Good afternoon. It's my pleasure to welcome you guys to the second day of the Citizens JMP Life Sciences Conference call. Another pleasure to welcome Adicet Bio to present. Presenting for the company is Chen Schor, President and CEO. Welcome, Chen. Thank you, Reni. Always a pleasure to be here and talk with you. Great. So, you know, I never know exactly who's in the audience. I don't know who's listening to the webcast, whether they know the Adicet story. So I always like to start these Q&As off with maybe a 2-5-minute overview of Adicet Bio as a whole before we jump into the pipeline. Absolutely. So Adicet Bio is considered to be the leader in the field of CAR-Gamma Delta 1 T cells. We're the only company with a program in the clinic for with this technology, and we have another program going into the clinic, shortly. Gamma Delta 1 T cells have a couple of unique advantages compared to other cell therapy approaches like Alpha Beta T cells or NK cells. Number one, we can dose them completely off-the-shelf. Gamma Delta 1 T cells do not require any gene editing, and we can dose them to patients in an off-the-shelf basis. That's advantage number one. Advantage number two, Gamma Delta 1 T cells are not eliminated by the NK cells once the immune system recovers for patients. And what that lends itself to a significant advantage when you look at the PK of our allogeneic approach compared to any other allogeneic approach that's in the clinic. If you look at the PK of our first program, if you look at the Cmax, it's pretty consistent with Yescarta. If you look at the day 28 concentration, it's still actually even a little higher than Yescarta. So a significant advantage in terms of showing decent exposure in the blood of patients. That is the second advantage. The third advantage is also very important. Gamma Delta 1 T cells have tissue tropism. So unlike Alpha Beta T cells or NK cells, our Gamma Delta 1 T cells are primarily in our tissues. They're in our kidney, they're in our lungs, they're in our skin, and other tissues. That is a very important advantage, and it's expected to serve us in two therapeutic areas that I'm happy to expand on. One is in autoimmune diseases, and the second one is in solid tumors. And specifically in solid tumors, there is another significant advantage for Gamma Delta 1 T cells, and it is that Gamma Delta T cells bring innate antitumor activity and can help address some of the tumor heterogeneity that we know exists in solid tissues. I'm happy to expand on these. I know these are a lot of words, but for every single item here, we have data either from clinical studies or from preclinical studies or publications by third parties. Yeah, no, that provides, like, a really nice kind of framework, and we can kind of build underneath each of those. Let's jump right into the pipeline, right? The flagship molecule at Adicet is ADI-001, a gamma delta, you know, CAR-T as you mentioned, targeting CD20. It was originally developed for NHL. You have, of course, a study going on in MZL, if I remember correctly. We've seen some amazing efficacy seen and published in the New England Journal of Medicine showing that, you know, these CAR-Ts that are targeting B cells have a profound impact on autoimmune diseases. And so I'd, I'd love to kind of talk through that strategy. Tell us a little bit about the potential advantages that 001 may have in autoimmune disease. Absolutely. So let's just start by briefly summarizing what we've seen in data from the New England Journal of Medicine and a few other sources. What we learn is that in autoimmune diseases, essentially, one of the key problems is that B cells secrete autoantibodies that lead to the progression of the autoimmune diseases, which eventually can result in kidney failure and other associated issues. What we have seen is that autologous approaches that essentially deplete B cells in the blood, that, what was reported, can essentially reset the immune system because if you can kill all the B cells that secrete these autoantibodies, essentially reset the immune system, and we can see quite profound responses in autoimmune diseases. So we indeed moved to autoimmune diseases, and we were very careful in our move into autoimmune diseases. I'll delineate what was really important for us in this move. So the first thing that is important if you move from autologous to allogeneic, is, are we seeing the same type of PK exposure? Because you want to make sure that there is enough in the drug in the system at the right time frame. It is. Actually, ADI-001, in terms of allogeneic approaches, it's actually the only drug that shows exposure in the blood that's consistent with the data reported by Schett. So we can see the same type of a Cmax, the same type of a day 28 persistence, and within three months, it's eventually eliminated by the host immune system. So same exposure in the blood as Schett. That was important to us. It just reduces the risk of not showing the right activity. That's number one. 2, we actually target CD20, but we measure in the blood historically, we've always measured CD19 positive B cells. The reason I'm saying this is because the autologous approaches use CD19 as their targeting moiety. And when we look at CD19 positive B cells in the blood, we so far have 24 patients that, you know, the data are in the public domain. 