Great. Thank you, everyone. Welcome to our next session. Up here on the front panel, we have Scott Wolchko, the CEO of Fate Therapeutics. Obviously, a lot going on this year and a lot of pipeline development across oncology and autoimmune. Yep. This is quite a dynamic space. I'm alluding to the autoimmune part. Last night I had dinner with another CAR T autoimmune company, and there's many, many companies- Yep. -that are looking at this. And so one of the key things actually that I would love to understand from you is your Fate's perspective about the different options that may come for CAR T autoimmune. And everyone just says, "It's crowded. Scott, it's crowded." It's like- It is! CD19 again, all over again. It is. I would love to start with your introduction to what you're doing in autoimmune- Yep how you expect to differentiate, given the fact that everybody on Wall Street seems to think it's quite crowded? Perfect. Great. Thank you. So I think one of the reasons it's crowded is because the therapeutic results that have been achieved to date in small numbers of patients have been quite remarkable. So patients with autoimmunity are often living their lives on immunosuppressive therapies. And what we've seen to date with CAR T-cell therapy, small numbers of patients, is that with a single intervention, patients can be effectively cured. Bit early to say that, but what we've seen is a profound reset of their disease, a turning back the clock, if you will, where these patients are no longer required to be on immunosuppressive therapies. What has enabled that? Well, the good news is that that is being achieved. Immune resets and effective long-term, durable, drug-free remissions are being brought to patients with autoimmune diseases. Terrific. The challenge is that the field has had to treat these patients with autoimmunity as if they were an oncology patient. And so what does that mean? So what that means is we've had to deliver high doses of Cy/Flu conditioning to patients. We've had to ask them to come off their therapies, undergo leukapheresis, hospitalize, travel, become hospitalized 10-14 days. There are toxicities associated with Cy/Flu as well as cell therapies, and so it's a challenging regimen today. And so what Fate Therapeutics is, is seeking to do is develop off-the-shelf, patient-friendly solutions for both oncology and autoimmunity. And so our product candidates are designed to enable patient access, potentially plug into regimens that are much more friendlier to patients, and ultimately achieve profound therapeutic outcomes. We're doing that with both a CAR T-cell program as well as a CAR NK cell program. Excellent. Let's start with the design of your construct and why we should be convinced that your CD19 CAR T, or iPSC- iPSC, yep ... CAR T, off-the-shelf, which is in a phase I- Yep -for lupus. Yep. Tell us about the construct, tell us about the design of the study, and tell us why you feel confident that it should work? Yep. So first thing, it, as you alluded to, it's iPSC-derived, right? So I think in autoimmunity, certainly safety is going to be at a premium. Patient access is going to be a premium. Ensuring product availability is going to be at a premium. And so with the iPSC-derived approach, we're essentially able to mass-produce a homogeneous product that is well characterized. We started, obviously, with this product candidate in oncology. Mm-hmm. We showed an exquisite safety profile, and we've certainly shown activity. Meaning it's already been in patients? It's already been in patients. Same construct? Same exact construct. Same doses? Same doses. Okay. Same doses. Same batch of product, actually. Same cell line. Same cell line- Okay ... that we've brought now into patients with autoimmunity. How many people did you treat? We treated about 40-50 patients in oncology. With the CD19 CAR T? With the CD19 CAR T. What were the results? The results in the oncology setting, we treated. Most of the patients we treated were post-autologous CAR T-cell therapy, so have been heavily pretreated and previously exposed to autologous CAR T-cell therapies. Despite that, we saw about a 50% response rate, about a 25% CR rate, and importantly, and an exquisite safety profile. And when you start looking at now the biomarkers that are potentially relevant for autoimmunity, what you are trying to accomplish? In autoimmunity, one of the first important steps is, do you achieve deep B-cell depletion with your CAR construct? Mm-hmm. We have been able to show that through translational data. We can achieve deep B-cell depletion with FT819. Secondly, it's believed that bad acting B cells are hiding in tissue, and that's also contributing to the autoimmune disease profile. Question then becomes: Can your product home and infiltrate tissue and deplete B cells, find those B cells that aren't in the blood? And we've been able to show that through translational data with FT819, that in fact, our cells, while administered to the blood, leave the blood home to tissue, are very active in finding, targeting, depleting B