Hi, everyone. Welcome to our fireside chat with Fate. I'm Li Watsek analyst at Cantor, and we're very glad to have Scott joining us today for the discussion, so I guess for our audience, we can start with a brief overview on what's coming up for Fate. Sure. Thank you for having me at the conference. So Fate Therapeutics is a cellular therapeutic company. We focus on developing off-the-shelf T-cells and NK cells, take a very different approach to the field of cell therapy. Most cell therapies being developed today, both in oncology and autoimmunity, are autologous, which means that the products are sort of go through a little bit of a heroic journey- Mm-hmm ... to reach patients. Mm-hmm. They're using the patient's own cells in terms of manufacture and engineering, and then delivery back to the patient. Typically requires hospitalization, and it's basically an N of one process that's specific for the patient. I think what we've done at Fate Therapeutics is pioneer a new approach. We are aspiring to make cell therapy look more like monoclonal antibody therapy, essentially where cells can be engineered and mass-produced and can reach a significant number of patients, including outside of the traditional academic CAR T-cell centers, and reach into the community. We originally focused our platform on NK cells. Mm-hmm ... advanced into T-cells with initial sort of therapeutic aspirations in oncology, and more recently, based on some of the initial data that's been generated in the field, which has been very exciting for the space of autoimmunity, we've begun to advance into autoimmunity. We have three programs that are undergoing clinical development today: two are T-cells, CAR T-cell programs, FT825, which is for solid tumors. FT819, which is our CD19-targeted product for autoimmunity. Mm-hmm. We have an NK cell program that is initially currently in oncology and is advancing now also into autoimmunity. So, in the coming months, we expect to have very initial clinical data across all three clinical programs. Okay, great. So I want to talk a little bit about autoimmune. Scott, you alluded to there's a lot of, you know, investor interest here. So I guess if you think about your platform, what you're trying to do, obviously you have some, you know, access advantage, but then we're also seeing some T-cell engagers coming up. Yes. How do you think you are positioned relative to some of the T-cell engager programs? Yeah. I think when we think about our ultimate therapeutic paradigm, we think about us as Fate Therapeutics as advancing a cell therapy paradigm that looks like a traditional biologic- Mm ...so a T-cell, more T-cell engager-like, and so as we think about our platform and the potential for it, I think T-cell engagers, as we've seen in the oncology setting, have the potential to reach patients earlier in care. Mm-hmm. They do not require Cy/ Flu conditioning which is a challenge in treating patients. It's not the most patient-friendly regimen to give high-dose chemotherapy conditioning to patients, and the T-cell engagers actually also can be multi-dosed. Mm-hmm. And so as we think about our off-the-shelf platform, we think we share many of the attributes and patient sort of benefits that a T-cell engager can give. We can mass-produce cells. We can do that at relatively low cost. We can reach patients with an off-the-shelf cell therapy in the outpatient setting. Mm-hmm. We're aspiring to give our cells without conditioning chemotherapy, just like the T-cell engagers, and reach into the community, so we think our therapeutic paradigm that we're looking to pursue in autoimmunity is much more biologics-like- Mm-hmm ... than the traditional autologous programs. So how should we think about sort of the clinical profiles? Obviously, on one hand, we have efficacy, on the other hand, we have safety. So how would you size up, you know, your approach versus the T-cell engagers? Yeah. So I think the value proposition for patients needs to be acknowledged that in cancer- Mm-hmm ... the patients, unfortunately, are in a position of oftentimes life and death. Mm. There is much more tolerance for toxicity in order to treat patients. The autoimmunity patient is a very different type of patient, and based on all our conversations with KOLs and potential PIs, safety is absolutely going to be at a premium- Mm ... in treating patients with autoimmunity. And so I think it's incumbent as we think about developing cell therapies for these patients, that we recognize that we need to treat these patients as if they have autoimmunity. Safety is at a premium, and intervening with patient-friendly regimens is going to be important. Obviously, you need to deliver