Operator
Thank you for standing by. Welcome to Nkarta Conference Call to review the clinical update for NKX101. At this time, all participants are in listen-only mode. Please be advised that this call is being recorded at the company's request. I would now like to turn the call over to the company.
Greg Mann
Thank you, operator, and good morning, everyone. I'm Greg Mann, SVP of Public Affairs and Investor Relations at Nkarta. Thank you for joining our call this morning. Earlier today, Nkarta issued a press release announcing updated clinical data from the clinical trial of NKX101. This press release, today's webcast and corresponding slides are available on our website. We're looking forward to discussing these results as we advance the next generation of cell therapies for cancer patients. On the call today from Nkarta are Paul Hastings, President and Chief Executive Officer; Dr. David Shook, Chief Medical Officer; and Dr. Nadir Mahmood, Chief Financial and Business Officer. We're also honored to be joined by one of our distinguished investigators leading the NKX101 clinical trial, Dr. Carlos Bachier from the SeraCanon Transplant and Cellular Therapy Program at Methodist Hospital in San Antonio, Texas. Before we begin our prepared remarks, we'd like to remind everyone that comments made by Nkarta management in responses to questions on this call may include forward-looking statements, including statements concerning Nkarta's expectations regarding the therapeutic potential tolerability and safety profile of NKX101 and plans and time lines for the availability or future presentation of NKX101 clinical data and for the continued and future clinical development and commercial potential of NKX101.
These forward-looking statements are based on current information, assumptions and expectations that are subject to change and involve a number of risks and uncertainties that may cause actual results to differ materially from those contained in the forward-looking statements. These and other risks and uncertainties are described in our periodic filings made with the SEC such as our most recent and subsequent filings. You are cautioned not to place undue reliance on our forward-looking statements and the company disclaims any obligation to update such statements.
With that, I'd like to turn the call over to Paul Hastings.
Paul Hastings
Good morning, everyone, and welcome to our call. Earlier today, we announced an important update for Nkarta's NKX101 clinical development program in patients with relapsed refractory AML. As a reminder, NKX101 is a fully off-the-shelf donor-derived NK cell therapy that has been engineered with an NKG2D-based CAR to target cancer cells as well as membrane-bound IL-15 to enhance persistence and activation. Now the NKX101 findings that we're reporting today, build on the positive results that we presented last year. Our program continues to show promising antitumor activity in a heterogeneous disease, where response to therapy is poor and no standard of care exists without potentially life-threatening toxicities that are common with T cell therapies.
Now as with any Phase Ib study, we sought to identify a patient population with the best likelihood of response. We considered and prospectively evaluated patients with limited disease burden as well as a modified lymphodepletion regimen using fludarabine and Ara-C. We identified this regimen on clinicaltrials.gov in April last year prior to our first data announcement for NKX101. While it's still early, we're encouraged by the program's progress and the preliminary data from the modified lymphodepletion cohort.
We are seeing first cycle responders, deepening of response with additional cycles and limited CAR-T toxicities like cytokine release syndrome, ICANS or GVHD and are able to dose patients in the relapsed and refractory AML setting regardless of blast counts, eligibility for transplant or mutational subtype. Today's update includes outcomes for 13 new patients who received flu/cy lymphodepletion and 3 doses of NKX101. As you'll see, with the hope of identifying an actionable biomarker for selecting patients most likely to benefit from NKX101, we evaluated whether there was enhanced activity with NKX101 in patients with lower disease burden.
This hypothesis was built upon the data from April 2022 and the notion that NKX101 was generally more active in patients with lower peripheral blast counts. Now while these patients had up to 40% blast in the bone marrow, they had peripheral blast counts generally close to 0. We gave this hypothesis, our best shot even if this meant limiting the addressable patient population for NKX101. Unfortunately, low disease burden does not appear to be a consistent predictor of response. Now in addition to the flu/cy cohort, our other prospectively defined expansion cohort features a lymphodepletion regimen that may be better suited for patients with AML than the one-size-fits-all approach of standard lymphodepletion of flu/cy used with traditional CAR T cells.
Today, we are reporting outcomes for the first 6 patients treated with lymphodepletion comprising fludarabine and cytarabine, also known as Ara-C followed by 3 doses of NKX101 at 1.5 billion cells per dose. While considerable work remains to be done and more patients with longer follow-up will be needed, we're encouraged by these preliminary data, which reflect complete response rates that far exceed established regimens for relapsed/refractory AML. Now Ara-C is widely used as a component of treatment across different lines of therapy in AML, and we believe that it has the potential to be an effective lymphodepletion agent for allogeneic NK cells as well.
Additionally, Ara-C has been shown in the literature to upregulate NKG2D ligands, and we will share some preliminary data that suggests we can measure NKG2D ligand expression in patients and that increased expression of these ligands may enhance response. So we're very encouraged by the NKX101 data reported today. We expect to give our next update in the first half of 2024, which would include an additional 12 to 20 patients treated with 1 or more cycles of NKX101 at the 1.5 billion cell dose using flu Ara-C for lymphodepletion. Now we promised you an update in the first half of this year and the latest patient assessment came in just yesterday.
