Hello, everyone, and thank you for joining the H.C. Wainwright second annual Cell Therapy Virtual Conference. My name is Ed White, and I'm senior analyst here at H.C. Wainwright. We hope you have a productive and enjoyable day. I'd like to welcome Chen Schor, CEO of Adicet Bio. Adicet is a clinical stage biotechnology company, discovering and developing allogeneic gamma delta T cell therapies for oncology and autoimmune disease indications. Thanks for taking part in the conference, Chen. Absolutely. Hey, thank you for inviting me, and look forward to a great research chat. I do, too. All right, so for investors who aren't familiar with your gamma delta T cell program, could you please describe your ADI-001 product and discuss the differences and potential advantages over CAR T cell programs? And perhaps you could also discuss the advantages of being off the shelf versus an autologous product. Absolutely. Great question. So, you know, describing a product is always in the context of an indication, so I'll try to do it in the context of our autoimmune program. Happy also to discuss our oncology programs. So when you look at the ADI-001, the first thing that I think is very important is that the exposure with ADI-001 is consistent with the exposure of autologous CAR T. When you look at the Cmax with ADI-001, it's around day 9 or 10. When you look at day 28, persistence of the values, you actually see that the Cmax and day 28 persistence is consistent, if not higher, than autologous CAR Ts. So overall, the exposure of ADI-001 in the blood is consistent with autologous CAR Ts and is consistent with what we've seen from a data set like Schett et al. in autoimmune diseases. So that's the first thing that I think is really important with gamma delta T cells. We actually understand why this may be the case, and we published about this a couple of years ago. We see that the gamma delta T cells are less susceptible to the attack of NK cells on the graft, but the rejection is less so by NK cells, which results in a superior persistence of gamma delta T cell. The second advantage that we see with ADI-001, when we look at our data in oncology, we see that the CD19 B cell depletion, we actually measure CD19 positive B cells in the blood. We see that the CD19 B cell depletion in the blood is consistent with the B cell depletion that was reported by Schett and other data set in the field of autoimmune. So the first two items that I think are important in a product, i.e., exposure, is the same as autologous. B cell cytotoxicity we published is the same as autologous, and B cell depletion in the blood is the same as autologous. So that gives us a very good starting point to move into the autoimmune space. Now, we have advantages that are beyond these. The first one is the trafficking to tissues. In autoimmune diseases, we know that eventually the disease is in the organ, and we know that there are B cells in the organs that play a role in the disease, and gamma delta T cells are tissue-resident cells. Less of them are in the blood, and eventually, more of them traffic to tissues. It's been reported in multiple publications, and we also tested it preclinically. The other advantage, which I think will become more and more important over time, is the risk of T cell malignancies with autologous CAR Ts, and I'm happy to elaborate this later in the chat. But with allogeneic cell therapies like gamma delta T cells, we wouldn't expect the risk of a CAR T, this risk of CAR T cell malignancy, which, you know, is important in autoimmune. These are patients that have a disease, it's not necessarily a terminal disease like in cancer. The last thing you want is take a significant risk of giving them a CAR T-cell malignancy. And last but not least, very important is the off-the-shelf nature of ADI-001, and based on the safety profile that we've seen to date, we certainly see the potential to those in the community settings and expect to enable this in the future. So that was a longer answer, perhaps than expected, but hopefully, it gives you a couple of the key reasons why we see great potential for gamma delta T cells in autoimmune. Thanks, Chen. Yes, and actually, you answered a couple of my questions earlier, so that's great. So maybe now you can just discuss the study in lupus nephritis. It's just getting underway. Can you tell us about the study and your plans and perhaps even expected timelines to data in lupus nephritis? You know, what are the other potential in autoimmune indications that you may pursue? Sure, absolutely. So we're working to open centers as we speak. We expect to start opening centers in the second quarter of this year, and we'll continue to open more and more centers. We're starting with lupus nephritis. Most of the patients that were treated, yeah, that had SLE had also and nephritis component. And the nice thing with lupus nephritis, the endpoints, i.e., kidney function, are simple to measure, and eventually, the path to approval is reasonably clear. We're starting with a dose of 1e8, and we expect to escalate to 3e8, and then 1e9. You know, we see significant interest from different centers. You know, primarily these are centers, that, you know, the treating physicians in, lupus nephritis are rheumatologists and nephrologists. And, you know, for the reasons that I mentioned about the efficacy, i.e., same level of, exposure and same level of B cell depletion, that's very important to them. But, I want to say, these physicians do see this market as, eventually, likely in an off-the-shelf market. It's big patient populations. They don't necessarily want to be, dependent on the oncology and department of the hospital, waiting for a spot for leukapheresis, and then waiting for a spot to, infuse the cells. So they want to control their destiny and have something that's off the shelf available for their patients, and they do care about this CAR T-cell malignancy risk. You