Good afternoon, everyone, thank you for joining us today for Artiva Biotherapeutics Webcast and Conference Call on data presented at the EULAR 2026 Congress. I'm Noopur Liffick, Strategic Investor Relations Advisor for Artiva. Before we start, I'd like to remind you that today's call will include forward-looking statements based on current expectations. Such statements represent management's judgment and intention as of today and involve assumptions, risks, and uncertainties. Artiva undertakes no obligation to update or revise any forward-looking statements. I would also like to remind you that AlloNK has not been approved for marketing. The data presented are preliminary, and you should use caution when comparing data across studies or publications. Please refer to Artiva's filings with the SEC for information concerning the risk factors that could affect the company. Joining me as presenters on today's call are Fred Aslan, CEO of Artiva, Diego Miralles, President and Head of R&D of Artiva, and Dr. Paul Emery, Arthritis UK Professor of Rheumatology at the University of Leeds and Director of the Leeds NIHR Biomedical Research Centre. I will now turn the call over to Fred Aslan. Thanks, Noopur, and good morning to everyone joining us. We believe Artiva is well-positioned for significant value creation, and this slide provides a summary of our opportunity. The deep B-cell depletion mechanism, as demonstrated by auto CAR- T, is arguably the most exciting mechanism in autoimmune disease today. While auto CAR- T is not the ideal modality for this mechanism to gain scale, we believe our therapy has the potential to drive auto CAR- T like efficacy with the scalability, COGS, and safety to be offered in the community setting. The strategic interest in this field is very high. Almost every pharmaceutical company has a deep B-cell depleting program, with most of them not just focused on one modality, but exploring two or three modalities in parallel. Our lead indication, refractory rheumatoid arthritis, is a large commercial opportunity with the largest population of refractory patients. AlloNK's efficacy and safety has been quite promising. If things go according to plan, we could potentially have the first deep B-cell depleting therapy of any modality to get an approval in refractory RA. Our safety data demonstrates that low-dose Cy/Flu can be quite tolerable in the community setting, and we see a favorable competitive landscape with room for multiple players. Our TPP could be quite differentiated. A one-time treatment that can provide a durable treatment-free response with an opportunity for retreatment to potentially keep the disease in control over long periods of time. We have recently raised $300 million, which extends our runway into 2029, with sufficient resources and time to read out on our registrational trial in RA. This slide is a reminder of the deep B-cell depletion hypothesis, as described by Schett and others. B-cells can drive the pathogenesis in autoimmune disease in three ways: autoantibody production with downstream tissue damage, erratic antigen presentation and T-cell amplification, and erratic cytokine secretion and inflammation. We know rituximab monotherapy can reduce B-cells and drive a transient benefit. We know TCEs are exploring the concept of dimming with a deeper B-cell depletion than rituximab, but not too deep as to sidestep their narrow therapeutic index. Whereas technologies like auto CAR- T and our AlloNK are targeting a very deep B-cell depletion with the potential for more durable benefits. This slide highlights our mechanism of action and how our AlloNK regimen is administered in the clinical setting. AlloNK is a non-genetically modified NK cell, and because it's non-genetically modified and does not have a CAR, we use a B-cell targeting monoclonal to direct the NK cells. In autoimmune disease specifically, rituximab binds to CD20 on the B-cell, the Fc portion of the monoclonal activates AlloNK via the CD16 receptor, AlloNK kills the B-cells. Our regimen also includes low doses of cyclophosphamide and fludarabine as conditioning to prevent the host immune system from attacking AlloNK so it can do its work over a two to three-week period. This mechanism has been demonstrated first in oncology and now in autoimmune disease to drive a similar deep B-cell depletion as auto CAR- T. The bottom part of the slide describes how the regimen is being administered in a clinical setting. On days one, two, and three, the Cy/Flu is administered, there are two additional infusions on day six and day 20 when patients receive both AlloNK and rituximab. In all of these visits, patients are dosed in the infusion chair and go home afterwards. AlloNK has been extensively studied in clinical trials, we have seen consistent activity across indications. To date, we have treated over 40 patients with cancer and over 70 patients with autoimmune disease. On the left, you can see our experience in B-cell cancers. First, in a series of 14 patients where the vast majority had late line non-Hodgkin's lymphoma, AlloNK and rituximab had a similar complete response and median duration of response as CD19 targeting auto CAR- T. In a separate series of 24 patients with relapsed refractory Hodgkin's lymphoma using a CD30 targeting biologic, again, the complete response rates were in line with CD30 targeting auto CAR- T. The right side of the slide highlights our experience with AlloNK in autoimmune disease. This includes all 37 patients that have three or more months of follow-up from our IIT and basket studies as of the April 3rd cutoff. As you can see across indications, the vast majority of patients experience a clinically meaningful response. Importantly, there has been no discontinuation due to adverse events, no patient has been started on a new b/tsDMARD. Our lead indication is refractory RA, as this slide conveys, there's a large unmet need in patients that have failed two or more biologic or targeted synthetic DMARDs. The