Ladies and gentlemen, thank you for standing by. Welcome to the Gracell Biotechnologies Key Opinion Leader Webinar on Relapsed Refractory Multiple Myeloma. At this time, all participants are in a listen-only mode. After prepared remarks, we will open the call for your questions. Instructions for queuing up will be given at that time. I will now turn the conference call over to Kevin Xie, CFO. Please go ahead, sir. Dr. Shih, I apologize, we are not hearing you. Dr. Shih, we're still not hearing you on this end. This is the operator. Thank you, Kevin. Again, welcome everyone to our KOL webinar. I will commence today's webinar by providing a recap of Gracell's highly differentiated FasTCAR-T candidate, GC012F, and our upcoming phase Ib/II trial. I will introduce Dr. Saad Usmani and turn over the event to him. GC012F is a next generation autologous CAR-T therapy developed in-house by Gracell. It has several differentiating features that we believe would help improve patients' outcome and address some critical challenges faced by the cell therapy industry. The first key design feature is its unique BCMA/CD19 dual targeting mechanism action. By targeting two antigens, we hope to maximize elimination of multiple myeloma plasma cells and the CD19 progenitor cell reservoir. We believe this could help drive deep and durable responses. The preliminary but compelling evidence is the fact that the GC012F has achieved deep responses such as high sCR rate and 100% MRD negativity among all patients treated in our multiple myeloma IIT studies. We expect to provide updated clinical data at ASCO and EHA next month to further expand the clinical evidence supporting GC012F's depth and the durability of response in comparison to single CAR T products. In addition, GC012F utilize our proprietary FasTCAR-T next-day manufacture process. It enhances T-cell fitness, reduce the manufacture time to overnight. For a personalized therapy such as CAR T, manufacture time in innovation has always been a key topic. With FasTCAR, we hope to provide clinicians tech and the patients a shortened and a more predictable wait time. We believe this would help reduce the time when the disease is not optimally managed and positively impact patients' outcome. Since 2019, we have been conducting proof-of-concept studies on GC012F in multiple myeloma, NHL, and recently in autoimmune disease such as SLE. GC012F has shown a consistently excellent profile in these studies. On the safety side, it's worth noting that there was no neurotoxicity or ICANS observed in over 50 patients treated in our studies. CRS was mostly low-grade in the RRMM study, and 75% of patients didn't experience any CRS in the newly diagnosed multiple myeloma state. On the efficacy side, GC012F has achieved high overall response rates, high stringent complete response rate, and 100% MRD negativity rate across studies, including in the RRMM-IIT study, where 90% of enrolled patients were classified as high risk. We look forward to presenting long-term follow-up data from our RRMM investigator-initiated study at ASCO and EHA in early June. Gracell has reached a very exciting milestone as we plan to initiate a phase Ib/II trial in RRMM in the coming weeks. In the phase Ib portion, we anticipate to activate 5-10 sites and enroll around 12 patients. We will be evaluating two dose levels of GC012F, including 1 x 10^5 per kilo and 3 x 10^5 per kilo, which were the low dose and high dose used in the IIT study. The primary objective of the phase Ib portion is to assess the safety and tolerability, as well as to determine the recommended phase II dose. I'm honored to introduce the key speaker for today's event, the chief of the steering committee for our U.S. trial, Dr. Saad Usmani. He is a hematologic oncologist with more than 16 years of experience specializing in the care of patients with multiple myeloma and other disorders affecting plasma cells. He currently is a Chief of Myeloma Service at Memorial Sloan Kettering Cancer Center in New York. Dr. Usmani has led clinical development of several novel immunotherapies and small molecules for multiple myeloma. He has authored and co-authored more than 230 peer-reviewed research manuscripts and over 300 abstracts at national and international meetings. Dr. Usmani has served as the vice chair of the SWOG Myeloma Committee and has served as chair for the ASH Scientific Committee on Plasma Cell Neoplasia and ASCO Scientific Committee on Plasma Cell Disorders. Active in clinical translation research, Dr. Usmani's research interests focus on Plasma Cell Disorders, in particular high-risk multiple myeloma. I hand it over to Dr. Usmani. Usmani, please go ahead. Thank you so much. you know, it's a privilege to be here and speak to all of you. over the next, you know, few slides, I wanted to share my views around the landscape in the relapsed myeloma space. you know, we have made a lot of progress in myeloma therapeutics in the last, especially in the last 6 to 7 years. I wanted to do some groundwork in terms of you know, sharing with you know, where we've come from, where we're headed, especially in light of you know, the immune therapies that are emerging right now in early clinical development. These are my disclosures in terms of research funding and consultancy activity. I want to start with, you know, this particular slide, just sharing with you what the current global landscape for myeloma looks like. For our newly diagnosed patients for the most part, vast majority of patients receive now either a three or a four-drug