cells in the tissue. Okay. And that, therefore, enables. I think the view in the field is, if you're driving significant depletion of B cells, both in blood and tissue, your body's detecting that, your bone marrow is realizing that, and your hematopoietic stem cells are kicking now into overdrive to produce new, healthy B cells- Mm-hmm ... which are not harboring the autoimmune disease. Mm-hmm. A third thing that we showed recently was that the B cells that are coming back- Okay ... in the oncology setting are of the naive- Mm-hmm ... type. Mm-hmm. And so we do think we are seeing all the hallmarks early on- Mm-hmm ... of driving an immune reset. Yes. So in oncology, you have seen the B cells get depleted, you've seen new naive- Including in tissue. Including in tissue. You see new ones come back. Obviously, you saw T cell expansion. Yep ... and all those other things, and then we saw clinical responses in CRs in some pretty beat-up patients. Yes. So then to your lupus study, tell us about the design of this study. What are people doing? Where, like, I will tell you that, anyone who's been following this space, and there's various degrees of knowledge about this here and on the webcast, that it actually is, I understand, extremely challenging to open sites, get these things going, and one company I know says they have 17 sites up. One, a big pharma company says they have a bunch of sites, but everyone else pretty much has none or one, and that it's really difficult to get patients. In fact, one company, the stock went down a bunch because they had to completely change the guidance because they only had two patients to report on. Okay. Where are you with the design of the study? Yep. What is the design of the study, and are you gonna be able to really dose patients and enroll them? Yep ... and report data? Yep. Because it's pretty hard to get patients. Yes. So cell therapy is a brand-new modality for rheumatologists. Yes. I think one of the advantages we've had is that oncologists are obviously familiar with CAR T-cell therapy. We ran a study in oncology. Mm-hmm. We had sites, have sites up and running in the oncology study. We, as a strategy, approached our oncology sites- Mm-hmm ... and our PIs and oncologists to seek a partnership with the rheumatologist to bring our cell therapy to patients. Yeah, so like- And so- ... a site, I don't know. Can you disclose where the site is? Yeah, sure. University of Minnesota. University of Minnesota. University of Nebraska Medical Center. Those are the cancer centers that you're at. cancer centers, we were able to partner with the oncologist because we were running the studies already. Yes ... work with them to team up with the rheumatologist, and effectively launch the study. First of all, you've announced you have dosed patients, is that right? We've dosed it. You've dosed- We are open at 2 sites- Two sites ... today. Okay, there you go. Two sites. Two sites. We're open at two sites. Two sites, one- More to come. More to come. Okay. But we're open at two sites today. And yes, with just two sites, we were able to, from site activation to first patient dosed, was about eight weeks. Okay. Yeah. And so I think that partnership between the oncologist and the rheumatologist, having the oncologist already familiar with our product candidate, has provided one advantage. Okay. Number 2, I talked a little bit about how to date, the field has treated autoimmune patients using the same oncology paradigm, Cy/Flu conditioning. We launched our study with a little bit more of optionality on how patients are conditioned. So patients are able to either receive Cy/Flu, which is intense, they could receive Bendamustine, which is less intense, or they can actually receive Cyclophosphamide, which is actually given as standard of care, a later line standard of care treatment to patients with autoimmune. And so we are moving in a direction where we're bringing our cell therapies more to sites and patients alongside a treatment paradigm that they're already familiar with and receiving. So if a patient, for instance, today, in a later line, is getting Cyclophosphamide, we have that as an option, and we can add cells to that. So in the initial patients that are coming on, presumably they are being dosed first with Cy/Flu. It's an option. Yes, it's an option. So physicians have a choice of cy flu, bendamustine, or now cyclophosphamide. You'd stun me if the first couple patients did not have Cy/Flu. We will see. Hmm. Hmm. Because everyone else reports data with Cy/Flu. Mm-hmm. Hmm. We will see. Hmm. The options are what? They're bendamustine- Bendamustine, which we used on the oncology side. Okay. We did show in the oncology- Or cyclophosphamide- Or cyclophosphamide ... which is definitely gentler. Yes. One of the things I heard, and maybe you could just clarify for this, as people are definitely learning about this. Sure. We just had a big dinner with another company, and there's a lot of people in there asking different questions. There's different levels of understanding of this. Sure, absolutely. Is