Okay, good afternoon, everyone. Welcome back. Welcome to our Healthcare Innovation Conference. This is our inaugural conference. My name is Yatin Suneja, one of the biotech analysts here at Guggenheim. It is my pleasure to welcome our next presenting company, Adicet. From the company, we have President and CEO Chen Schor. Chen, why don't you sort of give an overview of the company, tell us some of the key milestones that are coming up, and then we'll go into sort of Q&A. Absolutely. So first of all, Yatin, thank you for inviting us. We're very happy to be in the conference, and you always have great questions. So looking forward to a great fireside chat. Adicet, as a company, we're considered to be the leaders in the field of CAR gamma delta one T cells. We have shown very nice proof of concept so far in oncology, specifically in NHL, where we show our better very potent activity, very nice CR rate, very nice durability, specifically in MCL. That's the dose level that we expanded, and very nice safety profile. Gamma delta one T cells, as a cell type, have a couple of key advantages. They home to tissues, they don't cause any graft versus host disease. They present very potent cytotoxic activity. And essentially, we have two key branches for the company. One focuses on autoimmune, where we believe we have some significant advantages, and the other is focused on solid tumors. Both programs are now entering the clinic, and we expect to have clinical data in the first half of next year for the autoimmune program and for the solid tumor program, as well as some more updates in the second half of next year. Got it. Got it. So I think you sort of talked about the gamma delta V1 T cells, right? How they are differentiated. But, you know, the one challenge that's there is that they are, that subtype is low in number. So how do you overcome that? Just talk about a little bit on the manufacturing side, the expansion, and also I don't think you touched on the off-the-shelf potential that you have off the shelf, right? It's allo approach. Yes, absolutely, so Adicet was founded by the founding CEO of Kite. And initially, the goal was to focus on solid tumors, and when you look at the type of cells that have best penetration to tissues, gamma delta ones present as the best cell type that is associated with overall survival in patients with solid tumors. Indeed, it's challenging to expand gamma delta one T cells, and the company was started in 2015, so nine years since the company got started, but so far, we have advanced a very significant portfolio of IP and know-how how to expand the cells we can manufacture in a consistent way in-house at Adicet, and so far with two different CDMOs, and we feel we're now in a very good position. The process takes approximately 14 days. Then essentially, we release the product, and there's certain release criteria that need to be met, and then we can ship it to patients off the shelf. Got it. So the majority of the validation for gamma delta T cell come from the oncology, especially, you know, some of the experiments that you have done or the data that you have generated. So could you maybe put in perspective of what you have seen, from in the clinic, inpatient, and how does that compare to other CAR T cell approaches? Perfect. In the oncology field or? Just in the oncology and then we go back. In oncology, we started the study in NHL, and then over time, we focused on MCL patients. Let me go through the different conclusions. First, PK. So what we've learned is that the PK of ADI-001, that's a program that started in oncology, is overall pretty consistent with autologous cell therapies. So when we look at the Cmax of our cells, at the higher dose levels, it actually exceeds the Cmax of Yescarta in patients that respond to Yescarta. So responders to Yescarta have high Cmax. In our case, in all patients, when you look at the higher dose levels, the Cmax is higher than Yescarta. If you look at day 28, our day 28 at the highest dose is consistent with the Cmax of Yescarta. By three months, we see that the cells are eventually rejected by the patient. So PK in the blood, very consistent with autologous. Mm-hmm. Number one, that's important. The second one, I mentioned earlier that gamma delta one T cells have tissue tropism. We actually conducted biopsies from patients, and when you look at the concentration of our gamma delta CAR Ts, and you compare them to Yescarta, it's about seven-fold higher compared to Yescarta. And when we look at these biopsies or in the blood, and we look for CD19, you know, although we're targeting CD20, we're actually looking for CD19 in the blood. That's the assay we have. We see that we completely deplete CD19 B cells both in the blood and in lymph nodes. In terms of CR, I'll focus on MCL. That's a data set that we announced less than two months