Thanks for attending Jefferies Healthcare Conference. My name is Kelly Shi, one of the biotech analysts here. In this first set of chat session, we are very pleased to have, Mr. Chen Schor, President and CEO from, Adicet. Welcome. Good afternoon, Kelly. Always happy to be here, and thank you for inviting us. Fantastic. Looking into cell therapy space, what do you think of the gamma delta T cells has advantage over the classic, alpha beta T cell for targeting both, oncology indications and now actually in autoimmune space? Sure, absolutely. So at Adicet, we're the leaders in the field of CAR gamma delta 1 T cells. Gamma delta T cells have a couple of unique features that make them very attractive for autoimmune diseases and for specifically, actually, solid tumors. And here are the key features. Number one, these are cells that we can dose completely off the shelf. They do not cause graft-versus-host disease. There is no need for gene editing in order to be able to dose them off the shelf. That's one key advantage. The second key advantage, and that's actually one of the key reasons why the company was started, is that gamma delta 1 T cells have tissue tropism to tissues. So most of our gamma delta T cells are actually in our organs, like kidney or skin or lungs, and that's a significant advantage in cell therapy because a part of the problem is just making sure the cells go to the right tissue. That's the second advantage. The third advantage is actually PK. So we've learned that once the immune system recovers, two cell types eventually will reject the CAR Ts. It's the NK cells and the alpha beta T cells, or the T cells, once they recover, they reject the cells, the CAR T. Gamma delta T cells are less susceptible to the attack by NK cells. And when you look at our PK, it does present itself. We see PK with a Cmax that's consistent with autologous, with day 28 persistence is considered, that's consistent with the autologous. So this translates to key advantages in autoimmune and in solid tumors. In autoimmune, the key advantages is, same exposure as autologous, tissue tropism that's likely better than autologous, than autologous, and no CAR T cell malignancy, which we have seen as a risk, with autologous CAR Ts. In solid tumors, we see the advantage of, again, PK that's very high for cell therapy, tissue tropism going into the tissues, and innate antitumor activity that should help address heterogeneity in the tumor. And I'm sure you'll have more questions, and we can talk about specific data in different programs. Terrific. Maybe another aspect of the cell therapy space, it is manufacturing. The manufacturing process has been a major challenge for gamma delta T cells. Maybe you can elaborate on what have been the challenges, and how does Adicet overcome it? Can you also comment on the manufacturing success rate, capacity, and maybe even if on costs? Yeah, absolutely. So indeed, in cell therapy, manufacturing is always a challenge. We started Adicet in 2015, so we're nine years into this. And we have improved in a very, very significant way. Specifically in gamma delta 1 T cells, one of the challenges is that we start from a relatively low population in the blood. It's about 1%-3% of gamma delta 1 T cells that we have in the blood, and we expand them to very high numbers to multiple patients. We have proprietary antibodies that can expand selectively the gamma delta 1 T cells, and eventually, we weed out the alpha beta T cells from the system. At this point, we can manufacture in a consistent way in three different locations at Adicet and with two different CDMOs. Both CDMOs have commercial capabilities. We use the same release criteria, we have quite significant portion of the cells that are positive CAR T gamma delta 1 T cells, and eventually, patients get just their dose off the shelf that needs to be infused to the patient. So indeed, a challenge, but I think we got pretty good at it. Okay, terrific. And, maybe today we'll start from autoimmune space for ADI-001, as this is a pivotal topic for the biotech industry. Could you help us to understand what is the advantage for ADI-001 to pursue autoimmune indications among, I think, more than 20 programs have been announced to take the initiatives into this space? Absolutely. So let me try to dissect the answer to this question to two. One, where you actually do not expect to see differentiation, which may correlate with probability of success, and where we do expect differentiation, which should suggest some potential advantages. So starting from the first one, where don't we differentiate? When you look at our PK, we actually don't differentiate from the PK of Schett. So Schett data show Cmax at day nine