Good afternoon and welcome once again to TD Cowen's 45th Annual Healthcare conference. I'm Phil Nadeau, a biotech analyst here at Cowen, and it's my pleasure to moderate a fireside chat with Troy Wilson, the President and CEO of Kura Oncology. Troy, I'll hand it to you to start. Can you give us a brief state of the company overview, biggest strengths, biggest challenges, and what does Kura need to do to create shareholder value over the next year?
Sure. Thank you for the invitation to participate in the conference and for the fireside chat. Kura is building, I think, a leading pipeline of targeted therapies to treat cancer. There is obviously a lot of investor and analyst focus on the menin inhibitors. We will talk about that. We are going to be pursuing opportunities in the relapsed/refractory setting, in the frontline setting, as well as other indications, including solid tumors and diabetes. We will also, later this year, show some early clinical data from two of our pharmaceutical transferase programs, which are targeting big solid tumor indications. That has the potential to create a lot of value for patients. As far as strengths, I think we are building an incredible integrated research, development, and commercial organization. We are extremely well funded, which is important in these trying times.
Anybody who's watching the tape, it's good to be able to put your head down. We've got, I think, really potentially life-saving medications, and we can advance them forward, stay focused, because eventually everything normalizes. We're really looking forward to our NDA submission, to sharing top-line data, to hopefully a successful NDA approval and a launch of ziftomenib. It's just going to be one thing after another for the next couple of years. A comment, Phil, that I made on one of our recent calls, I think it was our earnings call last week, we hope to have meaningful clinical data at every major medical meeting this year: ASCO, EHA, ESMO, ASH. There's going to be a lot to pay attention to across the pipeline. For those who can stay with it in these markets, I'm hoping we create a lot of value for people.
Let's start with ASCO and the pivotal data from ziftomenib in NPM1 acute leukemia. Can you summarize what you have disclosed about the data so far?
Yeah. The trial is obviously a phase two single-arm trial for registrational intent. We have guided that the top-line data, which is the rate of CR/CRh, is between 20% and 30%. That's what the trial was designed to deliver. That's, in fact, what it has delivered. That means two things. One is hopefully that that data set is comfortably above the null hypothesis, such that you can rule out chance. That's obviously important from an approvability perspective. Also, the benefit-risk as far as safety, tolerability, and clinical activity, we think is going to be compelling relative to other competitors in the class, of which there are several. Again, I think we'll be well positioned not only to compete initially in the relapsed/refractory population, as you indicated, but ultimately to be able to drive interest initially in trial enrollment and then ultimately into the frontline population.
We're going to try to do both, Phil. Sometimes people focus on one or the other. In the near term, you need to execute in the relapsed/refractory market. Our best guess is that's a few hundred million dollars. The frontline population, if we assume 18 months to 24 months of use, which is what we've now guided to a couple of times, the peak sales for the menin class just in AML could be as much as $7 billion or perhaps even more. You'll see our focus is really on how you build on that initial enthusiasm in the relapsed/refractory market and ideally get to these patients as early as you can in their treatment journey so that we give them the best chance of a long-term durable remission or potentially even a cure.
We will dive into the frontline market in a lot of detail given your novel trial designs. Before we get there, just knock off a few more questions. Relapsed/refractory.
Sure.
You've disclosed that the results have been submitted to ASCO and will be disclosed in the abstract. Can you give us some sense of what measures will be in the abstract versus the presentation? Will the presentation be the same data cut as the abstract? Will there be a new one?
Yeah. The principal data points in the abstract will be the CR/CRh rate, the duration of response, the safety and tolerability, obviously sort of the headlines from that, the presentation. We're targeting ASCO, obviously. There are no guarantees, but it's a positive pivotal study, so we're hopeful. That will have more data. We'll obviously sort of cut the data in different ways, as people can imagine. In terms of that data versus the data that is going into the NDA submission, that data is roughly contemporaneous. Our goal is we've now, I think, largely closed the gap in NPM1 and from a timing perspective. There was not that long ago that we were perceived as two years behind. We may even be ahead at this point. I don't know. We're guiding to an NDA submission in Q2.
You'll see the data between what's gone into the NDA and what you'll see ultimately, hopefully at ASCO, will be very consistent. Those are essentially a contemporaneous data cut.
