Good morning, and thank you all for joining us today. I'm Chen Schor, President and CEO of Adicet Bio. By now, you've seen the press release we issued this morning, announcing important updates for our lead asset, ADI-001. We're excited to share a corporate update today that we believe has the potential to unlock significant value for both patients and shareholders. Let's get right to it. As a reminder, we'll be making forward-looking statements today as detailed on this slide, including express or implied statements regarding ADI-001, our future plans and strategy, and other statements that are not historical fact. Please also refer to the forward-looking statements from today's press release, as well as the risk factor section in our most recent 10-K and subsequent SEC filings for more details. This call is being recorded. On the call with me today are Dr. Francesco Galimi, Chief Medical Officer, Dr. Blake Aftab, Chief Scientific Officer, and Nick Harvey, Chief Financial Officer. We're excited to kick off 2024 with the goal of unlocking the promise of our strong and diversified pipeline of off-the-shelf engineered gamma delta CAR-T programs in cancer, and now also in autoimmune diseases. As you saw in the press release we issued this morning, we announced important updates on our lead asset, ADI-001. Currently, ADI-001 is being evaluated in an ongoing phase I study for the potential treatment of relapsed or refractory B-cell non-Hodgkin's lymphoma or NHL. Based on ADI-001, clinical data to date and its therapeutic potential in B-cell mediated diseases, we have decided to broaden its development to autoimmune diseases. To that end, the US FDA recently cleared the IND application for ADI-001 in Lupus Nephritis, and we plan to initiate this clinical study in the upcoming second quarter. In addition to initiating development in Lupus Nephritis, we plan to expand the program in the near term to additional autoimmune indications. In today's update, we also announced our decision to focus on enrolling MCL patients to the ongoing phase I study in NHL. As noted in our previous data update in June 2023, the MCL patient population saw the greatest clinical benefit to date following treatment with ADI-001. We believe this step will enable us to build on the favorable product profile observed in this patient population, including the high complete response or CR rate, the favorable durability and safety profile, no significant risk of CRS and ICANS, lower risk of T-cell malignancies compared to autologous CAR-T, and the potential to dose off-the-shelf in community setting, which should enable broader, broader access to patients. These properties provide ADI-001 with significant differentiation and potential for best-in-class therapy for MCL patients. Additionally, we've been very diligent with our allocation of resources to streamline our programs and operations to deliver meaningful benefits to patients and shareholders. With that, we have updated our cash runway into the second half of 2025, which provides Adicet optionality and multiple opportunities for significant milestones, as we will outline in today's presentation. I'll now turn to discuss why we're excited about the potential of ADI-001 in autoimmune diseases. Let's go to the next slide. Considerable evidence from academic studies has shown profound and durable responses to autologous CAR-T therapies in patients suffering from severe refractory autoimmune diseases, including systemic lupus erythematosus, or SLE, systemic sclerosis, and idiopathic inflammatory myopathy. 3 diseases. Clinical data from these academic studies demonstrated that depletion of B-cells causes a reset of the immune system that is disease-modifying and allows patients to remain treatment-free across several autoimmune diseases. I would like to highlight that the B-cell depletion data from our ADI-001 in lymphoma, in lymphoma, on the left side of the slide in light blue, mirrors the B-cell depletion of autologous CD19 CAR-T in lupus patients who experienced robust efficacy from academic studies by Schett et al., presented on the right side of the slide in the darker blue graph. This B-cell depletion profile of ADI-001 is also consistent with the profile presented by Schett et al. in the American College of Rheumatology conference, less than two, less than two months ago in November, in 15 patients with lupus, systemic sclerosis, and idiopathic inflammatory myopathy who experienced robust efficacy. These data are also consistent with ADI-001 being the first and only allogeneic cell therapy with Cmax and exposure by AUC, or area under the curve, that meets or exceeds data reported by approved autologous CD19 CAR-T, as recently presented by Adicet at ASH last month. B-cell depletion via CD20 targeting is also supported by the long clinical experience with the anti-CD20 antibody rituximab, and by the recent data with obinutuzumab, an anti-CD20 with enhanced cytotoxicity, which demonstrated compelling efficacy on top of standard of care in lupus nephritis in a phase II clinical study. Let's go to the next slide. This slide summarizes the key reasons we believe ADI-001 has significant potential in autoimmune diseases. First, as I outlined, B-cell depletion from ADI-001 trial in patients mirror B-cell depletion by autologous CD19 CAR-T in lupus, systemic sclerosis, and idiopathic inflammatory myopathy. Second is the homing tissue, homing to tissues. The inability to deplete tissue-resident B-cells in secondary lymphoid organs and other tissues has been reported as a contributing reason for the failure of targeted antibodies in lupus. A critical advantage of gamma delta 1 T-cells is their tropism