Good evening, everyone, and hello to everyone who is listening to our webcast. Thank you all for joining us today for our investor and analyst event focusing on CARTITUDE program and also CARVYKTI. This is our standard safe harbor statement. Please take a moment to read the disclaimer about forward-looking statements we might make. This is the agenda for today's event. First, I'll make a few opening remarks, followed by the three KOLs we have. Dr. Dhakal will talk about the curative potential for CARVYKTI, and Dr. Hansen will talk about early treatment with CAR T is better, and then Dr. Sidana will talk about safety management in real-world management. Lastly, we'll open up the floor for questions. With that, I just want to provide some brief background on Legend and also on our lead product, CARVYKTI. Today, Legend Biotech is the world's largest standalone cell therapy company, and we're a pioneer in using immune cells to treat the toughest diseases, including multiple myeloma. With CARVYKTI, we are at the forefront of the CAR T therapy revolution, a one-time infusion treatment for multiple myeloma, which we develop, manufacture, and co-promote with our partner, Johnson & Johnson. CARVYKTI has been the fastest commercial launch among all CAR T therapies to date and generated nearly $2 billion in total sales in 2025. With CARVYKTI having validated Legend Biotech's science, manufacturing, and execution model, our strong balance sheet allows Legend to self-fund innovations to other indications. We currently have about 14 pipeline programs under development, and we are looking forward to presenting potential data in the near future at an upcoming major medical meeting on our first in vivo CAR T program in non-Hodgkin's lymphoma. Finally, we have built a durable global business while becoming the CAR T market leader in multiple myeloma. We have now treated more than 10,000 CARVYKTI patients to date. We have a cash position and liquidity of $835 million as of the end of the first quarter. This year, we do expect to achieve corporate profitability on an adjusted net income basis. Few companies in the biotech arena combine the commercial scale and also next-generation pipeline optionality that Legend does. Before turning the podium to the KOLs we have invited to present today, I'd like to do also a quick recap of the unique advantage of CARVYKTI as a proven leader among CAR T therapies in multiple myeloma, forging the path to a cure. CARVYKTI has proven data supporting its curative potential, whereas no other CAR T in multiple myeloma has been able to substantiate this kind of long-term efficacy over five years. There's also substantial clinical evidence on how earlier CAR T treatment is better for both safety and also efficacy outcomes, which bolsters CARVYKTI use sooner. Finally, CARVYKTI is a one-time infusion, which offers flexibility in both inpatient and also outpatient settings, as well as lifetime cost savings, benefiting patients, healthcare practitioners, and also payers. We are committed to building upon the most successful CAR T launch to date as we focus on the significant market opportunity for CARVYKTI in the years to come. Now, I would like to introduce you to three guest speakers. First, we'll hear from Dr. Dhakal on CARVYKTI's curative potential. He's with the Medical College of Wisconsin. We'll hear from Dr. Hansen on how early treatment is better. She's from the Moffitt Cancer Center. Then we'll conclude with Dr. Sidana presenting on safety management. She's with Stanford University. With that, Dr. Dhakal, over to you. Good evening, everybody. Thank you, Dr. Ying, for the nice introduction. Today, I'm going to make a case of the potential of a cure with CARVYKTI. As Dr. Ying pointed out, this is probably one of the biggest strengths of this product. Because of the CARVYKTI, I think we're talking about curing multiple myeloma. Historically, this is an incurable cancer, as you know, and every time we talk to the patient, we always tell the incurability of this cancer. However, that conversation is changing every day in the clinic with the patient because of the CARVYKTI. Because of this also, having a potential cure with CARVYKTI, the whole myeloma community is now talking about cure and probably formulating a definition of how to define a cure in multiple myeloma. In February of this year, IMWG proposed the first definition of cure in multiple myeloma. This is the first time we're talking about cure, and this is what is defined by sustained treatment-free MRD negativity for five years. I'm going to show you the data on why CARVYKTI has the potential to achieve that. Now, how we define cure in multiple myeloma is a proposed definition. Of course, that might change in the future depending on how the data pans out, but we could define cure in either a newly diagnosed or relapsed/refractory setting. The patient needs to be in sustained complete response by standard criteria. They need to be MRD negative at 10 to power -6 with either NGS or NGF, which is next-generation flow, and there has to be sustained MRD negativity for five years without any therapy. That is very critical. As you know, there are a lot of other therapies coming in the market, which can potentially have deep responses, but they need to be off therapy. This is a big, important step from the patient point of view, and they need to have at least four MRD assessments during the time period with no positive in between. You can't have an MRD negative turning to positive and negative to become a cure. You need to be sustained MRD negative for five years. Last but not least, given the spatial nature of the disease, you need to make sure that there is no evidence of disease functionally when you look at the MRD. By PET scan or MRI, you need to have no evidence of disease for five years. That needs to be sustained as well. How CARVYKTI meets that goal for that point of time. This is the data you might have seen. This was the big news last year at ASCO, which is looking at the patients treated in the CARTITUDE-1 program and followed for a long period of time, at least for five years. When they looked at that, out of 97 patients treated in the CARTITUDE-1 program, one-third of the patients, that's a big number, who were treatment-free and progression-free for more than five years after a single infusion. More importantly, in that, one-third of the patients, about 12 patients at a single center who has consecutive MRD done every year, as well as the PET scan done, they were all MRD negative, sustained for five years, and also PET negative for five years, meeting the proposed definition of cure. Clearly tells you that CARVYKTI has that potential. That is one part. More importantly, if you look at the median overall survival of this patient in the CARTITUDE-1 long-term follow-up, it is about 61 months. It's more than five years. Why that is important, the median prior lines of therapy in CARTITUDE-1 program was about six lines, and they were all heavily treated patients, including triple-class exposed patient. Historically, these patients would have a