Legend Biotech Corp - ADR Aktie

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 3 KOLs we have. Dr. Dhakal will talk about the curative potential for CARVYKTI and Dr. Hansen will talk about early treatment with CAR-Ts better. And then Dr. Sidana will talk about the safety management in real-world management. And then lastly, we'll open up the floor for questions. So 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 stand-alone cell therapy company, and we're a pioneer in using immune cells to treat 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 generate 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've now treated more than 10,000 CARVYKTI patients to date. In addition, we have a cash position and liquidity of $835 million as of the end of first quarter. And this year, we do expect to achieve corporate profitability on 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 who have been 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 cure. CARVYKTI has proven data supporting its potential curative potential, whereas no other CAR-T in multiple myeloma has been able to substantiate this kind of long-term efficacy over 5 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. And finally, CARVYKTI is a onetime infusion, which offers flexibility in both inpatient and also outpatient settings as well as lifetime cost savings, benefiting patients, health care 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'd like to introduce you to 3 guest speakers. First, we'll hear from Dr. Dhakal on CARVYKTI's curative potential. He's with Medical College of Wisconsin. Then we'll hear from Dr. Hansen on how early treatment is better, and she's from the Moffitt Cancer Center. And we'll conclude with Dr. Sidana presenting on safety management, and she's with Stanford University.

With that, Dr. Dhakal, over to you.

Good evening, everybody. Thank you, Dr. Ying, for the nice introduction. So today, I'm going to make a case of the potential of cure with CARVYKTI. As Dr. Ying pointed out, this is probably one of the biggest strength of this product.

And because of the CARVYKTI, I think we are talking about cure in 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.

And 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. So in February of this year, IMS 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 5 years. And I'm going to show about the data why CARVYKTI has the potential to achieve that.

Now how you 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 this we could define cure in either newly diagnosed or relapsed/refractory setting. The patient need to be in sustained complete response by standard criteria. They need to be MRD negative at 10^-6 with either NGS or NGF, which is next-generation flow. And there has to be sustained MRD negative for 5 years without any therapy. So that is very critical. As you know, there are a lot of other therapies coming in the market which can potentially have a deep responses, but they need to be off therapy. So this is a big kind of important step from the patient point of view. And they need to be have at least 4 MRD assessment during the time period with no positive in between. So you can't have MRD negative turning to positive and negative to become a cure. You need to be sustained MRD negative for 5 years.

And last but not the 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 -- I mean, by PET scan or MRI, you need to have no evidence of disease for 5 years that need to be sustained as well.

So how CARVYKTI meets that goal for that point of time. So this is the data you might have seen. This was the big kind of 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 5 years. And when they looked at that, out of 97 patients treated in the CARTITUDE-1 program, 1/3 of the patients, that's a big number who were treatment-free and progression-free for more than 5 years after single infusion. So that is really a very, very impactful data.

But more importantly, in that patients, 1/3 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 5 years and also PET negative for 5 years, meeting the proposed definition of cure.

So clearly, it tells you that CARVYKTI has that potential. That is one part. But more importantly, if you look at the median overall survival of these patients in the CARTITUDE-1 long-term follow-up, it is about 61 months, more than 5 years. Why that is important? The median prior lines of therapy in CARTITUDE-1 program was about 6 lines, and they were all heavily treated patients, including triple class exposed patients. And historically, these patients would have a median overall survival of less than a year.

So we have 5x the overall survival with 1/3 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.

So the next question is how we can achieve that better cure fraction if you move this therapy early line. So 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. Hansen?

Hello. Good evening, everyone. So yes, today, I'll be discussing earlier is better, and I wholeheartedly do believe that, that is the case. So 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% to 30% per line of therapy. So if we have treatments such as CARVYKTI, where you can give a onetime treatment, improve quality of life and have other treatment options, it really makes for a very good candidate and truly groundbreaking transformative type of therapy.

Now 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 3 years where it might have been with conventional systemic chemotherapy less than 6 months.

So truly impressive data there. If we look at CARTITUDE-1 and CARTITUDE-4 patients, so these are triple class exposed who had received 3 prior lines of therapy, the median progression-free survival can be as high as 50 months, which is truly impressive.

Now 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. Now 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. But 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 5-year mark, but we're also seeing improved safety.

At the 5-year mark, as you see, for example, in the CARTITUDE-1 study that we had 6% Parkinsonism. But when we look at CARTITUDE-4, meaning we give CARVYKTI earlier, we saw 1 patient with Parkinsonian features, which is less than 1%. So 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. But really the patients who are 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. And 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 with 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.

But 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. And 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 3, and 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, and we did not see any Parkinsonian cases in this particular cohort as patients were being bridged, and 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. And now we have a lot to -- a lot that we have learned about mitigating toxicity and making this treatment much better in terms of safety as well as efficacy.

And I will invite Dr Sidana to talk to you all more about safety. Thank you.

Thank you, Dr. Hansen. And again, we have CARVYKTI that we've seen how effective this is. But what are the practical steps we can take to be able to use it safely in the clinic. And Okay. It works.

So this is data from the CARTITUDE-4 trial that Dr. Dhakal presented at the ASH 2025 meeting. And 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. And 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 like the trial as it was an intent-to-treat analysis, there were significant safety signals in people who are just progressing and then getting to CAR-T. So 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. So how can we optimize bridging therapy?

In the late-line setting, which was the initial label for CARVYKTI with 4 plus lines, often our hands are tied. We didn't have good options when CARVYKTI first came to market. But now we have options, and this was with talquetamab, and this is a study, again, Dr. Dhakal and I, our senior authors here, our entire U.S. Multiple Myeloma Consortium participated in this, that talquetamab bridging in the real world is a very safe and effective option. And what we learned was it actually resulted in improved safety with CARVYKTI.

We saw no cases of Parkinsonism, and that's because of this significant disease debulking that we see. We also had our own institutional data presented at ASH last year, where we saw that we looked at both ide-cel and cilta-cel. And with cilta-cel in patients who are 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 reiterate. So 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.

And in this data set, where majority of the patients were in late line, about 85%, we saw 22 cases of Parkinsonism.

But again, the story that emerged was that 21 out of those 22 cases were in patients who had not responded to bridging therapy. So the risk of Parkinsonism was as high as 5% in nonresponders, 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-relapsed mortality was half in patients who had a response to bridging therapy with 1-year estimates close to 5% in responders and 10% in nonresponders to bridging therapy.

So again, what does this all tell us? Again, multiple data sets, different patients, trial in real world, they all come to a similar point that CARVYKTI should be used as a consolidative therapy with effective disease debulking -- and while it was challenging in the very, very early days of CARVYKTI, we now have very effective bridging options as CARVYKTI is available at second line, and we also have good bridging options in the late-line setting. And this is, again, a slide summarizing all of the data sets I talked about, a lot of detail.

But again, the best we can, and this is the message that we are working very diligently to communicate to all of our referring providers because this is a true partnership, and 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. So this is data within the last 9 months, and this is how quickly we're learning about things.

So now with the talquetamab real-world study, we have talquetamab as a bridging option, including in the NCCN guidelines. And 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.

And this was -- yes, Alan, I'll invite you to present this data, which is emerging data that is coming from the ASCO data sets that were just released.

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 we just came off the -- hot off the press at ASCO in the last 2 days. Alan?

So as a lead into the Q&A, we thought it would be important to share 2 additional data sets for your reference. The first is a publication that recently came out in the Journal of Oncology and Hematology, a registry database from Germany that looked at 606 patients and compared the cohort that was essentially the CARTITUDE-4 population, the 1 to 3 prior lines with the population that had received CARVYKTI in the later lines.

And as you can see from the data set in the 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.

So 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 analysis was presented today at ASCO that was looking at the TriNetX data set here in the U.S. And it looked like -- 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. And as you can see from this data set, it was complementary data set of 389 patients, 244 received CAR-T first.

And you can see that there was a longer survival, both the median OS and the 5-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.

So with that, let me turn it back to Ying to moderate our Q&A.

Thank you, Alan. So the first question, I'm going to kick off by asking all 3 panels here is that how are you currently prescribing CARVYKTI in your practice? And also, what has been your experience since you began prescribing CARVYKTI?

I can start us off. So CARVYKTI, certainly, when it was first approved, we gave it in later line. But now with the CARTITUDE-4 data as of April 2024 and given particularly the long-term follow-up with this 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.

Yes. Completely agree with Dr. Hansen. My practice is similar. We try to use it effective therapy as early as possible. That is like a core principle in oncology. You don't want attrition. You want to use your best therapy first.

And I would say, again, just the experience is also different. When we had limited bridging options in 2022 when CARVYKTI first came, I mean, some of the patients did have severe side effects. But now that we are debulking our patients going with as low disease burden as possible, I often change the bridging if it's not working. I mean it's very well tolerated. The risk of severe side effects, even talking about severe CRS or ICANS, I mean, virtually unheard of in the last year or so in our practice. I mean, so our practice has shifted to earlier line, but the patient experience is also changing.

Yes. 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. So there's a lot of interest in high-risk patients and then probably preserve in standard risk, maybe not go directly to the cilta-cel. But I think once you look 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 like even stronger plateau for that. So I think independent of the risk, anybody who is eligible for CAR-T, I think that's my recommendation to go to CAR-T at their first relapse, and that's what I do in my practice. And I think this is a 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. So can we get a microphone to. Please say your name and your affiliation so that the people on the webcast can listen.

Ted [indiscernible] from [Point Marsh High School ]. Thanks for having us. It's Really great to reinforce just how important and how powerful this medicine is. My question really builds right on Ying's question. So thank you for taking this early. But 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. So maybe you can walk us through kind of what those options are, typically, how long that will work, how long that will last? And then what percentage of your patients are getting CARVYKTI? I know the manufacturing throughput has increased dramatically. Is pretty much all of your patients getting CARVYKTI now?

Happy to take the bridging question. I would say that the manufacturing is a nonissue at this point. It was an issue in 2022. But at this point, there is no constraints on manufacturing, complete nonissue. And 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 I mean, we do CARVYKTI at 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.

So it just depends on their treatment history. So it's not a particular drug. It's just whatever they are not refractory to that you think has a good chance of working. If it's not working in a month, we switch it.

Yes. 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 VGPR is better. But you saw the data even early line CARTITUDE-4, we saw that patients at least achieve a PR and better, they do better than either not responding or having stable disease. The goal is to 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. But luckily, in late line, I think at least now we have talquetamab and then we can use some other agents kind of in combination and at least get a patient in responding patients to the CAR-T. The jury is still out like what is the best level of response to bridging so that they get the best outcome. That is still an open question. But as long as they're responding or the kinetics of disease is kind of on a downward slope, I think 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 we now have very good options. My colleagues mentioned DARZALEX based, talquetamab, we have Kyprolis based. We've heard SUCCESSOR-2 data with the new CELMoD. So 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. And quite frankly, I work at a very high -- 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.

So 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? And how do you decide when CARVYKTI makes the most sense for a patient in your practice?

For eligible patients 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. But if they are 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. And if we move it early line, might be even better. And also onetime treatment, treatment-free interval, quality of life, all those factor into conversation.

And then, of course, discuss that with the patient as well as the safety. And then I think that's why -- that's how we recommend that the next line of therapy. But again, if you look at the sequencing, it's better to give the CAR-T followed by bispecific and Alan showed the data as well from the real world. You get like long duration of response or a benefit if you do that sequencing rather than the other way around. So the CAR-T is the way first one to offer to the patient.

I completely agree.

Maybe another question I'll throw up 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 2 ongoing trials. One is CARTITUDE-5 in transplant ineligible or transplant delayed patients. And then the other one is CARTITUDE-6, where we're comparing CARVYKTI head-to-head against transplant in transplant-eligible patients.

So maybe, again, going back to the core principle of oncology, you want to use your most effective treatment early line, right? 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. Of course, we are heavily anticipating the results of those data, both from the transplant ineligible or deferred and the transplant eligible study.

And with -- we hope the study is positive, of course, we have to wait and see the data. I think it would be an excellent option, right? Because for frontline right now, we are telling our patients, you have years and years of treatment. So why wait for that treatment-free interval and potential curative therapy for later line. And 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, but I'm hoping that transplant has met its match in CAR-T. And I'm really hoping that finally, we'll be able to move to a different therapy. But of course, we're heavily anticipating those data.

No, I agree. I think in both transplant eligible and ineligible, if you can just give onetime therapy and get this prolonged PFS, that would be really meaningful from the patient point of view. And again, I'm more heartened in the cure this time because I think you might be curing some subset of patients with this onetime infusion. And with a median diagnosis of 69 years in these patients, if we can even achieve cure of half of the patients, then that is a big deal, right? They don't need any therapy in their lifetime.

So 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 on their in vivo CAR-T targeting BCMA for treatment of myeloma. So what do you guys think about the in vivo CAR-T as a potential therapy in myeloma? And also what are your thoughts on the data that was presented this morning?

So 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 a subset of patients. We're seeing Grade 2 CRS. So 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.

I would say very exciting technology, not just in myeloma. We'll see this like change our field in the future. We just have to keep in mind the technology we work on for the future and there's technology for our patients in clinic. I mean this is where CARVYKTI was probably 8, 9 years ago, where we are right now with in vivo. So 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 BCMA moving earlier, we'd like to see how this will fair when we have prior BCMA exposed patients. But so far, it looks pretty exciting.

Okay. So let's go with Konstantinos in the front row here.

Konstantinos 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-Dara approved?

And 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?

I can start. So -- to me, I don't -- 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 have 85% of patients who are 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 and 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. And really, one thing I'd like to really focus on is as you get some of these treatments earlier in the disease course, of course, the disease is more naive. The treatments are going to work better.

But 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. So I think that's where we need to be very mindful when we interpret all of this data, and that's where really utilizing kind of the CAR 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 onetime treatment that works well for a significant amount of years and improve their quality of life, that's critical. And 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. And you saw in MajesTEC-9 in terms of mortality from those severe infections about 5%.

I mean that would be really a shame to have a patient die of a severe infection early on. We are all utilizing IVIG, but I think we have to be very careful of this continuous strategy and risk for infections in our patients.

I would add, I mean, 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 is accessible and feasible for them. And 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 6 months. They can't keep up with it. But 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. Of course, there's a lot of pros in favor of CAR-T that my colleagues have already talked about. But all that 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 onetime therapy, you're less likely to have that. So there's a biological rationale for the data that we're seeing beyond just the infections and the schedules and the logistics. So -- but I think every patient deserves a conversation. And ultimately, it's a patient's choice, but every patient deserves a conversation.

Yes. I think one thing I would just add on top of what has been said is before TEC-9, any dara refractory patient, cilta-cell was the only option. Now with the TEC-9 saying that these patients could also benefit from teclistamab monotherapy. But having said that, the conversation of what first, CAR-T first or bispecific first for eligible patients, that doesn't change with the data.

It's just -- before TEC-9, they were all there naive or nonrefractory patients. [indiscernible] ]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 patients given the sequencing, given the -- all those benefits that we talked about.

We'll go to Eric next maybe.

Eric Schmidt from Cantor. Just coming back to the risk mitigation strategies around Parkinsonism. It sounds like you guys have a very clear view on what should be done, but 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?

Yes, we are actively working on those. That's an excellent question. And again, the field is moving so rapidly, right? All of this is happening in less than a year. So the International Myeloma Working Group, which comes up with guidelines actually now has living guidelines because the field is changing so quickly. We are also evaluating all of these risk mitigation strategies in different studies.

So bridging is one thing we talked about, but there's also other measures like 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. And then if someone has symptoms of toxicity, the best paradigm to manage it. We have learned something -- these things very quickly. So this is all being put into guidelines.

And again, the task ahead of us is not just for us experts to know, but how do we educate everybody else, right? Because, again, we live and breathe this 24/7, but that's not everybody -- they take care of many other types of patients. So that's cut out for us. That task is cut out jointly with the manufacturers, like how do we educate everybody -- for the -- it's a continuous -- I mean, all of these meetings, right, all of these efforts, part of it is to educate on the guidelines.

And we have seen the effect of that in the clinic already. I mean we used to -- even people who used to see a lot of Parkinson, the numbers are going down because prevent and treat the studies and monitoring the studies, I think, have worked very nicely, especially the efforts and the impact of bridging has really impacted that and then the monitoring of the CAR expansion and then potentially intervening that at certain point of time has impacted that. And even the treatment has evolved, right?

Now we know how to treat it, how to identify this as early as possible, identifying. So 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, and we are seeing the effect in totality of that effect in the incidents and the outcomes in the clinic.

So to answer your time line question, so the International Myeloma Working Group living guidelines are online and being updated continuously. So that should be readily available to anyone. Other studies certainly are ongoing.

For example, Dr. Sidana has the CITADEL 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. And then the ASGCT in additional to the IMS -- IMWG has some guidelines that was just recently accepted and should be in press soon. So certainly, this is an evolving field and a lot of data should be coming out shortly.

And 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, but it's in the publication that in the table of AEs, there was one Parkinsonism case in the 606 patients. So I think -- and that was in a later line patient.

So I think, again, it supports this concept of earlier better. And the question about how we work with -- 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. But 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.

Jon Miller from Evercore ISI. As you guys just said, you're the experts. You see this whole tail of every day, you get a lot of CAR-T, you're at very active centers. And you're moving CAR-T as early as you can. But what about the patients that you're getting referred from community? And I'd love to hear each of your experience with at what stage in their journey you're getting those patients, how -- what your experience is with that evolution over time? How often are you seeing patients that are already bispecific exposed from community treatment? And can you talk a little bit about where you're getting patients in that you're not starting with?

So I think we see a similar -- 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. So we can capture these patients very soon. And even the community doctors are seeing these patients, send a note to us if the patient is progressing in the need of new therapies, especially immunotherapy, right?

That might not be applicable to other different practices that is different. So 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 an important part of the work that is ongoing, including from us, from the sponsors, from different individuals working on that.

And in terms of like 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 first year where all these toxicities are bound to happen. We talk about CRS and ICANS and Parkinsonism, but there are a lot of other toxic. If you look at non-relapsed mortality, infection is the most significant one. So I think we want to make sure that all these things are managed properly when they go back to the community. So there is a constant communication and even seeing these patients at frequent intervals, making sure that they are following all the guidelines of managing and treating infections or preventing infections.

And in addition to all the things talked about 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 basis depending on how far they are from the therapy. And we have -- like some of the patients who are 5 years out in the CARTITUDE-1, I have 3 of those patients, they still see us on 6 months 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. It 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.

And I think that also says that there is now that we have so many immunotherapy options, education. And 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.

I guess just to add to it, I think CARVYKTI got approved in 2022. So 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, so we had control of those patients in terms of exposure to the different agents. But I think now that there's 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 more of -- I've had some referred in late line that I really have nothing else to bridge with but talquetamab and then fewer that are coming earlier in the disease course. But 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 indications and prior treatment history. I think that's going to be crucial.

And I would just add that to your point, I don't see patients who are treated with bispecifics referred to me just yet. So if they are thinking about immunotherapy, they're sending to us to have that conversation. The thing is that they're sometimes not thinking about immunotherapy. So I think to my -- to your point, it's not like they are 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.

Let's go to Etzer first and then maybe Ash after that.

Etzer Darout, Barclays. Just a related question around demand dynamics that you're seeing at your centers or maybe amongst your peers for CARVYKTI uptake, particularly given some of the emerging safety data that you've talked about today, just how that's shifting or changing?

As I mentioned that 3 years ago, 2 years ago, we actually had less referrals. We have many more referrals right now. So the patients are there. Can that pool be expanded? I think there's a lot of room to expand that with education. And it's not -- it's often community providers do not send patients to us because they're worried about safety. It's just that they're not thinking about immunotherapy at that point. So 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 is exhausted. And I think that's what we are trying to -- the data is otherwise that it's better than standard of care. So that's the mindset we are trying to change.

Yes, definitely, it's increasing. Patients -- 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. So I don't think it's the safety -- 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. And the numbers were clearly, the number shows that the early line CAR-T is increasing that tells you that a lot of patients are being referred for that.

And these 2 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. So in the most recent earnings call, we reported that 41% of our patients are coming from the second and third line. So again, it's consistent with the fact that there's an evolution towards the earlier patient treatment paradigm.

Ash?

Ash Verma from UBS. Yes. I guess, Alan, just to follow up on the 41% number that you talked about, right?

So 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. That -- I'm assuming that would require quite a significant push in the community setting. So just help us understand in terms of where your commercial marketing push is, -- how does that get heavy on the commercial -- on the community side? And then just secondly, on the -- like the Kelonia data today, so yes, like we saw one Grade 3 ICANS. I mean, small numbers like only 18 patients right now. But 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 the other available options? Or do you think that, that might be a negative?

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. So we have about 1/3 of our authorized treatment centers are in the regional and community hospitals. So 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. And 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. And then 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 and capability.

We have a number of those planned. We have some that have already started, Virginia Oncology Associates, Tennessee Oncology and more are planned. But 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. And 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 selective 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. So 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 patients, but definitely, so patients -- I would say myeloma patients are a little bit more savvy. That's my understanding is and 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. And then I have some patients, I would say 20% to 30% of patients coming with a lot of information, but also depends on where the patients come from, like rural Wisconsin, sometimes they come in, they don't have a lot of information about the CAR-T. So I think it's variable. But I would say that numbers of patients understanding and knowing about the CAR-T number is slowly increasing, and that's partly because of the outreach.

And if I can go back to your question about earlier line. I didn't know the 41% data. So it's interesting. But recently, we were analyzing our data over the past year for a multicenter study that you'll see hopefully at a coming congress. And 60% of our patients were the CARTITUDE-4 population. And I was very like pleasantly surprised in that data from the past year of patients receiving CARVYKTI at 4 major academic centers.

And that was -- to me, until I saw the data, I would not have picked on it. But it's actually the demographic is changing to more earlier line than later line. And I think patient education, the support groups are very strong, but there is a mix. So there are some very, very educated patients who come and ask you very nitty gritty. But other patients, they have heard about CAR-T certainly from the support groups. And so it's just -- it's a whole spectrum, but certainly people are aware.

And I think going back to your Kelonia question, right? I think it's too early. I mean, 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. So 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.

But I would say in one case, you cannot -- because you don't know if it will be 1 in 100, 1 in 50 when the numbers increase. So I think like with any Phase I, right? I mean, it's hard to comment on very small numbers.

Here, we have a question on this side, my left side here.

This is Yang from Raymond James. Maybe for the panel, this is a naive question. So following up on the comment before, if patients received dara or talquetamab given bridging therapy and suppose they to respond very well, then the assumption is why would they switch to CARVYKTI or other CAR-T cells? And 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, but it sounds like the -- for the CAR-T therapy, maybe there is more burdensome in terms of following the patients, monitoring the patients versus the patients receiving bispecifics. Would that be a concern that kind of making this issue for not a widely use of CARVYKTI in second line or earlier?

Maybe I'll take that question. So your first part, I would actually never give a patient the same target for bridging as the CAR-T, right? So I would -- after apheresis, I would not give them a BCMA bispecific because we don't want that target down regulated.

But just for the question's sake, if you gave them any effective bridging therapy and they're responding, actually -- and 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-Ts when your disease has responded to VGPR. It's best used as a consolidated therapy. And I would say to your second question, is the burden for CAR-T more? I would say no. It's just it's different. Actually, the long-term burden for bispecifics is much more a continuous therapy. You have to give every week than every other week, IVIG every month. Whereas with CAR-T, it's limited duration. Sure, the logistics of moving to 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, and it's now to 2 weeks with the FDA. They changed the REMS program to 2 weeks to makes it easier. So the burden is a little bit more for that first couple of weeks, 4 weeks. But after that, actually, it's much easier, in my opinion, from what I see for the patients.

So in the first case, I would like to add some of the anecdotal, 2 of my patients start talquetamab because they are very rapidly progressing disease because they were about to go to CAR-T. They would think of going to CAR-T, but they had to start some treatment because they're rapidly progressing. So I start talquetamab, got into excellent response. And after 6 months, they said they want to explore the CAR-T, they had to get the talquetamab all the time. So I collected cilta-cel.

Now they are almost 3 years, close to 2.5 years out, and they say they cannot be feel anything better than this because that tells you the patients have both the experience being on bispecific antibodies on continuous treatment and being onetime 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 cilta-cel or the CAR-T can bring to the patient. So I think that is an important conversation when you have effective therapies that you offer to the patient and then help patient make the decision.

Next question goes to [indiscernible].

[indiscernible] with TD Cowen. I want to go back to the in vivo programs. So 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? And then 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?

Do you want to speak to the 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. So the only thing I can say is that I believe EHA supposed to publish the late-breaker abstract on Tuesday. So we're happy to answer any questions maybe after that. Other than that, I can't really provide any comment today.

The manufacturing, -- 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. So we -- I don't think any of us can guess. I think we have to do the systematic studies to be able to answer that.

No, I agree. It could be heterogeneous from patient to patient, right, the expansion. So I think it's important they're exploring all the dose labels going to dose level minus 1, going to lipid. So they are a very cautious approach, and I think we will learn maybe after treat more patients and see the expansion. So it's too early to say.

Okay. We have time for one last question from James.

This is James Shin from Deutsche Bank. This one is for the experts. Is there enough BCMA CAR-Ts in the sense -- I guess the simple question is BCMA CAR-T is a zero-sum game. And you mentioned that IO is currently underutilized in second line, but there's a lot more coming. So how do you see the field or landscape playing out with more BCMA CAR-Ts?

There's always a room for more therapies. You can take an example of the bispecific antibodies. Right now, we have 3 BCMA bispecific already approved in late line. They are fastly moving in the early lines. And people are still using it. Of course, they are not the same. And it always important conversation is how they fare in terms of safety and efficacy, and that conversation is important. So we still have to see in terms of BCMA CAR-T, there's only 1 CAR-T approved -- I mean, 2 CAR-T approved right now. One, of course, is not because of efficacy, I think cilta-cel is becoming the preferred one. And the future one coming on to have to pass the test of both safety and efficacy, and there will be the conversation about those CAR-T. But to answer your question, I think there is room for those options at all time.

I mean 35,000 new cases in the U.S. Now if you expect everyone to get CAR-T in the front line as or immunotherapy in the front line, we need more than one option. And then 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 insights. Thank you.

Good day, and thank you for standing by. Welcome to the Legend Biotech First Quarter 2026 Earnings Conference Call.

