Hey, everybody. I think we'll get started here. Thanks for joining us here and tuning in to Piper Sandler's Annual Healthcare Conference. I'm Joe Catanzaro, one of the Piper biotech analysts. It's my pleasure to kick off this session with Gracell. Joining us is their CFO, Kevin Xie. A lot to discuss in these next 25 minutes or so, but maybe, Kevin, I could just give you a minute or two. You could just introduce Gracell, what you guys have been up to, what we have to look forward to, and then we'll jump into some Q&A. Sure. Thanks, Joe, and thanks, Piper, to invite Gracell to present at this conference. Gracell is a clinical stage cell therapy company, focusing on oncology and autoimmune space. We have three technology platform, and it's all developed in-house. On our target space, we have the FasTCAR, which is the fast manufacturing. In the allogeneic, we have the TruUCAR program, TruUCAR platform, and most recently, we share some data on our solid tumor program we call the SMART CAR. The lead asset for us right now is GC012F, which is under our FasTCAR autologous platform. It's a dual-target BCMA/CD19 that we have collectively reported 60 oncology patient data that's generated from multiple myeloma, that include RRMM, also NDMM, newly diagnosed multiple myeloma. And recently, we announced that this same program is expanding into autoimmune. The first indication is SLE. There, we have announced on Monday, we have obtained FDA clearance for our U.S. IND, so we're in the process of site recruitment and having the preparation for the phase one for SLE U.S. study. At the same time, we have also started patient enrollment in China for IIT trial, which is always part of clinical development strategy, is using the IIT process, to gain real clinical data feedback, before we start a sponsored trial. There, we have enrolled, you know, we said more than a handful of patients. We shared some preclinical or translational data during our Q3 call, not long ago. We're very excited with this particular construct, and it now has expanded into multiple indications, both in oncology and the autoimmune now. So, maybe I could just sort of ask this at the top, and admittedly, not even had a chance to sort of read through it, but there seems to be some news earlier that the FDA is looking into some safety questions around BCMA and CD19 CARs. Maybe you could just speak to whatever you know about that, and I would assume that since the U.S. IND for SLE was just cleared, there shouldn't be too much of a concern, but I'll leave it to you. Yeah. You know, I read same time as everybody else read, just about an hour or so ago, and, with the news. So, you know, I don't have any background to share, given we're all kind of trying to digest what that is. And what we-- what I can share with you is, obviously, number one, you know, you correctly point to that, we just on Monday announced the clearance of the SLE IND. So obviously, you know, safety is a very important focus for the FDA, and we just recently got it clear there. And, I mentioned, GC012F. We have reported about 60 oncology patient data. We have seen 0, secondary malignancy, from those studies. So safety actually has always been one of the key differentiation of this particular program, because I think we have... For those of you who have followed us, know that, you know, across the board, we have seen zero ICANS neurotox from those program on any indication. The CRSs, we have seen many low-grade CRSs. So the data so far give us a great comfort on the safety side for this particular program, and that's one of the foundations for us to move this program to autoimmune. Yeah, that, that's perfect. Maybe we'll get to, I think, a lot of questions on GC012F, but maybe first, just on the platform, I think there seems to be more and more companies speaking to fast manufacturing efforts. Gilead even most recently spoke to some of their efforts internally to try and speed up manufacturing. I guess when you look at your FasTCAR platform, what do you see as sort of key differentiating features there and what it allows you to do? And, you know, maybe feeding into oncology versus autoimmune, is it more relevant in one context versus the other? Sure. The you know, one of the major hurdle for CAR-T has always been, long manufacture turnaround time, and, it's been the goal for the whole industry to shorten that. And, our FasTCAR process essentially be able to, finish the manufacture process, within 22-36 hours. So what is that process? In a traditional CAR-T process, that involves three steps: activation, activate the T-cell, transduction, transduce the gene onto the activated T-cell, and then there's a lengthy ex vivo expansion step. Our process actually combine the first two steps. So we have our proprietary lentivirus, and that is able to transduce