Phil Nadeau: Perfect. That’s very helpful.
Keith Goldan: We got 30% — yeah. Thanks.
Phil Nadeau: Thanks again for taking our questions.
Michael Metzger: Thank you, Phil.
Keith Goldan: Thanks, Phil.
Operator: Our next question comes from Brad Canino with Stifel. Your line is now open.
Brad Canino: Good afternoon. You’ve provided peak sales opportunities, but how do you see the KMT2Ar launch playing out this year, things in terms of number of patients that are available in the relapse/refractory setting, where they’re concentrated and what to expect for the pace of uptake?
Michael Metzger: Brad, thanks for the question. I think maybe a little early to start speculating about sales ramp and projection. And we’ll reserve the ability to give a little bit more guidance as we get closer to commercialization. I think, as we stated in our remarks, we think it’s a — KMT2A is a really, I’d say, compelling opportunity commercially in the sense that we’ll have a first-to-market, best-in-class product to address patients even earlier than they are in a clinical trial. So we’re talking 2,600 patients overall, probably, about 2,000 of which are treated in the relapse/refractory setting. We believe that we’ll have the opportunity to address the vast majority of those patients. And as we’ve pointed out in previous discussions, that these patients are in dire need of therapy.
Many of them can go to transplant, hopefully, through the use of treatment with revumenib and potentially back on treatment in a post-transplant setting. So there is — we think a highly addressable population, physicians seem to be quite motivated to use the drug and so we’ve seen that in our trials, but we’ve also heard that from physicians. So I think this sets up as a really interesting new opportunity for a drug to come to market with really no competition at the current point — at this current point to get in the way of a very successful launch. So that’s where we — how we see it today in terms of projections and launch and ramp. We’ll maybe preserve that for future discussion.
Operator: Our next question comes from a line of Michael Schmidt with Guggenheim. Your line is now open.
Michael Schmidt: Hey, guys. Thanks for taking my question. I had one on the first-line setting for revumenib in combination with 7+3. In your opinion, what is the right way to view frontline combo data with menin inhibitors and 7+3? And specifically, given that one would expect very high CR rates, presumably, on top of 7+3 already, what are other benchmarks that you’re looking for in your own study, including MRD status, for example, transplant rates or any other efficacy measures that are important in your opinion?
Michael Metzger: Michael, thanks for the question. Important one, certainly, to get a handle on. I think the 7+3 regimen, as you know, is highly effective in frontline patients. NPM1 and KMT2A patients initially respond — upwards of 80% of patients respond to those treatment. However, they don’t usually respond for long. So there’s relapse that happens with most of those patients. Things to look for beyond just CR rates — CR/CRh, of course, would be would be MRD and transplant rates, which we would be looking for. Obviously, we’ve seen high rates of both in relapse/refractory patients. Now we’re moving to — we would be moving to frontline and you’d expect to see equal or better rates of MRD and certainly transplant in earlier line settings.
And so I think that’s the — those are some really important measures. Duration of treatment, of course, 7+3 is a short course. The ability to treat with revumenib and keep patients in remission for an extended period of time is obviously something that we’d want to see. Of course, it’s new days, right? And we haven’t — you haven’t seen a menin inhibitor perform in the frontline 7+3 as of yet. So I think it would be up to us to kind of set the trend for what the bar looks like there. But certainly from a CR perspective, you — and a safety perspective, you kind of know what you’d want to see, relatively clean profile and highly effective. But you need to continue on and see deep durable responses as well. Neil, do you want to add anything?
Dr. Neil Gallagher: Yeah. Maybe just two things that add to that and I think there may have been a regulatory context to the question about what the potential end point could be. It’s certainly too soon to talk about that. I think Michael has mentioned, MRD negative CR is not certainly an end point of interest, whether or not it could be an approvable endpoint remains to be seen and we will, of course, be engaging in discussions with the agency. As we move closer to — having now initiated our dose ranging trial, as we move closer to initiating our Phase 3 trial. And then the only other add that I would make would be, if you look at the 7+3 trials that have been conducted really over the last sort of 10 years to 12 years going back as far as my discipline, they’ve all included maintenance phases.
And you could assume that any 7+3 trial that we would conduct would also include a maintenance phase. And in support of that, what we have seen — recall that what we’ve seen in the relapsed/refractory setting post-transplant is patients who’ve remained on therapy for a protracted period of time, speaking to the tolerability of revumenib in a relapsed/refractory setting. And therefore, we anticipate that as we move towards the newly diagnosed setting, that patients who would be, for instance, given monotherapy maintenance after induction consolidation therapy would probably — would most likely tolerate the medicine very well as well or the molecule of it.
