FATE THERAPEUTICS INC — Call Transcript 2026

Good morning, everyone. My name is Daina Graybosch. I'm a Senior Equity Research Analyst here at Leerink Partners, and I'm excited to be hosting Fate Therapeutics and their CEO, Bob Valamehr, here for my first company fireside at this year's conference. That's exciting for me, and Fate is also one of the very first companies that I covered as an analyst. Actually, I think the only one that I still cover of the first few that I launched on. I'm excited about that history and also where you're going in the future. Welcome. Thank you, Daina. Thanks for the invitation. I wanna jump right in 'cause we only have 29 minutes to talk about FT819, which is your leading allogeneic cell therapy program. It's a CAR T, to remind everybody who thinks about Fate as an NK cell therapy company. The leading program's now a CAR T. I wonder if you could give us an overview of its program and the edits, then we'll jump into the data and where it's going. Sure thing. FT819, as you mentioned, Daina, is a CAR T-cell, is an off-the-shelf CAR T-cell. We view it very differently than other allogeneic, CAR T-cells in the fact that it has a master cell bank as a starting material. You essentially aren't chasing different donors, as your drug product, inventory, depletes. You have a starting population that with the concept of a master cell bank leading to a working cell bank using as a starting material to make trillions of cells, you actually end up with having over 10 million doses. That's what we calculate today, and I'm being a little bit conservative because that's. Per master, per donor. Per master- $10 million. Per master cell bank, you can make 10 million doses, and this is a dose that's around the magnitude of 1 billion cells. We're not cutting it low by, or we're not exaggerating the numbers by having a low dose. This becomes a drug product that pharmaceutical companies are used to. Just like a monoclonal antibody or even aspirin, the starting material is there. It's been already edited. It is pure in population because the starting population is a clonal product. It's very different than allogeneic or autologous programs that are from T-cells, and these cells have been engineered, of course, but they have been engineered in a way where it's heterogeneous. The e-engineering event is stochastic, so some cells have the engineered entity, some cells don't, and those that have been engineered may not be properly engineered. You're taking that heterogeneous population into the patient, and it could result in unexpected results, and that's not something we want with drugs. For us, you know, we've been working on this for 17 years, 18 years now, and the concept has always been using a master cell bank to start the manufacturing process. Every time we make a batch, it's uniform, it's consistent, it's the same. When we talk about FT819 in oncology, and we talk about FT819 in autoimmune, we're talking about the same product. It is essentially it starts from the same place and is tested to be the same. How do we come across FT819? FT819 stands for CD8, which is a 8, and it's targeting CD19, which is the 1 and the 9. It's a CD8 targeting CD19. Hopefully everybody remembers that going forward. When we started this, safety was important to us. Activity was important as well, but safety was also very important. We fine-tuned the CAR motif, the chimeric antigen receptor, has a costim domain, has a signaling domain, and we want to make sure that we preserve that ability of these cells to respond to antigen and expand because that's very important. That's why it makes CAR T so unique, and I'll get into that in a second. We also wanted to make sure that that expansion is controlled. Because CAR T has a safety component, if you have too much of an expansion, as these CAR T-cells come across antigen disease and they wanna expand, and that burden forces them to expand even more than you know, than you would like, you end up having adverse events. For us, it's controlled. We've treated nearly 70 patients now, and every time we get very similar results, similar product giving us similar results. Because we've tuned down the activity to compensate for and balance for safety, when we were in aggressive DLBCL, we did see the complete response rates. It was about 40% in CAR patients, but the durability wasn't there. That's because the CAR built in a certain way, so that when it went against aggressive disease like DLBCL and its 5 lbs of tumor, it ended up not being able to hold up 'cause it was designed that way. When we are shifting focus to autoimmune, we're seeing something very different. We saw that some of that glimpse in indolent lymphoma where the disease burden is less. When we shift over to autoimmune, that becomes a perfect balance between activity and safety. The tumor burden I mean, the disease burden is less, FT819 is capable of controlling the disease and eliminating it. At the same time, the safety is there. In this patient population of autoimmune where it's not a disease of urgency, it's more a disease of long-term maintenance. We're able to go in and give the patient a unique ability to have a safe and effective drug. That's where we are right now. We're advancing FT819 in lupus nephritis and renal lupus, but also in myositis, systemic sclerosis, and vasculitis. Tell me how you designed it that way that it wouldn't have durability. Help me understand that a little bit more. Like what specifically in the design led to the lack of durability? The items two and three of the CD3 signaling domain are mutated out. Typically a CAR, a chimeric antigen receptor, engages with its antigen that's targeting, and then you have the CD28 signaling domain or 4-1BB, 4-1BB signaling co-stimulatory, and you have the CD3ζ signaling domain. These two together give the T cells the ability to react and eliminate the target. What we've done is we've knocked out two of the three activating motifs, CD3ζ, and that allows us to still have expansion and activity, but not to the level that is uncontrolled. You think that it's just then you have activity, it's just not enough to get all that tumor burden clearance. You're not getting the depth. It's more about you just can't get the depth of response of high tumor burden? Yeah. I think in situations where you have disease levels of 10 to the 10 cells, for example, a 5-lb tumor is in the order of 10 to the 10 cells, you're not getting rid of every single cell because you're just not built that way. You end up having durability, not in a way that you prefer. In indolent lymphoma, where the disease burden is closer to 10 to the nine or 10 to the eight, you do get that durability. How many cells are in I mean, in autoimmune disease, you're targeting normal cells. Yes. The order, so we know the magnitude. 10 to the eight. We believe that in B cell diseases of rheumatology, the disease is somewhere between 10 to the eight and 10 to the nine. Normal levels, these are few B cells that are either some sort of environmental stimuli or, some sort of genetic predisposition has caused them to attack the host itself. There aren't as many as the 5 lbs of tumor. When the disease burden is different, then your effector target ratio is in your favor with FT819. Got it. Maybe I'll add any CAR T cell, the uniqueness of CAR T cells is that they respond to the disease. Unlike monoclonal antibodies or T-cell engagers, where you take the medicine and it decays over time in a declining manner from the get-go, this is very different. CAR Ts expand and rise up to the occasion depending on the disease burden they face. You have a living drug fighting disease in a very different paradigm than traditional medicine. Got it. With FT819 this year, in respect to what we're gonna see in terms of the maturation of the program and the clinical scale, and I know you're readying yourself for a pivotal trial, can you just give us a scope of what we'll see and what you're gonna accomplish this year? Absolutely. I think we made great progress with FT819 in lupus. Some of those things were already inherent in the product, such as accessibility. This is an off-the-shelf product, as I mentioned earlier. We are capable of making about 50,000 doses in our current facility at full scale. That's hiring more people, not requiring more space or more capital. It's just simply hiring a number of manufacturing folks to do that. That scale, with the cost of goods down already at $3,000 really gives us a unique advantage. On top of that, now you're on-demand and off-the-shelf, but as we mentioned a couple of weeks ago, we're now doing this in outpatient therapy. When you get this medication, you're not being held in the hospital 14 days. It's just like any other medicine. You get a CAR T, it's very unique for CAR T. You get it that day, and you go home. This really gives the patient accessibility. A lot of patients in lupus are working. They've been living with this disease for a very long time, and they have a life to live. They cannot stay in the hospital for 14 days. I don't think anybody wants to stay in the hospital for 14 days. There's a lot of pre-work to get your CAR T made that requires you to often go to the hospital to procure your T cells. You have to get off your current medication. It's a very complex process to get CAR T. What we've done is we've made it just like any other product, and you get the CAR T when the prescription is written. You take that element, you take the efficacy we're seeing in terms of decreasing the disease burden according to SLEDAI scores, improving the patient's health in terms of improving PGA and FACIT-fatigue. This is quite remarkable. You're getting patients that are bedridden that within a month or two are able to go out, be out and about and go back to their jobs. This is quite an amazing leap for autoimmune. You combine all that and the safety profile where we've had no ICANS, no GVHD, and also low-grade CRS, it's really takes the fear out of getting cell therapy and makes it accessible. We've had, under RMAT designation, we've had several meetings with the FDA where we have really paved the path in terms of, as you mentioned earlier, what it takes to get into a pivotal study. The phase II, the, as I've been saying, the domino pieces are falling and we're making great progress to commence that trial the second half of the year. This will be a phase II potential registration enabling study where we'll be focusing on lupus nephritis. Complete renal response will be the primary endpoint. We feel very confident that this will be a successful trial. The way we're enrolling, I think we can complete this single-arm study in short order. Talk about, so you've chosen lupus nephritis and complete renal response. Can you talk about what you've shown against that endpoint so far? I think you had presentations at ACR and ASH. Mm-hmm. What we'll see this year both in terms of how well you're doing, but maybe you could give it some context of compared to other standard therapies? We just had obinutuzumab approved, for instance. No, certainly. The first two patients that have reached six months have achieved a complete renal response. What we're hoping to show in additional conferences this year is further strengthening that observation. I think just like other CAR T-cells, we're seeing very dramatic responses within the first few months. This is very different than monoclonal antibodies or T-cell engagers. This is a single treatment, and I should add that with our paradigm, we're actually using less intensive conditioning. Traditional CAR T-cells, whether it's auto, allo, are doing three days of cyclophosphamide and fludarabine combination. That's very intensive, and in our experience, not preferred because that was an option in our study as well, and no PI took that option. Every PI took either cyclophosphamide alone or bendamustine alone. The results we're getting is even extra rosy because it's getting accomplished in such a way without intensive conditioning, which not only distracts patients from wanting to be treated, but also puts a question in the efficacy of the product. Here, we're very confident that FT819 has activity because we also have Regimen B that well, I'm sure we'll talk about that there's no conditioning, and we see activity there. To your question, we hope to further strengthen our results this summer. When we treat the first patient later this year, in our phase II study, I think that's where kind of it all comes together and everybody sees a path forward. How many patients? Just like the scope of how many we might see. You know, we've already treated 15 lupus patients and 20 total patients. There was a nice figure by Wedbush that showed us basically reaching second place now in terms of how many lupus patients treated. That has to do a lot with the last six months, the exposure we've gotten from different sites in terms of them being somewhat frustrated with the mechanics of auto CAR T accessibility to product, lack of patient interest, and also the activity we're seeing. A lot of the PIs are talking to other PIs, and we're getting more sites, more patients. We're, I think we'll be probably somewhere close to 25 lupus patients by summertime, but I think, you know, you obviously, you need a follow-up three to six months. We're expecting somewhere close to 15 patients with six-month follow-up by mid this year. They'll all be nephritis patients? No, some of them will be extra-renal. Okay. There will probably be half of those will be, lupus nephritis patients. Why are you doing that even though your registration study is gonna be in nephritis? Why not put every single one of these first patients a