Please be advised that today's call is being recorded. I would now like to hand the conference over to your speaker today, Robert Ang, President and Chief Executive Officer. Please go ahead. Hello, everyone. This is Robert Ang, CEO and President of Vor Bio. Thank you for joining this webcast dated December 9th, 2024, as we highlight the recent clinical data from a November data cut from the VBP101 clinical trial. I will point you to our disclaimer slide that you'll be able to access on the internet at your leisure. Today, we'll be covering our clinical data highlighted by our Chief Medical Officer, Eyal Attar. Following my closing remarks, we will also invite one of our investigators, Dr. Guenther Koehne, to provide comments on the data, and we will have time for Q&A. So just to set the context, Vor Bio is working on solutions to treat acute myeloid leukemia and other associated cancers by changing outcomes after a stem cell transplant. Stem cell transplants were revolutionary in their time in the treatment of bone marrow-based cancers, but unfortunately, despite that advancement 50 years ago, a lot of patients do poorly after the transplant, particularly patients who are identified as high risk of relapse, where they relapse very quickly following a transplant, and their outcomes are very poor. What we are trying to do is intervene by, instead of a regular transplant, providing a graft that is shielded from anti-cancer therapies. This shielding can potentially populate a whole new blood system that is also shielded from anti-cancer therapies that enables use of maintenance therapy where otherwise would not have been possible. And this, we hope, would allow changed outcomes in these patients. Now, in order to do this, the shielded graft requires several important attributes that we focus on at Vor Bio. Firstly, these shielded grafts need to engraft properly. They need to behave like any regular stem cell transplant and reconstitute the blood system. Secondly, there needs to be robust evidence that this shielding is effective, that these otherwise toxic therapies now behave differently in a much safer way in these patients. Thirdly, we'd hope to see a renewed therapeutic index where there is a greater margin between efficacy and safety of these maintenance therapies. And lastly, of course, we'd like to see early benefit for patients themselves, particularly in terms of relapse-free survival. We'll be showing you elements of all four of these attributes in early data from our VBP101 trial. As a reminder, before we get into the data, our shielded transplant is called trem-cel. trem-cel is a product derived from apheresis product that is otherwise normally used in regular transplants worldwide. Now, instead of using this unmanipulated, we put it through a number of different manufacturing steps, including a cell sorting step to make sure we isolate stem cells and, secondly, through a CRISPR-Cas9 gene engineering step. And that allows us to precisely edit the genome of these cells to remove expression of a protein called CD33. This is a protein that we believe is biologically dispensable. And by removing this protein, we can now shield the blood system while exposing the cancer, which still expresses CD33, and therefore allow for maintenance therapies after the stem cell transplant. This whole process takes around seven days, with another few days of product release. And with this, I'll hand over to our Chief Medical Officer, Dr. Eyal Attar. Thank you very much, Robert. The VBP101 study is for patients with high-risk AML characterized by having one or more high-risk features, including the presence of measurable residual disease, active disease, adverse genetic and molecular risk, and secondary AML after MDS. Patients with this risk profile have an approximately 70% chance of relapsing or dying within two years of a standard allogeneic transplant. In this study, patients are identified for transplant by their physicians, and as they are proceeding toward transplant, a match for related or unrelated donor is identified through standard means. Peripheral blood stem cells are collected from the donor, and the CD34-isolated, CD33-deleted drug product known as trem-cel is generated. Following conditioning for transplant for the patient, trem-cel is infused to the patient, and as patients get to day 60 and beyond after transplant, they are eligible to receive the CD33-directed antibody drug conjugate Mylotarg for the purposes of maintenance therapy. Mylotarg is administered once a month for eight monthly cycles. The following will present data regarding the engraftment of trem-cel, the hematologic protection or shielding provided by the trem-cel graft in the setting of Mylotarg administration, the broadened therapeutic window and safety profile of Mylotarg when administered after trem-cel, and emerging relapse-free survival data as a measure of patient benefit from this study. As of the November 1st data cutoff date, there were 25 patients infused with trem-cel, of which 15 had received Mylotarg across 64 Mylotarg infusions. trem-cel was generated for all of these patients with a high rate of CD33 editing efficiency of a median of 90%. The median time to neutrophil engraftment was 9.5 days, faster than the benchmark of 11 days for standard unedited CD34-isolated grafts. Similarly, platelet recovery occurred at a median of 16 days, one day earlier than reported for unedited grafts. As anticipated, there was full donor myeloid chimerism across all patients at day 28 and beyond. This demonstrates the hematologic protection afforded by trem-cel in the setting of Mylotarg administration, incorporating multiple cycles across all three doses of Mylotarg tested for a total of 64 