combination. For transplant eligible patients, you know, they go on and receive the autologous stem cell transplant, depending on which country you belong to in either Europe or Asia. There will be some patients, you know, who receive a double transplant or a tandem transplant, as we call it, before moving on to maintenance treatment. We still have a very small proportion of patients because of access issues, you know, who receive two drug combinations as well. You know, I just wanted to, you know, share with you know, this kind of landscape because it influences the outcomes for patients. You can see the expected median progression-free survival depending on the kind of treatments patients got. You know, depending on whether we look at the clinical trial or the real world data can be a little bit variable. This is because myeloma disease biology is different. Myeloma is not one disease. You know, there are therapies that help us in improving outcomes for certain high-risk features. There are other therapies that do not have any impact, you know, on the high-risk features. This is where we feel the immunotherapies are going to change our trajectory for those high-risk patients who do not have good outcomes. It also, you know, lends itself to the complexity of what kind of patients we see at first relapse, because the journey to that first relapse is so variable, you know, across, you know, across the patients around the world. You have to keep this in mind that it's not an easy answer. You know, while we think about creating algorithms, you know, many of those end up being more general guidelines. You know, when we think about selecting therapies at the relapse stage, you know, we kind of bucket the various factors into either patient-related factors, disease-related factors, or previous therapy-related factors. You can see when it comes to patient-related factors, it's r\eally about, you know, age, performance status, perhaps more than age, you know, different end organ reserve. you know, whether patients have chronic renal insufficiency or hemodialysis dependence. Do they already have pre-existing neuropathy because they've been diabetics for a long time? Do they have heart and lung issues that prevent them from, you know, receiving optimal treatments? Disease-specific issues, how quickly is the relapse happening? Are they, you know, getting new organ damage? Are there any high-risk clinical phenotypic features like extramedullary disease or plasma cell leukemia? Do patients now have, you know, more than one high-risk features at the time of relapse? From a treatment standpoint, you know, what kind of treatment patients received in the past? you know, what was the depth and duration of response? How did they get the treatment? You know, what was, you know, cause becomes an especially global concern, but, you know, previous side effects such as myelosuppression, neuropathy, thrombosis. Also, you know, taking into consideration the low risk, you know, the low percentage of patients who do have the second primary malignancy. You know, all of those things are very important considerations. The good news is, you know, that when we come to the early relapse, you know, depending on all of those factors, we have several options that we can utilize for patients, you know, that are currently like, you know, have regulatory approval. You know, there are some options that, at least in the United States, can be utilized off-label after insurance approval, through the appeals process, such as venetoclax for translocation 11, 14 disease. You know, when we think about lenalidomide combinations, you know, because majority of myeloma patients currently are on len maintenance, you know, this option is typically reserved for patients who have been off of lenalidomide for a while. You know, for the most part, patients do go on to receive either a pomalidomide-based combination or a carfilzomib-based combination, if patients are progressing on lenalidomide. This is something that I can share, you know, better on the next slide because, you know, when patients relapse, you know, the refractoriness to lenalidomide is a very important, you know, key in our decision-making on what kind of treatments we are going to pick. Because that len exposed or len-sensitive patient has many options. Whereas patients who are becoming len refractory, you know, their options are with second generation, you know, PIs or IMiDs typically. After patients move from the first to the, you know, second relapse or third relapse, the typical approach that we have is to try to find good clinical trials for them or give them treatments, you know, with therapies that they have not seen before. For patients who are transplant eligible, who either did not receive a transplant as part of their initial therapy, active stem cells for later use, we can use those stem cells. If they had a durable response for at least two or three years, you know, we can, you know, give them treatment with another autologous stem cell transplant. That ends up being an option that, you know, many countries utilize because of drug access issues. However, I mean, this whole landscape, you know, will be very different, I believe in the next 5 to 10 years, because of, you know, the wonders of immunotherapies. I don't think that this crowd is indifferent to this, you know, wonderful CAR T-cell therapy technology. you know, CAR T-cells are, you know, currently FDA-approved for both B-cell and myeloma indications in the United States, you know, as well as in Europe. They