Good morning, everyone, and thank you for being here for our second research and development day. I'm Joanne Choi on the investor relations team here at Legend. Before we kick things off, I do need to mention that today's webcast contains forward-looking statements that are subject to risks and uncertainties that could cause actual results to differ materially from the information being presented here today. These are discussed in our filings with the SEC and can be found under the investor section of our company website. Today's presentation will begin with an update with the latest developments in our CAR T program. Afterwards, we will take a coffee break and then move into our R&D pipeline before opening up for Q&A. Now I will turn the meeting over to our CEO, Dr. Ying Huang. Thank you. Well, good morning, everyone. It's really nice to see a full room of people here. Also, I know we have a lot of investors and analysts dialing in from maybe Europe, so good afternoon. For folks in Asia, good evening. On behalf of Legend Biotech team, I'm very excited to welcome you all to our 2022 R&D Day. In October of last year, we knew we couldn't fill the seats in this exact room, but we went ahead and held our first ever R&D Day as a hybrid meeting. We made that choice because we believed that it was important for our leadership team to come together, and we felt we owed that to you, the investors, shareholders, and analysts, to give you the most comprehensive view of the pipeline that we're delivering. While the doors to most businesses were still reopening, our teams of researchers, scientists, technical operations specialists, and engineers were busy at work all year long. We wanted to use an R&D Day to tell you why they were showing up every day. Of course, it was in part now with the brand name CARVYKTI. At that time, cilta-cel was our lead product candidate and is now approved as CARVYKTI in the United States, Europe, and also just most recently in Japan for the treatment of relapsed and refractory multiple myeloma. We were gearing up for our first product launch and significant clinical developments in the CAR T program, which we run in partnership with our colleagues at Janssen Pharmaceuticals. Yet our R&D team was also at work on several promising agents within our pipeline. They were focused on harnessing our broad ambition to realize the potential of cell therapy and to do so in serious illnesses just such as gastric cancer, hepatocellular carcinoma, and non-Hodgkin's lymphoma. We're excited to show you today where those efforts are going, and we hope you're encouraged by the remarkable progression of our pipeline programs. Along with our partner, Janssen, we are launching CARVYKTI, but we're also working hard to realize the next frontier of cell therapy, which goes beyond CARVYKTI. Despite the challenges, we're making inroads into solid tumors, including gastric cancer and colorectal cancer, which are among the leading causes of cancer deaths in the world. Just this summer, our IND program, application evaluating LB1908 in adults with late-line gastric and esophageal cancer was cleared by the US FDA. We're now preparing for that trial, and we look forward to launching it early next year. We're also actively exploring allogeneic platforms to create new cell therapies. We recognize the potential of allogeneic cell products to address the issues of scale and capacity in CAR T, and we hope to be the ones that prove that allogeneic CAR T can become a mainstream treatment in the future. Today, our head of research and early development, Dr. Guowei Fang, will walk you through several programs that we believe will help us achieve this goal and position Legend well. One relies on the CAR-NK technology, while the other one is a CAR gamma delta T platform. As a company, we have always been technology agnostic, and we're better positioned than ever to push the limits of the cell therapy on that belief. Before the day is over, you will learn more about how we're doing that, and you'll hear also from several of my colleagues on what lies ahead for the remainder of the year and also into 2023. First up is Dr. Lida Pacaud, VP and Clinical Development Head, and also, we have Steve Gavel, VP of Commercial Development and head of our commercial operations here in the U.S. and Europe. They will share updates on our BCMA program and touch upon the clinical and commercial plans for CARVYKTI in newly diagnosed patients as well. Dr. Guowei Fang is a new face, this year. He's the SVP and Global Head of Research and Early Development at Legend Biotech. Dr. Fang will outline our R&D pipeline, including programs in solid tumors and allogeneic cell therapies for hematologic malignancies. Again, thank you very much for joining us today, online or offline. I hope that you will enjoy today's presentation and share our excitement about the future of cell therapy at Legend. With that, let me give the podium to Lida. Great. Thank you, Ying. Welcome everyone. I will start with CAR T program, clinical development program. I will start highlighting some of the recent data we have reported this year, and then I will focus on ongoing clinical trials. We have participated in many conferences like ASCO, European Hematology Conference, IMS, as well as we made some publications. First, to highlight updates of LEGEND-2 study. This was proof of concept study by investigators in China, which was basis of transfer of this program to global development and collaboration with Janssen. LEGEND-2 study investigators published now four-year follow-up data, so this is in the journals. We do continue to see in these patients sustained benefit from cilta-cel. You can see here progression-free survival as well as overall survival. Half of the patients are past four-year follow-up now and sustained benefit of the patients. Median overall survival has not been reached. When we also look to the patient who achieved complete response after CAR-T infusion, their PFS as well as overall survival, the top of the top lines on the picture here are very sustained in a range of 75% for survival. In terms of global programs, everyone is very familiar with CARTITUDE-1, our registration study, which served as the basis for all worldwide approvals. We have CARTITUDE-2 multi-cohort study, which explores different settings of early or relapsed/refractory different patient population and subsets to inform us in our phase 3 studies. That's CARTITUDE-2. We have three phase 3 studies CARTITUDE-4, which is in patients with 1-3 prior line failures in lenalidomide refractory and CARTITUDE-5 and CARTITUDE-6. Those are studies in frontline myeloma. For CARTITUDE-1, we did present and published as well in JCO, median of 28 months follow-up, long-term follow-up data. It's 2 years post last patient. All patients have 2 years follow-up or greater, and median follow-up for this analysis is 28 months. This, again, publication, we did see, of course, the response rates, I think, audience is familiar. We have 97% overall response rates and stringent CRs are 82.5%. We have reported responses are deepening over time, increasing in terms of like VGPRs evolving in CRs and CRs evolving in stringent CRs. More importantly, with this updated analysis, we also reported subgroups with high risk characteristics, and we did see consistent benefit in those high-risk subgroups like, for example, cytogenetic abnormalities, ISS stage, high tumor burden, or presence of plasmacytomas. These are curves from that updated analysis, and if we focus. It represents PFS as well as overall survival. If we focus on a blue curve on the left side, so that's the patient who achieved stringent CR, and these patients have like overall population is a purple, but if you look to the blue curve, stringent CR patients are doing better. Then even more importantly, if we look to the top two curves on the left side panel, so these are patients who have sustained MRD. MRD negativity sustained for more than 6 months, that's green line, and then more than 12 months. We see even greater benefit, which speaks of a value of MRD negativity. As you know, in this trial, 91% of the patients who were available were MRD negative. MRD negativity definitely is a very predictive of sustained median PFS and survival. In terms of safety, we did start reporting some more long-term characteristics of safety. We did see 16 patients having SPMs, so secondary primary malignancies. Those ranged some hematological malignancies in 9 patients with low-grade lymphomas or MDS and AML. Some patients have MDS which then evolves in AMLs, and then there are some non-hematological malignancies. These numbers are probably expected because we know that these patient populations on these prior 6 lines of therapy heavily pre-exposed to alkylating agents, which is melphalan. 83% of the patients were pre-exposed to cyclophosphamide as well as IMiDs has primary second malignancy rates in between like 5%-10% in from this treatment alone. Right now, our investigators, we do not have any concerns. We continue to monitor, and patients live longer, so these rates definitely is acceptable based on our discussions. We reported one case of Parkinson-like symptoms which occurred, so this is new case in day 900. This patient is stable in terms of Parkinson's syndromes and functioning adequately in their life and continues to be in stringent complete remission. As we have reported, we did implemented this Parkinson-like or neuro moment in neurocognitive type of disorder. We did implemented measures. We have seen some factors like tumor burden, cell expansion, and CRS neurotox, for example, were risk factors to see this event, so it's a high rate in CARTITUDE-1 study. Since CARTITUDE-1, we have treated over 200, even maybe 300 patient now, and incidence of this type of events is very low, now 0.5%. We also know this Parkinson-like case has been reported in another BCMA CAR T as well in the FDA label. I think with this, I will hand over to Steve. Thank you, Lida. Can you hear me okay? Good. Very good. Thanks. Good to see everyone. It seems like since last year, we've got a lot more folks in the room, and I know in speaking with folks who've organized the meeting, we have a lot more people on the line. What I thought I would do is just go over some numbers with you. I apologize for folks who may have been in the room last time, because this will be a little bit repetitive, but I do wanna go over some of the market opportunity assumptions that we are making as relates to our initial indication in the CARTITUDE-1 trial. As Ying Huang had mentioned in his opening remarks, a lot has gone on over the last 12 months in terms of regulatory approvals. On February 28th, obviously this compound of ours, CARVYKTI, was approved. Just as a reminder, this is a fifth-line indication, and in terms of an eligible patient opportunity, our estimates, our assumptions we're working on is about 12,000 patients that will meet the eligibility criteria for a fifth-line indication in the U.S. We also received approval in May 25th in Europe. In Europe, just as another reminder, that's a fourth-line indication as opposed to the fifth-line indication here in the States. That represents roughly about a 6,000 patient opportunity in terms of eligible pool. Then finally, you heard from Inge, we just received an approval in Japan on September 26th. That, like Europe, is also a fourth-line indication. That represents approximately 4,000 patients that meet the eligibility criteria. Before I go on to the next slide, just wanna kinda qualify what these opportunities represent. This is patients that, in essence, meet the eligibility criteria. Often, after the conference, I get a lot of questions about, "Is that a treated population?" That doesn't necessarily represent a full treated population. There's a lot of discounting and so forth that come off these numbers. Because I'm often asked for them. Okay. Ying Huang had mentioned, obviously, we launched in late February Janssen, as well as some of the things that my team is actively involved with. Again, maybe for some of you who may not be familiar with the Janssen relationship commercially, we're a 50/50 co-promote equal. Here in the United States, the way that we are structuring our commercial group or groups across the collaboration is that Legend is basically our commercial footprint is residing within the institutions that we are certifying. Often, the question I often get is, "Well, how many sites have you certified to date?" In the United States today, we have roughly about 40 sites that have been certified to administer CARVYKTI. It is our intention to raise that number up as we launch, and you'll hear about CARTITUDE-4 in a moment from Lida, up to 70-80 sites. We'll be rapidly increasing our site coverage here in the U.S. as we start rolling into that second indication. Since launch, the demand has been so great, we've been actually outstripping supply, so many of you who've been covering this for quite some time are aware of that. Because of that, we basically changed a bit our commercial strategy in terms of how we intended to roll this asset out. We're phasing this program over time. Really, the key tenet that we are adhering to is ensure that we are very predictive in our supply to our sites that we are certifying, and that they could then obviously base their planning decisions and their patients' decisions based upon our supply. I wanted