Mylotarg infusions at this data cut. For reference, the few studies that have attempted administration of Mylotarg after a standard transplant have demonstrated high-grade neutropenia and thrombocytopenia and the ability to administer only a very limited number of cycles. In contrast, in this graph, where day one represents the first dose of Mylotarg and generally occurs between day 60 and 70 after trem-cel transplant for these patients, the top line represents the platelet counts, and the bottom line represents the neutrophil counts of these patients following initiation of Mylotarg administration. The stability of the platelet and neutrophil counts over time demonstrates that trem-cel is effectively shielded from Mylotarg, enabling the use of Mylotarg maintenance after transplantation. Like other antibody drug conjugates, Mylotarg is metabolized following binding to its target. Whereas Mylotarg is approved in AML at doses of six, three, and 2 mg/m², depending on the setting, the VBP101 study intentionally explored lower doses of Mylotarg in maintenance, given patients had received a CD33-deleted graft and thus had lower levels of CD33 by design. The left panel shows the PK profile of Mylotarg across the three dose levels tested. The top right panel shows the area under the curve, or AUC, from the VBP101 study in colors corresponding to the administered doses of Mylotarg, and in gray, the bars represent the population PK analyses of Mylotarg from the FDA ODAC minutes in standard AML patients. AUC is the Mylotarg parameter related to efficacy. These data demonstrate that the dose of 2 mg/m² Mylotarg in the VBP101 study achieves an area under the curve of 90,000 ng/ml, similar to a dose of 9 mg/m² Mylotarg in standard AML patients. Considering AUC is related to efficacy, this is viewed as favorably. The bottom right panel indicates the Cmax, the Mylotarg parameter related to safety. The goal has been to target a Cmax below approximately 2,000 ng/ml, where the risk of liver toxicity increases. The Cmax in VBP101 in patients treated with 2 mg/m² Mylotarg is approximately 1,000 ng/ml and well below the 2,000 ng/ml threshold. In addition, this is below the Cmax of the approved Mylotarg dose of 6 mg/m² in standard AML patients. The increase in AUC at 2 mg/m², with only a modest relative increase in Cmax at 2 mg/m², corresponds to a favorable broadening of the therapeutic window of Mylotarg in patients who have received trem-cel. This table indicates the baseline features of the 24 AML patients enrolled to the study as of this data cut, of whom 15 have received at least one dose of Mylotarg, and others are awaiting reaching day 60 to begin maintenance Mylotarg. As you can see, the population is at high risk of relapse, with more than half of the patients having adverse molecular or genetic risk by ELN criteria, 33% having a TP53 mutation, 42% having secondary AML, and 26% of the patients having either MRD or active disease at the time of transplant. Furthermore, more than half of the patients have more than one risk factor. By comparison, the third column reports the demographics from a published population of high-risk AML patients from the Fred Hutchinson Cancer Center in Seattle who underwent transplantation. In addition, the fourth column provides a reference population, which has been published, reflecting patients with adverse risk by ELN who underwent transplantation from a cohort in Germany. This data depicts the relapse-free survival of the VBP101 population in blue relative to the two published comparators. The red line reflects the relapse-free survival for the MRD-positive population in the Seattle study, and the green line the ELN adverse risk patients from the German study. With a median duration of follow-up of 7.4 months, the median relapse-free survival for the VBP101 population has not yet been reached and appears favorable relative to these two published cohorts. Importantly, there are no new events in the VBP101 population compared to the July 19th data cut. This swim plot demonstrates continued progress in the study, with purple diamonds showing timely engraftment across all 25 patients treated, one of whom had MDS, a recently added population to the study. The green triangles indicate the Mylotarg doses, which include 64 administrations among 15 patients, with others not yet eligible to receive Mylotarg as they are not yet at day 60. New data includes that six patients have received at least one dose of Mylotarg at 2 mg/m², which, following completion of cycle one in the last patient, the dose escalation committee met and reviewed safety, PK, and other data, and concluded that the recommended phase II dose for Mylotarg following trem-cel is 2 mg/m². Note still, only two patients have relapsed after receiving Mylotarg and two before, and while one patient discontinued to receive a donor lymphocyte infusion for treatment of post-transplant viral infections, they were in remission at that time. As the adverse event profile for trem-cel at this point is similar as for unedited CD34-isolated grafts, this table focuses on the safety profile for the patients who have received Mylotarg and on the adverse events of interest, specifically hematologic adverse events in the top and hepatic in the bottom. For comparative purposes, Mylotarg is associated with hematologic toxicities across patients and studies that have applied Mylotarg after transplantation, and these studies have reported frequent advanced grade three and four adverse events. The top panel here, in contrast, shows that hematologic toxicities are infrequently reported and are largely related to adverse events in the settings of other routine post-transplant medications and infections, which