Morning, everyone. Welcome to our day one of the Cantor Healthcare Conference. My name is Li Watsek, a biotech analyst here at Cantor. It's my great pleasure to introduce our next company, Kura Oncology. With me today, we have Troy, CEO, and Brian, CCO from Kura. Very nice to have you guys. I would love to maybe turn it over to Troy to give us sort of the 10,000-foot view of Kura and what investors should be focused on over the next year.
Sure. Yeah. Thank you, Li. Thank you to you and Cantor for the invitation to participate in the conference. Kura is at a point where we think of the business as sort of two halves of a much larger whole. On the one side, you have our program for menin inhibition in acute leukemia. That's ziftomenib, where we're now leading new patient starts in the commercial setting in our labeled indication. We have a number of data updates coming here in the fourth quarter that will expand both the breadth and depth of what one can do with a menin inhibitor as monotherapy in combination. We have big two phase III's underway that are evaluating ziftomenib in the frontline setting with both intensive and non-intensive chemotherapy. Li, that's all working toward top-line results for the first phase III in 2028.
Our estimates are a potential peak sales of $3 billion as part of a $7 billion TAM. We're really looking to transform the treatment of acute leukemia. That's one side of the house. The other side of the house is darlifarnib. The simplest way to think of darlifarnib is darlifarnib is a farnesyl transferase inhibitor that has the potential to make other targeted therapies better. We've now evaluated farnesyl transferase inhibitors in combination with KRAS inhibitors, with PI3 kinase inhibitors, as well as tyrosine kinase inhibitors. We have a two-pronged development strategy currently underway. We're pursuing a phase I-B study of darlifarnib plus cabozantinib in kidney cancer. We will, next year, be pursuing the combination of darlifarnib plus the recently FDA-approved daraxonrasib in pancreatic cancer.
The hope there is the message to patients is, if you like these therapies, whether it's cabo or daraxonrasib, we think we can potentially make them better by combining with darlifarnib. That, Li, is a similarly sized, probably peak sales, even an even larger TAM, obviously in kidney and pancreatic. But we're going to continue to push things. I suspect you'll ask more about it. We are the leaders, the pioneers in menin inhibition. Today, we proudly announced the creation of Caspian Therapeutics, and that is to pursue menin inhibitors as a potential disease-modifying therapy in diabetes. We're going to do that through a new company, a dedicated team, dedicated capital. But there's a lot of exciting things coming and all for the benefit of patients.
Very good. I was going to ask you about this morning's news, which I thought was a pretty cool idea that you can actually advance menin into non-oncology indications, like diabetes. How does that fit with a Kura Oncology story?
Yeah. It starts with menin inhibition. Menin is a target that keeps teaching us new things that it can do. As your audience probably knows, we obviously have a significant development and commercial effort underway in acute leukemia. We're evaluating menin in solid tumors, starting with gastrointestinal stromal tumors. To your point, there's very strong genetic and biologic data that supports using a menin inhibitor to selectively expand pancreatic beta islet cells. You can't create something out of nothing, but if you have some beta cell reservoir, by blocking menin, you actually selectively allow the pancreatic beta cells to enter the cell cycle and proliferate, and we're going to show preclinical data on the new Caspian compound, KO-7246. We'll show that data in Milan at the EASD meeting. From a Kura perspective, we have a lot to do.
Brian, Molly, Jennifer, our new CFO, we have a tremendous amount to do as a team. We can't do everything, so we wanted to make sure we put the diabetes and the cardiometabolic programs into a separate company. Again, we'll build a new team. We have fresh capital. I think that will become its own independent story over time. It allows us to really focus and apply our resources to being a best-in-class precision medicine oncology company.
That's great. Maybe let's talk a little bit about concept launch. You did fairly well in Q2, take the market leadership in terms of the new patient starts. I wonder, where do you see the trend grow from here and now we're well into Q3. I wonder if you can talk a little bit about things that you're seeing, any seasonality that we should keep in mind.