to solid tissues. This property may be ideally suited to deplete B-cell mass located in peripheral tissues, including secondary lymphoid organs and kidneys, which may better enable an effective reset of the immune system, a highly desirable outcome for the treatment of autoimmune diseases. Third is safety. ADI-001 has shown to be well-tolerated, with no significant CRS, ICANS, and lower risk of T-cell malignancies compared to autologous CAR-Ts. This profile, and ADI-001 off-the-shelf availability, makes it suitable for the treatment of autoimmune diseases and provides the potential to dose patients in the community setting. I'll now hand it over to Francesco to expand on the planned clinical design of the study and provide additional detail. Francesco. Francesco? Thank you, Chen, and thanks, everyone, for joining us this morning. As Chen covered previously, we are pleased to be expanding the development of our lead pipeline asset, ADI-001, into autoimmune diseases. Let me start by illustrating on slide 8 the dose-finding phase I trial design that we will initiate soon in lupus nephritis as a first indication. We will perform a 3 + 3 dose escalation, starting at 100 million CAR-positive cells, flat dose, which we know provides compelling efficacy in our Non-Hodgkin's Lymphoma trial. Subject to safety findings, higher doses will be explored, up to 1 billion CAR-positive cells. Before ADI-001 infusion, each patient will be conditioned with cyclophosphamide and fludarabine lymphodepletion. The dose-limiting toxicity reporting window is set to 42 days, six weeks, for this study. Safety events during this period will be driving dose escalation decisions. The first efficacy assessment is scheduled on day 28 after infusion, and then on months three, six, nine, 12, 18, and 24 thereafter. Once the maximum tolerated dose or maximum administered dose is determined, a dose expansion cohort will be opened to further characterize the safety and efficacy of ADI-001 in Lupus Nephritis patients. The next slide illustrates the endpoints of the study. Primary endpoints will be focused on safety, given this is a phase I study. Preliminary efficacy will be measured starting on month one after infusion and will be centered on recovery of kidney function as a secondary endpoint. Additionally, cellular kinetics and a panel of relevant pharmacodynamic measures will also be monitored over time, such as anti-nuclear antibodies, anti-double-stranded DNA antibodies, and complement levels. Systemic lupus, lupus responses will also be measured as exploratory endpoints with a consolidated scoring system used in the clinic called SLEDAI-2K, which accounts for a broad panel of clinical assessments, including neurological, psychiatric, dermatological, nephrological, and hematological parameters. In summary, with B-cell depletion that has been observed to mirror autologous CD19 CAR-Ts in autoimmune diseases, exposure that has been observed to match or exceed autologous CAR-Ts, trafficking to peripheral tissues, favorable safety profile, and off-the-shelf availability, we strongly believe in the potential of our first IND in lupus nephritis, and we plan to expand into additional autoimmune diseases in the near future. Before I turn it over to Chen, I'd like to provide an update on the progress of our non-Hodgkin's lymphoma program on the next slide. As we announced this morning, we're focusing our current enrollment efforts on mantle cell lymphoma, where we believe we can deliver a highly differentiated, potentially best-in-class therapy. While the sample size is still small, we're optimistic about its potential, given the favorable safety profile observed in our May data cut, with no significant risk of CRS, ICANS, or T-cell malignancy, the high complete response rate of 80%, and the favorable durability in late-line patients, with 60% of patients in complete response beyond six months. We are evaluating the option of advancing ADI-001 to a potentially pivotal study in mantle cell patients under an accelerated approval pathway. As previously announced, we expect to provide a clinical update in the second half of 2024 for ADI-001 in Mantle Cell, and we may also provide a clinical update of ADI-001 in autoimmune diseases in the second half of the year... We are excited to expand our program to autoimmune indications, and look forward to updating you on the progress, both in autoimmune and in Mantle Cell Lymphoma. With that, I'll turn the call back to Chen. Chen? Thank you, Francesco. We've outlined our strategic and disciplined development plan for maximizing the ADI-001 opportunity across lines of therapy in MCL and in autoimmune diseases, as presented on this slide. I'll now briefly discuss our second clinical candidate, ADI-270. Let's go to the next slide. ADI-270 is an investigational next generation allogeneic CAR-T program targeting CD70 via CD27 ligand. This approach has shown superiority to single chain F- CARs, and provides anti-tumor activity in tumors with relatively low antigen density. Coupled with the innate and adaptive targeting mechanism of the gamma delta one T-cells to address tumor heterogeneity, Cmax and exposure by AUC profile that meets or exceeds autologous CAR-T for our gamma delta one CAR-T platform, and the homing of gamma delta T-cells reported in renal cell carcinoma, ADI-270 is highly differentiated for the treatment of renal cell carcinoma, or RCC. With ADI-270, we have incorporated third generation costimulatory signaling, which, when coupled to CD70 binding, is designed to enhance durable activity while potentially improving the graft resilience. We also included TGF-beta dominant negative receptor armoring to ADI-270 