Hello, everyone. Thanks for joining this fireside chat, and sorry about the delay. My name is Kuan Hong Lim, part of the biotech equity research team here at Wells. Today, we are fortunate to have Kura Oncology with us. On the stage with me is Troy Wilson, President and CEO, and Brian Powl, Chief Commercial Officer. We know the company has been having a strong commercial launch on KOMZIFTI, but to kick things off, can you start with a brief overview of the company?
Sure. Yeah, and thank you, and apologies for the delay. We're trying to get down on the elevators. Kura has two major pillars to our business. On one side, we have our product for acute leukemia, ziftomenib or KOMZIFTI. As you said, we're off to a very strong launch in the initial relapsed/refractory NPM1 mutant setting. We have a number of data catalysts coming here in the second half of the year, both as monotherapy and in combination, in frontline and in later lines. We have two large randomized phase III studies underway, and if those are positive, and we've guided to initial top-line results in 2028, we think that could unlock a multibillion-dollar opportunity. So that's the acute leukemia side. On the other side of the house, we have darlifarnib. Darlifarnib is a farnesyltransferase inhibitor.
We have shown data with it in combination with both cabozantinib in kidney cancer, as well as adagrasib in KRAS G12C mutated solid tumors. We're doing a sort of a two-prong strategy. We're moving it forward in kidney cancer. We're in a phase I-B study with cabozantinib. We think that could open up opportunities in the second or third line in kidney cancer, either as the doublet or potentially as a triplet. We also expect to begin dosing next year patients with daraxonrasib, recently approved in pancreatic ductal adenocarcinoma and darlifarnib, looking really to extend what we've done so effectively with adagrasib, but now do that with the approved standard of care. The easy way to think about darlifarnib is darlifarnib is an agent that makes targeted therapies much better.
We should see phase I data leading up to potential registrational studies right around the time that the AML studies we're beginning to get the results from those phase IIIs. So it's a nice setup between the two sides. We had $518 million in cash as of our last quarterly update. We expect $180 million in additional milestones from our partners, Kyowa Kirin, tied to ziftomenib development. The company is in a strong capital position, and we think we could develop two potential blockbusters, one in liquid tumors, one in solid tumors, which should position us really well the rest of this year, next year, and on into 2028.
Got it. Thank you for the overview.
Sure.
Let's talk about the commercial launch of KOMZIFTI. You report strong second quarter sales. Can you talk about net sales? From our understanding, your new patient starts also existed Syndax, Revuforj, Celgene's new patient starts. Can you also talk about the dynamics there, and how you plan to further grow the market?
Yeah, absolutely. Thank you. We reported in the second quarter that we had $9.1 million in net revenue. That was in our second full quarter of launch. That was a growth of about 57% quarter-over-quarter, where we had $5.8 million in that first full quarter in Q1. We also had an increase in new patient starts. We had 115 new patient starts, about 250 total prescriptions in the quarter. The new patient starts to us is really the story when you're coming into a launch because that really signals where market leadership may be possible and how we've been able to achieve that. So in this last quarter, we achieved the majority share of new patients that started in the NPM1 mutant population. We expect to see that to grow.
I think the reasons why we have those expectations is that the profile of KOMZIFTI is something that has been resonating with physicians, with payers, with pharmacists, that KOMZIFTI is viewed as the differentiated menin inhibitor based on its efficacy, its safety and tolerability, the ability to combine with other agents, both concomitant medications and other therapeutic agents, and also the simplicity of a once-daily dose that makes it easier for patients to potentially benefit.
Right. Got it. Can you talk about the split of new and repeat prescription and if it eventually stabilized, what kind of ratio are you expecting?