Michael Schmidt: Okay. Thank you.
Michael Metzger: Thank you, Michael.
Operator: Our next question comes from Yigal Nochomovitz with Citi. Your line is now open.
Ashiq Mubarack: Hi, guys. This is Ashiq Mubarack on for Yigal. Thanks for taking my questions. I had a few on axatilimab. I guess first, congrats on the PDUFA date. I’m just wondering how involved you are in the regulatory process from this point out. Obviously, we know Incyte is leading the proceedings, but will you be part of the mid-cycle review? Will you be able to weigh in on labeled negotiations? How should we think about that?
Michael Metzger: Yeah. Ashiq, thanks for the question. Look, we’re very involved with — obviously, with axatilimab. We generated the data and it’s been a very close collaboration with Incyte. And so we are involved in the regulatory process and are working with them closely to get this drug approved in all facets. So you’re thinking about label negotiations and things like that. We are, I’d say, suffice to say, very involved with what’s going on. So that’s an exciting development for the company, and obviously, we have great experience with the molecule and want to think that we’re involved. So that’s certainly what it is. Was there a second part to your question or was that — did I cover it?
Ashiq Mubarack: No. That’s very clear. I wanted to ask another one on IPF. Maybe I’m forgetting…
Michael Metzger: Sure.
Ashiq Mubarack: … or simply just don’t remember this from prior calls, but we — I know you’re evaluating the 0.3 mg per kg dose, which was obviously the dose that looked best in AGAVE-201. I’m just wondering what kind of gave you confidence that’s the right dose specifically for IPF? I guess why didn’t you need to do dose optimization work or disease biology really similar enough that you felt confident enough not to do that? Obviously we’re dealing with a different end point here, so just curious what your thoughts are?
Dr. Neil Gallagher: Yes. Hi. It’s Neil. I’ll take the question. So, no, it’s a good question. We did have a long discussion internally about the dose selection. So a couple of things. Quite clearly the 0.3 milligram dose in AGAVE — in the AGAVE trial was superior to the other two doses and we don’t need to read — to go back over that. It’s quite clearly the superior dose in terms of efficacy, as well as tolerability. And what we have talked about a number of times over the past year, particularly before we announced the details of the IPF proof-of-concept trial that we talked about today was that we were looking for an efficient trial design. And therefore the most efficient trial design which would get us to a robust proof-of-concept answer efficiently, meaning efficiently in terms of the design of the trial, but also in the time to execute the trial was the one that we have described today.
And we felt that on the balance of everything that it was reasonable to go ahead with one dose in this trial and that dose should be 0.3 milligram. So I think to one point that you alluded to, yes, I think, there is sufficient overlap from a biological perspective to have made that decision and that partly led us to that decision.
Michael Metzger: Maybe I would add on to that. You probably know we did extensive dose ranging in the course of the Phase 1, as well as the pivotal trial. We also looked at — early on we looked at healthy volunteers. We know how this antibody behaves and so — and the effect that it has on the macrophage. And so, I think, the understanding the pharmacology here and therefore how we think it would translate to patients in IPF kind of gave us some — I think some good confidence that 0.3 milligram would be the appropriate dose in addition to what Neil added.
Ashiq Mubarack: Very helpful. Thanks very much.
Michael Metzger: Thank you, Ashiq.
Operator: Our next question comes from the line of Jason Zemansky from Bank of America. Your line is now open.
Unidentified Analyst: Hey, guys. This is Alex Hanab [ph] on for Jason. Thanks for taking my question. Appreciating somewhat early, so with regards to your regular submission for revumenib, can you provide some color on what you expect to be included in the label? Are the eight efficacy viable ALL and PAL [ph] patients with a 12.5% CR/CRh warrant a tumor agnostic label? And what are your basic expectations on potential safety monitoring requirements for DS in QT prolongation? Thank you.
Michael Metzger: Maybe I’ll turn it over to Neil. He will talk about the label and then maybe talk about any kind of safety.
Dr. Neil Gallagher: Sure. Our anticipation is the label, I mean, let me say, appreciate what I am about to say by reminding everyone that we got BTD back in December 2022 for KMT2A AML and ALL adults and kids. So the development program moving forward from there those based on Phase 1 data. The development program moving forward from there was based around premise that we would have a potential for a broad indication. As you know, we actually pooled cohorts 2 and 2b and the submission for KMT2A acute leukemia is based on pooled analysis which, of course, include AML ALL adults as well as pediatric patient. So our anticipation is, and of course, the agency has been fully unlock, it is — coming on that journey with us the whole way, including from BTD, before BTD, through BTD and onwards.