have really revolutionized the way that we think about treating multiple myeloma, you know, specifically. you know, there are several surface markers that are being explored for myeloma, but the B-cell maturation antigen is the farthest along in clinical development. This slide provides you a good summary of the different products that have been reported in the literature, showing very high response rates. Just to give you a context, before we had, you know, these wonderful immunotherapies, for the relapsed/refractory multiple myeloma patients, if we were to get a 25 to 30% response, you know, with any small molecule or therapy, we would be jumping over the moon as multiple myeloma researchers. Now we are seeing, you know, such, you know, wonderful high response rates and good depth of response and durability of response with therapies. So it's very, you know, gratifying to see these kind of responses and durability of response for these advanced multiple myeloma patients. Just to be mindful, you know, the median prior lines is, you know, therapy, it says here 5 to 6, and for some therapies up to eight lines of treatment. To give you the context, you know, these patients typically only have a progression-free survival of about 4 to 5 months and a median overall survival of about 8-9 months. Seeing these depths of responses and durability of response is quite gratifying to see. What we are finding, in addition to this, and here I'm only giving one important example, is the depth of response. You know, if we get utilizing two different assays measuring the same, you know, similar things, so either by flow cytometry or next-generation sequencing, if we look at minimum presence or absence of minimal residual disease, CAR T-cell therapy is able to drive patients into MRD negativity status, and that's what's correlating with sustainability of response and the outcomes. Here patients get, you know, remember, you know, just one infusion of therapy, and then they're not getting any maintenance treatment after that. The quality of life, you know, for majority of these patients is quite remarkable in absence of, you know, any additional therapy. That's a very important piece of information. Of the two products that are currently available in the United States, there are differences in safety profile in terms of when the, you know, Cytokine Release Syndrome happens, when does the neurologic event happens. Most of these events are grade one and two are quite, you know, well-managed, you know, in the clinic. It's just that we have to be mindful of, you know, the timelines when they're happening. Another important aspect of targeting BCMA here is that unlike our experience with the CD19 targeted, you know, CARs than, you know, in the past, you know, we're seeing a very different kind of a profile, very manageable profile with, you know, this, these kind of CARs. Then, you know, lastly, I think, you know, we've already heard, you know, what, you know, a little bit about the GC012F, you know, which is the first, dual targeting CAR targeting BCMA and CD19. It's showing, you know, very high overall response rate. You can see in this early experience that was presented, you know, at EHA last year, the depth of response that you're seeing is kind of unprecedented in this experience. You can see triple class exposure and high-risk cytogenetics. You know, these are patients who are at a very high chance of the myeloma coming back very quickly. You know, this patient population is, you know, heavily pre-treated and has enriched for high-risk features. We are seeing, you know, very high overall response rate, you know, and MRD negativity, you know, that's been seen as, again, you know, very remarkable. I'm looking forward to, you know, hearing more about, you know, these data at ASCO EHA this year and hopefully updates at ASH. It shows that we're moving from the earlier generation of treatments to, you know, making CARs, you know, that are dual targeting and that are able to be delivered to patients in a reasonably quick duration of time. Perhaps, you know, we can talk a little bit more about that during the Q&A. You know, before I, you know, kind of end my talk, I do want to, you know, say that, you know, it will be very important for us to move these therapies into the frontline setting. You know, autologous cell transplant has been the mainstay of, myeloma treatment globally. I think, you know, CARs have the, you know, inherent potential of replacing that as the preferred cellular therapy intervention that we do for our patients. You know, we are in the process of generating that data right now, you know, I really look forward, you know, to the time when we can move these therapies to the frontline setting. You know, we've gone from considering myeloma as an incurable disease with outcomes of, you know, an average of two years to more than 10 years. I do feel that, you know, better future is ahead for our patients. You know, it's, you know, it's very gratifying to be part of that journey and making this happen for our patients. With that being said, you know, I am going to, you know, acknowledge, you know, our wonderful myeloma service team members who care for patients as well, as well as our transplant cellular therapy team, members, you know, who help, deliver the CAR T-cell therapies commercially as well as on clinical trials to our patients. With that, you know, I'm going to hand things back over. Thank you so much for listening. Thank you, Dr. Usmani, for providing the perspectives for treating, from