to make note of that. Outside the United States, the way the collaboration works is Janssen will basically lead all commercial activities and deployment activities, with the exception of China, where we take point there. I did wanna just end this first point around three different areas around the positioning of this asset, and this is global positioning. One thing that is coming through loud and clear, as you would expect, you heard Lida go through the efficacy data and the fact that our median PFS is yet to be reached. We're clearly the winner here in this class, and it's what's driving that demand so high, of course, and we're working feverishly to remedy that situation from a manufacturing perspective. I did wanna touch on this issue of operational flexibility. The other thing that is resonating very clearly is not only are we the clear winner in terms of the efficacy and safety profile for this asset, what many of the sites are also drawn to is what we call operational flexibility. We see with a delayed CRS profile with this asset. In our toxicity profile, we're starting to notice and many of our sites are now moving to administer CAR T in a hospital outpatient setting. That's very important as you start rolling into and looking at much larger patient population, and we'll talk about that population in a second in CARTITUDE-4. Because right now, sites need to look at ways to scale on their end, and they're looking at our operational flexibility in terms of outpatient administration as a means to getting there. From a patient access perspective, this product is available very widely across all of our commercial as well as government payers in the United States, so we're very proud of the work that our partner, Janssen, has done in that regard. With that, I think I'm gonna turn it back to you. Thanks. We will continue with late line setting. We did disclose our CARTITUDE-2 Cohort C data at IMS conference in August, and as well as we published in a journal in Blood. This is a cohort of patients. You may remember this multi-cohort study in Cohort C here. These are patients, basically are same population as CARTITUDE-1, but in addition, patients are pre-exposed to prior BCMA therapy, non-cellular prior BCMA therapy. It's basically antibody drug conjugate or bispecifics. This is efficacy results from Cohort C. On the left side, we see a prior ADC group, and on the right side, a prior bispecific group. We had 13 patients in ADC and 7 patients in bispecifics. We did see roughly 60% of response rates in these patients. Median follow-up here is 11 months. Importantly to note, 80% of the patients, of these patients were refractory to those prior BCMA agents, yet we still achieved 60% of response. Which is definitely benefit for these patients. These patients had median of 8 lines of therapy, so it's again, compared to CARTITUDE-1 where this was 6, so it's much heavily pre-treated population. In terms of safety, nothing really to note because we did see CRS neurotox in line, like start of CRS in average 7 days. All grades, duration of CRS or neurotoxicity events are comparable to CARTITUDE-1. We did not see any neurocognitive or Parkinson's-like adverse events in this group of patients. Overall, and then of course, there was some deaths which occurred, one treatment-related, and others not treatment-related or due to progressive disease. Overall, these data tell us that in more heavily pre-treated patient population compared to CARTITUDE-1, safety profile remains consistent, as well as cilta-cel had favorable risk-benefit in heavily pre-treated patients who were 80% refractory to prior BCMA. Now I would like to move to earlier line settings, so 1-3 prior lines. We have two data sets, so the CARTITUDE-2 Cohort A and CARTITUDE-2 Cohort B. These are data at 20 patients each we have reported, and this is a population, so 1-3 prior lines and which is also informing us for our ongoing phase 3 study, which is CARTITUDE-4 study. Again, to highlight Cohort A, our patients who exactly same population actually as CARTITUDE-4, patients who have one to three prior lines of therapy and lenalidomide refractory. Cohort B are patients who had early relapse within 12 months after frontline therapy or after frontline autologous stem cell transplant. This is results for Cohort A. We did see 95% response rate and more than 90% complete response rate, so the data are very consistent here. We have 17 months of follow-up and very consistent with CARTITUDE-1 and informing us for our phase 3 study. In terms of safety profile remains manageable and similar, again, to CARTITUDE-1. We did see, it's not shown here, CRS neurotox is similar in terms of severity grades. We did see some maybe better resolution of cytopenias, so we have reported that. Cytopenias are very important because these are patients in earlier line, and recovery of cytopenia tends to be slightly better in this earlier population. This is Cohort B. Again, we see 100% response rate, 90% of the patients are more than CR, and here we had 13 months of follow-up. Totality of this data, of these two cohorts, lead us to our ongoing phase 3 study. CARTITUDE-4 is a randomized study with 400 patients, with one-to-one randomization. Patients in control arm are receiving PVd and DPd as an investigator choice. These are treatment regimens we selected based on current practice and try to meet more like worldwide standard of care. In CAR-T arm, there is bridging therapy, which can be one or two cycles of the same regimen of PVD or DPD. Conditioning with lymphodepletion and cilta-cel infusion. After cilta-cel infusion, there is no treatment, so this is observation when in comparator arm patients are continuing PVD or DPD therapies until progression. I would like to highlight a key inclusion criteria I mentioned, but also to highlight, yes, we require prior proteasome inhibitors and immunomodulators exposure, as well as daratumumab exposure, but patient does not need to be daratumumab exposed. This is also difference from we know KarMMa-3 study is reported actually at least in press release. There are differences between these trials. One is, our trial here is one to three prior lines, when KarMMa-3 is two for prior lines. CARTITUDE-4 is one line earlier. Second is we do not require daratumumab pre-exposure. Which is probably important because there is still a good proportion of patients worldwide in United States or elsewhere who are not getting daratumumab in very early lines. This study has fully enrolled. It's worldwide, and it's event-driven primary endpoint. We are waiting for primary endpoint, and we will report when number of events we need is reached. This is summary of current literature, which can give indication how these patients are treated currently and what outcomes they have with current treatment. You can see different studies here. Then again, it's lenalidomide refractory population, right? Like OPTIMISMM, IKEMA, APOLLO or CASTOR study, the patients are getting 9 to maybe 12 months benefit from current treatment. Okay. Dave? Yeah. Thank you, Lida. I'm extremely excited about this study for a number of different reasons. The big reason, and Lida mentioned this, right? This is in a 1-3 prior lines population. Strategically, what we intended to do with this brand is drive the brand market share, brand awareness in this initial indication in CARTITUDE-1. In essence, what CARTITUDE-4 allows us is, in essence, to leapfrog the current CAR T of Abecma that's in market today. We're assuming, as Lida had mentioned, an indication that will come on the back half of next year into 2-4 prior lines of therapy. We'll be coming in at a 1-3. In essence, we'll be able to leapfrog in front of the existing CAR T in market today. It's an extremely important piece. The second piece behind this, and I'll get into the opportunities in a second here, and I can't state this loud enough, is the lack of daratumumab requirement. In other words, we do not require dara exposure as part of this indication. That's extremely important because today, about 80% of all patients in second line today are not dara exposed. That's an extremely important piece of this study that you see a dara exposure requirement with Abecma. Very important from a modeling perspective in terms of eligible patient population, which leads to the next point on this slide. In the United States, we're anticipating about 36,000 patients will meet the eligibility criteria for this indication. That's a 3x increase what you saw in our initial indication. This is a major inflection point for this brand, and it will continue on as being a major inflection point for many years. In Europe, this indication will represent about 16,000 patients, and in Japan, about 5,000 patients. We're not giving guidance yet around CARTITUDE-4, but as I mentioned earlier, one of the key elements of our launch is to expand this commercial footprint to accommodate 36,000 patients in the United States. You'll see, for this brand, a rapid increase in terms of what we call our site certification or commercial footprint, going from 40 up to roughly 80 very rapidly to accommodate this particular opportunity in the United States. With that, I will pass it back to you. Okay. Now we are moving to a newly diagnosed setting, and I would like to explain what we try to achieve and how we try to achieve helping patients in newly diagnosed and where do we see role of CAR T therapy with our trials. First, you know, the treatment, this is to really set a background here, to understand how patients in newly diagnosed settings are treated in myeloma. Patients are characterized as transplant-eligible based on age and comorbidities, vital organ functions. Myeloma is a disease of relatively advanced age. There is significant proportion of patients who will not be physically fit or by age criteria. Different countries, different institutions have like different definition of it, but age and comorbidities, organ functions, and frailty index are criteria which you define if patient is eligible for transplantation. If patient is eligible, they undergo induction therapy, which is usually 6-8 cycles. There is high-dose chemotherapy conditioning with melphalan, which is a very strong treatment, of course, and requires, you know, after transplantation, patients have long hospitalization. It has a lot of comorbidities, infections, cytopenias for months at least, if not more. That's, you know, very from patient perspective, quality of life perspective, and comorbidity and adverse event risk perspective. This is, and then after transplantation, patient may still receive two cycles of consolidation, depending what is outcome after transplantation in terms of response, if it's complete response, partial, et cetera. Then there is also plus or minus maintenance therapy in some high-risk patients. What we try to achieve with CARTITUDE-6 is to basically trial is going ahead of transplant, right? We try to save patients from autologous stem cell transplantation and high-dose conditioning. There is another option, you know, CAR T can intervene maybe after transplantation patients who have no optimal response. That was another option. We have thought about that. I think with the product profile we see with this very long-sustained PFS we see with cilta-cel, we developed this program, CARTITUDE-6, in head-to-head with transplant. Lower part, we see transplant-ineligible patients or patients who are deferring transplant. They would undergo, again, six to eight cycles of induction and receive maintenance therapy. This is CARTITUDE-5 target population. After induction, basically, we are consolidating with one infusion of CAR T cell, one-time treatment. In terms of this latest transplant ineligible or transplant deferring population, I would like to explain. There are patients who are not eligible because of this age and comorbidity I mentioned, but there is also change in clinical practice. We see that there are more and more patients and physicians who are choosing to defer transplant and not to undergo it in front line. They are deferring it to second, third line and not front line. There is reason why. There is SWOG S0777 study. This study has reported a VRd regimen in transplant-ineligible patient who would be eligible for transplant but did not decided not to undergo transplant. This had similar outcome to transplantation. This trial was not randomized versus transplant, but showed same PFS benefit as transplantation. More importantly is the second study, which is shown diagram here. This is in IFM, Intergroupe Francophone du Myélome study. This is randomized study when patients you see on the diagram, right? They have VRd treatment, and then one arm they decided not to receive transplant, and then second arm received transplant in front line. Outcome of this study is that PFS is different, right? This first PFS, however, overall survival is no different in this patient. This paper and this Phase 3 concluded and influenced that clinical practice is that, patients or physicians more and more are choosing not to take transplant in front line. We also checked on this in, databases like, this is CancerLinQ, to see what is happening in real practice. This is confirmed. Basically what we see that 50%-60% of the patients that we show here, US and Europe, will be transplant not eligible. That's not eligible, because of age and comorbidity again. Remaining patients who would be