patient benefit- Yeah ... but you need to really do that, taking into account safety. You need to do that in consideration of the fact that, at least in our therapeutic aspirations, we do not intend to treat patients, for instance, in academic medical centers. Mm. We are trying to reach much more into the community, where patients can be treated safely. So let's move on to your CD19 CAR T program, FT819. Obviously, this is a program where we've seen a lot of, you know, interest. So maybe tell us a little bit about the construct of this CAR T and then what you've shown in oncology, and how do you extrapolate that- Mm-hmm ... into autoimmune? ... Perfect. So FT819 was our, is our first ever iPSC-derived CAR T-cell therapy. Mm-hmm. In developing an off-the-shelf cell therapy for, with a T cell, there are certain considerations you have to take into account. One of them is that when T cells are delivered to patients, there's the risk of creating or delivering GVHD. Mm. or GVHD as a toxicity. In order to eliminate that, what folks do is you knock out the T-cell receptor, and you, in this case, insert a CAR in replacement of that T-cell receptor. So we have a CAR-T cell that is null with respect- Mm-hmm ... to the T- cell receptor, and therefore, can be delivered off the shelf to patients. We use a very interesting CAR construct. Most CAR T- cell therapies either use a CAR construct- Mm ... that uses CD28 or 4-1BB as the co-stimulatory domain. Mm-hmm. We use a novel construct that was developed at Memorial Sloan Kettering, known as the 1XX construct, which we think balances both potency as well as safety, and so that program we advanced initially into the oncology setting. Yeah. We treated approximately 40 patients in- Mm-hmm ... dose escalation. Mm-hmm. In the oncology setting, we saw a very clean safety profile, very low incidence and low rates of CRS, which is Yeah ... significant complication seen with autologous CAR T- cell therapy. No ICANS. Mm. We certainly generated responses in very difficult-to-treat patients that had, many of them had already received autologous CAR T- cell therapy. When we look at sort of the translational data, we're very excited about the translational- Mm ... data as it relates to autoimmunity, because what we saw when we delivered our product, we saw the cells essentially thrive- Mm ... with respect to their ability to target and deplete B cells. So when we think about the necessary mechanism of action that's relevant for autoimmunity, where you're looking for rapid and deep depletion of B cells, and then you're looking for the reconstitution of the B cell compartment. What we saw with FT819 was delivering... We saw CD19-mediated expansion- Mm-hmm ... in a dose-dependent fashion. We saw rapid and deep depletion of the B cell compartment, and we saw very good, reconstitution of the B cell compartment in these patients. Maybe walk us through your phase trial design, and my understanding is you're trying some, you know, novel conditioning regimen here. Yeah. Yeah, in the spirit of trying to develop patient-friendly regimens and move away from Cy/ Flu conditioning, we certainly thought it was important to start with a first principles approach. The data that had been initially generated in the autoimmunity space, as well as in the oncology setting- Mm-hmm ... is based on Cy/ Flu conditioning. Mm-hmm. So we have an initial regimen, in that study, which we call sort of the regimen A, the conditioning regimen. Mm. Regimen A provides physicians and patients a choice. They could receive Cy/ Flu conditioning. Mm. They could receive an alternative conditioning regimen, bendamustine. Mm. They can receive potentially a third alternative conditioning regimen of Cy/ Flu- Cy alone. There are really three different choices with respect to conditioning that we're looking at in regimen A of the study. We've continued to work with the FDA to expand the patient population for that study and to explore new therapeutic paradigms that we think are more patient-friendly. We're working with the FDA to open regimen B, what we call regimen B, and regimen B is where we begin to add FT819 on top of less intensive regimens. Patients today receive that are being treated for many B-cell-mediated autoimmune diseases. Mm-hmm ... are living on immunosuppressive, various immunosuppressive regimens. Mm-hmm. For instance, mycophenolate is a regimen that is often given to patients, and they are receiving that and being dosed with that every day. Mm. And we're considering adding on to some of those immunosuppressive regimens in a more patient-friendly way. Mm. How do you decide which regimen to go forward with? Is that just a function of the data you