or day 10. They show persistence up to 30-60 days. We show persistence up to 90 days. So PK-wise, it looks the same. We're not looking to differentiate from a PK perspective. Then when you look at the B cell depletion, to remind everybody, we target CD20, not CD19. When you look at the Schett data, they measure CD19 in the blood, and they show essentially complete depletion of CD19 positive B cells in the blood. Well, it just so happens that we, since the beginning of this study, don't ask me why, but we measured the B cell in the blood based on CD19 positive B cells. As of the last data set, we had patients with data in 24 patients. In 23 out of the 24, the CD19 positive B cells goes to absolutely zero. But we probably did not get lucky 23 x. So we see exactly the same B cell depletion as Schett. So that's where we do not differentiate. Where do I expect to see differentiation? Number one is in tissue tropism. So we know the more patients we treat with autoimmune diseases, you know, for example, lupus nephritis, tissue tropism to the kidney will be a positive thing because we know that some patients will have B cell islets that contribute to the progression of the disease. Systemic sclerosis. You'll have some B cell islets in the lungs contributing to the disease and so on. Eventually, all these autoimmune diseases, many of them, eventually the damage is in the organs. Gamma delta 1 T cells are the only type of immune cell that is actually tissue tropism. That's where they reside. So as you expand to larger data set, this will probably present itself in terms of efficacy, whether it is high response rate, not that you can improve 100% at Schett, but small, small data set, or it might be better durability. So tissue tropism, definitely an advantage. The other advantage that I can't claim that it's only for Adicet, it's also for other allogeneic companies, is to reduce risk of CAR T cell malignancy. With autologous cell therapies, you know, the... It was published in New England Journal of Medicine. Peter Marks commented on this. There is a risk of CAR T cell malignancy, and it's just unavoidable. If you're dosing millions of cells to patients, if one of those cells has been, you know, got, edited in the wrong way, and it, and it leads to, essentially malignancy, the body will not reject it. So in autologous cell therapies, there is this, CAR T cell malignancy. In off-the-shelf, you don't expect it because these cells will be, rejected. So bottom line, same PK, same, CD19 B cell depletion, better tissue tropism, really reduced, probably no CAR T cell malignancy, off-the-shelf, no leukapheresis. So pretty simple and very well tolerated so far. Terrific. And you have announced to target lupus nephritis, so the lupus patient population with kidney complexity involvement. Could you help us to understand why you have this strategy in terms of compared to, like, other programs? And in terms of clinical path, regulatory path, does lupus nephritis has a clear endpoint- Mm-hmm. Or vice versa? Yeah, absolutely. Okay. Great question. So first of all, why we started with lupus nephritis, the vast body of data set with proof of concept with cell therapy in autoimmune actually is in lupus nephritis. If you look at all of Schett paper, all of Schett patients, all of them were tagged as SLE, but all of them actually had also lupus nephritis. And if you look at other small data set, you see most of the patients have lupus nephritis. The patients that want to get this cell therapy probably haven't responded to prior therapies, and the disease progressed and caused damage, to cause damage to their kidneys. So that's why lupus nephritis. In terms of endpoint, for lupus nephritis, it's essentially kidney function. It's the protein in, proteinuria, protein in urine, and the eGFR. So these are markers for kidney function, and these are eventually the pivotal endpoint. So it's quite easy to measure. Not a lot of judgment by physicians in rating these kidney function. So it does make sense to go after lupus nephritis. I wanna stress one point. I know we had a press release today about getting fast-track designation from the FDA, and, and we mentioned it will provide an update to investors in the very near term. You'll see that this question very quickly will become less relevant. We guided that we're gonna go to other indications, so you'll realize that this is a very, very comprehensive program. Terrific. And could you also share the progress update for the trial to get started in terms of study size engagement, and also how do we think about the geographical location of a distribution for the study sites? We hear some feedback like in Europe, that autoimmune indications is probably