eligible for transplant, there is 35%, 38%, 32% who will decide to defer, by choice. Remaining 16% who would be eligible transplant will undergo transplant. I think to go in again give you more details on our phase 3 studies, and I will come back to this transplant practice. This CARTITUDE-5 is transplant-ineligible patients or patients who choose to defer transplant, and patients will undergo 1:1 randomization. It's 650 patients study. Patients will have VRd induction in both treatment arms, so 2 cycles of VRd, and then maintenance by Rd in control arm when cilta-cel infusion will be given in CARTITUDE-5. Here again, there is no treatment after cilta-cel infusion, so patients are in observation and treatment-free versus control arm who is continuing Revlimid dexamethasone maintenance. This study is ongoing in very large study worldwide with very high interest. We are recruiting very fast. In CARTITUDE-6 trial going ahead, comparing to stem cell transplantation. This, as I mentioned, these are patient who receive DVRd as a induction regimen and after transplantation. Total each arm, if you look, we will receive 6 cycles of DVRd. In control arm is 4 DVRd transplantation and 2 DVRd when in cilta-cel arm is upfront 6 cycles and then therapy with cilta-cel. Here we have Revlimid maintenance in up to 2 years. This is again outcome of different country practices. We decided to suggest to have Revlimid up to 2 years. However, we know Revlimid tolerance, it has been reported some patients are not able to tolerate that long, but that's what protocol is designed. This study is actively opening, so not yet recruiting, but opening. This is also study in collaboration with European Myeloma Network, but this is not European study, this is global study. This is to summarize how we see potential role of CAR-T therapy and all is this database and clinical practice data I have showed you. This is really conceptual. This is not how commercial, how many patients will be used, but this is what is clinical practice right now. If you take 100 newly diagnosed patients, 50%-60% will be transplant ineligible, another 15% will be deferring it. That population basically goes in CARTITUDE-5, and then remaining 25% of the patient who will receive transplantation will be in going in CARTITUDE-6. As I mentioned, you know, we are intervening much earlier in the course of disease than there is patients who this 30 in the middle, small middle box here, 30%-40% patient who receive transplant may have suboptimal response. Of course, this is unmet medical need group. But you know, we do see CAR-T role earlier than that, before even patient receive transplant. I think, Steve, back to you. Lots of numbers. Frontline, the holy grail. We're always being asked when are we gonna go in frontline. CARTITUDE-5, right? You heard from Lida, CARTITUDE-5 represents two growing populations, folks who are not candidates for transplant, and folks who are, but are deferring for different reasons. From a market perspective, it's a much bigger population than once thought of just because of the current modalities that are in market today, especially United States. Lida mentioned and described some of the studies that compared drug therapies versus existing transplant, and you saw how well those patients did who were receiving triplets, et cetera, up front. Let's take a look here. CARTITUDE-5. 64,000 newly diagnosed patients across the three regions, US, Europe, and Japan. This transplant not intended, right? Those two segments that we just discussed represent the US, about 17,000 patients, in Europe, about 9.5, 9,500 patients, and in Japan at 3,000. I mentioned this at this last bullet. I think it's extremely important. We're getting a lot of feedback on this study from our payers, in particular, commercial payers. The good news, and the reason why so many patients are deferring transplant, we saw the efficacy results with the upfront therapies. But with those upfront therapies all come also comes incremental cost over time, right? There's the cost of the upfront triplet or quad, depending upon what that physician is choosing for that patient, but also maintenance. When you take a look at that, the cost of that, and start comparing it to a one-and-done therapy or potentially a one-and-done therapy, the cost differential can be significant. Even with the cost of CAR T therapy, and we all know that that is not insignificant, but when you take a look over the life of that patient, you start to see tipping points in terms of just purely from a cost perspective. The second thing I think is important, I don't know if Lida mentioned this, is that one of the other reasons why patients defer, even though they're eligible, if you've ever talked to patients who've received transplant, they'll tell you it's one of the worst experiences in their life. From a quality of life where you do not have to go through that experience like transplant, and as patients and physicians become more familiar with CAR T therapy, from a quality-of-life perspective, it makes a whole lot more. You're gonna see this, I think, over time, physicians as well as those patients will start opting into CAR T therapy that may have been deferring transplant. At least that's what our models are showing us. I wanna make sure we touched on that. That's it. Yeah. I think we're gonna turn it over to our. I have one more. You have CARTITUDE-6. I think I have one more. Sorry. The holy grail versus transplant, CARTITUDE-6. This is the first phase 3 for a CAR T therapy versus transplant. We're obviously very excited to see this study, given the fact that no other CAR T has gone up against transplant this way, at least BCMA CAR T. I mentioned already about the economics. They play out and obviously this transplant population as well, but I also wanted to give you some ideas of relative numbers, right? Again, 64,000 newly diagnosed across the three regions. This is the breakout in terms of eligibility for the indication by region. 10,000 U.S., in Europe 8,500, and in Japan 1,000. And again, as I mentioned, we run unopposed in this study. There are no other CAR T therapies studying CAR T in BCMA upfront against transplant. This ought to be very interesting to see how this plays out once this data is published. With that, I think we're gonna turn on down to R&D. Are we taking a break right now? Yeah. Yeah. I Yeah. I think we're taking a break. For those joining virtually, we'll return in about 15 minutes. Thank you. You're welcome. Hello, everyone. Lida and Steve just gave an update on the clinical development and commercial side, and it has been a very busy and productive year. On the research and early development side, it also has been very busy and productive. I'm very excited to provide the update today. I'm going to divide the update into three different sections and first provide an overview for our R&D strategy, our technology platform, and also describe our end-to-end capacity in cell therapy. From there, we will dive deep into our program in solid tumor, our platform in allogeneic therapy, and then also introduce a new product program in the allogeneic platform. In the past three years, cell therapy as a field has made tremendous progress and accomplished substantially. Cilta-cel product has been approved by FDA, including our breakthrough CARVYKTI product. Our goal is to, from the research and early development perspective, realize the full potential of cell therapy. To achieve that, there are quite a few hurdles we have to address. On the tumor side, it's the antigen heterogeneity, it's immunosuppressive environment, and it's also the disease pathology. On the cell therapy product side, the constraint include the insufficient immune cell expansion, persistence, trafficking, infiltration, treatment-related toxicity, very complex manufacture process, high cost. Allogeneic platform also come with its own challenge, including GvHD and allo allo rejection issues. As a cell therapy company, our overall R&D strategy is geared towards addressing those major challenges. This slide just outlines our current strategy. First, this is a complex therapeutic modality. We need to invest in research to develop various mechanism to tailor the disease itself, tailor the immune mechanism, and in the form of developing novel armor. Then for allogeneic program, we need to address GvHD and the allorejection issue. In term of platform and the product design, we want to establish, differentiate the allogeneic platform in the form of alpha beta T and NK and gamma delta T. I will share some of those progress at today's presentation. Once we have differentiate the platform, we want to quickly move into allogeneic product research and development. We focus on three major blood cancer diseases initially, multiple myeloma, AML and non-Hodgkin's lymphoma. We will continue to explore the solid tumor space with the right target, right diseases. For our product design, we want to engineer individual product tailored to the disease pathology, addressing the unique immunosuppressive tumor microenvironment. The product can come in the form of autologous as well as allogeneic modality. The cell therapy is a very complex treatment modality and preclinical evaluation only can provide a certain level of information. We need to validate different mode platform and product in clinical setting, and we will continue to use the investigator-initiated clinical study to fast-track the approval concept. From there, continue to develop product in R&D and regulatory trials. Just to sum up, we are interested in both hematologic malignancies as well as solid tumors in the form of autologous and allogeneic product design using diverse modalities such as CAR T, alpha beta T, NK, and gamma delta T. Exactly which platform to use is gonna be tailored by the immune mechanism and by the disease itself. We are happy to report that we have heavy investment in all those areas, which give us option and choice to design optimal product. To achieve our R&D strategy, we have been very busy in the past eight years to build various toolboxes. Starting from the antibody discovery, generating multi-specific CAR design. We take heavy learning from our success of cilta-cel, try to understand and then optimize the CAR T design so that we can enhance the immune synapse structure and optimize the immune activation mechanism. Those CAR activity are further augmented by the unique armor mechanism we have been developing internally. For armor mechanism, we focus on three area: to drive the immune cell expansion persistence, to enhance the immune cell trafficking infiltration, as well as to overcome the tumor microenvironment. Mechanistically, we focus on four different characteristics, categories, which I will share in the subsequent slides. One area is in form of cytokine, membrane anchored, mutational engineering as well as intracellular trapped. We also focus on the immunosuppressive tumor microenvironment and using armor mechanism to address that. Our effort in immune modulation or immune engineering go beyond adaptive immune response, but also take advantage of innate immune mechanism, as well as engineering the intracellular signaling and the functional circuit, developing the intracellular modulate. Some of those armoring mechanisms can also apply to the allogeneic platform as currently we are doing, and we also develop a various strategy and engineering effort to address the GvHD and allorejection. Let's talk about the binder itself. We have internal antibody discovery and protein engineering capacity, mostly focused on the single domain binder VHH-based. This type of binder is being used in cilta-cel, and it provide opportunity for us to improve the CAR expression and stability, allows to access membrane proximal epitopes. Those small binders also give us opportunity to engineering a complex, multi-targeting CAR construct. Equally important, through the engineering process, we can optimize the immune synapse to enhance the immune cell activation and the response. Next, I'm going to spend a few minutes talking about our effort in the armoring mechanism because this is important component for all cell product. Let's focus on the cytokine for a minute. We all know that cytokines are very potent immune regulator which can activate the immune cell response, and yet the systemic exposure of cytokines can generate a systemic toxicity. Therefore our engineering effort on cytokines is focused on a good balance of efficacy versus safety. Improving the safety profile is a high priority for us. This slide illustrates one example. For example, we can take an ectopically expressed cytokine and then anchor to the cytoplasmic membrane. Cytokine can then signal back through the endogenous receptor in an autocrine mechanism, and therefore activate the immune cell response. As you can see from those two illustrative data point, indeed, those membrane-anchored cytokine can further enhance the immune response and drive the immune cell expansion. At the same time, given that it's membrane-anchored, it would also reduce the systemic exposure and improve the safety profile. We can even go one step further beyond this. We can trap the ectopically expressed cytokine intracellularly before it's reached the cytoplasmic membrane, and this actually is a very interesting and novel way to engineering a cytokine. If you look at those two data panel, indeed, intracellular trapped