Sure. Thanks, Li, and appreciate the opportunity to be here. We're very pleased, as you said, with the launch of KOMZIFTI. The fact that, as we shared, we've reached the majority of new patient starts in only our second full quarter of launch demonstrates not just the strong commercial execution, but the differentiated profile of KOMZIFTI and the growing physician adoption. We've grown from the first quarter of the year to, I think we said we're about 40% of new patient starts. Now we announced that we're at the majority share. We've also seen growth in our TRX and overall revenue in that timeframe. I think the directionality of all these show that we're on track to be the market leader overall in the NPM1 mutated space.
We can't share details of where we are in terms of third quarter so far, but I can say that the profile has resonated of KOMZIFTI, showing that it's differentiated on efficacy, safety, combinability, and the simplicity of once-daily dosing. Those are what's resonating with physicians, with payers, and with pharmacists, and I think that's what's helping to drive the success we've had so far.
I know it's still relatively early in the launch, but what can you share in terms of duration of therapy for these patients? Especially now we learn substantial of these patients actually on combination use. Are you seeing a lot of patients maybe coming back on therapy after transplants?
Sure. As we came into the launch, we have been guiding that this market is at the relapse refractory NPM1 mutated market, is about $350 million-$400 million TAM. That is assuming about a six-month average duration of therapy. It is still a little too early for us to verify whether or not that is coming through, but I can say that everything is trending in that direction. We do need more time to be able to see that. As you mentioned, we have a significant amount of combination use. While our team is promoting on-label as a monotherapy, physicians want to have the opportunity and choice to be able to treat how they like to treat, which is often in combination with other standard therapies.
We anticipate that patients who would be getting treatment with KOMZIFTI in combination with venetoclax, azacitidine, or FLT3 inhibitors may be treated earlier in their course of disease, which could lead to a longer duration. It's something we're following and tracking, but of course, duration is a story that has to play out over time.
Okay. As your launch matures and you'll get longer treatment duration, how should we think about that translation into revenue growth? Should we think the speed of growth should potentially accelerate, just given it seems like you're doing really well in terms of new patient starts, so you're adding patients. On the other hand, the treatment duration is also getting longer. I think eventually, should we assume that it's going to translate into a high growth of revenue?
Sure. Yeah. Obviously, at the point in our launch right now, the focus is getting patients on and getting the majority share in a new patient start.
Our team's focus is to get patients as early as possible in their disease course because we know that patients who, if they're in a third or fourth line, unfortunately, they're pretty beat up, and they may not be able to benefit from any therapy at that point in time. The sooner we can get a patient onto therapy, and if the physician chooses to use it in combination, it gives them a better chance for that duration. Our team is not just focusing on getting new patients onto therapy, but also making sure they can stay on therapy, maximize that benefit, and to be able to communicate for both the payers and for the physicians, and ultimately for the patient, that they'd be able to stay on therapy.
Our strategy, of course, is to support the needs for physicians to publish data in combination so that they will be better understood as to how they can maybe be able to use in combination, potentially earlier in therapy as well.
Li, maybe I can just add a thought to that.
We get this question a lot. There are three launch dynamics to think about. There is the NPM1 launch, there is the KMT2A for our commercial competitor, and then there is frontline. KMT2A, those patients really have no other option, so that launch is going as fast as you see new patients. As Brian was saying, NPM1, you have entrenched therapy. You have venetoclax and gilteritinib, both of which are used. We are trying to publish data that helps physicians understand they can use ziftomenib earlier and in combination.
Once you get to frontline, then your launch kinetics look more like KMT2A because every patient, whether that patient is intensive or non-intensive for ziftomenib, will take seven days of therapy, and then on day eight, start ziftomenib. A lot of what we are looking at is a proxy for ultimately overall market leadership and the fact that we have now taken leadership in NPM1. I think we are going to have the most robust, most advanced data with FLT3 combinations. The frontline data is looking good. The whole goal here to win for patients is to get to the frontline and get as many patients as possible on therapy.