to address suppressive tumor microenvironment factors and enhance serial killing capacity. We believe these properties make ADI-270 differentiated for RCC and other CD70-expressing tumors. We look forward to filing the IND in the second quarter and initiating clinical development with RCC as the initial indication, as well as progressing our next program targeting prostate cancer. Let's review our near-term milestones on the next slide. Well, in summary, we're excited with the prospects for 2024, with significant milestones ahead and runway into the second half of 2025. Let me walk you through the potential near-term milestones. With regards to ADI-001 in NHL, we expect to provide clinical update in the second half of 2024, with the latest, with the latest data set from our MCL clinical study, including additional patients, updated response, and durability data. We plan to potentially initiate the pivotal study in third line MCL, which represents a significant unmet medical need, and we're also evaluating the possibility of expanding ADI-001 to earlier lines of therapy in MCL. For the development of ADI-001 in autoimmune diseases, currently, we're completing the startup activities for the clinical study in lupus nephritis, including getting new sites up and running. We expect to initiate the phase 1 study in the second quarter of this year, and pending rate of enrollment, may provide a clinical update in the second half of the year. In the near term, we expect to expand ADI-001 clinical development into additional autoimmune diseases. Finally, in terms of our pipeline programs, we plan to leverage the meaningful differentiation of gamma delta 1 T cells. For ADI-270, we expect to file IND in the second quarter for RCC, and we look to see significant differentiation in this indication and other CD70 positive tumors. Lastly, we aim to file at least one IND every 12-18 months. With that, we thank you for joining us this morning, as we look forward to a productive year ahead. I'll now turn it over to the operator to open up the call for Q&A. Operator, please. We will now move into our Q&A session. For those of you who are joining us via Zoom, if you would like to ask a question at this time, please raise your hand by clicking the Raise Hand button under Reactions at the bottom of your Zoom window. If you are dialed in via phone, please select star nine to raise and lower your hand, or star six to mute and unmute. Once called upon, please unmute your audio to ask your question. Thank you. We'll just pause a moment to assemble the queue. Our first question comes from Kelly Shi from Jefferies. Kelly, star six will allow you to unmute. Thank you for taking my questions. You mentioned, focus will be enro... Can you hear me? Yeah, we can hear you. Yeah. Okay. So you mentioned the focus will be to enroll mantle cell lymphoma patients for ADI-001. Just curious, what is the status for the post-CD19 CAR-T program in large B-cell lymphoma patients? Is it entirely paused or, like, just evolving at a slower pace? Yes, absolutely. Thank you for the question. So, when you look at the data in a Mantle Cell Lymphoma, if you look at our last update, you see 80% CR rate, you see 62% of the patients with a CR beyond six months, and you see great, safety profile. So the decision, essentially, it's a budget-driven decision. We decided to focus right now for at least for in the near term, on exclusively MCL patients and progressing this indication as potentially our first pivotal, study. In the future, we may pursue other forms of, NHL, such as follicular, maybe even LBCL, but in the near term, the focus is on MCL patients. Yes. Okay, great. And also, can you talk about the site activation for the trial in lupus nephritis with multiple grants and also different mechanism of action for the program to initiate the trials in the first half of this year? Do you expect a slow enrollment pace because of the competition? Enrollment to lupus generally is, you know, not as quick as one would wish for, and there is competition. What I can share with you is that in our discussions so far with the different KOLs, once they saw the B-cell depletion data with ADI-001 and comparing it to what we've seen with the Schett in multiple autoimmune diseases, and the fact that it's off the shelf and essentially very nice safety profile. So we have seen significant interest in the study. So, you know, hopefully we'll see decent enrollment, and I want to emphasize, Kelly, we will be going to additional indications in the near term. You know, when we say something, we usually execute on it, so you'll see more indications as well. Okay, great. Thank you. Absolutely- Our next question comes- Thank you for the questions. Our next question comes from Michael Schmidt, from Guggenheim. Hey, guys. Good morning, and thanks for taking my questions. Yeah, no, interesting move into lupus, obviously, Chen, really, really interesting. I noticed you're focusing on lupus nephritis. I know there's a lot, a lot going on in SLE. Can you talk about your decision to move into that category specifically, as opposed to SLE more broadly? Francesco, do you want to take this question? Obviously, we're looking to SLE and lupus nephritis. I don't think there is a significant difference in terms of the ability to show difference - to show efficacy in SLE versus lupus nephritis. But Francesco, do you wanna- Sure. Do you wanna comment on this? No. Absolutely. Can you hear me okay? Yeah. Perfect. Okay. So Michael, that's a very good question. So lupus nephritis, as you know, is just a kidney manifestation that frequently affects patients with lupus. The reason why we are starting from that