median overall survival of less than a year. We have five times the overall survival with one-third potentially curing. This is, I think, really very important kind of data, and that is the conversation that we have in the clinic when you offer this therapy to the patient. The next question is how we can achieve that better cure fraction if you move this therapy early line. We have that data already, and Dr. Hansen is going to come and show some data and say that how we might cure even more patients with the early line of therapy. Dr. Hansen. Hello. Good evening, everyone. Yes, today I'll be discussing earlier is better, and I wholeheartedly do believe that that is the case. We do know that multiple myeloma is very much a heterogeneous disease, and with each line of therapy, the disease becomes more difficult to treat and more genomically complex. We also lose patients with each line of therapy. That rate of attrition can be somewhere between 10%-30% per line of therapy. If we have treatments such as CARVYKTI, where you can give a one-time treatment, improve quality of life, and have other treatment options, it really makes for a very good candidate and truly a groundbreaking transformative type of therapy. CARVYKTI hasn't really necessarily just raised the bar, but it has set the bar very high for our patients. We've seen unprecedented response rates, unprecedented survival outcomes. We see in CARTITUDE-1, where a heavily pretreated population, the median progression-free survival was about three years, where it might have been with conventional systemic chemotherapy less than six months. Truly impressive data there. If we look at CARTITUDE-1 and CARTITUDE-4 patients, these are triple-class exposed who had received three prior lines of therapy, the median progression-free survival can be as high as 50 months, which is truly impressive. When we think about the actual CARTITUDE-4 study in patients who are PI and IMiD exposed and lenalidomide refractory with a 30-month follow-up, we've seen a median PFS that has not been reached. Again, truly outstanding results for our patients with multiple myeloma. Certainly from a survival standpoint, we do see that overall survival is improved, particularly if you treat patients in second line as opposed to third line, as opposed to fourth line. Not only are we seeing very impressive results from a survival standpoint, whether that be progression-free and overall survival, as my colleague demonstrated with that 33% of patients being alive and well at that five-year mark, we're also seeing improved safety. At the five-year mark, as you see, for example, in the CARTITUDE-1 study, that we had 6% Parkinsonism. When we look at CARTITUDE-4, meaning we give CARVYKTI earlier, we saw one patient with Parkinsonian features, which is less than 1%. We've also learned a lot about who might be the patients that might develop this toxicity. We've learned about mitigation strategies and modifiable risk factors, such as bridging therapy, which my colleague Dr. Sidana will talk more about. Really the patients who were debulked well and had achieved a response to bridging in CARTITUDE-4, we did not see any Parkinsonian cases in patients who had a partial response or better. In addition, from a manufacturing standpoint, as we move CAR T earlier in the disease course, we are seeing a 99% manufacturing success rate. T cells are fitter. We have an immunocompetent immune system or bone marrow microenvironment and less inflammatory burden for our patients. Certainly, this is better earlier than later in the disease course. Now, another question has been, should CARVYKTI be given to patients in second line for those who have functional high risk or genomically high risk disease, or should it be given to all patients in second line? This was a very elegant analysis, was a subgroup from CARTITUDE-4, essentially showing that patients who have standard risk disease have a lot to benefit from this treatment. We see significantly improved progression-free survival for patients who are treated earlier in the disease course compared to those who are treated later, such as CARTITUDE-4 versus CARTITUDE-1, as you see there, both in terms of progression-free and overall survival. Now that we're talking about this possible functional cure, well, these are the patients that are going to benefit the most and actually get to that functional cure. Last but not least, there are some new data that are emerging. This is a small data set from our center at the Moffitt Cancer Center, where we treated patients in early line with CARVYKTI. Here we saw about 70% who had high-risk cytogenetics. Median prior line of therapy was three. We saw really very impressive outcomes. Overall response rate, 98%, MRD negativity, 92%, 12-month progression free and overall survival at 85% and 95%, which is really truly impressive. We did not see any parkinsonian cases in this particular cohort as patients were being bridged. We have mitigation strategies in place. With that, I very much hope that the lesson here is we should be giving CARVYKTI earlier rather than later. N ow we have a lot that we have learned about mitigating toxicity and making this treatment much better in terms of safety as well as efficacy. I will invite Dr. Sidana to talk to you all more about safety. Thank you. Thank you, Dr. Hansen. Again, we have CARVYKTI that we've seen how effective this is. What are the practical steps we can take to be able to use it safely in the clinic? It works. This is data from the CARTITUDE-4 trial that Dr. Dhakal presented at the ASH 2025 meeting. This is a story you will see now repeated in multiple data sets that I'll show you. Patients who did not have a good response to bridging had bad outcomes for both progression-free survival and overall survival. Of course, the worst were those who had progressive disease, but even those patients who had a minimal response or stable disease did much worse than if you had a partial response or VGPR. It's not only about PFS and OS. If you look into the details of this data, some of these patients, if you had a progressive disease, you could get CAR T, but just not on the trial as it was an intent to treat analysis. There were significant safety signals in people who were just progressing and then getting to CAR T. Going into CARVYKTI with high disease burden is not a good idea, and that's a lesson we have learned, and that is a lesson that we now need to practice in our clinics widely. How can we optimize bridging therapy? In the late line setting, which was the initial label for CARVYKTI with four-plus lines, often our hands are tied. We didn't have good options when CARVYKTI first came to market. Now we have options. This was with talquetamab. This is a study, again, Dr. Dhakal and I are senior authors here. Our entire US Myeloma CAR T Consortium participated in this, that talquetamab bridging in the real world is a very safe and effective option. What we learned was it actually resulted in improved safety with CARVYKTI. We saw no cases of Parkinsonism. That's because of the significant disease debulking