Legend Biotech Corporation (LEGN) Earnings Call Transcript & Summary

Good afternoon everyone from the 40th Annual JPMorgan Health Care Conference. My name is Cory Kasimov. I'm the senior large cap biotech analyst here and it's my pleasure to introduce Legend Biotech and CEO, Ying Huang. Please note that following the presentation, we will move right into a Q&A session where you can send in questions via the conference portal. And I'll do my best to work them into the conversation. So with that, Ying, thanks for joining us today, and let me turn things over to you for an update on Legend.

Thank you, Cory, for inviting Legend Biotech for the JPMorgan Conference. So this is our standard safe harbor statement. Please go to the SEC website for any up-to-date filings and update. So just on a very high level, Legend Biotech has been in operation for the last 7 years. The company was founded in 2014. Today, we have over 1,000 employees across the globe. And we're working on more than 10 clinical and also preclinical programs in the field of solid tumor and hematology malignancies. Within our R&D platform, we're working with different modalities, including autologous CAR-T, allogeneic CAR-T, T-cell receptor or TCR and also NK programs. Along with our global partner, Janssen Pharmaceuticals, J&J pharmaceutical companies. We're operating 3 global manufacturing sites in 3 major continents in the U.S., in Europe and in China. As of end of third quarter 2021 we had $636 million in cash, cash equivalents and also time deposits and yield producing securities. So we aspire to be a fully integrated global cell therapy company, and we have generated compelling clinical data with our pipeline program, cilta-cel, which is the lead asset in the clinical stage along with our partner J&J. We have also established a broad portfolio of earlier-stage autologous and also allogeneic product candidates. Within the global collaboration with Janssen, which started in December 2017, we received an upfront payment of $350 million and also a total of additional $200 million in mass loan payments to date, and Legend is eligible to receive additional $1.15 billion in potential future milestone payments. We have built an in-host generation and optimization technology. and we have been able to produce early clinical proof-of-concept data. Along with our J&J partner, we've been building large-scale manufacturing facilities across the globe. And as I said, we have over team members across the globe today. This slide summarizes all the key milestones achieved since the company was founded. In 2016, the first multiple myeloma patient was dosed with our BCMA CAR-T in China in the Phase I trial called LEGEND-2 study. By end of 2017, we entered into a global collaboration with Janssen Pharmaceuticals for the development of cilta-cel. And in 2018, the IND was cleared in both China and also in the U.S. for further restoration trials for cilta-cel. In 2019, we received the PRIME designation by European Medicine Agency for cilta-cel. Also, we received a breakthrough therapy designation by the U.S. FDA. In 2020, cilta-cel became the first ever breakthrough destination issued by CD in China. We also went public in the same year. Last year, the BLA to the U.S. FDA and also the MAA to the EMA were accepted, and we have a PDUFA date of February 28 of this year for the FDA action. We also started the first Phase I trial of our asset called LB1901 for the treatment of T-cell lymphoma in the U.S. in 2021. A little bit more detailed look at our R&D. Today, we have a team that's composed of more than 300 R&D scientists. And we're working on several potential best-in-class assets using different platform technologies, including CAR-T, TCR-T, NK and also Gamma-delta T. We're working on both autologous and also allogeneic assets. Right now, we have multiple Phase I programs ongoing in the clinic in China. And also, we have 1 Phase I trial for T-cell lymphoma in the U.S. besides the comprehensive CAR-T program for collaborating with J&J. If you look at Legend Biotech's R&D capability, we're establishing what we call the end-to-end capability that starts from the antibody screening and also antibody optimization based on single demand antibodies generated from the Llama and also conventional antibody libraries. After that, we have already built a proprietary methodology to select the demand for antibody and also the T-cell construct design. And we have also started a platform with a robust in vitro and also in vivo screening to prioritize our clinical programs. And lastly, in both the U.S. and in China, we have already built a clinical team that will generate clinical data. This slide summarizes the details about our global collaboration agreement with Janssen Pharmaceuticals. In the U.S., we have a 50-50 partnership with J&J. This is also a co-promotion territory where the Legend commercial team will work alongside the Janssen commercial team pending FDA approval to promote cilta-cel. In Europe and Japan, this is what we call the Janssen territory. So Janssen Pharmaceuticals will lead the commercial development and also the clinical development