nephritis one? We treat all comers in lupus. It just happens to be half of the population of SLE are lupus nephritis patients. We also have intention of moving forward with extra-renal. On that front, we're in discussion with the FDA on the primary endpoint. We're still discussing that strategy, but we believe that somewhere between SRI-4 and DORIS, there is a meaningful path. The challenge with DORIS is it hasn't been used previously for approval, and current therapies are being basically approved on SRI-4. From my perspective, you know, potentially SRI-4 with a safe product can be a path forward. We're having that conversation now whether extra-renal is a confirmation study to lupus nephritis or extra-renal is its own study. We're developing that, but there is a path forward here for extra-renal as well. We'll have more information on that second half of the year. As we accumulate extra-renal data, I think it's prudent to consider that as another product that will go into commercial stage. What's wrong with SRI-4? You just think it's not gonna demonstrate how great you are? No, I don't think there's anything wrong with SRI-4. Okay. I love it, but I think the auto CAR T stigma is holding CAR T accountable to a different level than all other approved products. I think it's our burden to show the FDA and other regulatory agencies the safety of FT819, the uniqueness of FT819, and allowing us to play in the same field as currently approved products. When you do that, FT819 is far superior over obinutuzumab, is far superior over voclosporin, things that are currently being used today. You just see the dramatic difference. It's, it's up to us to show the safety, the accessibility, and once we do that, and the costs are good, and once we do that, I think we should be in the same ballpark as other approved products. The auto CAR T are gonna go after DORIS. They might have to. That's the bar. You assume they're gonna go for DORIS. That's the bar. Do you think, can FT819 meet the same DORIS? I mean, we see all this data, but it's all small and from different institutions. Mm-hmm. Like, what do you think? Yeah, you know, that's a good point. Let me say, we have achieved DORIS with the first patient, and it was a meaningful durability. I think that while DORIS is a great bar to achieve, you don't need to go that far. I think a lot of patients today will significantly benefit from the improvements in disease that we're seeing, with a product that can be accessible. While I think auto CAR T's being held to a higher bar because of all the cost, the challenges, safety, we're starting to be treated looking like and feel like any other medicine today that's out there, such as a mAb or a T-cell engager. I would say we're at an advantage because of the single administration as well. The patient comes in on Thursday, gets conditioning, goes home, comes back on Monday, gets treated, and that's it. That's very different than mAbs and T-cell engagers that you're constantly being treated and which also has its issues with safety as well. Let's talk about the conditioning. You said that you had a lot of options in the trial. You had cohorts that you could either get regular conditioning, Benda alone, Cy alone, also you had this cohort or patients stay on their immunosuppressive drugs. Mm-hmm. Rather than going off of them and getting a different conditioning, that's sufficient. Can you tell us about that regimen, and what it looked like? Is there a path forward there and where you would take that sort of non-conditioning, use your regular standard therapy? That's excellent, lead into question because here this is where you're thinking about SRI-4 now because now you have Regimen B. There's no conditioning here. You give FT819 on top of maintenance therapy with the hopes of having the patient actually come off their maintenance therapy with improvement in disease. Here, this is simply now FT819 given on top of current therapy. That's how every mAb or T-cell engager is being tested. What we're seeing here is that we are seeing a significant, and meaningful, decrease in disease, especially as with patient one, as we've shown. We have additional patient data, and I hope we are able to show that by summer, or we're planning to show that by summer timeframe. Here now, this is where I'm talking about SRI-4. You're just like every other biologic out there. You, you're being added to what patients are currently getting. You're gonna have a meaningful results, and then you might come off maintenance therapy. That is something that as I talked about a confirmation study in extrarenal, as I talked about a follow-up to the lupus trial, this could be the second part of the lupus story for us, where now we're talking about extrarenal either chasing regimen A, or chasing Regimen B and being part of the package of the lupus, commercialization. But to be fair, the data you've shown so far, you weren't able to reduce the disease burden as much as when you used Cy or Benda. Mm-hmm. You're saying that that trade-off and having this option of treating just in the normal course of your standard lupus treatment is worth it. Or do you think that in some patients you will get deeper responses, or can you do redosing? Yes. Absolutely, and that's where I was going. The results you've seen, which did achieve LDAS, is at dose level 1, single dose. We have the green light to go to a higher dose, and we have the green light to multi-dose within a treatment cycle. I'm hoping that the combination of those two, higher dose, multi-dose, will give you increased depth of response. As we talk about that as well, there's always FT839 and FT836 that we'll get to that are made to not require conditioning whatsoever and will give that depth of response. I'm sure we'll talk about next generation in a minute, but right now with FT819, in Regimen B, we are looking to increase the dose and look for a higher depth of response. Is there at some point it starts to get cost prohibitive to have multi-doses? Like, how many doses do you think is reasonable from your cog standpoint? To your point, there is a financial toxicity here as well. Definitely. I think once you start having five doses, six doses, seven doses of 1 billion cells, then, you know, it could potentially tilt. As I say this, tilt in the side of maybe not being preferred. Right now, our cost of goods is $3,000 a dose. The margins for that, in terms of having the ability to have meaningful revenue is still there. That's just at the current scale of 100 L volume. As we get to 1,000 L, as we get to 10,000 L scale, that 3,000 L becomes 1,000 L, becomes couple of hundred. As we might need to increase dose, we will increase scale, and then you can see that offset as again. There is a lot of levers to pull here as we think about multi-dosing. At the same time, there are next generation products that could go back to a single dose and no conditioning. I want to start to go down the commercial implications, which I think are interesting. Let's actually look because we only have six minutes left. Let's talk about the next generation. Maybe let's stick with the ones for autoimmune disease. Sure. What are you doing, and how is that gonna step up, and how are you gonna prioritize? I think the challenge with it has always been you can always do a next generation. How do you balance commitment to the current generation with moving to, like, what benefits you're gonna get? Absolutely. In the quick last few minutes, the next generation is multiplex edited. As FT819 was a tuned-down CAR into the TRAC locus for very defined specific activity, FT839 and FT836 are multiplexed. The Sword and Shield technology is common between the both of them. Sword and Shield is our way of eliminating the need for conditioning. It's not a way of hiding from the host immune system. It's a way of actually of completely eliminating the need for conditioning. As rejections and conditioning overcomes re-host rejection, conditioning overcomes the lack of space or creates space, conditioning creates a cytokine surplus by eliminating host immune system. All these things are important to CAR T as it needs to expand and grow. Others have used a more kind of, as I would capture it, as hide strategy, which would be kind of our Sword and Shield side. There is CD47, there is HLA-E, there's CD300a. These things are being used to suppress the in-host immune system. They all None of them are sufficient because if they were, every cancer in your body would be CD47, you know, would be expressing CD47, would have HLA-E, or would have CD300. Therapies have been made for CD47 and HLA-E. I don't think CD300's got much attention. In general, these things are not the holy grails. We do have a version of this. It's CD58. We eliminate cell-cell interactions, so effector cells cannot really interact with us as much. Even though CD58 is prominent in cancer, it's not the holy grail either. This is where our sword side comes in. It's an activating receptor that actually eliminates any effector cell that is activated upon cell-cell interactions. B cells, T cells, and NK cells, when they come and interact with us, if they overcome the CD2, CD58 interaction, and they interact with us, they will have to turn on 4-1BB to do something. Whether it has to kill us or have a response against us, we will kill it first because we will sense that, and our activating receptor will eliminate that cell and at the same time, give signal to our product to expand. It offsets all the, those unique attributes of conditioning. That's great. We have that. CD FT839 has a CD19 and a CD38 CAR. CD19 to deplete the B cell population as FT819 does as well, but also CD38 to eliminate the other aberrant cell types found in the immune compartment such as T cells. This gives you really a large breadth to go after multiple complex autoimmune diseases such as RA, that where the T cell compartment is playing a role, type 1 diabetes as well, and gives you a unique ability, and we haven't really talked about this, but to create immune tolerance. As you take on a graft and you give FT839, it can potentially give you the ability to eliminate the need for immune suppression because it can give you immune tolerance to the graft. We'll talk more about that second half of the year. For now, this is a broad targeting strategy that goes after complex diseases, including hematologic malignancies such as myeloma and lymphoma. It's almost a catchall for multiple diseases. It's also the brakes have been turned off, so it could actually expand in a very aggressive manner. Now, that's very different than what I said with FT819. Right now it's a safe product that we're very excited about because of the safety and efficacy profile. I don't think FT839 will come tomorrow and completely cannibalize our phase II trial because there's a safety component and then there's an efficacy component. The FT839 is reserved for more considerations where the disease is complex, the burden is high and conditioning is not used. That's a very different profile than FT819. You took those two mutations that we talked about previously, and you put them back in? Yeah. The, the CAR composition, in some scenarios does have the full intact CD3ζ ITAMs 1, 2, 3 are there, and it also has a T cell enhancer that we haven't talked about right now because I just don't want anybody to copy us until we have all the patents figured out. It actually, there's an inherent boost as well as intact CAR that drives the activity. You turned it up a lot. Did you turn it up too much? A lot of our safety studies suggest that it still behaves like a T cell. It expands and contracts as expected, but the peak of the expansion is very different than FT819. It's still CD8 only, and so that you get some advantages from that. Yeah. I actually haven't talked about that, so maybe you could mention the advantages of CD8. Sure. CD4s are helper, cells, so they actually augment CD8 activity. The actual killing comes from CD8. For us, when you have CD8 only is another way of controlling your product, the defined expansion and contraction. This again goes back to control. It's a single-layered product. You don't have the CD4s that may, change things. Again, you listen to Kite or you listen to Juno, they always had the CD4 CD8s discussion to how much- Yeah. how important are fours. In immunology, fours help eights. Again, we only have eights because we wanna have a more defined product. Got it. There's 30 seconds left. I'll see if anybody in the audience has a question. Bob? Yeah. I have one. Yeah. Thanks. Do you like Benda or cyclophosphamide? I like Benda more. That's what we're going with for our phase II. The reason I like that is because some of these patients have been exposed to Cy for a number of times. There's a discourage of using it. Also, Benda appears to have that initial improved kinetics in B cell depletion. It adds value with B cell depletion, but also it appears to be a different agent than what the patients have been getting, and that helps with patient enrollment. Is that gonna be challenging regulatory-wise for approval? I don't- Without the contribution in a single arm study? Translational data is actually nicely shows what Benda contributes and then what FT819 contributes because the effects of Benda are only for several days. When you see control of B cells and even further depletion of B cells after a week, it's you know that it's FT819 activity. That's well established, like outside of your own studies, the duration of Benda? Yeah. In terms of the immune cell compartment coming back after a couple of weeks, yes, that's well established. Okay. Awesome. Well, thank you all. Thanks for your attention.