ACR50s on the left side of the slide are from the product labels for each therapy. You can see that the ACR50 opportunity when you are taking your very first b/tsDMARD is in the 39%-45% range. If you fail your first b/tsDMARD and you are now taking your second, the ACR50 opportunity is in the 20%-36% range. We are focused on the patients all the way to the right who have failed two or more b/tsDMARDs. Here, we need to rely on the literature and real-world registries since no product has been approved for these refractory patients. You can see that the ACR50 opportunity is only in the 10%-20% range, and our goal with AlloNK is to drive an ACR50 response in over 50% of patients and to provide a durable response. Refractory RA is a very large opportunity. If we look at the U.S. alone, out of the $20 billion spent on b/tsDMARDs, approximately 25%, or $5 billion, is being spent on b/tsDMARDs in refractory RA patients that, as you saw on the prior slide, only have a 10%-20% opportunity to achieve an ACR50 response. We believe these patients can do a lot better. We are excited about the potential to become the first B-cell depleting agent to start a phase III trial in RA. If we are successful, we could be the first to potentially get approved in this large indication. We had a constructive end of phase II meeting discussion with the FDA where we aligned on our registrational strategy. We will be conducting a single registrational randomized control trial in approximately 150 RA patients who have had an inadequate response to two or more b/tsDMARDs. Patients will be randomized two to one to receive AlloNK + rituximab or rituximab alone. The primary efficacy endpoint is ACR50 at six months. Patients on rituximab alone who do not achieve an ACR50 at 6 months may cross over into the AlloNK + rituximab arm. Our expectation is that AlloNK + rituximab patients would have an ACR50 response at six months of 50% or higher, whereas rituximab-only patients would have an ACR50 response in the 20%-25% range. We will be using 4 billion cells per dose times two doses, so 8 billion cells total. For most of the clinical data we are presenting, patients were dosed with 3 billion cells total, so 8 billion should provide more consistent AlloNK exposure with an opportunity for deeper B-cell depletion. This randomized control trial will be a global trial with over 80 sites, and I'll note that we already have north of 40 sites active in our basket study. The proposed safety database will be comprised of 250 patients with autoimmune disease treated with AlloNK and rituximab. Now I will turn the presentation over to Diego Miralles, who recently joined the Artiva team as President and Head of Research and Development. Thank you, Fred. I will now share highlights from our recent EULAR presentations, along with an additional publication-only abstract, which together showcase the breadth of our AlloNK autoimmune data. Here, we've highlighted our five accepted abstracts. The first poster includes data from the study conducted as an investigator-initiated trial in patients with rheumatoid arthritis. This was the first IND accepted and first patient treated with an allogeneic cell therapy in RA. We had a late-breaking oral presentation of our phase II-A company-sponsored basket trial, where we describe the experience of 31 patients with rheumatological diseases, including rheumatoid arthritis, Sjögren's disease, and scleroderma. We had an oral presentation describing our first treated patient with Sjögren's disease that demonstrated a remarkable response. We had one poster highlighting translational insights. Lastly, we had an additional accepted abstract that included safety observations with AlloNK across all the patients treated to date. Having shown potency and durability similar to what has been seen with CAR- T cell therapy in oncology. We rapidly assessed whether similar results could be observed in autoimmune diseases. We worked with a U.S. outpatient rheumatology clinic to run an investigator-initiated trial, which was the first clinical trial for any allogeneic cell therapy in rheumatoid arthritis. The result of this study showed potent and sustained efficacy, as demonstrated by a significant drop in CDAI and DAS28 in highly refractory patients. This is shown by the fact that all six patients had received at least two prior targeted therapies, and 1/3 had received three or more targeted therapies. The graphs on the right show a rapid improvement in CDAI and DAS28-ESR at three months, and the responses deepened further by six months. The next few slides will show the initial data from our phase II-A basket trial across several indications, including RA, Sjögren's disease, and scleroderma. Similar to the data shown in the investigator-initiated trial, we have recruited highly refractory RA patients with high baseline disease activity in this study. As shown, 73% had received at least two prior distinct targeted therapies, and 27% had received at least three prior targeted therapies. As observed in the investigator-initiated trial, patients had consistent deep CDAI and DAS28 responses. Many had a deep response by three months, with continued improvement in CDAI, DAS28-ESR, and DAS28-CRP by six months. Importantly, ACR responses was achieved in 71% of the patients that reached six months, while the other 29% demonstrated an ACR 20. This swimmers plot shows the durability of the responses observed across studies as the data cutoff date. The first six patients in light blue are those in the investigator-initiated trial. The next 15 are those in the basket trial, for a total of 21 patients. The time of observation ranges from three months to more than 18 months, and it's important to note that as of the data cutoff date, no patient had a loss of response, needed high-dose steroids, or was put on a new targeted therapy. Five of the six patients in the investigator-initiated trial reached an ACR50 or modified ACR50 at six months, while five of the seven