in those territories. However, we're still partnering with J&J on a 50-50 cost sharing and also future profit sharing agreement. In Greater China, we have a 70-30 relationship. Legend Biotech is the IND holder in Greater China, and we're leading with 70% of the cost contribution and also future 70% profit sharing. All this cannot be done without a very experienced management team. As you can see, we have a very experienced management team in both the U.S. and also in our China operation. these folks came from the likes of Novartis, Merck, Eli Lilly, Celgene, and other leading pharmaceutical companies. And today, I'm actually joined by 2 colleagues of mine, Dr. Lida Pacaud, who has a clinical development team here in the U.S. and also Mr. Mike Hirschmann who works as Executive Director and also Head of our sales organization in the U.S. So this is a quick intro for CARTITUDE-1 program, which is a Phase Ib/Phase II study that formed the basis of our BLA submission to the U.S. FDA. And as you can see, this molecule cilta-cel has a unique design with 2 single-domain and refragment attached to the T-cells. If you look at the design of the study, we are really managing the patients who have been treated with the minimum of 3 prior therapies, order double refractory. And the patients must have prior exposure to a class of protease emitter such as Velcade or Kyprolis a class of emit molecules such as Pomalyst or Revlimid and also a class of anti-CD38 antibodies such as Darzalex. The target dose in CARTITUDE-1 was 0.75 million cells per kilogram body weight. And in CARTITUDE-1 trial, the median amidst dose was 0.71 million cells per kilogram body weight, which is very close to the target. If you look at the baseline characteristics of these patients, as you can see, these are very sick and also heavily pretreated patient population with the prior lines of therapy at a median number of 6 with a range of 3 to as many as 18 prior lines. And some of the red boxes highlight the baseline characteristics and indicating how difficult this population is to treat. For example, 20% of these patients have plasmacytomas, including 13% extramedullary plasmacytoma and also another 6% bone-based plasmacytoma. About 1/4 of those patients had high-risk cytogenetics at the baseline. And 84% were exposed to 5 different drugs in those 3 major classes I described earlier. 8% of the patients are triple-class refractory, which means they are actually refractory to all 3 major casino therapy for micro myeloma in the market today. In the median years since diagnosis was about 6 years. This is the most recent data we presented for CARTITUDE-1 at the ASH Annual Meeting in December of last year. As you can see, we produced a 98% response rate. What's more remarkable is the 83% of stringent complete remission rate achieved in this heavily pretreated patient population. One interesting phenomenon is that, over time, we're seeing a deepening response. For example, at the medium 1-year follow-up, the stringent CR rate was 67%. Now with a median 2-year follow-up, the stringent CR has now deepened to 83%. This slide is what we call the capital myer curve for both PFS or progression-free survival and also overall survival. In the left side of the slide, you will see that at a 2-year mark, we still have 71% of patients in CARTITUDE-1 remaining in progression-free survival, and we have not reached median PFS for these patients yet. In the right side, you will see, again, for overall survival at a 2-year mark, almost 3/4 or 74% of patients remain alive at this point. And what's encouraging is that in both the case of PFS and also OS, we're seeing the so-called flattening of the curve after 24 months of follow-up. So this actually gives us the hope that many patients enrolled in this CARTITUDE-1 trial being treated with cilta-cel can achieve long-term survival. Along with Janssen, we are also conducting a multicohort Phase II study called CARTITUDE-2. This trial evaluates cilta-cel in early lines, including frontline of multiple myeloma patients. We presented 2 cohort data at the recent ASH meeting. In cohort A, which enrolled 20 patients who had progressive multiple myeloma after 1 to 3 prior lines of therapy, and these patients were also refractory to Revlimid. In cohort B, we enrolled 19 patients who had early failure or early relapsed of initial therapy, including bone marrow stem cell transplant and also standard cocktail therapy, including a produce inhibitor and also IMiD. Again, we're seeing very, very consistent and highly encouraging results in this patient population. In Cohort A, so these are patients who have been treated with 1 to 3 prior lines of therapy, we achieved 95% response rate with a median follow-up of 14.3 months. And again, we're seeing very deep response. 