particular approach and that particular indication is that it offers the opportunity of very clear and unequivocal short-term endpoints to be measured, because recovery of kidney function is something that is known, if the data are positive, of course, to be straightforward and unequivocal to measure. As you know, the endpoints in systemic lupus are more complex. They take longer to be established and to be measured. So the Lupus Nephritis, first of all, is a clearly unmet need in the lupus population of patients, and then offers the opportunity to have a relatively short-term readout and unequivocal measure of efficacy. All right, that makes sense. And yeah, interesting analysis on the, the B-cell depletion. Mm-hmm. What you on the need for cell persistence, perhaps in lupus versus in, you know, the need for that in B-cell lymphomas? Mm-hmm. Francesco, do you want to take that? Yeah, definitely. So that's another excellent question. If you believe and remember the data that were discussed in recent forums from the academic experience with anti-CD19 autologous CAR-Ts, there is a consensus that what really matters in that setting is not so much the persistence of the cells sticking around for as long as the disease needs to be kept under control, but it's rather the resetting of the hematopoietic system. There is a consensus that what happens is that the CAR-T approach has the ability to provide a profound B-cell depletion that essentially results in a resetting of the faulty B-cell clones. So that even though the cells, the transplanted cells eventually disappear or go below pharmacologically active level, the immune system actually recovers with a healthy B-cell mediated immunity, as opposed to the faulty one, so to say, that was responsible for the disease. The field, it has to be said that the field is still in its infancy, so we'll see how the data unfolds, but that's the current model. So in that sense, our ability for ADI-001 cells to stick around for a number of weeks, as you might have seen in our oncology experience, is plenty of persistence, so to say, to trigger the resetting that I was alluding to. Yeah, Michael, let me- Uh, okay. Let me add two points for you. Let me add two points. One, when you look at the Cmax and the AUC, and even the day 28 levels of ADI-001, they actually meet or exceed the autologous CD19. So that's one. Second, I think if you look at the Schett presentation from ACR, there's a nice presentation where they presented data from 15 patients with SLE, systemic sclerosis, and IAM, so three autoimmune diseases. What you learn are two things that I think actually address your question. One is that the peak CAR-T expansion is around day nine, and actually, Schett says that the long-term levels are very low and not detectable. So you can see that the B-cell starts to return on average around about 100 days. So it seems like in autoimmune, you want to reset the B-cell compartment, and then it starts to recover. When you look at our B-cell depletion profile, you can see that that's what you would expect from us as well. Okay. Super, super interesting. And then the last question, just on the MCL, you know, sort of news on the phase one study. When we think about this update coming later this year in the second half, will you include meaningfully new patients in the phase one with MCL, or will it be mostly more follow-up on the existing cohort? Look, we are right now focusing on MCL enrollment, and there is significant interest in the study in MCL. The data in MCL, again, as of the last data update, look great, and when you think about the current alternatives for MCL, we have some significant advantages. So definitely additional patients, more durability for the current patients, and durability data for new patients. Great. Thank you. Thank you. Our next question comes from Asthika Goonewardene from Truist. Star six will allow you to unmute. Hey, Astika. Asthika, the floor is yours. You may unmute by dialing star six on your phone's keypad. Perhaps we'll go to the next person, and we'll return to you, Asthika. Let's take a question from John Newman from Canaccord. Hi, guys. Hey, John. Good morning. Thanks for holding the call and taking my question. Just had two quick questions here. The first one is regarding the lupus study, wondering if you'll be allowing patients previously treated with Rituxan, and if so, will you be utilizing a washout period? And the second question is, should we expect you to use the enhanced lymphodepletion in the lupus study that you've used in the NHL study? Thanks. Mm-hmm. Francesco, why don't you go ahead? Sure, yeah. To the first question, the answer is yes, we will allow patients with a prior exposure to Rituximab, and yes, we do have washout periods for Rituximab and for every other prior therapy that we might have in our patients. The study will be in patients who have been exposed to a number of prior therapies. Regarding the second question, we have not disclosed, and we're not disclosing, right now the exact regimen for the lymphodepletion. You know, the field is still in its infancy, so to say, so we want to preserve that type of information. What I can tell you is that it will be lower than the enhanced lymphodepletion regimen that you are familiar with in our non-Hodgkin lymphoma study. Great. Thank you. We'll return to Asthika Goonewardene from Truist. Hey, guys. Can you hear me okay now? Yes. Yes. Hey, Astika. Oh, sorry about that. Okay, so just to, John just asked part of the question I wanna ask earlier, but let me just build on that. So if you, so Francesco- Mm-hmm ... if you're going to reduce the amount of lymphodepletion that you're giving, would