patients that had six months of follow-up in the basket trial also achieved an ACR50. The major takeaway here is the significant durability of the observed responses. One of our oral presentations at EULAR highlighted that the first Sjögren's patient treated with AlloNK demonstrated a dramatic initial response and improvement across all domains. This was a female patient who had positive autoantibodies, had a very high ClinESSDAI of 23, and by six months, achieved low disease activity. The ClinESSDAI in the individual constitutional, articular, and cutaneous domains showed a significant improvement from baseline to six months. Further, we saw significant improvement across patient-reported and functional measures with the results in the patient global assessment, FACIT-Fatigue, and stimulated salivary flow on the right. As of the data cutoff date, we had a total of 11 patients with Sjögren's disease with three months or more of follow-up, and we observed compelling initial responses across clinical measures and function. As shown on the left, the baseline disease activity was high, with a ClinESSDAI of 16.1 and an ESSPRI of eight. These patients were refractory to multiple prior immune modulators. As shown in the figures, there was again a significant and rapid drop in the ClinESSDAI, which was enhanced from three to six months, and a similar pattern of response was observed in the ESSPRI. Additionally, as shown on the right, patient had their stimulated whole salivary flow measured and had significant hyposalivation at baseline. At six months, they had a very good response with average salivary flow now in the normal range. Similarly, we reported initial results for patients with scleroderma in the phase II-A trial as of the data cutoff date. These patients had received a large number of prior immunosuppressive therapies, with three out of five having received rituximab and failed. Again, the figure shows a rapid drop in the disease activity at three months that continued to deepen over six months. All four patients achieved an ACR 20 at six months, with 50% reaching an ACR50. We also had an abstract published that highlighted the safety profile that was observed in all patients treated to date. The tolerability profile of AlloNK and rituximab compares very favorably to autologous CAR-Ts and BCMA-targeted T-cell engagers. When analyzing all 55 patients, we did not observe any CRS or the need to use tocilizumab, and none had to use IVIG for hypogammaglobulinemia. When we look at infections, 29% had an infection with only 2% with severe infections. That compares very favorably to auto CAR-T and T-cell engagers, where the rate of CRS is high. There is a need for an IL-6 antibody and the use of IVIG, with a significant number of patients experiencing a Grade 3 infection. The results observed with AlloNK are comparable to serious infection rates for approved RA therapies. The most common treatment-emergent adverse events observed were consistent with those associated with rituximab or Cy/Flu. This slide shows the results of hospitalization over the first 28 days. Each row highlights one of the 55 patients that we are reporting, while each column is one day of the first 28 days. As shown, only two patients out of 55 patients over the first 28 days require hospitalization, one for dehydration from diarrhea, the other one for diabetic ketoacidosis. Neither was related to treatment. This, again, compares favorably to CAR-T treatments or TCEs and reinforces why this is a regimen that is optimal for the community setting. Rheumatologists in the community setting don't have the bandwidth to manage the complications that are observed with other treatments. Lastly, we had a poster showing the observed effect of AlloNK + rituximab on B cells. As shown on the left, there's a very significant uniform and consistent B-cell depletion by day 13. In all 51 patients treated with Cy/Flu, AlloNK, and rituximab, there is B-cell reconstitution observed at 6- 12 months following treatment. Shown in the middle, we see that the phenotype of the returning B cells in these patients is that of naive cells. Previous studies with rituximab have shown a correlation between a high proportion of naive transitional cells with good response in RA patients. Our presentations at EULAR highlighted a substantial body of encouraging patient data accrued over the past several years, and the response from the rheumatology community has been very positive. I will now hand the presentation over to Dr. Emery. Hello, I'm Paul Emery, Arthritis UK Professor of Rheumatology at Leeds, where we have studied advanced therapies for RA for decades, in particular B-cell depletion, a topic on which I have published over 60 papers. Artiva will focus their pivotal trial in RA on patients who have failed two or more classes of targeted therapies, still with moderate to severe disease activity. These patients represent the largest current unmet need in RA management, as despite all the approved therapies in RA, they do not have adequately controlled disease. From a clinician's point of view, these patients have diverse disease pathogenesis, require frequent and complex hospital visits, including sensitive imaging, which together with the multiple costly medications, makes them very expensive to the healthcare system. Fred went through the benchmark earlier, but I can confirm that there are no existing therapies that offer consistent chance of response for these patients. This leaves us to cycle through existing targeted therapies, switching between drug classes. Unfortunately, patients suffer from this because the longer the underlying disease goes incompletely treated, the more inflammation they are exposed to. The majority of these patients have extensive joint destruction and comorbidities as a consequence of this untreated inflammation. This produces a ceiling effect response to subsequent therapy. Thus, the treat-to-target approach becomes more difficult as patients advance