Good morning, everyone. Thanks for joining us. My name is Jonathan Chang. I'm part of the Leerink Partners Equity Research Team. It's my pleasure to host the management team of Kura Oncology. We have with us today President and CEO Troy Wilson and CMO Mollie Leoni. Thank you both for joining us.
Pleasure.
Let's get started. Would you like to briefly introduce the company?
Sure, Jonathan. Thank you. Thanks for the invitation to participate in the conference and for hosting this fireside chat. Kura is advancing a pipeline of targeted therapies in oncology. Our lead asset is a menin inhibitor for treatment of acute leukemia. We are expecting to submit an NDA, a new drug application, in the second quarter. Hopefully, that will support an approval around the end of the year, and then we would look to launch that. We have an expansive development program, which I know we'll talk about. We are undertaking two phase three trials in the frontline population in AML.
Beyond that, we're looking at other indications in AML, as well as menin inhibitors in gastrointestinal stromal tumors, a trial which will start later this in the first half of the year, solid tumors and diabetes, as well as our pipeline of farnesyl transferase inhibitors, which are directed at large solid tumors. The final thing, Jonathan, I'll share is we are in a very strong and, I think, de-risked position financially. We had $750 million, approximately, in cash and cash equivalents as of the end of the year.
We are on track to receive an additional $420 million in near-term milestones under our collaboration with Kyowa Kirin. That will do two things. It should give us cash into 2029 through commercialization of ziftomenib in the frontline AML indications, and it should allow the company to stay in a very strong cash position as we prosecute our pipeline.
Great. Thank you so much for the introduction. What do you see as the potential opportunity for the menin inhibitor ziftomenib in AML?
Yeah. Maybe we can talk clinically and then commercially. In the relapsed/refractory setting, you're really looking to improve these patients' quality of life to sustain survival. We would expect durations of treatment of approximately six months. The frontline setting is quite different. When you treat patients at what we've seen with menin inhibitors in the frontline setting, you're able to do two things. It looks like you're able to deepen responses. You're able to extend the duration of responses.
In the case of the NPM1 population, which is about a third of AML, we're seeing fewer patients needing to go to transplant with all the complexities. What that means commercially, Jonathan, is the relapsed/refractory market, our best guess is that's several hundred million dollars. I think we've guided to $350-$400 million.
The frontline indication is our best guess is ziftomenib could drive peak sales in AML of $3 billion, and the total class could drive peak sales in the US of approximately $7 billion. The way we get there is we think menin inhibitors will treat half patients with AML, think about durations of therapy of 12-24 months, and then we've seen analog pricing from one of our competitors in the menin space. It is a significant opportunity and one we think is ripe for innovation.
Understood. Can you discuss the path to the frontline opportunity and discuss maybe the KOMET-017 studies?
Sure. You want to take that?
Sure. Yeah. Our plan has always been to be able to get our menin inhibitor, ziftomenib, to the broadest patient population, essentially have a spot for anyone that has a menin pathway-dependent leukemia. The best way to do that is in the frontline. Currently, we have designed our KOMET-017 trial and are operationalizing it so that we can start enrolling by end of year. It is a trial that essentially contains two studies in one, one for the fit population and one for the unfit population.
For the fit population, they can receive 7+3 in conjunction with ziftomenib versus placebo. In the unfit population, it is venetoclax/azacitidine plus ziftomenib versus placebo. With that, we hope to be able to obviously treat both the fit and unfit.
The 7+3 portion of the study is designed to really focus on being able to keep these patients on their post-consolidation maintenance, so post-transplant, etc., to be able to stay on therapy for very long term.
Understood. Can you discuss the utilization of MRD negative complete response as an endpoint and the 017 intensive combination study?
Sure.
Maybe also provide some color on the regulatory interactions.
Right. In designing a trial to get it to your frontline patients, if you go with a normal "full approval" endpoint, it's many years in the making before you're going to be able to get this therapy to patients. The FDA does have a method called accelerated approval that'll help you get there a little faster with an endpoint that they feel is a surrogate for overall survival. To this day, they've really only used complete response as that endpoint.