you still expect to see the same level of expansion of ADI-001 in the patient with lupus nephritis? I would expect the same essentially profile to happen. So we're not planning to go to a non-lymphodepleted type of setting, obviously. So lymphodepletion is being designed in order to allow 001 cells to expand as efficiently as as in our prior experience. Yeah, Asthika, I just want to add on this. We are using a lymphodepletion that is clinically validated. It's, you know, minor differences from the enhanced lymphodepletion. The only reason that we're not sharing it is just for competitive reasons. If you look at other peer companies, they have not shared the specific lymphodepletion regimen. We've worked with FDA to agree on this, so that's not a concern for us at all. Minor difference but from enhanced lymphodepletion, but just for competitive reasons, we're not sharing it. Got it. Okay, that's clear, guys. Thank you. Now, I apologize, I got a little bit of a harder question here. I get the rationale for going to MCL. Obviously, it's an unmet medical need. There's your data that you have presented in that setting is-- looks really good, looks promising. You know, it has needs for therapy like that. But what specifically was it about the large B-cell lymphoma cohort that you were pursuing, that made you want to scale that back and park that? Was it the competition in the space that's happened right now? Is it the need to conserve capital and focus on these two other programs? Maybe just walk us through what got you to this point, guys. Absolutely. Yeah, thank you for asking, and it's not a hard question at all. So let me tell you what it was not, first of all. It was not additional clinical data from the study. Let me tell you what it was. It was purely a budget driven decision and focus for the company and for the clinical team. When you look at our competition, you know, you see at least with the B-cell specific, durability hasn't been a, you know, something to write home about if you look at the recent data in ASH. In LBCL, we think that consolidation dosing is probably preferred with 2 doses of ADI-001 and 2 lymphodepletion. And, you know, when we look at the potential in autoimmune diseases, we see such a vast potential in multiple autoimmune diseases that we can go after, and we just decided at this point to focus on autoimmune and MCL. So that's really what drove our decision. Hopefully, that is helpful to you. Yeah, that's very helpful, guys. Thanks for the color on that. Absolutely. Our next question comes from Reni Benjamin, from JMP. Hey, guys. Hey. Can you hear me okay? Perfect. Hey, good morning. Thanks for taking me. Maybe just to start off, you know, as I kinda compare the data that you guys showed on, on the, you know, third or fourth slide, with ADI-001, the B-cell depletion that occurs looks nearly complete, but it seems like there might be some residual B-cells remaining. In the academic data, it looks like a complete depletion, and I guess I'm kinda curious, how important is the complete depletion of B-cells in an indication like this? And, you know, are you thinking about anything that you might combine B-cells with, you know, at least initially, to maybe push, you know, the level of B-cells down if that's what's needed? Yeah. Blake, do you wanna take, this, this question? Yeah, sure. You know, I think when you look at the B-cell depletion levels for our existing NHL experience, it's you know, quite complete, and actually lasts quite long and definitely beyond the 100-day median time for recovery that's shown in the autoimmune disease setting. Now, of course, NHL isn't necessarily predictive of what we can see in autoimmune, since the B-cells there may be healthier and have a faster recovery time. But as far as the completeness of B-cell depletion, our NHL experience is quite complete, analytically. Okay. And then, you know, I guess as I try to complete, compare the two indications and the, call it the translatability, you know, is there outside of the academic experience, which I think is great, and that data looks amazing, is there anything else? You know, you guys mentioned trafficking, right, of the gamma delta T-cells. Is there anything else from this profile, you know, that you think could actually make it better or do better than the academic setting? Sure, absolutely. I can try to address that. So the first point is trafficking to tissues. I wanna say gamma delta 1 T cell is probably one of the only types of cell therapy that actually traffics to tissues and can deplete the B-cells where you want them to be depleted in the right compartments for autoimmune diseases. So that could be a significant advantage when you think about gamma delta 1 T cells compared to any other types of T cells. And, you know, for example, when you think about Lupus Nephritis, getting into those T cell nests in the kidney are gonna be very helpful. And we know that there is homing to kidneys of gamma delta 1 T cells. So homing in autoimmune diseases, I think, is a significant advantage. The second one is safety. When you think about these patients, many of these patients are young and, you know, have failed a couple of therapies. You know, CRS and ICANS hasn't been a big issue in these patients with their cell therapies. We don't expect them to be any issue with gamma delta 1 T cells. But, you know, the T-cell malignancy risk is kind of disturbing when you're young, younger, for example, lupus patients. So having something that's allogeneic will provide you essentially no, or, you know, very, very much lower risk of T-cell malignancy should be advantageous for these patients. And I think the last one is