Got it. What has to be completed before the NDA can be submitted? Any key rate-limiting factors?
No. Just people are finishing the clinical module. A number of the other modules are complete or very nearly to complete. There is a whole sort of QA, QC process that you step through. We are targeting Q2. We know we are in a foot race, and we are going as quickly as we can, but not sacrificing quality. Quality has to be the most important thing.
What are you doing today to prepare for the launch?
Yeah. We've continued the theme of, I mean, I think we've just hired. In these markets, you can actually be a buyer of talent. We've recruited an outstanding commercial team to stand alongside our development and our research teams. We are building out a lot of the strategic functions: marketing, market access, medical affairs, beginning to build out the organization underneath those functions, everything from pricing to competitive intelligence, insights, and analytics. There's a lot that goes into it. We haven't yet recruited a sales force, and we'll wait to do that until we get closer to when we have line of sight on a potential PDUFA date. We, as Kura and then in collaboration with our partners, Kyowa Kirin, intend to be formidable competitors in the market against the one established competitive player out there. We may have a bigger footprint.
We may be able to reach more docs. This is still a specialty market, but I think our goal is to get out there and promote where we can within the label, but also educate physicians as we continue to see data on this menin inhibitor class evolve over the next year to several years.
Do you mind, is under the collaborative agreement, who is in charge of the sales force? Is it a joint steering committee? Is it Kura? Is it Kura?
Kura leads commercial strategy. There is a joint commercialization committee reporting to a joint steering committee. We're really working, I think, well together. There is a recognition. I mean, there's a recognition between the two companies. Let's not be duplicative. Let's try to, if there's something Kyowa Kirin already does or does better, let's go with that. Kura is leading global development. We're leading commercial strategy. We're booking U.S. sales. It is important that we sort of set the tone. Our teams are working very, very closely and I think so far very well together.
Perfect.
It's a new relationship, so on the honeymoon.
With that, we'll transition to first line. The KOMET-017 design was recently disclosed. It has some novel elements in it. Can you outline the design of the KOMET-017 trial?
Sure. For the audience, the KOMET-017 trial is actually a single protocol that encompasses two independent randomized placebo-controlled phase three trials. One trial is evaluating ziftomenib in what we call the intensive chemotherapy setting. That is in combination with 7+3. A second independent trial is NIC for non-intensive chemotherapy. That is combining ziftomenib with venetoclax and azacitidine. We now have alignment from both FDA and EMA that I will tell you exceeded my expectations before we went into it. The alignment pertains to the potential for pathways to accelerated approval in each setting, as well as full survival-based endpoints in each setting. In the case of non-intensive chemotherapy, the endpoints will be complete response or CR rate as a potential endpoint for accelerated approval, overall survival as the full approval endpoint.
In the intensive chemotherapy setting, now with 7+3, you have a novel endpoint of MRD negative or measurable residual disease negative CR as the accelerated endpoint and event-free survival as the full approval endpoint. The advantage of those accelerated endpoints is they can shave at least a year, potentially more, off of the timelines to get to data and ultimately to market. I will say we've now engaged with both FDA and EMA. The feedback we received from both of them was, or from each of them was consistent. You'll notice that the intensive chemotherapy design is actually a three-arm study, and that's intended to support a label of ziftomenib with 7+3 for induction, consolidation, and then continuation therapy. That is obviously a big value driver for patients, as well as potentially commercially.
In the non-intensive setting, it's less frequent that those patients go to transplant, so they'll stay on Ven/Aza. They'll stay on ziftomenib with or without Ven/Aza really until progression. That is how that is intended to proceed. The statistical analysis plans, there are separate ones for the U.S. and Europe. We will pursue the survival-based endpoints in Europe. For those who are familiar, our view is if you're going to argue for reimbursement with the European payers, you want to put your best foot forward with a survival-based endpoint. The trial is designed to deliver accelerated endpoints in the U.S., as well as full endpoints eventually. It is overpowered to deliver full endpoints in Europe, but that should support a cohesive global development strategy. One final thing I'll mention, and this is a little bit in the weeds, but it's important as people think about how companies work.