ago. The CR rate was 60%, and if you look at the median durability of complete response, it was 17 and a half months. So, CR rate and durability was consistent with autologous programs in MCL. Safety-wise, we do have an advantage because, as you probably know, alpha beta T cells, upon their activation, secrete IL-6 and are associated with high-grade CRS and ICANS. Gamma delta T cells, upon activation, secrete significantly less IL-6 and are associated with less CRS and ICANS. We actually had patients that, after dosing, asked if they got placebo. Mm-hmm. Remained cancer-free for a while. Bottom line, consistent PK, complete B cell depletion, consistent CR rate, and consistent durability in the field of MCL. Got it. So now I think it's a good segue into discussing, you know, the antigen, right? CD20, CD19, right? You pick CD20, and I think you are pretty, vocal about saying that CD20 drives similar level of, I think B cell depletion. Yes. So, put the data that you have generated. I think it's the lymph node biopsy that you did. Just like, talk about that. Why do you believe that CD20 that you have chosen is an optimal one? Yes. So, you know, I'm not religious, so it's not about belief. It's about data. So, you know, we just look at the biopsies, and I'll provide why we believe this is the case. So factually, we have, I think the data set that we released in NHL was from 24 patients. Yeah. 23 out of the 24. We dosed them with ADI-001, which is a gamma delta one targeting CD20. We always actually happen to measure CD19 B cells in the blood. We never measured the CD20. So when you look at the blood, 23 out of the 24 patients, their CD19 B cells go to absolutely zero. And when we look at the lymph nodes at day 10, and we looked at, you know, multiple lymph node biopsies, we have never seen at day 10 a single CD19 B cell, not a single one. Mm-hmm. First of all, it's absolutely a fact. Mm-hmm. Why do I believe this is the case? Most of the B cells express CD19 or CD20. Some of the plasmablasts or short-lived plasma cells express maybe a little more CD19 versus CD20, but these cells have a lifetime of five days. So if you deplete everything before and you just wait five days, they're gone. They're gone. So it's a fact. You know, at day 10, we cannot find CD19 positive B cells. Got it. So the other feature that you mentioned is this tissue tropism, right? What is the relevance of that, especially in autoimmune indication and especially the indication that you have chosen, which I don't think other CAR T therapies have? Yes. It's extremely important. So it was presented at EULAR, at last EULAR, we compared, or not we, actually, Dr. Schett compared cell therapies versus antibodies that deplete B cells. And he showed that in the blood, both cell therapies and antibodies would deplete B cells. But if you look at the lymph nodes, the cell therapies depleted the B cells, but not the antibodies. And indeed, the antibodies were not associated with durable CRs, and the cell therapies are. So it's very important for durable remissions in autoimmune to deplete the B cells in the lymph nodes. The other key aspect of gamma delta T cells is that they also have tissue tropism to other tissues, for example, kidney. Mm-hmm. As you know, in lupus nephritis, there's gonna be some B cell islets in the kidneys, and gamma delta one T cells are more likely to deplete those B cells. Or in systemic sclerosis, there's gonna be some B cell islets. It has been documented that there are B cell islets in the lungs, and gamma delta one T cells, because of their tissue tropism to lungs, are more likely to deplete those B cells. So we believe this is a key advantage together with the off-the-shelf availability and the tolerability. Okay. So now just talk about where you are in terms of clinical development for ADI-001, right? I know the studies are open, but where exactly you are. Some of the other companies have taken close to nine months or maybe 12 months to enroll the first patient. Mm-hmm. Where exactly you are? Yeah, so we have so far cleared six indications with FDA. We started with lupus nephritis, then we expanded to SLE, systemic sclerosis and myositis, and we also added the ANCA-associated vasculitis. We're now open for enrollment in lupus nephritis. Obviously, these patients have also lupus in Q1. We expect to start enrolling for SLE without LN. We expect to start enrolling myositis as well as systemic sclerosis. In the second half of next year, we expect to start enrolling to ANCA-associated vasculitis. We expect to share data specifically in autoimmune with investors in the first half of next year. Mm-hmm. It's probably gonna be primarily lupus nephritis because now we're starting to enroll lupus nephritis, while the other indications primarily we'll start enrolling them in the first quarter, so we're not sure how