Good morning, and thank you for coming to the 2021 virtual UBS Global Healthcare Virtual Conference. My name is Michael, and I'm happy to be your host for this session. Our next presenter will be Chen Schor from Adicet Bio. A Q&A session will follow immediately after the presentation. To submit a question anonymously to be answered at the end of the session, please type your question in the Q&A prompt on the presentation screen. We now turn over to Chen. Thank you. Perfect. Good morning, everybody. Thank you for your interest in Adicet. Michael, thank you for inviting us to present at the UBS conference. At Adicet, we're leading the development of off-the-shelf gamma delta T cells that we engineer to fight cancer. Gamma delta T cells is a therapy that is expected to be an attractive option for patients when we compare it to other allogeneic types of cell therapy, such as alpha beta T cells or NK cells or bispecifics. It's my goal for you guys to understand a little bit of differentiation during this presentation, and I'm happy to address any additional questions in the Q&A. We have a pipeline of programs targeting multiple cancers and multiple antigens presented on cancer cells. We're the first company that ever cleared an IND for CAR gamma delta T cells. We initiated our phase I in the first quarter of this year, we expect proof of concept data later this year, that we believe will validate the gamma delta T cells as an approach and the multiple programs that we have in the pipeline. We will fund it with $220 million in cash, a little more than that as of March 31st, into the second half of 2023, meeting multiple milestones, as you'll find out during the presentation today. Why don't we start with slide number three, let's talk for a second about what makes gamma delta T cells so attractive. The first piece of evidence comes from multiple publications that we did not sponsor or we currently don't have a relationship with the investigators that published these publications. The conclusion from these publications is very clear. The presence of gamma delta T cells in tumors is strongly correlated with improved overall survival in patients. Let's jump for a second to slide number six, I'm going to refer to one of the charts here, the one on the left by Gentles et al. What they did, they took 6,000 tumor biopsies from patients from 25 different malignancies, they tried to correlate the different immune cells with overall survival. As you can see, gamma delta T cells ranked the highest compared to cell types like alpha beta T cells or NK cells. It's really important to bring those gamma delta T cells to tumors, if we do, it looks like there's a significant advantage in terms of overall survival. The references for some of the other charts on this slide are in the bottom of the slide, again, I'm happy to discuss them during the Q&A. The conclusion is the same. The presence of gamma delta T cells in tumors strongly correlates with the overall survival. I'm going to go back to slide number three, and let's continue with the summary. I guess one of the key reasons gamma delta T cells are potentially attractive for patients is that they express both the T cell receptors and the NK cell receptors. This enables us to facilitate an attack against the tumor, both with the innate anti-tumor response and the adaptive anti-tumor response. That means that the tumor has more limited ability to escape. If you look at the bottom right of slide three, you can see a very simplified figure of a gamma delta T cell. You can see in green, it's the CAR that we engineer into the cell. You can see in blue and red, gamma delta TCR, and in gray, the different NK receptors such as NKG2D or NCRs or DNAM-1. When you take, for example, a bispecific or an alpha beta T cell, they primarily target the target for the tumor, the antigen. The tumors are smart. Once they downregulate the target for the tumor, essentially, there is very little benefit that can be derived from a bispecific or an alpha beta T cell. Unlike gamma delta T cells, we have all the receptors marked in gray that will continue to exert their cytotoxicity consistent with the NK cells. When we started Adicet, we developed antibodies that can expand any type of gamma delta T cell. It's like a menu. We can expand gamma delta one, we can expand gamma delta two, we can expand gamma delta three, we can expand a combination of gamma delta one, two, or three. We compare them. What we found out is that gamma delta ones show the best cytotoxicity profile, and they have one key advantage. Gamma delta ones generally localize and reside in epithelial tissues that serve as a barrier function, like skin, like lungs, like intestines, uterus, and other types of tissues. The reason this is important is because gamma delta one T cells function very well in an environment that's hypoxic and low on nutrients, and this is what we see in solid tumors. As we all know, one of the biggest unmet medical needs in oncology is cell therapy in solid tumors. From that perspective, gamma delta one T cells are quite optimal for solid tumors. Gamma delta T cells do not have an alpha-beta TCR. Graft-versus-host disease is not a concern. We don't need to edit out the alpha-beta TCR because we just don't have it. There's also no significant spike in IL-2 once we dose gamma delta T cells to patients, and hence we're less concerned about the CRS syndrome or neurotoxicity, and that should, over time, translate to potentially dosing in outpatient settings and making cell therapy available to so many more patients compared to the very few centers that currently dose cell therapy to oncology patients. A few years ago, we acquired a company that brought