a treating physician as well as a leading researcher, for such a complex disease. Indeed, advancements in cell therapy is revolutionizing the treatment landscape for multiple myeloma, but there's still significant opportunity for improvement. That's really what motivates our team every day. Now, I will kick off the discussion session. For the listeners on the phone line, you can press star one on your telephone keypad to be placed in the queue. For the ones that are listening on the web, you can also key in the questions on the web, and then, I will be able to read these questions to Dr. Usmani. As the operator taking in question from the callers, maybe I'll start with some opening questions that we collected. Maybe the first question, Dr. Usmani, autologous CAR T is a highly personalized therapy with complex manufacturing, therefore, the manufacturing time has always been a key aspect that everyone is watching for. Can you provide an overview of a current patient wait time, and the manufacturing issues faced by the CAR T players? Certainly I can provide, you know, the general experience we've had in the United States, you know, with the availability of the two commercial, you know, BCMA-directed autologous CAR T-cell therapies. I think, you know, the rollout was a little bit challenging because of slot availability at each of the transplant cell therapy centers, you know, with both products. There were, you know, initial, you know, challenges in getting the products back in a reasonable amount of time. Sometimes, you know, there were delays even up to six or seven weeks. This is something that was felt across the board at, you know, throughout all the transplant cell therapy centers around the United States. This posed, you know, a challenge for managing these difficult to treat patients and keeping their disease controlled. On top of this, you know, there was also, you know, concern around out of specification products that, you know, was being seen with, you know, both the commercial products. You know, I think, you know, there were many challenges. Some of those challenges are improving this year, but, you know, that did dampen a little bit of the enthusiasm that we had, you know, for this technology, you know, early on because, you know, we want to provide this to our patients, but, you know, I think access was an issue. Yeah. Maybe I can just follow up on that with the long wait time and also inconsistent, time before, between the apheresis and infusion. What's your experience in managing these patients between apheresis and infusion? We would, you know, try to get these patients apheresed and then try to control their disease sometimes with conventional chemotherapies or with treatments, you know, that they have seen before but, you know, not in that combination to try to, you know, control the disease while we're trying to wait for the CAR product to come back to us, you know, from the manufacturer. You know, it did pose quite a bit of a challenge. You know what we look forward to is, you know, ways in which we can shorten that time for our patients and make it more reliable. You know, right now that's what's, you know, lacking a little bit, you know, with our experience. Our collective experience as a myeloma community, I should say. Great. Thank you. Operator, are there questions in the queue that you can bring in? Yes. We'll take our first question from Yigal Nochomovitz with Citigroup. Hi, this is Carly on for Yigal. Thanks so much for hosting this event and for taking our questions. We have a few for Dr. Usmani. I guess just to follow up on some of those prior questions. Given some of the limitations you mentioned around the current approved autologous CAR-T, I'm just curious what proportion of the addressable population are ultimately receiving autologous BCMA CAR-T therapy currently and how you think that could potentially be improved upon. Then I guess another related question is just how you're thinking about the FasTCAR manufacturing platform relative to maybe some of the allogeneic CAR-T that are currently in development. Thank you for... It's a two-part question. You know, the, the first question, you know, relates to, you know, how we were, you know, how many patients were actually able to get BCMA CAR. We always had more patients than slots leading up to the end of 2022. You know, we have more slots being provided by the sponsors, and that has really helped in, you know, in managing that queue to a point right now where we don't have as much of a wait time. I think there were several factors, in terms of the raw materials, some of the regulatory restrictions that were placed on the manufacturers to first prove that they can deliver good quality product to centers before the regulatory authorities allowed to open things up for them. However, even with that right now, I think the bigger challenge has been getting products in time, and that out of spec concern. The sponsors have provided out of spec protocols through which we can get that out of spec product for our patients, and get it to them. However, early on, you know, just like in the clinical trial experience, you know, there were patients who get deprioritized. Because, you know, these are very difficult to treat patients, you know, who are, you know, have, you know, run out of, you know, other treatment options. You know, there are patients, you know, who have fairly rapid disease progressions, and don't, you know, get the product. The proportion of that patient, you know, those patients, I would say