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

Well, good morning, everyone. My name is Jason Zemansky. I'm 1 of the SMID cap analysts here at BofA. Thank you so much for joining us on this -- on second day of our 2024 health care conference here in Las Vegas. I'm so pleased to introduce for this current talk, Troy Wilson, President and CEO of Kura Oncology. Troy, thank you so much for joining us.

My pleasure. Jason, thank you to you and BofA Securities for the invitation.

Absolutely. Well, maybe to start broadly to provide some context, especially for those a little bit newer to the story. Can you talk about the emergence of the menin inhibitors. I mean how did we get here? Especially when some of the mutant classes you're pursuing have been known or recognized for decades.

Sure. So spoiler alert, KMT2A or MLL has also known for decades. It just took us that long to really get chemical matter. Way back 20, 30 years ago, people recognized there were a class of leukemia called mixed lineage leukemias. They've done a lot of the genetics. It was the great work of a number of academic groups that figured out that there was actually druggable matter here. And that by developing menin inhibitors and they're called menin inhibitors because they block the interaction of menin with the MLL protein. It's also called the KMT2A protein. That basically -- by disrupting that protein-protein interaction, you disrupt a lot of downstream gene expression. And when I got involved, I was actually introduced to a group at Michigan that did a lot of the pioneering work by the Leukemia and Lymphoma Society and they had some pretty amazing nonclinical data in leukemia models, in vitro and in vivo. Along later, came the story around NPM1. There's another story around diabetes. There is potentially -- as we'll talk about, I'm sure, later this year, a story in solid tumors, I think, menin is going to end up being a really interesting target for a lot of reasons. And the work that we and other companies are doing in leukemia, I think, is just the beginning.

Well, great. I think that's a perfect segue. The next 12 to 18 months are likely to be pivotal in Kura's evolution. So let's walk through a number of upcoming catalysts. But -- given the background that's inherent in this question, you announced yesterday, enrollment has been completed for the registration of KOMET-001. This is a study of ziftomenib monotherapy for RR NPM1-mutant AML. By any measure, this was extraordinarily rapid. Why do you think interest is so robust?

Interest is so robust because the drug works. That's the bottom line. Right? These are patients who, until relatively recently, this was a death sense. And these are very sick patients. Relapsed/refractory patients with leukemia have a very poor prognosis. And the power of menin inhibitors is, ziftomenib in particular, very encouraging safety and tolerability. So you're not dragging along a lot of toxicities with you. And something I didn't touch on in your previous question. You're doing something pretty fundamental. Most of the targeted therapies, they block enzymes. And that means you've got to block that enzyme 100% of the time. What a menin inhibitor does is it breaks up 2 proteins, and it actually tricks the cell from going from an immature cell to a mature cell. That's a one-way trip. So you only have to block that protein-protein interaction long enough to trick leukemic blast to become a mature cell, lives a few weeks, and it dies off. The power of that, Jason, is we're seeing activity in patients who failed IDH inhibitors who failed FLT3 inhibitors, who failed venetoclax, for example. We internally set a goal of 18 months for enrollment in KOMET-001, we actually came in at fewer than 16 months. Had we not had the 007 and the 008 trials also enrolling in relapsed/refractory, we would have come in even faster than that. And I think it's -- again, it speaks to when you have a great drug and you have a high unmet need, the patients come out of woodwork.

Yes, absolutely. Well, help us put this into context here. At the recommended Phase II dose, zifto led to 35% CR rates. Can you put this into context here for this patient group in leukemia, what does it mean? And then what should we expect moving forward, at least for the -- this new 85-patient cohort?