us another capability. We call it T cell receptor-like, or TCRL. What this enables us is to develop single-chain FVs that target very selectively peptide MHC complexes. Essentially, in our pipeline, we can target either targets that are presented on the membrane or targets that are part of the peptide MHC complex. As you'll see from our pipeline, we have multiple milestones that we expect to meet in the next few years. I referred earlier to our cash position and until when we expect to have cash. Switching to slide four. Slide four just outlines some of the differences between gamma delta one and gamma delta two. I'm not going to go through the entire slide. I'll mention perhaps three key items. One is that gamma delta one T cells versus gamma delta two T cells seems to suggest a better cytotoxicity profile. Gamma delta one's localized to tissues and seems to survive very well in the solid tissue environment. The biggest challenge with gamma delta ones is that there was no way to manufacture them at scale. This is something that we've worked on at Adicet for more than five years, and I'm glad to update that at least in our first IND that we submitted to the FDA, we had information about the five different manufacturing lots, GMP of course, and the CMC review went seamless with the FDA, now we're dosing patients. Slide five, I'm very happy to be surrounded by a very accomplished executive team. Some of you who are listening to this presentation probably know them from prior meetings. Why don't we go to slide seven and let's review the pipeline. The first program is targeting CD20. CD20 is one of the most validated targets in the field of oncology, and the indication are different types of non-Hodgkin's lymphoma. The key goal in selecting CD20 was to minimize risk, maximize chances of success with a program that is differentiated, and I'm going to delineate the differentiation that we expect. In terms of status, as I mentioned, we're in patients, and we expect to report data from this program later this year. In terms of the differentiation, the differentiation really comes from the properties of gamma delta one T cells with the CD20 compared to other cell types. One is facilitating the adaptive and innate anti-tumor response, with the more limited ability for the tumor to escape the therapy. That should potentially lead to better durability when we compare to alpha beta or bispecifics. The second is persistence. We expect to see persistence in the range of one to a few months, significantly better than the persistence, for example, of NK cells. That's why NK companies generally dose about once a week. Better persistence should lead potentially to better durability and certainly for less frequent dosing. In terms of safety, we expect significantly lower CRS or neurotoxicity, especially when you compare to alpha beta T cells or bispecifics that may be a little more comparable to the safety profile of NK cells, and hence the potential to administer in the outpatient setting. Bottom line, ADI-001, our candidate for the non-Hodgkin's lymphoma program, is expected to be a nice alternative and competitive for patients with non-Hodgkin's lymphoma. When I describe the clinical study, I will also refer to the expansion cohorts that we're planning. Some of them we expect to be pivotal, and some of them are reasonably small in terms of the number of patients. Our second program is our first solid tumor program targeting glypican-3, or GPC-3. Glypican-3 is an antigen that's presented in a couple of solid tumors, hepatocellular carcinoma, squamous cell carcinoma of the lung, and a few others. The first benefit that we're getting, even without Adicet, if you take gamma delta one T cells, they will home to the liver and the lung. We're first of all going after tumors that reside in our target tissues. We're adding the GPC-3 targeting, so there's two ways for us to target the tumor. Again, in solid tumors, one of the biggest parts of the problem is making sure there's enough of those cells that go to the tumor and then that they function. We know that gamma delta T cells can potentially function in solid tumors. The second advantage is that benefiting from the adaptive and innate antitumor activity. We all know that in solid tumors, heterogeneity is expected. We better have a cell that can kill the GPC-3-expressing tumor cells, but if there's a neighbor cell that does not express the GPC-3, then the innate receptors will also kill those cells. With this program, we expect to file an IND in the second quarter next year. I do want to mention that this program is included in the collaboration that we have with Regeneron. So far, Regeneron paid about $55 million to Adicet, and in proximity to us filing the IND, there will be a short window where Regeneron will have to decide whether they want to exercise their options and develop this program. In such case, we have the option to keep 50% of the profits and participate in the cost of this program. Then we have about seven other programs at different stages, and we will unveil these programs in the near future. Transitioning to slide eight, we have multiple milestones that we expect to hit in the near future, from a clinical study, from clinical data from our first program in non-Hodgkin's lymphoma, to planning our expansion cohorts in DLBCL, MCL, and potentially other types of non-Hodgkin's lymphoma, to filing an IND. In the GPC-3 program, there's a few other publications or abstracts that we expect to publish regarding our programs we haven't published so far, and Adicet has worked on our gamma delta platform for more than five years. There's going to be more programs that will be unveiled in the near