is, you know, maybe about, you know, 5 to 6%. We have gotten better in trying to manage their disease, you know, during that wait period than, you know, we are very proactive about it, you know, from the get-go. That's, that's, you know, one comment. I think, you know, even that, you know, 5 to 6% I think, you know, could be down to 0% if we were getting, you know, the product in a reliable and fast, you know, time period. This is where, you know, I think, you know, the FasTCAR platform comes into play. If we have a consistent and quick time, turnaround time, for vein to vein, for our patients, I think that, you know, that will be ideal for our patients, you know, while not compromising, you know, efficacy of the product. I think those will be important, you know, issues. I think, you know, that, you know, to your other, you know, second part of the question, you know, what about the AlloCAR? I think, you know, we do need, you know, a bit of long-term safety data, you know, because, you know, with targeting, you know, targeting CD52, there is an inherent concern about the long-term infection risk profile that may be very different than an Allo than an auto product. You know, we do need a bit more information there, but, you know, before we can, you know, decide one way or the other. I suspect that the infection safety profile will be different for those products. Okay, great. That's super helpful. We also wanted to get your thoughts on the small cohort of data we've seen for GC012F in high-risk, newly diagnosed multiple myeloma patients, and just broadly your thoughts on the potential for BCMA CAR Ts in that setting. Thank you. I do feel that, you know, the CAR T-cells are going to be important for both standard as well as, you know, high risk eligible patients. I think the strategy for high-risk patients will rely on multi-mechanism of action kind of an approach. While, you know, the BCMA may be, you know, a good target for, you know, BCMA on its own may be, you know, good for standard risk patients, you know, in terms of trying to get them to a durable duration of response. I think the approach for high risk will have to be different. This is where I think, you know, dual targeting, you know, would make sense. This is a nice, good first step, you know, in that direction. You know, there was, you know, a study being done, you know, in the frontline setting with, you know, the first commercial product that was FDA approved. You know, I don't think those data are in the public domain, you know, and I can't share them. I had, you know, the privilege of leading that effort. You know, I think, you know, BCMA CARs, I would say benefit, you know, patients in the frontline setting, but the degree of benefit, I think would be different for standard versus a high-risk patient. That's just my, you know, opinion based on the disease biology for those high-risk patients. Got it. Thank you so much for taking the questions. We'll go to our next question from Joe Catanzaro at Piper Sandler. Hi, everybody. Thanks so much for taking my questions. Maybe just two quick ones for Dr. Usmani. Dr. Usmani, you alluded a, I think a bit to the sort of timelines to toxicity earlier in your talk. I wanted to follow up a bit there and see if you could speak a little bit around the delayed parkinsonian symptoms that's been observed for some of the commercial products and, you know, how challenging that is and, you know, how notable it would be for GC012F up to potentially avoid that. A follow-up. Just curious to hear your thoughts on sort of off-the-shelf BCMA bispecifics and what role they will play relative to autologous CAR T product. Thanks. To answer your first question, you know, with the cilta-cel product, you know, in CARTITUDE-1, you know, when patients were being enrolled, you know, many patients were not in a position to reduce. We had patients who had, you know, higher burden of disease getting pre-produced and then going on to receive product. You know, we saw this, you know, delayed neurocognitive kind of, you know, Parkinsonian effect in patients. Even though it was, you know, somewhat self-limiting and got better over time, you know, some patients did receive, you know, maybe, you know, steroid courses or, you know, some conservative management measures. What was recognized was that, you know, the disease burden has to be well controlled before you give the CAR product. You know, if you have higher grade of CRS, high burden of disease, that puts, you know, a little bit, you know, of a challenge with neurocognitive signal later on. You know, even with the commercial experience, you know, many colleagues, you know, around the country have noticed this, you know, issue to surface in patients. Because remember, in the real world, you know, we are treating patients with higher burden of disease, maybe seven, eight line of treatment. You know, they might have, you know, renal insufficiency. They might not have the ideal counts to qualify for the, you know, clinical trial. You know, it's the real world. You know, it is being seen, you know, and, you know, it is something, you know, somewhat of a quality of life, you know, concern. You know, it's, it doesn't appear to be, you know , overtly debilitating for patients or something that one can manage. At least, you know, in the current experience, you know, with the GC product, you know, there is no, you know, signal that's being, you know, observed here. You know, we don't know what that dual targeting, you know, how does that influence, you know, that