Speaker 2: Good morning, everyone. My name is Daina Graybosch. I'm a Senior Equity Research Analyst here at Leerink Partners, and I'm excited to be hosting Fate Therapeutics and their CEO, Bob Valamehr, here for my first company fireside at this year's conference. That's exciting for me, and Fate is also one of the very first companies that I covered as an analyst. Actually, I think the only one that I still cover of the first few that I launched on. I'm excited about that history and also where you're going in the future. Welcome. Good morning, everyone. good morning everyone My name is Daina Graybosch. my name is daina graybosch I'm a Senior Equity Research Analyst here at Leerink Partners, and I'm excited to be hosting Fate Therapeutics and their CEO, Bob Valamehr, here for my first company fireside at this year's conference. i'm a senior equity research analyst here at leerink partners and i'm excited to be hosting fate therapeutics and their ceo bob valamehr here for my first company fireside at this year's conference That's exciting for me, and Fate is also one of the very first companies that I covered as an analyst. that's exciting for me and fate is also one of the very first companies that i covered as an analyst Actually, I think the only one that I still cover of the first few that I launched on. actually i think the only one that i still cover of the first few that i launched on I'm excited about that history and also where you're going in the future. i'm excited about that history and also where you're going in the future Welcome. welcome

Speaker 1: Thank you, Daina. Thanks for the invitation. Thank you, Daina. thank you daina Thanks for the invitation. thanks for the invitation

Speaker 2: I wanna jump right in 'cause we only have 29 minutes to talk about FT819, which is your leading allogeneic cell therapy program. It's a CAR T, to remind everybody who thinks about Fate as an NK cell therapy company. The leading program's now a CAR T. I wonder if you could give us an overview of its program and the edits, then we'll jump into the data and where it's going. I wanna jump right in 'cause we only have 29 minutes to talk about FT819, which is your leading allogeneic cell therapy program. i wanna jump right in 'cause we only have 29 minutes to talk about ft819 which is your leading allogeneic cell therapy program It's a CAR T, to remind everybody who thinks about Fate as an NK cell therapy company. it's a car t to remind everybody who thinks about fate as an nk cell therapy company The leading program's now a CAR T. the leading program's now a car t I wonder if you could give us an overview of its program and the edits, then we'll jump into the data and where it's going. i wonder if you could give us an overview of its program and the edits then we'll jump into the data and where it's going

Speaker 1: Sure thing. FT819, as you mentioned, Daina, is a CAR T-cell, is an off-the-shelf CAR T-cell. We view it very differently than other allogeneic, CAR T-cells in the fact that it has a master cell bank as a starting material. You essentially aren't chasing different donors, as your drug product, inventory, depletes. You have a starting population that with the concept of a master cell bank leading to a working cell bank using as a starting material to make trillions of cells, you actually end up with having over 10 million doses. That's what we calculate today, and I'm being a little bit conservative because that's. Sure thing. sure thing FT819, as you mentioned, Daina, is a CAR T-cell, is an off-the-shelf CAR T-cell. ft819 as you mentioned daina is a car t-cell is an off-the-shelf car t-cell We view it very differently than other allogeneic, CAR T-cells in the fact that it has a master cell bank as a starting material. we view it very differently than other allogeneic car t-cells in the fact that it has a master cell bank as a starting material You essentially aren't chasing different donors, as your drug product, inventory, depletes. you essentially aren't chasing different donors as your drug product inventory depletes You have a starting population that with the concept of a master cell bank leading to a working cell bank using as a starting material to make trillions of cells, you actually end up with having over 10 million doses. you have a starting population that with the concept of a master cell bank leading to a working cell bank using as a starting material to make trillions of cells you actually end up with having over 10 million doses That's what we calculate today, and I'm being a little bit conservative because that's. that's what we calculate today and i'm being a little bit conservative because that's

Speaker 2: Per master, per donor. Per master, per donor. per master per donor

Speaker 1: Per master- Per master- per master-

Speaker 2: $10 million. $10 million. $10 million

Speaker 1: Per master cell bank, you can make 10 million doses, and this is a dose that's around the magnitude of 1 billion cells. We're not cutting it low by, or we're not exaggerating the numbers by having a low dose. This becomes a drug product that pharmaceutical companies are used to. Just like a monoclonal antibody or even aspirin, the starting material is there. It's been already edited. It is pure in population because the starting population is a clonal product. It's very different than allogeneic or autologous programs that are from T-cells, and these cells have been engineered, of course, but they have been engineered in a way where it's heterogeneous. The e-engineering event is stochastic, so some cells have the engineered entity, some cells don't, and those that have been engineered may not be properly engineered. Per master cell bank, you can make 10 million doses, and this is a dose that's around the magnitude of 1 billion cells. per master cell bank you can make 10 million doses and this is a dose that's around the magnitude of 1 billion cells We're not cutting it low by, or we're not exaggerating the numbers by having a low dose. we're not cutting it low by or we're not exaggerating the numbers by having a low dose This becomes a drug product that pharmaceutical companies are used to. this becomes a drug product that pharmaceutical companies are used to Just like a monoclonal antibody or even aspirin, the starting material is there. just like a monoclonal antibody or even aspirin the starting material is there It's been already edited. it's been already edited It is pure in population because the starting population is a clonal product. it is pure in population because the starting population is a clonal product It's very different than allogeneic or autologous programs that are from T-cells, and these cells have been engineered, of course, but they have been engineered in a way where it's heterogeneous. it's very different than allogeneic or autologous programs that are from t-cells and these cells have been engineered of course but they have been engineered in a way where it's heterogeneous The e-engineering event is stochastic, so some cells have the engineered entity, some cells don't, and those that have been engineered may not be properly engineered. the e-engineering event is stochastic so some cells have the engineered entity some cells don't and those that have been engineered may not be properly engineered You're taking that heterogeneous population into the patient, and it could result in unexpected results, and that's not something we want with drugs. For us, you know, we've been working on this for 17 years, 18 years now, and the concept has always been using a master cell bank to start the manufacturing process. Every time we make a batch, it's uniform, it's consistent, it's the same. When we talk about FT819 in oncology, and we talk about FT819 in autoimmune, we're talking about the same product. It is essentially it starts from the same place and is tested to be the same. How do we come across FT819? FT819 stands for CD8, which is a 8, and it's targeting CD19, which is the 1 and the 9. You're taking that heterogeneous population into the patient, and it could result in unexpected results, and that's not something we want with drugs. you're taking that heterogeneous population into the patient and it could result in unexpected results and that's not something we want with drugs For us, you know, we've been working on this for 17 years, 18 years now, and the concept has always been using a master cell bank to start the manufacturing process. for us you know we've been working on this for 17 years 18 years now and the concept has always been using a master cell bank to start the manufacturing process Every time we make a batch, it's uniform, it's consistent, it's the same. every time we make a batch it's uniform it's consistent it's the same When we talk about FT819 in oncology, and we talk about FT819 in autoimmune, we're talking about the same product. when we talk about ft819 in oncology and we talk about ft819 in autoimmune we're talking about the same product It is essentially it starts from the same place and is tested to be the same. it is essentially it starts from the same place and is tested to be the same How do we come across FT819? how do we come across ft819 FT819 stands for CD8, which is a 8, and it's targeting CD19, which is the 1 and the 9. ft819 stands for cd8 which is a 8 and it's targeting cd19 which is the 1 and the 9 It's a CD8 targeting CD19. Hopefully everybody remembers that going forward. When we started this, safety was important to us. Activity was important as well, but safety was also very important. We fine-tuned the CAR motif, the chimeric antigen receptor, has a costim domain, has a signaling domain, and we want to make sure that we preserve that ability of these cells to respond to antigen and expand because that's very important. That's why it makes CAR T so unique, and I'll get into that in a second. We also wanted to make sure that that expansion is controlled. It's a CD8 targeting CD19. it's a cd8 targeting cd19 Hopefully everybody remembers that going forward. hopefully everybody remembers that going forward When we started this, safety was important to us. when we started this safety was important to us Activity was important as well, but safety was also very important. activity was important as well but safety was also very important We fine-tuned the CAR motif, the chimeric antigen receptor, has a costim domain, has a signaling domain, and we want to make sure that we preserve that ability of these cells to respond to antigen and expand because that's very important. we fine-tuned the car motif the chimeric antigen receptor has a costim domain has a signaling domain and we want to make sure that we preserve that ability of these cells to respond to antigen and expand because that's very important That's why it makes CAR T so unique, and I'll get into that in a second. that's why it makes car t so unique and i'll get into that in a second We also wanted to make sure that that expansion is controlled. we also wanted to make sure that that expansion is controlled Because CAR T has a safety component, if you have too much of an expansion, as these CAR T-cells come across antigen disease and they wanna expand, and that burden forces them to expand even more than you know, than you would like, you end up having adverse events. For us, it's controlled. We've treated nearly 70 patients now, and every time we get very similar results, similar product giving us similar results. Because we've tuned down the activity to compensate for and balance for safety, when we were in aggressive DLBCL, we did see the complete response rates. It was about 40% in CAR patients, but the durability wasn't there. Because CAR T has a safety component, if you have too much of an expansion, as these CAR T-cells come across antigen disease and they wanna expand, and that burden forces them to expand even more than you know, than you would like, you end up having adverse events. because car t has a safety component if you have too much of an expansion as these car t-cells come across antigen disease and they wanna expand and that burden forces them to expand even more than you know than you would like you end up having adverse events For us, it's controlled. for us it's controlled We've treated nearly 70 patients now, and every time we get very similar results, similar product giving us similar results. we've treated nearly 70 patients now and every time we get very similar results similar product giving us similar results Because we've tuned down the activity to compensate for and balance for safety, when we were in aggressive DLBCL, we did see the complete response rates. because we've tuned down the activity to compensate for and balance for safety when we were in aggressive dlbcl we did see the complete response rates It was about 40% in CAR patients, but the durability wasn't there. it was about 40% in car patients but the durability wasn't there That's because the CAR built in a certain way, so that when it went against aggressive disease like DLBCL and its 5 lbs of tumor, it ended up not being able to hold up 'cause it was designed that way. When we are shifting focus to autoimmune, we're seeing something very different. We saw that some of that glimpse in indolent lymphoma where the disease burden is less. When we shift over to autoimmune, that becomes a perfect balance between activity and safety. The tumor burden I mean, the disease burden is less, FT819 is capable of controlling the disease and eliminating it. At the same time, the safety is there. That's because the CAR built in a certain way, so that when it went against aggressive disease like DLBCL and its 5 lbs of tumor, it ended up not being able to hold up 'cause it was designed that way. that's because the car built in a certain way so that when it went against aggressive disease like dlbcl and its 5 lbs of tumor it ended up not being able to hold up 'cause it was designed that way When we are shifting focus to autoimmune, we're seeing something very different. when we are shifting focus to autoimmune we're seeing something very different We saw that some of that glimpse in indolent lymphoma where the disease burden is less. we saw that some of that glimpse in indolent lymphoma where the disease burden is less When we shift over to autoimmune, that becomes a perfect balance between activity and safety. when we shift over to autoimmune that becomes a perfect balance between activity and safety The tumor burden I mean, the disease burden is less, FT819 is capable of controlling the disease and eliminating it. the tumor burden i mean the disease burden is less ft819 is capable of controlling the disease and eliminating it At the same time, the safety is there. at the same time the safety is there In this patient population of autoimmune where it's not a disease of urgency, it's more a disease of long-term maintenance. We're able to go in and give the patient a unique ability to have a safe and effective drug. That's where we are right now. We're advancing FT819 in lupus nephritis and renal lupus, but also in myositis, systemic sclerosis, and vasculitis. In this patient population of autoimmune where it's not a disease of urgency, it's more a disease of long-term maintenance. in this patient population of autoimmune where it's not a disease of urgency it's more a disease of long-term maintenance We're able to go in and give the patient a unique ability to have a safe and effective drug. we're able to go in and give the patient a unique ability to have a safe and effective drug That's where we are right now. that's where we are right now We're advancing FT819 in lupus nephritis and renal lupus, but also in myositis, systemic sclerosis, and vasculitis. we're advancing ft819 in lupus nephritis and renal lupus but also in myositis systemic sclerosis and vasculitis