And in terms of payer access, what I found pretty interesting is that KOMZIFTI has preferred formulary for a lot of payers. I wonder if you can share what the primary reason is for the step edits? Then what the implications are for your ongoing launch, as well as your future expansion into frontline.
Sure. I think that the market access success we've had of getting over 95% of patients covered within that first six months with a favorable coverage, as you mentioned, in a significant number of plans, that speaks to the overall profile of KOMZIFTI.
Speaks to, as I talked about before, about the pillars of efficacy and safety, tolerability, simplicity, combinability. Payers have looked at the data and also added in terms of all of those elements. The predictability of cost is also important. Affordability, predictability is something that has resonated with the payers as well. Given KOMZIFTI's profile, we have a 600 milligram dose once daily, regardless of whatever concomitant medications a patient may be on, whatever combinations we have. That simplicity also helps for payers. As we continue to generate data, moving into the frontline, we think that it will be consistent, and we'll continue to see that similar success.
Those pillars of safety, combinability, convenience, become even more important as you get into earlier lines of therapy. I agree with Brian. What we're seeing now, the evolving dynamic should pull through. Obviously, one has to have success in the clinical development arena, but you're going to hear all the same things and even more so from physicians, patients, and payers when you get to frontline.
Mm-hmm. On the point of combinability, obviously, I think, QTc is a key differentiator here, especially as we think about going into FLT3-co-mutated patients, which is roughly half of NPM1-mutated population. As you, talking with physicians, do they also appreciate the difference here in terms of QT and the ease of combinability?
I think they do. These are highly sophisticated physicians. They will find a way.
But that is where, again, pointing to that data in the fourth quarter, if you can give them a path to safely combine a menin inhibitor and a FLT3 inhibitor, they understand the rationale for using them together. What they need is a clinical data set that supports that. To my knowledge, our competitor has not yet demonstrated they can successfully combine with FLT3. Look for us to give an update on our ability to combine. QTc is part of it, but the other part of it, Li, is also myelosuppression. Our competitor has reported 20%-30% severe thrombocytopenia. That becomes relevant. You can clear a patient's leukemia, and at that point, the patient really does not have any detectable disease. But if they are still having to contend, as Brian said, with concomitant meds and with things like severe myelosuppression, that is a differentiator.
That comes through when we talk to physicians and to pharmacists.
Okay. It sounds like QT and myelosuppression are two points that physicians do appreciate.
Yeah.
On the QTc warning on the label, are you guys still trying to collect data and trying to remove that from the label, or it is not really a big issue just from adoption perspective?
It has not been the highest priority. It has not hindered us taking-
Right.
-majority of new patient starts. I do not think it is going to hinder our ability to lead in that market. The FDA is data-driven. What the FDA is looking for is a randomized data set. We did not have that at the time we did the initial submission. I would say, Li, it is still on our to-do list. I know Mollie and her team are focused on it. I am not hearing any real pushback from the commercial team about it. All things being equal, we would like the label to be as clean as possible, and if we could get some of that QT language removed, we will certainly do it.
Okay. Then, let's talk about the frontline. Obviously, you guys are running the phase III trial. Maybe give us an update on the patient enrollment.
Yep.
I believe the initial top line may come out around 2028, so how does that compare to your competition?
Let's talk about enrollment, and then maybe we can put it in the competitive landscape. Enrollment is going well. Between the 2007 phase I-B studies, we have nearly 200 patients that we've enrolled between NPM1 mutant and KMT2A rearranged, Li. I think we have a pretty good understanding of where are those patients, how do we get them on study, and so forth. All indications are that's translating through to the KOMET-017 phase III pivotals. Enrollment is absolutely on track. In terms of the competitive landscape, we've been consistent. We've said we're expecting initial top-line results in 2028.
