Well, thanks, everybody. Welcome. Welcome to our conversation with Kevin Grayson. Thank you so much for coming down to Miami and joining us. I will give you a second to get your mic back on, but I really, really look forward to this conversation. Let's start with the elephant in the room, and before we even get to Gracell-specific questions, Kevin, sorry. Obviously, yesterday, FDA put out a press release suggesting that CAR- positive lymphoma and leukemia was a general liability with CAR T therapies, and they called out all of the approved CAR Ts, regardless of target, and presumably this would expand to any other CAR Ts in development. Market took the news rather hard, but I think we've seen already a lot of debate about what this update means and what it's gonna do to the CAR-T space. So I'd love to get your brief thoughts on that before we get to Gracell's programs. Yeah. Thanks, John. Thanks, Evercore ISI, to invite Gracell to this conference. Very kind of you to start with that question. Obviously, we, just like everyone else, is in the process of gathering information and try to understand what that news, FDA news, really means. You know, we know as much as probably everybody else in terms of, you know, the numbers and everything, but I, I guess what we-- what I can share is specific with Gracell, which is, number one, we... Among all the patients we have treated, we have not seen any single case of SPM. We have not seen any single case of T-cell lymphoma-related AE. Okay, and obviously, we just announced on Monday that we had our SLE IND cleared by the FDA, so that literally just happened a few days ago, and during our communication with the FDA in that process, this topic had never came up. But having said that, what does it mean? I'll... I I mean, John, I'll let you kind of pitch in what that mean to the industry, but we, for us, safety is always extremely important for oncology patient and probably more for autoimmune patients, right? And I think that's one of the areas we felt our leading product GC012F really offered significant advantage compared with most of the others, if not all, and among... You know, we have treated collectively 60 oncology patients. We're talking about 29 RRMM, 22 NDMM, 9 DLBCL, and also we have SLE IIT. We have treated close to 10 patients at this point, and we've seen very sound safety profile, other than the no SPM, no T-cell-related AEs. In general, for example, the infection rate, this is a dual CAR BCMA CD19, so that's one of the questions people often ask, is that the infection rate. Infection rate is in line with all the single CD19, single BCMA we've seen from other companies. There's no additional risk there we have observed. We, on the ICANS and neurotox, we have seen zero ICANS or neurotox of any grade from any of the patients treated. The CRSs we have seen are generally very low-grade CRSs. You know, that to us one in the oncology space offers advantages to our program, and the autoimmune space gave us tremendous amount of comfort to move this exact same design to autoimmune, given the safety bar is higher there. Makes sense. Let's dive into your data. You know, obviously, we're primarily focused on multiple myeloma at this point. This is where we've got the most data at this point. There's been an absolute ton of both investor and company debate about the most appropriate way to do cross-trial comparisons in this setting, given how many differences there are between trials. Your 38-month median PFS got a lot of attention at ASCO, but it was immediately followed up by this group debate about cross-trial comparisons. So what's the right comp for that number? Is it fair to put it next to Legend's 35 months in CARTITUDE-1, despite all those differences in trials? That's a good question. It's always very challenging to do cross-trial comparison, although everybody try to do that. And there are many different ways to slice and dice this in terms of, you know, the category of high-risk, the definition of high risk, the ECOGs, the EMD category. So, you know, I would just kind of make sure that everyone here knows that at least in our study, the 29-patient RMM study that you cited, that has a 38-month median PFS, 90% of the 29 patients are high-risk patients, defined by mSMART 3.0, and over 60% of those patients are ISS stage three patients. And... Interestingly, is that we never set out to say that we only want high-risk patients, or we just want to see these ISS stage three. This is just a function of the IIT works, right? The IIT is supposed to kind of mostly use for patients who have tried everything else and then have no other options. So, you know, the data we generate from those arguably very difficult to treat patients give us a lot of confidence. And now we're moving to the U.S. trial, and we aim to enroll more kind of balanced mix of late-line multiple myeloma patients. And speaking of high-risk patients, are you planning on sharing subgroup data analysis from phase 1? Like specifically efficacy outcomes, by specific baseline characteristics like EMD or- Yeah. It's too early for us to comment what specific level of details that we will be discussing on the Phase 1b, 'cause we're just in the early stage of that. Obviously, we will be disclosing all these metrics, and statistically, it's probably gonna be challenging to do the subgroup analysis, given we're only going to have 12 patients there, right? Makes sense. You also mentioned minimal neurotox and a really competitive safety profile on CRS, which of course, the trial is still small, but is there a biological reason or a mechanistic reason to expect that minimal neurotox signal to continue into larger trials? Or is a reason to expect mechanistic differentiation from other BCMA makers? Right. I guess the short answer is only time will tell, right? But the more patient we dose, the more data we have, the more confidence we have on how robust this construct and the CMC process is. So I