potential, you know, safety concern. Yeah, I mean, it's there for the commercial products, but, you know, it's manageable is what I'm trying to say. Okay, thanks. Your second part was the bispecifics. I'm sorry about the long-winded answer there. Bispecifics, I think, you know, there will be a place for both. There are many parts of the United States that do not have access to transplant cell or therapy centers for two, 300-mile radius. I think that there will be places where, you know, bispecifics are being utilized even at the, you know, transplant cell or therapy centers. Right now, you know, there are patients, you know, the older patients who may not be able to get CAR T-cell therapy, but they benefit from bispecifics. I think, you know, we are probably going to have this algorithm of, you know, having CAR-eligible or CAR non-eligible patients instead of transplant versus non-transplant eligible patients in the future. We would like to ask everyone to please limit yourselves to one question and one follow-up to allow everyone an opportunity to ask a question. We'll move next to Louise Chen at Cantor Fitzgerald. Hi. Thanks for the presentation, and thank you for taking my questions here. My first question is, Dr. Usmani, what kind of data do you wanna see at ASCO and EHA to keep up this sort of positive view that you have on Gracell's drugs, and technology? The second thing is, are there any additional targets that you think are interesting in this area? I know there seems to be a lot of BCMA, CD19, type of dual targeting. Anything else that you think is impressive? Thank you. Right. I'd like to see ongoing, you know, durability of response, you know, in the current studies. I would like to, you know, see more of the high-risk data in the frontline setting. I think that is very exciting. I would like to see that same consistency of win-to-win time, in terms of product delivery. So those are, you know, the key things. You know, reproducibility and durability of response, and then, you know, how consistently we can get the product. Then, you know, of course, you know, the safety profile, you know, remains consistent over time. This is where, you know, I also, you know, feel that for future trials, I think, you know, quality of life measures, you know, for patients will also be, you know, something to look at, you know, for future trials studies. In terms of other potential targets, you know, I think, you know, there are targets like GPRC5D that are being, you know, looked at. You know, it would be interesting, you know, to put GPRC5D together with BCMA as an example. You know, we will see, you know, how that data emerges over time. But I think, you know, dual targeting would be the way to go. We'll move next to Justin Zelin at BTIG. Thanks, Dr. Usmani, for taking the time for this informative call today. One thing that stood out to me from the presentation was the high percentage of patients that had a high risk set of genetics and presumably had extramedullary disease. Could you comment on the difficulty in treating these patients with conventional therapies and how you view the Gracell data in this population? I have a follow-up. Thank you. Well, certainly. You can see that, you know, as we get. You know, if you look at the percentage of patients who have, you know, high-risk disease or extramedullary myeloma, circulating plasma cells, things like that, you know, at the time of diagnosis to the time they're getting to fourth, fifth line treatment, you know, there is an enrichment badness, you know, of disease, you know, as patients get into that, you know, that fourth, fifth, sixth line of treatment. You know, looking at those overall response rates, especially the depth of response, is very encouraging. You know, I hope that signal, you know, holds true. you know, because that actually, you know, sets you up for frontline studies where you can incorporate that kind of strategy with your typical induction treatment or maintenance strategy. The key challenge with extramedullary myeloma, especially is making sure you get enough, you know, drug, you know, to that particular site. And this is where, you know, employing, you know, T cells, you know, or engineered T cells, you know, is helpful because, you know, they can go to places where a drug may not have access to. I think, you know, the whole nature of this kind of strategy is, you know, is appealing for those kind of, you know, clinical high-risk phenotypes. Thanks. That's helpful. I think the other thing to me that it's really quite interesting about the data is the high MRD negativity rate. Just in the context of the patients with extramedullary disease, it seems like there might be a differentiation here with the dual targeting to hit the last cells here, perhaps with the dual targeting. I'm just curious if you can comment just on the MRD negativity rate and how you view that in terms of predicting potential durability response? Yeah. I think that, you know, we know that, you know. I'm going to, you know, go back to historic times before we had these, you know, wonderful therapies in our armamentarium. What we had observed back in the, you know, 2000s when we were starting to incorporate IMiDs and PIs is patients, you know, who have high-risk features, it's important for them to not just get into a complete response but also stay in the complete response. This concept of sustained complete response was introduced by my mentor, you know, Dr. Barlogie back in the 2000s, and especially, you know, held true for high-risk. What I