know, it's been reported by Peter Marks that the risk is 0.1% in oncology, but that's only the cases reported to the FDA. It's likely that the CAR T-cell malignancy risk is higher, and as, you know, more and more patients are being treated, this may become an issue. So we do see significant interest in our cell type and in our therapy, and we hope to start reporting data either in Q4 this year or into Q1 next year. So that's for lupus nephritis. We do expect to progress with the other indications, at least one, maybe two, this year, other autoimmune indications, and we'll update in due course. But we're certainly focusing on starting additional studies in other indications. We see great potential for this field. Great, and as you mentioned, there are several competing technologies entering the autoimmune disease space, including the CD19 and CD20 CAR T products, CAR NK cells, and bispecifics. You know, with the data you've seen so far in preclinical data as well, you know, do you think there would be a shift in autoimmune disease treatment, and where could ADI-001 fit in this new paradigm? Mm-hmm. Yeah, absolutely. So first of all, based on the data that are published today, it looks like there will be a shift in treating patients with autoimmune diseases, and at some point, they might benefit from a cell therapy that will reset the immune system and, you know, essentially, almost cure those patients from the autoimmune diseases. If you look at the data by Schett, I mean, you've seen follow-up for years and no recurrence, so that's likely coming. Now, indeed, there are different types of therapies, and perhaps we can dissect them by the vehicle that we're trying to treat and the, versus the target. When you look at the vehicle, so starting with the biologics, so indeed, you know, these bispecifics are being tested, and there's other biologics that are being tested. One of the issues with biologics, at least, and we also see it in oncology, they don't have the same tissue tropism as cells that actually can move. So that's, that might be a challenge, and there's no data so far from biologics that show the same type of efficacy that you see with the, with the cell therapy. And then with cell therapies, there's the autologous that I think will continue to play a role. Complicated process to administer. You know, there is the risk of CAR T cell malignancy, but that's certainly, you know, a therapy that works, and I, I would imagine that companies will continue to work with autologous. And when you move to off-the-shelf, there's a, you know, three cell types. There is a alpha beta, allogeneic alpha beta, gamma delta, and NK cells, all going after pretty much the same target. The goal is to deplete the B cells. We have a couple of key advantages. The key advantage that we have is at least we have similar exposure to the autologous alpha beta, which seems to work. We have the same B cell depletion, and we have the tissue tropism to tissues, which, you know, gamma delta ones are known to have this tissue tropism. So that's for cell type. And then let's cut it through targets. When you look at the literature, it seems like depleting the CD19 positive B cells is essentially sufficient to show efficacy in CAR Ts, in autoimmune, and we're actually targeting CD20. But when we look at the CD20 and the CD19, the expression profile is overall similar. When you look at B cells, there's a little difference in the plasmablast and short-lived plasma cells, where CD19 might be a little more prominent, but these are very short-lived plasma cells. The lifetime of a plasmablast or short-lived plasma cell is 3-5 days. So once you eradicate all the CD20 positive B cells, these cells die within 5 days, and indeed, we measure in the blood CD19 positive B cells, and we see them going to absolutely 0, just as in 23 of the 24 patients that we treated with lymphoma. So it seems like whether it's CD19 or CD20, it doesn't matter because eventually, you deplete all the CD19 positive B cells. That's cutting it by cell type and cutting it by target. Thanks, Chen. You know, one of the topics on investors' minds in the cell therapy space, and you mentioned it several times already today, is the risk of T-cell malignancy. So I just wanted to, you know, perhaps get your thoughts, maybe you can elaborate a little bit more on that, and what you're seeing with ADI-001 regarding safety and tolerability. Sure. Absolutely. So first of all, I think it's a very important issue to understand. Because we know, as I mentioned earlier, Peter Marks published in New England Journal of Medicine in January, that the risk is 0.1% approximately, to get essentially autologous CAR T cell malignancy, i.e., it's a tumor that's growing with a CAR that detected in the tumor. So that's a risk. It's probably underreported because not all CAR T cell malignancy will be reported to the FDA. When you look at the patients with autoimmune diseases, let's take a look. Let's think about the SLE. If you look at Schett, he treated, for example, 8 patients, 7, 7 of them were women, and I think the median age was 27. We don't wanna give them cancer. If the risk is, let's say, 0.5% or 1%, you're not gonna see it in a data set of 8 patients. The question is, will we see it in a data set of 100 patients, and then what? So I do think this is the risk that we need to be aware of and watch in the field of autologous CAR T's in diseases like autoimmune. Regarding allogeneic cell therapies, this is a significantly reduced risk if it does exist at all, because these cells will eventually be rejected by the immune system, unlike autologous, which can survive for a long time. So I wouldn't expect that ADI-001 and most other allogeneic cell therapies that are rejected by the immune system to be associated with this risk of CAR T-cell malignancy, or if they are, then definitely to a significantly lower magnitude. So that will probably become important