With 7+3, the complete response rate is so high with the backbone that we had to get creative and come up with something else. That something else is MRD negative complete response, so minimal residual disease negative complete response.
This is something we proposed to the FDA as an accelerated approval endpoint, and they agreed to the endpoint with, obviously, the caveats that we provide all the necessary data at the time of submission. It was a big win for both the patients and for the field in general. Our KOLs are thrilled that now this will help them get drugs to patients much more quickly in the frontline.
Understood. How should we be thinking about timelines associated with the 017 studies?
We have previously guided that we will have that readout for the MRD negative CR in 2028. Obviously, the full approval will be coming after. We have not yet guided towards our venetoclax/azacitidine accelerated approval readout or full approval readout.
Understood. You've already touched on the cash position that you have, Troy, earlier in your introductory comments. How would you say the Kura-Kyowa Kirin partnership is helping facilitate your goals with ziftomenib more broadly?
Yeah. No, absolutely. There are three aspects to that, Jonathan. Excuse me. The first aspect is our ability to invest in maximizing the value of ziftomenib. The second is what we can do commercially to compete in the marketplace. The third is the pipeline. As Molly mentioned, not only did she and her team secure these pathways to accelerated approval, but very cleverly put two phase three trials under a single protocol. That allows us to operationalize that trial once, which is where large pharma companies can run circles around smaller companies. It is just the site activation, the contracting, the budgeting.
Kyowa Kirin is giving us support in territories where we, frankly, do not have people on the ground. They were involved with and supportive of the design.
It'll really be we get operational synergies out of running the trial, and we can invest in running these two trials in parallel such that we now have a protocol that's available, as Molly said, to nearly anyone in the frontline. That's a significant investment. Those trials are approximately $200 million-$250 million each. For a company our size, we can take these on. We can be very competitive with the other competitors in the menin space.
The second is we're working under a co-commercialization agreement with Kyowa Kirin. Kyowa Kirin is actually funding half of the commercialization expenses in the US, and we are prepared to compete for every patient. We think we're going to be very competitive in the space, and we're going to be out there both promoting on the label and educating about the benefits of menin inhibitors.
The final piece, Jonathan, and one that's perhaps overlooked, but I think is important, particularly in these challenging times in the markets, is this partnership allows us to also invest in our pipeline. As I mentioned, we'll be starting a trial evaluating ziftomenib in GIST. We think that's potentially a blockbuster opportunity, pursuing menin inhibitors in both solid tumors and diabetes.
As we've said, we're going to show data on our farnesyl transferase program later this year, potentially at ESMO. We would be very challenged to do all of this had we not done the partnership. It is allowing us to really invest for the future, to invest for growth.
Got it. And how do you see ziftomenib positioned in the competitive landscape?
Our hope is, again, we will be a significant segment of the market in up to half of all AML patients across all lines of therapy. Zifto continues to, Molly actually said to me very early in the development program, this is a drug that is intended to be used in combination. People lose sight of that as they watch the evolving monotherapy data. If you've seen our data at ASH, you'll see our upcoming data potentially at EHA and then later this year at ASH.
The clinical benefit just gets better as you go earlier and as you go in combination. Zifto is so active. It's so tissue penetrant. It's so well tolerated. We think it really could be the premier choice among physicians. It doesn't have any of the liabilities of some of its competitors as far as safety and tolerability.
That's what's hampered other drugs in the AML space. It's not a lack of efficacy. It's that patients have to either dose reduce or discontinue due to challenges with tolerability. We've not seen any of that with ziftomenib. I mean, we have a lot of work to do, but everything we're seeing and everything that Kura Oncology is seeing tells us that we need to invest aggressively and compete to try to maximize market share.
Understood. Earlier this year, you disclosed that the KOMET-001 registrational study in relapsed/refractory NPM1-mutant AML achieved the primary CR/CRh endpoint. When can investors expect to see those results, and how should we be thinking about the upcoming data?