23 out of the 24 patients, the B cells, the CD19 positive B cells goes to zero. So exactly the same immune reset as we've seen in terms of B cell depletion, from Schett. So that's another big advantage. So same drug, same exposure, the same reset of the immune system. The next thing, we have advantages in terms that Gamma Delta 1 T cells do have tissue residence in key organs. Like kidney, that's probably going to be helpful in lupus nephritis, like lung or skin. Maybe that might be relevant for systemic sclerosis and other indications alike. So this tissue tropism, we believe, eventually will translate to an advantage. The fourth one is the fact that, these are, allogeneic, cells. So that's important in two ways. Now, number one, we do not expect to see this CAR-T cell malignancy risk, which in oncology, as reported by the FDA, it's about 0.1% of the cases reported to the FDA as CAR-T malignancy risk. Indeed, it's probably higher, the risk. We don't know what it is. We just know what percent was reported. But with allogeneic approaches, you're less likely to see this CAR-T malignancy risk because they will be eliminated by the host. So that's one advantage. The second one is that this is an off-the-shelf approach, very well tolerated in patients, and we expect eventually to dose this in community setting. That's a big autoimmune space of B cell-mediated autoimmune diseases; it's a very big space, and off-the-shelf approach, if it works, will be very advantageous. So we're excited. These are, you know, same exposure, same B cell depletion with tissue tropism and off-the-shelf; we think should, hopefully will benefit well in patients. So you bring up, you know, a great point with, you know, the fact that this is a huge, unmet need and, and, and market. Why Lupus Nephritis? I imagine it's because it's been done in autologous, but I'd love to kind of pick your brains a little bit more, right? You can sometimes go after established, you know, indications or where you've seen an efficacy in certain indications, or go after different ones, right? And so maybe you can talk to us, you know, about that. And what are the primary and secondary endpoints that ultimately you and investors should be focusing on? Yeah, absolutely. So why lupus nephritis? A couple of key reasons. One, actually, if you look at the data, most of the patients that have been dosed with SLE actually had lupus nephritis. So for example, the Schett patients, we say SLE, but if you look at the data, they all had lupus nephritis. And that's not inconsistent because overall, this SLE eventually progresses and there is damage to the kidney. So that's reason number one. There is proof of concept in lupus nephritis. The second reason, and that's going to your endpoint regarding lupus nephritis, the endpoints for complete response in lupus nephritis are quite clear and easy to measure. It's proteinuria, essentially protein in your urine, and eGFR, which is a marker for kidney function. So we can see a response, and the response that has been observed so far with allogeneic approaches happens within three months. So these are two key reasons why we selected lupus nephritis. The other important reason is that we know that Gamma Delta 1 T cells have tissue tropism to the kidney tissue. So if there is a B cell islet in the kidneys, Gamma Delta 1 T cells are more likely to deplete this B cell islet in the kidneys. So these are the key reasons, and that's why we started with lupus nephritis. Excellent. So you can start with lupus nephritis, but clearly there's a lot of different, you know, B cell-mediated autoimmune diseases. So maybe you can just talk to us a little bit about, you know, how you're thinking big picture about additional indications that you might explore and when you might be clearing, you know, the INDs for those. Yeah, absolutely. Great question. So we committed to update the street about additional indications in the second or third quarter of this year. We're executing right per plan. So we absolutely are expanding this program to other indications, and that's underway. You know, we haven't shared the specific indications. We're thinking about indications where there are advantages to Gamma Delta 1 T cell approaches. We're thinking about tissue tropism. We're thinking about the execution of the study. What are the sites that we're going to cover and what indications we're going to be able to study in each site? So we're actually progressing very, very well, and we share that we expect overall to expand to one or two additional indications, and that is absolutely happening. On track. Okay. Everyone that we've been talking to, right? I mean, not just investors, but a lot of our cell therapy companies, are, of course, following the data, right? We want to follow the science and see where, you know, our programs might be able to fit. It seems like there's a gold rush, you know, that's occurring, like a California gold rush that's happening within the autoimmune space. I'm kind of curious as to how you're thinking about competition for sites and, you know, potential patients. Yes. How many sites in general do you think you might, you know, really need, you know, to get at least your proof of concept studies kind of underway? Yeah, absolutely. So I'll address the competition, and then I'll address the sites. So first of all, you're right. This is a competitive field. We're actually doing very well with sites. The reasons that I think sites are interested in our program are very consistent with the reasons I mentioned earlier. For some investigators, the issue of