Yes. So what it means -- so there's 2 aspects to that to the response rate of interest in this trial. So the FDA has sort of given everybody informal guidance that it wants to see a 20% to 30% CR/CRh rate and a median duration of response of 4 to 6 months. We've never deviated from that. I think our competitors have never deviated from that. And the reason for that is the survival of a fourth line patient, for example, with these tumors is like 2 months, 2.5 months. So if you've got a median duration of response of 4 to 6 months, that's clinically meaningful in the eyes of the FDA. I would expect -- I'd love to say you're going to see a 35% response rate. The trial is ongoing. I don't think you're going to see that. I think you're going to see between 20% and 30%. That's what we designed the trial for. That's what we powered it for. If it ends up being greater than 30%, that's great. It doesn't need to be to satisfy approval. We did -- just last week, ziftomenib was awarded breakthrough therapy designation in this indication, and that's actually a higher bar than approval now in oncology. I'll remind everyone, if KOMET-001 is successful, that enables Kura to submit a marketing application for full approval. The other thing it means, I mentioned there were 2 elements to this. So 1 is you clear the leukemia. The other is you allow the patient's immune system to reboot and you get counts back. That's important because, unfortunately, many of these patients with leukemia, they die of opportunistic infection. So there's a very strong push, pull among physicians to find regimens that are not immunosuppressive because that patients can get into trouble. The fact that we saw 35% CR rate with full count recovery in that Phase Ib. Those patients all had essentially a full immune system after having this devastating leukemia. That's important because as we -- and we'll talk about, I'm sure, in the questions to come. As you now think about moving ziftomenib to earlier lines of therapy, you think about moving it into combination with other standards of care. The fact that it's so effective at clearing leukemia and yet it allows the immune system, it's absolutely non-myelosuppressive, non-immunosuppressive. That's a really powerful combination.

Great. I think that's a perfect segue. I know [ Cameron ] from the team was anxious to ask some questions. [ Cameron ]?

Thanks. So earlier this year, you provided your KOMET-007 update, first insights into Zifto combos with 7+3 and ven/aza, given the context of smaller population, cycles and dosing, what were your biggest takeaways from the data?

Yes. I think there were 2 takeaways, [ Cameron ]. And I think we were surprised as well as many investors and analysts. The first big surprise was there was 0 incidence of differentiation syndrome. We had -- so just briefly, as a monotherapy, these menin inhibitors are inducing differentiation. That's what I talked about. That is a class effect. They all do that. Ziftomenib is so potent, it's so tissue penetrate that when it's on its own in the KMT2A subset, which is about 5% of AML, it differentiates the tumor so effectively. It can put the patient into a crisis. A lot of people may be familiar with like tumor lysis syndrome, same idea. It's called a differentiation crisis. We had said, when you do it in combo, that problem should be mitigated. And in fact, it was that we saw 0 instances of differentiation syndrome. I said at the time, I'll say it again, [ Cameron ], don't get emotionally attached to 0%. It's not going to be 0%. What you want it to be is low, manageable, Ideally, you give the patient a couple of days of steroids. They stay on drug and the differentiation. It never really becomes medically significant. That's where you want to go. That was the first big takeaway. The second big takeaway, I think, was even at a 200-milligram dose the combos were more effective than I think people expected. We saw 100% CR rate among 5 patients in the 7+3 cohort. The benchmark there is 30 to 35. That's the -- if you think about the control arm for the Jazz product, the chemo product, that's about what you saw. In the venetoclax azacitidine, it was more active than zifto alone. And importantly, it was active in patients who had already failed ven HMA. So those patients -- physicians will tell you, if a patient has failed ven HMA, they don't have a lot of options left, and yet you're seeing both for Kura and for Syndax, you're seeing a significant number of patients who are responding. That's the 200-milligram dose. The cohorts are now enrolling so quickly. We're at 600 milligrams with 3 of the 4 cohorts. We're at 400 milligrams in the fourth cohort, the KMT2A 7+3, but that, again, I -- we are more than 70 patients on study at this point, and that's almost as large as the monotherapy registrational study. That's why I say to you, we have to be careful not to create internal competition among our studies, but people are just clamoring to get on ziftomenib. The enrollment has exceeded our expectation, but we had pretty high expectations.