off-the-shelf availability. You know, you can just go to your physician. You don't need to travel to an academic center and potentially get it right off the shelf in the community setting, given the safety profile that we've seen to date. So when you bundle all this, there is the potential for better efficacy, better safety, and availability in the community setting. So we think this could be quite significant in the market, assuming, obviously, we get approval. ... Got it. Yep, and you addressed the final question I had slightly. I'm just hoping you might be able to expand on it. The T-cell malignancy part, right? So we have the recent findings, the FDA is investigating. Mm-hmm. I'm just kind of curious how you kind of navigate that, you know, as you think about, I guess, the different outcomes, you know, from the- Mm-hmm ... FDA's investigation. You know, if you have autologous cell therapy, and you happen to provide a graft, it's not really a graft because it's autologous that does have the potential for malignancy, your immune system wouldn't necessarily reject it. So you could potentially, in a very low percentage of the cases, provide therapy that could potentially cause a malignancy for the patient. In the case of allogeneic cell therapy, our advantage is, one, that when you look at the Cmax and day 28- Mm-hmm ... persistence and AUC, it's comparable to allogeneic. But after a few months, the body will reject the graft, and that's why there is a significantly lower, risk of T-cell malignancy with the allogeneic cell therapy. Mm-hmm. We think this will be an advantage, and this is just a potential effect because of the type of therapy that you provide. Excellent. Thanks for taking the question. Absolutely. Thank you. Our next question comes from Rob Driscoll from Wedbush. Star six will allow you to unmute. Hey, Rob. Hey, thanks, guys, for taking the question. Hey, everyone, and Happy New Year. I think you kind of touched on this in a few answers, but just trying to, I guess, match the profile of ADI-001 with the patient population here in lupus nephritis. I think there are different kind of severities of the disease. You know, would maybe most, if not all patients here be eligible ultimately, and you know, I guess how that aligns with the patients you expect to enroll? And then second question, just are you going to wait for initial data here before moving into additional AI indications, and I guess what would be the gating outcomes there? Thank you. Yeah. Francesco, why don't you start with the first one, and I'll go to the next one? Sorry, I was on mute. Sorry, guys, I do that every time. I'm not sure I understood your first question. Could you be so kind as to repeat it? Yeah, I guess just within lupus nephritis itself, you know, what proportion of those patients, you know, would really match a treatment for ADI-001? You know, would it be kind of all patients, refractory patients, all refractory patients, and so on? Just trying to get a sense- I see ... you know, the ultimate patient population here in the market. Sure, sure. I cannot predict exactly at the end of the game what type of percentage of the overall population will be eligible. What I can tell you is that the study will start from patients who are relatively late-line, so they will have to be exposed to prior therapies. We have negotiated with the FDA and discussed with the FDA, so it's all ready to go. It is likely that patients with a form of lupus who can be managed with a more traditional, shall we say, pharmacological measures will not get to the attention of a cell therapy approach. But we do know that there's a very significant proportion of patients who are really challenging to be managed in the clinic. And the challenge is compounded by the fact that these are relatively young patients, and so having a particularly effective therapy is highly relevant. Also, for a number of reasons, including the age group. So too soon to say exactly what type of TPP, so to say, will end up heavy, but it's unquestionable that there is a very significant unmet need in Lupus Nephritis in particular, in lupus in general. Additionally, there are other diseases that we'll expand into very soon who are also maybe less famous, so to say, but very, very acute unmet needs. And Rob, regarding your second question, you know, we started talking to a couple of the KOLs, and once they saw essentially the PK profile in terms of the Cmax and the AUC that's consistent with autologous, and once they saw the B-cell depletion profile from our data, and the safety profile, there is interest in other autoimmune diseases. So I think the question, the answer to your question is no, we will not be waiting. So you might see this in the near future going into other indications as well. Got it. Thanks very much, guys. Absolutely. Thank you. Thank you. Our next question comes from Ed White from Wainwright. Star six will allow you to unmute. Hey, Ed. Happy New Year! Thanks for taking my questions. Most of them have been asked, but I do have a couple left. Just on the MCL patient population, I'm curious- ... that with the great data in the large cell population in post CAR-T, will you enrich the patient population to post CAR-T therapy or at least break that data out once we see it? You know, you'll see the data once we present it. We're not necessarily, and we haven't in MCL, prioritized pre-CAR T or post-CAR T. You know, the benefit that, we see is, you know, in all third line MCL patients, and at some point we might expand to earlier lines MCL patients. So, you know, there is significant unmet medical need in third line, and so far there was a lot of interest by, CAR T naive