that we see. We also had our own institutional data presented at ASH last year, where we looked at both ide-cel and cilta-cel. With cilta-cel, in patients who were responding to bridging, there were no cases of Parkinsonism. All of the cases were from earlier days when we didn't have good bridging options and had no choice but to take patients forward with high disease burden. Again, the same theme reiterates. This is data from our U.S. Multiple Myeloma CAR T Consortium in over 750 patients. This is one of the largest data sets we have for CARVYKTI. In this data set, where majority of the patients were in late line, about 85%, we saw 22 cases of Parkinsonism. Again, the story that emerged was that 21 out of those 22 cases were in patients who had not responded to bridging therapy. The risk of Parkinsonism was as high as 5% in non-responders, but 0.5% in patients who had a partial response or better to bridging therapy. We also saw in that data set that all-cause non-relapse mortality was half in patients who had a response to bridging therapy, with one-year estimates close to 5% in responders and 10% in non-responders to bridging therapy. Again, what does this all tell us? Again, multiple data sets, different patients, trial, and real world, they all come to a similar point that CARVYKTI should be used as a consolidated therapy with effective disease debulking. While it was challenging in the very, very early days of CARVYKTI, we now have very effective bridging options as CARVYKTI is available as second-line, and we also have good bridging options in the late-line setting. This is again, a slide summarizing all of the data sets I talked about. A lot of detail, but again, the best we can. This is the message that we are working very diligently to communicate to all of our referring providers because this is a true partnership. It's also a message that not even everybody in the myeloma community is appreciating right now because, again, the data has changed so rapidly. All of these data sets I talked to you about are from September onwards last year. This is data within the last nine months, and this is how quickly we're learning about things. Now with the talquetamab real-world study, we have talquetamab as a bridging option, including in the NCCN guidelines. I can personally say I've never had any pushback from any insurance company about using talquetamab as a bridging therapy even earlier line if we think it's the right therapy for that patient. This was, yep. Alan, I will invite you to present this data, which is emerging data that is coming from the ASCO data sets that were just released. Thank you. Thank you, Dr. Dhakal, Dr. Hansen, Dr. Sidana. With that, now I'm inviting my colleague, Alan Bash, the President of our CARVYKTI franchise, to actually discuss some of the data points that just came hot off the press at ASCO in the last two days. Alan? As a lead-in to the Q&A, we thought it would be important to share two additional data sets for your reference. The first is a publication that recently came out in the Journal of Hematology & Oncology, a registry database from Germany that looked at 606 patients and compared the cohort that was essentially the CARTITUDE-4 population, the one to three prior lines, with the population that had received CARVYKTI in the later lines. As you can see from the data set in this Germany registry database that, in fact, whether you look at response, depth of response, durability of response. The patients that received CARVYKTI earlier did better. I think this is an important complementary data set to the ones that we've seen already in the real-world. An additional real-world data analysis was presented today at ASCO that was looking at the TriNetX data set here in the U.S., and it looked at the question of sequencing, whether the patients who received CAR T before bispecific, how do they do relative to the patients who received bispecific first? As you can see from this data set, it was a complementary data set of 389 patients. 244 received CAR T first. You can see that there was a longer survival, both the median OS and the five-year landmark survival in the patients who received CAR T before bispecific, as opposed to the patients who received bispecific first. Again, this is a real-world data set. You can't perfectly match all the patient characteristics. This is not a randomized study, but I think it is supportive of the concept that we can get patients to CAR T earlier. That is how the field is moving, and I think that's a good lead-in to the conversation that we want to have with our panel here. With that, let me turn it back to Ying to moderate our Q&A. Thank you, Alan. The first question I'm going to kick off by asking all three panelists here is that how are you currently prescribing CARVYKTI in your practice? Also, what has been your experience since you began prescribing CARVYKTI? I can start us off. CARVYKTI certainly when it was first approved, we gave it in later line. Now with the CARTITUDE-4 data as of April of 2024, and given particularly the long-term follow-up with its curative potential, I've started treating all of my patients in second line with CARVYKTI, whether they be functional high risk or standard risk, unless there's other logistical comorbidities or other situations in which I might not be able to do so. Completely agree with Dr. Hansen. My practice is similar. We try to use an effective therapy as early as possible. That is a core principle in oncology. You don't want attrition. You want to use your best therapy first. I would say, again, just the experience is also different. When we had limited bridging options in 2022, when CARVYKTI first came, some of the patients did have severe side effects. Now that we're debulking our patients, going with as low disease burden as possible, I often change the bridging if it's not working. It's very well tolerated. The risk of severe side effects, even talking about severe CRS or ICANS, virtually unheard of in the last year or so in our practice. Our practice has shifted to earlier line, but the patient experience is also changing. Yeah, I think one thing I would like to add on. When the CARTITUDE-4 data just read out and got approved, I think the question was, "Is it really going to benefit all patients independent of the risk?" There's a lot of interest in high-risk patients and then probably preserve in a standard risk may not go directly to the cell, but I think once you looked at the data, long-term follow-up data for both standard risk and high risk, and it looks actually it's benefiting standard risk even more. You might be seeing the plateau, even a stronger plateau for that. I think independent of the risk, anybody who is eligible for CAR T, I think that's my recommendation to go to CAR T as early as first relapse, and that's what I do in my practice. I think this is the conversation that you have with the patient of how impactful this therapy is if you try to give it sooner than later. Thank you. Okay. I do see Ted raising hand. Can we get a microphone to Ted here? Please say your name and your