We always strive to present data at medical meetings, and we will continue to do so time permitting. Before Dave reviews the data, it's my pleasure to introduce Dr. Carlos Bachier, who will be sharing his views on the treatment landscape for AML and the unmet medical need faced by patients with the disease. Dr. Bachier is from the Cyrocanon Transplant and Cellular Therapy Program at Methodist Hospital in San Antonio, Texas and serves as the Medical Director of Research and Cellular Therapy at the CeraCannon Research Institute. He specializes as a principal investigator in Phase I/II clinical trials of hematopoietic cell transplantation and cellular therapies for hematologic malignancies.
Now at the conclusion of our prepared remarks this morning, Dr. Bachier will join us for the Q&A discussion. I'll now turn the call over to Dr. Bachier and Dave to provide an update on NKX101. Dr. Bachier?
Unknown Executive
Thank you. Acute myeloid leukemia, or AML, is a rapidly progressing cancer of immature blood cells called blast in the bone marrow. Treatment for AML includes multiple rounds of intensive cytotoxic chemotherapy in patients fit enough to receive such treatment. Unfortunately, while some patients may initially respond to chemotherapy, most patients were relapse. Among patients who are older or not fit to receive intensive therapy, few achieve remission and relapse is virtually inevitable. If AML is refractory to treatment or recurs after previous responding, it is difficult to treat even low numbers of blast may quickly multiply over on the bone marrow and blood and lead to death either due to disease or from treatment-related complications like infections and bleeding.
Patients with relapsed/refractory AML have very poor outcomes. Based on recent publications, only 12% to 18% of patients with relapse refractory AML achieve remission after salvage chemotherapy. This translates to poor survival with only 1 of 8 patients survive into 5 years. Hematopoietic cell transplantation is often the only opportunity for patients with relapsed/refractory AML to achieve long-term remissions. Those patients who achieved complete remission or CR before transplant enjoy far better survival and response to salvage therapies, therefore critical. Options are limited for most patients with relapse refractory AML.
A small number of patients have AML caused by specific genetic mutations that can be treated with various approved agents. Unfortunately, due to the targeted nature, these therapies only address a minority of the overall population with relapsed/refractory AML. And even with these therapies, response rates remain unacceptably low, we see our rates only modestly better than traditional cytotoxic chemotherapy. The combined impact of these agents result in less than 10% of all patients with relapsed/refractory disease, having their disease controlled.
In summary, AML is a historically hard-to-treat disease and people with relapsed/refractory AML are faced with few options. Thank you. And now let me pass the call back to Dave.
David Shook
Thank you, Dr. Bachier. NK cells kill tumors through a combination of activating and inhibitory signals driven by ligands on target cell surfaces, unlike T cells, NK cells LAC surface T cell receptors and thus do not need prior antigen stimulation for target cell recognition or killing, and they do not cause graft-versus-host disease. NK cells have been explored as potential therapy for AML for almost 2 decades when they were first described as having activity in patients with relapsed refractory AML. Since that time, various small academic studies have evaluated NK cells for AML, predominantly in the haploidentical setting.
While these studies reinforced the safety of NK cell therapy with limited toxicities such as cytokine release syndrome or neurotoxicity, clinical activity has been inconsistent with CR rates less than 20%. Building on the historical profile of NK cells in AML and our best-in-class NK cell platform, we opened the NKX101 study in patients with relapsed/refractory AML. Today, we are excited to present the latest data from our dose finding and early dose expansion cohorts of our Phase I study. This study enrolled a high-risk population with a poor prognosis as reviewed by Dr. Bachier. All patients must have received at least 1 prior therapy as well as any approved appropriate targeted agents.
Patients in the dose-finding phase were treated with NKX101 following lymphodepletion with fludarabine in ciphospamide or flu/cy, 2 regimens were evaluated, 3 doses on day 0, 7 and 14, and 2 doses on day 0 and 7. As discussed at our last announcement, our expansion cohorts all used the 3-dose regimen. Efficacy assessments using standard consensus criteria occurred on day 28 and patients could receive up to 5 treatment cycles based on efficacy and safety. This slide reviews the characteristics of all 30 patients with AML treated with NKX101 following flu/cy conditioning. The majority of patients had adverse risk disease. Patients have been treated with a median of 2 lines of therapy, including 5 patients who have prior allogeneic transplant, and almost all patients had received prior [indiscernible].
NKX101, following flu/cy lymphodepletion was well tolerated across all dose levels, including no dose-limiting toxicities up to 3 doses of 1.5 billion cells. The most common higher-grade toxicities were myelosuppression and infection, consistent with the use of lymphodepletion in a population of patients with relapsed/refractory AML. 5 patients or 12% had low-grade infusion reactions and another 12% of patients had low-grade cytokine release syndrome or CRS. One patient, an 81-year-old man with Alzheimer's dementia who developed worsening mental status changes in the setting of progressive disease and multi-organ system dysfunction was described as having Grade 2 ICANS by the investigator out of an abundance of caution.