and, and post-CAR T. Okay, thanks. And the other question I have is just on 270, is there any other information you can give us? You know, assuming that the IND is approved, you know, do you think you can start the trial in this year? You know, any guidance you can give us on the number of patients or what endpoints you will be looking at? Is the first just going to be safety data, or should we be looking for efficacy? Just any thoughts you can give us on that study. Sure. I'll start, and Francesco and Blake may expand. So first of all, we had a pre-IND meeting with the FDA. It was a very successful meeting, and based on that, we slotted the IND filing in the second quarter of this year. We're, you know, drafting the protocol. We're gonna start with RCC and then expand to other indications. We haven't provided guidance exactly when we expect to start the study, but as you know, by now, we have CRO-- CDMO manufacturing capabilities as well as in-house manufacturing capabilities. So I would expect that we would start the study in the short term after we cleared IND with the FDA. Regarding the number of patients and endpoints, I think it's premature. We'll just show the design of the study, but you know, it's a RCC study and probably not completely different than prior RCC studies. Francesco or Blake, anything you want to expand here? Yeah. So on the study design, obviously, it would be phase one, first in human for that particular asset. And so there would be a dose-finding portion of the study, and the primary endpoints will obviously be safety. But as usual, preliminary efficacy will be carefully monitored and will be a, you know, secondary, secondary endpoint. So it's going to be a pretty standard phase one. We expect that those dose-finding exercise to be relatively quick, relatively, because some information we can cross-reference from our prior asset. It's no longer a completely new platform, but we have quite a bit of clinical experience with the platform, not with the app. Yeah. Maybe, maybe just adding to this, that I, I, I personally am excited about this program. You know, in cell therapy, the first part of the problem is get the cells to where they need to be, and in solid tumors, it has been a challenge. With gamma delta T cells, there is tissue tropism to the kidney tissue. So that's one. So that you wanna get there. Then once you get there, you wanna try to hit the tumor, well, and that's why we chose the CD27 ligand because it has shown better, better cytotoxicity, and you need lower antigen density. So you wanna hit the tumor hard. Then you have some heterogeneity, potentially in the tumor. We know that in gamma delta T cells, we have the innate and adaptive as additional mechanism of actions, and we know, at least based on our experience with ADI-001, that one would expect Cmax and AUC, which is comparable to autologous CAR T. So there is a couple of contributing factors that really differentiate it, and it's not by coincidence. We're following as a strategy, the tissue tropism of the gamma delta 1 T cell, then the additional components that you've seen, you'll see in other programs as well. So the emphasis is on differentiation for patients and high probability of success. Okay, great. Thank you for taking my questions. Absolutely. Thank you. Our next question comes from Justin Zelin from BTIG. Hey, Justin. Justin, star six will allow you to unmute. Looks like you're currently muted. Thanks for taking the questions. So maybe first in the Lupus Nephritis study, I understand you're not disclosing the lymphodepletion regimen exactly today, but could you just let us know if you're planning to move forward with a single lymphodepletion dose or if you plan to assess multiple doses in that study? Yeah, single. Okay, great... And you also mentioned the possibility to move into additional autoimmune indications. Could you give us an idea of what indications might be in that list? Like, are you looking at MS or rheumatoid arthritis, and maybe just any additional color there would be helpful. You know, not necessarily MS and RA, although they're also potentially plausible, but there is a host of B-cell-mediated autoimmune diseases. Honestly, there is an interest in quite a few of them. We have to prioritize and focus on a few. So I would just stay tuned until we provide additional update there. There is a huge unmet medical need. You just need to pick on what patient population you wanna focus on. The mantle cell, do you feel comfortable with the dose level for cell dose in this population? Or is there any potential that you might have additional data from any of the repeat or cyclic dosing cohorts here that might inform your thinking about a dose moving forward? We feel very comfortable. When you look at our data in MCL, starting with the lower doses, you see nice complete responses, you see nice durability. When you look at the maximum administered dose, as you know, we reached 29, and then hence lymphodepletion was well tolerated. So, you know, the enrollment currently is with a enhanced lymphodepletion and dose level 4 in this patient population, and that, that's the focus. Keep it simple. Great. Thanks for taking my questions. Absolutely. Thank you. We have time for one more question, and the final question will come from Soumit Roy from Jones. Hey, Sumit. Hi. Good morning, everyone. Good morning. Yes, first, the lupus nephritis program. Could you give us a little detail? I apologize if you talked about it already. Have you tested out in mouse model to see cell-free DNA levels and how it affects or how effective it is compared to the comparative drugs on reduction of cell-free DNA levels? And second