through subsequent lines of therapy. ACR50 improvement criteria, therefore, are a meaningful threshold and not just a statistical endpoint. As clinicians, we would welcome a novel therapy that could offer a high chance of response for these patients and arrest the cycle of inflammation and continuing therapies with limited efficacy. Why are they so difficult to treat? Well, there are multiple reasons which can be summarized under four headings. First, comorbidities. Second, damage with secondary OA. Third, longer disease duration and inflammation exposure leading to more dysregulated pathways. Finally, pain sensitization. If requested, I can expand on these in the discussion later. I have studied rituximab in RA for decades now. We know from this work that B cells are a good target in RA. When you get complete depletion of B cells, we see two things. One, better clinical responses. Two, a repopulation with more naive B cells consistent with what has recently been called immune reset. Unfortunately, rituximab is a relatively poor B-cell depleter, so a large percentage of patients treated do not get full depletion and response. This slide outlines this point. In 2008, we published a study where we looked at B-cell depletion with a high-sensitivity assay. As shown in the left-hand graph, we saw that after a dose of rituximab in the majority of patients, B cells were reduced but still detectable, and this incomplete depletion in peripheral blood correlated with poor tissue B-cell depletion. Consistent with this, as shown in the graph on the right, for the subset of patients who did achieve peripheral blood B-cell depletion after the first dose, which we call fast depletion, their clinical responses were better, especially over the long term. For example, at 12 months, there was a threefold increase in response over the slow depleters. As an outcome measure, we used moderate to good EULAR response, which represents at best only a moderate improvement. The ACR50, which we'll talk about shortly, is a more stringent and harder to achieve response metric, and we can discuss more of this in discussion at the end. Now contrast this with the data Diego just showed. I worked with Artiva as they developed and deployed a high-sensitivity B-cell assay with a similar limit of quantification to our publication. As you see highlighted on the right, every single RA patient treated with AlloNK + rituximab achieved complete B-cell depletion by this sensitive assay. Therefore, I would expect, based on the previous data observed with rituximab, that many of these patients will have a deep and prolonged clinical response. Next, in this study, we looked at the phenotype of repopulating B cells. The flow plot on the left is an example of the patients who achieved complete fast depletion, where we saw predominantly naive B cells repopulate, and different from that which is seen with incomplete depletion and is shown on the right. This is in line with what has been referred to as immune reset. As Diego showed, after the AlloNK and rituximab regime, B cells reconstitute after about six months, and we see the naive phenotype. While reset is still a hypothesis, Artiva's data align with the desired biological pattern of complete depletion followed by naive reconstitution. As far as we know, this is a surrogate of B-cell reset. Now to the clinical data in RA that were presented. Here, I'm focusing on three disease characteristics. First, the RA subjects in this basket study had long-standing disease with average duration over 13 years. As discussed earlier, there is often long-term damage and other comorbidities in these types of patients, leading to a ceiling effect on efficacy. Second, these patients had very high baseline disease activity. Recall that the cutoff for high disease activity is a CDAI of 22 and a DAS28-ESR of 5.1. These patients are significantly beyond that. It is also well-established that those starting from a higher DAS with the same improvement trajectory will take longer to reach a state such as LDA. Finally, I talked about targeting patients who have failed two or more classes of prior targeted therapies. This will be the focus of the pivotal study. 73% of the patients in this dataset fit that inclusion, with a number of them having failed three or more prior classes. Patients with these three adverse features would be predicted to produce low response levels. Looking again at the efficacy data, the magnitude of improvement in CDAI and DAS28 is highly encouraging in these long-standing, high disease activity, refractory RA patients. The 71% ACR50 response at six months is particularly striking, exceeding the 50% ACR50 response rate that would be very impactful in clinical practice. Most past studies used ACR 20, and by that measure, all patients in this cohort had responded at six months. As no controlled clinical trials have been undertaken in such a population, there are no benchmarks. The nearest comparable study for rituximab was the REFLEX study that we conducted in patients who had failed only anti-TNF, which were then the only approved agents. There we saw only a mean 2-point decrease in DAS28-ESR and only a 27% ACR50 rate at six months. These data with AlloNK and rituximab are therefore highly encouraging. With the ACR rate of over 50%, this would be expected to separate well from the rituximab-only arm in the pivotal study. Finally, what's impressive about these data are the early signs of durability. The blue lines show patients remaining on study with no steroids outside the clinical protocol, and importantly, on no new targeted therapies. This is a real-world measure of durability, since as clinicians, we're looking for patients to remain well on stable therapy without needing to cycle through additional targeted therapies. Finally, from this chart, you see patients with ACR50 response rates, some as early as three months, with the majority achieving it by six months, providing confidence in the choice of this primary