affiliation so that the people on the webcast can know. Yes. Ted Tenthoff from Plymouth White Marsh High School. Thanks for having this. It's really great to reinforce just how important and how powerful this medicine is. My question really builds right on Ying's question. Thank you for taking this early. What are the options that you're really assessing for bridging therapy today? You mentioned, which I thought was really interesting, that if it's not working, you'll switch it. Maybe you can walk us through what those options are, typically how long that will work, how long that will last, and then what percentage of your patients are get ting CARVYKTI? I know the manufacturing throughput has increased dramatically. Is pretty much all of your patients getting CARVYKTI now? Thanks. Happy to take the bridging question. I would say that the manufacturing is a non-issue at this point. It was an issue in 2022, at this point, there is no constraints on manufacturing. A complete non-issue. I would say the choice of bridging therapy depends if it's a second-line patient, third line, or fifth line, based on what they're not refractory to. I would say the more refractory patients get a lot of talquetamab bridging. Some of the earlier line patients, we do CARVYKTI as second line, and some of these patients are not even dara refractory, or some are not even dara exposed. I might just give them dara bridging since logistically it's easier than talquetamab bridging. It just depends on their treatment history. It's not a particular drug, it's just whatever they're not refractory to that you think has a good chance of working. If it's not working in a month, we switch it. Yeah, I think the other thing I would like to add one more is in terms of response to bridging, I think ideally get a CR or a VGPR is better. You saw the data even early line CARTITUDE-4, we saw that patients at least achieving PR and better, they do better than either not responding or having stable disease. The goal is we try to see if they can respond. In early line, the choices are many, so if the patient doesn't respond to one therapy, you can switch to different. Luckily in late line, I think at least now we have talquetamab, and then we can use some other agents in combination and at least get a patient and responding patients to the CAR T. The jury is still out, what is the best level of response to bridging so that they get the best outcome? That is still open question, but as long as they're responding or the kinetics of disease is on the downward slope, I think that is the right time to get the CAR T. I fully agree. I think the main thing is, as we move CAR T earlier, I'd say bridging is not as difficult as it used to be because now we have very good options. My colleagues mentioned DARZALEX-based talquetamab. We have KYPROLIS based. We've heard SUCCESSOR-2 data with the new CELMoDs. I don't necessarily think that bridging is as big of a problem, and we really should be able to get patients into a deeper response earlier in the disease course. Quite frankly, I work at a center that has very high CAR T numbers, and all of our patients that need CAR T get CAR T. That's not a problem. Neither is manufacturing time, by the way. My next question is about Tec-Dara, because recently FDA approved Tec-Dara combination as a second-line therapy. What is your current treatment approach to prescribe bispecific like Tec-Dara versus CARVYKTI? How do you decide when CARVYKTI makes the most sense for a patient in your practice? For eligible patient who could get either CAR T or bispecific, I think the conversation is equal in terms of efficacy and safety and all those. That conversation goes in the clinic. If they're CAR T eligible, I think my preference is to give to CAR T for multiple reasons. One is, of course, potentially curative option with the cilta-cel. We saw that data, if we move it early line might even better. Also one-time treatment for improve quality of life, all those factor into conversation. Of course, discuss that with the patient, as well as the safety. I think that's how we recommend that the next line of therapy. Again, if you look at the sequencing, it's better to give the CAR T followed by bispecific, Alan saw the data as well from the real world. You get the long duration of response, a benefit if you do that sequencing rather than the other way around. The CAR T is the way, first one to offer to the patient. I completely agree. Maybe another question I'll throw off is, what do you think about CARVYKTI as a potential treatment in first line? I know that obviously we and our partner Johnson & Johnson are conducting two ongoing trials. One is CARTITUDE-5 in transplant ineligible or transplant delayed patients. The other one is CARTITUDE-6, where we're comparing CARVYKTI head-to-head against transplant in transplant eligible patients. Maybe again, going back to the core principle of oncology, you want to use your most effective treatment early line. dara started as fifth line, and now you cannot imagine a world that you would not give dara as front line. I would say that this is the way the field is going. Our most effective therapies will move earlier line. We are heavily anticipating the results of those data, both from the transplant ineligible or deferred and the transplant eligible study. We hope the study is positive. We know we have to wait and see the data. I think it would be an excellent option. For front line right now, we're telling our patients, "You have years and years of treatment." Why wait for that treatment-free interval, that potential curative therapy for later line? For transplant, we've been trying to get rid of transplant so as to say for the past 30 years, we have had negative studies. I'm hoping that transplant has met its match in CAR T. I'm really hoping that finally we'll be able to move to a different therapy. Of course, we're heavily anticipating those data. No, I agree. I think in both transplant eligible and ineligible, if you can just give one-time therapy and get this prolonged PFS, that would be really meaningful from the patient point of view. Again, I'm more harping in the cure this time because I think you might be curing some subset of patients with this one-time infusion. With the median diagnosis of 69 years in these patients, if we can even achieve cure half of the patients, then that is a big deal. They don't need any therapy in their lifetime. Maybe I have one last question to go through before we open the floor for Q&A? Today we just heard about the latest presentation from Kelonia Therapeutics on their in vivo CAR T targeting BCMA for treatment myeloma. What do you guys think about the in vivo CAR T as a potential therapy in myeloma? Also, what are your thoughts on this data that was presented this morning? Certainly we're living in exciting times in multiple myeloma. We have very exciting CAR T-cell therapies. We have bispecific antibodies and in combination, and now we're next generation in vivo CARs. The data is exciting, but there is very little follow-up. We know not as much about the safety. I'll