the gene onto the T-cell without having to fully activate the T-cell. And, because the whole process is short and, does not exhaust, fatigue the T-cell, therefore, we do not need the ex vivo expansion step. So the shortened time is not mechanically shortened. It's all built upon the younger phenotype of the T-cell, therefore, the T-cell is more potent. And what's the benefit of having a more potent T-cell? Obviously, but our dose are much lower than the conventional CAR-T process doses. The PK curve is more potent in terms of Cmax and AUC. So for oncology patients, the benefit of, especially for laid low oncology patients, the benefit of faster turnaround is huge because many patients cannot wait multiple weeks. And having the fast turnaround also enable the clinician not having to put patient on bridging therapy during the wait time. For autoimmune, and specifically for SLE as our first indication, some may feel that SLE is kind of a semi chronic disease, therefore, fast manufacturing may not be that impactful clinically. But in fact, those disease, patients disease, typically during the CAR-T treatment process, the patient are required to stop all the immunosuppressive drugs they otherwise will be on. So, usually the only thing they can still be on is low level steroid. And as a result, a longer wait time could lead to disease flare up and tissue organ being damaged. As a minimum, the quality of life is a huge setback for those patients during the long wait time, not having any immunosuppressive drugs. So, you know, the fast manufacturing, the benefit, clinical benefit is huge, together with economic benefits, right? In terms of a cheaper delivery. Yeah. Maybe last question on this topic, and I know it's still very much the early days of the U.S. myeloma trial. Wondering if sort of the early days of manufacturing and turnaround are sort of consistent with what you've historically seen within your sort of China IIT experience. Yeah. So our China IIT study, the 29 patient, RMM study, the manufacture turnaround time, the median time, in that study is about 16 days. And, what in our U.S. study, the protocol is designed such that, that time frame, we're aiming to do it between 12-14 days. The biggest component of that duration is the QC, which if, you know, if there's an in-house QC facility, that's a seven day process. We believe that, in the future, we could shorten that maybe to five days. So all things being equal, you know, there is opportunity to shrink the manufacture turnaround time in the future for us to as low as maybe seven days. So I want to shift now to specific questions on GC012F, and maybe specifically within oncology and myeloma. And I know you mentioned sort of the safety profile you've observed to date, but as we sort of look into the future of, you know, potentially three, four approved BCMA CAR products, what do you see as the biggest sort of selling point to the profile you've generated thus far? Yeah, that's one of the most frequently asked questions. Obviously, there are already two approved single BCMA therapies for multiple myeloma. And I think one thing we have seen is that, you know, first one to the market may not be the best one to the market, and we've seen that already from those two. For us, we always focus on differentiation because we know that we'll be competing with others once we get onto the market. There's three things that's the key to have to drive the adoption in the CAR-T, right? Is obviously, fitting oncology patient efficacy, and durability is very important. And number two is safety, and number three is the manufacture. On the first one, the most data update we reported on ASCO this year, in terms of, the first time we're able to report estimated median PFS of 38 months. And it gives people, you know, much higher confidence in terms of, how our durability is going to be able to compete with others. And the safety profile, I already mentioned, that's a key differentiator as well, together with fast manufacturing. So as data continue to mature, as we demonstrate the robustness of the CMC manufacturer, and, we believe this program is going to offer clinical benefit, to the patients and is going to drive adoption. So I know at ASH you guys will have an update for the frontline myeloma experience, which I wanna touch on. But maybe with regards to the China RRMM study, any expectations around whether you will take another cut of the data, provide another update, and, you know, is there anything else sort of new we learned there? The IIT, technically, the data ownership belongs to the PI. So, PI may have plans to have updated presentation or manuscript. For us, our focus is already shifted to the U.S. phase I trial for RRMM at this point. So, yeah, so then maybe, maybe with that, that's a good segue. I think there's still this