themselves can cause low blood counts. Similarly, only a limited number of hepatobiliary events have been reported in patients who have received Mylotarg on VBP101, and almost all are low grade. A patient had grade two and three ALT and AST elevation, respectively, but this occurred in the setting of fluconazole and resolved after discontinuation of this medication. There was one case of VOD, which was graded as mild by standard EBMT criteria, and which occurred in the setting of several confounding medical events. Specifically, this occurred approximately 100 days after their most recent dose of Mylotarg, which was at 0.5 mg/m², and this event was preceded by azole medication hepatotoxicity, norovirus gastrointestinal infection with diarrhea, and gram-negative bacteremia, which is important as systemic illnesses have been associated with risk of VOD after standard transplants. To summarize, the VBP101 study continues to demonstrate robust neutrophil engraftment and platelet recovery with full donor myeloid chimerism. The study demonstrates consistent shielding from Mylotarg-related cytopenias during repeated dosing across the different Mylotarg doses tested. There is immune reconstitution and multilineage chimerism in a safety profile similar to unedited CD34-selected grafts. Our data demonstrates a broadening of the Mylotarg therapeutic index following trem-cel, and the preliminary data presented suggests an improved relapse-free survival compared to published groups of high-risk AML patients who undergo allogeneic stem cell transplantation. With these data in mind, we have worked with our KOL to develop this registrational study design. It involves a one-to-one randomized study of an experimental arm consisting of trem-cel followed by eight cycles of Mylotarg versus a control arm consisting of patients assigned to standard of care transplantation. The eligibility is nearly identical to VBP101, except the patients with active AML are excluded, as they may be chemorefractory and relapse shortly after transplantation and therefore not have an opportunity to receive Mylotarg. Further, some centers do not transplant patients with active AML, and this would leave open the possibility that these patients would be removed from study if randomized to the standard of care control arm. Finally, at the suggestion of investigators who have treated patients on the VBP101 study, the Mylotarg start was brought in from day 60- day 30. The primary endpoint of the study is relapse-free survival with an approximate target delta of 20% at two years, 80% power, and two-sided alpha of 0.05. Upon recent favorable communication with the FDA, there is agreement that trem-cel engrafts neutrophils and platelets and has a similar safety profile to unedited CD34-isolated grafts. In addition, there's agreement that the trem-cel Mylotarg registrational clinical trial design with respect to study population, control arm, primary endpoint, stratification factors, and statistical design is appropriate. Vor Bio remains committed to providing the FDA additional updates from our VBP101 study as we continue to advance our clinical development plans in advance of submitting the full registrational clinical trial protocol. Thank you, Dr. Attar. We at Vor Bio are very proud of the data that we generate, and we particularly want to thank the patients and the investigators on our studies. As a reminder, trem-cel is a first-in-class stem cell product that is meant to be shielded against CD33-targeted therapy. We are also working on the combination of Mylotarg, as you've seen, getting supportive feedback from the FDA on a potentially registrational clinical trial design. In addition, we are still working on pipeline products, including VCAR33 Allo, which is an allogeneic healthy donor-derived CAR- T therapy targeting CD33, also meant to be complementary to trem-cel. And separately, an ADC called VADC45, which is an antibody-drug conjugate targeting a new target called CD45. With this, I'd like to thank Dr. Attar for summarizing the data, and I'll invite comments from one of our clinical investigators, Dr. Guenther Koehne. Yes, good morning, everyone, and greetings from the current ASH Meeting in San Diego. I think you heard that these outcomes I've described are very impressive and exciting news from my perspective at least. But just to reiterate everything, so where are we? Here we have a high-tech transplant approach, gene editing or downregulation of marker on the hematopoietic stem cell. And the current results are clear, showing it's safe to gene edit the product and administer this to patients with leukemia and high-grade MDS. It was clearly described that there is a normal engraftment at the same time than the non-gene-edited transplant products, and the recommended phase II dose for gemtuzumab has been now found. All in all, I think it's relatively clear that now there is strong evidence for a better outcome for these patients. But let me add another aspect to it that really relates to the platform of this gene editing approach, which is the purification of the hematopoietic stem cells by CD34 selection. That's a platform that I've been very familiar with and was a pioneer to implement this at the Memorial Sloan Kettering Cancer Center and therefore have a lot of experience with this. And it's an ideal platform for the gene editing and post-transplantation maintenance treatments or even treatment of minimal residual disease or relapse. But in addition to all the factors that were just mentioned, there is a potential that has been not described, and that is there is a limited development of graft versus host disease in these transplant approaches. There is no need for post-transplantation immunosuppressive