cytokine have better cytotoxicity against tumor cell compared to secreted cytokine. Yet, interesting enough, the trapped cytokine has lower expression, both intracellularly as well as secreted form, compared to free-secreting cytokine. Again, point to the benefit of balancing the safety profile, at the same time, drive a potent immune cell activation. For solid tumor program, we need to address the immunosuppressive tumor microenvironment. One way to approach that is to use dominant-negative receptor molecule, which can still bind to the immunosuppressive ligand but block the suppressive signaling mechanism, as illustrated in this slide. Indeed, those dominant-negative construct does work in the form of suppressing the signaling to inhibit the immune cell in the middle panel, and then you look at the functional consequence by expressing the dominant negative trapper. It can further drive the immune cell expansion on the right side. What's a bit unexpected for us is that those trapper molecule not only enhance the immune cell activation, prevent exhaustion, but at the same time, it's promote immune cell infiltration into tumor microenvironment. In terms of blocking the immunosuppressive signal, we can go one step further to use hybrid receptor molecule where we have extracellular ligand binding domain recognizing the immunosuppressive signal and then link that into a intracellular domain which activate the immune signaling and promote the immune cell expansion. This is the so-called switch receptor. As you can see from the middle panel, indeed, this type of switch receptor block the immune inhibitory signaling, but at same time activate the immune activating signal. Functionally, it provide a stronger cytotoxicity in terms of tumor cell killing. Innate immune mechanism is another area we invest heavily in the past 2 years to take advantage of the synergistic interaction between adaptive and innate immune mechanism. As we know that innate immune mechanism are the first line of defense, and they are fast and effective in terms of response. They also can communicate or signal to the adaptive immune cell. We take advantage of this unique immune mechanism to incorporate into our cell product design. One example is illustrated here. On the left side of the diagram, it's a traditional CAR design. Upon the tumor cell engagement, it activate the adaptive immune response and drive the cytotoxicity. On the right side is armor, which couple the tumor antigen engagement to the activation of innate immune response, leading to secretion of cytokine, which can then feed back in an autocrine signaling fashion to drive the immune cell expansion persistence. Some of the illustrated data was used here on the right side, showing that increased cytokine secretion as well as more robust immune cell expansion. Lastly, immune cell fitness is another key issue that we need to address in oncology settings. Immune cell from the cell therapy product has to be able to survive and function in a harsh, hostile tumor microenvironment. Therefore, we try to identify intracellular mechanism which can promote the immune cell fitness in the presence of low oxygen level, in the presence of limited nutrient condition. This is in vitro screening process. We take primary T cells coupled with CRISPR-mediated, the functional genomic screening, to identify key regulatory circuit which enhance the immune cell fitness, function. Through this effort, we identify a fairly large list of candidate molecules. Some of those are validated and been shown here. The intracellular modulator one and two, they drive higher cytotoxicity against tumor cell and then also more robust anti-tumor activity in vivo. We just want to use those example to illustrate our research effort. In order to maintain a leadership position in the cell therapy space, those give us a diverse toolbox to optimize our cell product engineering. With those toolbox, we quickly build an end-to-end R&D capacities from the identification, validation of target, engineering binders, incorporating to the CAR design and armor design. From there, we develop a robust in vitro, in vivo, in silico pipeline to really assess the efficacy and the safety parameter of those candidate cell product. Coupled with our internal CMC manufacture process, we can efficiently advance those molecule into clinical study in the form of both IIT as well as R&D study, engaging external KOLs to accelerate the product development process. With this end-to-end capacity we have been building a robust pipeline across the entire research, discovery, and development space. Some of those program we introduced the last year where we provide update. Three programs we will provide update today in terms of current development stage, which is autologous CAR T product targeting CLDN18.2, GPC3 targeting liver cancer, and DLL3 targeting small cell lung cancer. We will introduce a new program today, autologous program, GCC targeting colorectal cancer and other gastrointestinal cancer indications. We are also very excited about an allogeneic program, and I will provide update on those platform development as well as introduce new programs, new product programs. Let's focus on solid tumor. LB1908, LB2101, LB2102 was introduced last year at the R&D Day, and we will provide update on those three programs. Let's focus on LB1908. This is autologous CAR T targeting CLDN18.2. 18.2 is a familiar target to this audience. It's a component of a tight junction and highly expressed in gastric cancer and pancreatic cancer, in addition to other solid tumor indication. It also has some lower level expression in normal gastric tissues. We identify internal binders which specifically recognize the CLDN18.2 with high affinity. The selectivity of this binder is demonstrated in terms of its differential binding to CLDN18.2 to CLDN18.1, which is a close homologue of 18.2. Our binder only recognizes 18.2, which is a unique differentiation against some of other product in similar space. This product is currently under investigator-initiated study in China, targeting CLDN18.2 positive patients with the recurrent and/or metastatic advanced solid tumors. Those patients already failed prior line of therapy. Systemic therapies have very limited treatment options. The enrollment for IIT studies still ongoing to evaluate the safety tolerability as well as to define the initial efficacy signal. We are also very happy to report that this program also has been filed for US IND. The IND was cleared on June first this year. Next slide just introduce our US IND study design. We are targeting the CLDN18.2 positive patient based on immunohistological and cytologically confirmed, unresectable, locally advanced or metastatic adenocarcinoma of gastric and pancreatic among other cancer indication. We have two different parts in phase one design. Part A focus on gastric, GEJ and EC cancer patients at the initial dose escalation phase. To determine the tolerable dose and then part B, focusing on expansion and expand the patient indications, disease indication to include pancreatic patient as well. The second update I want to provide here is our program targeting GPC3. Again, this is autologous CAR-T therapy product. GPC3 is the oncofetal protein which is highly expressed in very specific tumor indication, including HCC and non-small cell lung cancer. We identify internal binders to the GPC3 with high affinity and specificity. Further, this product incorporate the switch receptor armor which convert immunosuppressed signal into a immunoactivation signal. Currently, this product is under first in human clinical evaluation through IIT study in China. Again, we target the GPC3 positive patients based on immunohistochemistry assay. Those are adult patient with advanced HCC. Those patients are already progressed or intolerant after previous standard systemic therapy. The first patient was dosed in June this year and currently the IIT study is ongoing. Last program, which we will introduce, last year we will provide update is Autologous CAR-T program targeting DLL3 for the small cell lung cancer. DLL3 is promising target due to its high expression in small cell lung cancer as well as in other neuroendocrine tumors. Its expression in normal tissue is minimum or not detectable. Small cell lung cancer is a disease with very limited treatment options, very aggressive disease with very high unmet medical need. We use a tandem binder discovered through internal effort and also coupled with a unique armor mechanism, a dominant negative armor, which blocks the immune suppressive signaling to enhance the immune cell activation potential as well as to promote the infiltration of immune cells into tumor microenvironment. Currently, this program is under IND-enabling study, and we plan to file US IND by Q4 this year. Those are a quick update on the three programs we introduced last year. For solid tumor, we are very happy to introduce another program at today's update. This is ILCAR08T. This is the autologous CAR-T program targeting GCC for gastrointestinal cancers. GCC is highly expressed in various gastrointestinal malignancy. This target itself is also weakly expressed in normal intestinal epithelial cell, but expression is restricted to the luminal membrane side, and therefore provide a mechanism to avoid the systemic immune toxicity against normal tissue. The binder itself is internally discovered. We also incorporate the armoring design and have generated a comprehensive preclinical characterization data package for cell product. Currently, this product is in preparation for the first in human study. Let's look at the expression in normal tissue first because safety is always our first priority. GCC, as you can see from this slides. The expression pattern analyzed by the messenger RNA expression level, you can see that it's only restricted to the small intestine and the colon. Looking at the exact location of expression in normal tissue, it is expressed in the colon epithelial cells, but only restricted to the luminal side. Happy to read a report that in the literature a few years ago, in that particular study, a CAR-T product targeting GCC was characterized. This particular GCC binder in that study cross-react with mouse GCC. In that particular study, the CAR-T generate a robust anti-tumor activity, but does not generate T cell immune mediated toxicity, indicating a safety a potential safety profile for this particular mechanism targeting GCC. Expression in tumor is highest in various GI cancers, for example, in colon cancers and in gastric cancer. Those indication enhance large patient population and high unmet medical need. In term of our product design, our targeted CAR T design using our internal discovered binder with high affinity and specificity, coupled with the armor which function to convert immunosuppressive signal into immune activating signal. I will share some of our preclinical characterization on this product. First, looking at the binder, we have high affinity binder at a nanomolar affinity. Importantly, we did extensive assessment of binding specificity across 6,000 membrane protein analyzed. Our binder only recognize GCC, as you can see from the bottom left panel. In terms of cytotoxicity against the tumor cell versus normal cell, which is illustrated on the right side panel, effectively kill the tumor cell, but with minimal or no activity towards the normal non-transformed common epithelial cells. We further characterize in the in vivo pharmacology study, taking one of the publicly released CAR in targeting the same target as the benchmark. We titrate on the dose such that our CAR still can generate durable and effective antitumor activity, leading to complete tumor remission, whereas at this particular dose, a benchmark design does not have any activity. Just to note, with this particular characterization, it is a CAR without armor already providing this level of strong efficacy. The PK profile in vivo is consistent with the efficacy data. Next, we want to assess the benefit of adding an armored mechanism. In this particular pharmacology study, we have an armored CAR versus unarmored CAR. Two products head-to-head comparison. We first titrated the dose, even at 0.1 million CAR T cells, single infusion. Our armored product can lead to complete tumor regression in a durable fashion, whereas the unarmored one can only generate a partial tumor growth inhibition, pointing to the benefit of this unique type of armored mechanism to drive the antitumor activity, as you can appreciate from the right side panel, also enhancing the exposure of the cell product. Just to summarize, this particular product, LCAR08T, this is our targeted CAR T product targeting GCC for gastrointestinal tumor indications. We use internally discovered and characterized binders with high affinity and specificity. Specificity is demonstrated across a large panel of membrane protein array. We couple this CAR design with a switch receptor armor mechanism, and currently this program is in first-in-human study. I will wrap up the introduction or the presentation on the solid tumor programs and switch gears and focus on the allogeneic platform. Here, I will introduce two different platforms we have been developing in the past several years. The first is CAR-NK program platform, and then second is gamma delta T platform. Let's focus on the CAR-NK for a minute. As we all appreciate, NK cell represent