Yeah. Since we are in a launch phase, we are expecting the leading indicator right now is to get new patient starts and to build that leadership in new patient starts. For the relapsed/refractory NPM1 mutant population, we have guided that the market size is about $350 million-$400 million per year. That is assuming patients get about six months of therapy, five and a half to six months of therapy. So it is going to take some time for us to get a better sense as to where that will even out. But we do anticipate that the patients that are on therapy who are new patients throughout the quarter will stay on and be able to help ultimately get us to the duration of what we have expected to guide so far.
Got it. That makes sense. Can you also talk about the mix of mono and combo use? If it is used as a combo, what kind of drugs is it used with, and in what population?
Yeah, absolutely. Yeah, so our commercial team, of course, is focusing on promoting per label, which is as a monotherapy. But physicians that treat AML patients, especially the relapsed refractory, have their discretion as to what they will treat. We have seen in the second quarter, we saw about 40% of patients receive KOMZIFTI in combination with other standard therapies. Largely, the majority of those have been in combination with venetoclax and azacitidine, which is a therapy that if they did not receive in the first line, that would be a second line setting. Then we have seen mostly in that, as I said, about 75% or so are ven/aza. The remaining are pretty much in the FLT3-mutated population with gilteritinib. The FLT3 population, when you think about the overall market within AML, 30% of patients have an NPM1 mutation.
Just 30% of patients who have a FLT3 mutation, about half of the NPM1 patients also have a co-mutation for FLT3. There is a significant overlap, given that physicians see an opportunity to combine with the two, that enables patients to get treated earlier in the course of disease rather than later on in third, fourth, fifth line. We do have data that we are expecting to present later this year in combination with FLT3 inhibitors. We have not published anything to this point yet, but physicians are starting to use that.
Yeah, that makes sense. We understand it is early in the launch, but anything you can comment on the duration of therapy of current patients, is there any difference between mono and combo use in terms of duration of therapy?
It is a little early for us to share because we need to see if we have guided that we have about six months of therapy is what we would expect. We need to see patients on therapy for a longer period of time to see that. There is nothing in the data that we have seen that would expect us to see much different to that six months of a median duration. Excuse me. From a combo versus mono, to your question, we do think that patients, and there is data that suggests that patients who are treated in combination may benefit for a longer period of time, largely because they are going to be treated in the second-line setting rather than in the later lines of therapy. So there may be some increase for those patients that move into the combination, but that is what we are expecting.
We have to see that play out.
Right. But in both settings, ziftomenib is used as a same dose, and you get the same monthly revenue?
Yes, absolutely. Every dose that we've tested in AML, we've seen it come through at 600 mg once per day.
Right.
That's both in combination with intensive chemotherapy, with ven/aza, and also you'll see as we start to present data, we expect the same with the FLT3 inhibitors, too. It'll be the same revenue for that.
Right. Anything you can comment on the gross to net, and how you expect it to change in 2027? Consider Part D redesign in 340B.
Yeah. Our gross to net is consistent with what you see with other oral therapies with Part D coverage. It is essentially in that 20%-30% range, and we are falling comfortably in that space. We have not given any guidance around 2027's gross to net expectations, but we have been tracking closely, and I think that gives us a good sense as to where we are.
Got it. Last question on the commercial side. On insurance part, can you share about what current patients have gone through and is there any ultimate denial so far?
No, great question. I would say that in this launch, our market access team has really been a strength for us. The coverage that we have been able to get so quickly in this space, being the second to market, has been something that we are very proud of the accomplishment from the team. We have over 95% coverage of covered lives in the U.S. We have about 16 million lives that actually have a favorable position of either step edits or preferred tier formulary for KOMZIFTI over other menin inhibitors, and that has really been a strength. You can see based on the uptake of the new patient starts, that we have not had a challenge with access. We have had very successful coverage for patients, and we continue to expect to see that as well.
Got it. Thank you so much for all the colors. Let us now switch gear to the front line. We know your phase III KOMET-017 study is ongoing in front line. Can you talk about the progress there? I think in second quarter update, you mentioned a positive momentum in patient enrollment. Can you also comment on that and what is the timeline for the program?