guys have to see? Ultimately, it will be data-driven- Yeah ... right? Mm-hmm. We will look at various different conditioning regimens. Mm-hmm. both regimen A, where we're looking at some of the more intense regimens, but also regimen B, where we're looking at the less intensive regimens. I think from my perspective- Mm ... there really is a premium on, or incumbent on us to really try and bring patient-friendly regimens to patients. And so we'll look at the data, certainly- Yeah ... but we are excited about the potential to give alternative regimens to patients that are more patient-friendly. You can reach patients in the outpatient setting, a lot less toxicity, much more safer. How are you thinking about the cell, doses that you use in autoimmune relative to oncology? Yeah, I think it's a great question, and the therapeutic index. Yeah ... that's necessary to achieve, attractive outcomes for patients is probably different- Mm-hmm ... in autoimmunity than it is in oncology. Obviously, in oncology, you're dealing with, you know, much higher sort of, let's call it sort of target burden, if you will, than you are in autoimmunity. We explored five different dose levels- Mm ... in the oncology setting, ranging as low as 90 million cells up to 1 billion cells. We saw safety across all dose levels. We saw activity at all dose levels. And so what we decided to do in the autoimmunity setting, we started at a dose level, the third dose level, the middle dose level of 360 million cells. In terms of duration of remission, obviously, we've seen some, you know, relapse cases- Mm-hmm. from, you know, CAR T. So how are you thinking about, in terms of, you know, duration that you guys need to achieve, and is there any possibility for redosing? Yeah, I think a lot of this duration of response, and ultimately what the therapeutic profile is for patients, is going to sort of be dependent on the paradigm they're receiving. So I think if you are a patient receiving Cy/Flu conditioning, I do think sort of the requirement for, if you will, a more curative long-term duration of response, a curative outcome, is going to be more significant. Mm. If you are intervening with an off-the-shelf cell therapy in the community without conditioning, I think, for instance, the ability to achieve durations of responses that are in, for instance, the six, 12, 18-month range- Mm-hmm ... can be much more attractive, and I think you have the ability to redose patients to try and achieve those types of duration of response. I think all of us aspire to deliver, and develop, curative therapies for patients, absolutely. But there is tremendous unmet need today- Mm ... for these patients, and there is tremendous opportunity to deliver significant therapeutic improvement, that is short of cure. Mm. We all aspire to cures- Yeah ... but there is lots of room for significant therapeutic improvement today. I wanna talk about enrollment. Mm. Obviously, we've seen some challenges in this space. Now you're sort of running the phase I. What are you seeing in terms of enrollment pace? Yeah, I think-... there are real challenges with enrollment, and I think some of the real challenges with enrollment have to do with, you know, elements that we've talked about today. Yeah. I mean, the reality is, today, what's being done for these autoimmunity patients is we've taken an oncology paradigm- Mm ... and we've brought it into autoimmunity. We're requiring patients to go through leukapheresis, we're requiring patients to come off their therapy, we're requiring patients to go through 14 days of hospitalization. That is what the field is requiring. Mm. And that is, at some levels, we know, a heroic journey, Yeah ... in the oncology setting. And the number of centers that can deliver these therapies is ultimately very limited. And so for us, certainly, we think it's important to start there with a first principles approach. That's where the field is today. Mm. But we are aggressively moving to promote- Mm ... better enrollment by reaching a different kind of patient, and this is where you, with an off-the-shelf cell therapy, with moving away from conditioning, you can reach more outside of the academic medical centers and into the community where these patients are living and breathing. So, I guess right now you have three conditioning regimen. I'm just curious, do you have a sense whether physicians or patients have a preference, or not yet? It's early- Yeah ... but based on our initial clinical experience, I think, consistent with my statements, there is a significant desire to avoid- Mm ... conditioning patients with Cy/Flu. Okay. I want to go back to the phase I data update that's gonna come later