therapy because of the elimination of the donor T cells, which enhances only the platform for maintenance therapies post-transplantation. Here we see and heard that gemtuzumab has been administered safely at doses as described, and we have a platform for additional post-transplantation immunotherapeutic approaches such as the CAR-T cells that were just mentioned by Robert Ang. With that, I think we have a new platform. I'm looking for a platform for patients with high-risk AML and secondary MDS that transfer to transform to AML that I feel is a very promising and exciting dose to have in the pipeline. Thank you very much for including me to this. Thank you. As a reminder, to ask a question, please press star one one on your telephone and wait for your name to be announced. To withdraw your question, please press star one one again. Our first question comes from the line of Stephen Willey with Stifel. Your line is now open. Yeah, good morning. Congrats on the data, and thanks for taking the question. Robert, I was just wondering if you could speak to who will comprise the efficacy-evaluable population in the proposed phase III protocol? Are these all patients who receive conditioning, or is it all patients who receive a transplant? And then secondly, is there anything that you can say just around preliminary powering assumptions on the primary endpoint of relapse-free survival? Sure. I'll address the first, and I'll have Dr. Attar address the second. So the patient population is very similar to what we are enrolling in the VBP101 trial. The eligible patient population will be transplant eligible, and so that's the basis on which they will be enrolled. And the high-risk features are spelled out in slide 18 on our new corporate deck. Again, this really resembles what we're enrolling in the phase III trial, aside from the fact that we are no longer enrolling active disease patients, so those of a 5% blast and marrow. Understandably, some transplanters may not want those patients to receive a standard of care graft. And so to avoid bias, we are steering away from those high-risk patients. But Eyal, would you like to spell out the statistical assumptions? Yes, thank you for the question, Stephen. The evaluable population will be patients who have been randomized to either the experimental arm or the control arm. And the powering of this study is 80% for an anticipated two-year RFS delta of 20% or more. To address the first point, as Robert mentioned, patients require one or more high-risk features, which would typically be secondary AML after MDS, MRD positivity, or ELN adverse risk. As you're well aware, the patients on our VBP101 protocol have a high degree of adverse risk features, with more than 50% of the patients having two or more of these high-risk features. The primary analysis is done on the ITT population based on the time of randomization, but of course, there will be additional subset analyses based on transplantation and receipt of the maintenance therapy. Okay, that's helpful. Then you obviously have a few patients in queue here, which I'm presuming will be dosed with 2 mg /m² given. That's now the declared recommended phase II dose. But how much clinical experience do you want to gain at that dose? How many patients should we expect to see over time? And how much clinical experience do you want to gain with a day 30 Mylotarg administration before you move into the registrational program with that protocol? And that's it for me. Thanks. Thank you again, Stephen. We'd like to get approximately 20 patients' worth of data at the 2 mg/m² cohort. As you saw from the swim plot, there are additional patients who are currently enrolled, transplanted with trem-cel, and are awaiting receipt of the Mylotarg at 2 mg/m², which is our go-forward dose at this point in time. The data continues to shape up, and as it matures, we will be able to put the final touches on our registrational protocol. Thank you. Our next question comes from the line of Andrea Newkirk with Goldman Sachs. Your line is now open. Hi, good morning. Thanks so much for taking the questions. Maybe just one follow-up there. In terms of thinking about the 20 patients that you'd like to see clinical data from, maybe based off of the pace of enrollment and treatment, if you could give a rough estimate of the timeframe over which you think that those 20 patients could accrue data such that you can move to the registrational program, that would be helpful, and then I have a follow-up. Sure, Andrea. Thanks for the question. We are almost fully enrolled for those full 20 patients at 2 mg, and so we'll continue to prosecute them along the protocol with treatment with Mylotarg starting around day 60. Got it, and over what timeframe of follow-up would you expect or would you like to see before feeling comfortable moving to the registrational program? Sure. So, I think there's several aspects here that are important. We do want to follow up these patients over time to give us more confidence around the primary endpoint, in particular, relapse-free survival. We also have preparations we'd like to do prior to commencing the phase III, particularly regarding CMC. And all of these things can happen in parallel. So I think what we are planning to do is provide guidance soon regarding the start of the phase III. I think notably that the FDA did not require any particular data before starting it. I think they're looking for us as a sponsor for our own guidance in terms of what we deem as sufficient. But I think it's a prudent strategy to further enroll patients at the 2- mg cohort, which will de-risk the phase III design. Okay, thank you. Thank you. Our next question comes from the line of Matt Biegler with