Speaker 2: Tell me how you designed it that way that it wouldn't have durability. Help me understand that a little bit more. Like what specifically in the design led to the lack of durability? Tell me how you designed it that way that it wouldn't have durability. tell me how you designed it that way that it wouldn't have durability Help me understand that a little bit more. help me understand that a little bit more Like what specifically in the design led to the lack of durability? like what specifically in the design led to the lack of durability

Speaker 1: The items two and three of the CD3 signaling domain are mutated out. Typically a CAR, a chimeric antigen receptor, engages with its antigen that's targeting, and then you have the CD28 signaling domain or 4-1BB, 4-1BB signaling co-stimulatory, and you have the CD3ζ signaling domain. These two together give the T cells the ability to react and eliminate the target. What we've done is we've knocked out two of the three activating motifs, CD3ζ, and that allows us to still have expansion and activity, but not to the level that is uncontrolled. The items two and three of the CD3 signaling domain are mutated out. the items two and three of the cd3 signaling domain are mutated out Typically a CAR, a chimeric antigen receptor, engages with its antigen that's targeting, and then you have the CD28 signaling domain or 4-1BB, 4-1BB signaling co-stimulatory, and you have the CD3ζ signaling domain. typically a car a chimeric antigen receptor engages with its antigen that's targeting and then you have the cd28 signaling domain or 4-1bb 4-1bb signaling co-stimulatory and you have the cd3ζ signaling domain These two together give the T cells the ability to react and eliminate the target. these two together give the t cells the ability to react and eliminate the target What we've done is we've knocked out two of the three activating motifs, CD3ζ, and that allows us to still have expansion and activity, but not to the level that is uncontrolled. what we've done is we've knocked out two of the three activating motifs cd3ζ and that allows us to still have expansion and activity but not to the level that is uncontrolled

Speaker 2: You think that it's just then you have activity, it's just not enough to get all that tumor burden clearance. You're not getting the depth. It's more about you just can't get the depth of response of high tumor burden? You think that it's just then you have activity, it's just not enough to get all that tumor burden clearance. you think that it's just then you have activity it's just not enough to get all that tumor burden clearance You're not getting the depth. you're not getting the depth It's more about you just can't get the depth of response of high tumor burden? it's more about you just can't get the depth of response of high tumor burden

Speaker 1: Yeah. I think in situations where you have disease levels of 10 to the 10 cells, for example, a 5-lb tumor is in the order of 10 to the 10 cells, you're not getting rid of every single cell because you're just not built that way. You end up having durability, not in a way that you prefer. In indolent lymphoma, where the disease burden is closer to 10 to the nine or 10 to the eight, you do get that durability. Yeah. yeah I think in situations where you have disease levels of 10 to the 10 cells, for example, a 5-lb tumor is in the order of 10 to the 10 cells, you're not getting rid of every single cell because you're just not built that way. i think in situations where you have disease levels of 10 to the 10 cells for example a 5-lb tumor is in the order of 10 to the 10 cells you're not getting rid of every single cell because you're just not built that way You end up having durability, not in a way that you prefer. you end up having durability not in a way that you prefer In indolent lymphoma, where the disease burden is closer to 10 to the nine or 10 to the eight, you do get that durability. in indolent lymphoma where the disease burden is closer to 10 to the nine or 10 to the eight you do get that durability

Speaker 2: How many cells are in I mean, in autoimmune disease, you're targeting normal cells. How many cells are in I mean, in autoimmune disease, you're targeting normal cells. how many cells are in i mean in autoimmune disease you're targeting normal cells

Speaker 1: Yes. Yes. yes

Speaker 2: The order, so we know the magnitude. The order, so we know the magnitude. the order so we know the magnitude

Speaker 1: 10 to the eight. We believe that in B cell diseases of rheumatology, the disease is somewhere between 10 to the eight and 10 to the nine. Normal levels, these are few B cells that are either some sort of environmental stimuli or, some sort of genetic predisposition has caused them to attack the host itself. There aren't as many as the 5 lbs of tumor. When the disease burden is different, then your effector target ratio is in your favor with FT819. 10 to the eight. 10 to the eight We believe that in B cell diseases of rheumatology, the disease is somewhere between 10 to the eight and 10 to the nine. we believe that in b cell diseases of rheumatology the disease is somewhere between 10 to the eight and 10 to the nine Normal levels, these are few B cells that are either some sort of environmental stimuli or, some sort of genetic predisposition has caused them to attack the host itself. normal levels these are few b cells that are either some sort of environmental stimuli or some sort of genetic predisposition has caused them to attack the host itself There aren't as many as the 5 lbs of tumor. there aren't as many as the 5 lbs of tumor When the disease burden is different, then your effector target ratio is in your favor with FT819. when the disease burden is different then your effector target ratio is in your favor with ft819

Speaker 2: Got it. Got it. got it

Speaker 1: Maybe I'll add any CAR T cell, the uniqueness of CAR T cells is that they respond to the disease. Unlike monoclonal antibodies or T-cell engagers, where you take the medicine and it decays over time in a declining manner from the get-go, this is very different. CAR Ts expand and rise up to the occasion depending on the disease burden they face. You have a living drug fighting disease in a very different paradigm than traditional medicine. Maybe I'll add any CAR T cell, the uniqueness of CAR T cells is that they respond to the disease. maybe i'll add any car t cell the uniqueness of car t cells is that they respond to the disease Unlike monoclonal antibodies or T-cell engagers, where you take the medicine and it decays over time in a declining manner from the get-go, this is very different. unlike monoclonal antibodies or t-cell engagers where you take the medicine and it decays over time in a declining manner from the get-go this is very different CAR Ts expand and rise up to the occasion depending on the disease burden they face. car ts expand and rise up to the occasion depending on the disease burden they face You have a living drug fighting disease in a very different paradigm than traditional medicine. you have a living drug fighting disease in a very different paradigm than traditional medicine

Speaker 2: Got it. With FT819 this year, in respect to what we're gonna see in terms of the maturation of the program and the clinical scale, and I know you're readying yourself for a pivotal trial, can you just give us a scope of what we'll see and what you're gonna accomplish this year? Got it. got it With FT819 this year, in respect to what we're gonna see in terms of the maturation of the program and the clinical scale, and I know you're readying yourself for a pivotal trial, can you just give us a scope of what we'll see and what you're gonna accomplish this year? with ft819 this year in respect to what we're gonna see in terms of the maturation of the program and the clinical scale and i know you're readying yourself for a pivotal trial can you just give us a scope of what we'll see and what you're gonna accomplish this year