easier to start compared to U.S. Yeah, absolutely. So we will provide more update in the coming investor update. But what I can say at this point is that it's actually going pretty well for us. We see very significant interest from investigators and from sites, more than we initially expected.... And I think the key benefits that the investigators see in this drug are the key benefits that I outlined earlier for autoimmune, and some of them are actually really concerned about safety of autologous, mainly the CAR T cell malignancy. Some of them completely ignore this risk, but overall, when they look at our data, there is significant interest. So I actually expect in terms of execution, that we will do quite well. You highlight, safety differentiation. So in terms of a trial design, do you plan to reduce? No. Okay. And also, you also mentioned that tissue trafficking is a unique differentiation for gamma delta T cells. So for the phase one trial, do you plan to do translational research to actually show the evidence for your program? Just stay tuned for more data on that point. The only thing that I would encourage everybody in the crowd is do your research and try to find data about tissue tropism of alpha beta CAR Ts, and whether you can find alpha beta CAR Ts in lymph nodes or in tissues, and just if you find that, hold that reference. What about the lymphodepletion regimen? Are you going to adopt the same regimen as for your lymphoma trials? No, we're gonna go with something much closer to what Schett tested, which is essentially standard lymphodepletion. We also have some thoughts about even further reducing this lymphodepletion regimen. We do have an advantage, as I mentioned earlier, that we are significantly less susceptible to elimination by NK cells. So we have not explored that aspect yet with this program, and we have some further thoughts how to reduce the lymphodepletion regimen, but we can't share them at this point, but we will share them in the near future. Okay. Any other autoimmune indications under consideration beyond lupus nephritis? Absolutely. And we will update them in the very near future. But again, as I mentioned, this is a very comprehensive plan, and there is much more beyond what we currently see in the public domain, but we will guide in the very near term. Okay, terrific. Maybe it's a good time to pivot to another program, ADI-270. That is a CD70-targeted CAR T program. Can you talk about the features differentiated from other CD70 programs, given this is a popular target? I would love to. I really, really look forward to data in this program. This program is very significantly differentiated than other approaches with CD70. So if people update themselves about the, what's known, there's data with alpha beta, with a single-chain Fv targeting CD70, that show that in renal cell carcinoma, for patients with high CD70 density on the tumor, we see responses. So there is some proof of concept. Let me walk you through the data where we have significant differentiation. I'm gonna start with how we engage the tumor. We engage the tumor in a significantly better way compared to alpha beta T cells. Every single point that I'm mentioning is backed by data, and this data have been presented in an oral presentation a couple of weeks ago at the American Society of Gene & Cell Therapy. Number one, we target CD70 using CD27. CD27 is the natural receptor for CD70. It requires significantly lower antigen density of CD70. We compared head-to-head, and we confirmed this. Number two, if we all recall, gamma delta T cells have innate antitumor activity. If you take CD70 RCC, or if you take CD70 positive cell, and you knock out the CD70 in a malignant cell, gamma delta T cell will still kill that malignant cell, although it does not have CD70. Alpha beta will not. We have published this. We added a TGF-β dominant negative receptor. That's a bolt-on that we selected quite a while ago. There's been data by AstraZeneca, this recent ASCO, showing that TGF-beta added in a different solid tumor in a liver cancer, hepatocellular carcinoma, shows significant benefit. So we have TGF-beta DNR in this construct. So these are how we engage the tumor and how we operate in the tumor, significant differentiation. The other significant differentiation that we have is tissue tropism to the kidney. We know that our cells will go to the kidney. And PK, very significant advantage, because keep in mind, gamma delta T cells are less susceptible to detect by NK cells, but they are to detect by alpha beta T cells. But activated alpha beta T cells express CD70, so we will also fight back the activated alpha beta T cells. So I actually expect Cmax to be potentially