85% of these patients achieved complete remission. In Cohort B, these are patients who have early treatment failures or relapse after initial therapy of bone marrow stem cell transplant or standard care, including a protease emitter and also a IMiD. In this case, we have a median follow-up of 10.6 months amount of 19 patients and we have observed 95% overall response rate with 79% of complete response rate. So as you can see, in different settings, including late line, including second and beyond and also patients who have early failures or relapsed after initial therapy. We're seeing across the board, 95% or plus response rate. Again, we're seeing also about 80% or above CRS in different settings. With regard to safety, I'm happy to report that since Janssen and Legend instituted the risk mitigation strategies, we're not seeing any new incidence of neurotoxicity in the CARTITUDE-1 program. And also within the CARTITUDE-2 program after we instated that risk mitigation strategy, we were able to see a very significant decrease in movement in neuropathic disorders. In CARTITUDE-1, we had 5 cases of movement and neurocognitive disorders. However, within the whole car program, we have treated additional 200 patients already in CARTITUDE-2,CARTITUDE-4 and also CARTITUDE-5 trials yet we're able to decrease that amount to less than 0.5% because so far, we have seen only 1 case of neurocognitive and movement disorders. This summarizes the very comprehensive clinical program for cilta-cel. Right now, Janssen and Legend are conducting 2 global randomized Phase III trials, the first one being CARTITUDE-4. It's our first Phase III trial in the study. And this is evaluating patients with prior 1 to 3 lines of therapy and also for refractory to Revlimid. We completed enrollment of more than 400 patients in October of 2021. And right now, we're in the follow-up. We also started our first Phase III trial in frontline multiple myeloma called CARTITUDE-5, and this is a Phase III open label study of cilta-cel. So we're comparing to an active control arm where the patients are being treated with standard of care RVD, Revlimid, Velcade, dexamethasone followed by RD or Revlimid maintenance therapy, and PFS is the endpoint. We're planning to enroll 650 patients in this Phase III trial in trona. This is actually the first Phase III trial for any BCMA targeting CAR-T in the study of monopole myeloma. As you know, it's not an easy path to manufacture cell therapy. So along with our partner, J&J, we have established 3 major facilities in U.S., in Europe and in China. In the U.S., we have a large-scale GMP operational facility already in Raritan, New Jersey, which is in the campus of Janssen Pharmaceuticals. This is where we have been supplying the clinical trial material for CARTITUDE program. And this will also serve as our launch facility for U.S., Europe and Japan pending FDA approval. In Europe, last year, J&J and Legend started construction already for the Ghent Belgium facility. And we're expecting the commercial production to start about 2 years from now. In China, we have on GMP operational facility in Nanjing, and that will serve as our clinical and also first launch site for Chinese market. At the same time, we're building a large-scale commercial manufacturing site in our new campus, this Building E as noted in this slide here. So this is our pipeline chart. Besides the BCMA CAR-T program, which is partnered with J&J, we're also working on a few other programs in both solid tumor indications and also hematology indications. The first one is an autologous CD4 targeting T-cell lymphoma program. We're conducting Phase I trial in China and also a Phase I trial here in the U.S. after FDA clearance of the IND. We're planning to go into the clinic this year. for a trispecific CD19, CD20, CD22 targeting autologous CARTITUDE-4 non-Hodgkin's lymphoma. Right now, we're also working on a couple of other programs in the allogeneic field, one targeting CD20 for NHL. The other one is targeting BCMA for myeloma. In the field of solid tumors, we're in the clinic for 2 programs. There's 1 Phase I ongoing for a CLDN18.2 targeting autologous CAR-T for gastric cancer. And then we're planning to file the IND for this program this year in the U.S. Also, we're conducting a Phase I trial for autologous CAR-T targeting mesothelin for the treatment of ovarian cancer. Meanwhile, we're planning to put into clinic trial for 2 other programs. One is the GPC3 targeting autonomous CAR-T for HCC and non-small cell lung cancer. The other one is a DLL3 targeting autologous CAR-T for small cell lung cancer. We're planning to file the IND for the DLL3 program in the U.S. by end of this year. We're also planning to file IND for the GPC3 program in China early next year. So that's the pipeline programs we're working on. And I hope to leave you with a message that Legend will continue to show growth. And also based on the promising clinical data we have generated in the BCMA program. And we are doing a very comprehensive global CARTITUDE program, along with our partner, Janssen, for the band of cilta-cel. At the same time, we're building a fully integrated platform with end-to-end R&D capability and also manufacturing capabilities with multiple core technology and platforms. and we're being led by a very experienced and strong management team here in the U.S. and also in China in drug discovery, development and also commercialization. With that, Cory, I'm happy to go into the Q&A format.