[Operator Instructions] Today's conference is being recorded. I will now hand the conference over to your speaker host for today, Jessie Yeung, Vice President of Investor Relations and Finance. Please go ahead. Good morning.

This is Jessie Yeung, Vice President of Investor Relations and Finance at Legend Biotech. Thank you for joining our conference call today to review our first quarter of 2026 performance.

Prior to this call, we issued a press release announcing our financial results for the quarter. You can find the press release on our IR website at legendbiotech.com. Joining me on today's call are Ying Huang, the company's Chief Executive Officer; Alan Bash, the company's President of CARVYKTI; and Carlos Santos, the company's Chief Financial Officer. Following the prepared remarks, we will open up the call for Q&A. We also have our President of R&D, Guowei Fang, joining the Q&A session.

During today's call, we will be making forward-looking statements, which are subject to risks and uncertainties that may cause our actual results to differ materially from those expressed or implied here within. These forward-looking statements are discussed in greater detail in our SEC filings, which we encourage you to read and can be found under the Investors section of our company website.

In addition, adjusted net loss is a non-IFRS metric. This non-IFRS financial measure is in addition to and not a substitute for or superior to measures of financial performance prepared in accordance with IFRS. There are a number of limitations related to the use of these non-IFRS financial measures versus their closest IFRS equivalents.

However, we believe that providing information concerning adjusted net loss and adjusted net loss per share enhances an investor understanding of our financial performance. We use adjusted net loss as a performance metric that guides management in its operation of and planning for the future of the business. In particular, we exclude unrealized gain or loss from foreign exchange rate changes. We believe that adjusted net income or loss provide a useful measure of our operating performance from period to period. Our press release includes IFRS to non-IFRS reconciliations for these measures.

With that, I will now turn the call over to Ying.

Hello, everyone. Thank you for joining us today. We began 2026 with strong momentum as we executed commercially and continue to advance our pipeline. Legend is the largest stand-alone cell therapy company anchored by CARVYKTI, our market-leading and profitable CAR-T therapy for multiple myeloma. In parallel, we're working to advance CARVYKTI into the first-line treatment setting to help reach more patients and further broaden its long-term opportunity.

Beyond CARVYKTI, we also have a strong pipeline of potentially transformative cell therapies across additional therapeutic areas where curative options remain limited. As this pipeline matures and generates more meaningful clinical data, we're looking forward to presenting some of the data at upcoming medical conferences this year.

During the first quarter of 2026, CARVYKTI net trade sales were approximately $597 million, representing 52% growth compared to the first quarter of 2025. This was comprised of 36% growth in the U.S. year-over-year and more than 200% growth from ex U.S. sales. This performance reflects strong demand in early line settings, continued global expansion and consistently best-in-class manufacturing execution.

Importantly, the myeloma treatment paradigm continues to shift towards earlier use of CAR-T. In the recent social media poll for KOLs conducted by Dr. Ben Derman from University of Chicago, 66% of respondents indicated they would recommend CAR-T at first relapse for contemporary myeloma patients followed by DVRd induction and maintenance, assuming Daratumumab resistance. We view this sentiment as further validation that CARVYKTI is increasingly considered a foundational therapy earlier in the disease course.

Before transitioning to the pipeline, I want to highlight an important step we announced earlier this month. We recently engaged six distinguished scientific advisers, Renier Brentjens, Spencer Fisk, Carl June, Maximilian Konig, Tony Polverino and Georg Schett, who bring deep expertise across oncology, immunology and in particular, cell therapy as well as translational research.

As we broaden our pipeline, we believe their input and advice will help guide critical scientific and clinical decisions and strengthen the rigor behind our long-term R&D strategy.

At the top of pipeline, we have some of the larger active CARVYKTI trials. Most importantly, CARTITUDE-5 and CARTITUDE-6 are pivotal Phase III studies designed to assess CARVYKTI in frontline multiple myeloma following its label expansion in earlier lines.

Turning to our earlier-stage pipeline. You're going to start to hear more about these programs as clinical data starts to mature from our next-generation cell therapy platforms. Our BCMA In Vivo program in autoimmune diseases has entered Phase I. Beyond BCMA, our GPRC5D In Vivo program in multiple Myeloma has also entered Phase I.

In parallel, our other In Vivo CAR-T programs continue to progress, and we remain on track to report initial data this year in Non-Hodgkin's Lymphoma. We continue to expect to file one to two U.S. INDs in 2026 and are excited by the differentiated potential of our approach.

Financially, our strong balance sheet provides us with flexibility to invest in our priorities while maintaining a clear focus on profitability. We believe this combination of commercial leadership, pipeline innovation and financial discipline positions Legend well to deliver durable value for patients and shareholders over the long term.

With that, I will turn the call over to Alan.

Thank you, Ying. I'll start with a high-level view of CARVYKTI's commercial performance and then spend time on what's driving growth beneath the surface.

In Q1, CARVYKTI delivered another quarter of sequential growth, reflecting continued share gains, strong site productivity and increasing penetration in earlier lines of therapy. Demand remained healthy across all major geographies, supported by our expanding global footprint and consistently reliable manufacturing execution.

CARVYKTI net trade sales in the first quarter were approximately $597 million, representing 8% sequential growth from Q4 2025. In the U.S. growth was driven primarily by increased utilization in earlier line settings, continued activation of new authorized treatment centers and steady throughput at existing sites.

Outside the U.S. demand was supported by continued uptake in established European markets and contributions from recent launches with CARVYKTI now available across 18 global markets and more than 300 global treatment sites. As expected, international growth continues to scale as site experience, manufacturing slots and referral patterns mature.

Turning to the next slide. We want to highlight how we are accelerating growth through our manufacturing optimization and earlier line momentum. From a manufacturing standpoint, we continue to optimize. This past quarter, we achieved a 99% manufacturing success rate and a median turnaround time of approximately 29 days with delivering more than 95% on-time order releases for final product delivery.

We believe these metrics are a testament to our commitment to broadening adoption, particularly as physicians move CAR-T earlier in the treatment paradigm.

Now importantly, although we do not intend to break this out every quarter since we think about our business on a longer-term basis, we wanted to provide a glimpse of the traction made in earlier line settings in the U.S. where nearly 80% of patients are treated in the community setting.

As you can see on the far right-hand part of the slide in the color teal, patients in second line and third line represented 41% of CARVYKTI apheresis volume in the U.S. in the first quarter of 2026 compared to 29% in the same period a year ago. This trend reflects growing physician confidence in CARVYKTI's benefit risk profile earlier in the disease course and our ability to reliably support that shift at scale. We expect this trend to continue and be a major driver of future growth, especially as we advance towards a potential label expansion into the first-line setting.

With that, I will turn the call over to Carlos to walk through our financial performance.

Thank you, Alan, and good morning, everyone. I'm pleased to walk you through our financial performance, which reflects an important quarter of commercial growth and disciplined investment.

Turning to the next slide. This chart highlights our progress towards profitability. As you can see, revenue has continued to scale, driven by CARVYKTI performance and profitability metrics have improved steadily over time. We anticipate company-wide profitability on an adjusted basis in 2026 and expect continued margin improvements from our ongoing expense discipline.

Regarding Q1, the next slide illustrates how revenue growth is translating into operating leverage. Collaboration revenue was approximately $298 million in the first quarter, primarily driven by CARVYKTI net trade sales under our collaboration with Johnson & Johnson. License and other revenue was approximately $7 million, resulting in total revenue of $305 million for the quarter.

Gross margin on net product sales was 41%. The decline from the fourth quarter at 57% was primarily due to onetime expenses associated with ramping up manufacturing in the newly expanded section of our Raritan site and the ongoing Tech Lane facility ramp.

Looking ahead to the second quarter, we expect gross margin to be back over 50% as the economies of scale from our manufacturing investment are realized with increasing utilization.

Research & Development expense was $86 million, reflecting continued investment in our In Vivo CAR-T platform and next-generation programs. As the Phase III CARTITUDE-5 and 6 studies for CARVYKTI mature, we expect a substantial decline in the associated R&D expenses. This allows an increasing proportion of the R&D budget to be reinvested into the pipeline as we leverage the benefit of CARVYKTI profitability to fund the future growth of Legend that will come from the promising In Vivo programs and extensive earlier-stage pipeline that Ying showed earlier.

SG&A expense was $90 million, driven by targeted commercial investments supporting CARVYKTI growth. Operating loss narrowed compared to the prior year with an adjusted net loss of $11 million in Q1. We feel very comfortable in maintaining our projection for achieving company-wide profitability on an adjusted basis in 2026. On a non-IFRS basis, this represents $0.03 per diluted share compared with an adjusted net loss of $27 million or $0.07 per diluted share in the same period last year.

Turning to the next slide. We ended the quarter with approximately $835 million in cash, cash equivalents and time deposits and no long-term debt. We believe the strong balance sheet provides us with flexibility to advance our In Vivo CAR-T pipeline, support continued CARVYKTI profitability expansion, pursue focused business development opportunities and fund modest capital expenditures tied to manufacturing capacity. Based on our recent progress, we remain confident in our company-wide profitability trajectory as we continue to invest prudently in long-term growth.

In summary, the first quarter reflects a business that is scaling efficiently, generating increasing operating leverage and approaching sustained profitability.

With that, we're happy to take your questions.

[Operator Instructions] First question coming from the line of Terence Flynn with Morgan Stanley.

Obviously, there's a growing focus on In Vivo programs, platforms. Maybe, Ying, you could give us a little bit of update in terms of how much data we should expect from your lymphoma program? And any more specifics on timing? Is EHA a possibility? Or is it more likely ASH? And then how are you thinking about durability? And what will we learn from this first data set with respect to that question?

Terence, thank you for that question. So as typical with our disclosure practice, we cannot really comment on the data without the abstract being officially accepted and also published by the major medical meeting. The only thing I can confirm is that we are planning to potentially present the data set for the first time in patients with non-Hodgkin lymphoma at a major medical meeting around midyear. So that's the only thing I can confirm right now.

In terms of durability, I guess it's really depending on how many patients and how much follow-up we have. But in general, because this is the first disclosure for our clinical data here. So, I wouldn't expect a very, very long follow-up. But we do expect a reasonable number of patients in this first disclosure. I hope that answers your question.

And our next question coming from the line of Umer Raffat with Evercore ISI.

I wanted to touch up on this In Vivo CAR-T theme in a little more detail, perhaps. And maybe for everyone listening in, Ying, because this is a new theme popping up beyond CARVYKTI beyond Arcellx, could you just remind everyone, first of all, that the CD19, CD20 CAR-T you have is not the gamma delta, which is Allo. We're talking about In Vivo, A, if you could just clarify that B, the name of the program, like the number? And number three, and I acknowledge you can't say if it will be at EHA or not and the scope of the data. But could you just give us a sense for what the trial design is that's being run? And should we expect efficacy data as well? Or should the data disclosure only be limited to whether you dosed it and they developed CAR-T and then what the safety looks like? Or should there be some early efficacy as well?

Umer, thanks for your question. I will answer the first two parts, and then I'll ask my colleague, Hui, President of R&D, to answer the third question regarding the design and everything else.

So first of all, yes, we can confirm that this is not the Gamma Delta T program. This is actually an In Vivo CAR-T targeting CD19 and CD20, using a lentiviral vector delivery. So that's first. Secondly, I can confirm that the internal codename we use for the program is LB2501. And this program is already up on clinicaltrials.gov, if you want to search for the details on the protocol and enrollment. And on the third question, I'll ask for Guowei to answer.

Yes. In terms of the clinical data to be released, the trial was initiated last year. We do expect to release both safety and efficacy data. We have to wait until the data presentation to really disclose specific information. But in terms of our internal expectation, our expectation for In Vivo program is to have manageable safety and promising efficacy, including deep response. That's our expectation.

Our next question coming from the line of Jessica Fye with JPMorgan.

A couple on kind of the existing business. First, I appreciate the additional detail on the breakdown of CARVYKTI use across lines of therapy. If we look out another year or two, what do you think that pie chart mix will look like? And then second, just on the higher COGS this quarter, how much of that about $100 million year-over-year increase was onetime versus sort of ongoing?

It's Alan. Thanks for the question. So, in terms of our business mix, we're very pleased to show the data that reflects the fact that in earlier lines, specifically in second and third line, we have about 41% of our patients coming through those lines. And I think that's important for a couple of reasons.

One is it does speak to the fact that we're getting community adoption because those earlier patients start in the community and are getting referred into the authorized treatment centers. It also speaks to the fact that our clinical data is resonating with the earlier is better data both for efficacy, safety and manufacturing, all based on the data that we shared at ASH and in previous conferences that earlier is better.

And I think it also sets us up well from a competitive standpoint to make sure we are penetrating the second and third line businesses in the face of whether it's bispecifics or potential future BCMA CAR-T competition. To answer your question, we've also shown progression in the overall second through fourth line at about 2/3 of our business, and we do expect that, that will continue to grow. Probably to about 3/4 of our business is where we would anticipate that emerging over the next year or so. So, all segments continue to grow, and we're very excited by the penetration in earlier lines.

Related to the gross margin question, we did see a sequential decline in the first quarter since we brought new capacity into our network, specifically to our Raritan site. And this, together with onetime expenses associated with the expansion resulted in this onetime impact to gross margin. However, we do expect that gross margins will return to over 50% in Q2.

Can you quantify the onetime impact a little more?

We do not disclose those particulars.

Jess, this is Ying. I just want to add that you heard from Carlos that we fully expect the gross margin to recover to prior level in the second and also the ensuing quarters of the year.

Our next question coming from the line of Konstantinos Biliouris with Oppenheimer.

Congrats on the progress. Maybe a couple of quick questions from us. One on the commercial side, do you see any meaningful impact after TECVAYLI approval in the second line now, perhaps on any particular segments of patients or any particular geographies? And the second one on the In Vivo CAR-T, can you help us understand what the benchmarking is there, some investors are trying to compare your upcoming data to other ex Vivo CAR-T therapies in NHL. Some other investors are looking to benchmark it to In Vivo CAR-T from multiple myeloma. Any thoughts on where the benchmarking is in your view would be helpful.

Our business continues to grow. And as you saw from our report today, it continues to grow, particularly in the earlier lines. So, in terms of competition from TECVAYLI or the prevalence of bispecifics, I'll remind you that this is a large market in second and fourth line, about 100,000 patients, only about 5% have seen a BCMA. And so, there's significant growth potential for multiple options in the earlier lines. And I think that's also reflected by the IQVIA data that you see, while other products are growing, CARVYKTI has also shown healthy growth as well. So, through potential competition with bispecifics, I think this is a large market that's severely underserved and underpenetrated, and that portends well for the opportunity for CARVYKTI.

So, for the second question, in terms of benchmark for In Vivo CAR-T program, this program is CD19, CD20 dual targeting In Vivo CAR-T program targeted for non-Hodgkin lymphoma patients. Our current thinking is that we are expecting or we are looking for deep and durable response, and therefore, the benchmark would be expected to align with that type of efficacy response. Currently still early, and we are accumulating more data.

And if I can add a follow-up here, if you see the type of responses in NHL, deep responses, as you call it, would that translate to multiple myeloma to some extent as well for the In Vivo CAR-T platform?

Excellent question. Yes, we do think that the In Vivo CAR-T platform has a transformative potential by moving all the cell engineering and the cell expansion into the body of patients, therefore, generate better cell thinness. And therefore, that could translate into even better clinical response. That's our expectation across different disease areas.

And our next question coming from the line of Etzer Darout with Barclays.

A couple of questions. Maybe on the CARVYKTI side, if you could maybe provide any updates, new updates on the timing for CARVYKTI 5 or 6. And then on the pipeline, just wondered if you could maybe talk about the scope of the BCMA trial that you're initiating with the In Vivo CAR-T, I think, LB2505. Maybe you can comment on the scope and then the trial design there.

CARTITUDE-5 and CARTITUDE-6 are fully enrolled, but these are event-driven. So, we don't have an update here on the timing, and we'll continue to monitor in terms of how the events accrue.

So, for In Vivo CAR-T program, we are excited about our platform and product. We are exploring this platform across different diseases. Multiple myeloma is an important disease area. BCMA certainly is a top target within the multiple myeloma disease space. Our partnership with Johnson & Johnson cover all and any BCMA-directed cell therapy in multiple myeloma that both companies are working on. And therefore, at this point, there's nothing more we can share.

This is Ying. I also want to add that we are initiating another trial for the same construct LB2505 targeting BCMA, and this will be in autoimmune diseases. And you will learn in the near future about that program once we include that in clinicaltrials.gov.

Our next question coming from the line of Eric Schmidt with Cantor Fitzgerald.

Maybe just a quick follow-up on the CARTITUDE-5 event rate. I think at one point, we had expected it would be possible to have data toward the end of this year. Is that still the case, Alan? And then a financial question on the adjusted net income guidance for profitability in 2026. The adjustments in Q1 are about $44 million to net income. Is that sort of a non-GAAP adjustment that we'll see on an ongoing basis? I guess I'm looking for some help on the differential between adjusted and GAAP financials.

On CARTITUDE-5, Eric, we would plan to see data at some point in either '26 or '27. Again, this is event-driven. So, it's really reflective of how the events accrue.

Yes. So, on the adjusted net income, as we approach profitability, we wanted to be more specific with our definition. And as we mentioned, when we introduced the non-IFRS reconciliation last year, we view adjusted net income as a more accurate reflection of profitability and our financial performance since it excludes certain non-cash items that are not representative of our core business operations. And this is aligned with the way most of the industry reports, and it will also allow a better comparison both with peers and consistently year-over-year.

Okay. I understand why you're doing it, is the $44 million differential between the two metrics something that might exist on an ongoing basis?

Yes. So, as I mentioned, we do exclude the certain non-cash items. So, this would be primarily share-based compensation, depreciation, amortization and impairments and foreign exchange.

Our next question coming from the line of James Shin with Deutsche Bank.

Circling back to the pipeline. There's three autologous and one In Vivo variant for the GPRC5Ds. Are these GPRC5D binders consistent across all the variants? Or are the FasTCAR variants using a different manufacturing process and therefore, have different binders? And then just following up on the onetime cost of collaboration question. If you exclude this onetime charge, would Q1 2026 been profitable on an adjusted basis?

On the GPRC5D front, all autologous program use the same binder. We are testing, have tried to validate the binder as well as try to understand how the patient responds using different design of the CAR-T molecule.

Yes. And on the onetime charge question, the answer is yes. If we wouldn't have had that onetime charge, we would have been profitable on an adjusted income basis.

Our next question coming from the line of Leonid Timashev with RBC Capital.

I wanted to ask on community adoption. I think before you've talked about how you've onboarded Virginia Oncology, Tennessee Oncology. I guess how is uptake looking in those centers? I guess I'm specifically curious about the actual use of CAR-T in those centers, not necessarily referrals and sort of what the plan and cadence is of adding additional community centers that can actually administer the CAR-T.

It's Alan. So, as we've said before, the community adoption has a couple of components to it, one of which is the one you're speaking to, which is administration in the community among the community networks. And we're seeing positive responses from the clinicians in both those sites. We mentioned two of them, and we also have the West Clinic in Tennessee as well. So, there are additional sites that are coming online this year.

I would say that it's a bit of a longer cycle to make sure that those sites are set up well and have the infrastructure, but we do expect additional sites this year. And the experience has been quite positive, again, speaking to the fact that CARVYKTI can be administered in the outpatient setting relatively easily and clinicians are getting more and more comfortable with patient management dynamics.

The other part of the community adoption is the referral piece, which you alluded to as well. And again, there, we're seeing strong indications that we are getting additional referrals, again, speaking to the fact that our earlier line business is growing significantly. And then finally, as a point, we're up to 148 authorized treatment centers in the U.S., about 1/3 of those are community and regional hospitals, and that's an important component to our mix because that means that we're bringing CARVYKTI closer to patients in those settings as well.

And our next question coming from the line of Sean McCutcheon with Raymond James.

One on CARTITUDE-5 for me. Can you speak to how you're framing and what you need to show to drive utilization in the frontline transplant-eligible or transplant not intended population on a cross-trial basis relative to and how you think about the scale and opportunity that could be unlocked by CARTITUDE-5.

Sean, this is Ying. So, if you look at the design for CARTITUDE-5, we are enrolling patients who are not eligible for stem cell transplant or eligible, but who choose to defer transplant for various reasons. So, if you look at comparison arm, it is RVd. So, it's a three-drug cocktail composing of Revlimid, Velcade and dexamethasone. Historically, if you look at RVd in the frontline setting in this transplant ineligible population, you have two trials. One is the IFM trials run by Celgene. The other one is the SWOG SO777 trial.

And if you look at the median PFS for RVD in this setting in those two Phase III trials, it's in the range of 35 to 40 months, and that is our assumption when we and J&J designed this trial for CARTITUDE-5, so if you look at, again, we're looking at cross-trial comparison, as you rightfully mentioned, 35 to 40. If you recall, Sean, in CARTITUDE-1, where we enrolled 97 patients with heavily pre-treated regimen, the median line of therapy prior therapy was 6.5, yet we still achieved a 35-month PFS for CARVYKTI treated patients.

So, this is why we and J&J are highly confident that we will be able to achieve the superiority against RVd in this specific patient population. Now if you compare that to CEPHEUS and other trials, of course, you do see certain numbers shifting because of better standard of care. On the other hand, still given what we know about CARTITUDE-1 and also CARTITUDE-4 where with a median follow-up of nearly three years, we have not reached median PFS yet in that second to fourth line patient population. So, we remain highly confident that CARVYKTI will demonstrate superior in PFS compared to RVd. That is our assumption here.

Our next question coming from the line of Ashwani Verma with UBS.

Maybe just on the CD19, CD20 CAR-T. So, can you talk about the safety differentiation with some of the other programs out there? Some of these programs have seen CRS or ICANS or neutropenia. Are you confident that your program can have minimal to no cases of grade three and above CRS and ICANS. And then just like secondly, on CARVYKTI, I mean, the 4Q to 1Q sequential growth in U.S. is up 3%. Any seasonality dynamic going on there? Just like trying to understand what is the growth trajectory from here? Can you continue to see sequential growth for the rest of 2026? And any impact of MajesTEC-3 on CARVYKTI sales?

Thanks, Ash. Yes, I can answer the first question on the safety side. Certainly, safety is paramount for a novel platform in oncology patients. I cannot disclose specific safety clinical safety profile at this point. We have to wait until the clinical data is presented. What I can say is that the safety is a key parameter we focus on from the get-go in the design phase. And our unique design mechanism as well as the CMC manufacturing process, I think that will provide a differentiated safety profile in the clinic. And in terms of how the research data correlate with the clinical data, let's wait, stay tuned until we are ready to disclose.

And on the CARVYKTI performance in Q1, yes, coming out of the holidays, there is a little bit of a lag in patient appointments as patients get re-upped in their insurance and they get rescheduled. But we're very encouraged with the trends that we've seen in the patient bookings through the progress of the quarter and even beyond that. And I would say that we would expect to see sequential growth quarter-on-quarter, both in the U.S. and OUS for the remainder of this year.

And Ash, maybe this is Ying. I want to add that you guys all follow IQVIA weekly scripts and weekly sales. As you can see, we had a very strong March, followed by a very strong April. And now we're early in May, but again, ordering looks quite strong. So, you guys can track that every week. As we have mentioned before, it's not a zero-sum game. You see both TECVAYLI & Daratumumab and you see CARVYKTI steadily growing in second line.

Our next question in the queue coming from the line of Yaron Werber with TD Cowen.

Maybe just the first question, Alan, for you, the seasonality that you mentioned in Q4 with some of the bags sort of remaining over and ultimately being infused in early Q1. And it seems like as you're moving upstream in Q1, J&J talked about having the same effect. Can you give us a little bit of a sense kind of net-net, how that worked out on a quarter-over-quarter basis? And is that sort of phenomenon of just a little bit of a delay to infusion will continue as you move into second line?

And then a question for In Vivo, I mean, for BCMA. Can you maybe share a little bit about the construct itself? Are you using sort of the same camelid antibody targeting BCMA with the same dual epitope targeting? Is it sort of the same stem? And are you doing any de-targeting through the LDL receptor and CD3 to try to avoid the sort of liver uptake in the sink and reduce some of the ICANS and inflammation?

Yaron, it's Alan. I'll just go back to what I said previously, which is that we do continue to see a strong order flow, both as the quarter progresses as well as, as Ying mentioned, going into April and beyond. So, we do expect to continue to see the growth and in particular, in that earlier line setting, where we are gaining more and more patients, more and more referrals, setting us up well from a competitive standpoint as well.

So, with regard to the BCMA compound in terms of the binder design, we are not ready to disclose specific information at this point. On the platform side, I do want to add that we generate glycoprotein mutations on the virus itself, and therefore, the virus, engineered virus does not recognize the receptor, and we use internally discovered and optimized the CD3 binder for T-cell targeting, which is differentiated from many other players in the space that they use existing CD3 binder from other.

Our next question coming from the line of Mitchell Kapoor with H.C. Wainwright.

This is [Indiscernible] sitting in for Mitchell Kapoor. So, I have a question on the LB2501, the In Vivo CD19/20 program. You list the studies enrolling and you have pointed to this In Vivo data coming later in the year. But separately, you have J&J recently announcing that discontinued its ex vivo CD20 mono and CD19/20 bi-CAR-T programs in LBCL. Without asking you to comment on their program specifically, I just want to get a sense of how you're thinking about the competitive bar for LB2501.

So, this is a dual targeting mechanism and cumulative data across autologous cell clinical data on a front comparing CD19 versus CD19, CD20 dual targeting medicine do point to the promise of dual targeting in terms of driving deeper and more durable response. J&J recently announced that they discontinued the development program for the dual targeting mechanism. And I will not be able to comment on the specific rationale. But we do believe that the dual targeting mechanism provides a benefit mono targeting and In Vivo data is evolving, and we are very much looking forward to disclose our clinical program.

And I'm showing no further questions in the queue at this time. I will now turn the call back over to the CEO, Ying Huang, for any closing remarks.

It's great hearing from everyone this morning. We are really pleased with the momentum of CARVYKTI. As you heard from Alan, we look forward to stronger quarters in the rest of the year, and we do expect sequential growth in both U.S. and ex-U.S. We continue to see deeper penetration in the community and also in second line. And we're actually all full speed on with our In Vivo programs. We look forward to seeing you all at upcoming major medical meetings. Thank you.

Ladies and gentlemen, this concludes today's conference call. Thank you for your participation, and you may now disconnect.