Of note, this patient tolerated Cycle 1 without such toxicity. This swim lane summarizes responses and follow-up from the 12 patients treated in the early dose-finding cohorts using flu/cy lymphodepletion including both the 2-dose and 3-dose regimens. These responses were all previously detailed in our update last April. Upon comprehensive review of these data, responses appeared more consistent in those patients who had less than 5% blasts in their blood. At the time, this group represented approximately half of the patients who were presented for enrollment consistent with published reports of detecting relapsed AML prior to detecting over leukemia in the blood.
The second swim lane includes the 18 patients with AML who were treated with the 2 highest levels of the 3-dose regimen, 1 billion and 1.5 billion cells after flu/cy conditioning. We previously reported 3 patients with CR of the 2 patients with MRD negativity, 1 underwent allogeneic transplant and remains an MRD-negative CR over 18 months after therapy. One patient deferred transplant relapsed and declined further therapy. The patient with MRD-positive CR was also not consolidated and progressed. No further CRs were noted in the 1.5 billion dose level or subsequent expansion cohort, although 2 patients achieved MRD negativity. One had a best response of CRI or CR without adequate platelet count recovery and the other had a best response of MLFS or lack of adequate neutrophil and platelet recovery.
Of note, the association of low peripheral blasts and response suggested in earlier cohorts was not as consistent in these cohorts. Fludarabine with ARC is used in combination with other chemotherapies like anthracyclines in salvage therapy for relapsed/refractory AML. These combination regimens such as flag IDA have therefore been used as part of standard of care comparator arms for recent large registrational studies providing robust information on antitumor activity and toxicity that is impossible with small academic studies. In these studies, arms containing flag IDA result in true CR rates of approximately 10% and composite response rates of approximately 20%.
Of note, the addition of anthracycline such as idarubicin or [indiscernible] are added to flu Ara-C to increase antileukemic activity and thus 1 could expect flu Ara-C alone to be less active than the rates seen with those regimens. Further, these agents carry significant toxicity, some life long and, therefore, limit the addressable patient population. Ara-C is a DNA damaging agent that is potently immunosuppressive and is thus well suited for lymphodepletion. It has also been shown to upregulate NKG2D ligands and increased sensitivity to NK cell-mediated killing. In this cohort, patients received fludarabine and Ara-C once daily for 5 days prior to 3 doses of NKX101 at 1.5 billion cells per dose on day 0, 7 and 14, with efficacy assessment on day 28.
Like the flu/cy cohort, patients had the option for additional cycles to deepen response. These patients represented an especially high risk group with AML. 5 of 6 patients had poor risk genetic features, including TP53. Disease burden was also significant with median bone marrow blasts of 35% with a maximum of 86%. Patients had received a median of 2 lines of therapy and 100% had seen venetoclax-based regimens. The toxicities in this cohort were similar to the flu/cy cohorts. All patients were treated at the 1.5 billion cell dose and there were no dose-limiting toxicities. Myelosuppression and infection remained the most common higher-grade toxicities as expected with the underlying disease and exposure to lymphodepleting chemotherapy, but there were no infections above grade 3.
Importantly, there were also no cases of CRS, ICANS or GVHD of any grade in any patient. This slide summarizes responses in the Flu Ara-C cohort. As mentioned, this group carried several high-risk genetic and clinical features, including early relapse after allogeneic transplant chemo refractory disease and a patient who is medically unfit to receive anthracyclines. I'll highlight a few patients illustrative of the encouraging activity seen in this cohort. The first patient was a 70-year-old man with TP53 mutated AML who progressed within 6 months of transplant. He achieved a CR with full count recovery after 1 cycle of NKX101. And as this physician did not want to pursue a second transplant, they're requested to use a second cycle of NKX101 for consolidation which was not part of the clinical protocol at the time.
After FDA agreement, he was treated with cycle 2 and remains in CR. Patient 2 also relapsed after allogeneic transplant and was driven into successively deeper response with each of the 3 cycles of NKX101, ultimately achieving MRD-negative CR. Patient 3 failed to respond to traditional 7+3, cytarabine plus anthracycline chemotherapy, additional cycles of high-dose Ara-C FLT3 inhibitor therapy and venetoclax. After achieving CR with full count recovery, he was taken to consolidative transplant. Together, the 4 of 6 CR/CRI rate and the 3 of 6 CR rate was encouraging for this high-risk patient group. Our cumulative PK data is shown here and highlight 2 important things.
First, there is persistence of up to 3 weeks with NKX101 despite being an allogeneic non-HLA-matched cell product. This is consistent with published data on persistence of HLA haploidentical NK cells in combination with IL-2 support. In addition, these graphs support that Flu Ara-C can replace flu/cy as lymphodepletion without compromising PK exposure. Though preliminary, here are our data on the expression of various NKG2D ligands in patient bone marrow samples. These are stress ligands targeted by the CAR on NKX101. In this assay, we stain for MICA, MICB, ULBP1 and ULBP3 by immunohistochemistry and evaluated a composite 8 score.