future. I'm going to switch to slide 11. I'm going to try to identify the differences between gamma delta T cells and NK cells. I'm happy to discuss versus alpha beta T cells as well in the Q&A, but let's start just understanding versus NK cells. Both NK cells and gamma delta T cells have innate antitumor response. Gamma delta T cells also has adaptive antitumor response, so there's multiple ways to exert the cytotoxicity. Gamma delta T cells do actively home to tumors, and we've seen the prognostic value of this tumor infiltration when we reviewed slide six. The more gamma delta T cells in tumors, we see the better overall survival. In NK cells, there's this balance of activating versus inactivating receptors. In gamma delta T cells, we have mostly activating receptors, which suggest lower threshold to exert cytotoxicity once they encounter the tumor. I'm going to review with you the persistence in vivo in animal models, but as far as we can see, we expect a nice persistence from gamma delta T cells, especially compared to NK cells, which might lead to better durability and less frequent dosing. Graft-versus-host disease, we do not expect this to be a problem with the gamma delta T cells. It's not a problem with NK cells. We don't expect a significant increase from grade three CRS, and we do have a very nice and scalable manufacturing. Talking about manufacturing, let's transition to slide 12. Essentially what you see here is the chart of manufacturing. I'm going to quickly review it. We start with leukapheresis from qualified donors. With qualified donors, we have a proprietary antibody, AM3579. We use it to activate the gamma delta one T cells selectively, not the gamma delta twos or threes with this specific antibody. We transduce the gamma delta T cells with the CARs, and then we expand them, and we bank them, we freeze them, and before we d ose patients, we thaw them. Every single slide that I will present to you today essentially went through this process. These are all cells that were frozen and then thawed, and then dosed, in this case, to different preclinical models. Slide 13 shows a little more data about our manufacturing. I want to mention that Adicet was able to successfully manufacture essentially in multiple facilities. We do the process development and pilot lots in-house, and then we transfer to a CMO. In blue, you can see the expansion in-house, and in green, you can see the expansion in one of the leading CMOs, that's CMO, that's in green. Bottom line, the processes develop essentially the same expansion, and the expansion we expect it to be highly cost efficient, and we should potentially be able to dose up to 1,000 patients from a single batch. I do not believe that costs will be an issue for us in dosing patients at all. Moving to slide 14, these are data from our CD20 program. The data are very clear. We inject cancer cells into the mice. These are multiple models. We wait for the tumor to grow to about 200 cu mm. We dose our gamma delta T cells targeting CD20, and essentially, we completely eradicate the tumor. I think actually the more interesting model is actually on slide 15 because that's a repeat tumor challenge, which is probably the most stringent model in oncology, in preclinical models, because it also kind of shows the effect of a potential relapse, which is an issue in patients. We start the model in the same way. We inject tumor cells, we wait for the tumor to grow to 200 cu mm. We dose ADI-001, and you can see in light blue complete eradication of the tumor. We wait two months, 60 days, and the tumor is gone from the animals. We go back and inject the animals with tumor. We did not inject again ADI-001, our cell therapy. What you can see is that without another dosing after 60 days, we again completely eradicate the tumor in light blue. This shows that at least in preclinical models, we have at least 100 days of essentially functional persistence. When we look at our gamma delta one T cells subject to attack from NK cells or alpha-beta T cells, which are the type of cells that come back after lymphodepletion, we can talk about it during the Q&A, we're also expecting humans to see nice persistence. In the interest of time, I'm going to switch to slide nineteen. Here you can see the design of our clinical study. We start with lymphodepletion. It's the canonical lymphodepletion that we've seen in many studies. We dose a single dose of infused ADI-001, 28 days. It's a relatively short time to observe the initial safety and the responses. In non-Hodgkin's lymphoma, we've seen complete responses sometimes within that 28 days window, sometimes it can take a little longer. We follow the patients for 12 months. We expect data from this study this year. Generally small, short studies, and we can get a pretty good sense of complete response and safety. Overall, what to expect this year, we expect data by the end of the year. We started the study in Q1. We're going to have preliminary data about the safety and efficacy, potentially from multiple doses. We might get some information about the persistence, and more will be unveiled as we progress in the study and get closer to announcing the data. Why don't we switch to slide 21 and transition to our second program in solid tumors? I just want to remind everybody, gamma delta one T cells are one of the most optimal types of cell therapy for solid tumors because they home to tissues and to solid malignancies, and they function well in an environment that's hypoxic and low in terms of nutrients level. G amma delta one T cells can provide both innate and adaptive anti-tumor response, which is really helpful in solid tumors that are generally heterogeneous in terms