Release Date: February 26, 2025
For the complete transcript of the earnings call, please refer to the full earnings call transcript.
Q: Troy, you guided to the Phase III top-line in frontline intensive AML setting in 2028. Just curious what assumptions went into that guidance? And anything you can share on the trial size, that plan or enrollment timeline? A: Yes, Li, thanks for the question. We thought it was important because we've been getting questions from both analysts and investors to give people some idea of the timeline, particularly now that we've gained alignment with both FDA and EMA, but specifically with FDA on pathways to accelerated approval in the U.S. and we feel comfortable. We think we're being conservative, but we feel comfortable saying that we think we can have top-line results for that accelerated approval endpoint in 2028. We'll give you more detail on the trial size, the powering, et cetera, as we get a little bit closer to the trials actually going live and being posted on clintrials.gov.
Q: And then just wondering what the remaining items that you may need to work through before the NDA submission. Any notable feedback from the pre-NDA meeting? A: No. I mean, that's -- thank you for the question. I don't know if at the time we made that announcement a few weeks ago, if that -- if people sort of read over that. We were deliberate actually in not saying anything until after we've had the pre-NDA meeting. And the team -- Mollie and the team did a phenomenal job of again gaining alignment with the agency on all the aspects of the submission. Clearly, the clinical data is always the long pole in the tent, and that's what is driving the timing of the submission at this point. But given that we have BTD and given that we've had pretty constructive engagements not only on the monotherapy, but now in the combination setting with FDA, we feel like we're in good shape. And again, we're guiding to a second quarter submission. The team is doing everything in its power to accelerate those timelines. But so far, I think we have everything we need and we've gotten very -- it's been a very constructive series of interactions with the agency.
Q: So the first question I have is that when we look at the commercial opportunities for ziftomenib, I guess, the most important variable is the treatment duration. Could you share the reason behind your confidence that frontline AML patients will be able to stay on the treatment for more than a year? A: Yes. Let me actually -- Yen-Der, thank you for the question. I'm actually going to do this in 2 parts. Maybe Mollie can speak to how we've informed the duration of treatment from our experience with KOMET-007. And then I'll ask -- after she answers, I'll ask Brian to comment on how does that translate into our assumptions around the commercial potential in the frontline. Mollie, if you would? Sure. As Troy alluded to, the 007 trial has been highly informative to how we handle designing and our expectations for the 017 trial and for use in the frontline in general. I think initially, we thought that, especially with the intensive chemo setting, the use would be some induction, some consolidation, then the patient will go off to transplant and potentially some proportion would come back after transplant, post consolidation maintenance. What we're seeing is incredibly different, especially for the NPM1 patients that make up such a large majority of the patient population. These patients are coming on doing induction, consolidation and post-continuation consolidation immediately with few trips to transplant, except for the KMT2As who get to transplant whenever possible and then almost universally either have returned or intend to return to post-consolidation, post-transplant maintenance. Similarly, with the ven/aza, we have patients that are staying on for very prolonged periods of time on treatment in the frontline even when -- or if the backbone drops away or is decreased in intensity or used a little bit differently from when it's used prior to gaining control of disease. So we're seeing good prolonged use in each of these that was probably more significant than what we initially thought. But with that, Brian, I'll turn it over to you to how you see that translating. Sure. And based on the assumptions that we are observing -- or what we've observed in the trial, like Mollie said, we do think there's a tremendous potential that menin inhibitors could transform the treatment of AML with patients being able to get on therapy, stay on therapy for a long period of time. When you think about our opportunities with -- and as we've stated that we think this could be -- as Troy said, it could be a $7 billion potential market. If you're able to get patients to receive menin inhibitor for 18 to 24 months, and there could be potential for longer than that, but if you think between that 18 to 24 months in the FIT intensive chemo population and then 18 months plus within the non-intensive, that gives you a significant duration that we think really could reflect that transformative potential and really kind of align with what we've seen in some other markets like multiple myeloma where long duration of treatments with IMiDs have really transformed the market and also the outcomes for patients.
Q: Congrats on the progress. I was curious, as you look to the additional dose expansion data from the 007 study, what in your view would be encouraging from the 7+3 combo as you start to expand into the non-adverse risk group? Specifically in terms of MRD negativity, what gives you -- what would give you confidence that addition of zifto would ultimately give you a survival benefit? A: Yes. Jason, thanks for the question. I'm going to ask Mollie to speak to it. But Molly, maybe you can take a minute and help folks understand how we think about the MRD negativity and sort of what the standard is as you answer Jason's question. Absolutely. So what we understand, obviously, we're part of a consortium of a large amount of pharmaceutical companies that are really looking into this MRD negativity for this patient population. And we have access, therefore, to both published and unpublished data from those other pharmaceutical companies as well as from some of the key opinion leaders that are really advancing the MRD as an endpoint in AML. So we understand that a good outcome for these patients with the current treatments available would be to see about a 40% to 45% MRD negativity in the bone marrow. And that's for the better performing patients, so your NPM1s, for instance. So we would expect that any incremental increase in that would be due to the influence of having a targeted agent in the mix as well and maybe getting into the 50s and 60% MRD negativity rate would be encouraging for translation into the overall survival as well. So that's the way we're thinking about our data as we continue to look at these patients enrolling. Obviously, you've seen the patients do very well from a response perspective. So I wouldn't expect to see much difference in that. They're going to continue to do well. But it's -- as you're pointing to, the MRD that is what we're looking at to make sure we're headed in the right
For the complete transcript of the earnings call, please refer to the full earnings call transcript.
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