We are now able to consistently detect the ligands on patient sample cells, which will help further translational analysis. This is a small and exploratory data set, but early data suggests responders may have higher ligand expression than non-responders. Of note, there are some responders who had relatively low ligand expression and vice versa, indicating further factors may contribute to NK cell resistance. Various cytokines are associated with inflammation and are correlated to the clinical syndromes of CRS and ICANS. Here, we show that after exposure to NKX101, these inflammatory cytokines are only marginally elevated. This contrasts considerably with elevation seen in patients who have had severe CRS as a result of CAR T cell therapy where multiple cytokines can exceed 100 fold increases above baseline.
Additionally, unlike CAR T therapies where there is obligate tethering of toxicity and a response, we see no association between cytokine elevation and response. In summary, relapsed/refractory AML is a highly heterogeneous disease. Response to traditional chemotherapy is dismal and while recent approvals of targeted therapies provide a treatment option for a limited number of patients, responses are still unacceptably low. The 67% composite CR in rate the flu Ara-C cohort is encouraging, although additional patients and longer follow-up will be needed. The safety profile, pharmacokinetics and cytokine profile, all further differentiate CAR NK cell therapy from CAR-T and support further development of NKX101 and AML.
In terms of next steps for the NKX101 program, a clinical amendment is in process to include consolidation or post-remission dosing as well as the option for retreatment in the case of relapse. We intend to continue dosing patients with AML at 1.5 billion cells per dose in the 3-dose regimen with flu Ara-C lymphodepletion and plan to announce additional data in the first half of 2024. This concludes our remarks on the clinical data for NKX101. I would like to thank everyone for their attention and interest in NK cell therapy. I would especially like to thank Dr. Carlos Bachier for his participation this morning, his contributions, along with other investigators and their respective institutions, and most importantly, the patients and their caregivers who have trusted Nkarta with enrollment onto this trial. I will now hand the call back to Paul. Paul?
Paul Hastings
Thanks, Dave. Now we will stop and look forward to hearing your questions. Operator, if you would please review the instructions for the Q&A section.
Operator
[Operator Instructions] Our first question comes from Stephen Willey from Stifel.
Stephen Willey
Just I guess on the completion side, have you looked at cellular PK as a function of flu Ara-C versus standard fleet side in cycle 2 and beyond. And I guess, does the cycle 1 similarity you're showing us hold up? And are you seeing a lower Cmax with subsequent redosing when you use either of the depletion [indiscernible] ? And then I just have a follow-up.
David Shook
Yes. So thanks for the question. So the numbers for [indiscernible] cycles are small, so it's hard. But generally speaking, the PK of 1 cycle versus the next seems similar.
Stephen Willey
Okay. And can you speak to just whether or not I know it's small numbers, but are you seeing, I guess, meaningfully lower Cmax with subsequent redosing?
David Shook
Yes. I don't -- again, I don't have the complete numbers, but in general, the exposure is pretty similar.
Stephen Willey
Okay. And then I guess with the incremental flu Ara-C data, you noted the 1 patient who had slow determined MRD negativity, can you just comment on how MRD negativity was determined in the other patients?
David Shook
Yes. So at this phase of the study, the MRD is all still local. So there's no central assessment of MRD. So and depending on the disease biology, mutational status, et cetera. Some patients were followed by a combination of PCR, NGS, et cetera. So it's whatever measure the investigator uses to determine MRD negativity for that patient's care. And if any of those are positive, the patient is determined to be positive. So whatever -- if we reported MRD negative, then that patient is MRD negative per the investigator to that patient and determines that care. So it's not a central assessment, but it's consistent with the level of disease control that they use to guide their own clinical care.
Stephen Willey
Okay. And then maybe just one quick question for Dr. Bachier. Again, I know it's fairly small patient numbers, but I think the slightly higher rates of hematological toxicity with flu Ara-C is probably understandable relative to flu/cy. I think there's a very small number of infections that we're seeing. Just wanted to get your feedback on how you think about being able to administer multiple cycles of lymphodepletion using flu Ara-C to an individual patient and whether or not that number is something lower than you think you'd be able to achieve with flu/cy?
Unknown Executive
Yes, I think -- thank you for the question. I think it's a good question, right? And so far, the patients that have been retreated have tolerated repeated cycles well. But point is well taken, right? If you start thinking about additional doses to patients that are a little older or more unset that may become a little bit limited. And the decision of giving subsequent cycles with additional rounds of lymphodepletion it's also using kind of clinical judgment on whether patients will be able to tolerate additional cycles I mean I think the good part is if you're getting a second cycle, those patients, in general, have entered remissions. They have obviously more robust hematologic recovery and our -- from a hematologic standpoint are better able to tolerate additional cycles. But the decision on whether to move forward with additional cycles based on the intensity of lymphodepletion type needs to be considered.
Operator
Our next question comes from Daina Graybosch from SVB Securities.
Daina Graybosch
Looking at the PK data, you noted that you're seeing cells after the third dose, day 14, but the Cmax is obviously much lower there. Do you think this 0, 7 and 14 days is the most optimal schedule after lymphodepletion? And will you consider bunching up dosing earlier after the depletion?