be curious to see long term, how does the safety pan out and how does durability of response look in these particular patients? Certainly early on we are seeing lymphocytosis in the subset of patients. We're seeing grade 2 CRS. I think it's a bit too early to really make any definitive conclusions, and I think we're years away from really getting to the bottom of that. Yeah, I would say very exciting technology, not just in myeloma. We'll see this change our field in the future. We just have to keep in mind there's technology we work on for the future, and there's technology for our patients in clinic. This is where CARVYKTI was probably eight, nine years ago, where we are right now with in vivo. While I'm very hopeful for it, very exciting data, I think it needs a lot of time to mature before it can get into clinic. No, I agree. It's very exciting. I'm looking forward to more data, more trials with the prior CAR T-treated patients, and just to see how the field is evolving with the BCMA moving earlier. We'd like to see how this will fare when you have prior BCMA-exposed patients. So far it looks pretty exciting. Okay, let's go with Kostas in the front row here. Thanks for taking our question. Kostas Biliouris from Oppenheimer. The first question is on MajesTEC-9 data, teclistamab data was just presented here. Any thoughts around this data and whether it can change the treatment paradigm in the second-line plus, given that we already had the combo tec data approved? The second question is relevant to the first one. How big of a concern is the infection rate of bispecifics? Is it a main concern that patients would consider and avoid bispecifics for? Thank you. I can start. To me, MajesTEC-9 is certainly very exciting data. I think what it adds to the MajesTEC-3 data is that you see 100% exposure to CD38, and you had 85% of patients who were refractory to daratumumab or CD38 monoclonal antibody. Beyond that, I don't necessarily think that it necessarily shifts our treatment paradigm as much given recent approval of Tec-Dara in MajesTEC-3. As my colleagues mentioned, certainly we do have a lot of data in bispecifics following CAR T and vice versa, and we do have guidelines from the Immunotherapy Working Group should patients be eligible for all of these treatments. They do recommend a CAR before a Bi. Really one thing I'd like to really focus on is as you give some of these treatments earlier in the disease course. Of course, the disease is more naive, the treatments are going to work better. I think what we really need to think about is how are we going to sequence all of these drugs to give our patients the most benefit in the long term and that curative potential. I think that's where we need to be very mindful when we interpret all of this data, and that's where really utilizing the CAR T when you're able to manufacture it best when the T cells are fitter, as I mentioned, when you have an immune microenvironment that looks good, when you have less inflammation, and you're going to make your best product, and you're going to give your patients one-time treatment that works well for a significant amount of years and improves their quality of life, that's critical. Then you move on to your bispecifics or other combinatorial strategies. In terms of infections, yes, I do have a concern, particularly you saw in MajesTEC-9 that severe infection rate was 41%, in MajesTEC-3 it was about 50 or so. You saw in MajesTEC-9 in terms of mortality from those severe infections, about 5%. That would be really a shame to have a patient die of a severe infection early on. We are all utilizing IVIG, I think we have to be very careful of this continuous strategy and risk for infections in our patients. Yeah, I would add, these are all excellent options to have because right now only a minority of our patients in the second-line setting are getting immunotherapy. Hopefully this makes the conversation wider that the right therapy for someone in the second line is immunotherapy. I would certainly prefer for patients to get CAR T if it's accessible and feasible for them. I think this is a message that us who work in academic centers need to reiterate to our community partners because they see patients with solid tumors. They see all of hematology. The field is changing every six months. They can't keep up with it. Every patient deserves at least a discussion and a referral. Now, what that patient chooses with their doctor, discussing the pros and cons is their choice. There's a lot of pros in favor of CAR T that my colleagues have already talked about. Also it makes sense, right? If you look at it biologically, a continuous duration therapy, T cell exhaustion, you're probably not going to manufacture a very good CAR T if you use CAR T after. We also know that BCMA can have a lot of mutations with continuous bispecific therapy, whereas with a one-time therapy, you're less likely to have that. There's a biological rationale for the data that we're seeing beyond just the infections and the schedules and the logistics. I think every patient deserves a conversation, and ultimately it's a patient's choice. Every patient deserves a conversation. Yeah, I think one thing I would just add on top of what has been said is before TEC-9, any dara refractory patient, cilta-cel was the only option. Now with the TEC-9 saying that these patients could also benefit from teclistamab monotherapy. Having said that, the conversation of what first, CAR T first or bispecific first for eligible patient, that doesn't change with the data. Before TEC-9 they were all dara naive or non-refractory patient. Tec-Dara was very effective, but I think they'll have another option, but the conversation of giving CAR T or bispecific, that remains the same, and we still offer CAR T for eligible patient given the sequencing, given all those benefits that we talked about. We'll go to Eric next, maybe. Thanks guys. Eric Schmidt from Cantor. Coming back to the risk mitigation strategies around Parkinsonism. It sounds like you guys have a very clear view on what should be done, how will the rest of the field sort of codify this view? Is there going to be some consensus recommendation at some point that tells folks how and what to do and when? Thank you. Yeah, we're actively working on those. That's an excellent question. Again, the field is moving so rapidly, right? All of this is happening in less than one year. The International Myeloma Working Group, which comes up with guidelines, actually now has living guidelines because the field is changing so quickly. We're also evaluating all of these risk mitigation strategies in different studies. Bridging is one thing we talked about, but there's also other measures based on how quickly we see CAR expansion and absolute lymphocyte count being a surrogate in the clinic available at bedside. At a certain level, we are giving patients steroids, sometimes something else. If someone has symptoms of a toxicity, the best paradigm to manage it. We have learned these things very quickly, so this is all being put into guidelines. Again, the task ahead