endpoint for the pivotal study. Taken together, what I find encouraging is not any single isolated aspect, but the consistency of the story. We have deep B-cell depletion measured by a high-sensitivity assay. There is reconstitution with a naive phenotype consistent with the reset hypothesis. There are clinically meaningful responses in a very refractory RA population. Finally, there's early evidence that some patients can remain controlled in the longer term without moving on to other targeted therapy. It has to be said these are still early data, and the results from the RCT will be crucial. From a clinician's perspective, this is precisely the type of approach we would want to see evaluated in patients who have exhausted multiple therapies. I'll now turn it back over to Fred for closing remarks. Thank you, Dr. Emery. Our goal as a biotech company in this exciting deep B-cell depletion space is to be first in class in refractory RA. We believe AlloNK could be a highly impactful treatment for patients that have already tried and failed other approved drugs. If we are successful, we could have a very unique target product profile, a one-time treatment that can provide a durable treatment-free response with an opportunity for retreatment to potentially keep the disease in control over long periods of time. Most importantly, our regimen is an IV therapy that rheumatologists can own and administer in their own infusion chairs, which is what is needed in order to reach such a large population of refractory patients. This slide outlines our potential catalysts over the next two-three years. The first row represents the maturation of our RA data. You can see that over the next 12- 24 months, our data set grows from the 21 RA patients that we shared at EULAR with limited follow-up to 50 or more RA patients where we will have a clear picture of their ACR50 potential and the durability of response. This data will be generated in our basket study in parallel to our phase III study, which is slated to initiate in the second half of this year with a readout in the second half of 2028. Finally, we will be sharing data on additional indications in our basket study and providing updates on our plans for a potential registrational path in a second indication. Thanks to our recent $300 million financing, combined with the cash we already had in hand, we have sufficient funds to take us into 2029, which would give us an opportunity to potentially accomplish everything you see on this slide. With that, I want to thank you for your time and hand the presentation back to our operator to open the call for questions. Thank you. As a reminder, if you would like to ask a question, please click on the raise hand button, which can be found on the black bar at the bottom of your screen. When it is your turn, your name will be called, and we will ask you to please unmute your audio and ask your question. We will wait one moment to allow the queue to form. Thank you. Our first question will come from Roger Song, Jefferies. You may now unmute your audio and ask your question. Great. Congrats for all the data update, thanks for putting this together and taking our questions. Maybe a question for Dr. Emery. How do you think about this AlloNK, the durability will be promising, that you will be using your clinical once it gets approval. Also, could you comment on this Flu/Cy conditioning, how you think this regimen will be used in this highly refractory RA population? How you think about the patient will be willing to redose it if they need it. Thank you. Okay. There's three questions there. The first question, really, I can relate to from rituximab. With rituximab, if you get a very good response as a consequence of very deep depletion, we've had patients be in remission for several years. We don't know how long AlloNK and rituximab will work, but it does have the potential to have long-lasting benefit. We're just going to have to see, and the basket study will give some information regarding that duration. The Flu/Cy, how will they tolerate that? Well, we've given much higher doses. I ran the autologous stem cell program for RA. We were giving much higher doses then. People at this stage of their disease, they're used to IV therapies, provided they're not made too sick. Before we had rituximab for vasculitis, we had patients who'd had cyclophosphamide on over 100 occasions. Patients, there's no problem, patient tolerability. We know a great deal about managing these patients. Of course, apart from the safety, one of the great things with this AlloNK is the repeatability. When patients do relapse, we will have the ability to retreat them. Of course, Artiva are going to get some information about a dose response. As you heard, the original data will come from 3 billion, and 5 billion or more will be in the later. It's 8 billion, I think, actually, in the later RCT. It could be possible that some of these early ones would relapse, but actually would respond for longer periods when they get 8 billion. We will know more about handling the patients. I think Fred and Diego very clearly articulated many of the advantages. These are very severe patients. As I said in the presentation, there's a huge unmet need for them. Excellent. Thank you so much. Thank you. Our next question comes from Joshua Schimmer with Cantor. You may now unmute your audio and ask your question. Great. Thanks very much for taking the questions. Just a couple from me. First, how is refractory rheumatoid arthritis defined in terms of residual disease activity? Is there a threshold in terms of DAS or something else that's the answer to that differ between clinical trials and real-world setting? Second, how are you thinking about the path forward in Sjögren's and systemic sclerosis, and do you anticipate controlled trials for those indications as well if so against what? Thank you very much. Thanks for the question, Josh. Why don't I turn to Dr. Emery to discuss a little bit the definition