Thank you for standing by. Welcome to the 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. Thank you, operator. 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 Sarah Cannon Transplant & 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 and 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 timelines 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 10-Q 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. Good morning, everyone. 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. 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 the potentially life-threatening toxicities that are common with T-cell therapies. As with any phase I, I-B 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 three 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. While these patients had up to 40% blasts in the bone marrow, they had peripheral blast counts generally close to zero. 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. 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 six patients treated with lymphodepletion, comprising fludarabine and cytarabine, also known as Ara-C, followed by three 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. 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. 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 one or more cycles of NKX101 at the 1.5 billion cell dose using Flu/Ara-C for lymphodepletion. 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 Sarah Cannon 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 Sarah Cannon Research Institute. He specializes as a principal investigator in phase I/II clinical trials of hematopoietic cell transplantation and cellular therapies for hematologic malignancies. 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? 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 will 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 previously responding, it is difficult to treat. Even low numbers of blasts may quickly multiply, overrun 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%-18% of patients with relapsed/refractory AML achieve remission after salvage chemotherapy. This translates to poor survival, with only one of eight patients surviving to five years. Hematopoietic cell transplantation is often the only opportunity for patients with relapsed/refractory AML to achieve long-term remissions. Those patients who achieve complete remission, or CR, before transplant enjoy far better survival. Response to salvage therapy is therefore critical. Options are limited for most patients with relapsed/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. Even with these therapies, response rates remain unacceptably low, with CR rates only modestly better than traditional cytotoxic chemotherapy. The combined impact of these agents results 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. 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 lack 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 two 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 and cyclophosphamide or Flu/Cy. 2 regimens were evaluated: three doses on days 0, 7, and 14, and two doses on days 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. Patients could receive up to five 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 had been treated with a median of two lines of therapy, including five patients who had prior allogeneic transplant. Almost all patients had received prior venetoclax. NKX101 following Flu/Cy lymphodepletion was well-tolerated across all dose levels, including no dose-limiting toxicities, up to three 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. Five patients, or 12%, had low-grade infusion reactions. 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 overt leukemia in the blood. The second swim lane includes the 18 patients with AML who were treated with the two highest levels of the 3-dose regimen, 1 billion and 1.5 billion cells after Flu/Cy conditioning. We previously reported three patients with CR. Of the two patients with MRD negativity, one 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 two 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 it in earlier cohorts was not as consistent in these cohorts. Fludarabine with Ara-C 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 anthracyclines, such as idarubicin or mitoxantrone, are added to Flu/Ara-C to increase anti-leukemic activity, and thus one could expect Flu/Ara-C alone to be less active than the rates seen with those regimens. Further, these agents carry significant toxicity, some lifelong, 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 increase sensitivity to NK cell-mediated killing. In this cohort, patients received fludarabine and Ara-C once daily for five days prior to three 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. Five of six 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 two 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 was 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 six months of transplant. He achieved a CR with full count recovery after 1 cycle of NKX101, as his physician did not want to pursue a second transplant, they 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 three 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 four of six CR/CRI rate and the three of six CR rate was encouraging for this high-risk patient group. Our cumulative PK data is shown here and highlight two important things. First, there is persistence of up to three 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. 