So that’s the indication that we’re looking for. So not the exact words, but KM22A rearranged acute leukemias in adults and children. With respect to your second question about safety monitoring, we don’t — so first of all, from a class perspective or a broad class, meaning targeted therapies in AML, we anticipate — we would probably anticipate about warning for differentiation syndrome, since that is typical of these agents in class, right? It’s on target, it happens, the agency knows it happens, so that’s that. We do not anticipate — we anticipate a warning and precaution for QT, but that’s it.
Operator: Our next question comes from Kalpit Patel with B. Riley. Your line is now open.
Kalpit Patel: Yeah. Hey. Good afternoon and thanks for taking the question. Maybe a couple on the 7+3 combo study, can you give us some color on what dose of revumenib you’re planning to start with? And then the second question is, how should we think about the enrollment split between the KM22Ar and the NPM1population in that combo study? Would it be a 50-50 split or are you seeing — are you anticipating a skewing of the KM22A patients as they’re more fit?
Michael Metzger: Yeah. Maybe I’ll take the second question, I’ll give the first one to Neil. Yeah. So, I think, that — I think you just said it, in terms of KM22A versus NPM1, we don’t really know, but I think it’s — there — the KM22A patients overall are more fit than unfit, right? So, that’s where they skew. Whether or not we have a skewing in our population of patients to KM22A or not, we don’t know at this point, but we do expect representation of both. And Neil, do you want to talk about the 7+3 combo starting dose?
Dr. Neil Gallagher: Yeah. So — and just one thing to add on, it doesn’t really matter the split between KM22A and NPM1 patients in the first instance, right? What we’re actually seeking to demonstrate is the combined ability of revumenib with 7+3 and the — as we mentioned a little bit earlier on in the call, in all of the combination trials that we’ve described thus far, there have been two doses tested, 113 milligrams and 163 milligrams, and those are the doses or the equivalent doses, without CYP3A4, that strong CYP3A4 that we will be testing in the 7+3 trial as well. I mean, we know — based on the comments that we made earlier on and data that we’ve presented before, we know that they’re combinable with both chemotherapy and also venetoclax-based HMA therapy.
Operator: Our next question comes from the line of Justin Zelin with BTIG. Your line is now open.
Jeet Mukherjee: Great. Thanks for taking our question. This is Jeet Mukherjee on for Justin. Maybe just coming back to axatilimab, I was hoping you could provide a little bit of a sense of the opportunity for axatilimab and IPF, the subset of patients perhaps best suited for this therapy and what you’d be looking for from an efficacy perspective?
Michael Metzger: Yeah. I don’t know if, Anjali, do you want to take that question?
Dr. Anjali Ganguli: Yeah. Sure. I can start. And Jeet, I will preface this by saying that we need a little bit more efficacy data to really hone in the expectations, but I think we know that, as Neil mentioned on the call, there’s two drugs that are approved and though a lot of patients cycle through both of them and sometimes see them added onto one another, all they do is slow the decline. They’re not actually treating the disease and so there is still a huge unmet need in the marketplace. There are a very large number of IPF patients out there today, even in the U.S. alone and we would expect to be able to — we’re doing the trial to add on to standard-of-care, so we’d be looking at a second- or third-line utilization. And I think, we would expect, based on positive data, to get significant uptake in that population because of the large unmet need.
Jeet Mukherjee: Got it. That’s helpful. And maybe just one more on axatilimab. Is there any additional color perspective on the combo studies you’re doing with ruxolitinib and steroids in collaboration with Incyte, and just what you’d be looking there from an efficacy and safety perspective to move one or both of those forward ultimately?
Michael Metzger: Yeah. Anjali, do you want to follow on there?
Dr. Anjali Ganguli: Yeah. Sure. So, again, it’s axatilimab bringing this strong fibrotic effect to bear on patients and hopefully helping to manage the impact of the disease on organs and therefore potentially shifting the courses of the disease is what we’re trying to change with that combination therapy. So, moving up earlier, could you really have a bigger impact on patients and their overall disease profile going forward? We anticipate getting some data out of this trial in the coming years and I think that would govern what the uptake would really look like, but this is something that physicians are telling us they’re really looking for. Right now, the only thing they have is steroids, and unfortunately, those do as much harm as they do good.
And so, if you could get strong efficacy out of that combination, could you minimize the use of steroids and bring axatilimab up to an earlier population? I mean, we know the current estimated prevalent pool is about 14,000 patients and so you could access a big chunk of that population with good data.