I haven't yet heard anyone else articulate- their timelines. I don't want to speculate to them. I do think we probably have a significant time advantage on the intensive chemotherapy side because, and I give credit to Molly and her clinical team, we saw an opportunity to. Or what we saw was patients on the triplet of intensive chemotherapy plus ziftomenib, many of them were electing not to go to transplant. They were electing to just stay on ziftomenib in continuation therapy. So we put much more of an emphasis on intensive chemotherapy, I think, than competitors.
That's that first data release that you described. What we've said is we're anticipating top-line results. I read that as we can say, did we hit the MRD negative CR endpoint that we think will support a submission for accelerated approval? The data will, of course, come at a medical congress, probably either EHA or ASH. We'll be able to give folks line of sight on should they anticipate us to engage with the agency around a package for accelerated approval in the front line. That's that first 28 marker. The non-intensive, Li, will lag a little bit behind. It's still early days. Both trials are enrolling well. We haven't yet guided to the timing for the non-intensive chemotherapy phase III cohort.
I wanted to follow up on that point. Seems like you guys think, 7+3 regimen is gaining a lot of traction for the reasons that you just mentioned, Troy. But on the other hand, we heard from physicians, they're saying, the field, especially in front line, is shifting more towards, aza-ven regimen. But then on the other hand, to your point, Troy, you could have a finite sort of treatment induction period, then maybe just use ziftomenib as a maintenance therapy. Maybe you can expand on that view. It seems like you have a different perspective on where the field might shift.
Physicians have been trying to move away from 7+3 for the last 50 years.
Yeah.
7+3 is very effective at limiting leukemic blasts. What they didn't have until ziftomenib came along was the ability to clear the leukemia and then put the patient on a once-daily continuation therapy as opposed to a transplant. I don't want to substitute my judgment for the clinicians, but what we're hearing and what we're seeing, and Dr. Zeidan talked about this with the EHA data, the risk of a transplant, you have a 20%-25% risk of mortality. You have potentially lifelong complications, graft-versus-host disease, immunosuppression, versus, as he says, I can offer my patients a once-a-day pill and save that transplant for the future. I think that's really the opportunity that that triplet presents. Recently, the PARADIGM study was published. That was another of our investigators, and that's Dr. Fathi at MGH.
Dr. Fathi is one of the key investigators on the 017 study, and he hasn't encouraged us to move away from 7+3. The beautiful thing about the 017 study is there's something for everyone. If the physician believes the intensive chemotherapy regimen is right for her patient, they can go into that side. If she believes that it's ven-aza, she can go to that side. We're unique in that our study offers patients throughout to be able to go either intensive or non-intensive and gives the physician, the patient, and the care team the option to customize the treatment best for them. That's something we offer that I don't see offered by our competitors.
Mm-hmm. That makes sense. I know you guys have a pretty busy second half of the year in terms of data flow. Maybe you can give us a quick preview of what that is-
Yeah.
-what the key takeaways will be from that update.
Yeah. We've guided to four data updates in the fourth quarter. Ideally around a medical congress. They are in order, an update on the phase I-B study of ziftomenib plus venetoclax and azacitidine. You and your audience have seen this data already, but this is now another six, nine, 12 months onward. So there, Li, you're looking for, again, safety, tolerability. What are the landmarks in terms of the survival-based endpoints? Ideally, we'd be in a position where we really can't say anything yet about duration of response or OS. That would be good for patients. That's the other bookend to the intensive chemo data we showed at EHA. That's number one. Two data sets combining ziftomenib with FLT3 inhibitors. Remember that the FLT3 landscape has gilteritinib approved in the relapsed refractory setting, quizartinib approved in the frontline setting. We're combining with both, again, to give physicians the option.
You're going to see both of those data sets. The ziftomenib/gilteritinib is the doublet in relapsed refractory NPM1 FLT3 co-mutated patients. The quiz data is the quad of 7+3 plus quiz plus ziftomenib.