of the tumor cells. Switching to slide 22. The nice thing about GPC-3 as an antigen for solid tumors is that it has extremely limited expression on normal tissue in adults, and you can see on what type of tumors it is expressed. Hepatocellular carcinoma and squamous cell carcinoma of the lung are two great examples where most of the patients, based on literature, express GPC-3. Again, these are tissues that we target in two ways. One, through the GPC-3, and two, because the gamma delta one T cells will go there. Slide 23. In the case of our second program, ADI-002, we added the IL-15 to the construct, and we compared membrane-bound versus soluble IL-15. Eventually, we selected to include soluble IL-15. One of the key benefits of soluble IL-15 is to not only support the proliferation and persistence of our own gamma delta T cells, but it also can support the proliferation of other types of anti-tumor cells in the tumor microenvironment. On the right side, you can see the efficacy, and you can see a comparison between in green, that's our construct without IL-15, and in blue, it's with IL-15. You can see that in vivo, we see some advantages to including IL-15 in the construct, and hence it is included. Slide 24, I'm not going to go through it in details. Bottom line, you can see a very nice dose response, and you can see that the highest dose essentially completely eradicates the solid tumor. These are HepG2 tumor growth, which is a model for hepatocellular carcinoma. Slide 25. One of the advantages of gamma delta T cells, and there's a backup slide that we can refer to during the Q&A, is that these type of cells can show very nice cytotoxicity, even at extremely low densities for the target for the tumor. We have a lot of flexibility regarding how much is GPC-3 expressed in the tumor, and even if there is low expression, we should see cytotoxicity. Even if there is no expression, hopefully the innate receptors will exert their cytotoxicity. We added IL-15 to this program, and we believe this will enhance persistence. We have favorable preclinical data. IND is expected for this program in the second quarter of next year. I'm going to go to slide 27. Then we'll summarize and we'll go to Q&A. Slide 27 outlines our TCRL platform. What you can see here, essentially what we get from the TCRL, we're mimicking the specificity of a TCR with this higher affinity that we can get with molecular antibodies. Essentially, at the end of the day, we develop these as single-chain FVs that we introduced on a CAR. On the right side, you can see just an example that's in the case of tyrosinase. This is just an example. It's not a formal program that we updated our investors about. In the case of tyrosinase, you can see again, just complete eradication of the tumor with these gamma delta T cells with this TCRL targeting tyrosinase. Slide 28, just to summarize. We're the leaders in developing engineered gamma delta T cells. We can expand any type of gamma delta T cells. We're focusing on gamma delta one T cells. We're the only company that cleared an IND for CAR gamma delta T cells, and we expect to report data from our first program later this year. Gamma delta T cells are significantly differentiated from alpha beta T cells and NK cells, and have some potential advantages over these type of therapies. They provide both adaptive and innate anti-tumor response. We have a pipeline of programs in different oncology indications, and we're well-funded with $220 million that should take us into the second quarter of 2023 and meeting multiple milestones. It is 28 minutes after the hour, and hopefully everybody were able to follow. What if we open it for Q&A? Michael, I'm happy to transition to Q&A. Thank you, Chen. We will now move to the Q&A portion of the presentation. As a reminder, if you'd like to anonymously submit a question, please type your question in the Q&A prompt on the presentation screen. We'll give it roughly 30 seconds to one minute to get any questions down. I know it takes time to type. We'll move to the Q&A session. Thank you. All right. Our first question for Chen is, "Can you please discuss any challenges with ramping up gamma delta T cell manufacturing? Do you see commercial scale manufacturing being more difficult than other cell therapies? Absolutely. I'm going to move to slide 12. Are there challenges? Yes. In manufacturing every type of cells, there are manufacturing. Generally, it's easier to expand gamma delta two T cells. There's multiple ways that are documented in the literature how to expand gamma delta two T cells. In order to expand gamma delta one T cells, we developed multiple type of antibodies, and eventually we focused on AM3579. We worked on a process development for almost five years to really optimize it, and I believe that by now we are the leading company that can expand gamma delta T cells in GMP scale and actually also potentially in commercial scale. We've done it successfully. There are challenges. That's why we're the leaders and you don't see a bunch of other companies focusing on expanding gamma delta one T cells with a CAR. If you look at slide 13, this is GMP manufacturing in green, with a CMO. In our IND, we submitted five different manufacturing lots and had no comments to the CMC section. There's something that we're doing right. I do not believe there's going to be a commercial challenge in manufacturing. I think we're in a great spot. I think that right now we can potentially manufacture, I want to say, up to about 1,000 patients per dose. The cost of manufacturing these type of cells is very consistent with the cost of manufacturing autologous cell therapy. Think about it, autologous cell therapy eventually