this year. You've said you're gonna show maybe three to five patients of data. Maybe just set the stage for us. What is good data? What should we expect? Yeah. So the first patient we treated in the study was out mid-April- Mm ... maybe the first patient was treated in mid-April. Mm-hmm. And yes, you know, consistent with what you said, I think, you know, we're gonna be in a position where we'll have treated three to five patients by the end of the year. They'll be at various stages of follow-up. Certainly, the first patient we treated, we've said publicly, had a very favorable clinical experience. As of our last quarterly update, patient remained on study. Mm. And so for the first patient, we certainly think we're going to have significant follow-up with respect to that patient, probably about- Mm ... six months. Okay. We will have robust translational data with respect to FT819's ability to drive robust B-cell depletion. We will have data on, for instance, the reconstituting B-cell compartment, to understand what that looks like and whether we've delivered an immune reset. Mm. Certainly, we'll have biomarker data as it relates to the disease, specifically, like autoantibodies. And ultimately, we will have clinical assessments, important clinical assessments, the first clinical assessment being performed at three months- Mm-hmm ... and then a second clinical assessment being performed at six months. So for the first patient, we do think we'll have a robust set of translational data- Mm ... as well as, you know, duration of response- Mm ... at least six months. Some of the other patients that are coming on the study, they're less mature. They certainly expect to have important data as it relates to translation- Mm ... B-cell reconstitution, and it, you know, potentially, the clinical assessments on some of the other patients. Maybe just to follow up on clinical assessment, I think this is where a lot of us want to know, right? So where do you think the benchmark is? Obviously, we have some very high bar out there set by- Mm-hmm ... CAR T- cells. Mm-hmm. So maybe just talk a little bit about that, and do you think you actually have to match that, or is there any room, maybe for on the efficacy side, you may not need to achieve that level because obviously you have some, you know, access advantage and- Yeah regimen Yeah - advantage. Look, I think we should all aspire to deliver cures to patients. Yeah. So I understand the bar associated with the curative therapy. Mm. I do think we have to recognize, though, that we've treated a small number of patients to date. The community's treated a small number of patients to date. And I also think we have to recognize that one of the reasons there is so much excitement about this is because there is so much significant need- Mm for these patients. There is tremendous opportunity for therapeutic improvement that falls short of cure. We're all striving for that, but there is tremendous opportunity for therapeutic improvement. And so, as I mentioned, today, most of these patients are living day to day on immunosuppressive therapies. Mm. If you can deliver a therapy to patients, a one-time or a two-time intervention, including without conditioning, where you can drive a drug-free remission and get patients off immunosuppressive therapy and return significant quality of life to these patients, there's significant therapeutic value in that. Okay. Let's switch to FT522, which is your NK cell program. Yeah. And you're obviously gonna share some data later this year. Yeah. Help us understand what the expectations are. Yeah. So FT522 is, you know, you might refer to as our second or third generation- Yeah ... NK NK cell program. Mm. It has five different functional edits included within it. It has a CD19 CAR construct, so obviously we can target B cells and deplete B cells. It has a CD16 receptor. It's important, because the CD16 receptor is sort of innate within innate biology. Mm ... and allows the NK cells to synergize with monoclonal antibody therapy. It's also important obviously in oncology and autoimmunity, where monoclonal antibodies are given to these patients, so we have the opportunity to synergize with monoclonal antibodies that are already delivered to patients. It has an IL-15 receptor fusion, which allows, essentially acts as a fuel system for the cell. Mm. It has a CD38 knockout, which improves the cell's metabolic fitness, and importantly, it has a fifth edit, and it's the first time we're exploring this edit in clinical studies, starting in oncology, but moving into autoimmunity. It has a receptor, a novel receptor called an Allo-defense receptor, and that receptor is essentially designed to