felt, you know, at that time, you know. That was the time when MRD testing was just, you know, starting to emerge, it's really the MRD sustain and sustenance of MRD negativity that portends better outcomes for high-risk patients. As the technology emerged, you know, that's what we started to see even for standard-risk patients. My comment there is, you know, it's good for, you know, in the overall grand scheme of things for a high-risk myeloma patient to get to MRD negativity, they have to sustain it. I do feel immunotherapies will get us there. You know, what would be, you know, important to, you know, look at is, you know, MRD negativity being sustained across different time points as we follow patients. You know, that that would be, like you mentioned, you know, a distinguishing attribute for dual targeting approach for high-risk patients. Thanks for taking the questions. For those listening via the webcast, to ask a question, you can key in your questions in the Q&A box located in the lower left corner of the online webinar platform. We'll take our next question from Kelly Shi at Jefferies. Hi, everyone. Thanks for taking our question. This is Dave for Kelly Shi. Just one question from me. Doctor, do you think outpatient setting will be a good place for GC012F based on its safety that we are observing so far? Following up, like, do you think there'll be a need of trial in outpatient setting to gain such approval, or will it be based on physician discretion if they want to administer in outpatient setting based on their experience? The way that, you know... I guess, you know, my answer is, yes, the safety profile, you know, looks good. You know, most CAR T-cell therapies can be administered in the outpatient setting, especially at centers that actually already have a mechanism to give, you know, autos and allo transplants in outpatient settings. At MSK, you know, more than 80% of the procedures we do, you know, are typically in the outpatient setting. You know, that outpatient setting serves, you know, more like a day hospital model. You know, I think there's no reason why this product cannot be delivered there. With the first two FDA-approved products, you know, there is no requirement for inpatient stay, and that's what makes, you know, our management of these patients, you know, logistically easier. You can admit patients, you know, during the CRS risk period, for a day or two to observe and then discharge them. You know, if most of the CRS that you're observing is grade one and two with the product, then there's no reason why those patients can be managed simply in the outpatient setting. Great. Thank you. We'll go next to Emily Bodnar at H.C. Wainwright. Hi. Thanks for taking the questions. two for me as well. First, can you just discuss how you view the GC012F data on the efficacy side compared to CARVYKTI, and how you kind of think about what the most important thing for differentiation is for you, considering we now have multiple therapies in development in the space? Then second, now that we've seen the CARTITUDE-4 and KarMMa-3 studies were positive in earlier lines, how do you kind of plan to implement these therapies in your patients, and where do you kind of see it making the most sense in the earlier line setting? Thank you. Okay. If I, you know, understand both questions, the one is how do you distinguish between one product versus the other? That's, you know. The second is how do you incorporate them into earlier lines based on, you know, the emerging data with KarMMa-3 and CARTITUDE-4? Yeah. Exactly. Okay. All right. You know, I think, you know, it's simple: response rates, safety profile, and predictability of getting the product. You know, those are the three things that will help distinguish, you know, each of the products. We know what we get with each of the products right now. You know, the only challenge is the out of specification, you know, concern, and exactly when we get the product back. I think it's a general impression that the predictability of getting the product back in time is better for ide-cel versus cilta-cel at the moment. However, you know, cilta-cel appears to have better depth of response, higher response rates. You know, I think, you know, responses in this patient population are very important and so that's, you know, very important distinguishing attribute. We don't know when the label change will happen for both these products, based on the data. You know, I do feel that there are going to be, you know, capacity issues at both, you know, at all transplant cell therapy centers on how many, you know, products can be given to patients. You know, we are probably going to head into a phase where we have to, you know, have a queue again, you know, once the label changes, in trying to, you know, get patients' slot reservations. The slots will, you know, that will be a center-specific issue. It's not a sponsor issue. I think the sponsors will be, you know, or I should say, you know, manufacturing sites will be able to expand capacity to absorb. Every transplant center only has so many infusion chairs, so many apheresis machines, and so many procedures that they can do. The throughput will be an issue. Even if we expand, you know, that expansion will happen, you know, over, you know, over years. It won't happen over, you know, weeks or months. I think that's an important piece there. You know, I hope that answers your question because, you know, I think dual, you know. That's number one. The number two is, even if these therapies do move into