of us is not just for us experts to know, but how do we educate everybody else, right? Again, we live and breathe this 24/7, but that's not everybody. They take care of many other types of patients. That's cut out for us. That task is cut out jointly with the manufacturers, like how do we educate everybody? Is there a timeline for that? I mean, all of these meetings, right, all of these efforts, part of it is to educate, the guidelines, they are coming. Yeah. they are coming. Yeah. We're seeing the effect of that in the clinic already. Even people who used to see a lot of Parkinsonism, the numbers are going down because prevent and treat strategy and monitoring strategies, I think have worked very nicely. Especially the efforts on the impact of bridging has really impacted that, the monitoring of the CAR expansion potentially intervening that at a certain point of time has impacted that. Even the treatment has evolved, right? Now we know how to treat it, how to identify this as early as possible. The awareness is happening not only in the CAR T treated, but also in the community doctors, even the patient. I think the caregivers, I think that is definitely happening, we are seeing the effect in totality of that effect in the incidence and the outcomes in the clinic. To answer your timeline question. The International Myeloma Working Group living guidelines are online and being updated continuously. That should be readily available to anyone. Other studies certainly are ongoing. For example, Dr. Sidana has the cilta-cel study with dexamethasone mitigation. Certainly, a lot of that exciting data will be presented at upcoming conferences. We have bridging manuscripts that are going in publication and review now. The ASTCT, in additional to the IMS IMWG, has some guidelines that was just recently accepted and should be in press soon. Certainly, this is an evolving field, and a lot of data should be coming out shortly. I'll just add that in the data set that I shared from the Germany experience, it's in the publication. I didn't call it out, it's in the publication that in the table of AEs, there was one Parkinsonism case in the 606 patients. That was in a later line patient. I think, again, it supports this concept of earlier is better. To the question about how manufacturers work with our colleagues and our experts, this is what we've been doing, which is to work to make sure that the referring physicians have the education. They are well connected to the treatment centers. We're also expanding the footprint of treatment centers as you know. We're up to 148 centers in the U.S. and over 320 globally. Again, relying on the experts here to reach out with the education, that's something that we're doing to make that connection as well. We'll go to Jon here. Great. Thanks. Jon Miller from Evercore ISI. As you guys just said, you're the experts. You see this every day. You give a lot of CAR T. You're at very active centers. You're moving CAR T as early as you can. What about the patients that you're getting referred from community? I'd love to hear each of your experience with at what stage in their journey you're getting those patients, what your experience is with that evolution over time. How often are you seeing patients that are already bispecific exposed from the community treatment, and can you talk a little bit about where you're getting patients in that you're not starting with? I think we share more or less similar practice pattern. I would just say that patients who are initially seen by us, they are in our network somehow or the other. They are still on our radar. We can capture these patients very soon. Even the community doctor who are seeing these patients send a note to us if the patient is progressing in need of new therapy, especially immunotherapy, right? That might not be applicable to other different practices that is different. I think it's important to have education to the community doctors to refer, at least have a discussion of these patients to the center for the CAR T evaluation. That is important part of the work that is ongoing, including from us and from the sponsors, from different individuals working on that. In terms of the journey wise, I think it is very important that once the CAR T is given to the patient, they are monitored at some basis by you all the time. At least for the 1st year, where all these toxicities are bound to happen. We talk about CRS and ICANS and Parkinsonism, but there are a lot of other toxicity. I think we want to make sure that all these things are managed properly when they go back to the community. There's a constant communication and even seeing these patients at frequent intervals, making sure that they're following all the guidelines of managing and treating infections or preventing infections. In addition to all the things talked about with delayed toxicities and having constant discussion to the patient, to the caregiver, and to the community doctors about how to identify these subtle signs of delayed toxicities and monitoring them and preventing them. I think this is what we do in our in these patients, and we'd always like to have some kind of follow-up with us at certain bases, depending on how far they are from the therapy. We have some of the patients who are five years out in the CARTITUDE-1. I have three of those patients. They still see us once a six month or a year and still go over some of the data points. I would say it's a heterogeneous pattern. There are some providers who are like, "Everybody can reach us." Some will send early and some will send a little bit later. May have something to do with geography, right? If you live in California and Central Valley, you may come to us a little bit later. Maybe it's patient preference. It's hard to tease those out, but there is some heterogeneity. I think that also says that there is, now that we have so many immunotherapy options, education. I think, again, it depends. If they're more hematology leaning practices, they have more patients with hematology, they're more up to date with data, they send us patients early. If they're mostly solid tumor practices with very few patients with hematology, I see some trends that the patients may come a little bit later. Thank you, Dr. Hansen. I guess just to add to it, I think CARVYKTI got approved in 2022. At that point, a majority of our referrals came internally and also a lot of the community practices with the bispecifics, we were really starting up, right? We were doing the step-up dosing, we had control of those patients in terms of exposure to the different agents. I think now that there is a little bit more education about what these agents are, when they might be used, I'd say similar to your experience, I've had some referred in late line that I really have nothing else to bridge with but talquetamab, and then a fewer that are coming earlier in the disease course. I think it really goes back to that education piece where we really need to educate our community providers who are treating breast, lung, leukemia, lymphoma, about all of these new treatments