many patients we'll have from the other indications. Got it. So have you treated the LN patient yet? We haven't announced yet that we've treated the first patient, but we have announced that we open enrollment, and I'm very optimistic that treatment of patients is, you know, imminent. a minute. So first off, how much or how many patients worth of data, and is there a particular follow-up that you are thinking of presenting? Mm-hmm. When you present these first set of data from? Yes. Absolutely. Great question. So we haven't finalized the how we're gonna disclose, whether we'll announce like a case study or we'll announce all the data together. The longer we wait in the first half of next year, the more data that we'll have. What we've heard from investors is generally they're interested in three months follow-up. Mm-hmm. And if we have a couple of patients with three months follow-up, that would be very educating. So hopefully we'll have a couple of those as well. Okay. With regard to the, it's more on the competition side, right? I think, how do you view these T cell engagers fitting in? Because I think there is a lot of focus, we are hearing on T cell engagers now. Do they compete with you? Like, where in the patient spectrum of patient journey would they fit in? Yeah. Absolutely. Great question. So first of all, I think there's room for everybody. Yeah. Let's think, and different patients might have different preferences. We haven't seen so far that T cell engagers is a one-time immune reset. It's not. It's most likely gonna require some semi-chronic dosing where we deplete essentially the B cells on a chronic basis. So essentially to call it in a different way, it's a new class of immunosuppressants. Yeah. Which is a very viable class of therapy, is a new class of immunosuppressants, but we continue to immunosuppress the patient for years. The advantages of cell therapy is you give the drug once, and the patients are more likely to have very durable complete responses, so I do think there's room for everybody. I do think that in the long term, especially, you know, younger patients, we kind of need our B cells. If you look at the history of COVID-19 in patients that took rituximab, there was a very high mortality rate. Mm-hmm. In those patients, so I do think there's gonna be room for both classes, but I'm optimistic that one-time cell therapy might be a way to go for many patients. It's not very different than what we see in oncology. Yeah. Generally, when we compare efficacy of cell therapies versus bispecifics, cell therapies are considered to have better efficacy and durability. Yeah. One, maybe just on your product or this off-the-shelf approach, can you talk about the safety? I think you mentioned briefly that it's differentiated, but. Yes. You know, you have no ICANS, right? Almost no CRS. Correct. What is the relevance of that? How does that help, because this community or these autoimmune community generally is a little bit more safety. Yes. You know, risk averse. So just talk about the significance of that. Yes. Absolutely. So first of all, it's very significant for adoption in the market, because these therapies eventually will be provided in the community settings. In the community settings, there is less likely to know how to deal with grade four ICANS or CRS. That's, that's probably gonna be first time if it's done in community setting. So is it important? Very important. By definition, alpha beta T cells upon their activation secrete IL-6. IL-6 is associated with CRS and ICANS, and we treat it by providing these patients with Toci, which is anti-IL-6. So that's what we see with alpha beta now. Especially in autologous cell therapies, you might take one patient, and they might have great fitness into their cells. They'll proliferate great, and guess what? They'll secrete a lot of IL-6 and will cause CRS and ICANS, and a different patient might not because the cells barely proliferate. In our case, it's consistent. You know, it's the same release criteria. It's off the shelf that our cells do not secrete any significant IL-6 and are associated with less lower rate of CRS and ICANS and less severe CRS and ICANS. Got it. How is your protocol defined? Are there different requirements that you have in the protocol versus some of the other CAR T cell players where they need to be hospitalized for a certain amount of time? Sure. Absolutely, so it depends on the country. Mm-hmm. It depends on the institution. In cohort right now, our patients will be hospitalized for the first seven days. Yeah. Following ADI-001 dosing, in some countries, it's not necessary to hospitalize them, and over time, I would expect that we'll relax these criteria. Okay. But it's certainly not because we're very concerned about safety. It's required by some regulatory authorities. Could you talk about