innate immune cell expressing various activating and inhibitory receptor molecule. From the functional perspective, those NK activating receptor molecule can recognize various the stress-related related signal abundantly expressed in tumor cells. Therefore, NK cell represent a mechanism which can kill the tumor cell in a very fast timescale, given its innate nature, as well as they can provide serious cytotoxicity against the tumor cell. Mechanistically, it has multiple mechanism of cytotoxicity, CAR-dependent, CAR-independent, which actually is very important for cancer indication because target heterogeneity is one of the big challenge in oncology. Having CAR-dependent as well as independent mechanism would allow us to address the target heterogeneity issue. It also have antibody-mediated ADCC activity. It can secrete cytokine to communicate to the host immune system to further augment the antitumor activity. Those unique attributes of NK make it ideal for allogeneic cell therapy approach. It comes with its own challenges, and this slide is some of those challenges. For example, short persistence, multiple dosing requirement, low transduction efficiency, difficult to maintain activity and cryopreservation conditions. Lastly, but also equally challenging is the allorejection issue when we try to develop allogeneic product. When we try to develop our internal NK allogeneic platform, those are the challenges we focus on. I'm happy to report that with our current platform, we have been able to demonstrate the long-term anti-tumor activity at very low dose, even single dose, using our unique armored mechanism, and those are the preclinical data. Those programs are advancing into first-in-human study. We are very much looking forward to clinical response. From the manufacturing process, we engineer a very unique CMC process which provides the robust transduction efficiency. We also optimize the cryopreservation protocols to maintain the viability and functionality of CAR-NK product. Further, we are engineering the anti-graft-versus-host mechanism into our product with our own IP positions, and this would help to enhance the persistence and efficacy of our product. Let's spend a minute to talk about the product attributes coming from our unique CMC manufacturing process. In terms of purity, we routinely get the NK purity above 95% and CAR positivity above 60%. Our CMC manufacturing process, we can generate a robust NK expansion up to a few thousandfold. Those product has a very strong anti-tumor activity characterized in vitro as well as in vivo using preclinical system. Functional activity and the cryopreservation is a big challenge for the entire field. We have a unique formulation protocol to address this issue. As you can see that, through the in vitro and in vivo characterization, our cryopreserved product maintain the activity. This slide just summarize some of the key attributes of our product coming from the CAR-NK platform. On the CMC side, we have streamlined efficient manufacturing process. We can generate a few hundred doses per manufacturing process, assuming a flat dose of 3 million cells per dose. In terms of product efficacy and persistence, we have potent and long-term anti-tumor efficacy, which I will share in subsequent slide, characterized by various in vivo pharmacology study preclinically. Design-wise, we tailor the unique immune signaling mechanism for the NK to design the CAR construct. On the binder side, we leverage the learning from the ACETIOS cell to use the biparatopic or bispecific CAR design. HVG mechanism is another key component which we have been engineering, optimizing in the past several years. Now we have IP protected strategy in this particular position for this particular platform. In vivo pharmacology at relatively low dose, for example, at 1.5 million single dose, in this particular in vivo study, it generate complete tumor remission in a durable fashion. Looking at PK, it's a very happy surprise to us. You can see that a single dose of allogeneic NK product generate PK exposure up to 60 days. On a safety front, analyzing with body weight, we do not see body weight loss over this entire treatment timescale. We can even further lower dose to 0.5 million cell. Again, a single dose leading to a complete tumor remission and in a durable fashion. Similar to the other study, very robust PK exposure. We can even go a step further in this particular pharmacology study. Upon a single dose leading to complete tumor remission, we can challenge those complete remitted tumor with the same a second inoculation of the same tumor, but without any additional dose of NK cell. You can see that with this second inoculation, three out of four challenged animals remain in complete tumor remission without any additional dosing, suggesting indicating the potency and activity of our CAR-NK product. Allorejection is another major challenge with the current NK therapy. That's probably one of the reasons why the durability of clinical efficacy currently is to a large extent limited. For NK cells, there are at least two different mechanisms which impact the allorejection issue. First, the grafted NK cells express HLA alleles, which can be recognized by host T cells to trigger the host T cell-mediated allorejection. This can be addressed through a blockade of expression of HLA. What we utilized in our product is sort of knockdown of B2M, which blocks the surface expression of HLA. Which generates a secondary issue, that is HLA expression on the cell surface. You send an inhibitory signal to host NK cell, blocking the host NK cell-mediated activity. By knocking down the B2M, you lost this inhibitory signal like this. To address the host NK cell-mediated allorejection, in our cell product, we engineering knockdown of CD38. At the same time, with the clinical protocol, we dose the anti-CD38 monoclonal antibody, which can deplete the host NK cell without impact on the grafted NK product due to the knockdown of CD38 in our product. As you can see from the right bottom panel, if PBMC is incubated with allogeneic NK product, initially, there's some level of NK expansion shown in the blue curve, light blue curve. But over time, the grafted NK cell number reduce. By incorporating the CD38 knockdown in our NK product at the same time, with addition of, daratumumab, which, deplete the NK cell from the PBMC, it extended the expansion phase of the grafted NK cell. With this particular strategy, we can avoid the recognition of, allogeneic NK cell by host T cell and NK cell. From a CMC manufacturing process, our engineering process has advantage in the sense, in the form of it's a single vector, single transduction, which can introduce CAR module as well as introduce two different knockdown, and therefore, leading to a robust manufacture process. Just to summarize our CAR-NK platform, we have a unique armor mechanism, which augment the NK activity such that we can achieve a complete tumor remission at very low dose. At the same time, achieve very extensive prolonged PK exposure in preclinical model, up to 60 days. There's no obvious body weight loss based on the preclinical animal study. NK cell itself, at least in our platform, have robust expansion capacity, both in vitro and in vivo, which could offset some of an allorejection issue. At the same time, we engineer a unique anti-HBG mechanism to further address the allorejection challenge and hopefully enhance the persistence of our NK product. We develop a unique CMC manufacture process with the product characterized with high viral transduction efficiency and high NK purity. This manufacture process also enhance the metabolic fitness of NK product with lower exhaustion phenotype, leading to robust PK exposure. Single manufacture can generate hundreds of dose and optimize the cryopreservation protocols, maintain the NK cell viability and functionality. Currently, a lead program coming from this platform is undergoing IIT study, and we are very much looking forward to see the data and hopefully share update at next year's IRD presentation. Lastly, I want to focus on the CAR gamma delta T allogeneic platform. This is a very exciting platform, because of a unique biological nature of gamma delta T, as well as our unique design of this particular platform. Gamma delta T cell represent a bridge between innate and adaptive immune response. It express both T cell as well as NK cell receptor, and therefore can facilitate both adaptive as well as innate antitumor activity. This mechanism is particularly important to address the tumor target heterogeneity, as I already introduced in NK platform. That's true also here. Further, gamma delta T immune cell has intrinsic ability to infiltrate both into blood tumors as well as solid tumor microenvironment. That's also very important for the cell product activity. Lastly, but not least, large clinical correlation study, translational study over thousands of tumor samples indicate that the presence of gamma delta T in the tumor microenvironment has the strongest correlation with the improved overall prognosis survival and the PFS. Among all immune cell analyzed in that study, gamma delta T has the best correlation, pointing to the potential advantage of developing the allogeneic gamma delta T product. From a safety perspective, it's also relatively simple to engineer because gamma delta T does not have intrinsic GVHD risk. Manufacture-wise, it can easily expand from donor-derived cell population. Through our internal engineering and development, we have a robust GMP-compliant manufacture process. This particular cell lineage also come with its unique challenge as well. For example, gamma delta T really does not have a cytokine secretion to augment its own proliferation and activation. Lastly, the second challenge is the potential allorejection issue. Those are the two main area we focus our engineering effort. This slide introduce one of the internal platform currently we are developing for gamma delta T. It takes advantage of the synergy between adaptive and innate immune signaling, given that gamma delta T is a hybrid of innate as well as adaptive immune cell lineage. On the left side is a traditional CAR design leading to the activation of adaptive immunity and antitumor cytotoxicity. On the right side, we couple the innate immune activation with tumor cell engagement, such that binding to a tumor cell antigen leads to activation of innate immune intracellular signaling mechanism, driving the cytokine secretion, which can feed back and function in an autologous manner to drive the gamma delta T cell expansion. The level of cytokine secretion through this engineering is actually below what is commonly found in adaptive immune cell signaling mechanism, such as the alpha beta T. This is also we will share some of the preclinical data on that topic. Let's focus on the manufacture process for a minute because this is important issue for any cell product, especially when one actually begin to engineer a new cell lineage. Here, Legend has a tremendous advantage to leverage our cumulative learning from alpha beta T production process. Over the past year, we have developed a GMP-compliant manufacture process, which is feeder-free, serum-free, fully enclosed, and semi-automated. This manufacture process offer the consistency and scalability. Single manufacture process can generate hundreds and maybe up to 1,000 dose, assuming a flat dose of 100 million. That can be accomplished in the timescale of 10-15 days. The cell product has a heavy enrichment in the central memory phenotype with low expression of exhaustion marker. Expansion process, illustrated in this slide, we can in a single amplification and manufacture process, we can amplify the cell, expand the cell up to a few thousand fold. The end product is heavily enriched in the central memory phenotype as characterized in the FACS analysis. When we analyze the expression of exhaustion marker, it has the relatively low level of expression, as illustrated here with PD-1 and the TIGIT expression. I will introduce one product, a leading product, utilized in this particular platform, LB2103. This is allogeneic product targeting multiple myeloma using the BCMA as a target. We have a traditional CAR-T design recognizing the BCMA with one unique binder and then an innate arm coupled with the second binder, different binder, but against the same target, BCMA target. I will share some of the preclinical characterization of this product. Just the update, currently, the timeline for clinical development status. Currently, this product is under investigator-initiated study. Cytokine is important attributes, and we know that, one of the reason why, alpha beta T, is effective because, it's, CAR-dependent recognition as well as, cytokine, secretion profile. But cytokine also come with a liability, which is a potential systemic toxicity. We did a head-to-head comparison of cytokine expression profile from gamma delta T versus the alpha beta T. Let's focus on the gamma delta T first, as you will see here with the blue and the red bar. Those were to represent armored versus the unarmored version. Looking at the pro-inflammation cytokine, such as interferon gamma and the TNF alpha. Both forms secrete those cytokines, and in addition the armor itself does not further increase the cytokine secretion. When we did a head-to-head comparison with alpha beta T, you can see that in