one is a bit on the patient population. If these are late-line patients, you assuming these are gonna be the refractory standard of care, or you think you can still use your induction therapy with standard of care and then come in with your Mm-hmm. Perfect. Thank you for asking. Why don't we start with Blake for the first question, then, Francesco can address the second part of your question. Blake? Yeah, you know, I was trying to catch that question on the cell-free DNA, but do you mind repeating the context for me? Like, have you tested out in lupus nephritis mouse model? Ah, okay ... if there is a reduction in the cell levels or... Yeah. Yeah, no, thanks, thanks so much. You know, as Chen mentioned, and as we reported today, we cleared the IND, and of course, the non-clinical component of that included evaluation, not in mouse models. You know, mouse models, as far as predicting and testing for a human-based gamma delta T cell, like ours, you know, there's some compatibility issues you have to consider there. Are you really testing your clinical drug or a mouse surrogate? So what we actually did is, we actually looked directly at primary B cells from patients with lupus nephritis. And we obviously reported as part of that IND, significant impact on the B-cell compartment derived directly from those primary patient samples. So I think that's the best clarity that we can provide at this time, as far as the preclinical evidence for the activity of ADI-001 on the B-cell compartment in patients. Yeah. I think the best evidence, you can see it in our clinical studies to date, you can see the depletion of the B cells. So you know that at least in patients, we deplete the B cells, which is what you care about. And then the second part of the- Yeah, and- One of your questions, which would you do? Would you remind us? Yeah, it was about the. Yeah, the- ... the eligibility of the patients, correct? Yeah, trying to understand, like, how refractory these patients are. Would you be able to... If you see efficacy but not heavy efficacy, would you be able to combine it with standard of care induction therapy, or whether there is a steroid tapering in the protocol, or would you have an enrollment criteria based on the eGFR status or urinary protein level? So how are you thinking? What kind of patients would you be enrolling? Sure. Sure, that's a, that's a good question- Francesco ... as you- Yeah. Yeah, it's a great question. You know, I wouldn't give specific numbers, yeah. Go ahead. No, no, well, I will not provide specifics- Yeah ... but the general logic, it's a very important question. As you can imagine, we have discussed in detail with the FDA. We have agreed exactly on the plan in a variety of ways. So first of all, we have agreed on the definition of refractory. As you know, in autoimmune in general and lupus in particular, refractory is not always as clear-cut as in oncology, where you have, you know, therapies that come and go, responses that come and go, progression, et cetera. The management of these patients is far more complex in many ways. So we have a set of agreed criteria that define what prior therapies and what type of response to those prior therapies the patients have to have experienced in order to be eligible for our study. Also, we have agreed on a rather- ...thorough, I must say, set of criteria regarding what type of therapies have to be stopped when, and can be resumed when. The study is still a study that is not in combination between ADI-001 and any other anti-lupus agent. But of course, for the purpose of a healthy study conduct, you need to have provisions that govern what type of additional therapy, if necessary, can be given, with what timing, what dose, et cetera, et cetera. And all of that is, you know, carefully detailed in the protocol and agreed upon by the FDA. I'm not sure we wanna provide too many specifics right now, but we are essentially ready to go. Yeah. But I want, I wanna add that, you know, with- Yeah ... the type of B-cell depletion that we see and what you see from a check out in a couple of autoimmune diseases, you would expect essentially that following treatment, you could potentially see treatment-free patients that do not need any additional treatments. Understandable. One last question, a bit broader question on the focus of the company itself in 2024. How should we think it? Is it gonna be MCL will continue to... will be the lead story for 2024 as Lupus Nephritis program develops, and lupus would be a key story in 2025, or how should we think of it? Yeah. It's a function of the pace of enrollment. You know, pending how enrollment goes, we may have additional data in autoimmune indications in the second half of the year. So the focus from an operational perspective is MCL for the NHL study, autoimmune diseases, and for the additional indication for ADI-001, filing the IND for ADI-270, and then starting the clinical study in RCC, declaring it potentially a clinical candidate for our prostate cancer program that, you know, also has significant differentiation. We'll expand on this in the future. So that is the focus from an operational perspective. When you think about it and you step back, it's focusing where we see differentiation and potential significant benefits for patients, and so far, we expect it in MCL, autoimmune, Renal Cell Carcinoma, and maybe in this, in another CD70-expressing tumors, and potentially in the future, will progress to prostate cancer, to prostate cancer as well. Mm-hmm. Thank you. Thank you again for taking all the questions, and congratulations on the progress. Absolutely. Thank you. That completes our call for today. Thank you for joining.