that- It's great. I actually was told that Cy/Flu. I hear different things about Cy/Flu. Is Cy/Flu really that bad? Like, the idea of women who may not be able to have children, that's actually disproven, that's not true. Is that- Look, I can- true or not, for Cy/Flu? I can't speak broadly, right, to the- That's one of the- field of auto- That's one of the top- To the field of autoimmunity. Right. For autoimmunity. I can speak to the feedback that we have received from PIs at our first couple sites. What did they say? ... there's a preference on the part of patients to not receive Cy/Flu conditioning. Right. Because either- Doesn't mean they won't enroll in a study. Right. But it's clearly a preference. Either because you can Google and hear about these things, or they're not, but the idea that there's risk to the idea- There's risk ... of being able to have- We know children, it's a risk. We know that. Whether true or not, that's not- Yeah ... gonna help someone. Yeah. Okay. The toxicity profile of Cy/Flu- Yeah ... conditioning is well known in oncology. Yeah, remind me of those. Oh, and you can, you absolutely can have long-term B-cell aplasia. You can have severe infections- Yeah ... and B-cell aplasia and severe infections are not a good mix for patients with autoimmunity. Sure. Okay. And so, that's one. Now, we want to have data with Cy/Flu, and we want to show that you can be there and have great potency, 'cause I'm sure that it's helpful- Yep ... to, you know- Yeah, no, early- To treat first for that. ... early patient- Yeah ... experience from a first principles perspective. Yeah. Absolutely. We want to be able to show that with our cell therapy, FT819- Yeah ... we can recapitulate early data sets- Yeah ... and drive an immune reset. Okay. Absolutely. At the same time, we absolutely want to start pushing and pioneering patient-friendly treatment regimen. Are you, like, literally one of the only protocols that allows that, that I'm aware of? Uh- In the- ... I don't wanna say the only one- One of the only ... but one, one of only a few, yes. That allows- It's also important. ... different lymphodepletion regimens. Yeah, and I think it's also important to note under our protocol, too, hospitalization is a big barrier. Mm-hmm. It really is. With FT819, we only mandate three days of hospitalization. The FDA allowed us only three days of hospitalization. Because of, why? Remind me of that. Well, we have experience in oncology. Right. So, in the autologous, like, if you go look at the Bristol Novartis, there's some pretty long, I'd say up to 14 days or something- 10-14 days of- 10-14 days of Mandated hospitalization ... Mandated to watch the patients- Yes ... because of risk of all sorts of tox. Correct. That's a problem. It's a challenge. It's a challenge. It's a challenge. It's a challenge. Yeah. Okay. So others that I hear about... By the way, EULAR is next week. Yes. At EULAR next week, it's well known that at least one or two public companies. Yeah, we'll see some initial data. Including Cabaletta. Yeah. We'll see some initial data. And the idea there is that they could have positive data, initial data- Yeah ... and less hospitalization days. Yep. They're pushing that idea. Yep. You also would say that you will also have low hospitalization days. Our first patient- You mandated only three days. Our first patient that was treated with FT819 in the lupus study- Yeah ... was discharged on day three with no notable adverse events. Yeah. So that patient that was treated, whatever, weeks ago, Couple weeks ago. Couple weeks ago, they got treated, the 3 days, they're home, they left, and they're doing good? Correct. Okay. You have 2. Number 1 was, you believe that the efficacy will be as good as others. Number 2, you are offering different lymphodepletion regimens. You just listed out 3 of them. Yes. Number 3, you have only 3-day hospitalization, others are up to 10-14. Correct. What data will you have at the end of this year? Couple patients. Couple meaning at least two? 3-5 patients. 3-5 patients. We've guided to 3-5 patients of data by the end of this year. Okay. They'll be at various stages of follow-up. Sure. But at a minimum, on 3-5 patients, we're looking at early B-cell depletion. Mm-hmm ... which, obviously can begin to happen as soon as day one, right? So we're looking at B-cell depletion over the course of the first 3-4 weeks. Then you typically start to see the B cells reconstitute, and you can look at that phenotype- Mm-hmm ... so you can understand, is the B-cell compartment, was it fully depleted? Do you see a phenotype that is largely of the naive subset? It's 4-12 weeks to come back. Yep, yep. And then importantly, many of these autoimmune diseases are characterized by class switching, and the immunoglobulins class switch. Okay. And so what we can do is also understand the population that's reconstituting- Yeah ... are they still harboring class switching? If they're not harboring class switching, that is a first really important indication that you've changed course of potential disease here. So