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 stained for MICA, MICB, ULBP1, and ULBP3 by immunohistochemistry and evaluated a composite H-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 dataset, 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 pro-inflammatory cytokines are only marginally elevated. This contrasts considerably with elevations 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. Unlike CAR T therapies, where there is obligate tethering of toxicity and response, we see no association between cytokine elevation and response. In summary, relapse 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 rate in 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 in 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 three-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 in Nkarta with enrollment onto this trial. I'll now hand the call back to Paul. Paul? 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. Yes. For today's call, we'll be utilizing the Raise Hand feature for Q&A. To ask a question, click on the Raise Hand button at the bottom of your screen. Once called upon, please unmute and ask your question. If you've dialed in via phone, use star nine to raise your hand and star six to mute and unmute. Our first question comes from Stephen Willey from Stifel. You may unmute and ask your question. Good morning. Thanks for taking the questions. Just I guess on the lymphodepletion side, have you looked at cellular PK as a function of Flu/Ara-C versus standard Flu/Cy, in cycle 2 and beyond? 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 lymphodepletion regimen? Then I just have a follow-up. Yeah. Thanks for the question. The numbers for subsequent cycles are small, so it's hard. But, in generally speaking, the PK of one cycle versus the next seems similar. Okay, 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 re-dosing? Yeah, I, you know, I don't have the complete numbers, but in general, the exposure is pretty similar. Okay. I guess with the incremental Flu/Ara-C data, you know, you noted the one patient who had flow-determined MRD negativity. Can you just comment on how MRD negativity was determined in the other patients? At this phase of the study, the MRD is all still local, so there's no central assessment of MRD. And depending on the disease biology, mutational status, et cetera, some patients were followed by a combination of PCR, NGS, et cetera. 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. Whatever, if we report it's MRD negative, then that patient is MRD negative per the investigator to that patient and determines that care. It's not, 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. Okay. Then maybe just one quick question for Dr. Bachier. Again, I know it's fairly small patient numbers, but I think, you know, the slightly higher rates of hematological toxicity with Flu/Ara-C is probably understandable relative to Flu/Cy. I think there's, you know, a very small number of infections that we're seeing. Just wanted to get your feedback on, you know, 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. Thanks. Yeah, no, I think. Thank you for the question. I think it's a good question, right? You know, 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. You know, the decision of giving subsequent cycles with additional rounds of lymphodepletion is, you know, it's also using kind of clinical judgment on whether, you know, patients will be able to tolerate additional cycles. I mean, I think the good part is that, you know, if you're getting a second cycle, you know, those patients, in general, have entered remissions. They have, you know, obviously more robust hematologic recovery and are, you know, from a hematologic standpoint, are, you know, better able to tolerate additional cycles. But, you know, the decision on whether to move forward with additional cycles based on the intensity of lymphodepletion, you know, needs to be considered. Great. Thanks for taking the questions. Our next question comes from Daina Graybosch, from SVB Securities. You may unmute and ask your question. Hi. Thank you, guys. Thanks for the question. Looking at the PK data, you know, 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? Will you consider bunching up dosing or earlier after lymphodepletion? Yeah. Thanks, Daina. Yeah, I think the short answer is yes, absolutely. I think we have experience using 0, 7, and 14, and as we explored the Flu/Ara-C cohort, I thought it was, you know, we thought it was important to demonstrate that they're relatively comparable. That window related to, you know, being more proximal to lymphodepletion is certainly of interest. I think it would be. You know, it would certainly make a lot of sense to look at compressed dosing. It's something that we're looking at very closely. Maybe one more question on the Cy/Flu updated patients, and, you know, 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? In the Flu/Cy cohort? Yes, yes, in the Flu/Cy. Yeah. I think one, obviously, these were patients that were pretty heavily pretreated and had refractory disease. We've annotated the ones that had less than 5% peripheral blasts there, but the marrow burden was pretty wide-ranging. You know, fludarabine, cyclophosphamide, this would provide a lot of inherent disease control. You know, many of these patients went on to receive further therapy and were chemo-refractory even after that. I think it probably was a reflection of the nature of the underlying disease. Yeah, it's a... You can see the, you know, the annotation of those that had a lower peripheral burden, but, yeah, pretty sick patients, and, yeah, I don't think there's anything in particular. Thank you. Yeah, thank you, Daina. Our next question comes from Salim Syed from Mizuho. You may unmute and ask your question. Hey, good morning, guys. Thanks for the data. I guess a couple from me. One, when you looked at you guys, so have you guys filed for your protocol amendment on retreatment? Just curious, what are the guiding factors there, and when do you think we'll be able to actually start to retreat patients between now and the data that's gonna come in the first half of 2024? 