Good day, and welcome to the Legend Fourth Quarter 2025 Earnings Call. [Operator Instructions] Please note, this call is being recorded.

I'd now like to turn the call over to Jessie Yeung, Vice President of Investor Relations and Finance. Please go ahead.

Good morning. This is Jessie Yeung, Vice President of Investor Relations and Finance at Legend Biotech. Thank you for joining our conference call today to review our fourth quarter of 2025 performance. Prior to this call, we issued a press release announcing our financial results for the quarter. You can find the press release on our IR website at legendbiotech.com.

Joining me on today's call are Ying Huang, the company's Chief Executive Officer; Alan Bash, the company's President of CARVYKTI; and Carlos Santos, the company's Chief Financial Officer. Following the prepared remarks, we will open up the call for Q&A.

During today's call, we will be making forward-looking statements which are subject to risks and uncertainties that may cause our actual results to differ materially from those expressed or implied here within. These forward-looking statements are discussed in greater detail in our SEC filings, which we encourage you to read and can be found under the Investors section of our company website.

In addition, adjusted net income loss is the non-IFRS metrics. These non-IFRS financial measures is in addition to and not a substitute for or superior to measures of financial performance prepared in accordance with IFRS. There are a number of limitations related to the use of these non-IFRS financial measures versus their closest IFRS equivalent.

However, we believe that providing information concerning adjusted net income or loss and adjusted net income or loss per share enhances and investor understanding of our financial performance. We use adjusted net income or loss as a performance metric that guides management in its operation of and planning for the future of the business.

In particular, we exclude unrealized gain or loss from foreign exchange rate exchanges. We believe that adjusted net income or loss provides a useful measure of our operating performance from period to period. Our press release includes IFRS to non-IFRS reconciliation for these measures.

With that, I will now turn the call over to Ying.

Hello, everyone. Thank you for joining us today. We closed out 2025 as largest stand-alone cell therapy company with both commercial scale and next-gen pipeline optionality and we look forward to becoming a fully scaled CAR-T leader this year and presenting new data at upcoming medical conferences this year. We are pleased to have achieved CARVYKTI profitability in 2025 and believe we are poised to achieve company-wide profitability in 2026. You'll hear Alan shortly about the impact that CARVYKTI has had on a global scale in recent months but I wanted to share a few highlights on this front.

During the fourth quarter of 2025, CARVYKTI net trade sales were approximately $555 million, which is a 66% increase year-over-year. We have brought hope to patients worldwide with more than 10,000 multiple myeloma patients who have chosen to be treated with CARVYKTI and with the physical expansion of the Raritan facility, we have the installed capacity to support annual production of 10,000 doses across all our manufacturing nodes. CARVYKTI's launch remains the strongest CAR-T launch to date.

The majority of its utilization is now in earlier line settings, CARVYKTI has 97% overall manufacturing success rate and is offered in 14 global markets. Not only is CARVYKTI raising the bar for manufacturing excellence and site growth, it's also setting new standards for survival outcomes in relapsed refractory multiple myeloma. Recently, at the 57th American Society of Hematology Annual Meeting and the 2026 Tandem meeting, we presented compelling data on CARVYKTI's efficacy and our manufacturing success.

Before we dive deeper into this, I want to highlight that we also presented at ASH on LUCAR-G39D, our first-in-class allogeneic gamma delta CAR-T cell therapy targeting CD19 and CD20 in adults with relapsed/refractory B-cell non-Hodgkin's lymphoma or NHL. As you may have seen, we're pleased that it demonstrated manageable safety and encouraging antitumor activity.

Turning to the recent CARVYKTI presentation. New long-term CARVYKTI data demonstrated durable responses in key subgroups and reinforced the improved outcomes associated with earlier treatment with CARVYKTI. Importantly, triple classic sports multiple myeloma patients with three [ polio ] therapy in CARTITUDE-1 and CARTITUDE-4, achieved a median PFS of 0.4 months after single infusion of CARVYKTI. This represents one of the longest PFS outcomes for BCMA targeting CAR-T therapy. Given that more than 50% of patients enrolled in the competing trial had only three prior lines of therapy, we believe the 50.4 month median PFS sets a new standard in this population.

Additionally, an analysis of patients with standard risk [ genetics ] from CARTITUDE-4 shows that early [ agreements ] with CARVYKTI [ include ] survival outcomes, reinforcing its curative potential. 80% of the patients remained progression-free and off treatment after 2.5 years. All standard risk patients in CARTITUDE-4 who are progression-free at [ 1 ] year. 93% remain alive and progression free at 2.5 years.

Furthermore, translational analysis of patients from CARTITUDE-1 and CARTITUDE-4 demonstrated a stronger immune fitness and more immunocompenent tumor microenvironment for patients earlier in treatment journey. Again, adding to the body of clinical evidence that earlier treatment was CARVYKTI leads to better outcomes.

Finally, Commercial CARVYKTI manufacturing data from July 2024 through October 2025 were analyzed to examine manufacturing outcomes across multiple prior licensed therapy. Overall, 99% of products were successfully manufactured. When using cells from patients with one to three [ prime ] lines of therapy with 6.5% out of spec product compared to 97% for the fourth line and beyond, with 9.2% out-of-spec product.

Not only are we [ unconcerned ] from a capacity standpoint, but we've also made significant progress on our manufacturing success rates. We are reinforcing this message about our manufacturing capabilities, and of course, the importance of earlier treatment and effective bridging therapy in the KOL committee. To sum up, we believe this recent presentation from ASH and Tandem further strengthen our robust body of clinical evidence supporting the long-term benefits of CARVYKTI in multiple myeloma. This is one of the main reasons why we and our partner, Johnson & Johnson, are moving full steam ahead on our capacity expansion plans.

Our partnership with Johnson & Johnson is built to scale CARVYKTI to its anticipated potential of more than $5 billion in peak annual sales. Beyond current indications of CARVYKTI, we are continuing to advance our earlier-line studies to potentially expand our addressable market. Notably, CARTITUDE-5 and 6 studies have both completed enrollment already. Based on the data presented recently, earlier treatment may deliver greater durability and lower lifetime costs. We look forward to sharing data when a number of prespecified events is reached.

Looking ahead at our long-term growth, in addition to moving CARVYKTI into the frontline, we remain focused on our R&D pipeline besides CARVYKTI. We have developed a lean approach to leveraging indicator initiated trials in China or [ IT ] to rapidly establish clinical proof-of-concept and each of our programs is gated by clear evidence thresholds, which avoids inefficient use of [ capital ]. For example, we advanced one of our first in vivo CAR-T programs from candidate selection to first patient dosing in 6 months. We continue to anticipate that we will present clinical data this year.

Additionally, we continue to invest in other blood cancers, solid tumors and autoimmune programs that we view as having transformative potential. Our plan is to file one to two U.S. INDs by the end of this year. In addition to investing in our own in-house R&D efforts, we will be opportunistic this year about generating new revenues through business development efforts. To recap, we have several important milestones ahead this year as we look to increase CARVYKTI penetration in earlier lines and advance our next-generation cell therapies.

With cash position of $949 million, we're balancing investment in future growth with disciplined expense management. We are pleased that CARVYKTI became profitable in 2025 and anticipate company-wide profitability in 2026.

And with that, I'll pass it over to Alan to provide an update on CARVYKTI.

Thank you, Ying. Turning to our fourth quarter results. CARVYKTI net trade sales grew 66% year-over-year and 6% from the third quarter due to seasonality of shipments. Our global growth was driven by continued share gains, site expansion and growing geographic footprint, now reaching 294 global treatment sites across 14 markets worldwide. U.S. net trade sales of $420 million grew 38% year-over-year and 6% quarter-over-quarter. We continue to move our business towards earlier line settings and are pleased to report that approximately 65% of our patients are from the second to fourth line setting.

Outside the U.S., we achieved sales of $135 million, representing an over threefold increase compared to the same period a year ago and a 5% increase quarter-over-quarter. This performance was supported by continued growth in key markets such as Germany, Spain and Belgium, and bolstered by the tech lane facility in Belgium, which came online in September 2025 for commercial production to serve ex U.S. markets.

Looking at the broader multiple myeloma opportunity, BCMA-directed therapies remain significantly underpenetrated in earlier lines with less than 5% of patients in the second through fourth line setting treated with a BCMA-targeting agent in 2025. The majority of patients in this population are BCMA treatment naive providing a unique opportunity for CARVYKTI to address unmet needs.

Our strategic focus on earlier line use is strongly supported by evidence showing that earlier intervention yields better outcomes. As Ying highlighted earlier with data from the ASH and Tandem meetings, CARVYKTI demonstrates durable long-term benefits and improved outcomes are associated with earlier use. No other BCMA targeting CAR-T therapy has matched this depth of long-term survival data or overall survival benefit over standard therapies. CARVYKTI's foundation of unrivaled evidence, coupled with our capacity to manufacture 10,000 doses annually with high success rates, positions us well to capture this sizable market potential.

Before turning to how this unique profile serves the community setting, I want to shed light on the patient management strategies we have been able to implement and explore with our patient [ assets ] and how things have changed since we and J&J launched CARVYKTI. Importantly, as we recently [ at ] the ASH and Tandem meetings, there is definitive evidence that effective bridging therapy can debulk tumor burden mitigating the risk of neurotoxic events such as Parkinsonism. It is associated with both improved safety outcomes as well as efficacy outcomes.

In the study across more than 20 academic centers published by Dr. [ Dukal ] for Medical College of Wisconsin, there were no cases of colitis or Parkinsonism following at least one cycle of talketumab bridging therapy and CARVYKTI infusion. The study included more than 130 patients with 98 patients treated with CARVYKTI. Furthermore, Dr. [ Sidana ] from Stanford published a very large study that looked at a total of 761 CARVYKTI treated patients across 15 large tertiary academic centers. Of the 22 patients with Parkinsonism, 21 of these cases occurred in patients who did not have a response to bridging therapy. Clearly, implementing effective bridging therapy results in better patient outcomes and we are educating physicians on the importance of this strategy.

Turning to the community adoption. We believe CARVYKTI is well positioned for success here. There is no other CAR-T with over 5 years of progression-free outcomes in late-line myeloma and a demonstrated overall survival benefit in earlier lines. CARVYKTI keeps raising the bar on efficacy as well. And as you saw at ASH, the median PFS was 50.4 months for triple class-exposed patients with relapsed/refractory multiple myeloma and three prior lines of therapy from CARTITUDE-1 and CARTITUDE-4.

As it relates to safety, CARVYKTI's profile is well understood at this point, multiple CAR-Ts have had cases of Parkinsonism documented. Patients and physicians don't have to ask when class effects might emerge as they can simply refer to CARVYKTI dataset. Furthermore, physicians have been using this data to improve patient management and now we know the impact of effective bridging on safety outcomes which can further reduce risks.

Lastly, CARVYKTI is suitable for appropriate multiple myeloma patients looking for a onetime infusion regardless of the treatment setting since it can be administered in outpatient settings as well. Given all these factors, you can see why CARVYKTI has had steady traction in the community setting. Community hospitals now comprise 1/3 of the $145 CARVYKTI authorized treatment centers in the U.S. with 80% of myeloma patients living within 50 miles of a treatment site. Additionally, we continue to see the outpatient setting comprise about half of CARVYKTI prescribing volume further supporting broad accessibility.

In summary, CARVYKTI remains the undisputed leader of CAR-T sales and is the only CAR-T with this sales execution track record as we focus on reaching its peak sales potential of more than $5 billion. Our core focus remains on unlocking the curative potential of CARVYKTI and accelerating adoption in earlier lines where we see the greatest impact for patients.

Over the course of this year, we expect to benefit from the following growth drivers: unmatched data maturity and survival data that is not seen in the class, extensive real-world experience treating more than 10,000 patients far outpacing peers, educating physicians and patients on the benefits of CARVYKTI and advantages of earlier use, global expansion supported by capacity for 10,000 annualized doses, additional adverse event mitigation strategy to improve outcomes for CARVYKTI patients.

Now I will turn it over to Carlos Santos.

Thank you, Alan, and good morning, everyone. I'm pleased to walk you through our financial performance, which reflects another quarter of progress towards company-wide profitability. During the fourth quarter, we delivered strong top line growth driven by the continued momentum of CARVYKTI and the expanding global footprint that Alan outlined.

Revenue reached $306 million, representing 64% year-over-year growth and our gross margin remained consistently strong at 61% with a gross margin on CARVYKTI net product sales of 57%. What is most important is that this growth is increasingly translating into operating leverage. Our operating margin has improved dramatically from negative 142% in the second quarter of '23 to just negative 6% in the fourth quarter of '25. And this improvement has been steady across 10 consecutive quarters.

This reflects two things. First, the scalability of the CARVYKTI franchise, and second, our disciplined approach to managing the cost structure as we grow. Given this trajectory, the CARVYKTI franchise became profitable in 2025, and we believe we remain on track to achieve enterprise-wide profitability in 2026. With a revenue compounded annual growth rate of 77% since the second quarter of '23, and gross margins starting to stabilize at 55% or more over the past 4 quarters. We have a clear line of sight to achieving this milestone.

Turning to the next slide. Revenue growth of 64% significantly outpaced our 6% growth in total operating expenses, reflecting our commitment to scaling responsibly. R&D declined 3% year-over-year as our BCMA frontline clinical programs mature, and we increasingly shift investment into our next-generation in vivo platform. SG&A grew 22%, driven by targeted investments to reinforce our leadership position in BCMA CAR-T, such as sustaining share of voice leadership by expanding our sales force as well as investing in direct-to-consumer campaigns.

Back office and administrative functions continue to scale efficiently as the business grows, reflecting strong internal cost discipline. Our operating loss improved by 75% versus the prior year to approximately negative $20 million. And after excluding items that are not representative of our company's core business, including stock-based compensation and unrealized FX gains or losses, we have reported positive adjusted net income of $2.5 million, a meaningful transformation from a $59 million adjusted net loss a year ago.

Our adjusted diluted income per share was $0.01 compared to negative $0.15 for the same period last year. We ended the year with $949 million in cash, cash equivalents and time deposits. Operating cash flows continues to trend in the right direction as evidenced by our $12 million in operating cash flow outlays this quarter compared to $82 million in operating cash flow outlays for the same period last year.

This cash position provides with optionality as we focus on the following investment priorities. First, advancing our in vivo programs. Second, focused, synergistic business development. Third, supporting CARVYKTI profit expansion through focused commercial and medical investments. And finally, modest capital expenditures tied to manufacturing capacity expansion. We will continue to prioritize disciplined expense management as we invest in our future. Importantly, we believe we remain on track to achieve our expectations for company-wide profitability this year.

In summary, our financial performance reflects the collective strength of Legend's differentiated cell therapy platform, the scalability of the CARVYKTI franchise and our disciplined approach to growth. We have a market-leading CAR-T therapy in a vast multiple myeloma market, a robust balance sheet, expanding margins and an innovation engine that is advancing at speed with more than 10,000 patients treated globally and a growing footprint of treatment centers. We believe we are well positioned to translate our clinical leadership into long-term sustainable value. And now it's time to take your questions.

Operator, we're ready for the first question, please.

[Operator Instructions] Our first question comes from Terence Flynn with Morgan Stanley.

Great. Maybe two for me. I was just wondering if you can comment broadly on your expectations for the pace of CARVYKTI growth in 2026 and maybe how to think about U.S. relative to rest of world.

And then the second one is on your business development comments. You mentioned focused synergistic business development. Just what exactly does that look like? What are the types of asset stage size that you guys are potentially considering?

Thank you for the questions. So on your first question, we are planning and also we're committed to sequential growth throughout the year that includes all four quarters 2026. And we have said that we feel reasonably confident of delivering CARVYKTI according to the Street consensus number which is about 50% top line growth from last year, right? So that's what we are feeling confident about.

And then on the second question about [ BD ], I think it's about two directions, right? We obviously are interested in certain technologies that are complementary to what we have in-house. As you know, we have a couple in vivo CAR-T programs that are in the clinic today, dosing patients already and those are lentiviral vector-based delivery. So certainly, there are other technologies that are out there, which may be useful for other indications besides oncology and hematology.

So those are certain technologies we're interested in bringing in-house or potentially codeveloping with other partners. And then I think by the same [ van ], there are also other interest in potentially partnering with our existing assets, right? Because as you have seen in the tariffs, there's a lot of transactions recently in the in vivo CAR-T field. So we're also thinking ways to potentially accelerate the global development of our own in vivo assets as well, and obviously, there's no lack of interest on that. So that's what we mean by this development and being trying to be focused.

Our next question comes from Jon Miller with Evercore.

I guess I would ask now that we've had a couple of months post Majestic for you to get feedback from the actual providers and commercial sites, how are you hearing that docs are going to position the use of bispecifics in early lines relative to CARVYKTI?

I mean, you went through some of the differences in the trials, but in the real world, how has the feedback been in terms of positioning? And how do you foresee driving growth in those early line settings where Alan, you mentioned adoption is still very modest?

Yes, this is Alan. So obviously, the majestic data is good news for patients, but I would remind you and we have heard multiple times that this is a very large opportunity in second and third line in fact. There are over 100,000 patients second line plus globally. And that means that there is a significant unmet need and a significant opportunity for the CAR-T adoption in second and third

line. We have seen -- as our business has evolved, the fastest-growing segment of our business has been in second and third line, and we expect that to continue. We continue to hear very significantly that there is a very unique value proposition for CARVYKTI in these earlier line settings as a onetime infusion, delivering overall survival and 5-year treatment-free remissions in the patients that -- in the later line base as well.

So we also have heard very significantly that the IMWG guidelines really help physicians understand that the sequencing here is important that you want to get patients as quickly to CAR-T as you can and that putting a BCMA bispecific in front could diminish the efficacy that you could get from CAR-T. So a very strong alignment with the IMWG sequencing guidelines, the significant opportunity and the unique profile of CAR-T is what we're hearing in the marketplace.

Our next question comes from Etzer Darout with Barclays.

This is Luke on Etzer. Quick on the community setting expansion. What do you see as some of the bigger hurdles for continued expansion there? Like is it just site opening? Or is it like training those community positions?

So in terms of the community adoption, we're very pleased with where we've been. And as I've mentioned earlier, we have about 1/3 of our activated treatment centers our community hospitals. And this is an important part of the community story.

For example, I'll just give you a few examples. Orlando Health in Florida or [ Sutter ] Health in California. These are examples where we've been able to bring CARVYKTI closer to patients. Another example is we had an academic medical center, a activated [ Hakuba ] University in the northern part of New Jersey. And now we have the southern part of the state covered regional affiliate the Jersey Shore Medical Center. So those are examples where we are hearing very significantly that bringing CARVYKTI closer to patients with these community hospitals is a value add.

We are also expanding the use in the physician practices. And I'm very excited to announce that in addition to the Virginia Oncology Associates activation that we had in 2025. We have now activated in Tennessee Oncology in Nashville, and that helps us again as we step forward into these community practices. We also have seen the referrals increase and we are having more and more conversations between the activated centers and the referring base, so these are all the steps that we are heading towards.

I think to your question, it's all about continued education and making sure that the community physicians understand that as they [ rerent ] they are going to be getting their patients back without the REMS now in place, and we've heard that again as a significant gating factor that without the REMS in place, more patients can be monitored closer to home more [ community ] physicians are more comfortable of getting their patients back and monitoring them locally, and that is enabling the referral base as well.

Our next question comes from Linhai Zhao with GS.

This is Linhai from Goldman Sachs. You mentioned about the current CAR-T penetration less than 10% in the fifth line and also less than 5% in second to fourth line multiple myeloma. Just curious what would be your practical target? Or can you further comment on the potential ceiling values for these CAR-T penetrations in this both late line and early line multiple myeloma. And that's the first question.

And the second question is about [ Tegra ]. Just wondering, given that [ Teptera ] may not or not be a favorable treatment option in community setting, would you consider the community hospitals as a bigger growth opportunity? Or are you going to still purchase the majority of the growth in the academic centers?

This is Ying. So I'll answer the first part of your question. in terms of current CAR-T penetration. So we and our partner, J&J, are firmly believers that newer drugs, including CARVYKTI and also [ osotectar ] should be the preferred option based on the clinical data that shows superiority of these regimens over the [ triple ] standard of care, right?

And as Alan mentioned, if you look at community practice in the second to fourth line setting in the U.S., still all BCMA targeting modalities only account for about 5% market share. That shows us there's plenty of growth for these new regimens in the community setting, right? Now in terms of what we're trying to target, obviously, I think, number one, we can lead with our efficacy because it is better efficacy in both progression-free survival and also survival. And that resonates really well with both patients and also the physicians in the community setting.

Secondly, we also talk about the onetime convenience, which is a great quality of life improvement for patients because if they invest about 1 month with us and then we can provide years of progression-free survival and also treatment-free remission here. That's our second selling point. And then lastly, even in terms of health economic benefit, right, if you look at the total treatment cost we're providing savings -- significant savings over standard of care over a certain period of time, given the clinical evidence we have accumulated from [ CARVYKTI ] trial.

So that is our strategy, how we can completely go into the community. Now in terms of our assumption, right, I think, first of all, we're getting to that important amount of delivering annual supply of 10,000 doses per year from all of our network in the supply chain. Secondly, with the current and ongoing CapEx we and J&J are planning to supply up to 20,000 doses into the -- both the U.S. and European markets. So that is our plans.

And these plans obviously are based on our projection of the demand. and also the real-time market research. So we have a lot of confidence in the penetration of CAR-T into this market. And then I'll ask Alan to answer the second part of your question.

Because CAR-T in general is under penetrated across all the segments. We see significant growth across all the segments I outlined previously, the academic medical centers, the regional and community hospitals as well as the community practices. So I think all three segments represents significant growth opportunity for us.

Our next question comes from Eric Schmidt with Cantor.

It's on the Raritan facility. Congrats. It seems like you got full approval earlier this year. Just wondering when exactly that happened. And your initial efforts to fill up demand for that facility, how those are going? And then on gross margins, we've seen CARVYKTI gross margins kind of flatten out in the last few quarters at 57%. That facility now potentially being utilized? Are we going to see that ramp up over time?

Thanks, Eric. Yes, we have the installed capacity to support 10,000 doses, as Ying outlined. And we are now, as we've outlined earlier, have all four commercial nodes supply in the marketplace. Raritan is continuing to expand, and we anticipate a high utilization rate to support the growing demand. So our capacity is fully meeting the demand. We have high utilization of all four nodes, and that is supporting the 10,000 dose achievement that we have.

Yes. With regards to gross margin, I mean, we've seen an improvement of gross margin year-over-year from the utilization improving in all of our manufacturing nodes. However, we did ramp up the Tech Lane facility in 2025. And as you see, as that starts to grow at volume, we will see the cost of goods manufacturing coming down in Tech Lane than adding to the overall network improvement.

Our next question comes from Konstantinos Biliouris with Oppenheimer.

Maybe a question on recent M&A in the space. One of your competitors was recently acquired by a larger company, Gilead, do you foresee any changes in the competitive dynamics there following this acquisition and a follow-up on the review of the application, it wasn't a priority review. Any comments or thoughts around that?

First of all, I think the acquisition you referred to validate the value of this market, right, because we're looking at the multiple myeloma market for autologous CAR-T. And certainly, that lends to the support of the valuation of market we're targeting. And we have already said, like how much the market is. You're looking at a $35 billion plus market for multiple myeloma and CAR-T will become an increasing portion of that high.

Secondly, as you correctly pointed out, the PDUFA date is December 23 by FDA assigned on a [ net ] cell. And as you know, based on the FDA published guidance document, there are only two criteria when the agency decides whether application of certain drug candidate, [ marry ] standard review or private review. The first criteria here is whether the disease or target is a serious life-threatening disease. I think those without saying multiple myeloma is a life-threatening disease.

And the second criteria is whether the agency deems the candidate has any clinical differentiation over existing therapies, now clearly, based on the FDA determination of standard review, you know the answer, how FDA views this application based on the data supplied in that package. So we feel this is really another validation of that.

CARVYKTI really has the unmatched efficacy and durability in the field. And we agree with the FDA view on this point. And that's pretty much what I can say about this. In terms of the competition implication, I'll ask my colleague, Alan to comment.

We are prepared and continue to prepare for any timing for Aida Cell. And again, I think as Ying mentioned, we feel very strongly that the data maturity that we have, the 10,000 patient experience, the length of follow-up and the data that we presented at ASH around the three prior lines in triple-class exposed patients having a median PFS, 50.4 months really raised the bar in the efficacy story as any other potential competitor comes to market, that's the bar that they're going to be looking at.

Our next question comes from James Shin with DB.

I have 2. First one is for Ying and the team. I appreciate the comments on CAR-T being underpenetrated and the runway for CARVYKTI meeting it's $5 billion or north of $5 billion bogey. But there's a lot of discussion on competitive dynamics on clinical profiles amongst CAR-Ts. But this is -- I'm talking about autologous CAR-Ts, -- is it feasible for Legend, Kite and even maybe AstraZeneca down the line to manufacture enough BCMA CAR-T to really saturate the market or make one player the dominant -- like is there a way to make this a zero-sum game?

And then secondly, I appreciate the comments on biz bev as well. And it sounds like -- well, I guess the question is, is Legend set on leveraging its lentiviral infrastructure and focusing on viral delivery platforms for its in vivo efforts? Or is it early enough that Legend is also exploring nonviral platforms such as nanocarriers?

Thanks, James, for the questions. On your first question about CAR-T, we certainly do not believe this is a zero-sum game for our CAR-Ts. Because if you look at our growth, right, we have been treated already more than 10,000 patients, and we think there are still tens of thousands of more patients that will be treated by CARVYKTI.

So we are on a pace to increase our capacity from annualized 10,000 to 20,000. Meanwhile, we're also looking at other options, for example, automation to increase efficiency and also output within the current square foot footprint, right? And we believe others, including AZ and Gilead are using similar approaches. So clearly, we all believe that this is a space that is worth investing. And given, again, the efficacy, we believe that more and more patients will opt for CAR-T. So we still think there's a lot more to come in terms of supply to the market. And also, obviously, that will be measured by demand from the market.

On your second question about [ let ]. So as you know, since the company was founded in 2014, we have been working on lenti vector as a delivery vehicle for CAR-T. So we have accumulated a lot of experience and expertise on this and our first couple in vivo CAR-T programs in the clinic today are using lenti vector as a delivery for the in vivo CAR-T programs in both [ now ] lymphoma and also demand from myeloma indications, respectively. Now on the other hand, we also realized that there are other competing technologies, including what you mentioned, the LNP in calculated RNA or DNA. That's another way to look at it. So we're obviously interested in other technologies as well.