mentioned so far, almost—we have almost 60, almost 70 patient data across all the indications we treated. So come back to why we haven't seen any neurotox, ICANS of any level, we believe it's multiple factors. Obviously, CAR-T is a very complex process, and you know, our fast manufacturing, essentially, the key there is the younger phenotype of the T cell. Therefore, our dose are significantly lower than most of the other conventional CAR-T in the same target. That's number one. Number two, we have a dual CAR approach, BCMA and the CD19. The binder, the BCMA binder, matters. That's number two. We haven't specifically disclosed what kind of binder we use, but we know that matters. Number three is how the dual CAR is configured. Gracell done a lot of work on different configurations of the dual CAR, parallel tandem loop, before we settled on this loop configuration that give us, the best safety outcome. So it's difficult to quantify each, which piece we wish we could. We wish we could say we found a key for no ICANS, and we would have used that on every single program we have. Mm. Unfortunately, we do have ICANS from other programs, and... But this particular one so far gave us a very robust result. Yeah. Makes sense. Before we move on from talking about the previous myeloma data, I want to ask that with an expected launch in 2027, it's likely you'll be fourth or even fifth to market in myeloma in the U.S. Assuming other competitors that are in late-stage trials now get approved, what do you view as the market opportunity at that time, and what do you view as the key factors that would allow a new entrant to take market share and launch successfully in that market? Yeah. That's definitely the question that we focus and the investors focus as well, that given we are not among the first to be on the market, obviously, first mover always have the advantage, but that varies. We-- you know, there are two approved the drug on the market, and the, the success is not in order of the launch. And why? Because to us, that the three factors matters, right? Efficacy, durability, obviously, that's number one. You know, we're treating cancer patients. Safety, right? We talk about safety, is very important. And the three is the speed of manufacturing, right? I think we kind of touched on the first two. Let me maybe just touch on the third one, which obviously is, we believe is our platform advantage, the FasTCAR. The FasTCAR, the manufacturer itself, is we call it 20-36 hours, so call it 1-2 days, versus in a conventional CAR-T process is days or weeks. What we focus on, people ask vein-to-vein time, what we focus on is the manufacturer turnaround time, which is essentially from the apheresis to the FasTCAR after QC, going back to the hospital prior to lymphodepletion, right? So, our current process is able to deliver that within 12-14 days. If everything's all kind of done perfectly, we probably can do even shorter than that, but 12-14 days is the range we give, and that offers advantages on multiple levels. Obviously, it's, it goes without saying that the faster is better for late-line oncology patients. But the other important relevant factor is the ability not having to put those patients on bridging therapy while they're waiting. Those are among the top reasons that the clinician wanted to be part of our program. So we believe those three attributes, efficacy, safety, and fast turnaround, is going to continue be the cornerstone that drive the adoption of 12F by the time we launch. Yeah, and we next wanted to touch up on upcoming data readouts that you have. It's like you have data at ASH for newly diagnosed multiple myeloma, some follow-up data, and you guys are the first company to show CAR-T data in this first-line setting. So given that, what would you say would be, like, a meaningful data set in first line at this point? Because we don't have really any comps. Like, yeah, so how should—how will we be able to comp this data? And just generally, like, your thoughts on the first line CAR treatment setting, and where do you think CAR-T will be in that algorithm? Yeah, that's a great question. CAR-T treatment of multiple myeloma is rapidly moving to the earlier line and the potential front line, given the efficacy and the comfort level in terms of managing the safety profile compared to other type of treatments. And, you know, the multiple companies running multiple trials for earlier front line, and we are the first company reported the front-line data, so far. So I think the abstracts are already out for ASH, and so we're gonna be reporting 22 patient in that study with 96% SCR, 100% MRD negativity. I think the median follow-up time is... We're gonna have a fresh cutoff, obviously, by the time, going to ASH, it will probably be around 15-16 months. So, so extremely and plus the very sound safety profile, right? In terms of no ICANS, Neurotox. Almost 70% of those patients even did not have any grade of CRSs. Mm. And, I believe we only have one grade two CRS, actually, in that study, so kind of ideal profile for the front line. And the other topic is that what's definitely front line? Actually, it varies from company to company, right? And, front line typically means in a, you know, currently the standard of care is, like, what? 6 or 8 rounds of induction therapy- Dara- Plus, right, plus Dara, plus, you know, whether it's transplant or whether it's that CAR-T, and then there is a level of maintenance drug. I believe that our current construct is probably the cleanest, among those combinations in terms of, we use fewer rounds of induction therapy. And, so we are very encouraged, by the data so far we have generated, right? I mean, when you think about front line, are you thinking about a replacement for Dara-Rev-Dex induction? Are you thinking about a replacement for stem cell transplant? Right. Where in the algorithm is this? Right. So for this particular study, the enrollment criteria is high risk, transplant