of refractory RA. As you know, Josh, there is a European definition of refractory RA, which is around difficult to treat. Your question is more around how does one think about refractory RA and some of the measures that can be used in order to define that. I can take our next steps with our Sjögren's program. Thanks, Fred. It's a very good question. We're in transition at the moment. As Fred mentioned, there's difficult to treat, which actually a lot of the time isn't that difficult to treat. It just means they've been exposed to a couple of different modes of action. There's refractory disease, there's polyrefractory disease, there's polyrefractory disease with continued inflammation, there's polyrefractory disease without inflammation, these all have different pathogenesis. Artiva, it's fair to say, have taken the toughest group, which is really those who have failed at least two and probably three, and in several cases, three. These are refractory. We do subdivide them. To subdivide them on inflammation, we can use imaging, MRI or ultrasound, and there are differences. These patients, as I mentioned, have pain sensitization, which gives them very high DAS scores when they don't have a great deal of inflammation. There isn't a cutoff in terms of disease activity score. The cutoff is more your history of how you responded to previous therapies. There isn't currently an adequate one. We in Leeds have actually produced a lot of these definitions. I would be the first to admit we're not there yet. I can tell you Artiva is treating the right population. Thank you. Maybe Dr. Emery, just to build on Josh's question, when you went through the baseline characteristics for our patients and you looked overall, was there anything in particular there that, for example, would give other people an opportunity to appreciate the extent of how refractory they were? Do you look more for the disease duration? Was it the disease severity at entry? Was it the number of drugs? Is it just the combination of those three? I think Josh is trying to help understand how does one look at a lot of these baseline characteristics that are shared with more color on how to see how refractory they are. Yes. If you can take an individual patient, the profile becomes clearer. If you take the population, as I said, the duration, you've got 13 years, if you've been cycling through therapies, that either means you've got very bad disease and very resistant, or you have a disease that isn't responsive to treatment. It may not be responsive to treatment because it's not inflammation, it's pain. That has to be separated out. All these patients have a degree of what's called fibromyalgia, which is a sensitization to pain. For some patients, they have post-inflammatory pain sensitization, which means that they will score very badly on tender joints, but they won't have much in the way of swollen joints or a raised acute phase protein, such as CRP or the erythrocyte sedimentation rate, which reflects largely fibrinogen. You can profile these patients. If you have a lot of pain sensitization, a different approach is required, one wouldn't really expect the standard therapies, although some standard therapies do have a degree of pain relief. What you're seeing is surprising because these patients weren't phenotyped beforehand. They had all the bad characteristics, yet you're getting ACR50s, which means that you're getting most of the components of that. It's improving by more than half at six months, which we haven't seen before, apart from CAR- T. CAR-T in RA, of course, is very, very preliminary and has nowhere near the data that Artiva have. Thank you, Dr. Emery. Josh, to answer your question around Sjögren's disease, as you know, in our basket, we're currently evaluating RA, Sjögren's, myositis, and scleroderma. We haven't guided yet what the second indication is. As you know from the data we presented, that we do have more data in Sjögren's than we do in the other indications. We do like Sjögren's for many of the reasons we like RA. It's a big indication. Its patients are spread out in the community. If you want to have an impact in this population, you need a scalable solution. What exactly the registrational strategy's going to be is still TBD if we do choose it as the second indication. There's many reasons why we chose to run a randomized trial against rituximab. It was our first indication. Rituximab is approved in RA. We wanted to demonstrate a clear separation of the signal against an agent that works arguably as well as anything else in late-line RA. Those circumstances are actually different in different indications, it really will be an indication by indication decision on how we move forward. More on that to come. Thank you. Our next question comes from Sam Rollenhagen with TD Cowen. You may now unmute your audio and ask your question. Hi, this is Sam on for Tyler Van Buren from TD Cowen. Congrats on the great initial data and the big weekend at EULAR. I was wondering if you could discuss a little more on the rationale to select the 4 billion AlloNK cell dose. For the pivotal study, are you able to share how many of the initial 21 patients received that 4 billion dose? What are the main observed differences in terms of efficacy and safety you saw versus the 1 billion cell dose? Also just curious if the FDA preferred or asked for the 4 billion dose as well. Thanks. Thank you for the question, Sam. Just to clarify, we have utilized two different doses in our basket study. We used a 1 billion cell dose, which is three doses of 1 billion for a total of 3 billion, or we also started to experiment with 4 billion cells per dose. The decision to go with 4 billion is because 4 billion, we know, provides a higher exposure in patients and a more consistent exposure in patients. Because we don't see any increased safety signal from actually utilizing 4 billion, it gives us an opportunity to actually ensure that we are giving these patients the best opportunity