On the other hand, I believe that if we can show safety proven in the clinic, then there's no reason why lenti vector cannot be used in other indications, such as autoimmune disease as [ far ]. So we look at the space with a very broad net and we're very open mind in terms of potentially a partnership or development activity to bring other technologies here.

Our next question comes from Sean McCutcheon with Raymond James.

One for me. With [ Iberdomide ] NDA now accepted by FDA on MRD results and [ Veneto ] leaving soon. How does this alter your calculus on potential for filing on MRD results for 2026?

Thanks, Sean, for your question. I think you have seen the agency published recently a draft guidance document for the industry based on MRD, the registration endpoint for [ access ] approval in multiple myeloma.

On the other hand, there is a footnote in the FDA document that says that the ODAC discussion was based on meta-analysis for modalities, such as small molecules and also on injectable antibodies, right? To date, there's no data out there that actually suggests a correlation between the clinical outcomes such as PFS and survival and margin activity in CAR-T modality. And we're very much aware of that.

In fact, we are probably the trailblazer in this field because we will expect CARTITUDE-5 top line data in the near future, right, this year or next year. And based on that, we did actually prospectively include some MRD activity in the measurement. So we might be the first one actually in front of the FDA to discuss the correlation between MRD activity and clinical outcomes such as PFS and survival in the CAR-T trial.

And based on that, of course, if FDA agrees, we potentially can accelerate the FDA filing time for CARTITUDE-6, which is the frontline doll that is comparing CARVYKTI head-to-head against stem cell transplant in [ neutrons ]. So that is how we view this MRD endpoint and how that potentially can accelerate CARVYKTI [ entranto ] the frontline for patients who are eligible for transplant.

Our next question comes from Ash Verma with UBS.

This is Natalie on for Ash. Just two quick questions from us. The first is, can you provide any color on how you're thinking of a potential [ TeCDARA ] launch ex U.S. And then our second question is just could you provide the current breakdown of how many CARVYKTI patients are second and third line?

So on your second question on the share is that the second through fourth line population continues to grow, and that is now 65% of our business, which is exciting because it shows an evolution and it shows that the majority of the patients in our mix are getting it in a [ line ] and the only other sort of color on that one that we've shared is that -- and we have seen this very significantly that second and third line patients, while all lines are growing second and third line continues to grow the fastest.

As far as your question about [ TECDERA ] ex U.S., I can't speak to the J&J plans there. I would just say that for CARVYKTI, we continue to see significant uptake in the ex U.S. markets. We are now in 13 markets outside the U.S. more major markets are coming online in 2026 and beyond. The uptake has been very significant in markets such as Germany, Spain and Belgium and others.

And that's because, number one, they've been taking the learnings from the U.S. launches, applying them to patient selection and management of patients as well as the health care system really support this concept around a onetime infusion and getting patients from a budget impact into a long-term remission based on a single infusion. So there's very strong support ex U.S. [ model ] and CARVYKTI specifically.

And also, I just want to add to Alan's comments. For example, we only launched CARVYKTI in Spain last year in 2025. But right now, you look at 75% of the use already in certain in the Spanish market. So clearly, there's a very quick update in European market for the early line use of CARVYKTI. And I think that position is really well. This is an early line indication in Europe.

Our next question comes from Leonid Timashev with RBC.

I just want to ask two on the pipeline just in terms of broad strategy. I guess, first, you guys have explored allo approaches, gamma delta, 10K, in vivo. I guess, how are you thinking about what the winner is going to be. Are you leaning into in vivo? Is that sort of the direction you're going to go in?

And then second, you've talked a lot about the importance of long-term data and follow-up, especially as it relates to CARVYKTI and multiple myeloma. But as you develop these new programs in the spaces that already have existing CAR-T options such as myeloma, lymphoma, I guess, how do you get confident that what you're going to see early on in terms of response rate is actually going to translate to better long-term outcome data and make it worthwhile to move that program forward.

Thanks for your questions. On your first question, yes, you're right. We have explored obviously, auto modalities in the field of CAR-T, including autologous, allogenic that includes open [indiscernible] team. And then most recently, also NK as well as our latest entry into the field that is in vivo.

So I think based on the clinical data we have seen to date, and also based on what we're seeing in the field. Yes, we are particularly interested and also excited about the in vivo CAR-T approach because on one hand, the in vivo CAR T approach can provide a ready-to-go off-the-shelf version that's very convenient for both patients and physicians.

In the meantime, you don't have to worry about rejection, right? Because that is the biggest hurdle for allogeneic modalities in T cell therapy. Here, you're leveraging the patient's own immune cells, therefore, you really don't have to worry about rejection. So that is why I think the field is very excited about the promise of in vivo CAR-T.

And obviously, you have seen some clinical data, and we have not published any clinical data yet, but based on data we have seen in patients so far. We're also quite excited about the manageable safety and also the preliminary efficacy signal as well, although we need more time to follow up in terms of durability compared to autologous. So there are certain metrics, for example, we can look at in multiple myeloma, you can look at margin activity.

That is very early, but also a very reliable sign for a longer-term clinical outcome. And that is how we can measure whether in vivo CAR-T target in myeloma is effective or not, right? We also look at PK/PD, for example, if you look at the copies of T cell transfused in circulation, does that match the level we see, for example, in CARVYKTI, in the CAR-T program. So there are certain metrics we can compare contracts between our in vivo program in the clinic and also our experience with CARVYKTI in the planet.

On your second question about the long-term data. I think if you look at [ Informa ], right, just take a page from the [ Escada ] clinical development program. You know that the 6-month CR, the 6-month complete remission rate is actually quite predict for a longer term out again. So that is something that we track in the clinic as well. So I think the prior clinical experience in CAR-T really taught us a lot how to look at the efficacy in the very beginning of the program. That's how we track the clinical progress.

Our next question comes from Yaron Werber with TD Cowen.

This is [ Jen ] on for Yaron. Two from me. One, over, you have several motion trials looking -- investigating different strategies to mitigate some of the delayed neurotoxicity events that we see with CARVYKTI, including the [indiscernible] trial and other trials at Wisconsin and [ Mosit ]. Can you give us a sense of how those are progressing and the early signals you're seeing and when we might see data from that trial for those trials and then secondly, on the vivo programs, you said that we could see data in 2026? So how many patients, how much further would you want to -- would you see to share that data at a medical conference?

The Citadel study, which is a multicenter study looking at ALC monitoring and then management and treatment approaches should have data presented at some point this year. And I would also point out that another significant data set are the data sets around bridging therapy because as we hear more and more, this becomes a crucial strategy for physicians, both in the community and at the activated treatment centers to do -- and we see very strong support for and significant acceptance of bridging as a standard of care.

In fact, we were very pleased in January to see the NCCN guidelines updated to include the use of [ talcetumab ] as a bridging therapy and a larger discussion about the need for gene therapy in advance of reinfusion of manufactured CAR-T cells. And this is important because this is what is actually helping feed both the tumor and then get to better outcomes, both on a safety and efficacy standpoint, both the study that I referenced earlier from Stanford with Dr. Sadana, as well as the publication from Dr. [ Decal ] and ongoing new studies from Dr. Decal reinforce this concept that bridging therapy is really helping mitigate some of these concerns.

Jan, on your second question, as you know, it is our corporate policy not to comment on aspect until they're officially accepted by a major medical meeting. However, we are planning the first batch of clinical data in patients for our first in vivo program to be published and presented at a major medical meeting potentially in the middle of this year. That's the plan. So please stay tuned.

And our last question comes from Mitchell Kapoor with H.C. Wainright.

This is Katie on for Mitchell. I was thinking about your manufacturing scale-up. And what I'm trying to get my head around is -- do those 10,000 doses represent the number of samples processed or the number of transfusable doses produced? Are you making adjustments to patient selection and how you -- as you learn more moving into the clinic? Or are you kind of expecting that rate to be about the same going forward?

That figure represents our overall capacity to produce doses. Of course, from there -- there are some drop-off there are -- we also account for days of shutdown. We account for nonclinical runs. We account for out of spec, which actually those numbers are going down. So that's a lower portion of it. But so the 10,000 represents our overall capacity to support the marketplace. And then there are some adjustments from that number.

And this concludes our question-and-answer session. Thank you for your participation. You may now disconnect. Everyone, have a great day.

Great. Welcome. Good morning, everyone. My name is Jess Fye. I'm a biotech analyst at JPMorgan, and we're continuing our 44th Annual Healthcare Conference this morning with Legend.

First, you're going to hear a presentation from the company and then we're going to go into a Q&A session. So for all of you in the room, if you want to ask a question, just raise your hands, someone will bring over a microphone. And if you're listening online, you can submit questions to the portal, and I can ask them up here.

So with that out of the way, let me turn it over to Legend's CEO, Ying Huang.

Thank you. Thank you, Jessica, and also thank you, JPMorgan for inviting Legend to be participating in the JPMorgan conference. This is our standard safe harbor disclaimer. I might be making forward-looking statements during my presentation. We undertake no legal obligation to update. For up-to-date information, please refer to our SEC filings and also go to our company website.

It's really a great pleasure for me to speaking with you about Legend on behalf of our more than 2,900 team members across the globe. Today, Legend Biotech is the world's largest stand-alone cell therapy company, and we're a pioneer in using immune cells to treat the toughest diseases. Legend Biotech is at the forefront of the CAR-T therapy revolution with CARVYKTI, our onetime treatment for multiple myeloma which we develop, manufacture and also co-promote in the U.S. with our partner, Johnson & Johnson.

CARVYKTI has been the fastest launch among CAR-T therapies today and has generated about $1.7 billion in net trade sales in the last 12 months throughout the third quarter of 2025. With CARVYKTI having validated Legend biotech's approach of science, manufacturing and also our execution model.

Our strong balance sheet allows Legend to self-fund innovation in our pipeline development. We have about 10 pipeline programs under development today, and we recently opened a brand-new research and development facility in downtown Philadelphia, where our research focus will be in vivo CAR-T, utilizing our operating model that emphasize speed to generating clinical proof of concept.

And 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 patients with CARVYKTI. And below this code number 10,000, it is 10,000 lives being touched, 10,000 families, 10,000 patient journeys.

In addition, we have also a cash position of nearly $1 billion in cash and liquidity, and we have generated positive operating profit already in Q3 for CARVYKTI. Few companies in our sector, combined this commercial scale and also next-generation pipeline optionality that Legend has.

This year, we expect to become a profitable, fully scaled CAR-T leader. As you can see in this slide, during the past two years, revenue has increased substantially, and we have maintained roughly 60% gross margin even as we added multiple manufacturing nodes in our global network.

Our overall operating margins have improved meaningfully since second quarter of 2023. As a result, you can see from the right side of the slide, our non-GAAP operating income has also dramatically increased since 2023 and we do anticipate achieving company-wide profitability this year. In fact, CARVYKTI is already a profitable franchise for our partner, Johnson & Johnson and also Legend.

In addition to our goal of driving profitability in 2026, our other top priorities include maximizing commercial leadership for CARVYKTI in multiple myeloma and also advancing our innovative pipeline for cell therapies, we continue to anticipate CARVYKTI will ultimately generate more than $5 billion in annual peak sales, and we're not stopping there. We're shaping the next generation of cell therapy innovation, and we're committed to building upon our leadership position in years to come.

Now I would like to focus on why our CARVYKTI franchise is becoming more durable over time. I would like to discuss some evidence maturity, our real-world scale and also our expansion opportunities in early line and in community setting. As I just mentioned, we have brought CARVYKTI to more than 10,000 patients to date, who have chosen to be treated with this life-saving medicine. Not only is CARVYKTI raising the bar for survival outcomes in relapsed/refractory multiple myeloma, it's also setting new standards for manufacturing success and also site growth.

Today, CARVYKTI has an overall 97% overall manufacturing success rate and is offered and available at 279 global treatment sites in 14 countries. We recently completed the physical expansion in our Raritan, New Jersey facility and also testing of this facility, making it the largest cell therapy manufacturing facility in the world. It also provides installed capacity to support the treatment of 10,000 patients annually across 4 of our global supply sites. While United States remains a primary area of focus for us, we have been gradually expanding our presence globally, and we continued globalization expected this year.

Our partnership with Johnson & Johnson is built to scale CARVYKTI to its potential for more than $5 billion in peak sales. As most of you know, we entered into a global collaboration agreement with J & J in December 2017 to address the unmet medical need in multiple myeloma with a 50-50 cost sharing and also profit split.

Within multiple myeloma, Johnson & Johnson is the #1 global leader that has deep experience in both community settings and also in academic settings. Together, Johnson & Johnson and Legend have built a leading BCMA CAR-T commercial organization. This collaboration derisks the global execution while also preserving innovation velocity as well as benefiting patients globally.

Here is a snapshot of the unique long-term survival profile of CARVYKTI which is the only and also first CAR-T therapy in multiple myeloma to achieve 5-year remission survival in 1/3 patient after single infusion in a study called CARTITUDE-1 where patients had a median 6.5 prior lines of therapy, a heavily pretreated patient population. Since ASCO publications such as the New York Times, and Forbes have highlighted CARVYKTI's survival and also unique curated potential. And the paper on this topic was published in Journal of clinical oncology, it was ranked #1 in readership. Our data maturity and also long-term follow-up create an advantage that is difficult for any later energy to overcome.

CARVYKTI has demonstrated profound efficacy in terms of PFS and survival outcome in patients with relapsed refractory multiple myeloma and continues to raise the bar of efficacy. As you can see from this slide, in CARTITUDE-1 study, where we enrolled 97 patients with 6.5 median prior lines of therapy. The median progression-free survival was nearly 3 years or 35 months. In last month, at the Annual ASH meeting, we presented data from 34 patients between CARTITUDE-1 and also CARTITUDE-4 where patients have been treated with triple class and also had 3 prior lines of therapy. In this patient population, the median progression-free survival was 50.4 months.

Now if you move forward to the right side, in CARTITUDE-4 Phase 3 trial, where we enrolled more than 400 patients with prior 1 to 3 prior lines of therapy. The median progression-free survival has not even been reached with a median follow-up of nearly 3 years. So clearly, these data demonstrate that CARVYKTI is a category-leading therapy. And this data is category-defining has transformed treatment of multipole myeloma.

Underscoring earlier use of CARVYKTI, you can see here meaningfully better survival benefits to patients compared to late line. For example, on top of this line, you will see that in CARTITUDE-4, patients with only one prior line of therapy, as denoted in this red curve here, derive the best survival outcome compared to patients with 2 or 3 plus prior lines of therapy. This should not come as a major surprise given that the current IMWG or International Myeloma Working Group guideline recommends CAR-T therapy before bi-specific T-cell engagers in patients who are eligible candidates for both.

Additionally, by treating patients earlier and also using appropriate risk mitigation strategies, we were able to reduce a side effect called Parkinsonism from 6% in CARTITUDE-1 study to less than 1% in CARTITUDE-4 study. And in fact, in patients enrolling CARTITUDE-4, there's no case of delayed parkinsonism in patients who responded to bridging therapy. This again emphasize the importance of effective bridging therapy. We're now able to meet demand and also need of all patients that are eligible for CARVYKTI, which is critical for our expansion in community and also outpatient expansion.

With each year of additional experience in the market, significantly more patients have been treated with CARVYKTI. However, despite all the strong outcomes I just laid out, BCMA-directed therapy still remains very low in penetration in the market. As you can tell from this slide, in fifth line and beyond, the BCMA target therapy occupies less than 10% of the market share, while in second to fourth line, BCMA-targeted therapy occupies less than 5% of the market. So clearly, there's a large untapped opportunity here in the commercial market for drugs such as CARVYKTI.

Following the recent ASH meeting and also MajesTEC-3 data presented here, we want to see also how treatment will be evolving. So this is the treatment out recommended by Dr. Vincent Rajkumar from Mayo Clinic. Based on data presented at ASH, he recommends that CARVYKTI be considered in all second-line eligible patients after first relapse, which aligns with the long-term data we have generated with CARVYKTI today, and also supports the hypothesis with immune therapy such as CARVYKTI earlier, better. This is why we and our partner have initiated frontline trials such as CARTITUDE-5 and CARTITUDE-6. We are evaluating CARVYKTI in newly diagnosed multiple myeloma patients. In fact, we have already recently completed the enrollment for both CARTITUDE-5 and CARTITUDE-6 studies.

So as you can tell from the last slide, we're trying to address additional 50,000 patients per year in the newly diagnosed frontline study. And based on the data generated, we know that earlier treatment may deliver greater durability and lower lifetime cost. As we look to increase prescription of CARVYKTI in the community and also in an early line setting, the community adoption is the key. In fact, 70% of relapsed and refractory multiple myeloma patients are being treated in the community study.

The growth in this setting will come from two main areas. First, we'll continue to grow our presence in the community hospitals, which comprise nearly 1/3 of our hospitals and sites available in the U.S. today. Secondly, we look to additional community network expansion in 2026 where we're having meaningful dialogues. In this slide, you can see two examples. Today, CARVYKTI is available for treatment at Virginia Oncology Associates in the state of Virginia and also in West Cancer Center as well.

CARVYKTI's unique advantage in the outpatient setting should also help to help further growth because CARVYKTI's unique delayed CRS profile at 7 to 8 days. Health care practitioners are able to utilize outpatient utilization administration to support the patient needs as well as also the existing hospital infrastructure. Today, outpatient use of CARVYKTI comprised roughly half of our CARVYKTI volume.

As you can see, CARVYKTI leads the BCMA CAR-T category on data maturity, survival outcome and also real world use. CARVYKTI is and remains the only CAR-T therapy in the treatment of multiple myeloma to deliver superior survival outcome over standard of care as early as in second line. We also saw a 5-year treatment-free remission in 1/3 of heavily pretreated patients in a study called CASTRATED-1. More than 10,000 patients have already been treated with CARVYKTI compared to about 150 of some of our competition here. Claims that another drug may have best-in-class is inappropriate and also flawed.

We also know that cross-trial safety comparison must consider patient population at baseline and also management of side effects. For example, in our most recent clinical data for CARVYKTI that we presented for CARTITUDE-4, we had only one case of Parkinsonism in the larger number of patients compared to CARTITUDE-1. Our main focus continues to emphasize the curative potential of CARVYKTI and driving adoption in early lines and in community.

In the next slide, this is an example of an important risk mitigation strategy that we saw at ASH. There's a growing body of emerging clinical evidence to show that bridging therapy that is used to control and also deep out the tumor burden. It can be very effective in terms of preventing and also lessens the incidence rate of Parkinsonism case. It is also associated with improved safety outcome as well as efficacy outcome.

For example, in the top of the slide, there is a paper published by Dr. Dhakal from Medical College Wisconsin joined from experience of 134 patients across 20 academic centers, 18 in the U.S., 2 in Germany. Among those patients, 98 were treated with commercial CARVYKTI. They also received at least one cycle of talquetamab, which is a GPRC5D bi=specific antibody. Following that bridging therapy and CARVYKTI infusion, there were no case of colitis or parkinsonism.

In another paper that's presented in ASH. The lead doctor here is Dr. Sidana from Stanford. And they looked at a total of 761 CARVYKTI treated patients among, again, 15 large tertiary academic centers. In those patients, you see 22 case of Parkinsonism cases. However, 95% or 21 out of 22 cases occurred in those patients who failed to have a response to bridging therapy. These two papers clearly denote the importance of effective bridging therapy, and we have found a very effective tool to prevent parkinsonism.

Before turning to our innovative pipeline, I would like to do a quick recap. In fact, by the way, this is a heart of the press. Last Friday, NCCN, the National Comprehensive Cancer Network updated their treatment guidance for multiple myeloma and based upon the data I just presented in the last slide, the panel now recommends talquetamab can be considered as a bridging therapy to BCMA CAR-T therapy in relapsed and refractory multiple myeloma. And we do expect this guideline to quickly be adopted among treatment physicians.

Before turning to our innovative pipeline, I would like to do a quick recap of the unique advantage of CARVYKTI as the proven leader among CAR-T therapies in multiple myeloma forging the path to cure. CARVYKTI has proven data supporting it's potential curative benefit, whereas no CAR-T in myeloma has been able to substantiate this kind of long-term efficacy. There is also substantial evidence on how early treatment with CARVYKTI will derive better benefit in terms of both safety and also efficacy outcomes. And finally, CARVYKTI is a onetime treatment that offers flexibility in both inpatient and also outpatient settings as well as lower lifetime cost savings, benefiting patients, health care practitioners and payers. We're committed to building upon the most successful CAR T launch to date as we continue to focus on the significant market opportunity for CARVYKTI in the years to come.

Now let's turn to our pipeline. We look to leverage the successful and unique R&D model we built with CARVYKTI into other therapeutic areas. We're focused on leveraging our end-to-end research and development capabilities across 3 key areas. The first is blood cancers and also next-generation multiple myeloma therapies. For example, we're developing allogeneic therapies and also in vivo therapies. The second is on solid tumor programs. And one example of that is our DLL3 auto CAR-T partnership with Novartis. And finally, we have also recently initiated Phase I studies in autoimmune diseases, where CAR-Ts have not been approved, but there is a significant market opportunity. Each of those programs is gated by clear evidence thresholds which avoids inefficient use of capital to expand our cell therapy leadership.

Our platform capabilities enable parallel rather than sequential demand capabilities. We have developed a lean approach to leveraging investigator-initiated trials to rapidly establish clinical proof of concept. For example, recently, we advanced one of our in vivo programs from candidate selection to first patient dosing in 6 months. And our goal continues to drive speed and also capital efficiency as we invest in next-generation cell therapies. We have highlighted in recent months how in vivo technologies holds much promise for multiple indications by limiting some of the manufacturing complexity while expanding reach. And recently, we have dosed a few patients in our in vivo program, and we're hoping to present data this year. We're one of the only handful of companies out there with an active Phase I program for in vivo CAR T in human testing.

As you can see on this slide, this is in vivo CAR T data in monkeys. In the top left graph, you can see that you're seeing a dose-dependent CAR-T expansion here. The blue curve denotes a higher dose and the low dose is denoted in the record. While in the left side, the bottom graph, you can see that we're seeing a dose-dependent B-cell depletion in the peripheral blood from day 8 throughout 36 days. Not only can we eliminate B cells in the peripheral blood, we're also observing complete B-cell depletion in bone marrow as well as lymph node in monkeys. It is this kind of preclinical data that gives our confidence and also gives us information about human dosing in Phase I.

In addition to investing in our own in-house R&D efforts, we're also planning to be opportunistic about business development this year. On one hand, we continue to look into opportunities that could enable and also complement our internal effort. On the other hand, we also could identify potential opportunities for non-dilutive financing through strategic partnerships.

Moving into our last but not least, priority for 2026, which is driving corporate profitability. As you can see in this slide, our triple-digit compound annual growth rate. Since launch of CARVYKTI represents two category leadership, our financial profile now resembles other scaled biotech leaders as exemplified by our strong balance sheet with nearly $1 billion in cash and equivalent and how we have already generated operating cash in the third quarter for CARVYKTI. We continue to expect CARVYKTI sales trajectory to be strong in 2026 with sequential quarterly growth, which should help fuel further growth and cash flow.

Throughout 2026, we have several important milestones ahead. First, we'd like to continue to deliver sequential growth for CARVYKTI. We expect three quarters of CARVYKTI orders will come from early line or second to fourth line in the market. And we'll continue to roll out CARVYKTI through international markets. We also continue to invest in cell therapy innovation with the goal of finding one to two U.S. INDs by end of this year. And finally, we look forward to achieving company-wide operating profit by balancing investment in future growth with disciplined expense management. We look forward to providing you with updates throughout the year.

With that, I'm happy to ask any questions. Jess?

Great. And as a reminder, for those of you in the room, if you have a question, just raise your hand, someone will bring over a microphone. So I guess as you look ahead to '26, can you expand on what your biggest goals are for the company this year?

Yes. I think I just laid out the three top priorities. First of all, we'd like to continue to maximize commercial opportunity in second line in community and also international launch.

And secondly, we would like to continue to push forward in our pipeline. For example, we just presented for the first time in oral presentation at ASH last month, gamma delta T CD19/CD20 program for non-Hodgkin lymphoma. We have seen already an efficacy in terms of ORR and CR that is on par with autologous CAR-T. So we'll continue to expand the dosing and the enrollment of that program. And I just mentioned that in vivo is now becoming a big focus for our research so we'll continue to put more programs in the clinic. And hopefully, we'll present some data this year.

And then lastly, we're steadfast in maintaining our goal of achieving operating profitability here this year in '26. Those are the top 3 priorities for the company.

So -- and as the company has now kind of transitioned through breakeven into profitability, how does that kind of influence how you make decisions?

Are you talking about investment decisions or?

Kind of balancing how profitable you could be with how much you invest.

Sure. Yes. So if you look at the first three quarters of last year, our R&D investment in fact, was flattish, right, compared to the same period of 2024. And that is because of the maturing program of CARTITUDE, we're not seeing actually a lower investment in R&D for CAR-T program. So we're deploying our capital from CARTITUDE program to now internal R&D effort with a focus on allergenic and also in vivo development. That is how we think about this. And of course, at the same time, we're very cognizant of shareholder value creation. So at some point, we could potentially deploy the future cash flow for cash buyback or other measures as well.

What do you think is most underappreciated or maybe misunderstood in the Legend story?

I think, first of all, maybe invest under appreciate the importance of this onetime treatment for patients. I did not notice until we met patients in the field, right? Because if you look at patients who are in remission following a onetime infusion of CARVYKTI, they look like normal human beings. While if you look at other treatments, they may continue to provide CR for patients, but because of that continuous treatment, specialty treatments with immunosuppressive treatment, right? those patients, they don't look normal even though they don't have cancer. They don't have cancer cells in blood, right?

Beyond that, it's also a significant improvement in quality of life because with this onetime infusion following the 1-month treatment period after CAR T, patients can go about their normal daily lives, right? They can travel, they can work. That is, again, a significantly underappreciated benefit for CARVYKTI, I think. That's first.

And secondly, I think, I mean, obviously, there's a lot of competition, which is not surprising at all. Multiple myeloma is a very large commercial market. Last year, the commercial sales was about $30 billion in this market. So I'm not surprised there's a lot of future competition coming into this field. On the other hand, we really stand by the benefit of CARVYKTI with 3-year PFS, 5-year survival in heavily pretreated patients, and we're also functionally curing 1/3 of those patients. We're looking forward to future update for CARTITUDE-4. So in second-line patients, we expect a higher proportion of patients will be able to enjoy that multiyear treatment-free cancer remission. And that is, again, something I don't think any other competition has been able to demonstrate.