sort of like background sort of discussion of how data generated from a China IIT translates to a U.S. trial and a U.S. population, even though I don't think it's grounded in much evidence. But, but I guess, what do you see as, you know, the potential biggest risk of what you saw in China, maybe not translating to what you will see in the U.S.? The quick answer is that, you know, we're not anticipating, there is and there's reason to believe the patient response will be different. And, you know why? Because, we have seen from another program that's on the market, that's transported from China to the U.S., and, you know, where data actually improved. And the, and the so there, there is no evidence to support, the, the demographic would have an impact on the patient outcome. But obviously, that's, you know, we can, you know, we just kicked off the patient enrollment in the U.S., for our phase I-B trial, and that's the focus of the FDA in terms of safety. And so we're gonna be focusing on, getting that program run and, to support, continue to support the robustness of the profile. Yeah. So you mentioned your focus within myeloma has largely shifted to the U.S. study. What can you say is sort of how the early days of that trial are going, sort of your expected timelines, you know, when we could maybe see some initial data from that trial? The phase I-B is a 2-dose, 12-patient together program, and so 6 + 6 were required to dose patient in a staggered fashion, especially in the earlier patient dose schedule. So collectively, it would take about 9-10 months to enroll the 12 patients. We anticipate, timing-wise, we'll finish that around midyear next year. So the first public data readout for our U.S. phase I-B study will likely be second half 2024. Got it. Maybe expectations for like, again, in the early days, like the types of patients you're enrolling in terms of number of lines of prior treatment, prior BCMA exposure, if that's allowed or not, I forget, and any other sort of considerations there. Yeah. So in general, the treatment inclusion and exclusion criteria is fairly all-inclusive. So maybe I just step back one step in terms of the data we generated from China IIT study with the patient baseline. There, the 29 patients, 90% of them are high-risk patients by mSMART 3.0 criteria. Over 60% of those patients are ISS stage three patients. So those are very difficult to treat patients. It's just a function of IIT usually is just reserved for patients who tried everything else, have no resources. In the U.S. trial, we aim to have a balanced patient mix in terms of regular risk and high risk. You asked specifically on the prior BCMA or prior CAR-T. We're not completely excluding those patients, but we do have minimum requirement on the wash out time. I think in reality the plan is not to enroll significant prior BCMA relapse patient for the phase I portion. Maybe we'll consider we have a separate cohort once we move to the phase II. Maybe last question with on the oncology side. I mentioned sort of the ASH update from the frontline high-risk myeloma. What new do we sort of learn within that data set? And ultimately, sort of how do you leverage that data into a sort of bona fide clinical development strategy? Right. So that the NDMM study, the patient baseline were 100% high risk and the transplant eligible. Basically, that is aiming to replace transplant, for the frontline multiple myeloma patients.... we had reported a 19-patient data most recently in September at IMS, a symposium. This ASH update, what you will see, is three additional patients. So it will be 22 patients, will be a slightly longer follow-up. So probably, if I recall, will be somewhere around, between 15-20 months of median follow-up time. Yeah. Okay, got it. That's helpful. Maybe, in these next six minutes to go or so, we could shift to SLE. Maybe actually work backwards. So, you know, you mentioned the US trial is designed in a way where it's exploring two dose levels in sort of a stepwise, fashion with the U.S. IND and SLE now cleared. What's the dosing strategy there within the, the design of the, the, the trial? Is it a similar sort of explore two doses in a stepwise fashion? Is it the similar doses you're looking at, within myeloma and what you've looked at in the China SLE experience? Yeah. For U.S. phase 1, we are planning to explore similar dose levels as we use for multiple myeloma study. And, we continue to gathering feedback from the ongoing SLE IIT trial, that's in China. I mentioned that we have enrolled, you know, between five to 10 patients, and we're dosing them up. The China IIT trial, we're using the same three dose levels as for multiple myeloma. So, we will see. We'll gather feedback. We'll see whether there's opportunity or need for us to dose it up, whether there's additional