Speaker 1: Absolutely. I think we made great progress with FT819 in lupus. Some of those things were already inherent in the product, such as accessibility. This is an off-the-shelf product, as I mentioned earlier. We are capable of making about 50,000 doses in our current facility at full scale. That's hiring more people, not requiring more space or more capital. It's just simply hiring a number of manufacturing folks to do that. That scale, with the cost of goods down already at $3,000 really gives us a unique advantage. On top of that, now you're on-demand and off-the-shelf, but as we mentioned a couple of weeks ago, we're now doing this in outpatient therapy. When you get this medication, you're not being held in the hospital 14 days. It's just like any other medicine. Absolutely. absolutely I think we made great progress with FT819 in lupus. i think we made great progress with ft819 in lupus Some of those things were already inherent in the product, such as accessibility. some of those things were already inherent in the product such as accessibility This is an off-the-shelf product, as I mentioned earlier. this is an off-the-shelf product as i mentioned earlier We are capable of making about 50,000 doses in our current facility at full scale. we are capable of making about 50,000 doses in our current facility at full scale That's hiring more people, not requiring more space or more capital. that's hiring more people not requiring more space or more capital It's just simply hiring a number of manufacturing folks to do that. it's just simply hiring a number of manufacturing folks to do that That scale, with the cost of goods down already at $3,000 really gives us a unique advantage. that scale with the cost of goods down already at $3,000 really gives us a unique advantage On top of that, now you're on-demand and off-the-shelf, but as we mentioned a couple of weeks ago, we're now doing this in outpatient therapy. on top of that now you're on-demand and off-the-shelf but as we mentioned a couple of weeks ago we're now doing this in outpatient therapy When you get this medication, you're not being held in the hospital 14 days. when you get this medication you're not being held in the hospital 14 days It's just like any other medicine. it's just like any other medicine You get a CAR T, it's very unique for CAR T. You get it that day, and you go home. This really gives the patient accessibility. A lot of patients in lupus are working. They've been living with this disease for a very long time, and they have a life to live. They cannot stay in the hospital for 14 days. I don't think anybody wants to stay in the hospital for 14 days. There's a lot of pre-work to get your CAR T made that requires you to often go to the hospital to procure your T cells. You have to get off your current medication. It's a very complex process to get CAR T. What we've done is we've made it just like any other product, and you get the CAR T when the prescription is written. You get a CAR T, it's very unique for CAR T. you get a car t it's very unique for car t You get it that day, and you go home. you get it that day and you go home This really gives the patient accessibility. this really gives the patient accessibility A lot of patients in lupus are working. a lot of patients in lupus are working They've been living with this disease for a very long time, and they have a life to live. they've been living with this disease for a very long time and they have a life to live They cannot stay in the hospital for 14 days. they cannot stay in the hospital for 14 days I don't think anybody wants to stay in the hospital for 14 days. i don't think anybody wants to stay in the hospital for 14 days There's a lot of pre-work to get your CAR T made that requires you to often go to the hospital to procure your T cells. there's a lot of pre-work to get your car t made that requires you to often go to the hospital to procure your t cells You have to get off your current medication. you have to get off your current medication It's a very complex process to get CAR T. it's a very complex process to get car t What we've done is we've made it just like any other product, and you get the CAR T when the prescription is written. what we've done is we've made it just like any other product and you get the car t when the prescription is written You take that element, you take the efficacy we're seeing in terms of decreasing the disease burden according to SLEDAI scores, improving the patient's health in terms of improving PGA and FACIT-fatigue. This is quite remarkable. You're getting patients that are bedridden that within a month or two are able to go out, be out and about and go back to their jobs. This is quite an amazing leap for autoimmune. You combine all that and the safety profile where we've had no ICANS, no GVHD, and also low-grade CRS, it's really takes the fear out of getting cell therapy and makes it accessible. You take that element, you take the efficacy we're seeing in terms of decreasing the disease burden according to SLEDAI scores, improving the patient's health in terms of improving PGA and FACIT-fatigue. you take that element you take the efficacy we're seeing in terms of decreasing the disease burden according to sledai scores improving the patient's health in terms of improving pga and facit-fatigue This is quite remarkable. this is quite remarkable You're getting patients that are bedridden that within a month or two are able to go out, be out and about and go back to their jobs. you're getting patients that are bedridden that within a month or two are able to go out be out and about and go back to their jobs This is quite an amazing leap for autoimmune. this is quite an amazing leap for autoimmune You combine all that and the safety profile where we've had no ICANS, no GVHD, and also low-grade CRS, it's really takes the fear out of getting cell therapy and makes it accessible. you combine all that and the safety profile where we've had no icans no gvhd and also low-grade crs it's really takes the fear out of getting cell therapy and makes it accessible We've had, under RMAT designation, we've had several meetings with the FDA where we have really paved the path in terms of, as you mentioned earlier, what it takes to get into a pivotal study. The phase II, the, as I've been saying, the domino pieces are falling and we're making great progress to commence that trial the second half of the year. This will be a phase II potential registration enabling study where we'll be focusing on lupus nephritis. Complete renal response will be the primary endpoint. We feel very confident that this will be a successful trial. The way we're enrolling, I think we can complete this single-arm study in short order. We've had, under RMAT designation, we've had several meetings with the FDA where we have really paved the path in terms of, as you mentioned earlier, what it takes to get into a pivotal study. we've had under rmat designation we've had several meetings with the fda where we have really paved the path in terms of as you mentioned earlier what it takes to get into a pivotal study The phase II, the, as I've been saying, the domino pieces are falling and we're making great progress to commence that trial the second half of the year. the phase ii the as i've been saying the domino pieces are falling and we're making great progress to commence that trial the second half of the year This will be a phase II potential registration enabling study where we'll be focusing on lupus nephritis. this will be a phase ii potential registration enabling study where we'll be focusing on lupus nephritis Complete renal response will be the primary endpoint. complete renal response will be the primary endpoint We feel very confident that this will be a successful trial. we feel very confident that this will be a successful trial The way we're enrolling, I think we can complete this single-arm study in short order. the way we're enrolling i think we can complete this single-arm study in short order

Speaker 2: Talk about, so you've chosen lupus nephritis and complete renal response. Can you talk about what you've shown against that endpoint so far? I think you had presentations at ACR and ASH. Talk about, so you've chosen lupus nephritis and complete renal response. talk about so you've chosen lupus nephritis and complete renal response Can you talk about what you've shown against that endpoint so far? can you talk about what you've shown against that endpoint so far I think you had presentations at ACR and ASH. i think you had presentations at acr and ash

Speaker 1: Mm-hmm. Mm-hmm. mm-hmm

Speaker 2: What we'll see this year both in terms of how well you're doing, but maybe you could give it some context of compared to other standard therapies? We just had obinutuzumab approved, for instance. What we'll see this year both in terms of how well you're doing, but maybe you could give it some context of compared to other standard therapies? what we'll see this year both in terms of how well you're doing but maybe you could give it some context of compared to other standard therapies We just had obinutuzumab approved, for instance. we just had obinutuzumab approved for instance

Speaker 1: No, certainly. The first two patients that have reached six months have achieved a complete renal response. What we're hoping to show in additional conferences this year is further strengthening that observation. I think just like other CAR T-cells, we're seeing very dramatic responses within the first few months. This is very different than monoclonal antibodies or T-cell engagers. This is a single treatment, and I should add that with our paradigm, we're actually using less intensive conditioning. Traditional CAR T-cells, whether it's auto, allo, are doing three days of cyclophosphamide and fludarabine combination. That's very intensive, and in our experience, not preferred because that was an option in our study as well, and no PI took that option. Every PI took either cyclophosphamide alone or bendamustine alone. No, certainly. no certainly The first two patients that have reached six months have achieved a complete renal response. the first two patients that have reached six months have achieved a complete renal response What we're hoping to show in additional conferences this year is further strengthening that observation. what we're hoping to show in additional conferences this year is further strengthening that observation I think just like other CAR T-cells, we're seeing very dramatic responses within the first few months. i think just like other car t-cells we're seeing very dramatic responses within the first few months This is very different than monoclonal antibodies or T-cell engagers. this is very different than monoclonal antibodies or t-cell engagers This is a single treatment, and I should add that with our paradigm, we're actually using less intensive conditioning. this is a single treatment and i should add that with our paradigm we're actually using less intensive conditioning Traditional CAR T-cells, whether it's auto, allo, are doing three days of cyclophosphamide and fludarabine combination. traditional car t-cells whether it's auto allo are doing three days of cyclophosphamide and fludarabine combination That's very intensive, and in our experience, not preferred because that was an option in our study as well, and no PI took that option. that's very intensive and in our experience not preferred because that was an option in our study as well and no pi took that option Every PI took either cyclophosphamide alone or bendamustine alone. every pi took either cyclophosphamide alone or bendamustine alone The results we're getting is even extra rosy because it's getting accomplished in such a way without intensive conditioning, which not only distracts patients from wanting to be treated, but also puts a question in the efficacy of the product. Here, we're very confident that FT819 has activity because we also have Regimen B that well, I'm sure we'll talk about that there's no conditioning, and we see activity there. To your question, we hope to further strengthen our results this summer. When we treat the first patient later this year, in our phase II study, I think that's where kind of it all comes together and everybody sees a path forward. The results we're getting is even extra rosy because it's getting accomplished in such a way without intensive conditioning, which not only distracts patients from wanting to be treated, but also puts a question in the efficacy of the product. the results we're getting is even extra rosy because it's getting accomplished in such a way without intensive conditioning which not only distracts patients from wanting to be treated but also puts a question in the efficacy of the product Here, we're very confident that FT819 has activity because we also have Regimen B that well, I'm sure we'll talk about that there's no conditioning, and we see activity there. here we're very confident that ft819 has activity because we also have regimen b that well i'm sure we'll talk about that there's no conditioning and we see activity there To your question, we hope to further strengthen our results this summer. to your question we hope to further strengthen our results this summer When we treat the first patient later this year, in our phase II study, I think that's where kind of it all comes together and everybody sees a path forward. when we treat the first patient later this year in our phase ii study i think that's where kind of it all comes together and everybody sees a path forward

Speaker 2: How many patients? Just like the scope of how many we might see. How many patients? how many patients Just like the scope of how many we might see. just like the scope of how many we might see

Speaker 1: You know, we've already treated 15 lupus patients and 20 total patients. There was a nice figure by Wedbush that showed us basically reaching second place now in terms of how many lupus patients treated. That has to do a lot with the last six months, the exposure we've gotten from different sites in terms of them being somewhat frustrated with the mechanics of auto CAR T accessibility to product, lack of patient interest, and also the activity we're seeing. A lot of the PIs are talking to other PIs, and we're getting more sites, more patients. We're, I think we'll be probably somewhere close to 25 lupus patients by summertime, but I think, you know, you obviously, you need a follow-up three to six months. You know, we've already treated 15 lupus patients and 20 total patients. you know we've already treated 15 lupus patients and 20 total patients There was a nice figure by Wedbush that showed us basically reaching second place now in terms of how many lupus patients treated. there was a nice figure by wedbush that showed us basically reaching second place now in terms of how many lupus patients treated That has to do a lot with the last six months, the exposure we've gotten from different sites in terms of them being somewhat frustrated with the mechanics of auto CAR T accessibility to product, lack of patient interest, and also the activity we're seeing. that has to do a lot with the last six months the exposure we've gotten from different sites in terms of them being somewhat frustrated with the mechanics of auto car t accessibility to product lack of patient interest and also the activity we're seeing A lot of the PIs are talking to other PIs, and we're getting more sites, more patients. a lot of the pis are talking to other pis and we're getting more sites more patients We're, I think we'll be probably somewhere close to 25 lupus patients by summertime, but I think, you know, you obviously, you need a follow-up three to six months. we're i think we'll be probably somewhere close to 25 lupus patients by summertime but i think you know you obviously you need a follow-up three to six months We're expecting somewhere close to 15 patients with six-month follow-up by mid this year. We're expecting somewhere close to 15 patients with six-month follow-up by mid this year. we're expecting somewhere close to 15 patients with six-month follow-up by mid this year

Speaker 2: They'll all be nephritis patients? They'll all be nephritis patients? they'll all be nephritis patients

Speaker 1: No, some of them will be extra-renal. No, some of them will be extra-renal. no some of them will be extra-renal

Speaker 2: Okay. Okay. okay

Speaker 1: There will probably be half of those will be, lupus nephritis patients. There will probably be half of those will be, lupus nephritis patients. there will probably be half of those will be lupus nephritis patients

Speaker 2: Why are you doing that even though your registration study is gonna be in nephritis? Why not put every single one of these first patients a nephritis one? Why are you doing that even though your registration study is gonna be in nephritis? why are you doing that even though your registration study is gonna be in nephritis Why not put every single one of these first patients a nephritis one? why not put every single one of these first patients a nephritis one