Lastly, I think people may forget that what cancer patients care the most is survival. And as you know, many other drugs have been approved by FDA without a survival benefit, we have demonstrated survival benefit in both last line and now second line over standard of care. It's also written in the label in both U.S. by FDA and also in Europe by EMA. That is very, very high, I think, barrier for entry, which we look forward to any competition to demonstrate there. Hopefully, they can show the data and show the curve so that we know how good they are.

As you continue to ramp capacity now that you've achieved this kind of 10,000 dose capacity run rate, what are the milestones from here that are going to define success for the manufacturing network?

Yes, sure. As you can tell, in the last 4 years, our manufacturing colleagues have worked really hard in terms of improving supply in terms of lowering out of spec rate in terms of reducing the median turnaround. In fact, today, our median turnaround from [indiscernible] to supply side is below 30 days. It's about 4 weeks, in fact. So we have done a lot of hard work. We're the trailblazer in CAR-T because, as you know, CARTITUDE today is the largest selling CAR-T in the category. And we're really proud of what we have achieved However, looking forward, we'll continue to increase our supply from 10,000 to 20,000 in the next 3 years. We and our partners have already decided to invest further in the capital expansion in our Tech Lane site in Belgium, although we just received commercial licensing in last quarter.

Okay. A question in the audience?

Yes. You pointed out that China is not included in the J&J transaction, but in the total revenue, I imagine that China is included with the numbers you've given us. Can you talk about the China opportunity there, please?

Can you repeat the question?

Yes. So the question is what is our collaboration with J&J? Does that include China? And what's the plan of commercialization? So the answer here is that China is part of the collaboration agreement. That is not 50-50. It's a 30-70 arrangement, which means Legend leads, and we will be responsible of 70% of the cost and also profit. And the J&J will be responsible for 30%.

But because of the supply constraint and also the valuation and the reimbursement pricing considerations, we have not launched Carve yet in China. So our research colleagues are working super hard on allergenic and also in vivo CAR Ts, which is off the shelf, and it will be lower in terms of manufacturing cost. So that is our future direction for markets such as China because we believe that an off-the-shelf version with the lower cost and lower pricing will be likely the commercial path for a CAR-T therapy in China.

Can you also just take us through your 2026 expectations for second line plus penetration in multiple myeloma? Where does that stand now? And where could it go over time?

Yes. So Jess, as a reminder, we received FDA approval in April of 2024. So it's been only just a year in terms of commercial launch. However, we're very pleased with the outcome that is today the second to fourth or early line revenue mix is about 60% of our revenue already for CARVYKTI And our goal is to achieve about 75% or three quarters of our revenue by end of this year should come from early lines. So we have made a lot of strides in terms of penetrating into the community, penetrating into the second line. Again, we're the trailblazer here because ahead of us, I don't think there's any significant community use for any CAR T therapy in this category. So we'll continue to push for that. And we believe that with our unique survival benefit and also real-world evidence we should be able to get wider adoption in the community in the second line.

The 60% going to 75%, that's the proportion of early line use within CARVYKTI, right? What about penetration into the overall market, kind of how much room is left to run there?

Yes. That's a great question, Jess. As I showed in one of the slides, today, despite all the strong clinical evidence from our trials and others, the BCMA targeted therapy remains very, very low in terms of penetration rate is about 5% in that market. So I believe that or not, today, the market in that second to fourth line remains dominated by older regimens such as doublets or triplets, for example, RD or DRD, DKD. So we have this goal that we need to, again, emphasize the clinical evidence of the superior survival PFS, MRD activity and CR rates so that eventually we'll be able to replace those older regimens with stronger clinical evidence here.

So if it's at 5% now, what's the ambition of where that could go over time?

I mean I think a reasonable penetration will be 20%, for example, in those early line, second line.

Can you expand a little bit on your progress driving community uptake for CARVYKTI? And just how you see the interplay between outpatient use and community use?

Yes. I mean I think these two are really correlated. As I mentioned, if you look at today, we are 141 treatment centers certified in the U.S. and about 1/3 of those sites are hospitals and sites in the community setting. So these are regional community hospitals or completely clinics like Virginia Oncology associate that do not even have beds, right? So that continues to be our focus. And because of the unique profit of delayed CRS about 7 or 8 days for CARVYKTI, in fact, more than half of the patients with CARVYKTI today already are receiving a treatment in our patient study. So of course, if you think about those community patients, really, they're rather either commute to a site, which is within driving distance rather than going to Tertiary center. So this is really hand in hand. And that is why we're seeing actually more adoption second line, more adoption in the community.

For example, today, about 80% of all multiple myeloma patients in this country we'll be able to find a treatment center within 50 miles. And our goal is to increase that to maybe 100% within 30 miles actually. So essentially, we're actually bringing this life-saving therapy to the patients to the community. And that is why we're continuing to work hard to expand that into the community.

What specific factors do you see supporting CARVYKTI's ability to maintain a leadership position in the BCMA CAR-T space heading into the potential launch of anito-cel?

Yes. I mean, I'll continue to emphasize that in the treatment of oncology in general, efficacy is always, always the #1 decision factor. And in fact, there was a large survey that was published by, I think, IMS, International Myeloma Society meeting in September of last year. They surveyed hundreds of treatment physicians and also patients in both community and academic setting. So the difference is that in the community setting, the #1 decision factor for patients and also physicians who choose the therapy for myeloma is survival, followed by PFS and the response rate. While in the academic setting, PFS tends to be the #1 factor.

So clearly, like I mentioned, I think patients with cancer, they really care how much they can survive and how long they can live with their treatment. And that is our leading advantage, right? Because like I mentioned, even among those patients who have been heavily pretreated with 6.5 lines of prior line therapy in CARTITUDE-1, our material data shows a median survival of just over 5 years. And that is 5 years of additional life this patient can derive. And then CARTITUDE-4 compared to the gold standard, the triplet, right, standard of care, such as DPD, DARZALEX, POM and dexamethasone. Again, we have shown has a ratio of 0.55, which means 45% risk reduction in death. So I think these data points are hard data points and also they clearly convenience the patients that this is a life-saving therapy here. And that is our #1 advantage. I don't think we have seen that from any other competition in the CAR-T category yet.

Secondly, we have increased the supply substantially in the last 4 years. Today, we can stand here to say that we can satisfy order demand or the demand from patients who want CARVYKTI for eligible. So there is no supply shortage anymore in that. And we have also the real-world use. No other therapies in CAR T myeloma has demonstrated this kind of patient experience with more than 10,000 patients in real world receiving CARVYKTI. That evidence grows by day. So these are all our advantage, I think.

Maybe turning to the ongoing clinical trials. What's the soonest that CARTITUDE-5 could realistically read out? And what data specifically give you confidence in positive results in that setting? And maybe as a follow-up to that, kind of like what clinical questions will that trial answer about earlier line CARVYKTI use and what will still be unanswered?

Yes, sure. So CARTITUDE-5 trial is an event-driven trial, which means we have to reach a prespecified number of events before we can online the trial and conduct any analysis. So really, even though we completed enrollment a while ago, but it's a bit difficult to really pinpoint exactly when the trial will read out. I mean, broadly speaking, I think it's going to be in the next one, two, maybe two years, so '26, '27. I think we'll have a more reliable estimate once we're getting close to that event number.

On the other hand, the slowing event rate is actually not a bad thing because that means patients are not progressing, right, or not progressing as fast as we expected when we designed the trial. So that's potentially a positive sign for this. But I think we have said that, broadly speaking, maybe in the next one to two years, we'll have a readout.

Now in terms of what questions we're answering. So these are patients who are either transplant ineligible because they're very weak in physical status. They're 70 years or older. There's also subtype patients we enrolled that is transplant delayed. That means they're eligible, but they have decided not to go through bone marrow transplant. So for these patients, current gold standard is RVD, which is a triplet of Revlimid, Velcade and dexamethasone and our registration primary endpoint is PFS, progression-free survival. So really, we're looking for superior PFS or longer PFS than RVD. So you ask, what gives us the kind of confidence. I would say we're highly, highly confident in demonstrating superiority. The reason is if you look at historical trials done in this setting, typically, RVD had a demonstrated PFS of about 34 to 43 months in that range, that is our assumption when we designed the trial. Now if you look at CARTITUDE-1 where these patients really have reached the end cycle, right? It's the last result. And even in that case, we demonstrated nearly 3 years of PFS. And then I just mentioned in our slide that in CARTITUDE-4, for second to fourth line patients, again, so far, median PFS has not been reached after about a 3-year follow-up. This gives us the confidence that we're sure to see a longer PFS than 35 or 40 months in this patient setting. That is why we feel really good about demonstrating superiority against RVD here.

And then another important point is that, remember, if these patients are getting RVD for, let's say, 2 or 3 years in that setting, they're being continuously treated. Again, these drugs are immunosuppressive, you have neutropenia, you have infections. You have other untoward effects. While this is a onetime treatment, right, like that, it is a really great improvement for our quality of life for those patients. So they can enjoy a few years of treatment-free period. That's another advantage. And of course, I think under this FDA, we also think that survival is very important. So hopefully, we'll see not only a significant PFS benefit and superiority over RVD, we're going to see also at least a trend in longer survival as well. That's what we're trying to see from the trial.

And then kind of similar question but for CARTITUDE-6 in the transplant-eligible newly diagnosed patients, can you remind us of the bar established by the control arm on the key metrics? When could we see data from that trial? And what do you think it needs to show to drive a paradigm shift?

Yes. CARTITUDE-6 is really a very important them. Like you said, this could be a paradigm shifting because in the last 50 years, the gold standard of care for frontline has been bone marrow transplant. Even though in a large Phase 3 trial, it was demonstrated only PFS, but no survival benefit. But still, every year, about 9,000 transplant cases were performed for myeloma patients in the U.S. alone. So we intend to show, again, superiority that is we want to see actually a longer PFS compared to transplant.

And if you look at the design of CARTITUDE-6, in both arms, CARVYKTI and also transplant those patients will all receive 6 cycles or 6 months of DRVd plus therapy. So already, they're getting the best possible therapy in consolidation, DRVd. And then we want to see, again, a onetime treatment of CARVYKTI will perform better than transplant.

So the primary endpoints, we have co-primary endpoints. One is PFS. The other one is MRD activity. And we're hoping to show superior PFS. If we can show that, I think it will be a dramatic shift in the treatment paradigm because when we go to ASH, when we go to ASCO, right, physicians tell us that if we can show superiority against transplant, that will be something that's never been done in the treatment of myeloma and that is why we are really also anxious to see when the results come out.

So given the long survival and PFS in this setting, we completed enrollment of CARTITUDE-6 in the summer of last year. By the way, that's way ahead of our plan. It shows you how much demand we're seeing from the patients in the clinic. So we think the earliest likely readout for CARTITUDE-6 will be probably a couple of years after CARTITUDE-5. Again, it's a very good guess because right now, we're still just starting the follow-up period for those CARTITUDE-6 patients. However, I agree, it is a very, very important trial. If we can show that then I think there's no reason why patients would not opt for CAR-T therapy over a transplant.

Okay. Great. We are out of time, so we'll stop there. Thank you.

Thank you very much.

Ladies and gentlemen, thank you for standing by. Welcome to Legend Biotech's Third Quarter 2025 Earnings Call. [Operator Instructions] Please be advised that today's conference is being recorded. I would like now to turn the conference over to Jessie Yeung, Vice President of Investor Relations and Finance. Please go ahead.

Good morning. This is Jessie Yeung, Vice President of Investor Relations and Finance at Legend Biotech. Thank you for joining our conference call today to review our third quarter of 2025 performance. Prior to this call, we issued a press release announcing our financial results for the quarter. You can find the press release on our IR website at legendbiotech.com.

Joining me on today's call are Ying Huang, the company's Chief Executive Officer; Alan Bash, the company's President of CARVYKTI; and Carlos Santos, the company's Chief Financial Officer. Following the prepared remarks, we will open up the call for Q&A. We have our President of R&D, Guowei Fang, joining the Q&A session.

During today's call, we will be making forward-looking statements, which are subject to risks and uncertainties that may cause our actual results to differ materially from those expressed or implied here within. These forward-looking statements are discussed in greater detail in our SEC filings, which we encourage you to read and can be found under the Investors section of our company website.

In addition, adjusted net income or loss is a non-IFRS metric. These non-IFRS financial measures is in addition to and not a substitute for or superior to measures of financial performance prepared in accordance with IFRS. There are a number of limitations related to the use of these non-IFRS financial measures versus their closest IFRS equivalent.

However, we believe that providing information concerning adjusted net income or loss and adjusted net income or loss per share enhances an investor's understanding of our financial performance. We use adjusted net income or loss as a performance metric that guides management in its operation of and planning for the future of the business. We believe that adjusted net income or loss provides a useful measure of our operating performance from period to period.

Our press release includes IFRS to non-IFRS reconciliation for these measures.

With that, I will now turn the call over to Ying.

Hello, everyone. Thank you for joining us today. The third quarter was marked by significant milestones that I will elaborate on momentarily, and we are looking forward to presenting new data at the Annual American Society of Hematology Meeting in December. During the third quarter, CARVYKTI net trade sales were approximately $524 million, which is an 84% increase year-over-year. We have now treated over 9,000 patients with CARVYKTI, and our launch remains the strongest CAR-T launch to date. In the U.S., the majority of our utilization is in the earlier line setting.

Additionally, we continue to see a lot of excitement about our long-term survival data presented at ASCO on CARTITUDE-1. As a reminder, 1/3 of patients with heavily pretreated relapsed/refractory multiple myeloma remain alive and progression-free for 5 years or more after being treated with CARVYKTI. This is especially impressive considering that today's bridging protocol did not exist at the time of the CARTITUDE-1 trial, and patients in the trial had received a median of 6.5 prior lines of therapy.

Ever since our CARTITUDE-1 results were first presented in 2020, we have been setting new standards for efficacy in CAR-T for multiple myeloma. We're now changing that standard to curative potential. In fact, a recent article from Nature stated that 1/3 of the treated individuals had no evidence of detectable myeloma after 5 years without further therapy, an outcome widely thought of as a prerequisite to consider using the term cure.

This kind of efficacy for heavily pretreated patients is unprecedented in the field of multiple myeloma. On the regulatory front, the FDA recently approved an update to include CARVYKTI's overall survival benefit in this label. This was based on an analysis from the Phase III CARTITUDE-4 study showing a statistically significant improvement in overall survival for CARVYKTI compared to the standard of care therapy in patients with relapsed/refractory multiple myeloma after 1 to 3 prior lines of therapy.

Importantly, CARVYKTI is the only approved CAR-T in multiple myeloma with a demonstrated overall survival benefit in this label, which represents another step forward towards educating the physician community on CARVYKTI's unique profile as we work to bring CARVYKTI to more second-line patients in need across the United States.

We expect label updates such as these and previous REMS updates will continue to improve the patient experience and enhance access in both community and academic settings. In fact, I want to share findings from a recent survey that was presented at the International Myeloma Society meeting, where 237 patients and 267 physicians were represented across U.S., U.K., Spain, France, Germany, Italy, Japan and Brazil.

In terms of what patients value when selecting a new line of treatment, overall survival was clearly the most important attribute for patients. Also on the topic of survival, we are pleased that there will be 2 oral presentations on CARVYKTI at this year's upcoming ASH meeting. Before we dive deeper into this, I want to highlight that there will be an oral presentation at ASH on LUCAR-G39D, our first-in-class allogeneic gamma delta T CAR-T cell therapy targeting both CD19 and CD20 in adults with relapsed/refractory B-cell non-Hodgkin's lymphoma. As you may have seen in the abstract, we are pleased that preliminary efficacy showed an encouraging response rate and sustained durability in patients.

Turning to the CARVYKTI oral presentations. Based on the CARTITUDE-4 subgroup analysis, 80% of patients with standard risk cytogenetics were progression-free and off treatment at 2.5 years. In patients with standard risk disease who achieved MRD-negative CR at 1 year, this rate increased to 100%. The low rate of progression events in CARVYKTI-treated patients with standard risk cytoenegative shows the profound benefit of a single infusion in this population.

In the second oral presentation on CARVYKTI, based on correlated biomarker data, longer PFS is associated with better immune fitness at baseline and stronger immune responses post CARVYKTI infusion as observed in peripheral blood and within the tumor microenvironment of patients with relapsed/refractory multiple myeloma in CARTITUDE-1 and CARTITUDE-4 studies. The peripheral immune fitness was more pronounced in patients with 1 and prior lines of therapy versus 3 prior lines of therapy and beyond, where deterioration plateaued.

Similarly, on this topic, on the next slide, featuring data we presented at ASCO, you can see that while CARVYKTI has a favorable benefit risk profile across all different subgroups and lines of therapy, its PFS improvement diminishes with each line of therapy, which is why it's important to follow the latest international myeloma working group guidelines on obtaining CAR-T therapy as early as first relapse.

This slide also contextualizes the significance of our efficacy data from CARTITUDE-1, where there were 6.5 median prior lines of therapy and CARVYKTI still demonstrated a median PFS of 35 months. As we approach 10,000 annualized dose manufacturing capacity, we continue to extend our leadership in cell therapy through further advancing the field of CAR-T in multiple myeloma.

We recently initiated another study called CARTITUDE-10, which is a Phase II multi-cohort trial to further characterize the efficacy and safety of CARVYKTI, which speaks to our commitment to investigating new protocols. Furthermore, a recent blood paper on effective bridging strategies across 20 centers found that among the 119 patients who proceeded to CAR-T therapy after receiving TALVEY, including 98 patients receiving CARVYKTI, not only were these deep responses, sustained soluble B-cell maturation antigen decline and consistent CAR-T expansion, there were also no cases of peripheral neuropathy, Parkinsonism or colitis reported.

As we focus on educating the physician community on our overall survival benefit based on the extensive CARVYKTI data that's been generated, we're also taking the opportunity to remind physicians about the latest research on bridging therapy and ALC monitoring as well as the most recent IMWG guidelines on CAR-T.

In a few moments, you will hear from Alan on how we and our partner, Johnson & Johnson, are bringing CARVYKTI to more multiple myeloma patients in need. In light of the demand we continue to see across the U.S. and overseas, we are moving full steam ahead on our capacity expansion plans. On a final note on CARVYKTI before we turn to our pipeline, we continue to expect to complete enrollment for CARTITUDE-5, 6 this year. We believe the CARTITUDE-5 and 6 trials are key to moving CARVYKTI into the frontline setting.

Looking ahead at our long-term growth, in addition to looking forward moving CARVYKTI into the front line, we remain focused on solidifying our leadership in cell therapy more broadly. We are making progress in new indications such as solid tumor and NHL programs, as you have seen with the data at recent medical conferences.

Additionally, we are looking forward to the ribbon-cutting ceremony tomorrow for our new research facility in Philadelphia, where in vivo delivery will be one of its key focuses, positioning us well to pursue this area of innovation. We remain excited about the new frontier of cell therapy. To sum up, Legend is the largest stand-alone cell therapy company with over 9,000 CARVYKTI patients treated as we forge the path to cure.

With a cash position of nearly $1 billion, we are investing in our core differentiators in cell therapy and remain focused on delivering operational efficiency in order to ensure durable long-term growth. We continue to anticipate achieving profitability for CARVYKTI by the end of 2025 and company-wide profitability in 2026, excluding unrealized foreign exchange gains or losses.

And with that, I'll pass it over to Alan to provide an update on CARVYKTI.

Thank you, Ying. CARVYKTI remains the undisputed leader of CAR-T cells in a single quarter with net trade sales of $524 million during the third quarter. In addition to being the highest-selling CAR-T ever, CARVYKTI has also achieved a CAGR of 111% since launch, which is unmatched in this class. Despite these record-setting numbers, we continue to believe there is a significant opportunity for further market penetration for CARVYKTI, given the magnitude of the addressable multiple myeloma market opportunity for CAR-T.

While we are continuing to expand our footprint of authorized treatment centers in the U.S., the next frontiers of growth are also expected to come from expanding our presence in the community setting in the U.S. and expanding our market leadership outside the U.S.

Diving deeper into our performance this quarter, CARVYKTI net trade sales grew 84% year-over-year and 19% from the second quarter. Our global growth was driven by continued share gains and site expansion. U.S. net trade sales of $396 million grew 53% year-over-year and 11% quarter-over-quarter. Quarter-over-quarter growth in the U.S. was primarily driven by continued strong demand with 60% utilization in earlier line settings.

Regarding our performance outside the U.S., we had sales of $128 million, which is nearly 5x the amount over the same period a year ago and represents a 58% increase quarter-over-quarter. Our performance outside the U.S. was driven not only by continued growth in Germany, but by strong launches in Spain and Belgium.

In terms of supply tailwinds to further build upon our CAR-T market leadership in multiple myeloma, I would like to provide some incremental updates since the second quarter. We are proud to announce that our manufacturing network growth and continued efficiencies mean that we are now able to fully supply the demand and there is no longer a wait for patients.

We expect both supply and demand will continue to expand together to help ensure a seamless customer experience. In the U.S., we are currently in the final stages of the expansion of the Raritan facility that will significantly expand capacity to support continued U.S. market growth. As it relates to supporting growth outside the U.S., I am pleased to announce that our Tech Lane facility recently initiated commercial production. This is an important milestone for serving patients in Europe to meet the increasing demand.

Turning to demand drivers. First, of course, is the recent unprecedented long-term survival data that we presented at ASCO on CARTITUDE-1. Second is our demonstrated overall survival benefit, which has now been added to the U.S. label. We are focused on educating both treating and referring physicians in the academic and community settings on how CARVYKTI is the first and only multiple myeloma cell therapy via a single infusion to significantly extend overall survival versus standard therapies and on our long-term survival data.

In the community setting, we continue to raise awareness, drive referrals and educate oncologists and nursing staff on managing patients once they transition back to their offices. And as Ying mentioned, we are also educating them on the IMWG guidelines and the importance of treating eligible patients as early as possible to take advantage of T cell fitness and potentially improve survival outcomes.

Lastly, in the U.S., the number of authorized treatment centers now stands at 131 sites across the U.S. with about 1/3 of our sites being community and regional hospitals, which serve an important need in the community setting. We are also pleased with the discussions we have had with many stakeholders about the need to bring CAR-T even closer to the community and with adoption by community networks or practices.

Our early experience with Virginia Oncology Associates indicates that this is an area of large need and opportunity. Currently, we estimate that 80% of myeloma patients live within 50 miles of a CARVYKTI authorized treatment center. While that is strong coverage, we think we can do even better over the next 1 to 2 years. And outside the U.S., we will continue to benefit from the new launches.

And with reference to new markets, we are proud to say that we have currently launched in 14 markets around the world. With the help of our partner, Johnson & Johnson, we have activated 246 treatment sites. We continue to be excited about bringing CARVYKTI to more eligible patients in Denmark, Sweden, Belgium, Luxembourg, Spain, Portugal, Saudi Arabia and the private markets of Israel and the U.K.

With the approval of commercial production at our Tech Lane facility, we are well on our way to being able to treat over 10,000 patients on an annualized basis around the world. Now it's time to take a closer look at the financials.

So I'll turn the call over to Ying as we provide a warm welcome to Carlos.

Thank you, Alan. As many of you already know, in August, we announced that Carlos Santos was joining Legend as our new Chief Financial Officer. I'd like to extend my gratitude to Jessie Yeung for her outstanding leadership and significant contributions in guiding our finance organization prior to Carlos's arrival.

Carlos joins Legend from AstraZeneca, where he held various positions over the last 10 years, including CFO for U.S. Oncology, CFO of Latin America business and acting Area VP of the Latin America Commercial Unit. His extensive experience in the biotech sector and wealth of financial leadership expertise will be invaluable as we continue to execute on our commercial and clinical plans and seek to obtain company-wide profitability in 2026.

We are pleased to welcome Carlos to our executive team.

Thank you, Ying, and good morning, everyone. I am very excited to join Legend at this pivotal moment in its global development and growth. After my first 3 months here and visiting our Tech Lane facility, I can confidently say that there is a clear vision and path for Legend to be the global leader in cell therapy. I also see a strong path to profitability through our revenue growth and operational efficiency.

First of all, CARVYKTI continues to grow at a strong rate with net sales up 84% year-over-year in the third quarter. And as Alan mentioned, we have a number of tailwinds that should continue to generate demand in the vast multiple myeloma market. I believe there's a significant opportunity for growth in the community setting, especially with our unique outpatient administration advantage, which provides physicians with flexibility. As Ying has mentioned previously, both CARTITUDE-5 and CARTITUDE-6 approvals have the potential to significantly expand the opportunity for our already proven commercial therapy, CARVYKTI.

In terms of Legend's operational efficiency, our operating expenses as a percentage of revenue have significantly improved over the last 12 months due to our focus on disciplined expense management and increasing automation throughout our organization, and we continue to look at ways to further unlock efficiencies.

Drilling deeper into our third quarter, we delivered solid financial results with CARVYKTI net sales up 84% year-over-year. Total revenues were $272 million, driven by collaboration revenue growth of 84% year-over-year. In Q3, we delivered a $40 million net loss, but was $19 million on an adjusted net loss basis after excluding items that are not representative of the company's core business, such as $15 million in stock-based compensation.

Importantly, our operating loss of $70 million in the same period 1 year ago was reduced by 38% to a $43 million operating loss during the third quarter. This meaningful improvement in operating results was driven by our operational efficiency and disciplined expense management. Even though we continue to invest in our robust pipeline and supporting the second-line indication launch and our manufacturing capacity.

Our third quarter gross margin on net product sales remained consistent at 57%. As expected, R&D expense on an IFRS basis grew slightly to $113 million or 42% of revenue, while SG&A on an IFRS basis grew 10% from the prior year to $87 million in the third quarter or 32% of revenue. Overall, we have made significant progress on operating cash flow generation as evidenced by our $29 million in cash flow from operations this quarter, and we are continuing to make strides towards profitability. Our adjusted diluted earnings per share was a negative $0.05 compared to a negative $0.11 for the same period last year.

Now turning to capital allocation. We have maintained a strong balance sheet with approximately $1 billion in cash and equivalents and time deposits. We will continue to prioritize disciplined expense management as we fund our operating and capital expenditures, including future innovation until we achieve company-wide profitability, excluding foreign exchange gains and losses, which we anticipate in 2026.