Yeah. We have two phase III's running in parallel under a single protocol. The intensive chemotherapy study is running slightly. They are both running at or slightly ahead of expectation. We have guided initial top-line results in that intensive chemotherapy combination in 2028. Those may permit us to file for accelerated approval with the agency. We seem to have alignment there. So that study is nicely enrolling. The venetoclax azacitidine ZIFTO triplet is enrolling in the other phase III. There, the accelerated endpoint is CR, complete response rate. Each of the two phase III's have survival-based endpoints. We guided for the initial top-line results really to put a stake in the ground to say, this is a 2028 story. This is not 2029 or 2030 or 2031. We seem to be tracking to that quite well. We have not guided to any subsequent updates.
The only color we have given is we are still relatively early in the enrollment, but enrollment is going well. We have a lot of experience from the KOMET-007 phase I-B studies that we conducted where we have approximately 200 patients across those two phase I-Bs. That has given us a lot of color on the patient types, the enrollment kinetics, sort of what to do to help facilitate that the phase III's are run as well as they possibly can be.
Got it. Very helpful. You mentioned AA path, you mentioned 2028 data from the intensive chemo cohort. I assume the 2028 data would be based on EFS. Is that?
No, the 2028 would be based on an accelerated endpoint of measurable residual disease negativity.
Correct
complete response. A complete response that has no detectable disease to a limit of detection of like 10 to the minus fourth. The benchmark for traditional intensive chemotherapy is about 44%. That is as measured in bone marrow at the end of cycle two. What we have said is you would like to do clinically meaningfully better than that. Call that maybe somewhere in the 50s, 50% range, 50%-60% range. In our phase I-B update at the European Hematology Association meeting in Stockholm, we reported a 56% rate of MRD negative CR at the end of cycle two for the triplet. Again, sort of right on track, right where we want to be, and maybe to just take a moment, as far as I know, we are the only menin sponsor that is actually running both intensive and non-intensive studies as Kura sponsored studies.
We have sized them to not take unnecessary risk. You want to have a success, but we are being, I think, very reasonable about the effect sizes and any sort of degradation that one might see from phase I-B to phase III. That first readout as you mentioned, that is the MRD negative CR, and we have said top line results, and what we mean by that is did we hit it or did we not hit it, right? Is that going to support a discussion with the agency around accelerated approval? Ultimately, you are going to need to have a survival-based endpoint to support the full approval. That will come a little later. That is in the case of intensive chemo, an event-free survival endpoint. For the non-intensive, it is an overall survival endpoint.
Right. Since you mentioned your phase I-B data, can you comment on whether there is a difference in the patient you enroll for phase I-B versus phase III? Any difference in patient population?
There shouldn't be any difference between the patients who were enrolling in I-B and the patients who were enrolling in the phase III. The major difference is you are going to have very many more sites. We expect to have approximately 200 sites globally. Again, importantly, because it is a two for one, every time you activate a site, you are actually activating two phase IIIs simultaneously. Although we might have started a little later than our competitors, I think we are actually going to be very competitive. We may even be ahead in terms of enrollment when all is said and done. There are multiple phase IIIs enrolling. I think we are very well positioned.
Got it. Very helpful. For the non-intensive part of the study, you haven't guided on the data timeline, but can you tell us what we can expect next for that part of study and what is the bar there?
Yeah. So, this actually, what I'll say is that I mentioned there are four data updates expected here in the fourth quarter. The phase I-B for the non-intensive chemotherapy combination is going to be one of them. So you're looking at a CR rate of maybe 50%-60% in the NPM1 category. You'd like to do better than that. There are survival-based endpoints as well. Just as we did around EHA, look for us when that data's presented and hopefully it'll be presented in the context of a medical congress. Look for us to provide additional color to help you and investors understand the phase III design and how it relates to the phase I-B data.