Speaker 1: We treat all comers in lupus. It just happens to be half of the population of SLE are lupus nephritis patients. We also have intention of moving forward with extra-renal. On that front, we're in discussion with the FDA on the primary endpoint. We're still discussing that strategy, but we believe that somewhere between SRI-4 and DORIS, there is a meaningful path. The challenge with DORIS is it hasn't been used previously for approval, and current therapies are being basically approved on SRI-4. From my perspective, you know, potentially SRI-4 with a safe product can be a path forward. We're having that conversation now whether extra-renal is a confirmation study to lupus nephritis or extra-renal is its own study. We treat all comers in lupus. we treat all comers in lupus It just happens to be half of the population of SLE are lupus nephritis patients. it just happens to be half of the population of sle are lupus nephritis patients We also have intention of moving forward with extra-renal. we also have intention of moving forward with extra-renal On that front, we're in discussion with the FDA on the primary endpoint. on that front we're in discussion with the fda on the primary endpoint We're still discussing that strategy, but we believe that somewhere between SRI-4 and DORIS, there is a meaningful path. we're still discussing that strategy but we believe that somewhere between sri-4 and doris there is a meaningful path The challenge with DORIS is it hasn't been used previously for approval, and current therapies are being basically approved on SRI-4. the challenge with doris is it hasn't been used previously for approval and current therapies are being basically approved on sri-4 From my perspective, you know, potentially SRI-4 with a safe product can be a path forward. from my perspective you know potentially sri-4 with a safe product can be a path forward We're having that conversation now whether extra-renal is a confirmation study to lupus nephritis or extra-renal is its own study. we're having that conversation now whether extra-renal is a confirmation study to lupus nephritis or extra-renal is its own study We're developing that, but there is a path forward here for extra-renal as well. We'll have more information on that second half of the year. As we accumulate extra-renal data, I think it's prudent to consider that as another product that will go into commercial stage. We're developing that, but there is a path forward here for extra-renal as well. we're developing that but there is a path forward here for extra-renal as well We'll have more information on that second half of the year. we'll have more information on that second half of the year As we accumulate extra-renal data, I think it's prudent to consider that as another product that will go into commercial stage. as we accumulate extra-renal data i think it's prudent to consider that as another product that will go into commercial stage

Speaker 2: What's wrong with SRI-4? You just think it's not gonna demonstrate how great you are? What's wrong with SRI-4? what's wrong with sri-4 You just think it's not gonna demonstrate how great you are? you just think it's not gonna demonstrate how great you are

Speaker 1: No, I don't think there's anything wrong with SRI-4. No, I don't think there's anything wrong with SRI-4. no i don't think there's anything wrong with sri-4

Speaker 2: Okay. Okay. okay

Speaker 1: I love it, but I think the auto CAR T stigma is holding CAR T accountable to a different level than all other approved products. I think it's our burden to show the FDA and other regulatory agencies the safety of FT819, the uniqueness of FT819, and allowing us to play in the same field as currently approved products. When you do that, FT819 is far superior over obinutuzumab, is far superior over voclosporin, things that are currently being used today. You just see the dramatic difference. It's, it's up to us to show the safety, the accessibility, and once we do that, and the costs are good, and once we do that, I think we should be in the same ballpark as other approved products. I love it, but I think the auto CAR T stigma is holding CAR T accountable to a different level than all other approved products. i love it but i think the auto car t stigma is holding car t accountable to a different level than all other approved products I think it's our burden to show the FDA and other regulatory agencies the safety of FT819, the uniqueness of FT819, and allowing us to play in the same field as currently approved products. i think it's our burden to show the fda and other regulatory agencies the safety of ft819 the uniqueness of ft819 and allowing us to play in the same field as currently approved products When you do that, FT819 is far superior over obinutuzumab, is far superior over voclosporin, things that are currently being used today. when you do that ft819 is far superior over obinutuzumab is far superior over voclosporin things that are currently being used today You just see the dramatic difference. you just see the dramatic difference It's, it's up to us to show the safety, the accessibility, and once we do that, and the costs are good, and once we do that, I think we should be in the same ballpark as other approved products. it's it's up to us to show the safety the accessibility and once we do that and the costs are good and once we do that i think we should be in the same ballpark as other approved products

Speaker 2: The auto CAR T are gonna go after DORIS. The auto CAR T are gonna go after DORIS. the auto car t are gonna go after doris

Speaker 1: They might have to. They might have to. they might have to

Speaker 2: That's the bar. You assume they're gonna go for DORIS. That's the bar. Do you think, can FT819 meet the same DORIS? I mean, we see all this data, but it's all small and from different institutions. That's the bar. that's the bar You assume they're gonna go for DORIS. you assume they're gonna go for doris That's the bar. that's the bar Do you think, can FT819 meet the same DORIS? do you think can ft819 meet the same doris I mean, we see all this data, but it's all small and from different institutions. i mean we see all this data but it's all small and from different institutions

Speaker 1: Mm-hmm. Mm-hmm. mm-hmm

Speaker 2: Like, what do you think? Like, what do you think? like what do you think

Speaker 1: Yeah, you know, that's a good point. Let me say, we have achieved DORIS with the first patient, and it was a meaningful durability. I think that while DORIS is a great bar to achieve, you don't need to go that far. I think a lot of patients today will significantly benefit from the improvements in disease that we're seeing, with a product that can be accessible. While I think auto CAR T's being held to a higher bar because of all the cost, the challenges, safety, we're starting to be treated looking like and feel like any other medicine today that's out there, such as a mAb or a T-cell engager. I would say we're at an advantage because of the single administration as well. Yeah, you know, that's a good point. yeah you know that's a good point Let me say, we have achieved DORIS with the first patient, and it was a meaningful durability. let me say we have achieved doris with the first patient and it was a meaningful durability I think that while DORIS is a great bar to achieve, you don't need to go that far. i think that while doris is a great bar to achieve you don't need to go that far I think a lot of patients today will significantly benefit from the improvements in disease that we're seeing, with a product that can be accessible. i think a lot of patients today will significantly benefit from the improvements in disease that we're seeing with a product that can be accessible While I think auto CAR T's being held to a higher bar because of all the cost, the challenges, safety, we're starting to be treated looking like and feel like any other medicine today that's out there, such as a mAb or a T-cell engager. while i think auto car t's being held to a higher bar because of all the cost the challenges safety we're starting to be treated looking like and feel like any other medicine today that's out there such as a mab or a t-cell engager I would say we're at an advantage because of the single administration as well. i would say we're at an advantage because of the single administration as well The patient comes in on Thursday, gets conditioning, goes home, comes back on Monday, gets treated, and that's it. That's very different than mAbs and T-cell engagers that you're constantly being treated and which also has its issues with safety as well. The patient comes in on Thursday, gets conditioning, goes home, comes back on Monday, gets treated, and that's it. the patient comes in on thursday gets conditioning goes home comes back on monday gets treated and that's it That's very different than mAbs and T-cell engagers that you're constantly being treated and which also has its issues with safety as well. that's very different than mabs and t-cell engagers that you're constantly being treated and which also has its issues with safety as well

Speaker 2: Let's talk about the conditioning. You said that you had a lot of options in the trial. You had cohorts that you could either get regular conditioning, Benda alone, Cy alone, also you had this cohort or patients stay on their immunosuppressive drugs. Let's talk about the conditioning. let's talk about the conditioning You said that you had a lot of options in the trial. you said that you had a lot of options in the trial You had cohorts that you could either get regular conditioning, Benda alone, Cy alone, also you had this cohort or patients stay on their immunosuppressive drugs. you had cohorts that you could either get regular conditioning benda alone cy alone also you had this cohort or patients stay on their immunosuppressive drugs

Speaker 1: Mm-hmm. Mm-hmm. mm-hmm

Speaker 2: Rather than going off of them and getting a different conditioning, that's sufficient. Can you tell us about that regimen, and what it looked like? Is there a path forward there and where you would take that sort of non-conditioning, use your regular standard therapy? Rather than going off of them and getting a different conditioning, that's sufficient. rather than going off of them and getting a different conditioning that's sufficient Can you tell us about that regimen, and what it looked like? can you tell us about that regimen and what it looked like Is there a path forward there and where you would take that sort of non-conditioning, use your regular standard therapy? is there a path forward there and where you would take that sort of non-conditioning use your regular standard therapy

Speaker 1: That's excellent, lead into question because here this is where you're thinking about SRI-4 now because now you have Regimen B. There's no conditioning here. You give FT819 on top of maintenance therapy with the hopes of having the patient actually come off their maintenance therapy with improvement in disease. Here, this is simply now FT819 given on top of current therapy. That's how every mAb or T-cell engager is being tested. What we're seeing here is that we are seeing a significant, and meaningful, decrease in disease, especially as with patient one, as we've shown. We have additional patient data, and I hope we are able to show that by summer, or we're planning to show that by summer timeframe. Here now, this is where I'm talking about SRI-4. That's excellent, lead into question because here this is where you're thinking about SRI-4 now because now you have Regimen B. that's excellent lead into question because here this is where you're thinking about sri-4 now because now you have regimen b There's no conditioning here. there's no conditioning here You give FT819 on top of maintenance therapy with the hopes of having the patient actually come off their maintenance therapy with improvement in disease. you give ft819 on top of maintenance therapy with the hopes of having the patient actually come off their maintenance therapy with improvement in disease Here, this is simply now FT819 given on top of current therapy. here this is simply now ft819 given on top of current therapy That's how every mAb or T-cell engager is being tested. that's how every mab or t-cell engager is being tested What we're seeing here is that we are seeing a significant, and meaningful, decrease in disease, especially as with patient one, as we've shown. what we're seeing here is that we are seeing a significant and meaningful decrease in disease especially as with patient one as we've shown We have additional patient data, and I hope we are able to show that by summer, or we're planning to show that by summer timeframe. we have additional patient data and i hope we are able to show that by summer or we're planning to show that by summer timeframe Here now, this is where I'm talking about SRI-4. here now this is where i'm talking about sri-4 You're just like every other biologic out there. You, you're being added to what patients are currently getting. You're gonna have a meaningful results, and then you might come off maintenance therapy. That is something that as I talked about a confirmation study in extrarenal, as I talked about a follow-up to the lupus trial, this could be the second part of the lupus story for us, where now we're talking about extrarenal either chasing regimen A, or chasing Regimen B and being part of the package of the lupus, commercialization. You're just like every other biologic out there. you're just like every other biologic out there You, you're being added to what patients are currently getting. you you're being added to what patients are currently getting You're gonna have a meaningful results, and then you might come off maintenance therapy. you're gonna have a meaningful results and then you might come off maintenance therapy That is something that as I talked about a confirmation study in extrarenal, as I talked about a follow-up to the lupus trial, this could be the second part of the lupus story for us, where now we're talking about extrarenal either chasing regimen A, or chasing Regimen B and being part of the package of the lupus, commercialization. that is something that as i talked about a confirmation study in extrarenal as i talked about a follow-up to the lupus trial this could be the second part of the lupus story for us where now we're talking about extrarenal either chasing regimen a or chasing regimen b and being part of the package of the lupus commercialization