general, gamma delta T has lower cytokine secretion compared to alpha beta T, which is shaded hatched blue bar. This calculation points to a potential benefit of gamma delta T platform, lower cytokine secretion in terms of a pro-inflammation response could lead to a better safety profile. Even though the cytokine secretion is lower than alpha/beta T, if you focus on the right panel, looking at the cytotoxicity, gamma delta T actually has more robust anti-tumor cytotoxicity, pointing to a good balance between anti-tumor activity versus the potential safety profile. Anti-tumor activity is further characterized in the in vitro and the in vivo pharmacology models. Again, here we compare armored versus the unarmored construct. Looking at the in vitro anti-tumor activity upon repeat tumor incubation and repeat tumor killing, unarmored version failed to kill tumors after 6 or 7 rounds, and that's the blue line and consistent with lack of gamma delta T cell expansion after 6 rounds. Whereas with our unique innate armor mechanism, the anti-tumor cytotoxicity is much more robust, extending to 9 or 10 round of repeated tumor incubation. That's also very nicely correlated with the gamma delta T cell expansion in vitro. This in vitro finding is nicely translated into the in vivo anti-tumor activity. Unarmored version only provides partial anti-tumor activity, which is not durable. Whereas with armored version, you can see that we see complete tumor regression in a durable fashion. This profile, pharmacology profile, is consistent with the in vivo gamma delta T cell expansion. Armored version provide lead to a much more robust PK exposure. Allorejection is another concern, and we have two ways to address that. First, we want to assess the potential liability of allorejection, and this is what you see in this slide. In a mixed lymphocyte experiment where we take allogeneic CAR gamma delta T mixed with PBMC plus tumor, and then analyze the expansion of allogeneic gamma delta T in this in vitro system. The experimental condition is highly biased towards allorejection, since we have 30-fold excess of PBMC over the allogeneic gamma delta T product. First, let's look at the intrinsic ability of gamma delta T to expand. Under autologous setting where the gamma delta T and PBMC come from the same donor, that's represented in the rightmost panel. You can see that with or without armor, gamma delta can expand in this timescale, up to 9 days. We take this analysis into allogeneic format as shown in the two left panels using the two different donors. With our armor mechanism, we can see that even in this allogeneic settings with potential allorejection liability, our product can expand probably at least to 60%-70% of the level the autologous cell can expand, suggesting that the robust, intrinsic expansion capacity and to some extent, a limited liability of allorejection using this particular platform. Furthermore, we have developed a internal HVG mechanism which can incorporate into our product. Just to summarize, taking advantage of the innate armor mechanism with our own strong IP protection, this unique armor mechanism lead to robust expansion of gamma delta T-cells and potent anti-tumor activity. This anti-tumor activity come both in the flavor of CAR-dependent, targeting-dependent, as well as CAR-independent cytotoxicity. Safety-wise, gamma delta T-cell do not have the GVHD burden, and our unique armor mechanism also reduce the expression or secretion of pro-inflammatory cytokines relative to the alpha/beta T, and potentially provide advantage on the safety front. We have developed internal CMC process, which is fetal-free, serum-free, and a very robust manufacturing process, which offer consistency and scalability. The armor mechanism also enhance the expansion. Our CMC manufacturing process can lead to a several thousandfold expansion, leading to a few hundred up to 1,000 doses per manufacturing process. The product has enriched in the central memory phenotype and improved self-affinities with lower level expression of exhaustion biomarker. Currently, our lead program is in clinical study. Hopefully we can provide a clinical update at next year's R&D day presentation. Just to wrap up, our global R&D strategy and execution are really. We decide on four different pillar, and those are our people, our most important asset. We have a global research and development teams in U.S., in China, in EU. Our program platform are driven by science and we focus on global innovation, continue to maintain our leadership in the cell therapy space. Everything we do is for the patients. We want to discover and develop a first-in-class, best-in-class cell therapy product with strong IP position so that we can continue to benefit the patients. Clinical development-wise, we have clinical program in both U.S. and in China. We focus on diverse disease in malignancy as well as in solid tumor in the form of autologous and allogeneic platform, utilizing diverse technology platform, alpha beta T and gamma delta T, so that we have the option to develop the best product using the optimal platform to drive our R&D process. I will stop here, and we can entertain questions. Yeah. Steve. All right. We will now open the floor for questions. Please raise your hand. We'll bring a mic over to you. State your name and firm, please. For those attending virtually, you can use the chat feature to post your question. I will read them out loud. Okay. You can sit back. My name is Kelly Shi from Jefferies. Thank you for great presentations from all. Firstly, I have two questions for CARTITUDE-4 trials. What would be the estimated split of patients who has one, two, or three prior lines of therapy enrolled in C-four trial? Would it be more like equally distributed or like skewed to second line, third line? Given that we hear doctors commented that they look at a selection criteria with more focus on how many prior therapies instead of prior lines. Therefore, one triplet regimen could be considered equal to two therapies. Thank you, and I have a follow-up. Sure. I can try to answer that. In terms of maybe to start with line of therapy, clinical trials define line of therapy, right? Every clinical trial, including this one, will have conservative approach. It's not prior number of therapies, prior line of therapy. Like, for example, all frontline induction, transplant and consolidation maintenance is 1 line, right? That's how clinical trials usually define. Now, in terms of split of patient population, you know, obviously I have no data from CARTITUDE-4, so we cannot really comment on that. There are other trials in myeloma with 1-3 prior lines, and usually it's equally distributed from previous trials which have been phase 3s conducted and reported, but we have to see what CARTITUDE-4 will be. Thank you. Also, CARTITUDE-4 trial in the control arm allows for two standard regimens, PVd and DPd. I wonder if the subgroup analysis based on these two different regimens will be conducted to offer like a better understanding how CARVYKTI compared against each of the regimens. This also could like resonate Steve's point that the CAR chemistry design is different in terms of prior exposure to DARZALEX. Thanks. Yes, sure. That's very important, you know, data, of course, to look. Yeah, we will plan to report on subgroups by treatment comparison. As you said, it's randomized study, so it will compare DPD to the patients with CAR T and PVD versus the CAR Ts. Quickly to Dr. Feng in MA. I'm curious about when you mentioned that innate immunity activation arm, does it require co-stim domain and what would that be? And also for most of this, CAR T design, do you also follow the same design for bispecific CAR T has a dual binding domain? Thank you. Yeah. Probably twofold, you know, to your question. One is the binding itself. We take similar design, but in terms of binding itself it's different, CD19 cell and innate signaling mechanism, it's one from the common innate immune signaling mechanism. The exact MOA, we probably will disclose that in due time. Thank you. Thank you very much. Ted Tenthoff from Piper Sandler. I wanted to kind of discuss at a high level the strategy for bringing clinical studies both in China and then to the US. Is sort of the plan to kind of get initial proof of concept in China and then file in other global with other global regulatory agencies to conduct studies? Maybe you can just flesh that out a little bit more, sort of the high level strategy. Thanks. Sure. Maybe I can start, and anyone can add. Yes, that's correct. I think right now approach is to do proof of concept in China to generate some proof of concept while we are working on establishing IND package for FDA. Because as you know, IND requirements with FDA or Europe or other health authorities requires some additional in vitro or in vivo characterization. It takes a few months, as well as manufacturing package readiness. I think that's the approach. Yeah, probably I can. Ying, maybe you want to add. Please, go ahead. Go ahead. I can probably also briefly comment on that. I think having access to IIT study is a tremendous benefit. It allows to efficiently generate the clinical proof concept. Exact nature of how we approach this question probably would depend on the nature of the platform and the product itself. Overall, we want to achieve 2 major goal. 1 is speed, and we want to generate fast validation. The second is, we want to utilize the resource efficiently and enhance the overall success rate. For a new platform and new product, if we do not have sufficient experience and the preclinical data is uncertain in terms of the translation potential into clinic, then IIT study become the most effective way for us to reach the clinical proof of concept quickly. For a product which we have experience and that we have confidence in terms of its potential translation, then directly going after the IND filing would be a most efficient way. Which market to file would depends on the nature of product, the unmet medical need and the standard of care landscape. From there we can decide which market would be most attractive for us to go after in terms of R&D study. Ted, this is Ying. I just want to add a couple of things. If you notice on the history of development for cilta-cel, we did complete a phase 1 that enrolled a total of 74 patients in China first. In that case, we could actually come to US in a rather fast fashion because we go into a phase 1 with dose confirming and then seamlessly into a phase 2 pivotal, right? Same thing for the case of LB1908 for the gastric cancer program. We have accumulated some clinical data. That was actually included in the IND filing with the FDA. Later we got the FDA clearance for IND. For one program, maybe you have noticed that for DLL3, we have decided to go directly into IND in the U.S., for which we're planning for IND application by end of this year. Yeah, that's all really helpful and all very clear. Follow-up question, if I may. You know, I'm impressed by the suite of tools and innovations that you guys are bringing to different cell therapies. I'm wondering how you will ultimately prioritize different products. For example, maybe adding an armored technology or cytokine to an earlier product like LB1908 or something like that. I'm just using that as an example. How do you kind of bring those technologies forward and/or even develop iterative products? Then I guess the last question, if I may. Now that you've partnered cilta-cel, CARVYKTI with J&J, are you likely to do similar partnerships for the other assets in the pipeline? Now that the company is bigger and obviously has greater financial resources, is the plan really to take these assets further along yourselves? Thanks. I probably can address the first question, and then Ying Huang can address the partner and our development strategy question. We are excited about all those tools we generated. Those tools are always being explored and characterized and developed in the context of a program, the project. We do not play around with tools or develop tools for the sake of generating tools. The one way to look at this issue is always from the endpoint, and that's what we focus on, right? For a specific disease, specific product, what do we need to do to make it work? From there, think about what other toolbox we need to generate. For example, liquid tumor versus solid tumor, different disease indication, different tumor microenvironment. Then immune versus the tumor cell attributes. That will determine whether we need a cytokine, whether we need a switch receptor. In the context of product development, we're happy to report that now we have this very large collection. Again, how to use those tools into incorporating those tools into future product will be driven by the disease and by the product attributes we want to engineer. Again, with those predefined approach, we always get surprised given the lack of or gap in preclinical true clinical translation. Therefore, as you point out, iterative engineerings and forward translation, backward translation, taking the learning from the clinical study, especially in the early phase of IIT study, and then back translate the reengineering would be an important process for us. Ted, regarding the partnership question, I can tell you that we will look into the indication and then the addressable market. In the case of cilta-cel CARVYKTI, I mean, obviously