We're standing up a global randomized phase three. The reason we did two trials in one is twofold. The first is we can accept nearly any patient with the exception of FLT3 mutant fit patients. Those patients have to go to a FLT3 inhibitor first, but any other patient is eligible to come on KOMET-017. When you go to a site, that site, essentially any patient who walks in the door, if that patient is NPM1 mutant or KMT2A rearranged, that patient is eligible to come on to KOMET-017. That's a real attraction. It's like one-stop shopping for the clinical sites. The other is from the standpoint of the sponsors, you're standing up only one trial.
Everything from site selection to contracting and budgeting to site activation to monitoring to data cleaning, that's all happening one time, but you're getting sort of two phase three shots on goal through it. It's what gives us the advantage to compete with one of our other competitors, a large U.S.-based pharmaceutical company who, I like to say, their landscaping department is bigger than my entire company. You have to be smart and you have to do things that are a little unusual and fight to win, fight to get patients.
To drill down on a few more of the novel aspects of the trial, you mentioned CR and MRD negative CR as the endpoints for accelerated approval. Many companies have hoped to use those endpoints in the past, but you're the first one to successfully secure them. Can you talk about the regulatory discussions that enabled you to get those into the trial design?
Sure. Yeah. I mean, kudos to Mollie Leoni, who's our Chief Medical Officer and her whole team. To understand this, go back a few years. We at Kura are members of something called the Impact Consortium. Impact includes Janssen, BMS, Celgene was a member, Kronos was a member. The Impact Consortium has been working to make the argument with data that MRD negative CR is an appropriate surrogate for survival in acute leukemia. It's now accepted in multiple myeloma. It's accepted in other contexts. To your point, it hasn't ever been used, although Kronos did, I believe, have alignment from the FDA on its trial. We worked with the Impact Consortium using both public and nonpublic data, a meta-analysis looking across a number of trials to help substantiate the association between MRD negative CR and survival.
It was that effort, Phil, that really, I think, excuse me, was really essential to providing the FDA with the data it needed to say, "We're willing to consider this as an accelerated endpoint." We went in, and like anything, it's a discussion with the regulators. There's a recognition, I think, I can't say enough good things about the FDA, particularly right now. There's a willingness to be creative, to design these trials where you can do a single seamless trial that gets you both an accelerated endpoint and a confirmatory trial all in one. They recognize if there's a good argument to be made, why make patients wait for a survival-based endpoint? You want survival to go as long as you can. I think they were ready. They were primed. I was thrilled.
I think I made the comment to analysts and investors alike, that was not my base case. My base case was we were going to be looking at survival-based endpoints. Molly and our team were able to secure accelerated paths in both settings. Just a huge accomplishment. One other thing that's maybe a little less visible, we also got alignment from both health authorities on the usage of venetoclax and azacitidine that mirrors real-world usage. One of the challenges with venetoclax and azacitidine is it's myelosuppressive. Physicians often try to taper patients off of it to help their counts to recover. Previously, there's been a sort of a reluctance to use anything other than 28-day venetoclax dosing. You'll see the alignment that we got really mirrors what happens in the real world. There again, I think it's a golden age in AML.
It allows these frontline trials to go much faster, hopefully much better benefits for patients. Kudos to our team, to the Kyowa Kirin team, which participated in the discussions, and our partners at the FDA and EMA.
What's the significance of using the bone marrow to assess CR versus plasma markers?
Yeah. Most importantly, our best estimate, Phil, is the rate of MRD negativity with intensive chemo as measured in bone marrow is about 45%. If your goal is to demonstrate a clinically meaningful benefit over standard of care, that's a much lower hurdle rate. To date, what everyone has shown from all the different sponsors is MRD negativity typically as measured by sites, typically measured in blood. That's going to be much higher. That's not necessarily the best predictor of long-term survival. Bone marrow is a better measure. This was not something the FDA or EMA mandated. It was what we proposed to them. It also gives you a better margin of safety in terms of being able to demonstrate a clinically meaningful benefit over the standard of care. It's assessed at the same time a physician would make the determination about is a patient in response.
Importantly, it runs alongside. The physicians will be making treatment decisions based upon their local testing. They will decide, do I take a patient to transplant or whatnot? We will be running this in parallel to support the companion diagnostic and ultimately the accelerated approval endpoint in the study. That is why it works well for patients. It works well for the sites. We handle all of the, we sort of do it all on the back end. There were some questions, if you will give me like one more sec, there are some questions about, did we really have FDA alignment, et cetera, after we announced it? I can tell you, we do not have to go back to the FDA on anything related to MRD negativity. On any accelerated endpoint, the FDA is always going to say, look, it is a review issue. Bring us the data.