to have a higher exposure. When we tested 1 billion and 4 billion in oncology, we didn't detect significant differences. We have to remember that in oncology patients, you are confronting an immune system in an oncology patient that is much weaker than in a healthy patient or a patient that has autoimmune disease. It could be possible that we see differences between 4 billion and 1 billion. Most of the patients on the 37 patients that we presented at EULAR, particularly the ones that have six or more months of follow-up, those patients were tested on 1 billion, so 3 billion total. The patients at 4 billion, we have some of those. We didn't disclose details of who they are, but we can in the future. They were dosed at 4 billion. We don't have enough data to be able to say whether we are seeing better signs of efficacy with the 4 billion versus 1 billion. We figured since there is no cost from a safety perspective and our costs are pretty low, we would try to actually give these patients the best opportunity to have an effect. Got it. Thank you. Thank you. Our next question comes from Emily Bodnar with H.C. Wainwright. Please go ahead. Hi. Good morning. Thanks for taking the questions. Congrats on the data as well. Maybe if you could talk about the deepening of CDAI and DAS28 scores that you're seeing from month three to month six, and how you're thinking about potential for that to continue deepening and maybe see some additional deepening of responses, maybe from ACR50 to ACR70, and what timing of that might look like. Thank you. What I'll do is I'll start answering, then Diego, I'm going to pass it on to you. Emily, I would start with the fact that we have very few patients that have actually moved beyond the six-month mark. We do need more data to try to understand what is that deepening of effect. As we also discussed, and Dr. Emery pointed out, there is a ceiling with some of these patients that have had disease for so long. We will learn whether this is something that can continue to deepen or whether, at some point, you do hit a ceiling given the longstanding disease. Let me turn it to Diego, then Diego, feel free to pass it to Dr. Emery if you'd like. Sure. I have to say that the patients are very severe in that their scores are really high. It just takes time. As Dr. Emery has said, these patients have a chronicity of disease that it takes time for some of the inflammatory patterns to come down. Others have shown similarly that the results at three months are enhanced by continued observation at six months. That's pretty much, I would say, that is given some of the data that has been generated by us and others, that's an expected pattern, I would say, that responses deepen. I think we have to put into context what ACR50 means for these patients that are fairly advanced is that the results of ACR50 over 50% are higher than those observed according to the label of first-line treatments. I like to say we are observing the most refractory patients results that haven't been shown in first-line treatment. I think the responses are quite remarkable. Emily, one thing I'll point out is, maybe it's a question for Dr. Emery, and I'll help you ask the question, which is, have we historically seen in trials that if you achieve an ACR50 response at six months, that these response keep on deepening? Have we learned, over time, across the different agents, Dr. Emery, that there is, in a way, a ceiling effect? Like if you haven't seen the effect by three or six months, then it's probably unlikely that that continues to deepen by nine and 12 months. I personally have not come across a study that has suggested that level of timeframe, maybe you could comment on that. First of all, it depends on the height of your DAS. The trajectory of responders is the same whatever your DAS is. If you're starting from a very high level, you've got greater margin for improvement. Outside clinical trials, we're much more interested in states than improvements, because you can improve quite a lot but still be pretty bad. What we're interested in is ideally getting patients into remission, which will be virtually impossible in these patients. Some patients may be lucky enough. Getting them into a low disease activity state. If the patients continue to improve, they will actually reach that state, but much later the higher their starting point. What I would hope we would see later is that larger number of patients go into low disease activity state, which will be one outcome. Don't forget, the improvement criteria relate back to where they were at baseline. If they go on improving, they will improve their ACR50/70, and with B-cell and cellular therapy, it's not like anti-cytokine therapy. You would expect if they really have maintained their B-cell depletion and the cycling goes on and naive cells reemerge without the memory, then the possible disease activity will continue to drop. I think you've got to be realistic. That would be a real bonus if we do see that. I think if we can maintain the patients in the sort of state they've reached by six months, that would be a positive outcome, if it's that state without relapsing. Thank you. Our next question comes from Gil Blum with Needham. Please go ahead. Gil, you may now unmute your audio and ask your question. Hello, can you hear me? Yes. Excellent. All right. Congrats on the progress. Just a couple from us. First of all, has anyone looked through the potential causes of failure of rituximab in RA patients and how that might be related to the immune background of those patients? I'll pass that to Dr. Emery. The commonest cause of failure of rituximab is failure of depletion. That can be a variety of reasons. The most simple is people do get anti-drug reaction. They get anti-chimeric antibodies against the actual monoclonal. There are more complex genetic causes. Fc gamma receptors, because of the interaction with the Fc fraction, also influence responses. In certain genetic populations, there's