benefit to tweak around the lymphodepletion process. We're starting with essentially the same process as we use for multiple myeloma, because the data have give us the clean safety profile, give us a great starting point. We expand that to SLE patients. Maybe sort of going to the top of this discussion, or maybe what I should have started with is sort of your level of conviction that this dual antigen approach will give you the opportunity for best-in-class profile with within autoimmune indications relative to, say, CD19. And whether you think the early data you've shown in terms of sort of B-cell depletion supports the notion of a best-in-class profile. Yeah, the German study from Dr. Georg Schett's group late last year with a single CD19 generating very impressive result in SLE patients certainly is groundbreaking. That blocked the whole field with the CD in a single CD19 shifting to autoimmune. And we have a dual CAR CD19 and the BCMA. So the MOA for CAR-T treating autoimmune patients is all about resetting their immune system, right? So the immune system of B cell and plasma cell, and the CD19 has shown very effectively resetting the B cell. And we've shown that recently, you know, from our translational study that as part of our IIT study in our Q3 earnings call. But at the same time, there has been study, including our in-house study and some literature published in the past, that there are a group of autoantibody-secreting cells in the plasma that actually are CD19-negative. And those ASCs can stay in patients' plasma cell for a long time, maybe forever, and there's risk those ASCs would trigger autoimmune reactions down the road. So having the B, having the CD19 and the BCMA targeting both B cells and the plasma cells, we believe is going to offer additional benefit to achieve the immune system reset that this whole process is aiming to do, right? So in a way, this program is ready for the autoimmune study when the opportunity presents ourselves. And it's actually, we're very fortunate to have this program ready to go. So, you guys have guided towards, you know, another disclosure from the China IIT SLE study in first half 2024. What should we expect to see there in terms of patient numbers, but more so in terms of, like, additional measures of efficacy, whether we should expect some functional outcome endpoints, anything along those lines? Yeah. So, we will be... we're planning to have the public data release in a medical conference first half next year for our China SLE IIT study. What you will see is, you know, double-digit patients with at least a three-month follow-up time. Some of the patients will have much longer follow-up time, obviously. And we're tracking all the functional and the biomarker data. And there's a whole list of antibody data we're tracking and, you know, and including some disease, the renal disease function and some of that group into the SLE, that composite index. So all those will be published when we report our data first half next year. Great. Maybe last question in the limited amount of time we have here. Going back, maybe high level sort of strategy. You guys have sort of mentioned interest in partnership opportunities if they present themselves and they, it makes sense. I guess, sort of bigger picture, how do you think about that? Is it more program specific, platform specific, or maybe even like indication specific as we talk about, you know, GC012F within oncology versus autoimmune? Right. Yes. Our corporate development strategy has always that we feel there's huge advantage to have a global slash U.S. partner who have really the infrastructure for clinical development and potentially even commercial to push the program, you know, not only in terms of the speed, but the breadth of indications that we're aiming to target. So here, given the data we have generated, we're having, I would just say that, a very active conversation. And now that conversation have added new dimension on autoimmune. So there are different ways to structure that, depends on the strategic focus of the partner. Obviously, the economics, everything that needs to make sense. So we're excited, you know, where that conversation is going, and we think, you know, that something's going to take our program to the next level. Yeah. Perfect. Well, with that, I think we're out of time. I want to thank Kevin for his time. Thanks, everybody, for joining us. Take care and enjoy the rest of your day. Thanks, Joe. Perfect. Thank you. Okay, let's go ahead, get started. My name is, Ally Bradzel, one of the Senior Biotech Analysts here at Piper Sandler. So, thanks for joining us. It's, my pleasure to introduce, the team from Scholar Rock. So, joining us this afternoon, we have Jay Backstrom, President and CEO, and Ted Myles, COO and CFO. So, thanks all for joining us.