Speaker 2: But to be fair, the data you've shown so far, you weren't able to reduce the disease burden as much as when you used Cy or Benda. But to be fair, the data you've shown so far, you weren't able to reduce the disease burden as much as when you used Cy or Benda. but to be fair the data you've shown so far you weren't able to reduce the disease burden as much as when you used cy or benda

Speaker 1: Mm-hmm. Mm-hmm. mm-hmm

Speaker 2: You're saying that that trade-off and having this option of treating just in the normal course of your standard lupus treatment is worth it. Or do you think that in some patients you will get deeper responses, or can you do redosing? You're saying that that trade-off and having this option of treating just in the normal course of your standard lupus treatment is worth it. you're saying that that trade-off and having this option of treating just in the normal course of your standard lupus treatment is worth it Or do you think that in some patients you will get deeper responses, or can you do redosing? or do you think that in some patients you will get deeper responses or can you do redosing

Speaker 1: Yes. Absolutely, and that's where I was going. The results you've seen, which did achieve LDAS, is at dose level 1, single dose. We have the green light to go to a higher dose, and we have the green light to multi-dose within a treatment cycle. I'm hoping that the combination of those two, higher dose, multi-dose, will give you increased depth of response. As we talk about that as well, there's always FT839 and FT836 that we'll get to that are made to not require conditioning whatsoever and will give that depth of response. I'm sure we'll talk about next generation in a minute, but right now with FT819, in Regimen B, we are looking to increase the dose and look for a higher depth of response. Yes. yes Absolutely, and that's where I was going. absolutely and that's where i was going The results you've seen, which did achieve LDAS, is at dose level 1, single dose. the results you've seen which did achieve ldas is at dose level 1 single dose We have the green light to go to a higher dose, and we have the green light to multi-dose within a treatment cycle. we have the green light to go to a higher dose and we have the green light to multi-dose within a treatment cycle I'm hoping that the combination of those two, higher dose, multi-dose, will give you increased depth of response. i'm hoping that the combination of those two higher dose multi-dose will give you increased depth of response As we talk about that as well, there's always FT839 and FT836 that we'll get to that are made to not require conditioning whatsoever and will give that depth of response. as we talk about that as well there's always ft839 and ft836 that we'll get to that are made to not require conditioning whatsoever and will give that depth of response I'm sure we'll talk about next generation in a minute, but right now with FT819, in Regimen B, we are looking to increase the dose and look for a higher depth of response. i'm sure we'll talk about next generation in a minute but right now with ft819 in regimen b we are looking to increase the dose and look for a higher depth of response

Speaker 2: Is there at some point it starts to get cost prohibitive to have multi-doses? Like, how many doses do you think is reasonable from your cog standpoint? Is there at some point it starts to get cost prohibitive to have multi-doses? is there at some point it starts to get cost prohibitive to have multi-doses Like, how many doses do you think is reasonable from your cog standpoint? like how many doses do you think is reasonable from your cog standpoint

Speaker 1: To your point, there is a financial toxicity here as well. Definitely. I think once you start having five doses, six doses, seven doses of 1 billion cells, then, you know, it could potentially tilt. As I say this, tilt in the side of maybe not being preferred. Right now, our cost of goods is $3,000 a dose. The margins for that, in terms of having the ability to have meaningful revenue is still there. That's just at the current scale of 100 L volume. As we get to 1,000 L, as we get to 10,000 L scale, that 3,000 L becomes 1,000 L, becomes couple of hundred. To your point, there is a financial toxicity here as well. to your point there is a financial toxicity here as well Definitely. definitely I think once you start having five doses, six doses, seven doses of 1 billion cells, then, you know, it could potentially tilt. i think once you start having five doses six doses seven doses of 1 billion cells then you know it could potentially tilt As I say this, tilt in the side of maybe not being preferred. as i say this tilt in the side of maybe not being preferred Right now, our cost of goods is $3,000 a dose. right now our cost of goods is $3,000 a dose The margins for that, in terms of having the ability to have meaningful revenue is still there. the margins for that in terms of having the ability to have meaningful revenue is still there That's just at the current scale of 100 L volume. that's just at the current scale of 100 l volume As we get to 1,000 L, as we get to 10,000 L scale, that 3,000 L becomes 1,000 L, becomes couple of hundred. as we get to 1,000 l as we get to 10,000 l scale that 3,000 l becomes 1,000 l becomes couple of hundred As we might need to increase dose, we will increase scale, and then you can see that offset as again. There is a lot of levers to pull here as we think about multi-dosing. At the same time, there are next generation products that could go back to a single dose and no conditioning. As we might need to increase dose, we will increase scale, and then you can see that offset as again. as we might need to increase dose we will increase scale and then you can see that offset as again There is a lot of levers to pull here as we think about multi-dosing. there is a lot of levers to pull here as we think about multi-dosing At the same time, there are next generation products that could go back to a single dose and no conditioning. at the same time there are next generation products that could go back to a single dose and no conditioning

Speaker 2: I want to start to go down the commercial implications, which I think are interesting. Let's actually look because we only have six minutes left. Let's talk about the next generation. Maybe let's stick with the ones for autoimmune disease. I want to start to go down the commercial implications, which I think are interesting. i want to start to go down the commercial implications which i think are interesting Let's actually look because we only have six minutes left. let's actually look because we only have six minutes left Let's talk about the next generation. let's talk about the next generation Maybe let's stick with the ones for autoimmune disease. maybe let's stick with the ones for autoimmune disease

Speaker 1: Sure. Sure. sure

Speaker 2: What are you doing, and how is that gonna step up, and how are you gonna prioritize? I think the challenge with it has always been you can always do a next generation. How do you balance commitment to the current generation with moving to, like, what benefits you're gonna get? What are you doing, and how is that gonna step up, and how are you gonna prioritize? what are you doing and how is that gonna step up and how are you gonna prioritize I think the challenge with it has always been you can always do a next generation. i think the challenge with it has always been you can always do a next generation How do you balance commitment to the current generation with moving to, like, what benefits you're gonna get? how do you balance commitment to the current generation with moving to like what benefits you're gonna get

Speaker 1: Absolutely. In the quick last few minutes, the next generation is multiplex edited. As FT819 was a tuned-down CAR into the TRAC locus for very defined specific activity, FT839 and FT836 are multiplexed. The Sword and Shield technology is common between the both of them. Sword and Shield is our way of eliminating the need for conditioning. It's not a way of hiding from the host immune system. It's a way of actually of completely eliminating the need for conditioning. As rejections and conditioning overcomes re-host rejection, conditioning overcomes the lack of space or creates space, conditioning creates a cytokine surplus by eliminating host immune system. All these things are important to CAR T as it needs to expand and grow. Absolutely. absolutely In the quick last few minutes, the next generation is multiplex edited. in the quick last few minutes the next generation is multiplex edited As FT819 was a tuned-down CAR into the TRAC locus for very defined specific activity, FT839 and FT836 are multiplexed. as ft819 was a tuned-down car into the trac locus for very defined specific activity ft839 and ft836 are multiplexed The Sword and Shield technology is common between the both of them. the sword and shield technology is common between the both of them Sword and Shield is our way of eliminating the need for conditioning. It's not a way of hiding from the host immune system. sword and shield is our way of eliminating the need for conditioning. it's not a way of hiding from the host immune system It's a way of actually of completely eliminating the need for conditioning. it's a way of actually of completely eliminating the need for conditioning As rejections and conditioning overcomes re-host rejection, conditioning overcomes the lack of space or creates space, conditioning creates a cytokine surplus by eliminating host immune system. as rejections and conditioning overcomes re-host rejection conditioning overcomes the lack of space or creates space conditioning creates a cytokine surplus by eliminating host immune system All these things are important to CAR T as it needs to expand and grow. all these things are important to car t as it needs to expand and grow Others have used a more kind of, as I would capture it, as hide strategy, which would be kind of our Sword and Shield side. There is CD47, there is HLA-E, there's CD300a. These things are being used to suppress the in-host immune system. They all None of them are sufficient because if they were, every cancer in your body would be CD47, you know, would be expressing CD47, would have HLA-E, or would have CD300. Therapies have been made for CD47 and HLA-E. I don't think CD300's got much attention. In general, these things are not the holy grails. We do have a version of this. It's CD58. We eliminate cell-cell interactions, so effector cells cannot really interact with us as much. Others have used a more kind of, as I would capture it, as hide strategy, which would be kind of our Sword and Shield side. others have used a more kind of as i would capture it as hide strategy which would be kind of our sword and shield side There is CD47, there is HLA-E, there's CD300a. there is cd47 there is hla-e there's cd300a These things are being used to suppress the in-host immune system. these things are being used to suppress the in-host immune system They all None of them are sufficient because if they were, every cancer in your body would be CD47, you know, would be expressing CD47, would have HLA-E, or would have CD300. they all none of them are sufficient because if they were every cancer in your body would be cd47 you know would be expressing cd47 would have hla-e or would have cd300 Therapies have been made for CD47 and HLA-E. therapies have been made for cd47 and hla-e I don't think CD300's got much attention. i don't think cd300's got much attention In general, these things are not the holy grails. in general these things are not the holy grails We do have a version of this. we do have a version of this It's CD58. it's cd58 We eliminate cell-cell interactions, so effector cells cannot really interact with us as much. we eliminate cell-cell interactions so effector cells cannot really interact with us as much Even though CD58 is prominent in cancer, it's not the holy grail either. This is where our sword side comes in. It's an activating receptor that actually eliminates any effector cell that is activated upon cell-cell interactions. B cells, T cells, and NK cells, when they come and interact with us, if they overcome the CD2, CD58 interaction, and they interact with us, they will have to turn on 4-1BB to do something. Whether it has to kill us or have a response against us, we will kill it first because we will sense that, and our activating receptor will eliminate that cell and at the same time, give signal to our product to expand. It offsets all the, those unique attributes of conditioning. That's great. We have that. CD FT839 has a CD19 and a CD38 CAR. Even though CD58 is prominent in cancer, it's not the holy grail either. even though cd58 is prominent in cancer it's not the holy grail either This is where our sword side comes in. this is where our sword side comes in It's an activating receptor that actually eliminates any effector cell that is activated upon cell-cell interactions. it's an activating receptor that actually eliminates any effector cell that is activated upon cell-cell interactions B cells, T cells, and NK cells, when they come and interact with us, if they overcome the CD2, CD58 interaction, and they interact with us, they will have to turn on 4-1BB to do something. b cells t cells and nk cells when they come and interact with us if they overcome the cd2 cd58 interaction and they interact with us they will have to turn on 4-1bb to do something Whether it has to kill us or have a response against us, we will kill it first because we will sense that, and our activating receptor will eliminate that cell and at the same time, give signal to our product to expand. whether it has to kill us or have a response against us we will kill it first because we will sense that and our activating receptor will eliminate that cell and at the same time give signal to our product to expand It offsets all the, those unique attributes of conditioning. it offsets all the those unique attributes of conditioning That's great. that's great We have that. we have that CD FT839 has a CD19 and a CD38 CAR. cd ft839 has a cd19 and a cd38 car CD19 to deplete the B cell population as FT819 does as well, but also CD38 to eliminate the other aberrant cell types found in the immune compartment such as T cells. This gives you really a large breadth to go after multiple complex autoimmune diseases such as RA, that where the T cell compartment is playing a role, type 1 diabetes as well, and gives you a unique ability, and we haven't really talked about this, but to create immune tolerance. As you take on a graft and you give FT839, it can potentially give you the ability to eliminate the need for immune suppression because it can give you immune tolerance to the graft. We'll talk more about that second half of the year. CD19 to deplete the B cell population as FT819 does as well, but also CD38 to eliminate the other aberrant cell types found in the immune compartment such as T cells. cd19 to deplete the b cell population as ft819 does as well but also cd38 to eliminate the other aberrant cell types found in the immune compartment such as t cells This gives you really a large breadth to go after multiple complex autoimmune diseases such as RA, that where the T cell compartment is playing a role, type 1 diabetes as well, and gives you a unique ability, and we haven't really talked about this, but to create immune tolerance. this gives you really a large breadth to go after multiple complex autoimmune diseases such as ra that where the t cell compartment is playing a role type 1 diabetes as well and gives you a unique ability and we haven't really talked about this but to create immune tolerance As you take on a graft and you give FT839, it can potentially give you the ability to eliminate the need for immune suppression because it can give you immune tolerance to the graft. as you take on a graft and you give ft839 it can potentially give you the ability to eliminate the need for immune suppression because it can give you immune tolerance to the graft We'll talk more about that second half of the year. we'll talk more about that second half of the year For now, this is a broad targeting strategy that goes after complex diseases, including hematologic malignancies such as myeloma and lymphoma. It's almost a catchall for multiple diseases. It's also the brakes have been turned off, so it could actually expand in a very aggressive manner. Now, that's very different than what I said with FT819. Right now it's a safe product that we're very excited about because of the safety and efficacy profile. I don't think FT839 will come tomorrow and completely cannibalize our phase II trial because there's a safety component and then there's an efficacy component. The FT839 is reserved for more considerations where the disease is complex, the burden is high and conditioning is not used. That's a very different profile than FT819. For now, this is a broad targeting strategy that goes after complex diseases, including hematologic malignancies such as myeloma and lymphoma. for now this is a broad targeting strategy that goes after complex diseases including hematologic malignancies such as myeloma and lymphoma It's almost a catchall for multiple diseases. it's almost a catchall for multiple diseases It's also the brakes have been turned off, so it could actually expand in a very aggressive manner. it's also the brakes have been turned off so it could actually expand in a very aggressive manner Now, that's very different than what I said with FT819. now that's very different than what i said with ft819 Right now it's a safe product that we're very excited about because of the safety and efficacy profile. right now it's a safe product that we're very excited about because of the safety and efficacy profile I don't think FT839 will come tomorrow and completely cannibalize our phase II trial because there's a safety component and then there's an efficacy component. i don't think ft839 will come tomorrow and completely cannibalize our phase ii trial because there's a safety component and then there's an efficacy component The FT839 is reserved for more considerations where the disease is complex, the burden is high and conditioning is not used. the ft839 is reserved for more considerations where the disease is complex the burden is high and conditioning is not used That's a very different profile than FT819. that's a very different profile than ft819