Oppenheimer. Your line is now open. Hey guys, congrats. Especially not showing any new relapses. That's really impressive. We noticed the cadence of recruitment's really picked up. Rob, do you think that's a function of investigators getting more comfortable with the procedure? And I guess knowing that and knowing how many sites you want to target, how long do you think that randomized phase II is going to take to read out? And as a follow-up, I just wanted your thoughts on the proposed control arm. Does that include haploidentical patients, or are we just sticking to T cell depleted approaches? Thanks. Sure. Thanks, Matt. So at this point, to answer the last question, we are still looking at eight out of eight matches just given the conditioning regimen that we're using. We certainly have thoughts around haplo or potentially RIC regimens where we could expand the eligible patient population, but for now, we'd like to keep things relatively standard. I'm sorry, could you repeat the other part of your question, Matt? Just on the cadence of enrollment and what do you think's driving that? Is it a function of investigators getting more familiar with the procedure or just more sites or maybe a combination of both? We did add a handful of sites to the VBP101 study. This was really just based on interest from investigators. We're at a cadence of enrollment with 15 sites that is essentially exceeding the supply constraints from a single suite that is manufacturing for us now. We think this is a very plentiful demand for the current study. We think we can expand up to around 30 sites. We've actually had far more demand than this from new sites who'd like to participate in the phase II study. But approximately 30 sites, we think, will be able to robustly enroll the study where we could supply out of two production suites. At a future stage, we'll be able to provide further guidance on how fast we can enroll the study and timelines to read out. All right, thanks a lot. Thank you. Our next question comes from the line of Jack Allen with Baird. Your line is now open. Hey, thanks for taking all the questions and congratulations on the progress of the team. I just wanted to ask, is Dr. Guenther Koehne available for questions as well? Yes, Dr. Guenther Koehne should be available. Okay, great. Dr. Koehne, I wanted to thank you for your commitment to the program and pushing innovation forward in AML, and I wanted to give you a chance to field a question. I know there are some cross-cohort comparisons being made with external datasets here, but as it relates to VOR's patient population, what would your view be of relapse-free survival rates at maybe a six-month and a 12-month benchmark in that patient population with an unengineered graft and no Mylotarg treatment? Yeah, thank you for the question. It depends on the disease diagnosis a little bit. We heard there are different outcomes for AMLs now, and not all the AMLs are created equal if you wanted. Particularly what I think Eyal presented on TP53 mutated AMLs or TP53 mutated AMLs, those results are already very encouraging. That patient cohort with high-risk cytogenetic abnormalities has a very short time period of progression-free survival even after allogeneic stem cell transplantation, and I think the number that you heard was within six months. There's a median progression-free survival that means some of them relapse even earlier than that and others a little bit later than that, but six-month benchmark would be a really critical time point to assess already. Got it. Got it, and then just very briefly, in your practice, how many AML transplants are done for frontline or post-consolidation treatment versus in a relapsed patient population? I'm trying to understand what the relative opportunity is for relapsed AML. The majority of patients with a diagnosis of AML will go to undergo allogeneic stem cell transplantation. In fact, there is just a small subcategory of so-called good-risk AMLs that undergo induction chemotherapy consolidation and will be assessed by minimal residual disease whether or not they need to get a transplant. And by the time they convert to MRD positivity or remain MRD positive, they will also be transferred for transplantation. So that's, in fact, the majority of patients with newly diagnosed AML will undergo an allogeneic stem cell transplant. And in addition, all secondary AMLs that had preceding MDS, without question, require an allotransplant. Thank you so much for that context. And then maybe shifting gears to VOR, I know you've already fielded a number of questions around the pivotal study, and we expect to gain more guidance around the timing of enrollment and various factors there. But I wanted to ask if there's any opportunity for potentially an interim analysis of this study. I know you talked about powering on a two-year assumption on RFS, but it sounds like progressions could even occur at a six-month time point here. How are you thinking about the size of the study and potential for interim analysis? So Jack, I'll take that study. That question, rather. We have a group sequential design with that analysis. So it's a two-year enrollment rate. And the first analysis of this group sequential design takes place at last patient in plus approximately nine months. That's when about 75% of the data is available. It gives us the opportunity to get an initial look at the relapse-free survival delta and hopefully begin to prepare for what would be a BLA. We would anticipate the final data to be available at approximately last patient in + 24 months. Got it. Got it. It's very helpful context. And then finally, on the business development front, this is a very interesting program where you're protecting