higher, persistence to be higher, and better tissue penetration. So, I think this will be a very significant program for Adicet. Maybe the timeline to start a phase I trial? Yeah, sure. Absolutely. So we guided that we expect to submit an IND in the second quarter. Definitely on track for that, so stay tuned. And we guided that we expect to start the study shortly after, and we'll have data in the second half of next year. That's the current plan. We might have data actually sooner, but we haven't got it for sooner. Okay, terrific. Moving to oncology program, maybe you can share with us what are the key learnings from the lymphoma trial for ADI-001? Absolutely. So with ADI-001, when you look at the data, we treated patients that were later line. Median number of lines of therapies was four. A significant proportion of the patient, about 50%, were post-CAR T patients. In LBCL, we haven't seen the durability that we hoped for. In MCL, we actually saw quite nice durability. As of the last data cut, we had five patients in the data, four of them had a CR, and three of them had a CR beyond six months, which is kind of a marker that we look at. So in MCL, we definitely see the benefit. If you look at our, for example, RCC program, you see that we've learned. So CD27 is another costimulatory domain. It would enhance persistence in Cmax, and we added the TGF-beta DNR, which also adds a potency aspect to cells. When you look at repeat cell capacity of gamma delta 1 T cells, once you add the dominant negative TGF-beta, you see much better cell-killing capacity. So we have learned, and we introduced this into the 270 program. Okay, terrific. And, maybe you can also talk on the expansion cohort in mantle cell lymphoma and what is the status update? Sure, absolutely. So we continue to enroll. We're enrolling at the DLBCL with enhanced lymphodepletion. You know, we still work with the same centers. Enrollment is progressing well. It's a more rare indication compared to DLBCL. Pivotal studies in this field are much smaller. If you look at breyanzi label, breyanzi was recently approved for MCL. It's about 70 patients per pivotal study, so it's just smaller numbers, but we continue to enroll, we continue to follow up on the patients in MCL. What do you see the unmet needs in mantle cell lymphoma, especially for a CAR T therapy? Absolutely. So I think there's, for CAR T, right now, the products that are approved are autologous. So there's still very few centers in this country that can dose, autologous CAR T. So one, unmet medical need is just expanding into the community and to, into many more centers, and then just providing a therapy that is off the shelf and safer and doesn't cause another CAR T malignancy. I see. And for the expansion cohort, did you change any inclusion, exclusion criteria from phase 1? No. No. Okay, great. And, so for the ADI-002, and that's the Regeneron partnered program, maybe I don't know if you could share, like, any progress from there and what's the next step? Yeah. Unfortunately, there's nothing we can share unless Regeneron puts it in the public domain. The only thing that I can share that they're working on it, they're active, they're progressing with the program, and it was nice to see the data from AstraZeneca. The AstraZeneca data that I mentioned that showed great benefit together with TGF-beta dominant negative receptor was actually targeting GPC3. So they provided very nice proof of concept for GPC3 in hepatocellular carcinoma, and I'm sure Regeneron was very, very happy with this data. Yes. In the next 12 months, what are the milestones and the data catalysts that you would highlight? Absolutely. So I would highlight the following. One, in the autoimmune program, we expect to see data in a couple of autoimmune indication during the next 12 months. In the renal cell carcinoma, we expect to start dosing patients, and we'll start generating data in renal cell carcinoma and in MCL patients, we're gonna show some more data. So when you think about it, it's a couple of autoimmune diseases, renal cell carcinoma and MCL. I, I believe we have multiple shots and goals, and several of them have pretty good probability of success. Terrific. And, lastly, maybe an update on balance sheet and how are you going to allocate the resources across different programs? Sure, absolutely. So first of all, we're funded to provide all this data. We're funded into the second half of 2026. I'm looking at Nick, our CFO, to make sure I'm quoting it right. So we're well funded to all these programs, so I think we're—we have a very good trajectory with investors on the current funding. Terrific. I will wrap up here, and thanks for great discussion. Thanks for everyone for-