sell for about $400,000, and that's for one patient. It's the same process. I believe that we will get to about 1,000 patients per dose when we manufacture. I think overall, we should be in a great spot from a manufacturing perspective, and we were able so far to expand gamma delta T cells in a very scalable and reproducible way. Thank you for asking. Great. Thank you. Our next question is, apologies if this has already been covered, how might gamma delta T cells result in more durable responses seen in non-Hodgkin's lymphoma relative to CAR T cells? Sure. Absolutely. I'm going to transition to slide 11, and the question was CAR T cell, so I'm going to address CAR T cell and not NK cell. Indeed, in the presentation, we only compared to NK cells. When we say CAR T, assume we are talking about autologous or allogeneic CAR alpha beta T cells. Let's understand the differences. When you have an alpha-beta T cell, and let's talk about CD19 as a target, we're going to see nice cytotoxicity, and we'll see nice killing of all the cells that express CD19. We'll probably see very nice overall response rate and nice CR rate. These tumors are smart. Eventually, the target for the CAR, the CD19, is downregulated by the cell, and the tumor tries to expand. Do alpha beta T cells have a way to effectively continue to kill cells that do not express CD19? Alpha beta T cells do not have innate antitumor response. Nothing significant there. Essentially, once the tumor progresses, the alpha beta T cells have little utility, very consistent with the bispecific targeting the CD19. This is why, if you look, for example, at autologous alpha beta T cells, you can see that many of the patients eventually progress, about 50%, I want to say, during the first year and about 75% over time. When you compare it to NK cells, NK cells also have the innate receptors. We're targeting CD20. It would be the same if we targeted CD19, honestly. Even if the target for the CAR is downregulated, in NK cells, you have all the innate receptors that can still exert their cytotoxicity. I want to give you an example. I want to take you to slide. I hope the backup slides are available. Michael, please tell me if that's not the case. I want to take you to slide 30 for a second. What you see on slide 30 is the difference between a CAR gamma delta T cell versus unengineered gamma delta one T cell. This is just a 24-hour window of experiment. Let's take a look, for example, at the Mino cell line, which is on the bottom left. There's very high density of CD20 expression per cell, more than 90,000 copies. You can see that you kill all the tumor in 24 hours, whether you have the CD20 or you do not have the CD20 in red. Again, the red is pure innate antitumor response, which does not exist in any significant way in alpha beta T cells. Let's use the opportunity to look at the WIL2, which has extremely low density of CD20. This cell line would be completely resistant to rituximab, as an example. Again, you can see in blue, complete eradication of the tumor cells. In red, you can see the beginning of it. Actually, if you waited another 48 hours, you would see that it gets to 100% killing. That's just an example. Let's just go back to slide 11. One of the key advantages is the fact that in gamma delta one T cells, we will get innate antitumor response on top of adaptive antitumor response. The innate is extremely important. That's one key advantage. The other key advantage, and you wanted to refer to alpha beta T cells, and I think that I would expect that in this class, eventually the allogeneic alpha-beta T cells will move forward because of the challenges with allogeneic. If you want to develop an allogeneic alpha-beta T cell, what you have to do is essentially edit out the alpha-beta TCR. You take an alpha-beta T cell that expressed most of its cytotoxicity from the alpha-beta TCR, and you cripple it by taking out the alpha-beta TCR. This reduces the cytotoxicity performance of the alpha-beta T cell. It continues to exert cytotoxicity, but it's not necessarily at the same level of or type of toxicity that you see with the alpha-beta T cells. That's something that we do not need to do in gamma delta T cell because there's no alpha-beta TCR, and the gamma delta TCR can remain and provide potential efficacy as well. These are some of the key advantages. There's more, but I think I covered the key advantages, which is the innate anti-tumor response and not taking out the alpha-beta TCR. In terms of safety, gamma delta one T cells also do not expect to have a significant CRS or toxicity risk. Thank you again for asking. Michael, I'm happy to address the next question. Oh, Michael, I think you're on mute. Happens to all of us at least once a day. No problem. My fault. Looks like we have no further questions. With the remaining time, we can go through the backup slides if you like, or discuss financial performance year to date, or we can end the presentation early with the remaining time. In terms of financial performance, we're in a great position. We completed the financing in the first quarter of this year. It was about $150 million in size. Some of the best investors on Wall Street, very sophisticated investors that know oncology and know cell therapy, participated in the round. I believe some of the information of who invested is in the public domain. After this financing, we're well-financed with $223 million in cash as of March 31st this year, and this should take us into the second half of 2023 and meeting the multiple milestones. Michael and the participants that joined us today, thank you so much for your time, and look forward to the rest of the conference. Thank you, Chen. Thank you.