against CD33. And I know there are a number of other players out there beyond yourselves with your CD33 CAR-T program looking at assets against CD33. I know Mylotarg is marketed by Pfizer right now. Any thoughts as it relates to business development opportunities for the platform and opportunities for non-dilutive capital in that capacity? Sure, I can field this. So I think we've really come with the intent that trem-cel and similar shielded transplants are essentially a therapeutic platform upon which you can layer on other modalities, including our own CAR-T, including ADCs like Mylotarg, including even bispecific modalities. And so we've been intrigued with different combinations, and we have appropriate conversations ongoing with Big Pharma or Biotech with potentially synergistic targeted therapies. Great. Congratulations on the progress, and thanks so much for taking all the questions. Thank you, Jack. And while we have Dr. Guenther Koehne, I'm wondering if you would like to comment on Matt Biegler's question just in regards to being an investigator on the study and your willingness to put patients on and what you see is attractive for these patients. Well, you just induced a question with an answer that is full of excitement, as you know. So having the CD34 selected platform for transplant approaches, and I'm very familiar with this because I transplanted quite some patients on this approach with AML and MDS, seeing the quality of life of these patients, seeing the absence of immunosuppressive therapy afterwards, and seeing the platform for maintenance treatment, as I described before, induces even post-ASH in San Diego the excitement to continue to improve on. If you look at the comparative studies, so CD34 select allografts have already shown the best leukemia-free graft versus host disease-free survival compared to other transplant approaches. And here now we have an approach to even reduce the risk or the presence of MRD or relapse disease that all in all just provides me with a strategy or a discussion with the patient saying, "Look, you have a high-risk AML, and here we have a promising approach. Even after transplant with the risk for relapse, we can do something for you." That is, I think, would put every physician and every scientist into a completely different mode of discussion with these patients that need significant help and support to get through the diagnosis and this disease. Great. Thank you, Dr. Guenther Koehne. Thank you. Our next question comes from the line of David Nierengarten with Wedbush Securities. Your line is now open. Hey, thanks for taking the question. I had a couple. First off, on the potential registration design, moving the Mylotarg eligibility to 30 days, I assume there's an option you say 30 days or later if the patient hasn't recovered fully from the transplant that they could put that off. And then I had a question on how do you, I think you mentioned intent to treat for the statistical analysis. I was just wondering maybe more specifically, how do you treat or how do you calculate for patients who might relapse before the Mylotarg? Are they just not counted because they haven't been treated with Mylotarg, or how are they treated statistically? Thanks. Sure. So David, that is a great question. The moving of the Mylotarg from day 60- day 30 is at the suggestion of the investigators simply because as they have enrolled more patients and have gained more experience using the Mylotarg in maintenance, it became clear that because of the adverse event profile of this transplant, which, as Dr. Guenther Koehne has mentioned, is quite favorable, that it was at their suggestion that we moved the Mylotarg initiation from day 60 and beyond in our first-in-human study to day 30. And again, that was simply because the adverse event profile of the transplant concurrent with the adverse event profile of Mylotarg, which in their hands has been favorable, gives confidence that we can move it in and better suits the needs of these patients who are at high risk of relapse. Now, I'd like to address your question about the ITT population and furthermore how to deal with patients who might drop out prior to transplantation or even relapse prior to the opportunity to receive the Mylotarg therapy. We have modeled a dropout rate for patients from the time of screening and consent to the receipt of trem-cel. And as that proportion of patients has been small, we're confident that the ITT population will be very similar in number to the as-treated or as-transplanted population. Secondly, as Robert had mentioned earlier, and as we had the opportunity to discuss in the presentation, as you're well aware, we had only four relapses on study, and only two of those were after Mylotarg, and they occurred at the lower doses of Mylotarg, not at the go-forward dose of 2 mg/m². Concerning the two patients that relapsed prior to Mylotarg, they were both transplanted with active disease, namely 8% and 16% myeloblasts at the time of transplantation. To minimize the possibility that patients will relapse immediately after conditioning and prior to the Mylotarg, in conjunction with our investigators, we have excluded that ultra-high-risk population of patients with active disease from the pivotal study. Again, as many centers will not transplant patients with active disease, we knew that keeping them within the eligibility would potentially introduce an imbalance as patients randomized to the standard of care arm would fall off. So that's how we've dealt with this situation. Thank you for the great question, David. Thanks. Thank you. Our next question comes from the line of Silvan Türkcan with Citizens JMP. Your line is now open. Hey, good morning, and congratulations