What they're saying is we have a willingness to review your data. And if you generate that data consistent with what we've discussed, we're happy to take that into consideration. That's as much as you're going to get. Now it's on us as sponsor to do the right study. And we know exactly what we need to do.
Can you discuss the powering of the KOMET-017 trial?
Not yet.
No. That's what I thought you were going to say. When do you think you will be in a position?
I think when the trials go live on clintrials.gov, right around there, we have a responsibility to bring you, other analysts and our investors along. We're also in a competitive dynamic. Already I get questions as to whether other sponsors can change their endpoints. There's no point in having the Khan Academy to AML while we're running it. Let's keep it to ourselves. We've guided, we'll start this study in the second half. Look for a lot more detail on endpoints, powering, timelines to data. We've mentioned that one could have MRD negative CR top-line results in 2028. I wanted to put that stake in the ground because we were getting questions, is it 2032? Is it 2030? 2028 is, we'll be honest, before we know it. We put that stake in the ground.
We'll be more forthcoming and more specific probably in the second half of the year.
2028 does seem like an aggressive timeline. How confident are you you can hit that?
I wouldn't put it out if we didn't think we could hit it. One thing we've said, and I don't want that to sound like hubris, we have been consistently getting better and better on enrollment. If you look at the pace of enrollment in KOMET-007, which is the phase one trial that informs the design of KOMET-017, we are just enrolling those studies like gangbusters. We are using real-world data from KOMET-007 to inform KOMET-017. I will tell you, we've set a high bar internally, but as a shareholder, that's what our shareholders should want, is let's push ourselves to get out there and do it. It's reasonable. It's achievable.
What other registrational trials are you considering?
There is a clear and present opportunity with FLT3 inhibitors. FLT3 is 25% to 30% of AML. It is overlapping with NPM1. We have been doing studies in the relapsed/refractory setting with gilteritinib. We have gotten good safety data. That was a question, right? Can you combine two novel mechanisms? We know that. You should see us moving into the frontline setting in a phase one study combining ziftomenib and quizartinib. Our goal will be to go straight into the frontline if FDA will allow us to do that. We will generate data. It is an interesting question, and I will just leave it as a question for now. How big do you open that aperture? Do you go for all of FLT3? Do you go for all patients? How do you think about doing it?
If you step back and you say half of all frontline AML patients are eligible for menin therapy, the way I get there is I say it's NPM1, it's KMT2A-rearranged, and then it's other mutations including FLT3. If you include all of FLT3, it gets you above 50%. I think that's a reasonable assumption. With that, if you assume 18-24 months, depending on intensive or non-intensive duration of therapy, that's what's driving our estimates that the frontline opportunity for the menin class could be $7 billion peak sales. Again, you look at myeloma as an analog. You look at other heme malignancies. If you've got good durability, that's the kind of commercial opportunity that one can drive.
Another piece of your guidance for this year is that we'll get updated data from ziftomenib, 600 mg plus venetoclax and azacitidine during the second half of the year.
7+3.
Sorry, 7+3 during the second half.
Oh, 7+3 in the mid-year, Ven/Aza in the second half. I'm sorry, I stepped on your question.
Maybe set the table for that by outlining what was presented at ASH and what will be incremental in these new updates.
Yeah. At ASH, we did two dose escalation studies. We did 7+3 plus ziftomenib in frontline adverse risk patients. That study has now turned the corner and is enrolling at 600 mg in all frontline intensive patients. You'll see an update on the 600 mg dose data with 7+3 . With the non-intensive chemotherapy, the Ven/Aza, we showed data, we did a safety escalation in relapsed/refractory patients. That was just to ensure there's no drug-drug interactions, no additive toxicity. We will show you probably in the second half of the year data now at 600 mg with ziftomenib, Ven/Aza in frontline newly diagnosed patients. Those two populations, the significance of that, Phil, of course, is those two populations reflect the patient population you're going to see in the KOMET-017 trials.
You're looking for, of course, you're going to get high response rates because it's newly diagnosed. What are we seeing in terms of depth of response, durability? Are we seeing an improvement in CR rate, overall clinical benefit? Clearly, we and Kyowa Kirin feel sufficiently confident that we're launching these phase three studies. I think we'll fill that picture out throughout this year, hopefully at EHA and then again in the second half of the year, potentially at ASH.