David Shook
Yes. Thanks, Daina. Yes, I think the short answer is Yes. And absolutely. I think we have experience using 0, 7 and 14. And as we explore the flu Ara-C cohort, I thought it was -- we thought it was important to demonstrate that they're relatively comparable, but that window related to being more proximal to lymphodepletion is certainly of interest. So I think it would certainly make a lot of sense to look at compressed dosing, and it's something that we're looking at very closely.
Daina Graybosch
And then maybe 1 more question on the flu/cy updated patients. And you have a lot of patients here that died or had progressive disease. Anything you can tell us about these patients like their blast counts or their disease specifically?
David Shook
In the flu/cy?
Daina Graybosch
Yes, yes, on the flu/cy.
David Shook
Yes. So I think one, obviously, these are patients that were pretty heavily pretreated and had refractory disease. We've annotated the ones that had less than 5% peripheral blast there but the marrow burden was pretty wide ranging. And fludarabine [ cyclophosphamide ] this will provide a lot of inherent disease control. So many of these patients went on to receive for their therapy and were chemo refractory even after that. So I think it probably was a reflection of the nature of the underlying disease. But yes, so you can see the annotation of those that had lower peripheral burden. But yes, pretty sick patients. And I don't think there's anything in particular.
Operator
Our next question comes from Salim Syed from Mizuho.
Salim Syed
I guess a couple for me. One, when you are -- look at you guys -- have you guys filed for new protocol on retreatment I'm just curious what is the [indiscernible] factors there? And when do you think we'll be able to actually start to retreat patients between now and the data that's going to come in into the first half of '24. And then just curious on the one patient that we saw the longest durability with the modified lymphodepletion regimen how translatable do you think that patient is to the other patients you plan to enroll for this expansion cohort?
David Shook
Yes. Thanks, a couple of great questions. I think the -- in terms of what we'd be able to do with additional cycles or additional dosing with either retreatment or even consolidation. With the safety profile and the response in such a high-risk population. FDA was certainly very friendly to us in the discussions of being able to give additional cycles to consolidate and we think they'd be probably pretty supportive on kind of one-off cases. We want to make sure that we incorporate in the protocol. But we're working on that to get it formalized and normalizing across the platform. So hopefully, that will be a part of the program soon.
And in terms of translatable, I think patient 1, who you highlighted is really illustrative of the case of need in this disease, right? Super high-risk disease in an elderly patient who relapse post transplant. And this is one when the investigator had this response was really very pleased with the outcome because this is a patient that I think nobody would have expected to respond to chemotherapy, [indiscernible] et cetera. So this was a certainly encouraging result.
And this will be no restriction whatsoever on disease burden, mutational status, it remain agnostic to prior transplant or upcoming transplant, reflecting real world. So I think unlike other therapies. This is one we could really be broadly applicable to the entire relapsed/refractory population. And I think each of these patients really provides insight into a patient population we think could benefit.
Salim Syed
And doesn't this patient fit that, the question that Steve asked about flu Ara-C repetitive dosing, you've tolerated it pretty well.
David Shook
Yes. Yes. I think this is 1 patient who have actually better accounts coming out of the cycle than they did going in because nothing will promote normal count recovery like disease control. And so this is a patient who came in cytopenic and kind of beat up early relapse. And then actually, we looked much better after cycle 1 than they did before, and we're able to quickly go into cycle 2 in consolidation. So yes, like from a trial standpoint, I don't want to have all patients at high risk. And I think from an oncologist that it would be great to be able to offer a therapy for patients like this that really have no option.
Operator
Our next question comes from Damien from Raymond James.
Unknown Analyst
Thank you for the update. Maybe 2 for me, 1 clinical for kind of the panel here. And then two, just kind of a more of a detailed question. So maybe first for kind of the panel. Could you just give an idea of on a further update on this flu Ara-C cohort what would be the hurdle to see from some of these early initial responses in terms of durability, that would allow us to conclude that it is clearly an effect of the totality of the treatment versus kind of an initial effect of the flu Ara-C lymphodepletion regimen. I mean are we talking -- do we need to see some of these CRs last to 6 months or beyond 6 months? Obviously, longer is better, but I guess, what's the point of clinical differentiation here in terms of the durability of these responses.
And then secondly, could you just maybe clarify exactly what is going to change with the dependent clinical amendment and what, in fact, we mean specifically by including consolidation and retreatment and then just could we also just clarify the number of days and cycles that these patients are receiving fludarabine and Ara-C in the current cohort.
David Shook
Yes. So I'll take care of some of the logistics questions and speak briefly and then I'll let Dr. Bachier comment on the chemotherapy. I think from the amendment will allow something like patient 1 who received treatment. So obviously, standard of care would be to consolidate anybody that achieves a high-risk remission with an allogeneic transplant. Some patients won't be able to tolerate at or won't be eligible for various reasons, and we want to provide an opportunity for post-remission dosing. So in the setting of MRD negativity, right now, the protocol requires you to stop and not be eligible for additional cycles.