In summary, our third quarter results demonstrate continued commercial execution supported by CARVYKTI's unique clinical outcomes, along with increased operational efficiency. We are also pleased with our progress towards pioneering next-generation cell therapy treatments as we leverage our unique innovation model to maximize our cell therapy platform.

And now it's time to take your questions. Operator, we're ready for the first question, please.

[Operator Instructions] The first question comes from Gena Wang with Barclays.

Also, Carlos, congratulations on the new position. Since you closed the remarks, maybe I will ask you, I know 2026, we should start to see positive cash flow. And if given the robust revenue that CARVYKTI could generate, you actually in 2026, there could be very decent inflow of cash.

So maybe I wanted to ask you with this increased cash in hand, what will be the best way to prioritize the cash in terms of the pipeline assets? And then I have a very quick question regarding the ASH abstract. I do know both J&J and Legend actually withdraw a presentation for comparison between IMAGINE-1 and CARTITUDE-1.

So maybe, Ying, if you can or Alan, if you can give a little bit more insight regarding the rationale behind it? And then lastly, very quickly, regarding the Raritan site. I know you did say like the second half, there should be complete completion of expansion. And given we only have less than 2 months left, should we expect everything is on track? Is the -- I know the last step would need to be signed off by the FDA. And should we expect that should happen before year-end '25?

Okay. Thank you, Gena. This is Carlos. In terms of your inquiry about how we're going to allocate cash given our profitability expected in 2026, I would say that, first and foremost, we want to maximize our CARVYKTI franchise. So this is our priority in terms of capital allocation.

And as you know, we've been making significant capital investments in manufacturing and expanding our network. At the same time, we will also continue to significantly invest in our CAR-T platform. We're going to be looking into every opportunity to accelerate our existing programs that will strengthen our market leadership in CAR-T, including business development.

Yes, let me answer the other 2 questions. In terms of Raritan, the plan is very much on track to be able to have the facility expansion completed, and we've already started the submission process for that. So everything is on track for us to head into 2026 with the annualized doses for 10,000 doses. And that is complemented by, of course, as you know, the news we announced around the commercial production in Tech Lane. So now we have all 4 nodes operating on a commercial.

I did want to just address your question on the abstract. So there was a poster from ASH that was withdrawn. And due to the limited data available for Anito-cel in the public domain at this point, the abstract was withdrawn in alignment with the authors, and we are looking forward to future opportunities to share the data.

And our next question will come from Terence Flynn with Morgan Stanley.

I just wondered, I know you provided us with the ATC numbers, both in the U.S. and rest of world now. But as you look into 2026, where do you think those can go realistically? And then on the manufacturing capacity, again, great to hear all the progress there. You mentioned that the 10,000-unit number now. Again, when you kind of complete all of these ongoing efforts, where should that number end up approximately?

So regarding the ATC that you mentioned, we're at 131. Actually, we have an update. We have 132 sites in the U.S. So combine that with the OUS, we're past the 250 mark for total number of sites, and that's a recent update. We continue to update this every single day as we watch it. And to your question about where it could go in '26, we have our sights on continuing to expand, for example, making sure that we have full coverage in the 160-plus sites that some of the competition has.

So as you hear from competitors around their network, we're very confident that in 2026, by the time they are launched that we'll be able to have coverage in the same vein. I will also add that as we look even ahead, the total number of sites in the U.S. that have either started to do CAR-T or have seriously expressed interest and have started the process is something in the 180 number of sites mark. And we believe that we are well on track to be able to get there over time and then continue to expand further into the community setting.

I will also address your question about the plans beyond 10,000. So with all 4 nodes in the network, that being in the U.S., obviously, Raritan, the expansion there, Novartis, which continues to ramp for us and deliver. And of course, in Europe, with the increasing demand in Europe, we have the Tech Lane facility now coming online with full commercial production and Obelisc continuing to drive production as well and gaining efficiencies.

This is a network that we believe will enable us to get eventually to 20,000 doses annualized. And that's through not only continued ramp in all 4 of the nodes, but also continued efficiencies, lowering the out-of-stack, improving the manufacturing success rates.

And our next question will come from Eric Schmidt with Cantor.

As you move from a supply-constrained environment to a demand-constrained environment, what do you think the most important things are that you need to do to mobilize demand to fulfill your new supply? And how quickly do you think you can get to essentially near full utilization of the 10,000 doses?

This is Alan again. So in terms of accelerating demand, we have a number of plans in place to be able to do that. First of all, it's all about making sure that physicians around the U.S. and around the world really fully appreciate the benefits of treating earlier. And that's something that we have certainly gotten traction on, whether that's data that's coming out in the real world or some of the ASH posters that you see in presentations.

There's a broader and greater appreciation for the fact that efficacy is better when you treat in earlier lines, the safety, the incidence of neurologic events and other adverse events is lower when you have patients treated in the earlier lines. You have improved T cell fitness, which is another aspect of the poster that's going to be at ASH.

And as you see from the ASH posters, we also have data that clearly suggests that the step rates are lower. So in a word, everything is better earlier, and that's a key message that we'll continue to drive not only with the current authorized treatment centers, but also the referred in the community. Just to add one more point.

We have a network, as we talked about and a footprint today, but our community strategy is really based on not only continuing to leverage the 1/3 of sites that are in the community, the 1/3 of sites in our current network that are community and regional hospitals, but also driving referrals from the physician practices that are not in the network. And then ultimately, we're having conversations with some of the large practices such as the one you saw from our announcement earlier in the year in BOA to enable the community to actually start to administer CAR-T themselves.

And any sense on when you get to full capacity?

Well, I think as we said today, we are -- our capacity is now meeting the demand in the marketplace. And as we're going to be increasing capacity, we'll also be increasing the demand as well.

I meant in terms of having almost 10,000 doses to dose in the near future. Do you think there's a timeline to utilize that capacity?

Well, I think we'll be able to achieve those goals in 2026, and that translates into the consensus revenues that we see in 2026 that have been issued for 2026. So we're very much on track for that.

Eric, this is Ying. Maybe I'll just tell you that from where I sit, the latest data suggests that we're really running at nearly 100% capacity utilization at all 4 nodes right now. So we continue to expect that all 4 nodes will be utilized at very high-capacity next year as well.

And our next question will come from Jessica Fye with JPMorgan.

This is Tanmay on for Jess. I really have just one question here where I wanted to ask you if you guys could throw some color on anything that you'd be watching out for at ASH from a competitive standpoint?

Well, it might be the absence of information -- sorry, it's Alan here. It might be the absence of information that is most relevant. We're fully ready and prepared to compete with a potential BCMA CAR-T that's coming out potentially next year. But I will say that we haven't seen the Kaplan-Meier curve from Anito-cel yet. So it's quite hard to know what that data is going to look like.

But I will say that we're going to continue to be raising the bar on efficacy. We have a significant advantage in terms of the efficacy that we've seen in the CARTITUDE-4 population in the subgroups in the earlier lines in CAR -- and over the next year, we're going to be also demonstrating the fact that just as we did in CAR-T -- CARTITUDE-1, that CARTITUDE-4 has the long-term durability that physicians and patients are asking for. So we're very comfortable with the data that we're going to be presenting in terms of efficacy, and it's really just a question of when we might see that data from competition.

Yes. And this is Guowei. On the pipeline side, we are also going to release early clinical data for our internal gamma delta platform. And this is a product with unique design and unique CMC process. We see a highly manageable safety profile and good expansion in oncology patients. So the preliminary efficacy show encouraging response rate and also importantly, sustained durability.

And our next question will come from Jon Mill with Evercore.

Congrats on all the progress. I'd love to dial in more on the community progress that you've made. Specifically in the VOA network, have you been treating patients there already? How has the uptake been going in that patient network? Do you have plans to expand beyond the Virginia network near term? And when you say that 1/3 of your sites are regional or community centers, I mean, I assume most of that is regional centers. Can you talk a little bit more about adoption expectations in the community, specifically as we head into '26?

Sure. Yes. So let me unpack that a little bit. We think about the community strategy on a number of paradigms. The first is the fact that we have in our current network, as you mentioned, sites that are already community and regional hospitals. And it's a mix because sometimes a large regional hospital will be servicing a community, and that's what we mean by that group. It's about 1/3 of the 130 or so sites that we currently have.

And we see that, that segment of our network is already contributing about half the growth that we see. So it's a very healthy, robust part of our network. It's going to continue to grow, and it's going to continue to serve the community at large. The second part of the strategy is around engaging community physicians who are referrals. And we've been doing that over the last many months with our partner, J&J.

We have sales teams and medical teams who are engaging fully with the referring network. We're building a lot of good information there for them. We're communicating on the profile. We're communicating on the fact that referring earlier is better, and we're gaining traction there as well. The third leg of the journey, if you will, is then going to the community networks. And you mentioned VOA. So just to answer your question, yes, we have started to treat patients at VOA the feedback has been positive so far.

We're also learning a number of things about just how these community networks will need to be supported throughout their experience of coming online. But there is definitely a plan to engage not only with a VOA and continue to grow that network, but also to engage with other practices throughout the next several months and into 2026.

And when you think about the community-specific practices here, I mean, I guess I'm asking about your ability to dose in settings where your potential competitors absolutely would not be able to dose, at least not first, not just referring to academic centers, but folks getting treated in the community where competitors don't have reach. Can you talk about how that will evolve in '26?

Well, I think we're laying the groundwork for having that -- having all of that presence in the community. But also to your point, we have about half of our current patients are treated in the outpatient setting. And by virtue of the fact that we have a median onset of the CRS in the clinical studies at 7 days, that means that increasingly, practices are comfortable with making sure that physicians can dose patients in the outpatient setting, they can be monitored.

And then if they need to be readmitted for one reason or the other, they're able to do that afterwards. And in addition, as we've discussed before, the removal of the REMS is also an important tailwind because it's enabling patients to have only 2 weeks of local monitoring before they're able to go back home. And then also it removes the driving restriction of 8 weeks, and that's now down to 2 weeks. So that's another important factor for patients being able to get dosed, get infused and then be able to be monitored more close to home and get back with their lives.

And the next question will come from Yaron Werber with TD Cowen.

This is Dana on for Yaron. Congrats on an amazing quarter. I have a question on the ASH abstract. I think there were 2 abstracts from Mayo and Moffitt suggesting that prophylactic dex doesn't seem to reduce the risk of delayed neurotox with CARVYKTI. And given those results, how are you thinking about adjusting your strategy for mitigating delayed neurotox? Are you considering any alternative regimens or thinking about amending any Phase III protocols?

This is Ying. I'll answer this question. So obviously, if you look at both presentations at ASH, you see that ALC remains a very predictive marker. However, the dexamethasone prophylaxis may not be sufficient. And in fact, recently, you have seen publications from real-world studies, including the blood paper that was published in August, right?

So we think that the most important factor is you need to treat those patients with high tumor burden with effective bridging regimen. And you will see actually quite a few abstracts coming out in the ASH next month that various centers are using different recipes or different regimens. But again, all the commonality suggests that you have to use an effective bridging therapy.

In fact, one of the PIs from Mayo, right, Dr. Lin recently said at IMS that you have to switch to a different effective regimen if the first one does not work. So the critical factor here is we have to bring the tumor burden down. And once you do that, you will not see adverse events such as neurotox colitis or CRS. So that is actually a trend we're seeing. Like I said, you will see more real-world data and also more presentations at ASH about this.

And the next question will come from James Shin with DB.

I got a couple on CARTITUDE-10. I see fludarabine is being removed, but is there any change to cyclophosphamide dosing? And assuming this looks, I guess, to Legend standards, will this be somehow added to the label or formally, I guess, approved by the FDA and can be adopted broadly?

James, this is Ying. So you're right, we and our partner, Johnson & Johnson, recently initiated a Phase II study called CARTITUDE-10. And the first cohort would evaluate the fludarabine-free regimen for lymphodepletion. The reason being that we know fludarabine has been established as a neurotox factor here. So we'd like to see whether we can actually achieve similar level of lymphodepletion without using fludarabine.

So that is already up and running. We're enrolling and dosing patients now. Now on your second question, we have to generate the data first. And of course, if the data is positive, we would potentially take that to the FDA to see if that could be included in the label. But right now, it's premature to say anything about the label inclusion.

Can I ask one more on the primary being MRD? Was that any insight from the FDA? And do you have any insight on MRD becoming formally a surrogate?

Yes. So James, regarding MRD as a potential registrational endpoint, we're continuing our discussion with the FDA. And also, we'd like to see under which setting in which line, potentially can MRD activity be an endpoint. But you have to stay tuned. And when we have more to say, we'll disclose about that.

And the next question is going to come from Justin Zelin with BTIG.

I was curious if you could give us an update on outpatient administration? What percentage of patients are you seeing those in the outpatient setting? And any update on the contribution of revenue from earlier lines versus later lines?

Yes. So I think I mentioned this earlier, outpatient-based on claims data is about 50% of the patients currently, and we continue to expect that will be growing over time. Although as we onboard new sites, sometimes they tend to start with patients in the inpatient. So the growth of the site network is also a little bit of a drag on the outpatient overall mix, but those sites that have converted into outpatient are doing so with good success, and it's enabling additional capacity at each site and efficiency.

To answer your second question, we see about 60% of our overall scripts coming from the second through fourth line population. That does continue to grow, albeit a little bit more slowly than we had anticipated, but we see that evolution continue. And in fact, the fastest-growing part of that mix is in the third line. So what that tells us is that increasingly, there is adoption, there's acceptance and there's enthusiasm for bringing CAR-T and CARVYKTI specifically into the earlier line setting based on the CARTITUDE-4 data.

And the next question will come from Mitchell Kapoor with H.C. Wainwright.

This is Katie on for Mitchell. Regarding your guidance for profitability by 2026, what milestones and roadblocks are kind of underpinning that? And what should we be keeping an eye on to understand if you're on track to hit that goal?

Yes. Thank you, Katie. Our view on profitability has not changed. We actually expect to have profitability for CARVYKTI this year in 2025 and enterprise-wide or for Legend as a company in 2026. This is underpinned by our significant growth trajectory for CARVYKTI and our management of operating expenses, resulting in positive free cash flow in the year of 2026. Again, as we've mentioned, we have significant tailwinds in our revenue growth, and this should serve us well for profitability next year.

And the next question will come from Ash Verma with UBS.

So just maybe like I'm trying to understand the dynamic between the second to fourth line that you commented on. Third line, you said that is the post prominent. Can you give us a sense of how much is that? And just secondly, on the MaJESTIC-3 data, like the top line is available now, but just curious how that can start to impact the second-line opportunity for you in any way?

Yes. So we wouldn't break down -- we're not going to break down the split between how much is coming from each line. But I think it is important that all of the lines of therapy on an absolute basis are growing. We're getting more and more patients in the second line, more and more patients in third, et cetera, et cetera.

We also happen to be getting more patients in the later lines. That's just by virtue of the demand for CARVYKTI across all lines, and that's why the mix continues to be about a 60-40 split between the earlier lines of CARTITUDE-4 and the CARTITUDE-1 populations. But again, where the growth we're seeing most pronounced is in the third line, and that's because, again, physicians are recognizing that they want to try to get patients with -- into CARVYKTI treatment as quickly as possible post first relapse or perhaps second relapse.

Ash, I do want to answer your question about MaJESTIC-3. First of all, we're really pleased that there could be potentially another regimen for patients in second line with multiple myeloma. And secondly, I want to point out that the commercial opportunity for this addressable market is very large. You're looking at about 80,000 to 100,000 patients in that segment.

And thirdly, I think we're targeting potentially a different segment here, right? Because if you look at CARVYKTI, we want to emphasize that CARVYKTI has unmatched unprecedented survival data and also with durability. It's also a onetime treatment.

So there are certain patient population who really prefer that kind of a convenience, right, brought by a onetime infusion without further need for any other medication for myeloma. So that is how I view this market. And we don't really expect that MaJESTIC-3 data will really impact the uptake for CARVYKTI in second line.

And our next question comes from Clara Dong with Jefferies.

This is Jenna on for Clara. Could you give us some comments on your strong international growth? Maybe elaborate on where are you seeing the strongest demand and uptake now versus where do you see higher growth potential after Tech Lane comes on? And going into '26 and beyond, how do you foresee the Tech Lane capacity impact in new market share?

Yes. Outside of the U.S., which is obviously led by our partner, J&J, there's been strong uptake in Germany, Spain and Belgium, in particular, as well as the other markets that have launched. Many of the European markets really see the value here of a onetime infusion, the durability that you get with the PFS and OUS benefits as truly providing a strong value not only to patients but also to the health system.

So there's a lot of support for using CARVYKTI earlier in the treatment paradigm, and that's encouraging. We continue to advance the launches that we've already had in the 14 markets around the world, which we listed in the presentation. And we're very excited to have Tech Lane now online from a commercial standpoint to enable the supply both between Tech Lane and OUS together, we'll be able to meet the capacity demand for the growing European launches.

And our next question will come from Sean McCutcheon with Raymond James.

A couple of quick ones from us. You noted improving out-of-spec rates. Can you speak to the trend as you see more real-world patients in the earlier line setting and ongoing efforts to push that out-of-spec rate lower? And any commentary on what you think is a feasible kind of a minimum steady state there? And then secondarily, can you speak to any early impact of loosening of the REMS requirements for auto CAR T and whether you're seeing an uptick in referrals for earlier line patients?

Yes. There's an abstract at ASH that's reviewing about 3,000 patient records for out of spec and the out-of-spec rate is somewhere in the 6% to 9% according to that abstract. And in fact, it's lower in the earlier lines. So it's very consistent with what we're hearing around earlier is better. It's very consistent with the fact that the T cell fitness is stronger in the earlier patients, and that's enabling better dose and better viability and lower out of spec.

And we'll continue to drive that down over time across all the nodes in the network, and we believe that, that's going to be very competitive with other products on the market. In terms of the REMS, it's a little bit early. We're hearing sort of a mix of reactions from sites. One is that this is great news for patients and that it is enabling patients to get back home more quickly.

Other sites are taking a little bit more of a wait-and-see approach and saying they're going to decide on a patient-by-patient basis, which patients are able to go back and which patients they want to keep more close to home, but it's going to be a consultation. The bottom line is it's a burden lifted and it's one that is enabling a more robust conversation about the fact that we can extend the benefit and the efficacy we see with CARVYKTI to more and more patients.

Thank you. I show no further questions at this time. I would now like to turn the call back over to Ying for closing remarks.

Thanks, everyone, for joining today's call. As you can see, we had a really strong quarter, and we continue to expect another strong quarter in the fourth quarter as well as a very strong year in the next year in 2026.

So I just want to say that we look forward to seeing everyone here at ASH because we and J&J are very confident about the efficacy of CARVYKTI. And in fact, we will publish the data in an oral presentation of some data that's not including the ASH abstracts. And we strongly believe that the data at ASH will raise the bar even further for efficacy. So we look forward to seeing everyone in Orlando. Thank you.

Thank you. That does conclude today's conference call. Thank you for participating, and you may now disconnect.

Great. Thanks for joining us, everybody. I'm Terence Flynn, Morgan Stanley's U.S. biopharma analyst. I'm very pleased to be hosting Legend today. From the company, we have Ying Huang, company's CEO. Thanks so much for joining us Ying. Before we get started, I have to read my disclosures. Please see the Morgan Stanley research disclosure website at www.morganstanley.com/researchdisclosures. If you have any questions, please reach out to your Morgan Stanley sales representative. Again, thanks so much, Ying, for being here with us today.

I thought maybe just to start high level, you could give us a little bit of an overview of kind of your strategic priorities, particularly as you're approaching your goal of operational breakeven on CARVYKTI by the end of this year as well as profitability in 2026?

Sure. First of all, thank you, Terence, and also Morgan Stanley for inviting us. In terms of our top 2 strategic priorities are very clear, right? Number one, we want to maximize the market potential for CARVYKTI. On the heels of the recent data at ASCO, where we show that up to 1/3 of the patients who are in CAR-T1, very heavily pretreated patient population who actually can achieve 5-year treatment-free cancer remission. And some doctors would actually take this as a so-called functional cure.

And by the way, this has never been achieved in myeloma because historically, morale myeloma has always been accepted as incurable cancer. The patient cycles through different lines of therapy and eventually they [indiscernible] to disease. So that is a very unprecedented life-saving data for patients who are in fifth-line beyond. And then also recently, we achieved a label addition in Europe to include the survival data from CARTITUDE-4. And then we're looking forward to actually the FDA label update in the near future for that label inclusion in the U.S. as well because -- last year, we hit the first preplanned survival analysis. And we saw a very clinically meaningful and also statistically significant reduction of death by about 45%. And that is against the standard of care, which is a 3-drug cocktail, including DPD, [indiscernible] or 10% patients in that standard of care also chose PDD.

So in fact, at the recent ODAC held by DFA to discuss [indiscernible] approval, Dr. Paul Richardson from Harvard Medical School and Dan Pavey,he mentioned in one slide that in fact, in all second-line trials CARVYKTI was the only drug. And CARTITUDE-4 was the only second line trial to show a drug is actually better in terms of improving survival over standard of care. So that is very significant, and we intend to fully leverage that and we're actually going to the community and directly promoting second line. And hopefully, in the near future, we'll get the label update on survival, right?

At the same time, we and our partner, Johnson & Johnson also are conducting 2 global Phase III trials looking at frontline patients. So hopefully, in the next couple of years, we'll start to get the first readout, and then we can leverage this in the front line. So -- in short, we're trying very hard to really bring this life-saving therapy to early line patients as early as possible. Right now, we can do that in second line in both the U.S. and Europe, and eventually, hopefully, we'll get positive data in frontline so that is a big strategic priority, right? How do we actually deepen the penetration for CARVYKTI. So that this immune therapy can be accessed by many early-patient myeloma.

And then secondly, we also want to fund our internal proprietary pipeline, right? We're doing research in 3 large fields, right? The first 1 is a solid tumor. Recently at ASCO, we actually for the first time presented data for our DLL3 targeting CAR-T for small cell lung cancer. That is partnered with Novartis. We also published some data on the gastric cancer patient trial in BA auto Claudin18.2 trial. That's one focus of the research. The other one is allogeneic. We still have quite a few active Phase I programs running, including all afield. -- all commodity and also [indiscernible]. I think the most recent entry for our research effort is the third area, which is in vivo CAR T and that you can probably see from disclosure on clinicaltrials.gov. We're now actively running 2 trials. Both our CD19/CD20 dual targeting in vivo CAR T for lymphoma, anacolymphoma. And in fact, we have those patients already by now. So we're very actively pursuing that because we see that as an emerging new field for research and cell therapies.

Okay. Great. Well, I think we're going to dig into both of those priorities here in the next 20, 30 minutes or so. CARVYKTI posted no strong quarter of growth here on a sequential basis. As we think about the forward outlook here on growth into '25, '26, can you talk about some of those drivers? I mean, you alluded to a couple of these in your opening remarks here. But -- how are you thinking about the sustainability of that momentum that we've seen so far coming out of the second quarter?

Yes. So recently, in August, we reported our financial results for the second quarter. And just to reiterate, CARVYKTI brought in global net trade sales of $439 million. We're also very proud that it's the second quarter where CARVYKTI now is actually the biggest selling CAR-T product in the world, right? So hopefully, this will be the case for the many more quarters and years to come that this will remain the #1 stain CAR-T. So that was really a big milestone for CARVYKTI.

And also, I think it's also very important to say that CARVYKTI is the only CAR-T targeting BCM for myeloma. That's called a second-line label and also with the survival benefit. So we really intend to capitalize on that. And I think if you look at the multiple myeloma market, right, in the U.S. alone, you're looking at about total prevalence of 190,000, right? So 190,000 patients are the total patient number who unfortunately have been diagnosed with terrible disease. And then right now, in the second line and the young market, we're looking at the total addressable market of roughly 100,000 patients flow every year. Just in the U.S. alone, you look at probably 35,000 to 40,000 patients who fit into that label.

So I would say, even though we have a very strong second quarter, we're really just scratching the surface for these early line patients in multiple myeloma. We still have a long way to go, and we fully believe that with this onetime convenience and also the recent data from CAR-T in terms of 5-year follow-up and cure as well as the second-line data survival improvement in [indiscernible] I think a lot more patients will demand the therapy. And really, it's a response to increase the supply so that many more patients can access this therapy.

Yes. What -- and then maybe just can you walk us through kind of the ex U.S. side? Again, we'll unpack a little bit more in the U.S., but just where we stand on the ex U.S. side?

Yes. We're seeing meaningful growth last quarter as well. Last quarter, I think it brought in about $81 million in total revenue. That's becoming now a more important growth driver for CARVYKTI. So right now, we have a site in Gent, Belgium, it's called [indiscernible], which is already commercially producing CARVYKTI under the approval from the European regulatory authorities. But we're looking forward to in the very near future, an official commercial license from Europe for our tech land facility in Europe to supply the European market. So Tech [indiscernible] facility is going to be about a 220,000 square foot facility, state-of-art modern facility for CAR-T production. Right now, we're approved only to use that site for clinical trial production. But very -- in the very near future, we look forward to commercial license approval there. So that will take our revenue in Europe to another level.

But just if you look at the second quarter, right, we're already seeing very healthy growth. That is coming from our production from the site in [indiscernible]. Also, we do have some limited slots. We're deploying from the U.S. sites to supply European market. And so far, out of the 5 major EU markets we have launched in Germany. And last quarter, we also officially launched CARVYKTI in Spain. And in fact, we're seeing a very good uptake. Right now, we're already seeing a lot of incoming orders in Spain. So we're launched in 2 major markets. In total, we're not available -- coverage is available in ex U.S. market today. And we hope that by end of this year, we'll continue to launch in additional markets. And hopefully, next year, we'll launch at least 1 or maybe even 2 major European market as well.

What -- and then just can you frame for us -- I know you told us the Techwin site is 220,000 square feet. How big is get on a sizing basis, square foot?

So [indiscernible] is much smaller in terms of square footage. We don't discuss other detailed technical specs in terms of square footage. But in general, I can tell you that we're seeing a very significant upside in terms of the supply available from the tech side versus the opening side.

Okay. So at least like tenfold.

I don't want to go into most points fine. But I would just say that it's going to be one of the largest cell therapy production facility in the world.

Okay. And that's -- you said that's near term, like have you months.