Perfect. All right. Great. Thank you, Ying. And as a reminder, to our listeners. If you want to submit questions, you can do so via the conference portal, and I can work them into the conversation. So I guess let's start first things first here with the upcoming PDUFA next month for CAR-T. Can you just kind of talk at a high level about the launch preparations that are underway and how much of this is the responsibility of Legend versus that of your partner, J&J?

So with that, I'm going to ask my colleague, Mike Hirschmann, who heads up our U.S. sales organization to talk about our launch readiness and also the responsibilities between the U.S. commercial team at Legend and the Janssen commercial team. Mike?

So thank you very much for that question. Thank you, Cory. So we are in a 50-50 partnership in collaboration with Janssen in the U.S. and that applies specifically to the commercial organization. We work lockstep with our great partners over at Janssen in all things, marketing and market preparation and actually down to the field level and field FTEs. So the way that's going to shake out is we are fully hired, trained and ready to go from a field perspective on the Legend side. We've negotiated and worked hard with our partner. We wanted to leverage their expertise and leadership in myeloma. We will be in the institutions, our MSLs, our nurses and our reps working from the commercial side, the medical side to pull through those patients that come into the centers for brand choice for cilta-cel. And Janssen will be leveraging its strength and experience in the community to help create awareness and drive those patients into the center. And they will be building their own CAR-T sales force as well.

Okay. And then once cilta-cel is available, how do you expect physicians to choose between commercially available BCMA targeted CAR-T products?

Between the ones that are available?

Yes. For CAR-T and ABECMA.

So look, I think we believe we have some unique advantages. One, certainly, if you've seen the data at ASH, it's a pretty compelling story. We believe, certainly, clinically, we win the day. And then I believe -- we also believe in our approach to how we're going to activate the market or optimize, bring the market in. And then thirdly, we think with our delayed CRS, it gives us some unique advantages for those hospitals that are entertaining or actually starting to use patients in a step-down outpatient approach.

Okay. And there's a couple of points in there that I do want to explore. I wouldn't be interested though in kind of your broad takeaways from the launch of ABECMA and how that's done in the marketplace and the potential read-through that might have to CAR-T?

So yes. So CAR-T is complicated. It's hard. We've always intended to potentially do a different approach. I think observing ABECMA as a first player. We learned a lot from watching that. So rather than go too big and bring open all the centers and then try to open the market, we're going to take a sequential approach. So we've done a lot of work in looking at sites around the country through an algorithm in the model where we're going to prioritize. And we're going to bring sites on over time throughout '22. First and foremost, we want to make sure we ensure that there's population densities that we can serve across the country. And by doing so and by being selective out of the gate, we can ensure that those sites who are brought on board have access to therapy. Because one of the challenges we hear from our KOLs and our providers is I need certainty. I need to know if I'm going to have a slot this month and next month and the month prior because I have lines of people I'm trying to prepare for therapy. So by going a little more lockstep over time, we can bring sites on ensuring that we can give them or commit to what we can give them over time. And then as we continue to expand throughout '22, we can bring on more sites successfully.