CAR-T cell malignancy is really a big risk for them. And they're, you know, when you look at the lupus patients that Schett dosed, these were eight women in their late 20s. You know, they don't want to take that risk. So, for some KOLs or some sites, this, the fact that this is an off-the-shelf approach is really, really appealing. Other sites do believe that this needs to be off-the-shelf, and the fact that we have PK consistent with Schett is really, really important and B cell depletion consistent with Schett. So this is why we're actually doing great with sites. And we will update at some point in the near future, we'll update on the number of sites, but I think we will surprise people in terms of how this is progressing. Regarding competition, indeed, this is a competitive field. And I think what we see from even the investigators themselves, they need to understand, okay, what are the players, and they're essentially putting them in a few buckets. One, autologous. Autologous is more complicated studies for the investigators to run because they compete on beds for leukapheresis, and essentially you need to kick out a patient that might need leukapheresis for multiple myeloma in order to bring them in for a study in autoimmune. So that's autologous. They know, hey guys, if you think about patients with autoimmune diseases, the numbers are at least 30-fold higher than the number of patients with NHL. Like, this is a different, you know, beast. So they understand that off-the-shelf will be important. So that's autologous. And then there's Gamma Delta 1 T cells, NK cells, and allogeneic Alpha Beta T cells, and there's advantages and disadvantages to some of these approaches. So bottom line, we're progressing well. We expect to have sites in the U.S. and outside the U.S. and with multiple indications enrolling this year. So if we think about, you know, enrollment this year, I think it's supposed to start in the second quarter. Is that correct? Yeah, we expect to announce starting the study next quarter, yeah. Okay. And, you know, do you believe you'll be on track just based on physicians that you've talked to? You talked about obviously sites, you know, being excited, so I assume there's a decent amount of enthusiasm from the docs. Do you believe you'll be on track to provide some preliminary data. Yeah. Maybe by the end of this year, or is it something that, you know, likely is going to get pushed out in the. Yeah. You know, under promise and over deliver, I do believe in this. We guided that we expect to have data in Q4 or Q1 next year. And I think we're absolutely on track for this guidance. We might surprise positively even before, but, you know, let's see how enrollment goes. But so far, things are progressing per plan. So, with the same asset, 001, you know, we should remind investors that there's an ongoing study in MCL. Absolutely. This is a pivotal study. Yeah. You know, can you talk to us a little bit about how that study is going and kind of your latest? Not yet a pivotal study. We continue to enroll patients at DL4, which is the maximum administered dose in this study. Okay. We continue to collect patients, and pending data, we'll meet the FDA and align on the pivotal design. We expect this to be essentially a single-arm study in MCL patients. This enrollment is ongoing, and we currently expect to have more data in the second half of this year. Okay. Great. You had an amazing data update just last week. For those investors who don't know, there's a webcast that was done, I think, on Friday, for some data that was presented at ASGCT. And this was for your new asset, ADI-270. Would love to kind of get, you know, your thoughts, just help us understand a little bit about, you know, what is ADI-270 and maybe the highlights from the presentation. Yeah, absolutely. So, just one minor correction. It wasn't a webcast. It was a call with our covering analysts, including yourself and some of your team members. So if people have more questions about this program, please approach us or our IR or you, and you know, we can get more answers regarding this program. So this is our next program going into solid tumors, and I think the data that we have shown are really exciting, and it's worthwhile to review the data and fully absorb slide by slide what we're showing. Because when you think about cell therapy in solid tumors, so far it hasn't shown a lot of promise, a lot of promise, but that's with alpha beta, allogeneic Alpha Beta T Cells that do not have a lot of the advantages that Gamma Delta 1 T cells. So let's go kind of item by item what's different. So to define this program, this is ADI-270. It targets CD70-positive tumors. It targets CD70 using CD27, which is the natural ligand for CD70, and hence it's a third-generation CAR. It has three costimulatory domains as well as another bolt-on technology, which is TGF beta dominant negative receptor. Except for the name of the program that we're targeting CD70, everything about this program is different than all other CD70 approaches that has been tested to date. And let's go one by one. The first one, do we get enough exposure of the drug? You need exposure of the drug in order to show an effect. We expect to see very nice exposure of ADI-270 in the blood and in the relevant tissue. And let me explain why. Because we know that Gamma Delta 1 T cells are not rejected by NK cells. By adding CD70 targeting moiety, we can actually delay the rejection by the Alpha