone marrow for the MRD negativity. In the bone marrow with KMT2A, you're seeing in the 30%-ish area of MRD negativity, and in the NPM1, a little higher in the 40s. So depending on the mixture of patients we see, we expect to see about that control arm a 40% MRD negativity rate.

In just 3 minutes or so on the clock, I'd love to pivot a bit to the diabetes program and what we should expect to see over the next 6 to 12 months.

Yes. So our next goal is to nominate a development candidate for clinical development in diabetes. We have a range of potential candidates that we can choose from. One has to kind of ask like what exposure do you want? Do you want it to be a menin degrader or just a menin inhibitor? We have all of it. We have all of the various flavors. So I would look for us to nominate that candidate. We are currently evaluating different options for moving it forward into the clinic. We want to be mindful that we keep the company in a strong cash position, and we maximize the value for patients and shareholders. So we're running multiple options in parallel, and we'll have more to say about where we go beyond the development candidate in due time.

So the assumption would be it's probably not just your own spending as you go into something like that.

Yes. I mean, you could do some modest early clinical development, but I think it probably isn't appropriate for an oncology company to be considering doing mid- to late-stage diabetes trials, right? That's big pharma stuff. And there's certainly an appetite for novel therapies in diabetes, as you know.

And does the competitor menin drug, does that kind of help inform that process? Or are you looking more broadly?

You take all the data into account. At the moment, I would say we really only have preclinical data. Our preclinical data would not have us limit the utility of a next-gen menin inhibitor to what they're doing. I'm not entirely sure why they're making those decisions. We think there's an opportunity in both type 2 and type 1. And that's part of thinking about, Peter, how you develop it clinically and commercially; you want to maximize the value. And we'd also ideally be in a position where maybe you could take more than one menin inhibitor forward because when you're talking about millions of patients, I think you really want to have the very best compounds move forward. We certainly have the chemical material. We have our chemistry group, which is phenomenal. Now, we just have to find the right way to translate it into the clinic.

And so degrader versus inhibitor is that -- where are you in that?

Yes. And that's just one example. I can tell you, ziftomenib hits menin about as hard as it can be hit. It's not obvious to us that you need to hit it quite that hard in diabetes. You may be able to dial it back, you may actually want to do that.

Okay. It's perfect. Thank you so much.