Okay. So that brings in a question from the portal that speaks to all of this, just from the other side of it. And can you talk about capacity evolution from quarter-to-quarter? And when will you have enough capacity to serve the full market?

With that, I'm going to refer to Ying to speak a little bit to the manufacturing capacity and certainly happy to chime in.

Sure. So Cory, I think when we talk about the capacity, there are probably 2 important components. One is the supply of lentiviral vector. The other one is the physical manufacturing capacity coming from the plant. So on those 2 aspects, Janssen and Legend have been working hand in hand very hard in the last couple of years to prepare for the launch. First of all, we foresaw there's a potential shortage of the lentiviral vector, given that there are so many companies working in the field of cell and gene therapy. And there are only about a handful of GMP-grade lentiviral providers in the market today as a CDMO. So we have make -- we have basically made a decision that we want to take that inside the partnership. In fact, J&J will be responsible for manufacturing the lentiviral vector for this product cilta-cel or CAR-T by training. And we have made that decision because we want to make sure that we will have a long-term stability and also reliability of the supply of lentivirus factor. So that's why we did that. And once FDA is approved, in fact, we will only use the lentiviral vector produced by J&J in our commercial launch. So that's a very important step and also an important decision made by the partners to ensure the long-term supply of that. And then secondly, with regard to the manufacturing capacity from our Raritan New Jersey side here. So back in 2018, when we started the construction, we already have designed a 3-stage process in order to reach that peak demand based on our internal forecast. As you recall, our friends at J&J did point out that we believe this is a product with a piece of at least USD 5 billion. So with that number in mind, we started construction and also the capacity expansion. So by now, we have already completed 2 stages of the manufacturing capacity expansion in the site. And we're embarking on the last, the Phase III of that expansion. So this year, 2022 will serve as our launch year or year 1. And obviously, we'll take a lot of effort this year to make sure by end of this year or early next year, we will be in a position to satisfy our demand in terms of the supply and also in terms of the manufacturing capacity. So that's our commitment. That's what we're working hard towards to.

Okay. And Mike brought up the topic of outpatient use. What do you guys think will take to enable outpatient use of CAR-T in the real world? And how might this impact reimbursement once it's a possible -- once it happens?

Yes. So Cory, I think the movement is already happening. There are large centers across the country that are trying to do this already. We hear multiple more than that who are planning and putting SOPs in place to do so. And it's for a number of reasons. One, there's throughput issues in these institutions. They have multiple CAR-Ts now coming into their centers. They have clinical CAR-Ts and other programs that are competing for resources on top of boomer transplant. So there is a need to try to take some pressure off internal institutional systems and resources. But additionally, while things have improved, certainly, most CAR-T administrators would tell you that reimbursement for CAR-Ts is still not there yet, still not optimal. And part of that resides around this DRG. So it's kind of a capitated system, right? So if a patient comes in and a staining institution, the cost for the drug and all the services are bundled into one. Medicare has a rule, the 3-day rule that if you discharge and they come back at some point after that, you can break it into a separate charge and also charge for the therapeutic under Medicare Part B. With our CRS having a delay from 7 to 10 days, that kind of puts us in a unique position that it gives these institutions an opportunity to discharge them, keep them local within a half hour away in certain lodging situations or situations that are created by the hospitals. Ronald McDonald House made an example. When they present with CRS, you bring them back in, it's a new case event and also you can charge for that therapeutic under an ASP [ .4, .5% ]. So it's better financially for the institutions. I think it's probably better for the patient should they have the right support system to do it, and it's taking pressure off the hospitals. So it's kind of already going. We didn't start this. We observed it happening. We just want to be there to support it should it happen.