on the data. Thanks for taking my question. I just want to talk about the maybe perhaps information content you have in your relapse-free survival curve at this point. It seems like most of the two-milligram patients are out to four to six months, so they contribute significantly to this curve. How confident are you in the improved survival at this point versus your reference data and also thinking about the fact that the reference data perhaps has a little bit more active disease in it, which is a key indicator of fast progression? And then I have a follow-up. Thank you. Thank you for the question, Silvan. We are very confident in the RFS data as we have presented it across the program. In order to provide the most comprehensive look, we provided the RFS for the 25 patients on the study. But as we have looked at subsets, it continues to shape up very, very nicely. And as you point out, however, we don't have as long a follow-up on the 2-mg/m² cohort. But as you have seen from the RFS curve, at that point in time, certainly there have been no relapses in the 2-mg/m² cohort, and it's something that we continue to scrutinize very, very carefully. Now, as you point out, our comparator studies look at two distinct groups of patients, the MRD positive population from the Fred Hutch experience published in 2016, and a more modern look from the group in Germany based on adverse risk patients with high-risk ELN criteria. In review of these patients, concerning the fact that our patients, more than 50% of them have two or more high-risk features, we have a high degree of confidence that the appropriate comparative curve for our population would be that green EBMT curve, or perhaps even worse, even lower than what we've depicted on the RFS curve. Great. Thank you. The first caller here. And then can you talk a little bit about the exposure you measured with Mylotarg post-transplant? We talked a little bit about the PK at the poster, but it seems like the antibody is around until day 28. Could this altered PK/PD profile make Mylotarg a very different point that may be even more potent at this point? And what about that VOD in that patient that you measured? Thank you. Sure. I can tackle this. We think we've really changed the way Mylotarg behaves in these patients. As you know, Mylotarg is an ADC. It is generally cleared like a lot of ADCs through antigen binding, and there simply isn't an antigen in these patients. And so you see a phenomenon where the Cmax is really distributed across that volume of distribution, but the AUC is quite prolonged because of the lack of antigen binding. What this means is that there's a significant tail of Mylotarg in these patients such that we can even detect Mylotarg levels at the tail end at day 28 just prior to the subsequent dose. We think this is a good thing in these patients in that Mylotarg does not seem to be causing significant cytopenias in these patients because of the shielding effect of the CD33 deletion, but is available and potentially there to scrub any remaining CD33 expression, particularly from any AML blast that may be remaining in marrow, and so we view this as an ideal circumstance. This is pharmacokinetic data that the FDA was already privy to in our correspondence with them in the type C setting, and they had no comments or concerns regarding these pharmacokinetics. Great. Thank you, and congratulations. Let me just address the VOD question you had. As you referenced, and this is outlined on slide 14 of the new corporate deck, there was one instance of the veno-occlusive disease that we noted. It was classified as mild by the investigator. This VOD case was unusual in that it happened 97 days after the dose of Mylotarg at 0.5 mg. There were a number of predisposing factors in this patient, which included a zole toxicity that happened previously, as well as a concurrent norovirus infection and a gram-negative bacteremia that approximated the VOD. As such, it's impossible to rule out the contribution of Mylotarg for the VOD, but we think it's more likely that the VOD was triggered by some of these other predisposing factors. We have not seen any VOD in any other patient, and again, that patient was at a 0.5 dose, so we haven't seen it at 1 mg or 2 mg, but of course, we continue to be vigilant about any liver toxicity as we move forward. Thank you. Thank you. As a reminder, to ask a question at this time, please press star one one or your touch-tone telephone. Our next question comes from the line of Justin Walsh with Jones Trading. Your line is now open. Hi. Thanks for taking the question. I'm wondering if you can provide any color on the patients who went off study. I'm curious about what drove that in patients who didn't relapse while on study and if any of the patients who did relapse were able to receive subsequent treatments or transplants. Thank you very much for the question. We did have one patient who went off study, which was counted as an event, and that occurred in the setting where there was no leukemia relapse, but where unfortunately the patient was dealing with some post-transplant viral infections, which can be seen following any kind of allogeneic stem cell transplant. And in the setting of receiving medications to treat those viral infections, unfortunately developed some renal insufficiency and decided to withdraw their care and thus unfortunately passed away without AML relapse. As you're well aware, we've had only two patients relapse after receipt of Mylotarg. And for patients who relapsed after transplantation, particularly for those two patients who had mutant TP53 disease, their disease progressed quite quickly, and thus they were not eligible to receive extensive additional therapies