Beta T cells or by the T cells generally. And that should translate to better Cmax and better exposure in patients. So we expect building on the exposure that we've seen with 001 in the clinic, we expect to see higher exposure in the blood. Number one. Number two, we know that we have tissue tropism to the kidney, so there's going to be potentially even higher concentration in the kidney. So to begin with, we deliver the right type of exposure. Advantage one. Advantage two. When you look at the previous approaches with Alpha Beta T cells targeting CD70, they used a single-chain Fv targeting the CD70. We looked into 300 different single-chain Fvs, and we compared them to the natural ligand for CD70, which is CD27, and we see that with CD27, which is what we're using, we're able to engage tumors at significantly lower CD70 density. The reason this is important is because if you look at the alpha beta approaches targeting CD70, where they have shown responses, it was in patients with a very high CD70 expression. We can show responses, or we can show activity in much lower CD70 expression, and we actually compared head-to-head, same donor, alpha beta targeting CD70 versus our Gamma Delta 1. So, we show very robust activity in lower CD70-expressing environment. That's the second advantage. And the third advantage, we know that in solid tumors, there's going to be some cells that do not express CD70. The question is, can you kill those cells? To remind you, Gamma Delta 1 T cells have a very active innate antitumor activity. So we actually show that if you take, essentially a tumor that includes CD70-positive tumor cells and CD70-negative tumor cells, we can kill them all. And the way we kill the CD70-negative is due to the innate antitumor activity. So that should help us address the tumor heterogeneity that we see in the, in the tumor. So that's another key advantage. Another advantage, we added, TGF beta dominant negative receptor. We know that TGF beta is one of the, suppressing, immune-suppressing, key agents that, we see in solid tumors, and being able to be immune to TGF beta, is supposed is expected to be a significant advantage. And we do show it both, in vitro and in vivo. We've tested this program extensively, compared it to previous alpha beta approaches, and we see very significant differentiation. We're on track to file the IND this quarter. We had a pre-IND meeting with the FDA. It was very, very successful, and we expect to start the study this year. And so can you just, you know, once you've started the study, you know, I assume a typical phase 1 or, you know, are there learnings from 001 that you can, you know, translate to this new study? And when do you think we might see some data? Yeah. So, you know, we guided for data in the first half of next year. It's a little premature for me to discuss the specifics of the study because we just want to clear the IND with the FDA, make sure we're aligned on the key components of the study. I don't expect any issues given our pre-IND meeting with the FDA, but you just want to make sure that the IND was cleared with the protocol that you wanted, and then we'll update investors about the design. I want to say one of the learnings from ADI-001, just if you have the CD27, you're going to see even a better exposure because you're not going to have rejection by NK cells and reduced rejection by T cells. In terms of the exposure of the cell type in the blood, one would expect to see better exposure. Gotcha. And thank you for correcting me on the, on the webcast. I was remembering it was an oral presentation. Sure. You know, that was that which on, you know, by itself actually is a pretty big deal. Yes. to be selected for an oral presentation versus a poster. Congratulations on that. Sort of in the last, you know, minute or two that we have left, you know, I know that throughout our discussion we kind of sprinkled, you know, when we'd have data and things like that, but to bring it home for the investors in the audience and those on the webcast, kind of what are the key drivers, you know, and inflection points that you believe investors should keep in mind over the next kind of 6-12 months? And maybe just start off with, you know, what's the current cash position that's fueling, you know, this, this pipeline development? Absolutely. So we're extremely well-funded. We're funded until mid-2026. So first of all, and backed by, you know, investors that are very well-known to the street, and some of them are investors in other allogeneic approaches, in autoimmune autologous approaches, so very well-known investors, so well-funded. Some of the key data that we expect to have, 1, activity in autoimmune diseases, multiple autoimmune diseases, Number one. Number two, activity in MCL. Number three, activity in renal cell carcinoma and expanding into other tumors that express CD70. So essentially we have at least 3 shots on goals, with 2 of the shots having a very significant commercial potential. If you think about it, if we show benefits of our off-the-shelf approach in autoimmune diseases, you can imagine what's the potential. If we see benefit in, with our program in renal cell carcinoma, you can imagine the benefit for solid tumor patients in this program and in future programs to follow. I've never been more excited for the field and, you know, expect that this will be quite the ride. Chen, thank you very much for the update. Thank you. We appreciate it. Thank you.