eligible. Obviously, that's target to replace transplant, because, you know, the study is going in China. Transplant, everybody know, is not without its risk, both short-term and long-term. I think mortality rate for marrow transplant in China is somewhere around 3%-5%. The US might be lower, but it's not zero, and, let alone the long-term, safety issue. And so, GC012F so far, what safety profile has demonstrated and also the efficacy, we believe that, really offers outstanding choice to patients versus choosing the transplant. Yes. This time, the high-risk part is the one we asked for. Yeah ... because otherwise, I think it's, it may be hard to justify why you want to put patient on the front line, front-line patient on a kind of quote-unquote experimental therapy, right? Fair enough. One more question about this front-line therapy before we move on to lupus, which I do wanna make sure we talk about. Yeah. But, you mentioned that transplant's not without its risks. That's certainly true, but it's also the only therapy that is given in myeloma with potential curative intent. So, what's your expectation for curative potential of CAR-T if it's replacing a full recapitulation of the immune system, like a Yeah. Obviously, time will tell. But looks like, you know, from some of the other companies who had a longer follow-up on the late line studies, seemingly that the quote-unquote "the functional cure" is possible. And for late line patients, you would think that's even more promising for front-line patients, given their... The key of having more successful CAR-T treatment outcome is the T-cell quality. Mm. And obviously, you target everything else, but those being equal is the quality of T-cell from the patient. The front-line patient T-cell, before it got battered by all the chemos and all the other drugs, definitely is a huge advantage to achieve a you know, much higher efficacy, and you see that from our study as well, right? Yeah. Well, let's talk about autoimmune in our last couple of minutes here. Obviously, there've been a lot of entrants into this field recently, a ton of excitement about CD19 CARs in lupus. But your construct isn't just a CD19 CAR, it adds BCMA. So can you talk a little bit about what you gain by adding that second target, and what's giving you confidence that this dual CAR will differentiate from single target options? Yeah, great question. The, obviously, after the German study came out, that's really groundbreaking, late last year, and, so CD19, everyone with a CD19 is moving to this field. It's great news for the patients. And, so for SLE at least, right? That the, the disease is a B cell-related autoimmune disease, essentially is the autoantibody attack patient's own tissue. So the key is to eliminate those autoantibodies, right? Those are autoantibody-secreting cells, so-called ASCs. And, there has been study, including our own study, to show that, there are a group of ASCs in the plasma cell that's actually CD19 negative. So just having CD19 is not going to be enough to completely achieve the reset. And- That academic paper that you mentioned did have a 100% response rate. So where does that deficiency- Yeah ... show up for you? I think that's where the study and will give us more info on the... it's CAR T is individualized. The medicine is related, is patient dependent, and so BCMA definitely, we believe, offers a benefit on achieve cleaner and deeper immune system reset, and we have data showing that. Whether it's needed for every single patients, time will tell, right? Yeah. Mm. Makes sense. You're supposed to have from your investigator-sponsored trial data in a handful of patients, first half of 2024. Will this be enough data to differentiate from competitors like Novartis and iCell put out data recently, or even compared to Schett's data, like, your patients will presumably be older and sicker than the patients in the Nature Med publication? So the answer to your last question, the patient baseline, it will be sicker. That's for two reasons. One, well, the Schett data is really revolutionary. I think we all agree that the baseline of patient in the study is relatively modest, right? And the definition of refractory SLE, and the age is very young, ages are very young. And once again, IIT tend to, we tend to get those patients who have much wider variability. That's number one. Number two, to your question on what the essentially you said, what the bar is, right, to be successful. I think everyone is still looking to find that. And Schett data is 100%, you know, it's hard to beat a 100%. Someone says it's not even possible. But I would say safety is going to be the first cut-off, right? And then from there, there is what the standard of care is, which is pretty low, to the shared 100%. I think we'll see how each program settles in. Yeah. Makes sense. We are out of time, but I'm gonna eat into our passing period a little bit here, if you don't mind, to ask you one very important question, and that's about pharma partnerships. Given both the size and competitiveness of the multiple myeloma market, it's widely expected, I think, that a manufacturing or commercialization partnership will be important. Do you agree, and is this something that you're actively pursuing at this time? Yeah, I think we've been pretty consistent that having a U.S./global partner is very important to us. Especially at multiple myeloma, moving to the earlier line, potential front line, those are bigger studies, and the autoimmune, that's a much bigger space. So, we won't be able to guide the timing of that. I would just say we're having very good conversation. The opportunity in the autoimmune space adds more dimension to those discussions. So, we're encouraged. Excellent. Well, we look forward to seeing news both in myeloma and ASH, in lupus early next year, and on the partnership front, whenever that comes. Well, same for us. Thank you. Thank you, John. Thank you so much, Kevin.