beyond that point in time. And finally, on the swim plot, you're also aware that we had a patient who went off study without receiving Mylotarg, but that patient did so without active disease. It's simply that they received their backup graft in order to, or rather donor lymphocyte infusion in order to provide more lymphocytes to address some viral infections. Because of the way the protocol is written, patients that receive a donor lymphocyte infusion go off study. But again, that patient, which we have demarcated on the swim plot, did so without active disease, certainly without relapse. Got it. Thanks for taking the question. Thank you. Our next question comes from the line of Li Chen with H.C. Wainwright. Your line is now open. Hello. This is Li for RK. Congratulations on the data. My first question is about the safety profile, the safety data shown on slide 14. Can you help us understand what's the biology behind the heme toxicity where you only predominantly see only grade 3, but not much in grade 1 and 2, but the liver toxicity is primarily in grade 1? This is an excellent question. I think the important thing to keep in mind is that if these patients were receiving Mylotarg after a standard of care transplant, you would see a very high number of patients, for example, 13 or even 15 out of 15, who would have grade 3 or 4 thrombocytopenia and neutropenia when administered after the transplant. What we are reporting here at the request of the investigators is really a favorable adverse event profile for the 15 patients who went on to receive Mylotarg. Importantly, you see that there are only a few instances of grade 3 and 4 hematologic adverse events. The important thing to keep in mind is that these are highly related to polypharmacy. These patients, after a transplant or addressing multiple infections, and they are often receiving either prophylactic antimicrobial agents or agents used in the therapeutic setting, which they themselves will have associated neutropenia and thrombocytopenia. And so considering the polypharmacy, which is utilized after transplantation across any transplant, we were quite pleased that there are only few instances of grade 3 and 4 neutropenia and thrombocytopenia. I'd like to address the one case of grade 4 thrombocytopenia. And that occurred in a patient in their first cycle of therapy who then went on to get multiple additional cycles of Mylotarg therapy. We know that patients that start Mylotarg in the 60- 70 day window in time, that is a vulnerable time of hematopoiesis after a transplant when there's a handoff of hematopoiesis from intermediate to long-term hematopoiesis, which transplanters call the dip. That also coincides with the time that we start Mylotarg, and that really does address that one instance of grade four thrombocytopenia in the first cycle of therapy. So considering that phenomenon in conjunction with the polypharmacy of these patients, this is a favorable adverse event profile. Now, I'd also like to address the hepatobiliary adverse events, which again are low-grade. They occur in a limited number of patients. And as you can see, the one patient with the grade two and grade three ALT and AST transaminase elevations that occurred in a patient who was receiving fluconazole therapy, as you're well aware, azoles are known to cause transaminase elevations, and this adverse event promptly resolved following discontinuation of the azole. So from the perspective of what we hear from investigators, a favorable hepatobiliary adverse event profile. Thanks. Next caller. Second question or follow-up question is, do you see any correlation between the editing efficacy and the hematology toxicities profile? Well, we have a very clean hematologic toxicity profile, which is mainly guided by polypharmacy and ongoing infections in these patients. And so the profile looks quite favorable. We've really had only the two relapses after Mylotarg among a denominator of 15 patients. So there are too few numbers to draw conclusions around predictive biomarkers at this time or predictive clinical features associated with relapse. Thank you for the color. Thank you. Our next question is a follow-up from the line of Stephen Willey with Stifel. Your line is now open. Yeah. Thanks for taking the question. Just to clarify, are you going to try to incorporate day 30 administration of Mylotarg into the VBP101 trial protocol? Yeah. Thanks, Steve. So we don't think so at this point, only just because the enrollment is going so well. And at this point, we're almost fully done with the 2-mg cohort. We did ask FDA this particular question in our proposed phase III design. They were very open to the day 30 dosing and did not require any additional patients on the VBP101 study to be dosed at an earlier time point. Okay. And then maybe just lastly, I know there was the one patient who came off study because they received a donor lymphocyte infusion. Will that same, I guess, protocol be used in the confines of a phase III where if a patient receives a DLI, they're off study? The standard of care for patients who need additional lymphocytes to address the potential for viral infections does exist. And of course, any standard of care modality for the benefit of patients will be utilized. So certainly, if a patient requires a DLI, they would receive it on study. But more specifically, a patient on the pivotal study would certainly continue to be followed for relapse and for survival as those are important endpoints on the study. Okay. Thanks for taking the follow-ups. Thank you. And I'm sure no further questions at this time. This does conclude today's call. Thank you all for your participation. You may now disconnect, and everyone have a wonderful day.