it made tremendous sense for us to be partnered with a powerhouse in the field of multiple myeloma because Janssen's not only got the expertise in GMP manufacturing and also the clinical development, they also are developing some of the biggest hematology drugs, including IMBRUVICA, DARZALEX. It makes a lot of sense. For future indications, I think we will, again, like I said, look into the indication addressable market. If it's a large indication that will require thousands of patients in the clinical development globally, we most likely will enter into a partnership discussion. I mean, in fact, we are in many different discussions with the various partners for potential collaborations. Certainly, we also welcome the opportunity to form partnership with other biotech companies which can bring into complementing technologies that will advance our pipeline as well. Hi, this is Harshita Polishetty from Barclays, representing Gena Wang. Thank you again for the presentation. The first two questions perhaps for Steve Gavel and Ying Huang. Steve Gavel, you mentioned right now approximately 40 sites are active. If I remember correctly, that was the target for 2022. Do you plan on adding additional sites this year, or would the focus be more on increasing capacity at each site? That's the first question. Second one is on high-level safety for CARVYKTI and also market opportunity. As you mentioned, you know, the patient numbers that you disclosed for, you know, C four, C five, and C six. Parkinsonism, as you've implemented patient management strategies, and of course, the incidence has gone down to less than, you know, 0.5%. As you go into earlier lines, how do you see the risk reward? Do you take this into consideration? I know you mentioned like patient fitness and tumor burden, but how should we think about the, you know, incidence risk for parkinsonism, and how does that change the market opportunity? I have a last question for Dr. Guowei Fang. Thank you. Sure. Why don't I take a crack at the allocation methods, and then maybe you could take a crack at Parkinson. We'll talk what we're hearing in market as it relates to earlier lines and how our docs are thinking. The allocation question. The question is around today, we have 40 sites that are site certified. Really, our site build-out is really largely predicated on manufacturing capacity. Full stop. I mentioned earlier when I was chatting about these trials, the most important thing for us from an allocation perspective is ensuring that whatever we commit to in market to a site, we deliver on 100% of the time. Full stop. There's been some, like you said, examples in market where that hasn't happened, and quite frankly, I think it's damaging the class. We wanna ensure that for patients, most importantly, that whatever we're committing to, we're delivering on. The question about, you know, will we do more? It's our intention over time to get to 80. The magic number of 80, again, that's a flexible number, is largely predicated on supply. As I become more and more reassured on supply, I will make appropriate steps to expand the market. If supply sources rapidly ramp, you'll see a commensurate increase. The one thing I will just caution you, and I've said this in other presentations, is what I've been seeing is what happens a lot is people are getting kind of hanging on a number, 80 sites, 40 sites, whatever the sites are. The important number to take a look at, it's not so much the aggregate number. The aggregate number, don't get me wrong, is important, especially in large patient populations. I need mass in the market to pull that volume through. What's really important for us, though, and especially in this initial indication, is our sites today have more than enough patients to hit our targets, our financial and patient targets. My point is that in the United States, in particular, it's highly top-heavy in terms of number of sites. You have small numbers of sites with extremely large patient volumes. That's why we're being very judicious in how we ramp. We will be ramping, like I said, with an eye on the future in terms of this second indication, where I need to get to 70, 80. If I can get beyond 80, I'm gonna get beyond 80 as well, because that's gonna help patients because they'll get access to sites that are closer to our patient volumes. Do you want to talk about some of the toxicity? Sure. Yes, I guess from clinical perspective, I have mentioned, right now we see 0.5%, so this remains occasional adverse events, and it has been seen not only for this program, but we know also in a label for approved CAR T, second CAR T. There is parkinsonism. Totality, you know, from clinician perspective, and we have a lot of discussion, of course, with myeloma physicians, events remains occasional, and it's parkinsonism-like symptoms, so it's not parkinsonism per se. Patients are stable, not requiring intervention or requiring some steroid intervention for short period of time. From practice perspective, benefit drug can give, and this is oncology, right? Events like this are happening, and if it remains occasional, incidence is low and stable or manageable. I think would not preclude. That's at least feedback from experts as well. I'll get you. Now you're commercial. Yeah, no, it's an important question because we talked a lot. I talked to a lot of the docs about this at ASCO recently. One of the things, and you're right, your safety hurdle is getting higher the earlier you go in lines, right? Even with great data, rightfully so, that risk-benefit ratio is changing because these patients, there's other modalities, let's face it, in earlier lines. We just talked about some of the data that Lida shared on how well combinations are doing in earlier line of therapy. What you will see and what we are modeling, and I think folks who follow myeloma would agree to this, we're gonna see a high-risk population rapidly adapt, without question, right? You're gonna see quick conversion across. It's in that standard risk to lowish risk that you're right. You're gonna see that'll be more of a lagging adoption for us. That's why it's so important for us in the near term to get as many reps on this product and demonstrate the safety of cilta-cel, even in a late-line patient that is really, you would think very susceptible to some of these toxicities. It's very important, obviously, that we launch successful. We will. We are. But I think we do have, you're right, a greater hurdle as we get in earlier lines of treatment for sure. Did you have one more question? Yes. Actually, Harshita, maybe I'll add that, although we have not disclosed all the safety details from the other ongoing CAR-T program, including CAR-T 2, 4, and 5. However, what I can tell you is that categorically speaking, because we do have to report all the safety events to all the global regulators. I can tell you, if you go into earlier patient population, including patients enrolled in CAR-T 2, 4, and 5, overall, we may see similar incidence of CRS and neurotox. However, the severity of those CRS and actually it's much more tolerable than what we saw in CAR-T 21 in the heavily pre-treated patients. Got it. Really helpful. Thank you so much. One question for Dr. Fang. On the gamma delta program, you said the China IIT study is ongoing. Are you only screening patients or have you dosed patients yet? The reason I'm asking that is 'cause as you mentioned, you know, one of the better safety for gamma delta is, you know, lower risk for, you know, better safety on CRS. I wanted to see if you could comment on what you're seeing in patients if these patients have been dosed. Yeah. Thank you for asking this question. Yeah. It's an early stage clinical development program, and the sites are activated, and we do not have sufficient clinical data to share this at this point. Thank you. You've got to be next. Hi. Kostas Biliouris here from BMO Capital Markets. One question on the outpatient setting that Steve mentioned. We did talk to CareWell, and they really believe this is a key differentiating factor for CARVYKTI. I was wondering whether it's at the discretion of the hospital to administer CARVYKTI in the outpatient setting or there are things that you can do and you are doing to really impact this decision and fully leverage this characteristic. I have a couple of follow-ups. Yeah. Thanks for the question, and thanks for confirming what I was talking about earlier. Yeah. For a number of reasons, when you look at our 40 sites. I'll give you rather than talking just hypothetical, 40 sites. The overwhelming majority of these 40 sites that we're in today have expressed either the interest and/or are doing outpatient CAR T today. Now, again, you ask, "Well, then what is that driver?" Right? There's a number of different drivers. We're not doing anything overtly to move these hospitals there. What they're doing, though, they're anticipating what we talked about earlier in terms of they see this tidal wave coming in this CAR T for population that's gonna be substantial for them. They also recognize the fact many of them know that given the current resources they have internally, I'm saying resources defined as bed space, they know that these clinical trials, not only in CAR T therapies, but all these cell therapy programs or gene editing programs are consuming resources and space within their institution. They need to think about alternative ways to give CAR T therapy. They've been trying to do this since back in the day with the CD19s, quite frankly, right? They haven't been able to do that because that CRS toxicity event was so acute within 48 hours, or in some cases, like with our competitor, with the Abecma you see within 24 hours, they can't get there. That's why they're seeing this huge influx coming at them. They also recognize the fact that they have to be efficient on how they do this. Only literally with this program, I'm including the non-CD19s in this, you know, market basket of CAR T programs. This is the first one that's allowed them to do it. You know, you see this really delayed CRS onset. To your question about who's driving that behavior at the institution, all the institutions are dealing with different issues at their sites. What I'm getting at is many of these sites, for example, in New York City, you know, a patient population is fairly local to them. They'll manage that outpatient protocol very different than what you might see at Mayo Clinic. We see long commuting distances in. They're managing how they go about kind of putting an operational infrastructure to support those patients to keep them safe. Every site's a bit different. What oftentimes they'll come to us and ask for is assistance with how they could either different through patient assistance programs and operations and logistics programs of helping moving patients around. It's really case by case by the institution. Thank you. A second question is around the out of spec, and this is a question we very frequently receive. Novartis had published that with Kymriah, 1, 2 of the most frequent parameters that were causing the out of spec were viability of the cells and the interferon gamma release. I was wondering, of course, to the extent you can share, whether you are also experiencing challenges with these two parameters, and if you can provide any other color around the out of spec product. Kostas, I'll talk about this. Obviously the product release specifications for the U.S. commercial CARVYKTI product are actually more stringent than the specifications we use in the clinical study, in this case, CARTITUDE-1. The reason is that actually, when FDA approved CARVYKTI, they decided to narrow the ranges of certain metrics, including, for example, viability you mentioned. If you recall on our label, it says that 18% of the CARTITUDE-1 patients received the so-called OOS out of spec. That is when FDA retrospectively used this commercial spec versus, you know, the clinical spec we were using in the trials. In the beginning of the launch, we did experience somewhat higher than that 18% described in the label for OOS. However, we are doing everything we can. I think, you know, in the last few months, we are seeing some encouraging trend. We do believe that part of that is due to the patient baseline, because as you can imagine, in the clinical study, we screen those patients according to the enrollment criteria. Now, CARVYKTI's commercial drug today, we no longer have that capability to screen the incoming cell bags. So the patient baseline has to do with that in terms of viability or the number of cells we collect, right? Then we're also along with our partner, Janssen Pharmaceuticals, working very hard by looking at every single step of the manufacturing protocol to see if we can fine-tune that protocol and then improve the success rate as well. I think, at this point, you know, we feel very confident that we will be able to overcome this. Perfect. Thank you. Very helpful. One quick one. Given that KarMMa-3 study enrollment was completed pretty much at the same time with CARTITUDE-4 in last year, almost a year ago, and that the readout was last month, given also that you have a little more patients than KarMMa-3, and you are in an earlier line, how should we be thinking about the timelines of the readout for CARTITUDE-4 given all these parameters? Thank you. Yeah, I can address that. Obviously, CARTITUDE-4 is event-driven trials, so