Operator: Our next question is from Phil Nadeau at TD Cowen. Your line is open. Please ask your question.
Phil Nadeau: A couple of questions from us. First, congrats on the 36% CR/CRH trait with the 3 additional patients. In terms of the pivotal trial in NPM1 for revumenib, can you discuss in a bit more detail what’s the implications of the 16% of enrollment coming out of Israel? Is it that, there is a chance that those patients will be lost to follow-up or the data will be lost? How does that impact the timelines and the number of patients that you need to enroll?
Michael Metzger: Yes. Thanks for the question, Phil. Look, I think, it is an unfortunate set of events going there. Our trial sites are still up and running. In Israel, data is centralized, so we have obviously good control over the data, not the issue. The implications, we think are a little bit hard to predict, but we have a lot of other sites that we are doing quite well with enrollment elsewhere. And so, I think that is something we feel very confident we can pick up and complete the trial by the end of first quarter or very early in the second quarter. So it is something that is a little bit unfortunate, but these as I said or as Neil said in the remarks, these are typically high enrolling sites and it was just a little bit unfortunate. But we feel very confident that we will be able to get it done on time.
Phil Nadeau: And then a follow-up question on the SAFE trial. I believe the abstract said that enrollment continued in SAFE and additional on it or updated data we will be presented at the meeting. What can we expect in terms of patients at dose level one it, at ASH? I think there were two in the abstract. Would there be another four DASH or could dose level one enroll beyond the 6 that were enrolled at dose level zero?
Michael Metzger: Yes. Phil, thanks for the question. It is little bit hard to answer at this point. I think they are continuing to it? Enroll at that dose level, as you know, there are only a few that were enrolled so far. The results have been quite strong and striking. So they are looking forward to expand that to additional patients and that will be obviously presented at ASH in the presentation. But I can’t give you specific numbers on how many patients will be expanded to, I just don’t have that detail.
Operator: Our next question is from Jason Zemansky at Bank of America. Your line is open. Please ask your question.
Unidentified Analyst: Hi. This is [indiscernible] for Jason Zemansky. Thank you for taking my question. What sort of data do you think is necessary before the community can start to feel confident about revumenib common ability profile? What do we need to see in terms of both safety and efficacy?
Michael Metzger: Well, look, I think the data that we generated to date, both as a monotherapy and now in NPM1 and for KMT2A really is a good source of or I should say, it underpins well what we would expect to see a contribution of components, when you think about combining drugs such as with [indiscernible] and with chemotherapy. So we feel very confident now we have best in class monotherapy data and that is a good starting point. With combinations, first things first, and Neil made comments about this, you need to be combine these drugs safely and effectively, but full dose, monotherapy dose getting to those levels in a combination is extremely important. And the SAVE information, the SAVE trial information that came out today really supports that.
We will have data at ASH for the BEAT-AML trial, which is frontline patients, the SAVE trial, we are that is in relapsed refractory patients. But BEAT-AML trial is in newly diagnosed patients and the opportunity to not only safely dose patients, but dose them at the full monotherapy dose, as well as drive response rates as you would hope to be as good or better than what they see in the doublet, that is what we are looking for. And I would also say, MRD negativity is a big driver of physician choice and how they think about treating their patients. We have been able to show deep, durable responses signaled by MRD negativity and that is something we will look at in these combinations as well where patients are not necessarily getting to full MRD negative status.
So those are the types of things that we will look for, and we expect to have meaningful data for the end of the year to kind of elucidate all that.
Operator: Our next question is from Peter Lawson at Barclays. Your line is open. Please ask your question.
Peter Lawson: Just do you have enough data now to filed for a breakthrough designation and we can update this data at the Investor Day. And then, our patients going on to transplant and could that cause a downdraft in the CR, CRH rate in a pivotal trial?
Michael Metzger: Yes, Peter, thank you. So, I think you had a couple of different questions here. One was taking it from in reverse order here. So could patients go on to do we see patients go to transplant? I think the answer AMPM1 patient, I think the answer is obviously yes. You see that in the swimmer’s lane that we have on our slides as well as we have mentioned in the remarks, so patients are going to transplant, three of the patients of the 14 went to transplant, and many of them are staying on treatment for and also in remission. So I think that is an important fact pattern. Also important to note what we saw in the Phase I sorry, in the pivotal trial for KMT2A, we and Neil mentioned in his remarks, the number of patients who didn’t reach complete count recovery, so didn’t reach CR/CRH’s best response and were taken to transplant very quickly.
That actually ended up penalizing us a bit on the CR/CRH rate. As the owner marked, it could have been as high as 37% if all those patients had converted and maybe didn’t go to transplant as quickly. [Indiscernible] lower in terms of taking patients to transplant. So these patients are also not necessarily as fit as what you would see with KMT2A, younger patients. So we are actually not seeing, if you look at the data, we are not seeing patients at CRP or incomplete hematological recovery points. And so what you are seeing is all of our patients are CR/CRH an MRD negative and some of them are going to transplant. So it just tells you the time course probably has an impact in terms of reaching your full potential for CR/CRH as an NPM1 patient.
So we don’t think actually that is going to be meaningfully impactful, in the Phase 2. In fact, we see it as the opposite. We see that the CR/CRH could actually be more reminiscent of what we are seeing now, which is in the mid-30s or higher on NPM1, we will have to see what the data bears out. But we don’t think that same treatment paradigm in terms of the speed at which physicians take their patients to transplant is going to penalize in the same way it did for us on the CR/CRH and KMT2A. We will have an update. This is the data. We may have some more to say at our investor event on NPM1, but this is the data that we have in hand. And so we wanted to get it obviously out to you today. But we haven’t really bottomed out on what else we would analyze for our R&D day for or Investor Day for in and around ASH.
And maybe there was another question on obesity. Right, Peter. So, look, I think we have said in the past, you need approximately 20 to 30 patients at the RP2D to file for breakthrough therapy designation. As you see here, this is 14 patients at the RP2D. So, right now, we don’t expect that we would be able to make that application. Obviously, that is something that is open to us at some point in time relative to our pivotal data, which is obviously coming. So, That is it.
Operator: Our next question is from Michael Schmidt by Guggenheim. Your line is open. Please ask your question.