So this amendment would allow for patients to receive additional cycles beyond MRD negativity to allow for consolidation, similar to what happened with patient 1. And then the retreatment would be for patients that achieve a response in then, say, 6, 9, 12 months later, have a record essence of disease, they could receive additional cycles to try and track them back into remission. And then in terms of the -- what can we look at in this versus, say, what gives us confidence that this is the composite therapy and not just an initial effect of flu Ara-C. I think we pointed to some of the data in using flu Ara-C with anthracycline, which I think even from our standpoint, it's sort of an unfair comparison because of the added efficacy that comes with anthracycline.
But in those studies, you see looking at CR rates, the ability to drive patients into remission. And look at these cohorts, it's not prolonged disease control. It's our ability to drive patients in remission. I think Dr. Bachier can talk to the likelihood of being able to drive somebody back into a CR after say, a TP53 relapse within 6 months transplant or WT1 relapsing within 6 months of transplant, I think that's probably single digit, a possibility for CR. And I think obviously, small numbers, right? I don't think we want to extrapolate this too far, but I think there are some encouraging features here, and I'll let Dr. Bachier talk more in-depth about what he feels in terms of the composite response.
Unknown Executive
Yes. Thanks, Dave. So as explanation, there are 2 settings. One is patients that relapse after an allogeneic transplant. And so those patients, you can treat with different consolidation regimens, but the remissions don't last. I mean they -- these patients once they relapse after allogeneic transplant, you really don't have very good options. Some of these patients have gone on to receive second transplant. Some of these patients have gone on to receive donor lymphocytes, but they really don't have long-lasting remissions. And so we have at least 1 of those patients, the first 1 that with a TP53 mutation and a relapse within 6 months of transplant, you really with fludarabine and cytarabine would not expect.
These patients want to achieve the CR and if a patient achieved a CR, to have a CR that is really not lasting more than a few months. So that's 1 situation where you can kind of tease out the effect of the fludarabine and cytarabine and the NK cells because you wouldn't expect these patients to have long lasting remissions. So that's one. The second one as a clinician that we struggle with is it just getting patients into CR to get them into transplant, particularly if you're able to get them into MRD-negative CRs. And I can speak to 1 of the patients, a 27-year-old patients with AML he was my patient. And this kid went through -- I mean, it went through 4 cycles of therapy, and he never achieved a remission including consolidation with high dose cytarabine. And so you really wouldn't expect just the addition of fludarabine to cytarabine to just get this patient into a CR that allowed us to take into transplant.
And he's in CR right now. As Dave said, it's still a relatively small number. We kind of to wait a little bit longer follow-up but I think as a clinician that there is a clear signal of response and effectiveness that we typically would not see in this patient population that have received multiple cycles of chemotherapy that have never achieved CR that we are, in some cases, able to take to transplant and in others that have had transplant, we've seen some 1 or 2 of them that have had kind of longer remissions than you would expect. But so I think it merits evaluation of additional patients. How long do we wait to assess the durability of response in this patient population that would treat in 6 months would be my -- where I would say, yes, I mean, I think this is real.
Operator
Our next question comes from Gena Han from TD Cowen.
Unknown Analyst
This is [indiscernible]. Looking back at your flu/cy cohort, are you concerned at all that you aren't really seeing any long-term CR without consolidation with HCT. I know that you mentioned that, that is 1 kind of group of patients that you're interested in kind of working to transplant. But do you want to see any kind of CR for this therapy on its own?
Unknown Executive
Yes. I think that would be ideal. I can take this one, Dave. I think that would be ideal. And certainly, maybe the third patient population, I failed to mention is those patients that you don't think you can take to transplant for different reasons, right, not having -- not being suitable for transplant. And so that would be another setting where you would also not expect long-term remissions and where you can assess kind of efficacy outside of the effect of a transplant. And so that 1 and then as I mentioned the one that patient group where they already had a transplant where you know those patients that have really very limited options and nothing that can keep them in remission for significant amounts of time.
David Shook
So from our standpoint, I think first off, I think the flu/cy cohort, looking back. One, we don't intend to carry a flu/cy cohort going forward. So I think long term , I think is sort of in the would have been nice to see in this cohort. I do think we are evaluating like for patient of the flu Ara-C cohort that patient will likely not get consolidated transplant, so to speak, to Dr. Bachier's point about patients that can be consolidated in that case with a second transplant. I think that's what we're looking for. We certainly wouldn't ask patients that were -- that would otherwise be eligible for transplant to forgo that but I think that's still a possibility and an interest for us in the flu Ara-C cohort.
Looking at the flu/cy cohort, I think that this was we obviously we had hoped to see more consistent responses there. It's obviously something that do respond and did respond, but it's just too inconsistent. So yes, I think that's why we moved to flu Ara-C.
Unknown Executive
Yes, that makes a lot of sense. If I could actually pivot a little bit. Could you tell us about the status for your -- I think that you were planning to do a combination study with [ VENCLEXTA ]?
David Shook
No. So we don't have any -- we're obviously always looking at additional combinations. And as we planned ahead early to have this alternative lymphodepletion with flu Ara-C. And I think before we start getting into combinatorial studies, we want to see what we've got with this monotherapy of NKX101 following lymphodepletion. So it doesn't money the waters too much in terms of interpretation and efficacy or safety. So nothing planned right now using [indiscernible] regimens, but we're always looking for combinations and future directions.