allow the cell therapy to thrive without conditioning. Mm. It's a second CAR construct, whereby that cell becomes activated, actually in the background of a patient's immune system. Mm. So for FT522, we've begun exploring that. I mean, sorry, in oncology to start. We have a study right now that's running that has two different arms. One is a conditioning arm, and one is actually an arm without conditioning. Mm-hmm. So with FT522, we've really sort of initiated the clinical experience, asking the killer clinical question: Can we deliver FT522 to patients, and will that cell therapy thrive without conditioning? And we have now, submitted an IND to the FDA to bring that into autoimmunity. The design, at least, that we've proposed for the FDA for their review, not approved yet- Mm ... but approved for consideration is delivering FT522 to patients with autoimmunity without conditioning. I guess for the data later this year, obviously, that's in B cell lymphoma. Talk a little bit about what types of data that we can extrapolate. Yeah. So I think there's some important translational data that you- Yeah ... can take away from FT522 in the oncology study, starting with, FT522 includes the novel ADR technology. Are we able to see, without conditioning, the NK cells survive- Mm ... persist, thrive, and show some degrees of activity in the oncology setting without conditioning? I think that's really interesting and really important. We'll be, we obviously starting at the lowest dose levels here. Mm. As it relates to autoimmunity specifically, while it's an oncology study, we certainly can look at, for instance, B cell targeting with respect to CD19, as well as B cell depletion within the first thirty days following delivery of the cells. So really, if we are able to see, without conditioning, robust B cell depletion with FT522, I think that's very exciting for autoimmunity and its potential to drive a potential immune reset-... in that setting. So obviously, we are seeing more NK cell players out there. Maybe touch on the differentiation of FT522 relative to some of the other NK players. Yeah. I think as it relates to the NK cell therapy space, I think, as I look at the cell type, it's obviously CD19 targeted. Most of the NK cells being developed today, at least in the hematologic malignancy or autoimmunity setting, are also CD19 targeted. Mm. We've included the CD16 engineered receptor into this program, allowing it to synergize with monoclonal antibody therapy. We've also knocked out CD38. You see, knocking out CD38 is important, because if you desire to, for instance, target CD38 cells, potentially in combination with a monoclonal antibody, the knockout of CD38 allows or prevents fratricide, so you can, the cells- Mm ... can sort of thrive with a CD38 monoclonal antibody. It's important because it allows the cell therapy to potentially reach into the plasma cell compartment. They're autoantibody producing. They're bad-acting autoantibody producing cells. But most importantly, as we talked about, it's the ADR technology.... I mean, well, to date, I think we're the only cell therapy company that's exploring the delivery of these products without conditioning. And so as I think about whether it's the oncology setting, but especially the autoimmunity setting, I think it's very important that we understand the physician and patient requirements, and the challenges that conditioning brings to the table in trying to treat and reach patients with autoimmune disease. I guess just last question from me. Obviously, lupus is very crowded field, as you said earlier, Scott. I mean, there's a lot of unmet need here. Mm-hmm. So what other indications that you're considering right now? Yeah, I mean, I think this is also very exciting in the autoimmunity space. There's a whole host of B-cell mediated autoimmune diseases, where now data is being generated, whether that be myositis or scleroderma, ankylosing spondylitis. There's now sort of beginning to be exploration into other types of diseases that may have more sort of a neurological application to them, like MS. So I think there's tremendous excitement with respect to the autoimmunity field and the breadth of disease indications that could potentially be reached. As we look at FT819, we certainly started in SLE. Mm. We're currently looking to expand that into additional indications, and as I've said publicly before, the 522 IND, the CAR NK cell program, the IND that we have submitted to the FDA is designed to pursue a basket of autoimmune indications. That's interesting. So I wanna see if we got any questions from the audience. If not, thank you very much- Thank you ... for the discussion. Thanks for having me.