Speaker 2: You took those two mutations that we talked about previously, and you put them back in? You took those two mutations that we talked about previously, and you put them back in? you took those two mutations that we talked about previously and you put them back in

Speaker 1: Yeah. The, the CAR composition, in some scenarios does have the full intact CD3ζ ITAMs 1, 2, 3 are there, and it also has a T cell enhancer that we haven't talked about right now because I just don't want anybody to copy us until we have all the patents figured out. It actually, there's an inherent boost as well as intact CAR that drives the activity. Yeah. yeah The, the CAR composition, in some scenarios does have the full intact CD3ζ ITAMs 1, 2, 3 are there, and it also has a T cell enhancer that we haven't talked about right now because I just don't want anybody to copy us until we have all the patents figured out. the the car composition in some scenarios does have the full intact cd3ζ itams 1 2 3 are there and it also has a t cell enhancer that we haven't talked about right now because i just don't want anybody to copy us until we have all the patents figured out It actually, there's an inherent boost as well as intact CAR that drives the activity. it actually there's an inherent boost as well as intact car that drives the activity

Speaker 2: You turned it up a lot. Did you turn it up too much? You turned it up a lot. you turned it up a lot Did you turn it up too much? did you turn it up too much

Speaker 1: A lot of our safety studies suggest that it still behaves like a T cell. It expands and contracts as expected, but the peak of the expansion is very different than FT819. A lot of our safety studies suggest that it still behaves like a T cell. a lot of our safety studies suggest that it still behaves like a t cell It expands and contracts as expected, but the peak of the expansion is very different than FT819. it expands and contracts as expected but the peak of the expansion is very different than ft819

Speaker 2: It's still CD8 only, and so that you get some advantages from that. It's still CD8 only, and so that you get some advantages from that. it's still cd8 only and so that you get some advantages from that

Speaker 1: Yeah. Yeah. yeah

Speaker 2: I actually haven't talked about that, so maybe you could mention the advantages of CD8. I actually haven't talked about that, so maybe you could mention the advantages of CD8. i actually haven't talked about that so maybe you could mention the advantages of cd8

Speaker 1: Sure. CD4s are helper, cells, so they actually augment CD8 activity. The actual killing comes from CD8. For us, when you have CD8 only is another way of controlling your product, the defined expansion and contraction. This again goes back to control. It's a single-layered product. You don't have the CD4s that may, change things. Again, you listen to Kite or you listen to Juno, they always had the CD4 CD8s discussion to how much- Sure. sure CD4s are helper, cells, so they actually augment CD8 activity. cd4s are helper cells so they actually augment cd8 activity The actual killing comes from CD8. the actual killing comes from cd8 For us, when you have CD8 only is another way of controlling your product, the defined expansion and contraction. for us when you have cd8 only is another way of controlling your product the defined expansion and contraction This again goes back to control. this again goes back to control It's a single-layered product. it's a single-layered product You don't have the CD4s that may, change things. you don't have the cd4s that may change things Again, you listen to Kite or you listen to Juno, they always had the CD4 CD8s discussion to how much- again you listen to kite or you listen to juno they always had the cd4 cd8s discussion to how much-

Speaker 2: Yeah. Yeah. yeah

Speaker 1: how important are fours. In immunology, fours help eights. Again, we only have eights because we wanna have a more defined product. how important are fours. how important are fours In immunology, fours help eights. in immunology fours help eights Again, we only have eights because we wanna have a more defined product. again we only have eights because we wanna have a more defined product

Speaker 2: Got it. There's 30 seconds left. I'll see if anybody in the audience has a question. Bob? Got it. got it There's 30 seconds left. there's 30 seconds left I'll see if anybody in the audience has a question. i'll see if anybody in the audience has a question Bob? bob

Speaker 3: Yeah. I have one. Yeah. yeah I have one. i have one

Speaker 2: Yeah. Thanks. Yeah. yeah Thanks. thanks

Speaker 3: Do you like Benda or cyclophosphamide? Do you like Benda or cyclophosphamide? do you like benda or cyclophosphamide

Speaker 1: I like Benda more. That's what we're going with for our phase II. The reason I like that is because some of these patients have been exposed to Cy for a number of times. There's a discourage of using it. Also, Benda appears to have that initial improved kinetics in B cell depletion. It adds value with B cell depletion, but also it appears to be a different agent than what the patients have been getting, and that helps with patient enrollment. I like Benda more. i like benda more That's what we're going with for our phase II. that's what we're going with for our phase ii The reason I like that is because some of these patients have been exposed to Cy for a number of times. the reason i like that is because some of these patients have been exposed to cy for a number of times There's a discourage of using it. there's a discourage of using it Also, Benda appears to have that initial improved kinetics in B cell depletion. also benda appears to have that initial improved kinetics in b cell depletion It adds value with B cell depletion, but also it appears to be a different agent than what the patients have been getting, and that helps with patient enrollment. it adds value with b cell depletion but also it appears to be a different agent than what the patients have been getting and that helps with patient enrollment

Speaker 2: Is that gonna be challenging regulatory-wise for approval? Is that gonna be challenging regulatory-wise for approval? is that gonna be challenging regulatory-wise for approval

Speaker 1: I don't- I don't- i don't-

Speaker 2: Without the contribution in a single arm study? Without the contribution in a single arm study? without the contribution in a single arm study

Speaker 1: Translational data is actually nicely shows what Benda contributes and then what FT819 contributes because the effects of Benda are only for several days. When you see control of B cells and even further depletion of B cells after a week, it's you know that it's FT819 activity. Translational data is actually nicely shows what Benda contributes and then what FT819 contributes because the effects of Benda are only for several days. translational data is actually nicely shows what benda contributes and then what ft819 contributes because the effects of benda are only for several days When you see control of B cells and even further depletion of B cells after a week, it's you know that it's FT819 activity. when you see control of b cells and even further depletion of b cells after a week it's you know that it's ft819 activity

Speaker 2: That's well established, like outside of your own studies, the duration of Benda? That's well established, like outside of your own studies, the duration of Benda? that's well established like outside of your own studies the duration of benda

Speaker 1: Yeah. In terms of the immune cell compartment coming back after a couple of weeks, yes, that's well established. Yeah. yeah In terms of the immune cell compartment coming back after a couple of weeks, yes, that's well established. in terms of the immune cell compartment coming back after a couple of weeks yes that's well established

Speaker 2: Okay. Awesome. Well, thank you all. Thanks for your attention. Okay. okay Awesome. awesome Well, thank you all. well thank you all Thanks for your attention. thanks for your attention