We have said that definitely in the second half of this year. We look forward to European approval for commercial license in Techland.

Okay. Okay. Got it. Great. Now maybe if we pivot back to the U.S. here. I know the other big effort is, obviously, you talked about moving to earlier line setting. So that's where the [indiscernible] label comes into play, but also this expansion into the community setting that's pretty important. And I think there have been a number of fits and starts more so on the CD19 front, where we've seen some of these companies kind of face some challenges as they try to move out into the community setting. So maybe you could talk about your and J&J's strategy here to address some of those challenges that other companies have faced and as you think about any differences for myeloma versus lymphoma as we consider the ramp in the community setting, where I think it's what, 80% of myeloma patients are treated.

Sure. So first of all, we do believe that CARVYKTI has a unique process in all the trials we conducted to date, right? CARVYKTI has a very consistent median onset of CRS at about to days. That gives us a wide window, right, which means really there's no critical need to hospitalize the patient in the first report? So that is actually very unique compared to all the other CAR-Ts because typically, a CAR T would have immediate onset, like onset of CRS of 1 or 2 days. In that case, I think physicians are very shy about releasing the patients out of the hospital, right? Because what if CRS happens or in habits, then that patient needs to really come back to the hospital setting. And that's really not beneficial to either the physician or the patient itself.

Now in our clinical trial setting, because of the 7 or 8 day onset, we knew that commercially, this could be 1 advantage because we all know that -- right now, most of the card administration happens in a tertiary teaching hospital setting, right? In the U.S., you're looking at about maybe at a city of 180 to 200 tertiary centers because you don't have any more than that in terms of tertiary teaching hospitals around in this country. So you're limited by the number of sites, you're limited by the number of beds those hospitals may have.

Now in the case of CARVYKTI, we actually institute an outpatient program in the CAR-T program. So we actually expanded different ways to do this. And now if you look at the protocol, right, typically, when the patient is coming in for CAR T infusion for CARVYKTI, it takes a few minutes for that drip infusion. And then the patient will stay in the same facility for 6 hours for monitoring. If nothing happens, then the patient can check out, and then they'll come back maybe daily for money for the first 10 to 14 days. But there's no need to hospitalize that patient.

So now we're seeing in the commercial setting, in fact, we said on the third quarter financial earnings call that more than half of our use today in commercial setting actually happens in outpatient setting. So that is actually very consistent with what we saw in the clinical trials. And we're glad that we're seeing the majority of patients are being able to be treated with CARVYKTI outpatient setting, which is very convenient, right, which means you don't have to be away from your family of caretakers. You can actually either go home, if you dip in the vicinity of the CAR-T centers or you can find a facility where you can sell over that, but it's not in a hospital setting, right? So that's what we're seeing.

And in fact, we predict that with the second-line launch into the community, we should see even higher uptake of outpatient use for CARVYKTI. And recently, by the way, some assets come out from the IMS meeting, which will be held next week. And there's 1 abstract where they looked at -- I think that's so far the largest commercial real-world study for CARVYKTI. So about 20 academic centers in that CMBTR cohort registry. They published the app showing that out of 595 patients who received CARVYKTI commercially. The grade 3 or by was only 4% lower than what we saw in the trial setting, in fact. So that shows you that in the real-world setting safety is actually better, physicians know how to manage CRS. And really, there's no need to utilize a large number of patients, right? So this is why we're seeing this in the committee.

Now to your second question, how do we deepen our penetration in the community? I mean, as you correctly rightfully pointed out, really other CAR-Ts have not seen much success in terms of going into the community, even though they may have the second-line label, right? And on the second quarter financial results call, we did say that right now, actually, we're basically seeing that the CARTITUDE-4 patients, the second to fourth line patients in our revenue mix account for about 60% of our revenue. And out of that, probably 70% are actually referral from the community into the centers, right? So we're doing a lot of work educating both physicians and also patients about the benefit of CAR T and also the fact that you can actually get carve-in outpatient setting, you don't have to, hey, you have to stay in the hospital for 2 weeks, for example, right? And that is a big benefit, I think, and also convenience for the patient to receive -- receiving CARVYKTI.

So I think that's a good advantage we have in terms of educating the second line benefit for CARVYKTI patients here. We're seeing that also we're starting to see more and more referrals following the publication of the New York Times article talking about treating a lethal disease. Now hopefully, some of the patients can potentially be functional cure, right? -- that's another, I think, tailwind we have because we're seeing anecdotally, patients are coming in, they're calling their doctors, they're contacting the doctor, "Hey, I heard that CARVYKTI approved the second -- can I get that. So I think we're starting to see that benefit.

And lastly, I want to mention that recently, we and our partner, Johnson & Johnson, we started this direct-to-patient campaign. So you can actually see this message on channels, including Peacock, [indiscernible] YouTube, for example, right? It's a very targeted effort because we know that in the community setting, the awareness of CAR-T is low. In fact, based on our survey, 1/3 of the community-based hematologists. They're actually not aware of CAR-T, also CARVYKTI, right? And even in that 2/3 of community-based physicians, they are aware, but -- so far, only half of those physicians have referred a patient to CAR-T treatment. So clearly, there's a lot of upside opportunity here. There's untapped opportunity where we can educate those physicians about the benefits so that they understand the car to benefit, they also understand how to treat the patient with CARVYKTI.

Maybe a couple of follow-ups there. The community setting, you said it's about -- or -- sorry, the outpatient over about half of your use right now. Where can that ultimately go over time given some of these initiatives that you guys are instituting.

Yes. If you look at where the multiple myeloma patients are seeking care, right, typically in second line or second to fourth line in general, about 70% to 80% of the patients that are being cared for in the community study. They don't go to a tertiary teaching hospital such as loan catering in the New York City, right? So eventually, I think we would expect that is also consistent with what we should see commercially. That is maybe 70% or 80% of patients should be treated in a community or in the vicinity of that community, right? And that's our goal.

Obviously, we'll see. We have a lot of education and hard work to do, right? Because -- we also have to provide the logistics support. When you help those centers use carbon outpatient setting.

And what -- is there anything on CRS monitoring that you guys can do in terms of the outpatient setting because you mentioned onset 7 to 8 days. But I'd imagine it's still stressful for patients, physicians, if you are one of those people who unfortunately has those side effects. And so is there something you can do from a remote monitoring basis to kind of ease comfort?

In fact, we and Johnson & Johnson are expiring a new approach. -- where a patient can be sent 1 with a wearable device. So that wearable device is something like Apple Watch, for example, right? It does measure certain vitals, including body temperature, including the blood oxygen saturation level because, as you know, if a patient has a fever or the blood oxygen saturation level is low. That's -- these are the 2 [indiscernible]. So we can actually see that signal remotely, right? It can be bond to the hospital to the modeling centers. Therefore, we know even sometimes before the patient knows, right? Okay, there's the fans. And then we try to proactively manage sales at a low level, right? Grade 1 or Grade 2, but not anything above, right?

So if you can pull those patients back -- sometimes it's as easy to give them some wine short of IL-6 or some tilersome other antifever medication, for example.

And when will be a time line for like a broader rollout of that kind of thing?

Yes. It depends how we see this turn out in the field, right? But I would say, broadly speaking, unless you have a patient who lives in a rural area, which is really kind of far away from a center Otherwise, if they're living within the facilities, for example, 1.5 hour driving business, it may not be necessary to have forever on the other hand, if patients overwhelming to say, you know what, we want that, certainly, we can average that.

Okay. Great. And then just 1 more follow-up on the community side. You have this collaboration with Virginia Oncology that you guys recently talked about. Maybe just provide us a little bit more detail about why that was the initial focus, like what was it about Virginia oncology that they decided to move in this direction with you guys? And then how are you thinking about leveraging the learnings from that to other centers? And what are some of the metrics that we should focus on?

Yes. So even as recent as maybe 12 or 3 years ago, people would tell us, "You know what, you guys can never use this drug outside the hospital. Forget about community even, right? So we say, no, we believe based on what we see in the clinical trial experience and also the fact that you have this unique 7- to 8-day media onset CRs. We think we can. So -- we follow up with this, and we announced in our second quarter earnings call that we actually officially signed up Virginia Oncology Associates as the first truly community-based sign our customers to use CARVYKTI, right?

So Virginia oncology associates, they're not hospital chain. They're actually a conglomerate that operates mine clinics in the state of Virginia. So this is, like I said, truly community setting, right? Patients go in, they get the drug and then they go home, right? They don't stay overnight in Virginia associates. So first of all, we prove that we can actually do this. And secondly, anecdotally, I can tell you 1 interest story. So one reason we go to communities because we think that motor myeloma patients as a group, they're actually quite knowledgeable. I mean I don't know whether you try to reach some of those online forms where they discuss treatments and outcome, right? They're actually very knowledgeable in terms of how they understand the science or which treatments are available in the commercial setting.

So sure enough, -- the first patient who came from Virginia piesearch, it's actually through a patient increase. A patient walks in, ask the doctors to say, "Hey, I heard about CARVYKTI, can I get CARVYKTI. And sure enough, the patient got corrected and I'm happy to report that -- we finished manufacturing. We ship that drug and the patient was infused already. So it shows you that, yes, you can actually go to community with this new technology called CAR-T -- and it doesn't add too much burden for the patient because the patient can get treatment in heat on her own community, where they live, right?

This is the first, but definitely, it's not the last. We and our partner Jere engaging many different community-based clinics or group practices. So we'll continue to roll this out. And I believe in the future, right, we'll have the majority of the patient who can actually get treatment in their community. And they will be monitored and a follow-up also in their community.

And what does that look like? I mean, I think you mentioned it was 18,200 hospitals. Those are systems like Virginia Oncology or that's like an individual footprint number just so we think about mapping this, like how big is that set of potential similar facilities or health care providers, I guess.

So I think right now, we have about 126 hospitals of centers like VOA that are certified to use cavity in our network. But going forward, we'll continue to increase the tertiary hospitals in our network. But as you just mentioned, right, we'll probably push to that city maybe next year, you'll reach a maximum of the tertiary centers, but we're not stopping there because we'll continue to spend a lot of effort in going into the community, signing up more accounts such as Virginia cardio associates. There are a lot of regional clinics or even national GPOs, right? So these are organizations that are in the community. They have a big number of sort of like a chance to us, right? They all follow the standard protocol. So once you educate the whole chain, they can use that. And that is going to be our future business model to go to the community to go to the second rig. And does this -- is this now -- can this be a profit center for some of these community oncology centers? Or is this more breakeven when you think about the reimbursement economics I mean we do believe it can be financially viable for those centers. Because as you know, if you look at the total treatment cost for CAR-T, right, a big part of that is actually ascribed to the hospital cost, right?

So if you go to a CAR-T center, a tertiary center, right? And then if it's a patient covered by Medicare because he or she is 65 years or older, then under Part A, you get 1 single check. And apparently, many hospitals actually unfortunately lose money on that because if you calculate the cost for CAR-T drug and then the hospitalization, you probably know how much it costs, right, overnight stay in hospital in the U.S. And all those preferred care A lot of times, I mean, we have heard that maybe as much as half of the case where hospital could lose money because of that. Now because you're meeting this hospitalization and then you take a big part of that cost out, you can actually make that financially viable because you're using existing square foot in terms of the facilities in the chain or in the clinic. So you don't need to add anything special. There's not any extra cost of that.

Okay. Great. most like the typical, what I call, the Part B medication I just want to touch on a couple more CARVYKTI before you get to the pipeline. But just you mentioned the first-line studies that you guys are doing, CARTITUDE-5 and CARTITUDE-6. Obviously, there's the transplant population transplant ineligible population. You're doing separate trials in both of these maybe just level set us with kind of enrollment and then remind us like timing, what you guys have said. It sounds that you said something alluded to over the next couple of years or so. So it sounds like we shouldn't expect anything in '26. I mean it's more of a '27 type readout.

I wouldn't confirm that because as you probably know, Card and CATV are what we call event device. So we have filed with the global regulators, including FDA, we need to hit a so-called certain prespecified number of events before we can online the trial. So CARTITUDE-5 is done in patients who are either not eligible for transplant or they're eligible, but they have decided to defer a transplant because of comedians or other factors, right? So we finished that enrollment a while ago, more than a year ago, and now we're just in the follow-up period. So the comparison arm is standard of care called RVD. So it's a 3-drug cocktail, including REVLIMID, Velcade and dexa -- what we have disclosed in clinicaltrials.gov website is that the primary completion will be 2026. So we don't know exactly when, but broadly speaking, 2026, right? That's what we have said so far.

Now CARTITUDE-6 is another trial where we're comparing CARVYKTI onetime treatment with a standard of care called DRVD for 6 cycles, followed by revenue maintenance. So in that trial, we're planning to enroll a total of 750 patients, one-to-one randomized between CARVYKTI and the standard of care transplant arm. And we're happy to report that actually, we already closed the global enrollment out of our planning. And right now, we're just enrolling a separate cohort in Japan only for the Japanese approval in that setting. So right now, again, we're in the dosing and follow-up period. I believe the data readout probably likely will be 2030 and beyond. But right now, it's probably too early to talk about that because as you know, in those patients for edible for transplant, the median PFS can easily be 5 years or even longer, right? That is why it's not anything in the very near future. But for Car 5 right now, our disclosure on the ct.gov trial website is that it's going to be 2026. Okay. And you feel pretty good about that based on how events are tracking in CAR -- we don't talk about all these events. I think we'll disclose when we have more clarity about the readout timing.

Yes. And what just remind us like RVD, what it did, I mean, that was back when Prabu and I were both covering Celgene -- when that data read out, what's the median PFS in NASH for that [indiscernible].

-- In the Celgene trial registration trial, that on RVD, the FDA approving this setting, the median PFS was about 34, 35 months, so about 3 years, right? But recently, if you look at the PSUs trial done by JNJ, I think in that trial, the control RVD actually outperformed, it was at about 40 months PFS. So let's just call it in that range of 35 to 40 month range more. .

And I know you guys generated some data, I think it was a CARTITUDE-2 study that you said in the front line setting. -- that's, I'm assuming, what gives you confidence that pull the trigger on these studies. And so maybe just remind us like in that CARTITUDE-2 setting, what was kind of the key finding that gives you confidence that you can essentially beat this RVD benchmark that you just talked about?

So actually, when we started [indiscernible] trials, we do not have any data even internally for frontline at all. we did subsequently enrolled and treated 7 patients in CAR-T, those 2 cohorts are cohort me and cohort S. So far, we have not [indiscernible] he data yet. The reason is you do need a pretty long follow-up because these are frontline patients, right, 6 months or 12 months follow-up really is too short to show anything. That is why we have not touched the data yet. But we do have reasonable confidence that we should be able to have [indiscernible] trial. Because in CARTITUDE-1 trial, these are heavily pretreated sick patients, right, where the median prior lines was 6.5%, right? So variation. Still, -- we had a median PFS that was 35 months. And median survival that was 5 years, right? We just published at ASCO this year. And then for CARDI at this moment, we have not even reached median PFS yet. -- for the [indiscernible]. But suffice to say that it should be longer than that 3-year mark we saw in CARC1, right? So we feel pretty good about the chance of winning in [indiscernible].

Yes. Okay. Understood. The last one I just want to ask on is just the latest on MRD negativity as an endpoint to accelerate time lines here. I know there's new leadership at the FDA, but what's your sense of where FDA is shaking out on this? And is that something that you guys are considering here for, I'm guessing more [indiscernible].

So for CARTITUDE-5, the primary endpoint is progression-free survival or PFS. In CARTITUDE-6, we did put MRD as a potential and VR as a potential co-primepoint. But still, our banks has always been that we intend to go to FDA using PFS as a clinical outcome here for approval. You're right. Last year, in March of 2024, FDA convened all that. They looked at MRD as a potential endpoint for multiple myeloma. And in fact, the external experts on all that voted yes, to recommend FDA to use or endorse MRD as endpoint. But I believe that FDA may take a more [indiscernible] stance on this. We continue to engage with the FDA on this. But I can tell you that today, our base case remains that we would use PFS as the end point to go to the FDA to seek approval in frontline. And in fact, as you mentioned, right, under the new FDA, I think both Commissioner and also the division chief have said that, they really want to see survival, not for only PFS, in any oncology trial.

So I think that shows you the emphasis from the agency in terms of demonstrating a full-level benefit.

Is there an opportunity with CARTITUDE-6 because MRD is a co-primary to have an interim look at that? Or is that not built into the design such that you have to kind of wait longer?

I think first of all, we'll continue to engage with global regulators, including both FDA and the EMA to discuss the possibility of using RDS endpoint. I must say, like I said, we continue to think that FDA is pretty conservative on this. And in Europe, maybe EMA can be more, but still -- you've got to remember, right, in Europe, reimbursement is very important. So an EMA approval does not guarantee reimbursement. And I can tell you, when you talk about reimbursement to all these health care authorities, or country governments, right? They do want to see PFS or IMO. It's going to be difficult, I think, to use the margin to secure reimbursement in Europe.

Okay. So that's our baseline -- got it. Just in the last couple of minutes, you walked through very nicely our your pipeline? I'm sorry, we're not going to take questions right now, sorry. So we're going to talk about your pipeline. I know you outlined pretty nicely here what you're focused on. I guess there's been a lot of excitement around in vivo CAR T, also allogeneic for autoimmune. But as you think about these 2 programs, what's kind of the next milestone that we should focus on?

Sure. So we do spend a lot of research effort in those 2 areas, right? -- allergenic. We have active Phase I programs in allogeneic [indiscernible] T cell program. we have allogeneic [indiscernible] program. We also have 1 allogeneic NK program that's active now. And then I think the most exciting new area for research and cell therapies in vivo CAR T. And we actually started that effort a while ago, more than 2.5 years ago. And as I just mentioned, right, it's probably information on clinicaltrials.gov that we opened 2 clinical trials in Phase I both our CD19, CD20 dual targeting CAR-T for non-Hodgkin's lymphoma.

So obviously, we think a lot about in vivo part. That's what I would say. But right now, we're not in a position to disclose any data yet.

Is that a '26 event potentially, do you think.

Potentially, Yes. SP1 But we do believe that we're in a leading position now at this moment, given what we know in the field.

Okay. And what about on the allo side, obviously, more of a focus, I think, here in the autoimmune indications relative to cancer. But how should we think about updates from your progress there?

We're actually probably first want to know how our [indiscernible] cells or engage [indiscernible] perform in cancer first because if you can actually see efficacy in cancer, then more likely than not, you will see efficacy in all indications because the durability requirement is much higher in cancer treatment, right? So I do think that we're going to see a signal whether we can see field expansion and then once you see good expansion for the [indiscernible], but that lead to a durable cancer response or not, right? Then we'll look into all the new indications. But I do think that all the new indications have different safety requirements, also maybe cost as well as the need for for depletion. These are all different needs in all the mine, right? So this is why I think it's a different model in terms of how you look at safety, efficacy, convenience, cost and everything.

Okay. Great. Well, thanks so much. I think we're up on time, but I really appreciate the time today.

Thank you, Terence.

Thank you.

Ladies and gentlemen, thank you for standing by. Welcome to Legend Biotech Second Quarter 2025 Earnings Call. [Operator Instructions] Please be advised that today's conference is being recorded.

I would now like to turn your conference over to Caroline Paul, Associate Director of Investor Relations. Please go ahead.

Good morning. This is Caroline Paul, Associate Director of Investor Relations at Legend Biotech. Thank you for joining our conference call today to review our second quarter of 2025 performance. Prior to this call, we issued a press release announcing our financial results for the quarter. You can find a press release on our IR website at legendbiotech.com. Joining me on today's call are Ying Huang, the company's Chief Executive Officer; Alan Bash, the company's President of CARVYKTI and Jessie Yeung, the company's Interim Chief Financial Officer. Following the prepared remarks, we will open up the call for Q&A. We have our President of R&D, Guowei Fang and Chief Medical Officer, Mythili Koneru joining the Q&A session.

During today's call, we will be making forward-looking statements, which are subject to risks and uncertainties that may cause our actual results to differ materially from those expressed or implied here within. These forward-looking statements are discussed in greater detail in our SEC filings, which we encourage you to read and can be found under the Investors section of our company website.

In addition, adjusted net income or loss is a non-IFRS metric. This non-IFRS financial measure is in addition to and not a substitute for or superior to measures of financial performance prepared in accordance with IFRS. There are a number of limitations related to the use of these non-IFRS financial measures versus their closest IFRS equivalent. However, we believe that providing information concerning adjusted net income or loss and adjusted net income or loss per share enhances an investors' understanding of our financial performance. We use adjusted net income or loss as a performance metric that guides management and its operation of and planning for the future of the business. We believe that adjusted net income or loss provides a useful measure of our operating performance from period to period. Our press release includes IFRS to non-IFRS reconciliations for these measures.

With that, I will now turn the call over to Ying.

Hello, everyone. Thank you for joining us today. We had quite an eventful second quarter as we made history with our long-term survival data at ASCO and achieved the most CAR-T sales ever during a single quarter. During the second quarter, CARVYKTI net trade sales were approximately $439 million, which is a 136% increase year-over-year. We have now treated over 7,500 patients with CARVYKTI, and our launch remains the strongest CAR-T launch to date. In the U.S., more than half of our utilization is now in the earlier line setting. We continue to anticipate achieving operational breakeven for CARVYKTI by the end of 2025 and company-wide profitability in 2026, excluding unrealized foreign exchange gains or losses.

On the regulatory front, we're excited about the FDA's decision to remove risk evaluation and mitigation strategies or reps for currently approved BCMA- and CD19-directed autologous CAR-T therapies. As a result of this change, CARVYKTI's FDA label was also updated to reduce monitoring requirements, such as instructing patients to remain within proximity of a health care facility for at least 2 weeks instead of 4 weeks, and advising patients to avoid driving for at least 2 weeks following product administration compared to 8 weeks previously. We expect this label update to improve the patient experience and enhance access for patients in both the community and academic settings.

On another overwhelmingly positive note, we received a lot of great publicity following our presentations at ASCO and EHA in June. Starting with new data presented at ASCO on our pipeline candidates. In the Phase I study, LB1908, our autologous clouding 18.2 targeted CAR-T cell product demonstrated encouraging antitumor activity with manageable safety and tolerability and CAR-T cell expansion was observed in all patients. Additionally, in the Phase I dose escalating study evaluating LB2102, our DLL3 targeting CAR-T candidate, no dose limiting toxicity were reported and the preliminary efficacy signal was observed up to for those levels.

As a reminder, we have an exclusive global licensing agreement with Novartis to develop and commercialize LB2102 and other DLL3 targeting CAR-T therapies discovered by Legend.

Turning to CARVYKTI. There were 2 different analysis I'd like to spend some time highlighting from ASCO. First, you'll recall that in the final protocol-specified analysis of CARTITUDE-1, the median PFS was 35 months, and median overall survival has not been reached, which had already established a new benchmark for triple-class exposed patients with relapsed refractory multiple myeloma. Subsequently, at ASCO this year, in an analysis of remission and survival from CARTITUDE-1, 1/3 of patients with heavily pretreated relapsed/refractory multiple myeloma remain alive and progression free for 5 years or more after being treated with CARVYKTI without further multiple myeloma treatment. Furthermore, patients with high-risk telegenetics and those with extramedullary plasmacytomas, were equally likely to be progression free.

To put this into context, at our ASCO Investor Event, Dr. [indiscernible] noted that some of these patients were deciding between hospice and CAR-T therapy. The median overall survival of 5 years clearly set a new benchmark in this population. As a result of this groundbreaking data, numerous media outlets publicize these results as well as patient stories. A number of clinicians indicated to us that they have noticed increased patient awareness about CARVYKTI following some of these articles and TV news stories.

Second, based on analysis of subgroups in intent to treat population from CARTITUDE-4, CARVYKTI improved progression-free survival and overall survival versus the standard of care in all subgroups including patients with standard and high-risk cytogenetics, EMD and 1 prior line of therapy and beyond. For example, the median PFS for patients with high-risk strategy next was 37 months, compared to 10 months for the standard of care. These data continue to support a positive benefit versus risk ratio for CARVYKTI in patients with lenalidomide refractory multiple myeloma as early as after first relapse.

Turning to further improvements in CARVYKTI safety profile. We continue to leverage our learnings on extensive data that's been generated on over 7,500 patients treated with CARVYKTI. We are facilitating best practice sharing on predicting, mitigating and managing neurologic events, and we continue to highlight new safety data to patients and physicians. Importantly, we do not see a material impact on utilization and expect continued strong performance on CARVYKTI. In a few months, moments, you'll hear from Alan on how we and our partner, Johnson & Johnson, are trying to bring CARVYKTI to more patients in need of a CAR-T therapy with a demonstrated survival benefit.

On a final note, on CARVYKTI before we turn to our pipeline, we continue to expect to complete enrollment for CARTITUDE-6 this year. We believe CARTITUDE-6 and CARTITUDE-6 are key to moving CARVYKTI into the frontline setting.

Looking at long-term growth for Legend in addition to looking towards moving CARVYKTI into the frontline, we remain focused on solidifying our leadership in the field of cell therapy. We're making progress in new indications such as solid tumor programs, as you have seen with the recent ASCO data. Additionally, we remain excited about the new research facility currently being built in Philadelphia, where in vivo delivery will be one of its key focuses, positioning us well to pursue this area of innovation with the right infrastructure and resources. We believe this next-generation approach to off-the-shelf therapy holds a lot of promise for incurable diseases.

Our new platform, [indiscernible], which is showed for T-cell activation vector is being used to target oncology and autoimmune indications. It provides T-cell specificity, activation and safety through mutations in glycoprotein to block transduction of non-T-cell. We've already dosed a few patients in the IIT study for non-Hodgkin's lymphoma, and we're planning for multiple U.S. IND-enabling studies in the future. We're excited to be embarking on this next frontier of cell therapy innovation, and we look forward to providing additional updates as we make progress on this front.

To sum up, Legend is the largest standard alone cell therapy company with over 7,500 CARVYKTI patients treated as we forge the path to cure. With a cash position of approximately USD 1 billion, we are investing in our core differentiators in cell therapy and remain focused on delivering operational efficiency in order to ensure durable long-term growth.

And with that, I'll pass it over to Alan to provide an update on CARVYKTI.

Thank you, Ying. As Ying mentioned, CARVYKTI is now the highest selling CAR-T therapy in a single quarter. CARVYKTI net trade sales of $439 million during the second quarter surpassed the previous CAR-T industry record of $414 million in sales in a single quarter. And all of this was achieved in just 12 quarters, which is record breaking in the industry.