But I think my hope is we'll be sort of right on track with where we need to be in terms of CR rate, and ideally, you're not going to be able to say very much about the survival-based endpoints yet because it'll still be relatively early. If that's the case, then that's obviously good for patients. It's good for the study.
Got it. Last on this topic, can you talk about the differentiation versus J &J bleximenib?
Yeah. We don't know as much about bleximenib. J&J is pursuing, as far as we can tell, they are pursuing development both as a monotherapy and in the frontline setting. I don't really want to speak for their data because they didn't have data at EHA. It's reasonable to think they may have a data update at ASH. Let's see what we see. Bleximenib is very potent. It is so potent, in fact, that they've had some challenges with differentiation syndrome even in combination. Let's see. We're expecting that they may provide a data update here a little later this year.
Okay. Thank you for that.
Sure.
Now, let's switch gear to your KOMET-008 study.
We know you have an upcoming readout in NPM1 mutant, FLT3 mutant AML.
Yep.
That is a combo with gilteritinib.
Yep.
Can you talk about what we should expect at this readout and anything you want to comment on?
Yeah. So there are three things you want to think about: safety and tolerability, response rate, durability. First of all, safety and tolerability. Gilteritinib has a non-negligible rate of QT prolongation. It has some cardiac tox. Our commercial competitor has had challenges combining with gilteritinib. They've had dose limiting QT prolongation at every dose. They haven't at least shown that they have a path forward to combine. So I would look for that. Can you safely, as Brian said, combine ziftomenib at 600 mg with gilteritinib without any sort of unnecessary or additive tox? Then the question is, can you drive a higher response rate than either Gilt or Zifto alone in the co-mutated population? That may depend a little bit on line of therapy.
As Brian mentioned, you expect to get your best activity in those sort of second-line patients and then, it degrades a bit with each subsequent line. I would look for that. It may be a little early on the durability endpoints, but as we saw with the venetoclax and azacitidine Zifto data that was published in Blood in May, the combination of Zifto plus Gilt, if we're able to combine them successfully, should give you additive or maybe even synergistic activity. What we want to see happen is that the physician community isn't waiting for patients' disease to progress through Gilt before they give them Zifto. Ideally, they feel that there's good safety, good tolerability, potential for additive or synergistic activity. They actually give the doublet together. That would really drive both the best outcome for patients. It should further reinforce our market leadership.
It's an area where we're going that I don't see either of our competitors really going, and as Brian said, that's a third of AML, that's half of your NPM1 population. I don't know how you can be the market leader in AML if you can't compete in FLT3.
I see. Thanks for also commenting on the market opportunity there. What about the regulatory path looks like for this setting?
Yeah. At the moment, we're more focused on data generation. The FLT3 population is a bit fractured, so you have gilteritinib approved in the relapsed refractory setting. You have quizartinib and midostaurin approved in the frontline setting. That's why you see us actually doing studies to demonstrate combinability with both Gilt and Quiz. Once we get that out there, I think we can have a conversation about what, if anything, does a registration enabling study look like. We're just not quite there yet. I'd like to socialize that data, I'd like to get feedback from the clinicians, and sort of see where we go from there. If there's a potential path to doing a registrational study, we're certainly open to it.
Got it. Thank you for that.
Sure.
Let's also talk about your next-gen compound, KO-2806.
Yep.
Can you talk about IND enabling studies, how we may see data from these studies, and what do you hope to achieve with this next-gen compound?
Yeah. So just for clarity for everybody, we are now going to make a hard switch from acute leukemia to diabetes and metabolic disease. KO-2806 is a purpose-built menin inhibitor that is specific for diabetes, specifically Type 1 and Type 2 diabetes. We have shown preclinical data with ziftomenib in models of both Type 1 and Type 2 diabetes, as well as human organoid tissue. Look for us, we have an upcoming presentation at the EASD meeting in Milan here at the end of September. Look for us to say a lot more about what we are going to do with 7246. Look for us to compare that compound to the other compounds that are being evaluated in diabetes and metabolic disease. I think with 7246, much like with Zifto, we have potentially a best-in-class compound.