earlier line treatment, we know that patients can receive, you know, another BCMA product later down the line and get good mileage out of it. There is anecdotal experience out in the community. There's also experience from various clinical trials, you know, with bispecifics and CAR T that have actually looked into this. Single centers have published, you know, data to that effect as well. I think there is, you know, you don't lose BCMA, you know, for the most part, you know, for, you know, when the disease comes back and can, you know, utilize another BCMA, you know, plus minus something else strategy. Very helpful. Thank you. We'll go next to Yanan Zhu at Wells Fargo Securities. Hi. Thanks for taking our questions. Two questions from us. One, I wanted to get a sense of the doctor's view on the baseline characteristics of Gracell's China study. Whether those patients are more severe or more difficult to treat compared with the other studies that the doctor mentioned during the call. How does the patients' prior treatment experience, due to the lack of availability or the availability of certain drugs in China, might have contributed to or might affect our interpretation of the data. The second question is on enrollment, and I can answer that question as a follow-up. Thanks. The first question is, you know, how do the patient populations compare with the U.S. population? I think, there are, you know, inherent differences in drug access and standard of care treatments that we give here in the U.S. compared to China. The only way to address that is to actually, you know, do the study with the U.S. patients. I think, you know, that is something that is already, you know, in the works and being planned for. You know, the second, you know, question, if you can kindly repeat again, Right. I'd be happy. Yeah. The second question is on the enrollment of the U.S. study. Do you foresee any challenges in enrolling the study? What is your assessment of the kind of patient profile that are more likely to enroll given the availability of the commercial products? Would these indicate a more severe population than a typical relapsed or refractory population? Thank you. Okay. No, I don't foresee any challenges, you know, with enrolling patients, you know, on the study in the United States. If it were up to the patients, all the patients would be getting CAR T cell therapy because, you know, there is so much, you know, hope, you know, around, the data and what's, what this technology can bring to, you know, our patients, you know. The Emily Whitehead story is already out there, you know. Our patients are very well informed about, you know, the data when they come to see, you know, the tertiary care center. I don't think, you know, that will be a challenge. If anything, you know, the patients do seek out, you know, through, you know, the patient advocacy organizations, you know, these trials so that they can participate in them. You know, in terms of, you know, the acuity of care and the kind of patients we get, you're right. You know, I think, you know, that's going to be, you know, potentially different, you know, perhaps a little bit more challenging compared to, you know, the study done in China. You know, similar things have been done for the other commercial products, right, with cilta-cel, and we saw very strong, you know, efficacy signals. I don't, I don't anticipate that being a challenge. Great. Thank you. We have no further questions at this time. I'll turn the conference back to Dr. Kevin Shi. Thank you. Actually, we do have an online question, Usmani. The listener ask, "What median PFS benefit of GC012F will be competitive versus two commercial products?" The other question was, "Without ex vivo expansion, is that suitable for late line patients who are sicker? Yeah. You know, those are, you know, amazing crystal ball questions. I think, you know, the second question, you know, I think it makes intuitive sense. You know, again, you know, I think, you know, whatever helps get the product for our patients in a more consistent early timeline is going to be very helpful. In terms of median PFS benefit, you know, I think, you know, it's, it really depends on, you know, what the data shows. You know, anything, you know, around... Again, you know, I'm guesstimating here. I would feel that anything, you know, between, you know, the median PFS with the reported products, anywhere in between, is going to be fine by us. You know, because we see the responses, we see the consistency of getting the product, I think, you know, is totally going to be okay. I'm not going to guesstimate what the future holds, but, you know, that would be my, you know, general intuition. Even if I'm getting, you know, 12 months, you know, like the ide-cel product, but I'm getting the product consistently and I'm getting a, you know, deeper response, I'll go with that. You know, I think, there are advantages to this product that, you know, that the other two may not have at the moment. Great. Thank you, Dr. Usmani. We have now come to the end of our allotted hour. I will turn the call back to Dr. William Cao for closing remarks. Thank you and again, everyone, for joining us on the KOL webinar. We really wanna thank Dr. Usmani for his time today. We look forward to commencing our RRMM trial in the coming weeks, as well as presenting the updated clinical data of GC012F at ASCO and EHA in June. Thank you. Ladies and gentlemen, this concludes today's presentation. Thank you once again for your participation. You may now disconnect.