Great. And then maybe to provide some additional context here. There's optimism from the team that Zifto is going to be an ideal combo partner, especially when you think about safety profile. While these data were admittedly early, I guess, your expectations here? And can you kind of talk on that?

It did. It did. I mean we -- I think we were always optimistic. And I actually -- on the question of differentiation syndrome, I actually want to acknowledge, we have Bristol Myers Squibb as an equity investor in Kura. They made an equity investment attached to a right of first information. They were -- they actually strongly encouraged us to do the regimen that we're doing, which is 7 days of the backbone and then ziftomenib on day 8. They actually encouraged us to do that across the combos. That was a very good advice, right? They do research, development, commercialization in the space. They were spot on. I would say, [ Cameron ], something you said. So what do we know from that combo? No DLTs, no DDIs, no QT, no additive myelosuppression. Everything is looking good from a safety and tolerability perspective. You have to have -- a best-in-class agent is going to rest on a foundation of best-in-class safety and tolerability. That allows you to push the dose. That's why we were able to escalate so quickly to 600 is that -- once we've tweaked it and we figured out how to mitigate DS, we were off to the races. And everything else at that 200-milligram dose looked good. Looked I think as good or better than we expected. That's continued to look good as we climb through the cohorts.

Perfect. And then what duration and/or patient numbers would you need to see to maybe extend the confidence from this initial update or maybe what constitutes a full data set here?

Yes. That's a great question. So there's really at least 2 full data sets. So I mentioned there are 4 cohorts. Each cohort is 3 doses. Each dose is 6 patients, help your children learn like their multiplication tables. That 72 patients all in, we are over enrolling in some of those doses. And I'll remind you in ven/aza, we're recruiting in relapsed/refractory in 7+3, we're recruiting in patients who have adverse risk. Once the team identifies an RP2D, the Safety Monitoring Committee that can then waive the trial on to the expansion cohorts. We said on our earnings call, there are 7 potential expansion cohorts. Imagine NPM1 and KMT2A, now your frontline ven/aza, your frontline 7+3. No adverse risk. You are ven Zifto, I'm probably forgetting 1 of them. Oh, and you're still going forward in relapsed refractory. That's the expansion phase. There's a couple of big media updates. You should expect safety, tolerability, clinical activity to get even better as you go into the frontline setting into healthier patients. The fact that it's already so good in the relapsed/refractory, I think bodes well, but let's see. We haven't been a lot more specific, but that's the way we think about it is the expansion piece -- sorry, the escalation piece and then the expansion piece. And yes, I think we're moving towards that as fast as we can.

You're looking at 2 separate mutational subclasses. And so I'm curious with the data trickling in, does it appear that Zifto is more potent in, say, NPM1 versus KMT2A or vice versa at this point?

I think it's fair to say that KMT2A is a slightly higher bar in that if I had a criticism of the data at 200, it's perhaps that you wanted to see more activity in the KMT2A population that may come with higher dose. The KMT2A that's a very, very difficult prognosis. In terms of their sensitivity to Zifto, there really isn't a difference. In terms of the biology, the presence of co-mutations, when you're getting patients in the relapsed/refractory setting who failed ven, who have failed targeted therapy, who may be on multiple transplants, it's so confounded. It's hard to make sweeping statements. We've been very encouraged. I will tell you, and I think, again, our competitors will agree, physicians will use these drugs in combination. That is -- and in fact, if you give them the choice, we had to encourage them as the monotherapy study was enrolling. You can see how fast the combo is enrolling alongside help us get the monotherapy enrolled so we can get the drug approved. They will use these drugs in combination. We have to be careful with commercial promotion about what we do. But ultimately, that's where you're going to end up. In combination, ideally is early in the treatment course as possible and then keep them on menin inhibitors and maintenance.

Got it. Just out of curiosity, what is the benchmark for both 7+3 and ven/aza in these settings? I just kind of want to put a line in the sand in terms of beating that line to kind of justify that interest in using menin inhibitors?