that we have and the indications and prior treatment history. I think that's going to be crucial. I would just add that to your point, I don't see patients who are treated with bispecifics referred to me just yet. If they're thinking about immunotherapy, they're sending to us to have that conversation. The thing is that they're sometimes not thinking about immunotherapy. I think, to your point, it's not like they're keeping the bispecific patients, treating them, and then sending them later. That has not happened. Dr. Hansen has a plane to catch, so we thank her. Thank you all. Yes. Thank you. Let's go to Etzer first, and then maybe Ash after that. Great. Thanks for taking my question. Etzer Darout, Barclays. Just a related question around demand dynamics that you're seeing at your centers or maybe amongst your peers for CARVYKTI, particularly given some of the emerging safety data that you've talked about today, just how that's shifting or changing. Thank you. As I mentioned, three years ago, two years ago, we actually had less referrals. We have many more referrals right now. The patients are there. Can that pool be expanded? I think there's a lot of room to expand that with education. It's often community providers don't not send patients to us because they're worried about safety. It's just that they're not thinking about immunotherapy at that point. It's never been, Oh, I'm not sending you patients because I'm worried about some kind of safety signal or Parkinsonism or something else. It's usually like, Oh, I thought that comes later, when after everything's exhausted. I think that's what we are trying to. The data is otherwise, that it's better than standard of care. That's the mindset we are trying to change. Yeah, definitely it's increasing. Both the patient and the physician are aware that there is a CAR T as early as second line. It's quite effective and needs to be sent. I don't think safety is a part of the conversation that you have when the patient comes to you in the clinic. I don't think that becomes a part of conversation when the patient comes to us from the referring doctor. The numbers clearly shows that the early line CAR T is increasing. That tells you that a lot of patients are being referred for that. These two experiences, I think, are consistent with what we've seen in other accounts. We've reported the fact that not only is our absolute numbers going up and our overall order set is going up month-on-month, quarter-on-quarter, but also that the mix is also changing. In the most recent earnings call, we reported that 41% of our patients are coming from the second and third line. Again, it's consistent with the fact that there's an evolution towards the earlier patient treatment paradigm. Ash. Oh, yeah. Thank you. Ash Verma from UBS. Yeah, I guess, Alan, just to follow up on the 41% number that you talked about, right? As you guys have prioritized that more and more of the revenue for CARVYKTI needs to come, wants to come from earlier line, second to third line, I'm assuming that would require quite a significant push in the community setting. Just to help us understand in terms of where your commercial marketing push is, how does that get heavy on the community side? Just secondly, on the Kelonia data today, yeah, we saw one grade 3 ICANS. Small numbers, only 18 patients right now. As you think about the viability of in vivo CAR T for BCMA in multiple myeloma, is that a reasonable frequency you think that might allow it to compete with other available options, or do you think that that might be a negative red flag? To answer your first question, we've been talking to the community for many years now about the opportunity to do a couple of things. One is expand the footprint. We have about a third of our authorized treatment centers are in the regional and community hospitals. That's an important addition to the academic medical centers that we are perhaps represented here. We also have all of the education to the community practices to refer. I think that's what we heard from Dr. Dhakal and Dr. Sidana as well as Dr. Hansen when she was here about the fact that the referrals are increasing. The third piece is, ultimately, there will be some large community networks and community practices that want to do CAR T themselves. They obviously have to have the infrastructure, the capability. We have a number of those planned. We have some that have already started, Virginia Oncology Associates, Tennessee Oncology, and more are planned. Again, that's sort of a third leg, if you will. The other thing I will say about the dynamics in terms of our commercial efforts is around patient activation. I'd ask our experts here to comment on that because we've invested heavily on making sure that patients are aware of the opportunity for CAR T. We're doing the first direct-to-consumer advertising, not on broadcast television, but in very selected, targeted ways to make sure that patients understand CARVYKTI. We're also doing a number of educational efforts, and using all the channels such as social media to reach patients. I don't know, are you hearing more from patients about their understanding of CAR T? I'd love to hear about that as well. Depending on the patient, definitely some patients. I would say myeloma patients are a little bit more savvy. That's my understanding, they are aware of what is happening in the field. They are in the Facebook page. They are in this other platform and social media. I have some patients, I would say 20%-30% of patients coming with a lot of information. Also depends on where the patient come from, like rural Wisconsin, sometimes they come in, they don't have a lot of information about the CAR T. I think it is variable, but I would say that numbers of patient understanding and knowing about the CAR T number is slowly increasing, and that partly because of the outreach. If I can go back to your question about earlier line. I didn't know the 41% data, so it's interesting. Recently, we were analyzing our data over the past year for a multi-center study that you'll see hopefully at a coming congress, and 60% of our patients were the CARTITUDE-4 population. I was very pleasantly surprised, and that's data from the past year of patients receiving CARVYKTI at four major academic centers. That was, to me, till I saw the data, I would not have picked on it. It's actually the demographic is changing to more earlier line than later line. I think patient education, the support groups are very strong, but there is a mix. There's some very educated patients who'll come and ask you very nitty-gritties, but other patients, they have heard about CAR T, certainly from the support groups. It's a whole spectrum, but certainly people are aware. I think going back to your Kelonia question. I think it's too early. As I said, the bar is very high. Cilta-cel has set the bar very high, and that is the question that will come into play when you talk about this kind of technology. If durability, safety, and all the benefits, and the benefits in the post-BCMA space. I think right now we're just excited