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? Thank you very much. Yeah, thanks. That's 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, you know, FDA was certainly very friendly to us in the discussions of being able to give, you know, additional cycles for, to consolidate. Then we think they'd be probably pretty similar, supportive on kind of one-off cases. We wanna make sure that we incorporate it in the protocol. We're working on that to get it formalized and normalized across the platform. Hopefully, that will be a part of the program soon. In terms of, you know, translatable, I think patient one, who you highlighted, is really illustrative of the case of need in this disease, right? Super high-risk disease in an elderly patient who relapsed post-transplant. You know, this was one of the, you know, when the investigator response, you know, had this response, was really, you know, We were very pleased with the outcome because, you know, this was a patient that I think nobody would have expected to respond to chemotherapy. It was FLAG-Ida, et cetera. This was a certainly encouraging result, and this will be no restriction whatsoever on, you know, disease burden, mutational status. It remain agnostic to prior transplant or upcoming transplant, reflecting the real world. I think unlike, you know, other therapies, this is one we could just really be broadly applicable to the entire relapsed refractory population. I think, you know, each of these patients really provides insight into a patient population we think could benefit. Doesn't this patient fit that, the question that Steve asked about Flu/Ara-C and repetitive dosing? He tolerated it pretty well. Yeah. Yeah, I think this is one, you know, patient who had actually better counts going, coming out of the cycle than they did going in, because nothing will promote normal count recovery like disease control. This is a patient who came in cytopenic and kind of beat up early relapse, and then actually looked much better after cycle one than they did before, and we're able to quickly go into cycle two and consolidation. Yeah, I, you know, I, like I said, from a trial standpoint, I wanna have, you know, all patients at high risk, but I think from a, you know, as an oncologist, that would be great to be able to offer a therapy for patients like this that really have no option. Thank you. Thank you so much, man. Thank you. Our next question comes from Dane Leone, from Raymond James. You may unmute and ask your question. Thank you for taking the questions. Thank you for the update. Maybe two for me, one clinical for kind of the panel here, and then two, just kind of a more of a detailed question. 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, you know, an effect of the totality of the treatment, versus, you know, kind of an initial effect of the Flu/Ara-C lymphodepletion regimen? I mean, do we need to see some of these CRs last to six months or beyond six months? Obviously, longer is better, but I guess what's the point of clinical differentiation here in terms of the durability of these responses? Secondly, could you just maybe clarify exactly what is going to change with the pending clinical amendment and what in fact, we mean specifically by including consolidation and retreatment? Just, you know, could we also just clarify the number of days and cycles that these patients are receiving fludarabine and Ara-C, you know, in the current cohort? Thank you. Yeah. So I'll take care of some of the logistics questions and speak briefly, and then I'll let Dr. Bachier comment on the, you know, chemotherapy. I think for the amendment, it will, you know, allow, you know, something like patient one who received treatment. 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 that or won't be eligible for it for various reasons, and we want to provide an opportunity for post-remission dosing. In the setting of MRD negativity, right now, the protocol requires you to stop and not be eligible for additional cycles. This amendment would allow for patients to receive additional cycles beyond MRD negativity to allow for consolidation, similar to what happened with patient one. The retreatment would be for patients that achieve a response and then, say, six, nine, 12 months later, have a recrudescence of disease, they could receive additional cycles to try and drive them back into remission. And then in terms of the, you know, 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, you know, we pointed to some of the, you know, some of the data in, you know, using Flu/Ara-C with anthracycline, which I think even from our standpoint, is sort of an unfair comparison because of the added efficacy that comes with anthracycline. In those studies, you know, you see, you know, looking at CR rates, the ability to drive patients into remission. I, you know, in looking at these cohorts, it's not prolonged disease control, it's our ability to drive patients into remission. I think Dr. Bachier can talk to the likelihood of being able to drive somebody back into a CR after, you know, say, a TP53 relapses within six months of transplant or WT1 relapsing within six months of transplant. I think that's probably single digit, you know, a possibility for CR. I think, you know, obviously small numbers, right? I don't think we wanna 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. Yeah. Thanks, Dave. As a clinician, there are two settings. One is patients that relapse after an allogeneic transplant. Those patients, you know, you can treat with different consolidation regimens. They, their remissions don't last. I mean, you know, these patients, once they relapse after an allogeneic transplant, you really don't have very good options. You