Operator
Our next question comes from Emily Bodnar from H.C. Wainwright.
Emily Bodnar
First one, if you could touch more on the safety profile with the flu Ara-C cohort. Do you think there's any reason why you wouldn't see some of those typical CRS and ICANs toxicities? Or is this kind of just a function of small numbers so far?
David Shook
Thanks for the question. I think there's a very good reason that we're not seeing that on this because these are T cells, right? So we see NK cell, PK that we've shown is 1 that we get exposure and then clearance rather than this exponential expansion of T cells where -- which actually drives that cytokine response. And toxicity in the sort of joke you can't have CRS without the C and our cytokine data show that we really don't bump the cytokines and while we see post infusional fever fusion kind of reactions and sometimes are called CRS and sometimes they're called infusion reactions. I think clinically, how it looks and how it's named is 1 thing and how they -- and sort of what it ends up being to the patient is another.
So this is what the safety profile, quite honestly, those toxicities that we would expect. Those are related to massive expansion of cells, CRS, ICANS neurotoxicity and I think everyone on the Nkarta would expect those toxicities to remain low, if not absent.
Emily Bodnar
All right. Makes sense. And then on the consolidation and additional cycles, is there like an ideal time after the first cycle that you would administer that? Or is it kind of determined on the patient-to-patient basis?
David Shook
Well, from our standpoint, as soon as patients are safe, recovered from toxicities and are having a meaningful clinical benefit. Will certainly allow for those cycles. And I'll let Dr. Bachier speak to clinical judgment. But from our standpoint, we -- once we have these leukemia is kind of on the run. We want to make sure that we can quickly turn around and deliver additional cycles, this is a sort of benefit of having enough the cell therapy of being able to say, our investigators can call and say, I'd like to give another cycle and start tomorrow then we can do that. And maybe Dr. Bachier, you can speak to sort of timing of additional either deepening our consolidated cycles?
Unknown Executive
Yes. No, I think it's a good question, and it would always be a little bit of judgment, right, and patient characteristics. But certainly, recovery of hematopoietic function will be important, obviously, as we try to give additional cycles. And obviously, other comorbidities. But typically, when you give consolidation cycles, you usually give them somewhere between 4 to 6 weeks or with 4 to 6 weeks in between each 1 and so that if patients are otherwise doing well and in remission from a clinical standpoint, that would be the time that I would want to move forward. And so the rationale or the reasons to would be if you have disease and then you are in CR but still are MRD positive, then that is a patient population that you certainly would want to try and give them into a deeper remission before you take it to transplant or if you're not taking them to transplant so that you can deepen that remission and make sure that they stay in remission.
So that from a clinician standpoint, that is usually the case, 4 to 6 weeks, some of these patients may take a little longer to recover their accounts and may need to be a little longer than that. But in an ideal world, the patients have had hematopoietic recovery, then would want to move forward with additional cycles in that time frame.
Operator
Our next question comes from Bill Wang from Needham & Company.
Unknown Analyst
Thanks for the update as well. So maybe a bit of a moment of history here. Flu/cy is exactly the most common chemotherapy used in any life of therapy in AML but why is this the conditioning of choice? And again, as a historical reminder, flag induction was used by some companies in the space. And the data that you see is actually pretty consistent with transplant studies that are earlier. So I'd love to hear your points there.
Unknown Executive
In terms of using flu Ara-C or flu/cy? I'm sorry, go.
Unknown Analyst
So flu/cy, the CR rates that we're seeing with flu/cy have been seen before in transplant studies. Now I'm just curious as to the historical reason.
Unknown Executive
You mean flu Ara-C, not flu/cy.
Unknown Analyst
I mean what is the reason for most people using flu/cy, that's kind of a better way of asking it.
Unknown Executive
You want to go first, Dave I can follow or I can go first if you want.
David Shook
Take away Dr. Bachier.
Unknown Executive
Yes. No, I mean I think flu/cy has been traditionally used for immunofactor cells and you're absolutely right. It has no bear in the activity of treatment of AML. It just has been the traditional lymphodepletion that has been used for different type of immunofactor cells across different type of diseases. And it's allowed -- and in general, it allows for obviously lymphodepletion, kills out of lymphocyte and it's also the changes in cytokines that is associated with flu/cy that both trials have started with.
But to your point, I mean, I think as we learn more, it would make more sense that as we start developing clinical trials that we started using lymphodepletion that is more geared towards the activity of a particular drug towards the disease. But so that has been the rationale for using flu/cy just the traditional lymphodepletion that has been used because of the ability to deplete lymphocytes and create the appropriate environment from a cytosine standpoint. Dave?