We are going to have a lot more to say about that program and that molecule here a little later in the month of September.
Okay. Will that include a comparison to BioMarin's icovamenib?
It should include a comparison to icovamenib or BMF-219, yes.
Yeah.
That's a question we get often, and I think we'll show you why we think that 7246 has potential to be best in class.
Okay. Thank you for that.
Of course.
In the last couple of minutes, let's talk about darlifarnib. We know you have present lots of data on that program, and also you have lots of upcoming milestones. Can you give us a brief summary on that front?
Yeah. As I mentioned in the introduction, I think of the darlifarnib development program kind of in two broad buckets. One is in kidney cancer, initially in combination with cabozantinib, but darlifarnib is sufficiently well-tolerated. One could imagine combinations with HIF-2α, with checkpoint inhibitors, with other TKIs. We're working our way through that. Right now, we're in the middle of a dose optimization phase I-B to chart a course of the doublet of darlifarnib and cabozantinib. We chose cabozantinib because it is the market leader. It's very well established. It's well-liked by physicians. There's a lot one can do with it. But I would stress that similar to ziftomenib, darlifarnib could be combined with axitinib, with lenvatinib, with tivozanib. There's a bunch of different combinations one could pursue. We're focusing initially on cabo. On the other side, the other big bucket is in the KRAS-driven tumors.
We did initial proof of concept with adagrasib, because when we started, that was one of two approved KRAS inhibitors. We've now seen very recently the approval of deruxantinib. That has opened up an interesting opportunity in PDAC, and specifically, we're one of the few programs, PRMT5 may be the other, where we have the potential to improve on deruxantinib. Deruxantinib has ushered a revolution in KRAS therapy and pancreatic cancer, but we're still at a 30% response rate. We're at a median OS of about 13 months. If you see from our clinical data what we've done with adagrasib, and then you see the translation, the dots that we've connected to deruxantinib, I'm really excited to see us combine deruxantinib and darlifarnib. I think that could really further build on the incredible accomplishment of deruxantinib and do even better for patients.
In both of these cases, for both cabozantinib and deruxantinib, the message to physicians and patients is, if you like your therapy, you can keep it. We are just going to make it better. You can add darlifarnib to it. That should only enhance the activity, but at minimal to no added toxicity. That is a really strong message in this evolving landscape of solid tumors. It is a huge potential. You are talking about a $5 billion-$6 billion peak sales opportunity between those two. Quite a lot to come here on the darlifarnib side.
Right. For the study you plan to initiate in first half next year with divarasib, could that be a pivotal study?
It will start off as a phase I-A. We would likely do a phase I-A, phase I-B. The agency may still want you to do some amount of Project Optimus, just to ensure that you have the right sort of dose and schedule. If you saw sufficient activity, we have certainly heard from key opinion leaders as well as from investors, they would love to see us launch a pivotal study. You just want to have as much information as you can before you start that study. The unmet need is there. The patients are there. We are really right now in the midst of just getting the study operationalized. I would look for us to start enrolling sometime probably close to the middle of next year.
I see. Before we wrap up, anything you want to highlight to the investors?
I guess all I would say is the company is executing across the board, commercially, late-stage development, early development. There are not a lot of companies where you can have two potential oncology blockbusters within the next couple of years in a company that is so well-capitalized, and the risk-reward ratio is pretty asymmetric to the upside. Those of you who follow Form 4 filings know I vote with my own feet. I have made some significant market purchases, and those may not be the last. We would invite the audience and others anytime to let us know if you would like to learn more, but it is going to be an exciting couple of years.
Yeah. With that, thank you for being here with us and sharing your insights, and thank you for your attention.
Thank you.