Yeah. We have submitted the data for presentation at a major medical meeting here in the U.S. If the data is accepted for presentation, you will see the titles and then the abstracts. Our hope is that we get a highly visible venue in which to present the data. There may be an opportunity to present the data subsequently at another medical meeting. We will see. That is what we would guide to at this point. Again, assuming it is accepted, Jonathan, we will be able to speak initially to the abstract and then ultimately to the full data set, hopefully, again, at ASCO or potentially at EHA.
Understood. Can you talk about why you, I guess, we haven't seen more details around the top-line results from the initial disclosure?
Yeah. The number is the primary endpoint. Everybody wants to know the number, right? We have said it is 20%-30%. It is not on the boundary. It is stat-sig. There is no new safety. We understand in this environment people are impatient. The rules of at least one major international conference are very clear. If you disclose that, you put yourself at risk. It is not an absolute, but we have to make a decision. We are a more mature company now. We have an obligation to patients.
We have an obligation to physicians. We are potentially in a launch year. It is either this year or next year, hopefully. We need to get this data out to as high a visibility audience as we possibly can among physicians.
We do not want to put that at risk by disclosing the top-line results because your next question will be, well, why is it that number and not some other number, right? And then, well, what about this? Well, what did you see? Well, it is death by a thousand cuts. So understand, if I had it to do over again, I would have guided top-line results, perhaps, with data to follow at a major medical meeting.
I think we did the right thing. We did the right thing. If you do the right thing for patients, we can accept a little bit of short-term pain. We are looking forward to sharing the data and walking people through the full data set. It will be very competitive with what is out there.
Understood. I think you mentioned this earlier, but just to clarify, what are the timelines for the NDA submission?
We've guided to second quarter. We're on track to hit that. It's coming up on us quickly.
Yeah. Got it. Now, of course, you also touched on the combination data. This is for the KOMET-007 study with phase one B expansion cohort evaluating ziftomenib with intensive chemotherapy, the 7+3 expected in Q2, I believe, and ziftomenib with venetoclax and azacitidine in the second half. Can you discuss the combinability of ziftomenib with standard of care drugs in AML?
Yeah. When you're looking at a drug and whether or not it's going to be successful, the first, second, and third thing you should look at is its safety profile and your ability to combine it because ultimately, in the oncology space, that's the most important thing. That's the only thing that will allow you to get to the appropriate level of efficacy to really help patients. As you've seen from some of the data we've presented and as you will continue to see, ziftomenib remains extremely combinable, very easy to combine.
With 7+3, these patients combine it. They started on day eight, and then they continue on therapy as they go through the backbone therapy and even complete the backbone therapy. They maintain on it even after they complete their consolidation, be that chemotherapy or a transplant.
With the venetoclax and azacitidine, these patients are able to go on therapy, stay on our therapy from day eight continuously, and not have to reduce the dose of venetoclax due to any drug-drug interactions, not have to pause ziftomenib therapy to allow for count recoveries even when they pause venetoclax and azacitidine. Actually, the addition of ziftomenib appears to allow the patients to be able to really dial back the Ven/Aza, which is what physicians really want to do considering how myelosuppressive the therapy can be and trying to get these patients away from the risks of infection and bleeds that they have with venetoclax and azacitidine. The fact that ziftomenib does not have drug interactions, does not have QTc prolongation, and is very easily administered has made the combinability extremely easy.
Understood.
I'm good.
Can you help set expectations ahead of those combination updates later this year?
You want to do that?
Sure. For the 7+3 arm, you've previously seen it. We were at a 100% complete response rate. We can't hold on to that forever, but expect to see very consistent results. Be looking for, at the time of that data presentation, consistency, patient numbers, duration on treatment, and hopefully, we'll be able to present some MRD data along with that. For the venetoclax and azacitidine, this will be the first time we're showing the front-line combination because previously, we did the dose escalation in relapsed/refractory patients.
I would similarly point to look at how these patients are obviously doing from an efficacy perspective, but the safety will be extraordinarily important to observe, and the duration on treatment will be, I think, of great interest to everyone.