as we move forward in this field. Okay, thanks. You just touched a bit on persistence, and I just wanted to get your thoughts on the persistence of ADI-001. You know, again, why is this so important, not only in autoimmune disease treatment, but also in oncology? Absolutely. So starting with the autoimmune diseases, when we look at the exposure in autoimmune disease, it's actually shorter persistence compared to compared to oncology. If you look at the Cmax, and if you look at the AUC by day 28, we see the same exposure. So if you wanna develop something that's off the shelf with efficacy that's consistent with autologous, first of all, you wanna make sure that the exposure during that window where the cell is active is the same. So we know that our exposure is consistent with the autologous, and based on Cmax and day 28, we can certainly get to the same level of drug exposure as autologous. So in autoimmune, that de-risks our program in a significant way. In oncology, it's probably also advantageous, and we indeed see great exposure that's consistent with autologous. Again, if you measure Cmax and the AUC, you probably just keep the cell enough time to exert its cytotoxicity and potentially eradicate the tumor. So that's an advantage that we have with gamma delta T cells compared to other allogeneic cell therapies, longer persistence and better AUC and Cmax, likely because gamma delta T cells are not eradicated by the NK cells. Okay, thanks. And now let's move on to your studies of ADI-001 and NHL. Focus has shifted to mantle cell lymphoma in the Phase 1 GLEAN study in relapse/refractory NHL. Can you discuss the data you've seen there so far in the study and your thoughts on a potential pivotal program? ... Yeah, absolutely. So we had at some point to prioritize different indications, and that's where we're going with the MCL and a couple of the autoimmune indications. What we saw in the MCL seemed quite promising early, and as of the last data cut, it was 5 patients, but 4 of them had a CR, i.e., 80% CR, and 3 of them, 60%, had a CR well beyond the sixth month. So that's early, but quite promising for MCL, and this is why we're pursuing this patient population, and we continue to enroll to MCL. So we expect this program to have a leg in MCL and have a leg in multiple autoimmune diseases. Okay, and an IND submission is expected for another product, next quarter, ADI-270. What can you tell us about this armored, CD70-targeted allogeneic gamma delta T cell candidate, and what are your development plans there? Absolutely. So CD70 is a recently validated target in oncology, and specifically in renal cell carcinoma. Everything about ADI-270 is different compared to other programs, except that it targets CD70, and I think this is a very positive differentiation that we have, and let me walk you through the differentiation. So the first thing is, how do you engage the CD70 on the tumor? We're actually using CD27 to target CD70. It has shown superiority in multiple publications, and the Allogene also has a program using CD27 to target CD70. The key advantage of using CD27 is that it requires lower antigen density on the tumor. And when you look at the data by other alpha/beta T cell companies, you see that their efficacy is somehow associated with the CD70 antigen density. So first advantage is we require significantly lower antigen density on the tumor. The second advantage is that in solid tumors, we would like to see more tumor heterogeneity. So the fact that gamma delta T cells have innate anti-tumor activity is beneficial to potentially eradicate neighboring cells that may not express CD70. That's the second advantage. The third advantage, as you mentioned, this is an armored program, and we added the TGF-beta dominant negative receptor to address the tumor microenvironment, and indeed, when we tested it pre-clinically, we see advantage with this approach. The fourth advantage is expected better persistence. So CD27 essentially fights back the rejection by the host T cell, activated T cell. So we know that gamma delta T cells are not eradicated by NK cells. Fighting back the host T cell rejection will probably enable better persistence. That's the fourth advantage. The fifth advantage is, you know, for the first time in solid tumors, we're going with gamma delta one T cells, which are tissue- resident, actually home to tumors, and we published this also in pre-clinical models, and there's multiple publications from humans that show that the presence of gamma delta T cells in the tumor is correlated with the overall survival. These are five advantages that you have not seen in other programs targeting CD70, and we really look forward to clearing the IND and moving into clinical studies with this program. Great. Well, I know a lot of investors are looking forward to seeing data in that program as well, so good luck with that. Thank you. We're getting close to the end now. I just wanted to know if you have any closing thoughts, or things that investors should be focused on? You know, to summarize, we are excited about the rest of the year. We're well-capitalized with about $270 million in cash, you know, pro forma as of the end of last year. We expect to move into multiple autoimmune indications. We expect to enroll MCL. We expect to start the clinical studies. With ADI-270, we expect to start reporting data for these programs towards you know, the fourth quarter and then into next year. So there's a lot of milestones to hit, and we're well-capitalized to meet all these milestones. So thank you again for inviting me, and I look forward to some of the one-on-one meetings. You're welcome, Chen. Our time is up now. I just wanna thank everyone for taking part in our virtual conference. We appreciate the time and effort that companies went into preparing their presentations, and we're grateful for your participation in the conference this year. Thanks a lot, Chen.