They take 7+3, they roll off of it, then they're on the quiz ziftomenib doublet in the frontline setting. Look for safety, tolerability, combinability. Do we see enhanced activity relative to either the FLT3 inhibitor or ziftomenib alone? As Brian was saying, that's a real opportunity for us to give physicians options as we move from 2026 into 2027 to help continue driving growth and uptake of KOMZIFTI. The final data set to expect is actually kind of a personal favorite, that is activity of ziftomenib in the relapsed refractory setting for the non-canonical mutations. So these are non-NPM1, non-KMT2A patients. We've shown you one notable example from the Phase I-A, a patient who had a complete response in a SETD2/RUNX1. We've said consistently we believe menin inhibition could help 50% or more of patients.
You may not register in all those different genetic indications, but it's reasonable to expect that a menin inhibitor may have activity as monotherapy or combination. Look for us to update that data set. That's been kind of cooking in the background in the Phase I, the KOMET-001 study, and it's time now, the physicians are encouraging us to talk about it. So it's frontline in relapsed refractory, it's mono and combo, and it is KMT2A, NPM1, FLT3, and now other mutations consistent with this theme of we want to try to treat as many patients as possible and really further reinforce our leadership.
Okay. Very cool. I wanted to maybe switch to darlifarnib a little bit. You guys have shared some pretty nice data this year. What is the high-level pitch for darlifarnib?
Yeah, the high-level pitch for darlifarnib is, as I said, in solid tumors, pretty much wherever you look, the goal is move into safe, well-tolerated, more efficacious combinations. We see that on the kidney cancer side. People are combining checkpoints, TKIs, HIF-2α. You see it now increasingly in the KRAS space. Folks are combining with PRMT5, with EGFR. Darlifarnib offers the opportunity in both of those settings to enhance the activity of targeted therapy. It works by blocking activity of a protein called TORC1, which is a key node in the pathway in both of those diseases. To your point, we've shown darlifarnib plus cabozantinib has activity in patients whose disease has progressed on cabozantinib, in patients who are naive to cabozantinib, as well as on the KRAS side in lung, pancreatic, and colorectal patients who are being treated for KRAS G12C mutations.
The opportunity, Li, in kidney is bring a new mechanism of action forward. I think folks are very optimistic for what the players there are doing, but we're not curing patients. So long as we're not curing patients, there's a need for new mechanisms and new combinations. Look for us to do more there. On the KRAS side, I think if our preclinical data and our data with adagrasib is any indication, if we can enhance the activity of daraxonrasib, further drive response rate, drive those survival-based endpoints, we can build on the revolutionary advance of Revolution Medicines. That would be great for patients. We may also, Li, be opportunistic with some other combos. But I think if we can drive forward with cabozantinib and daraxonrasib, each of those opportunities is of a similar commercial opportunity as AML.
It would put Kura in the next year or two in a position where we have two potential blockbusters in oncology back-to-back, and that's an exciting place to be.
Great. Now, Troy, we talked about you got a launch going on KOMET-007, and then you have darlifarnib has a lot of potential. How are you thinking about capital allocation across the portfolio?
Yeah. We think about it a lot. Yesterday, you saw we were delighted to welcome Jennifer Fulk to our senior leadership team as our Chief Financial Officer. That's job number one for Jennifer as part of the SLT. We're going to continue to be creative. That was partly of what motivated the Caspian carve out.
We knew that that opportunity needed a meaningful amount of capital, and it allowed us to create an entity where Kura shareholders still own approximately 50% of the upside of a diabetes pure-play. We're going to continue to do that. We'll look at a range of options to help continue to fund and grow the business, but we think like owners, so we're going to be very mindful of being efficient capital allocators and try to create as much value as we can.
Okay, great. Looks like we have a lot to look forward to. Thank you so much, guys. Troy and Brian.
Thank you.
Thank you. Appreciate it.