Understood. Let me check with the audience, see if there are any questions on ziftomenib in AML before I move on. All right. How are you thinking about the opportunities for menin inhibitors beyond AML?
We see an opportunity to extend the use of ziftomenib to patients with GIST. There is very compelling scientific rationale and preclinical data supporting synergy between menin inhibition and KIT inhibition in GIST. You will see us start that study here in the first half. The significance of that study is we will be working in patients who are progressing or have progressed on imatinib, looking to restore sensitivity. You get a, we think, we do not know, we have not started, but we think a relatively quick proof of concept.
That could lead us then to pursue the combination either in the front line or in the front line and in later lines. It has been described by the clinicians as highly transformative to the GIST field. GIST is not a small market. It is 2,000-4,000 patients.
Most of them start on imatinib, stay on for a couple of years. Unfortunately, 60% or more develop resistance. That's what we're looking to address. And imatinib is the drug of choice among physicians who treat GIST. We're looking to make it that much better by adding Ziftomenib. Beyond that, Jonathan, there is an opportunity for menin inhibitors in diabetes. We've guided to a development candidate around the middle of the year. We're giving ourselves a little bit of buffer there because we want to pick the right compound.
We'll talk more about how we would move that compound forward in clinical development and/or in a partnership. The final opportunity is, and that's with a second distinct menin inhibitor. There's a third distinct menin inhibitor, and we're doing some early work on menin inhibitors in other solid tumors.
Nothing to report yet, but again, some compelling preclinical data for IP reasons, safety reasons, pricing reasons, IRA reasons. Our view is you'd likely do that with a different menin inhibitor. Just to one final question that's attached to that, ziftomenib is the focus of our collaboration with Kura Oncology. We are working together in acute leukemia. They have an option to opt in on GIST. The rest of the menin inhibitor research and development activities are outside of collaboration.
Understood. What is the right menin inhibitor for these other opportunities beyond leukemia?
I think you have to let the data drive you. We have been investing heavily in menin inhibitor chemistry for multiple years. We have compounds that look qualitatively more like Revumenib, look more like ziftomenib in terms of their PK profiles, their drug-like properties. Do they accumulate in certain tissues? Are they menin degraders versus simply menin inhibitors? Francis Burrows, our Chief Scientific Officer and his team, could essentially offer you any flavor you'd like.
Let the data, let the preclinical and ultimately the clinical data be your guide. Zifto, I think Francis says, Zifto hits menin about as hard as it can be hit. You may not need to hit it that hard for something like diabetes. You may just actually want to dial it down, but not actually erase it the way that Zifto does.
It's very potent in the preclinical models, but you may not need to do that. We'll have the option now of actually assessing that both preclinically and potentially clinically, which is where you want to be.
Understood. What are the timelines for these opportunities for menin beyond leukemias?
We've guided, again, development candidate in diabetes, sort of middle of the year. Once that moves into the clinic, think approximately 12 months for an IND. Too early to talk about menin inhibitors in other solid tumors. I think when we get closer to nominating a development candidate there, we have so many opportunities now for which we can create value that we need to be very thoughtful about undertaking clinical development.
We do an extensive amount of preclinical work and now increasingly competitive analysis, development analysis, commercial analysis. That's why we see an opportunity in GIST. Other solid tumors, we see opportunities, but we just have more work to be done.
Understood. Maybe switching over to the farnesyl transferase inhibitor efforts, can you discuss the opportunities for FTIs in solid tumors?
Yeah. Very simply, we're looking with our FTI program to work in combination to make targeted therapies more effective by addressing innate and adaptive resistance. This has been, our understanding of farnesyl transferase has evolved over the last number of years. What we understand is that when you treat a tumor with a TKI or a KRAS inhibitor or an EGFR inhibitor or a PI3 kinase inhibitor, the tumor cells respond. In some cases, they'll mutate, they'll upregulate certain signaling pathways.