the cost here? Because I think the cost is very high for autologous. Obviously, your approach is different here. Yes. Absolutely. So we've been at it for a long time. We understand how to manufacture gamma delta one CAR Ts. Our guidance has been that we expect our COGS to be significantly lower than 20%. So it checks the box for commercial viability, you know, for all players. Okay. All right. So I think I wanna move to the cancer program, right? The oncology program that you have, ADI-270. Could you tell us what that program is, what is the excitement around it, and what are the next readout? I think in the first half, you're gonna have a readout there. Yes. Absolutely. So we are equally excited about our first solid tumor program. So, again, these are gamma delta one T cells, the target CD70 with a couple of bolt-on technologies. So there's, first of all, CD70 as a target for cell therapy. There is certainly clinical proof of concept that this is a very viable target, specifically in clear cell RCC. Mm-hmm. If you look at data by alpha beta T cell companies, they've shown overall response rate in the range of 25%-38%, so it's almost double the alternative for these patients, after two lines of therapies, and we believe that we are significantly differentiated than compared to those alpha beta approaches, and we're differentiated in multiple ways. Number one, part of the trick in solid tumors is get your cells there. Gamma delta one T cells will go to the tumor. Number two, the way we engage CD70, we're using CD27, and CD27 is much more sensitive to CD70, so it requires significantly lower CD70 density to show efficacy. CD27 is also another costimulatory domain, so the cells have more potent killing. The next differentiation, gamma delta one T cells have very potent innate anti-tumor killing. Do we expect to see some heterogeneity in RCC? Probably yes. Not all cells will express CD70. We expect to kill some of those cells that have tumor heterogeneity, and the last but not least, we introduced into this product dominant negative TGF-beta receptor. We do expect in the tumor microenvironment to see some TGF-beta, and our cells are essentially immune to the effect of TGF-beta, so all these factors differentiate us from some of the alpha beta T cells, and every single statement that I made is backed by data, so we actually compared it and showed it in preclinical models. So what type of patient you are enrolling? Like, what line? These are clear cell RCC patients. Yeah. They need to protect to progress on a checkpoint inhibitor. Okay. A VEGF inhibitor. Okay, so it's basically first line. Essentially, it's actually many of the first-line patients get both. Get both. So in some. Second. You might get it's second to third line. So in this patient population, you're saying 25-38 is what we get with alpha beta. That's the exact patient population or similar patient population. Correct. The goal is to get to replicate this or sort of push the bar given all these high. The current alternatives the patients have is about 5%-20% overall response rate. Mm-hmm. A PFS of 5.6 months. Okay. That's what you need to beat, and then you can look at the competitive landscape from alpha beta or gamma delta. Are we gonna beat that, that threshold? I mean, data will tell, but I'm pretty optimistic. What about the PFS or the DOR for alpha beta? Too preliminary to say. Too. Too short of a follow-up. Too short of a follow-up. We don't know. In the first half of next year is when we're gonna get data? Yes. How many patients worth of it? Haven't guided, but I expect this will give us a good sense for preliminary efficacy. I mean, how much do you need? Like, if the response rate is only 20%, you probably need, I don't know, 10 patients. Yeah. That's too much? Yeah. It depends on the quality of the data as well. Yeah. Okay. Very good. Then final question is on the, actually not two questions. Who is doing the manufacturing for you? We have our own manufacturing, and that some of the products, we manufacture our own. And some products, we have two CDMOs that we worked with. Right now, we're focused on one specific CDMO. So ADI-001, we can manufacture in-house and a CDMO that we haven't named, but it's a very well-known CDMO. And ADI-270, right now, we continue to manufacture in-house. Very good. How is the financial health of the company? So we're in a great position. We raised money earlier this year in January. So we'll fund it into the second half of 2026. And by then, we expect to have multiple readouts, both in autoimmune and oncology. So we feel good about that. Exciting 2025 for you. Yeah. You know, two key readouts or two programs, I would say, both in oncology and the autoimmune. But very good, Ken. That's all I had for you. Awesome. Thank you. Good, good to meet you. Great discussion. Thanks, everybody. Thank you.