Diving deeper into our performance this quarter, CARVYKTI net trade sales grew 136% year-over-year and 19% from the first quarter. Our global growth was driven by continued share gains and capacity expansion. U.S. net trade sales of $358 million grew 114% year-over-year and 13% quarter-over-quarter. Quarter-over-quarter growth in the U.S. was primarily driven by continued strong demand with nearly 60% utilization in earlier line settings.

Regarding OUS performance, we had sales of $81 million, which is 4x the amount over the same period a year ago and represents a 59% increase quarter-over-quarter. Our OUS performance was driven by expansion in Germany, Switzerland, Austria and Brazil, and we continue to be excited about bringing CARVYKTI to more eligible patients in Spain, Denmark, Sweden, Belgium, Portugal and the private markets of Israel and the U.K. where we recently launched.

Turning to tailwinds to build upon our CAR-T market leadership in multiple myeloma. As it relates to manufacturing, we expect to receive approval for our physical expansion in Raritan by the end of the year. Our Tech Lane facility also remains on track to initiate commercial production later this year. This is another critical component of our plans for serving patients in Europe to meet the increasing demand.

The progress we've made in executing our manufacturing plan and investments has enabled us to be among the best-in-class. Our manufacturing success rate remains at 97%, which we believe is the highest in the CAR-T industry, and we are focused on continued reductions in our turnaround time, which stands at 30 days. We believe this turnaround time is more than sufficient based on our conversations with physicians.

As we expand manufacturing capacity and enhance our efficiency, we expect to benefit from a number of demand tailwinds as well. First, of course, is the recent unprecedented long-term survival data that we presented at ASCO on CARTITUDE-1.

Second is our demonstrated overall survival benefit. The superior efficacy we have compared to other CAR-Ts should be further aided by the recent REMS updates which are an incremental positive for patients receiving CAR-T therapy and their quality of life post CAR-T administration.

Lastly, in the U.S., we have expanded access to CARVYKTI in the community by continuing to activate more treatment sites. The number of authorized treatment centers have quickly increased since launch. We now have 123 sites across the United States. And outside of the U.S., we will continue to benefit from the recent launches I mentioned earlier.

I'd like to expand now on our strategy for second line plus adoption in the U.S. and provide an update on our progress outside the U.S. First, the opportunity to offer CARVYKTI to the second-line multiple myeloma patients and beyond remains significant. We estimate that there are about 80,000 patients globally in the second to fourth line who could potentially benefit from our treatment. Combined with the fifth line plus opportunity, this represents over 100,000 patients globally. Aside from targeting specific types of relapse refractory patients, who might benefit most from CAR-T based on their prognosis, we have now implemented strategies to engage treaters, referrers and patients.

In parallel with educating physicians on CARVYKTI's profile in order to increase referrals to CARVYKTI sites, we are also working to increase patient awareness through advocacy efforts and even direct-to-consumer education efforts. In fact, we know that multiple myeloma patients and their caregivers are highly educated and engaged in their care, which is why we think engaging them directly will be impactful. We recently launched an awareness campaign on multiple digital streaming and social platforms about the benefit versus risks of a onetime infusion of CARVYKTI. We are looking forward to building awareness through this ever patient campaign.

While we engage community physicians and patients today, we are also looking ahead to continue to expand treatment into the community as well. Our launch took us from a concentrated set of tertiary care and academic centers to where we are today with an expanded footprint, about 1/3 of which is made up of regional and [indiscernible] hospitals who have become local experts in CAR-T. And as we look to the rest of this year and beyond, we are embarking on bringing CARVYKTI even closer to the community with identifying community practices that can do CAR-T administration. We are pleased to announce that Virginia Oncology Associates, a network of practices serving a large part of the state is one of our first partners in this effort.

To sum up, I'm very pleased with our progress to date to reach more patients. Alongside Johnson & Johnson, we have activated 123 treatment sites since launch. And while practices in the community setting cannot be activated overnight, we have multiple strategies in place to make CARVYKTI a more readily available treatment option in the future.

CARVYKTI has also seen significant international expansion. In 2024, we launched 4 markets, and we've more than doubled that for 2025, and we are only in August. Our growing footprint in markets outside the U.S. is supported by our manufacturing facility in Obelisc and we will be further supported with the Tech Lane site expected to start commercial production for Europe later this year. Globally, with the help of our partner, Johnson & Johnson, we have activated 213 treatment sites. The record-breaking pace at which we have moved to expand access and become the highest selling CAR-T therapy in a single quarter with a demonstrated overall survival benefit is a testament to our joint ability to trail blades in the field of myeloma cell therapy.

Now it's time to take a closer look at the financials, so I will turn the call over to Jessie.

Thank you, Alan, and good morning, everyone. During the second quarter, we delivered solid financial results [indiscernible] net sales up 136% year-over-year. Total revenues were $255 million, driven by collaboration revenue growth of 136% year-over-year. Q2 delivered $125 million net loss, but $10 million in adjusted net income. After excluding items that are not representative of the company's core business, such as $111 million unrealized foreign exchange loss due to our treasury center based in Ireland.

Importantly, our operating loss of $41 million in the same period 1 year ago was reduced by almost half to an operating loss of $22 million during the second quarter. The meaningful improvement in operating results was driven by our operational efficiency and disciplined expense management. Even though we continue to invest in our robust pipeline and supporting the second-line indication launch and our manufacturing capacity, our second quarter gross margin on net product sales was 57%. As expected, R&D expense on an IFRS basis declined slightly to $98 million or 39% of revenue while SG&A on an IFRS basis grew 23% from the prior year to $81 million in the second quarter or 32% of revenue.

Overall, we believe we have been making strides towards positive operating cash flow generation and profitability. Our adjusted diluted earnings per share was $0.03 compared to negative $0.01 for the same period last year.

Now turning to capital allocation. We continue to have a strong balance sheet with $1 billion in cash and equivalents and time deposits. We will continue to prioritize disciplined expense management as we fund our operating and capital expenditures, including future innovation until we achieve profitability, which we anticipate in 2026 excluding unrealized foreign exchange gains or losses.

In summary, our second quarter results demonstrate strong commercial execution supported by CARVYKTI's differentiated clinical profile, along with increasing operational efficiency. We are also pleased with our progress towards pioneering like generation cell therapy treatments for intractable and incurable diseases, as we look to maximize our cell therapy platform.

And now it's time to take your questions. Operator, we are ready for the first question, please.

[Operator Instructions] The first questions comes from Terence Flynn with Morgan Stanley.

Congrats on the progress. Maybe two for me. I was just wondering if you can give us any update on potential timing of interim readouts from CARTITUDE-5 and CARTITUDE-6 recognizing the importance of these studies to moving into the first line setting. And then on the efforts in the community oncology setting, can you provide us any more details about Virginia Oncology, like why they elected to lean in here and how you think about that as a template maybe some other community oncology centers to follow and what the time line might be?

Thanks for your question. Regarding the interim readouts, I think we're monitoring the events closely and it's ultimately going to be driven by the events that we see. Obviously, we're in discussions also with the FDA about using MRD as a dual primary end point. And we don't have much to say beyond that, that we will continue those discussions and see -- continue to see how the data evolves.

Terence, it's Alan. Yes, our efforts in Virginia Oncology is, in fact, a template for how we're thinking about the community adoption. As we talked about before, it has the following components. We want to make sure that we are expanding our footprint into the community and regional hospital setting. We want to make sure we're driving referrals from city practices. And as VOA demonstrated as a key milestone for us, also starting to activate in the network of immuno-oncology practices. VOA is a leader in this space. They previously administered CAR-T, both in lymphoma and the myeloma space. So they're well respected in this area. They're part of the [ McKesson network ], and they were very excited to partner with CARVYKTI.

And the next question will come from Gena Wang with Barclays.

Also congrats on the strong quarter. So maybe I will follow Terence's question regarding the community expansion effort. So have you seen any percentage of revenue was driven by this effort in '25? If not, when do you see this effort was started to be shown in the revenue? And then also related launch questions. Of 123 treated centers -- treatment centers what percentage has outpatient set -- set up? And also for 2Q '25 revenue, what percentage of patients or revenue was from outpatient setting?

Gena, it's Alan. I'll share a couple of factors here. First of all, 70% of patients come from the community setting. So that's why the community setting and our continued penetration in that space is very important. And as I mentioned, those efforts will include not only expanding the footprint within the community and regional hospitals, driving referrals, but also starting to administer in the community practices. I think it's a little early for us to pin specific numbers on each element or the contribution of each element or any particular site.

In terms of outpatient though, I'll also give an update. We continue to see that a little over half of our patients are administered in the outpatient setting. That is both across any of these community sites, as I mentioned, as well as in the academic centers, their ability to use an outpatient setting. And that's important because that frees up capacity from the inpatient constraints and infrastructure constraints and enables us to not only improve the experience for patients, but also improve the experience for the centers.

The other element that we've talked about before is earlier line treatment. And as we go into the community, we expect to be able to see more patients referred into the academic centers and the authorized treatment centers from the earlier lines of therapy.

And the next question will come from John Miller with Evercore.

Congrats on all the progress. Two for me. I would love to hear more about the breakdown of your currently treated patients in these early line settings? I know you talk about the CARTITUDE-4 label from second to fourth line, but what about patients in the second line specifically and the third line specifically where you won't be overlapping at all with competitors. How much of your current revenues are driven by those second and third-line patients specifically?

And then just one on J&J's bispecific efforts. How do you expect that their next-gen T-cell engagers are going to interact with CARVYKTI eventually when they're competing on the market? And how do you expect J&J to be positioning them relative to cell therapy?

John, we don't plan to break down any more detail around the various lines of therapy. But what I can say is, as we said before, that nearly 60% of our orders are coming from the second through fourth line population. So those are the earlier line patients who we feel will provide us a significant advantage to any potential competitor who comes in, in later lines and that's from our ordering system. So that is self-reported data from physicians, and we're very excited about that growing each quarter and continuing to grow throughout the course of this year and certainly before any competitor launches.

In terms of the bispecifics, I think we've seen that CAR-T is very well regarded as not only a treatment because of its onetime infusion, but also the overall survival benefit and the durability that CAR-T and specifically CARVYKTI can provide. And so in terms of positioning, right now, CARVYKTI is really owning that second through fourth line opportunity within the J&J portfolio. This is an opportunity for us to really solidify our position with patients for whom they've already had one relapse. They're looking for overall survival. They're looking for long-term durability and J&J and Legend are combined, very committed to this positioning for CARVYKTI.

And also John, this is Ying. I want to add to Alan's comments. If you notice that you can find naturally trials on clinicaltrials.gov, where our partner, J&J, is actually combining and/or sequencing CARVYKTI with some of devices in their portfolio. So you will see the direction of that development. It is too early and premature to comment on strategy on developing the prices of it because right now it's still at a very stage in Phase I stage. Although we cannot disclose the breakdown of second, third, fourth and fifth line and beyond, and plus some of those are coming from actually insurance claims data. It's not necessarily coming from our own data, but I can tell you if you combine second and third line, those are probably the fastest-growing revenue contributor in the mix of CARVYKTI.

Also, if you talk to physicians, you will notice that, the large majority, probably 70%, 80% of patients are actually receiving a bridging therapy. So sometimes if you look at insurance claim, you will see a second-line patient who comes in and then received a bridging therapy for 1 or 2 cycle would actually be classified as a third-line patient. That is another reason why we should look at second and third line not combined.

Just one other comment regarding the trispecific from J&J. If the video that was released, a lot of it was in the BCMA naive population, which, as we know, is getting harder and harder to find. And so as we move CARVYKTI into earlier lines of therapy, it's really going to be in other BCMA products approved, it's going to be hard to find that patient population.

And the next question will come from Jessica Fye with JPMorgan.

This is Adam on for Jess. I really had two. Can you comment on the recent blood paper as it relates to real-world rates of neurotox with CARVYKTI?

And my second one, what is your latest perspective on CARVYKTI's penetration into the CARTITUDE-4 indication of second to fourth line?

Sure. Regarding the blood paper that you're referring to by Dr. [indiscernible] in that large data that 98 patients were treated with [indiscernible] at 20 various centers. And in those patients that used TALVEY as bridging therapy to a single infusion of CARVYKTI, it was noted that there were no events of parkinsonism or Guillain-Barré syndrome. And there are only 2 reports of [indiscernible] policies, both of which resolved. It really highlights the opportunity of an improved safety profile with strong bridging like with TALVEY. And if you compare that to the real-world data of about 2% decreases to 0% in the large data set.

In terms of the CARTITUDE-4 population, second through fourth line, again, as we said before, this is our main growth driver. We're focused on driving earlier lines of therapy. And as we said before, nearly 60% of our sales are coming from that population. But I would say, again, as we talked about before, this is a population that is about 80,000 patients worldwide. And so you can just based on -- on the numbers of patients that we treated to date, we still have a lot of opportunity in this space, a very large opportunity for us to continue to capture in the second through fourth line population globally.

Adam. Thanks for this question on blood paper. We actually think it's a very important paper here because if you compare this data set from the competing dataset, you're looking at a total of 134 patients receiving TALVEY out of which 119 per city to get a CAR-T and then 98 patients received commercial CARVYKTI. These are from multicenters, right, 20 centers, including 18 in the U.S. and 2 in Germany. If you also look at patient baseline, they received the medium 5 prime lines of therapy, 44% had high-risk telegenetics, 41% had EMD actual measured disease. So 85% of those patients would not have qualified for CARTITUDE-1. And yet still, if you look at the safety profile, we did not see any [indiscernible] such as parkinsonism or GBS. There were only 2 cases of mild cranial nerve policy and both resolved.

So if you compare this data sense, when you're competing dataset of about 120 patients, I would argue it's a very similar denominator here. And also, if you look at the neurotox, very similar as well. I think that is a very well-documented study, like I said, peer reviewed on blood journal. So this gives you a sense of the real world safety.

And the next question will come from Konstantinos Biliouris with BMO Capital Markets.

Congrats on the progress. We would love to hear your thoughts around the recent efficacy data from a competitor and specifically the 18-month PFS, which appears to be similar to CARTITUDE-1. Any thoughts around that, although the follow-up is sorted than what you have presented. And how do you think -- are you thinking about the positioning of CARVYKTI moving forward?

Thanks for your question. I'd like to stress that CARVYKTI is really the best-in-class BCMA CAR-T. We've treated over 7,500 patients, as you've just heard earlier. And it's really demonstrated an overall survival benefit in this early second to fourth line patient population as reported into the CARTITUDE-4 study. So in addition to that, the CARTITUDE-1 data from the ASCO has shown that with the onetime infusion of CARVYKTI, 1/3 of the patients in this very heavily pretreated population actually didn't progress after 5 years. This is unprecedented data and shows the long follow-up that we have with patients treated with CARVYKTI.

I would argue that the patient population [indiscernible] study that you're referring to is really fundamentally a different patient population. In particular, the prior lines of therapy, the CARTITUDE-1 study is a much more heavily pretreated patient population. And as you have mentioned, their data is immature and still evolving with not sufficient follow-up. So based on some other conversations we've had with physicians, they're really wondering how these patients have done when they reach the 18th month PFS, how many of them have actually reached that point. And without the evidence of the Kaplan-Meier curve, which actually the CARVYKTI we had reported around the 18-month time frame, it's really hard to tell the [ RSLC study ] how these patients did overall. That's why I think it's important that we see that data and stress the fact that CARVYKTI really key differentiated and have very durable responses with the large amount of data sets that we've provided to date.

And the next question will come from Yaron Werber with TD Cowen.

Congrats on the quarter. [indiscernible] you noted on the call that you're on track to finish enrolling CARTITUDE-6 this year. This sees incrementally pushed out versus mid-2025 previously to any reason that rule might be progressing a little more slowly than expected. And does this mean that we're still going to see an impact on Q3 revenues from slots being diverted to CARTITUDE-6? And overall, does that change your expectations that previously on accelerating growth for CARVYKTI in second half of the year versus first half?

Our enrollment in CARTITUDE-6 6 has been progressing quite speedily. In fact, we've completed enrollment [indiscernible] totally except for continuing to complete in Japan, which is the last country. So we're very excited about the fact that physicians were enrolling on the study, and it shows the excitement of this patient population with CARVYKTI.

And just to add in terms of your second part of your question, we're very confident in our ability to continue to drive capacity expansion in the second half of this year. Novartis continues to ramp throughout the year. The tech line clinical approval is taking on those patient slots and enabling more commercial capacity across the network as well as we continue to get efficiencies from our network in terms of out of step rates, improved turnaround time and better manufacturing success rates across the network.

And as we mentioned before, in the second half of this year, we anticipate the physical expansion for [indiscernible] as well as the commercial approval for Tech Lane.

And [indiscernible], maybe I'll just add that if you recall for the CARTITUDE-1 trial for that indication, we actually enrolled also very small, less than 10 patients cohort, just specifically for the Japanese approval because that's a requirement [indiscernible]. So we're doing the same for CARTITUDE-6. But like you just heard from our Chief Medical Officer that we have already completed global enrollment for CARTITUDE-6.

And the next question will come from Kelly Shi with Jefferies.

Congrats on another strong quarter. Curious as CARVYKTI has traded now over 7,000 patients, also follow-up on your commentaries on the overall safety profile, including [indiscernible] any noticeable difference that has been observed in earlier line patients versus [indiscernible]? If so, what are the factors that drive the difference?

Thank you for your question. As we've shown from the CARTITUDE-1 to CARTITUDE-4 data, the delayed neurologic event has decreased, particularly the parkinsonism from 6% to 1% in CARTITUDE-4. So we do believe that earlier line treatment does improve the safety profile quite significantly. And part of that success is the strong bridging therapy that is provided to these patients and these patients just have more options for [ good virgin ] therapy in the earlier lines.

As we discussed earlier in the call, the blood paper by Dr. [indiscernible] shows that in a large data set that there was no evidence of parkinsonism, further showing the importance of having good bridging therapy to decrease the neurologic events, but also improve the efficacy profile ultimately. Both of these things, I think, will be really important.

I think as we continue the mitigation strategies that we put in place are important and treating physicians are using them, and they continue to show improvement in these safety events.

Kelly, I'll just add a little color on what we're seeing from physicians and hearing from the field. The earlier the patients are referred in and treated the better experience overall. The T-cells were fitter, so that means that we have lower out of stack. We have better efficacy. We also, by virtue of what [indiscernible] outlined. Also, we have lower rates of any of the rare [indiscernible] effects. So we are in a situation where everything is better when you treat earlier, and that message is very much resonating. That's what the thought leaders are talking about from the podium get your patients in earlier and you get the benefit of CAR-T earlier in the treatment paradigm.

And Kelly, this is Ying. Maybe I'll just add to the last point, which is everyone follows the FDA AR database. Again, if you look at the overall incidents, it's increasing, but that's because we're treating more than 7,500 patients. However, if you do the math using the denominator, numerator, we just provided you will see. In fact, I've seen a few sell-side reports saying that the percentage [indiscernible] is actually coming down in terms of delay neurotoxicities.

And the next question will come from Leonid Timashev with RBC.

I wanted to ask on the -- where demand is going to be coming from in the future. I guess in the past, you've talked about your ability to titrate demand. So I'm thinking how are you guys thinking about 2026, specifically where the supply curve is going to be relative to the demand curve. And I'm curious if you can speak to that maybe on a geography basis, I guess, the U.S. and EU separately. Just given that CARTITUDE-1 have done well in Europe? And should we be expecting more growth coming out of Europe in 2026? And ultimately approach relative parity with the U.S. I guess just how are you thinking about the relative position of the supply and demand curves for U.S. versus EU?

We will be driving both supply and demand simultaneously. They don't grow necessarily on a linear fashion each, but as both grow, we'll be able to support the market with supply. And in terms of the breakdown in terms of geography, you saw in this quarter, increasing contribution from Europe with the 11 markets outside of the U.S. now launched we anticipate that, that will continue to grow over 2026 and beyond. Additional major markets are planned for 2026. And so ex U.S. contribution will continue to become an increasing and meaningful component of the CARVYKTI sales.

And in terms of demand, just to provide a little bit more detail on some of the demand dynamics within the U.S. We talked about it in the opening remarks, but the ASCO data and the recognition of the overall survival benefit and the long-term survival is something that's going to continue to grow in terms of awareness. And that will translate into not only driving referrals, but also increasing utilization in the earlier lines. We also talked about the fact that the REMS removal will be an important component of improving the patient experience. Patients can then be treated in an authorized treatment facility, but then monitored act closer to home, as you heard from Ying, lowered number of weeks in terms of monitoring, fewer number of weeks in terms of the driving restrictions. These things really do matter to patients and their family and caregivers when they're trying to get back into a normal functioning life.

So you think about the REMS removal, you think about the overall survival, the ASCO data. And then as we talked about as part of the opening remarks, we've also started to directly engage patients. So this is our DTC effort in a very targeted way, recognizing the fact that myeloma patients and their caregivers lot to hear about CAR-T. They want to learn about CAR-T. They want to be able to have the conversation with their physicians, and that's what we started to do. So I expect the demand to come from many of those drivers.

And the next question will come from James Shin with DB.

Appreciate DOA coming online, but what does the partnership should bring to Legend and I guess, broader question is, what percentage of the smaller community practices like VOA are still pending CARVYKTI slots? Secondly is the biggest driver for community adoption getting a lighter version of fact accreditation?

We're in the very early stages of having more penetration in the network practices like VOA. So VOA is the first key milestone for us. But as I mentioned, it's the first one in the ones that are planned with J&J and Legend. In terms of fact accreditation, there are several efforts underway both industry groups as well as legislation at the state level to lift the requirement [indiscernible] accreditation. So we want to make sure that authorized treatment centers for cell therapy and for BCMA CAR-T are of course, qualify to do so experts in that area, but not necessarily facing all the significant burdens required with fact accreditation. So there are multiple efforts as you mentioned, to provide some sort of either fact, light or create a fact umbrella from an academic center such as U-Penn to other community hospitals that are part of that umbrella.

So again, these are all efforts that will continue to bring CAR-T closer to patients, patients don't want to have to travel into the cities or the major centers for their treatment. And so this enables them to get CAR-T closer to home.

And James, just to supplement what Alan just commented. In fact, Texas is the first state in the U.S. that actually passed a State Legislature recently that in the state of Texas, there's no longer a requirement for fact accreditation for reimbursement by insurance carriers. And we do foresee that more and more states will follows it.

And our next question will come from Mitchell Kapoor with H.C. Wainright.

Have to -- the first one, could you just talk about since we're halfway through the third quarter at this point about now? Can you talk about the important CARVYKTI trends that you're seeing since the end of June that may show up in the third quarter numbers? And then second, on geography and mix. Could you talk about the ex U.S. mix trend? And if the 30% U.S. EU pricing delta is likely to hold as access broadens?

Our demand trends are strong. We're very comfortable with where things are headed for the rest of this year.

In terms of the mix, as I said before, we believe that the launches in Europe will continue to provide incremental demand, out of Germany is the largest of the markets ex U.S. and that is continuing to grow very nicely, and we continue to see that Europe will be a meaningful and increasing contribution to the overall sales picture for CARVYKTI.

And unfortunately, we cannot comment on pricing as you can understand. We believe that CARVYKTI offers a very, very strong health economic benefit based on the survival and also the PFS benefits we have seen. In fact, if you follow last month's ODAC held by FDA to evaluate [indiscernible], I think one doctor, [indiscernible] from Dana-Farber and Harvard Medical School actually pointed out in one of the slides that so far in the second-line setting, there's only 1 trial and 1 drug that proves survival benefit significantly over standard of care, and that is CARVYKTI in CARTITUDE-4. So we're very well positioned with all these benefits.

Okay. Yes. More specifically on the first question, is there anything since the end of June that you guys are seeing that is different than what we've heard on the call so far that may be a trend in Q2?

The only thing I'll add is, anecdotally, and Ying alluded to this earlier, since the ASCO presentation, we've heard more and more patients coming in and actually either holding up 1 of the local newspaper articles or the New York Times article or having heard about the data, and it's reaching patients, it started to have those conversations with physicians. We heard that from the physicians themselves that that's what patients are saying. So anecdotally, this is creating a lot of buzz and excitement both among the prescribing community. If you go to a medical conference, and there was one this past weekend, I think you'll see physicians start their talk by showing the New York Times headlines from ASCO.

And so again, the anecdotes are showing that there's a lot of interest in the long-term survival benefit that you get from CARVYKTI and we see that is starting to take shape in the marketplace as well.

And the next question will come from Justin Zelin with BTIG.

Congrats on the strong record-breaking quarter here. So with the $1 billion in cash here, you're approaching profitability, just curious how do you think about approaching reinvestment, with reaching profitability here across manufacturing your pipeline, licensing once you're reaching profitability with your, your vision and your position in the global cell therapy landscape?

Thank you for your question. We are committed to reach profitability with $1 million in cash. We are still very disciplined in funding, but we are committed to the next generation of cell therapies treatment [indiscernible] intractable and [ interpret ] diseases.

And then just another question that we get is do you expect any material impacts from the recent tariff changes under manufacturing costs or your supply chain and just any impact on how you're mitigating those?

Our understanding is that the details relating to any potential pharma-related tariffs are still being worked out, but because our U.S. products are predominantly make and sourced in the U.S., at this point, we believe that any potential exposure to tariffs will be immaterial based on our evaluation.

And the next question will come from Ash Verma with UBS.

So just quickly on the ramp of Novartis commercial supply, is that more steady for the remainder of second half? Or should we expect most of that to be reflected in the 3Q sales? And just on -- secondly, on the first-line data generation for CARTITUDE-5, like, do you have line of sight that you can get this data in calendar year 2026. And I know you've previously talked about this CARTITUDE-2 cohort [indiscernible], which we're still pending. Is that something that we could see later this year?

On Novartis, we got the approval earlier this year, as you know, for commercial production, and that has continued to ramp and we expect it to be at full capacity by the end of this year. So that will continue to contribute to our growth over the course of the year.

Regarding your other parts of your question regarding CARTITUDE-5, it will be events driven. So we really need to monitor those closely. So we will not be able to provide more details beyond that.

Regarding the CARTITUDE-2 E&S cohorts looking at frontline patients, we cannot disclose what is being submitted to conferences later this year at this time.

And this does conclude today's question-and-answer session and also concludes today's conference call. Thank you so much for participating, and you may now disconnect.