know, some of these patients have gone on to receive second transplant. Some of these patients have gone on to receive donor lymphocytes. They, you know, they really don't have long-lasting remissions. We have at least, you know, one of those patients, the first one that, you know, with a TP53 mutation and a relapse within six months of transplant, you know, you really, with fludarabine and cytarabine, would not expect these patients one, to achieve a CR, and if a patient achieve a CR, to have a CR that is really not lasting more than a few months. That's one 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. That's one. The second one, as a clinician, that we, you know, that we struggle with is just getting patients into CR to get them into transplant, particularly if you're able to get them into MRD negative CRs. You know, I can speak to one of the patients, a 27-year-old patient with AML. He was my patient, and, you know, this kid went through, I mean, went through 4 cycles of therapy, and he never achieved a remission, including a consolidation with high-dose cytarabine. So you really wouldn't expect, you know, just the addition of fludarabine to cytarabine to just get this patient into a CR that allowed us to take him to transplant and, you know, he's in CR right now. You know, as Dave said, you know, it's still relatively small numbers. You know, we kinda need to wait a little bit longer follow-ups. I think as a clinician, that, you know, there is a clear signal of response and effectiveness, that we typically would not see in this, you know, in this patient population that have received multiple cycles of chemotherapy, that have never achieved CR, that we are, you know, in some cases, able to take to transplant. In others, that have had transplants, we've seen, you know, some, you know, one or two of them that have had, kind of longer, remissions than you would expect. I, you know, I think it merits evaluation of additional patients. I think, how long do we wait to, you know, to assess the, you know, the reliability of response? You know, in this patient population that we're treating, six months, would be my, you know, where I would say, "Yeah, I mean, I think this is real." I don't know if that answered the question. Dane, any further follow-up? Yeah, that I think that was a good response. Appreciate it. Thank you. Great. Our next question comes from [Gena Ha] from TD Cowen. You may unmute and ask your question. Hi, thanks. This is [Gena on for Rian]. Thanks for taking my question. Looking back at your flu cycle 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 one kind of group of patients that you're interested in, kind of bridging to transplant. Do you want to see any kind of CR for this therapy on its own? Yeah, I think that would be ideal. I can take this one, Dave. You know, I think that would be ideal. You know, certainly, you know, 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 to for transplant. So that would be another, you know, another setting where you would also not expect long-term remissions and where you can assess the kind of efficacy outside of the effect of a transplant. That one, and then as I mentioned, the one that said patient group, where they already had a transplant, where you know those patients that have really very limited options and not nothing that can keep them in remission for significant amounts of time. Yeah. Okay. Yeah. If I could follow up or, yeah, actually. Hold on just a second, please. Yeah. Yeah, sorry. From our standpoint, I think, you know, first off, I think the Flu/Cy cohort, you know, looking back, one, we don't intend to carry the Flu/Cy cohort going forward. I, you know, I think long-term follow-up, I think is sort of in the, you know, would have been nice to see in this cohort. I do think we are evaluating, you know, like for patient one in the Flu/Ara-C cohort, that patient will likely not get a consolidated transplant, so to speak. To Dr. Bachier's point about, you know, patients that can't be consolidated, you know, in that case, with a second transplant, I think that's what we're looking for. You know, we certainly wouldn't ask patients that were, you know, that would otherwise be eligible for transplant to forgo that. You know, I think that's still a possibility and an interest for us, you know, in the Flu/Ara- C cohort. You know, looking at the Flu/Cy cohort, I think, you know, that this was. You know, we obviously had hoped to see more consistent responses there. Obviously, some that will, that do respond and did respond, but it's, you know, just too inconsistent. Yeah, I think that's. That's why we moved to Flu/Ara-C. Yeah. Did you have a follow-up, [Gena]? Great. Yeah, 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? No. We don't have any. You know, we're obviously always looking at additional combinations. You know, as we, you know, we planned ahead early to have this alternative lymphodepletion with Flu/Ara-C. I think before we start getting into combinatorial studies, we wanna see what we've got with this, the monotherapy of NKX101 following lymphodepletion. It doesn't muddy the waters too much in terms of interpretation and efficacy or safety. Nothing planned right now, using, you know, venetoclax-based regimens, but we're always looking for combinations and future directions. Great. Thanks so much. Our next question comes from Emily Bodnar, from H.C. Wainwright. You may unmute and ask your question. Hi, good morning. Thanks for taking the questions. First one, if you could touch a bit 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? Thanks for the question. I think there's a very good reason that we're not seeing that, and it's because these aren't T-cells. Right? We see, you know, NK cell PK, see that we've shown is one that we get exposure and then clearance, rather than this exponential expansion of T-cells, which actually drives that cytokine response and toxicity. You know, as we sort of joke, we can't have CRS without the C, and our cytokine data show that we really don't bump the cytokines. You know, while we see post-infusional fever or infusion kind of reactions, and sometimes they're called CRS, and sometimes they're called infusion reactions, you know, I think clinically, how it looks and how it's named, is one thing, and how they s ort of what it ends up meaning to the patient is another. 