David Shook
Yes, I think you covered it well. I mean, I think some of the earlier studies certainly with immunofactor cells used it. And I think people -- on various doses, I think the doses of flu/cy back then were several [ 50, 60 ] [indiscernible] per kilogram doses of flu. And so I think flu/cy evolved over time, and I think people want to sort of normalize to commercial CAR-T all flu/cy are not created equal. Sometimes it's even orders of magnitude, higher doses of cyclophosphamide. And as Dr. Bachier said, it just makes more sense for a lot of reasons for us to move towards disease-specific lymphodepletion regimen. And I think we're encouraged to see that we didn't have to compromise PK in doing so, it probably provides additional benefit for those patients.
Operator
Next question comes from Sami Gorman from William Blair.
Unknown Analyst
Congratulations on the update. Thanks for taking my question. Going back to the PK data, it looks like the decreasing expansion in the NK cell kinetics largely for late with immune cell reconstitution. But I was curious if you saw any CAR targeted antibodies or the development of those. And then as you're thinking about consolidation dosing for retreatment, how are you thinking about the use of using cells from different donors? And then Dr. Bachier, in terms of the durability of responses, particularly for patients that may not be eligible for transplant, I mean, I guess, what degree of durability would you think would be clinically meaningful? And do you think the durability we're seeing with that first patient treated with the Blue Ara-C is a pity meaningful durable response?
Unknown Executive
Yes. I can take the last one, and then I'll let Dave handle the first 2. So I mean, I think it's 6 months. I mean I think these patients they -- you just have a patient that had that in their first relapse and you give them fludarabine, cytarabine, then some of those patients can be in remission for some time, for a year. Not more than that. The durability of response with fludarabine, cytarabine in patients that do not go to transplant is one the CR rate patients who have failed initial therapy, it's low as we talked in the data slide and it's not long term, it's usually within the first year, they will relapse they can make it to transplant.
And so that's in the first relapse or in the primary refractory after first line of therapy. We're talking a patient population that have had multiple lines of therapies and where you what you really wouldn't expect CR rates that are more than 10%, 20% and leukemia-free intervals that are not longer than 6 months.
David Shook
Yes. And then to the other one, yes. So we look for anti-product antibodies, look for anti-HLA antibodies to see whether or not both -- not only to the product but the cells themselves and I don't have those data generally has not been an issue across platforms. I think relevant, these patients see a lot of blood products sometimes transplant had come in with anti-HLA antibodies. And so we select products that avoid that. So I think these are patients that are sort of primed to development funds, and we haven't seen that happen, but we're collecting those data as we go for all patients for anti-HLA and anti-product antibodies.
In terms of the PK, you're absolutely right. I guess it seems to be in accordance with host cell recovery. And I think mentioned earlier, cycle 1 to cycle 2, seem pretty similar in the small numbers that we've seen, and I think we'll continue to accumulate those data. In terms of switching donors, we certainly would -- any time there's a development of anti-HLA antibodies. We generally think a donor is a donor and haven't seen reason to switch. But I think as we look across our -- as we accumulate these data that makes sense to switch donors, we certainly can, these are old products or individual donor derived. So it would be -- we could relatively easily switch from 1 lot to the next if it was based on either something that we see or even a hypothesis.
Operator
Our next question comes from Bill Megan from Cannacord Genuity.
Unknown Analyst
So given the positive safety profile at this point, it seems like you settled in on a 1.5 billion dose level. Is there any reason not to go higher looking for potentially deeper upfront responses? And then second question, on the biomarkers, you showed response based on an NKG2D ligand composite score would there be any value? And do you expect to look at individual NKG2D ligands or do you just expect sort of that composite score to be probably the most appropriate biomarker?
David Shook
Yes. So I think the ligand data is it's a building data set. So we'll look at all of those. I think if we look at individual patients. I think the numbers get pretty small and then it will lag in and then you start seeing a great degree of variability. So I think that's challenging but interesting, right? I think whether it's [indiscernible] , percent positivity, 1 ligand versus the other. I think those are all good hypotheses that we want to evaluate. And in terms of dose -- maximum dose, no is the short intro to stop at 1.5.
And as I think another question came up earlier about dose compression, it may make more sense to compress using higher doses upfront during that earlier window of immune suppression. And with the safety profile that we have, as you mentioned, I think at some point, you get into logistics and a maximum number of cells and number of cells you can manufacture, deliver, et cetera. But right now, we're looking pretty closely at whether or not it makes sense to continue this 0714 dosing regimen.
As I've mentioned, it's important for us early to demonstrate that safety was similar in this, the DK was similar and we didn't want to make the data set more clouded. But I think now that we see the data that we have, we can start looking more intently at whether or not we want to update this regimen.
Unknown Analyst
And just a quick follow-up. You mentioned maximum cell dose. Do you have an idea of what a maximum cell dose is?
David Shook
No. No. I think it would be too early to hypothesize, but I'm very encouraged by our ability to safely deliver at least 1.5 billion. And that's 1.5 billion CAR positive, too. So I think we'll continue -- I don't think there's a reason to think or guess what a maximum number would be.
Operator
I'd now like to turn the call back over to Nkarta for closing remarks.
David Shook
Great. Well, then, again, thanks, everyone, for joining our call today. We appreciate your time, your interest in Nkarta and [indiscernible] , and we look forward to updating you on our progress again soon. Operator, you may disconnect.
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