Perfect. Actually, speaking of Kyowa Kirin, you recently signed that global strategic collaboration. Can you talk about the rationale for the collaboration and maybe a bit more about the structure?
Yeah. The rationale was the goal here is to maximize value for patients and ideally for shareholders. We've talked about it now. To maximize the value just in AML in the frontline, one needs to run three independent phase three trials, FIT, UNFIT, and FLT3. We didn't touch on post-transplant maintenance. Let's put a pin in that and come back to that next time. That's potentially a fourth, a good drive value. That's a big lift for a company at current stage while you're trying to commercialize your first drug, while you're trying to advance your pipeline. The alternative was we could have done royalty financing or perhaps equity financing. In these markets, that deal looks like a godsend. You have a very committed partner. We got $330 million upfront, which we received in December.
We believe we're on track, if all goes well, to receive another $240 million this year in milestones. That should put us at roughly break even given our projected operating expense. It leaves us in a very strong cash position. There are other things we want to do, right? You want to be, we've also, we get half of the commercial expenses paid for through that collaboration. That allows us to, we're going to start dosing patients with ziftomenib and imatinib in GIST. If that works, that's a billion-dollar opportunity. Look at Idorsia, look at Deciphera, some of the other players in that space. You're going to see us go into diabetes. We've talked about that. You're also going to see our pharmaceutical transfer rates program. Had we not done the partnership, Phil, I think the company would look very different.
We would not be able to take on our competitors and play to win. I am extremely grateful to Kyowa Kirin. They have been a great partner to this point. It caught some people. It was a little out of the box. Importantly, we retain development control. We retain U.S. commercial control. We book sales. From a strategic optionality perspective, if we can deliver on what we are doing, there is a lot of value to be created. We are in a very strong cash position. We had approximately $750 million in cash a week ago on our quarterly call. As I have said, we should end this year qualitatively in a similar position. Good place to be for companies in these markets.
It does seem like Kura is getting more and more enthusiastic about ziftomenib and GIST. Can you talk about the scientific rationale for that combination?
Yeah, happy to. Very simply, all the KIT inhibitors in GIST work by blocking the catalytic activity of KIT, which is essential to 90% plus of GIST tumors. KIT expression is under the control of menin MLL. When you combine a menin inhibitor and a KIT inhibitor, think about going at the oncogene or the oncoprotein from two different directions. As a result, you get very potent synergy. The reality in GIST is most of the time you'll see stable disease, perhaps PRs. In preclinical models, you see CRs. Why? I think because you so completely turn off KIT signaling that the cell has no choice but to undergo programmed cell death. Are we going to see that in patients? I don't know.
Given that we're starting in effectively just after the frontline, so patients who are progressing on imatinib, we'll know relatively quickly if we're seeing a signal because you're looking to restore sensitivity. If that works, you would go straight into the frontline on top of imatinib. Imatinib is used for a couple of years. It's generic, so you don't have financial toxicity. Same pricing paradigm as what we're doing in AML. You've got 4,000-6,000 patients a year who could be on ziftomenib for a year or two or more if we see synergy. You'd basically push all the KIT inhibitors sort of downstream. It's a pretty interesting near-term opportunity. We'll start dosing patients here in the first half of the year. Look for an announcement in the coming months.
Great. Maybe last question is on the FTI program, a brief update on the status.
Yeah. Just in the time we have, the goal there is an FTI is the preferred companion therapeutic for targeted therapies. We've said we have two drugs, tepotefarnib and 2806. We're going to show you data from the 2806 mono escalation, from the 2806 plus cabozantinib in RCC. A lot of interest in castatafan and that whole sort of IFTU alpha space. RCC is very rich. You'll see data of tepotefarnib plus alpelisib in PIK3CA mutant. I think in a best-case scenario, Phil, you end up with, this is what people have been trying to do with SHP2, with SOS1. You end up with a companion target that makes each of those targeted therapies, TKIs, PI3 kinase inhibitors, KRAS inhibitors, that much better. Look for the initial clinical data in the second half, potentially at ESMO.
Perfect. Thank you for making the trip to Cowen's 45th Annual Healthcare Conference.
Our pleasure.