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. I think everyone on the Nkarta team would expect those toxicities to remain low, if not absent. All right, makes sense. 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 a patient-to-patient basis? Well, from our standpoint, as soon as patients are safe, you know, they're recovered from toxicities and are having a meaningful clinical benefit, you know, we'll, you know, certainly allow for those cycles. I'll let Dr. Bachier speak to, you know, clinical judgment, but from our standpoint, we, you know, once we have these leukemias kind of on the run, we wanna make sure that we can quickly turn around and deliver additional cycles. This is a sort of benefit of having an off-the-shelf therapy, of being able to say, you know, our investigators can call and say, "I'd like to give another cycle and start tomorrow," than, you know, we can do that. Maybe Dr. Bachier, you can speak to sort of timing of additional either deepening or consolidator cycles. Yeah, no, I think, I think it's a good question, and it would always be a little bit of judgment, right? Patient characteristics. But, you know, certainly recovery of hematopoietic function will be important, obviously, as you try to give additional cycles and obviously other comorbidities. But, you know, typically, you know, when you give consolidation cycles, you usually give them somewhere between 4-6 weeks, or with, you know, 4-6 weeks in between each one. So that, you know, if patients are otherwise doing well and in remission, I, you know, from a clinical standpoint, that would be the time that I would want to move forward. You know, the rationale or the reasons to would be if, you know, 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 get them into a deeper remission before you take them 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. That, you know, from a clinician standpoint, that is usually the case, four to six weeks. You know, some of these patients may take a little longer to recover their counts and may need to be a little longer than that. In an ideal world, if patients have had hematopoietic recovery, then we would want to move forward with additional cycles in that timeframe. Okay, great. Thank you. Our next question comes from Gil Blum, from Needham & Company. You may unmute and ask your question. Good morning. Thanks for the update as well. Maybe a bit of a moment of history here. Flu/Cy isn't exactly the most common chemotherapy used in any line of therapy in AML. Why is this the conditioning of choice? Again, as a historical reminder, FLAG induction was used by some companies in the space, and the data that you've seen is actually pretty consistent with transplant studies that are earlier. I'd love to hear your points here. Thank you. In terms of using Flu/Ara-C, or Flu/Cy? I'm sorry, Gil. Flu/Cy, you know, the CR rates that we're seeing with Flu/Cy have been seen before in transplant studies. I'm just curious as to the historical reason. You mean Flu/Ara-C, not Flu/Cy? I mean, What is the reason for most people using Flu/Cy? That's kind of a better way of asking it. You want to go first, Dave? I can follow. Sure. I can go first if you want. Yeah. Take it away, Dr. Bachier. Yeah, no, I mean, I think Flu/Cy has been traditionally used for immune effector cells. You're absolutely right, it has, you know, it has no bear in the activity of treatment of AML. It just it has been the traditional lymphodepletion that has been used for different type of immune effector cells across different type of diseases. It's, you know, it's allowed, you know, and in general, it allows for, you know, obviously lymphodepletion, you know, it kills a lot of lymphocytes. It's also the, you know, the changes in cytokines that is associated with Flu/Cy that most trials have started with. To your point, I mean, I think as we learn more, it would make more sense that, you know, as we start developing clinical trials, that we start using lymphodepletion, that is more geared towards the activity of a particular drug, towards the disease. That has been the rationale for using Flu/Cy, just the, you know, the traditional lymphodepletion that has been used because of the, you know, the ability to deplete lymphocytes and create the appropriate environment from a cytokine standpoint. Dave? Yeah, I think you covered it well. I mean, I think, you know, some of the earlier studies, certainly with immune effector cells, used it, and I think people. You know, in various doses, I think the doses of Flu/Cy back then were several, you know, 50 mg, 60 mg per kilogram, you know, multiple doses of flu. I think Flu/Cy has evolved over time, and I think people want to sort of normalize to commercial CAR T. You know, all Flu/Cy is not created equal. You know, sometimes it's even orders of magnitude, higher doses of cyclophosphamide. As Dr. Bachier said, it's, it just makes more sense for a lot of reasons for us to move towards a disease-specific lymphodepletion regimen. I think we're encouraged to see that we didn't have to compromise PK in doing so and probably provides additional benefit for those patients. Any follow-up, Gil? No, I think that covers it. Thank you. Thank you. Our next question comes from Sami Corwin from William