a poorer response, but all these are minor. The fact is that rituximab alone is not a great depleter, and if you use some of the other B-cell depleting agents, you would get higher levels of B-cell depletion. Rituximab, you get a good or moderate response in about 70% of patients. As I said, that's not the level of response we're looking at here with ACR50s of over 50%. If you re-treat patients who don't get depletion, you can go on re-treating it. We've done two studies in which when we didn't deplete, we gave extra doses. We gave 50% extra dose of rituximab, and we got better responses. Part of the non-response is insufficient drug to produce the level of depletion that's required to impact clinically. In the absence of anything better at the moment, we're currently in Leeds. We've got many, many patients. We've got probably the biggest population of rituximab. We have patients who have failed it, and we're now giving them routinely, a cycle is two infusions. They're now getting six infusions, which shows that it is primarily the B-cell depletion where we're getting failure, and it's the potency of rituximab, which, of course, is what this whole approach improves by giving these Allo NK cells in combination. Gil, I'll remind you that we had a number of patients that had had an inadequate response to rituximab that by six months on our therapy did show an ACR50. It corroborates what Dr. Emery's suggesting around the depth of B-cell depletion. All right. In the investigator [basket] study, you had some patients who remained on their background DMARDs. Are we going to try and remove these? The DMARDs, not the patients. Dr. Emery, one of the discussions that we had is originally when we were all evaluating Dr. Schett's studies, particularly because it was in lupus, the goal there was just to eliminate every background therapy. Based on discussions that we had and others that are working with us on the phase III trial, there was this determination that it's very satisfactory to keep the patients on their background methotrexate if they're on it and low-dose steroids as you're getting through the endpoint. Could you comment a little bit more and provide a little bit more color on the rationale there? Yeah. For the moment, when we're doing the studies where we don't know the duration of response, if you produce more variables by stopping steroids, stopping methotrexate, it produces just too much noise. Like everyone else, I'm very keen to see how long this approach works for, and I don't think we'll be able to tell. You can withdraw steroids even if they're not needed, and you can get a rebound of certain metabolic impacts. For the moment, in these patients, if they're on a drug when they go into this study, it's not because the drug is toxic, it's because the drug is ineffective. They don't mind staying on them, and it actually simplifies the analysis of what's going on. I have no doubt if we come to further studies where we will be looking at withdrawal of DMARDs. I suspect if the DMARDs don't have an impact on the B-cell depletion, which I strongly suspect the impact they have will be very small, that I don't think they will impact on the outcome. At the moment, it's not appropriate to introduce variables. You only have to look at lupus studies where they tried steroid reduction and everything else at the same time as measuring the outcome. You can see how complex it gets. Gil, i t takes us a little while to have the answer on this because in the IIT and in the basket study, we were pretty much allowing the physicians to actually discontinue all the backgrounds as they wished. In an ideal world, we are keeping the background medications, understanding that, and then pairing off. We're almost taking a two-step approach where now we are in the RCT making them remain on the background medications, as Dr. Emery suggested, so that we can understand durability. It may take a little time for us to have a clean enough data set to understand what the impact may be of those discontinuations that many of the patients experience in the IIT and the basket. Thank you. Very helpful. Last one, a little bit of aspirational. The emerging product profile makes really excellent sense for later-stage patients. What do you think about the same TPP, including the lymphodepletion, if we're considering moving to earlier in the patient journey here? Thank you. Again, I'll turn to Dr. Emery to provide his insight. The question, Dr. Emery, is when you start utilizing a therapy like this in a later-line population, this makes a lot of sense because of the lack of additional options. Knowing how tolerable one dose of Cy/Flu is in order to get this treatment-free period, which we're still figuring out how long, do you envision this moving into an earlier line? I think the paradigm has changed. One thing is what we're doing at the moment is terrible for our patients, which is fiddling around and not treating them properly. We're doing two things, which is introducing biologics first line for poor prognosis patients. We will, I hope, be able to identify resistance within 18 months of onset. At that point, the obvious thing to do is give deep B-cell depletion, and Artiva's got a product for that. It'll take 10, 15 years to happen. I think we won't let patients sort of stagger along with a little bit of inflammation, steadily getting worse, less treatable. Now we've got the data that B-cell depletion is so effective, and it's something I've believed in since we first had rituximab. All we've got to decide is it a B-cell-mediated disease? If it is, if it's not being treated satisfactorily, well, you get rid of the B-cells. We didn't know how safe that was going to be at the time. It's taken us a while. It's taken us far too long. Thank you. This concludes the question and answer session. I'll now turn the call back over to Fred Aslan for closing remarks. I just wanted to thank everybody for their time. We look forward to continuing to demonstrate progress.