we are waiting to see number of events we need to analyze and report. In terms of recruitment, there was some overlap, so we started recruitment slightly after KarMMa-3. I think also main difference is line of therapy, right? They have 2-4 lines when PFS is much shorter. We do have 1-3 lines, so PFS, even in control arm, will be longer, right? That's the difference probably, which is also driving timing. Hi, Justin Zelin from BTIG. Thanks very much for the presentation. Steve, you outlined a pretty robust plan for your clinical strategy here and, you know, with a large amount of increased patients that you might have come on board, you know, how are you thinking about increasing your scale of manufacturing to meet that demand and, you know, reaching a steady state? Well, we work very closely obviously with our manufacturing colleagues in understanding what the demand curves look like. We're hand in glove. We literally, we have conversations daily. Do you wanna talk any more detail? Yeah, sure. Justin, I think, as we and Janssen have previously discussed, we are currently in a supply constrained environment, that's being driven really by 2 factors. Number 1, there's industry-wide and global lentivirus shortage. Our strategy to deal with that is we decided to bring that in-house. In fact, as you can see from the FDA approval letter, Janssen Vaccines right now is the sole provider for lentivector for the commercial CARVYKTI production today. Our partner J&J has been aggressively ramping up the production. Our expectation is that in the near future, we will not have to deal with this shortage of lentivector anymore because of our commitment to bringing the lentivector in-house. Now, the other factor is the physical capacity or what we call slots. If you look at that, this is obviously a multi-faceted effort involving expansion and also physical build out of our New Jersey manufacturing facility. In fact, I would use this opportunity to tell you that just recently, J&J and Legend have decided to double our investment in New Jersey. That will mean that the total investment for New Jersey facility will be about $500 million in total. With that acceleration of this investment, we think that in the next few years, we'll be in a position to actually have a capacity that accommodates to the $5 billion plus peak sales projected by J&J. By that, I mean the combined facility one from the New Jersey and also the facility that's undergoing construction in Ghent, Belgium. Great. That's very helpful. My other question is, with the expectation of additional BCMA targets being approved in the near term, how do you see CARVYKTI being used either in sequence or in combination with these novel agents? You can start. Sure. Maybe it's, I guess, commercial. Yes. I think it's combination. Okay. So the ADCs and bispecifics, I think it depends. I think in the near term, especially in the U.S., or for that matter in Europe as well, you're gonna see just by the very nature that if CAR T therapies are in short supply, whether it be ours or from BMS, you're gonna see ADCs and bispecifics being used for sure prior to CAR T therapies. That's why that data that Lida presented earlier is really important. I think you'll see a short-term phenomenon where we model this every day, right? You'll see that being used. That's one of the reasons why we wanted to generate that data, because the next question is, will a CAR T still work, right? Then you start to see the data that Lida presented. You definitely see a significant amount of efficacy carry through there. That's the first point. I think you'll see a short-term ADC bispecific spike, in just the very nature if we're having difficulty delivering to market. Then you'll see these indications, large indications hitting, whether it be through Abecma, then ours. Then as Ying said, by the time you start running into the second indications, manufacturing starts to really start ramping. Then you get to a point where bispecifics, in my mind, in my estimation, in terms of we're now gonna be jumping up in front of the bispecifics, right? ADCs just by earlier line use. CAR T, cilta-cel, moves up in front of them, and now you're in front of them. From a sequencing perspective, you'll leapfrog not only Abecma, but you'll also leapfrog in front of the bispecifics and the ADCs. I think that was a very important decision that was made early in the clinical development program, to do that, and then we're off and running. Justin, maybe I'll just add one more thing that is, so far, given all the data we have seen in the clinic, regardless of modality, regardless of lines of therapy, regardless which trial, cilta-cel or CARVYKTI has demonstrated the unprecedented clinical activity in terms of CR rate, OR rate, and then PFS. In this case, Legend and our partner, J&J, firmly believe that this is the best-in-class therapy. We think that presents a really significant barrier of entry to any upcoming competition. We believe that we'll position CARVYKTI as the most effective treatment option out there for multiple myeloma patients. Of course, we want the patient to come into CARVYKTI treatment as early as possible when they're young, when their immune system is relatively still strong, right? On the other hand, in that 5-7 year, you know, disease period, we do believe that, at some point, those patients will come to CARVYKTI for treatment. Great. Ted Tenthoff. Quick follow-up question. This has been a really great conversation, and you kinda triggered this question, which is, when it comes to the individual clinics accepting that supply is short, how are they prioritizing patients? And does this align with sort of some of the comments that were made in terms of out of spec? You know, are they saying, "Okay, we're gonna do all the worst patients because they're the last chance." Or are you kind of saying, "Okay, well, those patients may not respond. Let's save this for patients who are a little bit better off. Yeah. How are they going through that thought process? Thank you. Yeah, I'm happy to take that because we talk about that a lot with our sites. As I mentioned earlier, every site's a bit different in terms of how they go through their decision-making process. It's changed, quite frankly. In the beginning when we launched, it was a very different evaluation process in terms of how our sites were making their decisions, you know. What we found over time, to your point, is knowing that we are short supplied, the type of patient and patient clinical characteristics have changed as well, right? It's like we were talking about the other bispecifics and ADCs. Their thinking process has also changed, and that's why, again, that data was so important to say, "If I can now bridge, and maybe I wasn't necessarily gonna think about a bridge of a bispecific or an ADC when this product first came out." If they were going cilta early, and then they found out, unfortunately, cilta can't, in essence, meet their full demand. Now you're starting to see, that's why thinking of, let's think through maybe a bispecific or an ADC, and by the time I'm able to bridge, you know, the folks at Legend and Janssen will have enough supply then to bridge that patient on. Yeah, for sure, that thinking process has fundamentally changed over the last, you know, eight months or so, for sure. But that's the way that they are thinking. Hopefully we'll get to a point where all comers, obviously, could be put on cilta-cel when they meet the requirements. Right now, that's a thought process. Yeah. That's why that data is so important that we just brought up. You know, to add to this, we have seen not only for BCMA, but also for lymphoma, right? The physicians, because CAR Ts are in academic centers, more heavily pre-treated patients come first when it's commercial, because there is pool of the patients who are kind of waiting, you know, more curative therapy. I think that will be. That's what's observed early in the market. Okay, we have time for one more question. Hey, guys. Asthika Goonewardene from Truist Securities. I'm gonna follow suit and ask a couple of multi-part questions. Let's talk first about CARTITUDE-4. Just wanna drill in a little bit about prior daratumumab use, given that CD38 is expressed on early precursor T cells. Given you've finished recruitment, can you tell us about what% of your patients have had prior dara? And how do you expect prior dara to impact the number of harvested T cells? I mean, we don't have CARTITUDE-4 data, right? I cannot comment on that, like how many patients would have. Maybe Steve, you have some more practical experience. Mm-hmm. Probably, I mean, I would say from literature, maybe like 30% of the patients would not have dara in early, like, first line. It's about 20. Twenty. Yeah. That slide I presented earlier. Yes. It's about 20%. That's why I was saying it's so important that the majority of patients in second line have not been exposed. Now, granted, over time, they're getting more and more exposed as dara moves up, okay? In the short term, there is a lack of exposure. That's why it's so important in our trial, we didn't require that. Abecma has a requirement there that's, in my mind, kind of problematic because the patient population hasn't been exposed yet. Also thinking globally, right? Because it's maybe more That's right. Yeah. That's exactly right. Like U.S. versus rest of the world. Right. Which is also a big market. Right. To the question, how do you expect prior daratumumab to impact your T cell harvest? I mean, we don't really have issues in T cell harvest in general in our clinical programs, so including this trial. Okay. Maybe I can add one speculation, just from purely mechanistic perspective. Dara is heavily immunosuppressive in the mechanism of action, and the patients without dara exposure presumably has a better immune system. That's probably very important for autologous cell therapy. The clinical data will tell because we could do a separate group analysis. In our CARTITUDE-1 and 2, whatever we reported, these patients have dara, right, exposed, and we were able to collect and manufacture. I think from the like immunology perspective, I understand the question, but from practical perspective, we already have patients who have dara exposed, and my collection was not an issue. I guess the other angle I was taking was with CARTITUDE-4, would you expect to have even more on-spec product produced and probably better T cell fitness as a result of less dara exposure in your study? That's in theory we do. I think like in every case same for lymphomas, right, more earlier line T cells are more fit, not only dara, but also exposure to other agents like alkylating agents. Second multi-part question. When you think about your gamma delta product 2103, are you selectively expanding a delta one or delta two subtype, and why? Overall with the gamma delta efforts, would you be selecting subtype by tumor type? Yeah. Multiple follow-up questions here. In terms of the cell lineage, we know that the gamma delta T has a diversity very similar to T cell. You have CD4/CD8. We are exploring different approaches. We can probably disclose technical details at a later stage. At high level, we're interested in both delta one, delta two, and maybe even combination both from a therapeutic and manufacturing perspective. If there's a way to manufacture both in a single product, that would be ideal. There are literature reports indicating that the monoclonal nature of gamma delta T does perform better than a single lineage. Those are all opportunities that we are actively exploring. In terms of disease indication, I think it's again driven by biology, right? There are various characterizations in terms of different degrees of tissue infiltration for different sublineages of gamma delta T, and then we want to take full advantage of those intrinsic biological activities and then tailor to the disease. Again, our goal is to treat the patient and treat the disease. We don't want to have a generic product which apply to all different disease indication. That's why we put so much emphasis in early research to really try to understand the disease, understand immune biology. From there, produce tailored product, not a generic product. Well, if there's no further questions, again, thank you for showing up today, and thank you for your interest in Legend Biotech. I hope that after the presentations by my colleagues in R&D, in clinical development, and in commercial, you know that CAR-T CARVYKTI is actually a strong pipeline in itself because today we're launching in the first indication, which is late-line multiple myeloma. We hope in the near future, we'll be able to present the data from CARTITUDE-4 data, which will form the basis for label expansion. We hope to launch the second-line label pending positive data and FDA approval next year. We're also marching towards the frontline indication because CARTITUDE-5 is actually enrolling really well. We also have a CARTITUDE-6 protocol that's already up on ClinicalTrials.gov if you want to know the details. We really think that CARVYKTI has potential to change the paradigm for multiple myeloma treatment. We also are remaining in the front line of all the mechanisms of the cell therapy demonstrated by our progress in NK and also gamma delta programs. We hope to keep updating in future medical meetings and broker conference. Thank you very much for coming.