Blair. You may unmute and ask your question. Good morning. Congrats on the update. Thanks for taking my questions. I'm going back to the PK data. It looks like the decreasing expansion in the NK cell kinetics largely correlates with immune cell reconstitution. I was curious if you saw any CAR-targeted antibodies or the development of those. As you're thinking about consolidation dosing or retreatment, how are you thinking about the use of using cells from different donors? Dr. Bachier, I mean, in terms of the durability of responses, particularly for patients that may not be eligible for transplant, I guess, what degree of durability would you think would be clinically meaningful? Do you think the durability we're seeing with that first patient treated with the Flu/Ara-C is a clinically meaningful, durable response? Thank you. Yeah, I can take the last one, then I'll let Dave handle the first two. I mean, I think it's, you know, it's six months. I mean, I think these patients, they... You know, if you just have a patient that is in their first relapse, and you give them fludarabine, cytarabine, then you know, some of those patients can be in remission you know, for some time, for a year, not more than that. The durability of response on with fludarabine, cytarabine on patients that do not go to transplant is 1, the CR rate on patients who have failed initial therapy, it's low, as we talked in the data slides. It's not long term. It's, you know, usually within the first year, they will relapse if they can't make it to transplant. That's in the first relapse or in the primary refractory after first line of therapy. You know, we're talking a, you know, a patient population that have had multiple, you know, lines of therapies and where you really wouldn't expect, you know, CR rates that are, you know, more than 10%, 20%, and disease- and leukemia-free intervals that are not longer than six months. Sami, to talk to the other one. We look for anti-product antibodies, look for anti-HLA antibodies to see whether or not, you know, both not only to the product, but to the cells themselves. I don't have those data, but generally has not been an issue across platforms. You know, I think relevant, you know, these patients see a lot of blood products sometimes transplanted, come in with anti-HLA antibodies, and so we select products that avoid that. I think these are patients that are sort of primed to develop antibodies, and we haven't seen that happen. We're collecting those data as we go for all patients for the anti-HLA and anti-product antibodies. In terms of the PK, you're absolutely right. It seems to be in accordance with host cell recovery. As I think mentioned earlier, cycle 1 to cycle 2 seems 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 anytime there's a development of anti-HLA antibodies. We generally think a donor is a donor and haven't seen reason to switch. I think as we look across our. You know, as we accumulate these data, if it makes sense to switch donors, we certainly can. These are pooled products. They're individual donor-derived, so, you know, we could relatively easily switch from one lot to the next, if it was, you know, based on, you know, either something that we see or even a hypothesis. Great, thanks. Thank you. Our next question comes from Bill Maughan from Canaccord Genuity. You may unmute and ask your question. Hey, good morning, and thanks. Given the positive safety profile to this point, it seems like you've settled in on a $1.5 billion dose level. Is there any reason not to go higher, looking for, you know, potentially deeper upfront responses? Second question, on the biomarkers, you showed response based on an NKG2D ligand composite score. Would there be any value, 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? Yeah. I think the, the ligand data, you know, is, you know, it's a building data set. We'll look at all of those, and again, if we look at individual patients, I think that the numbers get pretty small in individual ligands, and then you start seeing a great degree of variability. I think that's challenging but interesting, right? I think whether it's H-score,% positivity, one ligand versus the other, I think those are all good hypotheses that we wanna evaluate. In terms of dose, maximum dose, no, is the short answer. No reason to stop at 1.5. You know, as I think, you know, another question came up earlier about dose compression. You know, it may make more sense to compress using higher doses upfront during that earlier window of immune suppression. You know, with the safety profile that we have, as you mentioned, I think at some point you get into logistics and maximum number of cells and number of cells you can, you know, manufacture, deliver, et cetera. Right now, we're looking pretty closely at whether or not it makes sense to continue this 0, 7, 14 dosing regimen. As I mentioned, it was important for us early to demonstrate that safety was similar in this, that PK was similar, and we didn't want to make the data set more clouded. 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. Thanks. Just a quick follow-up. You mentioned maximum cell dose. Do you have an idea of what a maximum cell dose is? No. I think it would be too early to hypothesize, but I, you know, very encouraged by our ability to safely deliver at least 1.5 billion, and that's 1.5 billion CAR positive, too. I think we'll continue. I don't think there's a reason to think or guess what a maximum number would be. Great. Thank you. Of course. Thank you. I'd now like to turn the call back over to Nkarta for closing remarks. Great. Well, again, thanks, everyone, for joining our call today. We appreciate your time, your interest in Nkarta and cell therapy, and we look forward to updating you on our progress again soon. Operator, you may disconnect.