about that the technology works, but whether it's going to beat what the standard has set by cilta-cel and other available immunotherapies is still too early. I would say one case you cannot, because you don't know if it'll be one in 100, one in 50, when the numbers increase. I think with any phase I, it's hard to comment on very small numbers. Here we have a question, this side. My left side here. The third one. That's me. Okay. Yeah, this is Yang from Raymond James. Thanks for the questions. Maybe for the panel, this is a naïve question. Following up on the comment before, if patient received dara or talquetamab during bridging therapy, and they supposedly should respond very well, then the assumption is why would they switch to CARVYKTI or other CAR cells? My second question is also, it sounds like for maybe there's some logistic issue in terms of maybe CAR T. I'm not very familiar, maybe the doctors should teach me. Sounds like for the CAR T therapy, maybe it is more burdensome in terms of following the patients, monitoring the patients versus the patients receiving bispecifics. Would that be a conc ern that kind of making this issue for not a widely use of CARVYKTI in second line or earlier? Thanks. Maybe I'll take that question. Your first part, I would actually never give a patient the same target for bridging as the CAR T. After apheresis, I would not give them a BCMA bispecific because we don't want that target down-regulated. Just for the question's sake, if you give them any effective bridging therapy and they're responding. My patients ask me, "I am in almost a CR. Do I even need CAR T now?" Absolutely. As all the data just showed you, that is the time to do CAR T, is when your disease has responded to VGPR. It's best used as a consolidative therapy. I would say to your second question, is the burden for CAR T more? I would say no. It's different. Actually, the long-term burden for bispecifics is much more. It's a continuous therapy you have to give every week, then every other week, IVIG every month. With CAR T, it's limited duration. Sure, the logistics of moving close to a treatment center if you live very far away with the REMS program and all of that can be a little bit more in the first month, now it's to two weeks with the FDA. They changed the REMS program to two weeks, it makes it easier. The burden is a little bit more for that first couple of weeks, four weeks. After that, actually, it's much easier, in my opinion, from what I see for the patients. In the first case, I would like to add some of the anecdotal. Two of my patients started on talquetamab because they were very rapidly progressing disease. They were about to go to CAR T. They were thinking of going to CAR T, but they had to start some treatment because they were rapidly progressing. I started talquetamab, got into excellent response. After six months, they said they would want to explore the CAR T because they had to get the talquetamab all the time. I collected the cilta-cel. Now they are almost three years, close to two and a half years out, and they say they cannot feel anything better than this, because that tells you the patient have both the experience being on bispecific antibodies on continuous treatment and being one-time CAR T-cell therapy. I think they can see the difference in the quality of life, one versus another one, and they can really attest to what the cilta-cel or the CAR T can bring to that journey. I think that is important conversation when you have effective therapies that you will offer to the patient, and then help patient make the decision. Next question goes to Jayna. Hi. Jayna with TD Cowen. I want to go back to the in vivo programs. At Legend, you have your own in vivo platform. I was wondering if you could provide any details on this platform and any areas where you might be taking a similar approach to your competitors, and maybe areas where you might be more differentiated. For our KOLs, for the in vivo approach more broadly, are you concerned at all about controlling the dose, given that in vivo manufacturing is a little bit harder to control than maybe ex vivo manufacturing? Thank you so much. Does someone want to take this? Ying, do you want to speak to the first question about the Legend in vivo program? Well, what I can say is that we would typically wait until the abstract is officially accepted and also published by any major medical meeting before we make a comment. The only thing I can say is that I believe EHA is supposed to publish the late-breaking abstract on Tuesday. We're happy to answer any questions maybe after that. Other than that, I can't really provide any comment today. Next question. The manufacturing, right? It's a whole new field, right? What dose should you give a patient, and how does that translate into CAR T expansion in a patient? Is it similar across all patients getting a dose level? Does it depend on what T-cell numbers they have, their lymphocyte count? I don't think we know. I think this is, again, we are at the brink of a completely new field. I don't think any of us can guess. I think we have to do those systematic studies to be able to answer that. No, I agree. It could be heterogeneous from patient to patient, right, the expansion. I think it's important they're exploring all the dose levels, going to dose level minus 1, going to a little bit. They're going very cautious approach, and I think they will learn maybe after treat more patients and see the expansion. Still too early to say. Okay, we have time for one last question from James. Hi, thank you. This is James Shin from Deutsche Bank. This one's for the experts. Is there enough BCMA CAR Ts? In a sense, I guess the simple question is, BCMA CAR T is zero-sum game, and you've mentioned that IO is currently underutilized in second line, but there's a lot more coming. How do you see the field or landscape playing out with more BCMA CAR Ts? Thank you. There's always room for more therapies. You can take an example of the bispecific antibodies. Right now, we have three BCMA bispecific already approved late line. They are fastly moving in the early line. People are still using it. Of course, they are not the same. It always important conversation is how they fare in terms of safety and efficacy. That conversation is important. We still have to see in terms of BCMA CAR T. There's only one CAR T approved, two CAR T approved right now. One, of course, is not because of the efficacy. I think the cilta-cel is becoming the preferred one. The future one coming on have to pass the test of both safety and efficacy. Then will be the conversation about those CAR T. To answer your question, I think there is room for those options at all time. Yeah. 35,000 new cases in the U.S. Now, if you expect everyone to get CAR T in the front line or immunotherapy in the front line, we need more than one option, we have to evaluate them on balance of safety and efficacy. Okay. With that, I just want to, again, thank you for coming, and also thank you for the doctors, Dr. Hansen, Dr. Sidana, and Dr. Dhakal, for all your insight. Thank you.