my- 'Cause those, the class- Yeah ... switch phenotype. They're the bad actors producing sort of the autoantibody. Right, right. So there's, in even simpler terms, we're trying to get rid of B cells and deplete them because they are bad actors. They're bad actors. They are making- They are the bad actors. Totally ... producing- We wanna get rid of them— Aberrant antibodies ... and go all the way down to- Correct ... basically zero. Yep. And then we want the new ones to come back because they're completely reset- Correct ... don't have any of the memory- Correct ... of the past. They are no longer producers of these- Yeah ... autoantibodies. And so how does one measure that? They can actually just count the ratio or what? Yeah, you can, so you can look at B-cell phenotype. Okay. Are they of the type that produce these autoantibodies? And then you can actually look at autoantibodies. Okay. Well, okay. And so, and then also we, so number 1, from a phase 1, the idea that it's safe- Yep, important ... well tolerated, I think that's- Critical ... important. What lymphodepletion they got, I mean, I've just heard today it's possible that they're not gonna be all Cy/Flu. Yep. Then we wanna see B-cell depletion, B cells recover in the naive form, and then also T cells expand. Yeah. I'm less concerned about T-cell expansion- That's obvious ... per se, as opposed to driving the B-cell-mediated mechanism. Okay. And then to a degree, although small numbers, you'd wanna see- Obviously you measure the disease. Right, right. Yeah. So that's the... You can use SLE, SLEDAI measurement. SLEDAI is the lupus measurement. ... at month three. Yeah, and there you should start to see de- Absolutely. Yeah. Absolutely. I recall that, like, being listed as, like, 4 points or 3, 4- Yeah. So, I mean, just to give you a magnitude of- Yeah … what the room for improvement here. Yeah. Typically, one of the people have used composite endpoints in the past to study patient benefit. Mm-hmm. One of the composite endpoints has been a reduction in SLEDAI score- Yeah ... of four or greater. This is like a response rate? Yes, a response rate. Okay, yeah. What we've seen in Schett was- Yeah ... I mean, we're talking about 8, 10-... 12, 14-point- Yeah, yeah, yeah - reduction in SLEDAI. Wiping it out, basically. Wiping it out of it. Yeah, yeah. There is significant room for- Yeah - improvement. And to be, and I don't know the time course. Yeah. I need to look back at the time course. Yeah, 3 months. This first- Three months? SLE SLEDAI was first measured in the German study at three months. What percent of Dr. Schett's patients or others, what amount of response on average or depletion would they get in, of the SLEDAI score in three months? In 3 months, I think, in small numbers of patients, if it wasn't 100%- Right ... it was very close to 100%. Nearly 100% reduction of SLEDAI. Reduction and drug-free remission- Yes ... which have shown to be- At 3 months. At 3 months, which have shown to be durable. Okay, excellent. All right, and then, I mean, I could go all over the place here. So that is, that is really, again, at least within a six... This is literally coming by the end of the year. Yeah, well, first couple patients, we'll get a good- I mean, I'm impressed. You know, my understanding is that it's been hard to enroll patients. It is hard. It is, it is, and I think we had some benefits. You're saying your advantage is that you've been able to cross-cultivate with your oncology relationships. Yeah. Minnesota was one of the sites- Yeah. I mean, you just- Nebraska. Nebraska. Yep, Nebraska. At least the two sites. Yep. Okay. Yep. All right. And then, if I may, what else should, or should we be paying attention to? Obviously, there's a Ono compound- Yeah, yeah, sure. In maybe in the last two one minute- Oh, gosh ... tell me what I should be paying attention to. So- Appreciating that that is the big thing. I'll go really quick- Yeah. I'll go really quickly on this. So, in the context of patient-friendly solutions, for cancer and oncology, 522. 522 is- Yeah ... a 5-point edited CAR, CAR NK cell therapy. Yep. It is built with a feature that is designed to enable cell therapy to thrive without conditioning. That's the NK? That's the NK cell program. That has data- That has initially been studied right now- Okay ... in oncology. We're bringing it into autoimmunity. We should have an early data set in oncology by the end of this year. ASH. Understanding whether ASH. Uh-huh. Understanding whether or not ADR technology can allow cells to thrive without conditioning. Exactly. FT825 is a solid tumor program under collaboration with Ono. Yeah. It's a seven-point edited CAR T cell therapy, multiple mechanisms of action that are designed to specifically allow CAR T cells to home and infiltrate and overcome immunosuppressive signals that are- Yes ... that have sort of, you know, challenged the field in solid tumors. I look forward to data this year in Lupus. That is absolutely fantastic, and then also in oncology as well. A first peek in solid tumors. Yeah, first peek-