Those tumor cells, when they are trying to work around a targeted therapy, they invoke pathways that are farnesylation dependent. While a farnesyl transferase inhibitor might not be effective as a monotherapy, it's highly effective in preclinical models at blocking innate and adaptive resistance. That's probably its highest best use, right? Now, I'm not going to say it's the panacea.
You can't use it everywhere, but we have four cohorts across two different trials. We have our KURRENT- HN trial, which is evaluating tipifarnib and dalpiciclib in PIK3CA mutant head and neck. We have three cohorts in the FIT-001 trial. We've pledged to show you three of those four. That's driven by enrollment, really. The KURRENT- HN trial, we know that dalpiciclib delivers at best stable disease. Tipifarnib is dead as a doornail in that population. If you see responses that are meaningful and durable, that's telling you you're seeing target synergy.
In the case of the monotherapy, you're really looking at activity in RAS mutant patients. Are you going to see tumor shrinkage or responses in HRAS mutant patients? What does the safety and tolerability look like? In RCC, a lot of excitement around HIF2 alpha and what that offers.
Again, if you look at our preclinical data, there's some very interesting synergy between Cabozantinib, for example, and other TKIs in RCC and FTIs. We'll spend more time, Jonathan, in the second half of the year educating analysts and investors about how to think about the science, the preclinical data, how to evaluate the clinical data, but that gives you a taste. The one cohort I left out is KRAS. That's just enrolling a little bit more slowly, but it's actually beginning now to gain some momentum.
We have put a stake in the ground. We intend to submit the data for a medical presentation in the second half, potentially at ESMO. We will look to do some education in advance of that so that people can think about it. As with menin, with FTIs, we have a stable of FTIs. 2806 is the lead new compound.
It's really a very, very, very compelling compound. Again, for a variety of commercial reasons, one may want to take different FTIs off into different directions. We'll have the ability to do that.
What would you say, are there lessons from the tipifarnib experience that apply to the next generation FTIs?
Yeah, I think the lessons are, so we can use the monotherapy activity that we saw with Tipifarnib to very rapidly determine the dose, right? Because HRAS mutant solid tumors are the unique case where when you see tumor shrinkage, you know you're over the zone. And when you see myelosuppression, you know you've gone too high. That's a relatively niche population, but it allows you to zero in on the dose quickly. That's why this FIT-001 protocol is so innovative because we could go very quickly into combinations.
Combinations are where it's at, Jonathan, for a couple of reasons. Resistance is a problem across all drugs in oncology. And you're now talking about large solid tumor opportunities. KRAS alone, lung, colorectal, pancreatic, PI3 kinase, you've got a range of opportunities. RCC, second line and potentially first line are significant. I think the learnings are, the target's compelling.
You have to figure out how to use the biology. What we were missing was the recognition that we actually needed to do it in combination with other targeted therapies. I think that's when it all kind of clicked and fell into place. All of the preclinical data is available on our website. People can go and review it. We're looking to recapitulate that in the clinic, right? If we can see that in, these are dose escalation studies, so it's early days. If you see evidence of overcoming resistance to these targeted therapies, that tells you you're in the right place.
As Molly was saying, the interesting thing that ties the two platforms together is safety, tolerability, and combinability. FTIs are unusual when we consider other targets like SHIP2, SOS1, in that they are so well tolerated.
If you can get that biology while at the same time maintaining really good tolerability, keeping patients on for long periods of time, that's the ticket.
Understood. Maybe just in our remaining minutes, catalysts and milestones for this year, what should investors be looking forward to?
I would say, obviously, the monotherapy data's up. NDA submission, monotherapy data, combination data from COMMON-007, likely in the middle of the year, starting the GIST trial. That'll go relatively quickly. We think enrollment will go relatively quickly. Shifting to the second half, you'll have obviously data from the FTIs, as we talked about. You'll have additional data from COMMON-007. Hopefully, we'll have a PDUFA and be able to actually transition into a launch. I think I've hit all of them in 2025. It's a busy year. It's a lot going on.
All right. Thank you very much for joining us.
Our pleasure. Thank you.
Thank you.