Okay. That makes sense. And then when we think about the toxicity profile of cilta-cel, I guess kind of 2 questions on this front. One, Ying, can you remind us of the risk mitigation strategies you undertook to improve the overall tolerability here? And then secondly, your expectations on what we'll see as you continue to move into earlier treatment settings in terms of potentially less toxicity with less tumor burden?

Sure, Cory. So I'll ask Dr. Lida Pacaud, who heads up our clinical team here in the U.S. to answer about 2 questions. First of all, about the details how we instituted the risk mitigation strategy and CAR-T program. And then how we're seeing that showing up in the clinic in terms of the initial safety we're seeing from early lines, Lida?

Thank you for the question. So yes, as you have highlighted, so we have reported some type of new movement and recognition neurological adverse events in this program. And I think Legend and Janssen has reported this data in more granular manner, usually, other companies probably reported altogether, but we have provided more granular kind of type of immunotoxicity happen in these patients. So we have reported initially in our pivotal studies was 5 out of 97 patients treated. And then we have looked and analyzed what are risk factors and how we can mitigate. So factors like we have presented this data at ASH as well as factors like high tumor burden or severe neurotoxicity and also high CAR-T cell expansion are factors associated to this type of neurotoxicity. Then we have done extensive education and training like enhancing tumor burden was one of the factors of enhancing region therapy or implementing, for example, earlier management for CRS and neurotox with steroids and tocilizumab. And after education and increasing awareness of this we have treated 200 additional patients in this program in our -- including our earlier line studies, so CARTITUDE-4 and 5 and in this additional new 200 patients, we have seen a decrease also it's basically one case, which is less than 0.5%.

Okay. Terrific. Another portal question is, in a world where COVID is still impacting hospital utilization, how does that potentially impact the use of CAR-T?

So maybe on a high level, I'll start and then maybe Lida and Mike can add more to that. So first of all, if you look at our clinical program, Cory, right, within a very short -- really 1 year and 4 months. we were able to enroll more than 400 patients in the ongoing trial called CARTITUDE-4. So yes, of course, everyone is facing, unfortunately, the aftermath of COVID-19 outbreak. However, we were able to finish this event very quickly because we're trying to be strategic. We opened actually about 100 sites in about 28 countries for this CARTITUDE-4 trial. So whenever there's outbreak in certain geography, what we did is we try to go to the other countries which were less impacted to enroll those patients, right? So in terms of clinical trial, we're really not seeing much negative impact on our clinical trial enrollment, given the impressive clinical efficacy we have observed and also the fact that we are very strategic in terms of where to go in terms of enrollment. Now in real world use once the drug is approved. So maybe Mike or LIda, do you guys want to weigh in terms of what this COVID-19 outbreak could actually affect?

Sure, sure. So from a commercial standpoint, just from commercial activities, we've kind of retooled and become pretty proficient with virtual engagement with our customers. So this education and training still has to happen. We've really spent a good bit of time, money and resources kind of retooling our folks to understand how to engage virtually successfully, so from a promotional standpoint. I think from a patient perspective and an institution's perspective, what we're hearing, again, coming back to this outpatient piece, it may be a benefit of being able to keep the patients outside the institution after the infusion and having limited exposure to the actual institution itself. So there's 2 sides to that story, but that's what we're hearing from institutions.

Okay. And then, Ying, you mentioned how well CARTITUDE-4 accrued patients. How should we be thinking about time lines for that now that the trial is enrolled? And when is the earliest we may get a look at data when you consider things like interim analysis and things like that?

Yes. So Cory, that's a question on top of my many investors. I'll ask Lida to comment on that.

So yes, we have CARTITUDE-4. It's a Phase III randomized trial with 400 patients in population who received 1 to 3 prior lines of therapy. And so we have reported actually Cohort A data, as Ying mentioned, right, in exactly the same population, 20 patients. So this very promising high response rates. So there is high interest in this trial, and we completed recruitment in October. Now we cannot give specific guidance on timing of additive and driven trial, as you can imagine. But what I can say is the standard of care treatment like median treatment like 9, 10 months in this population. So 9, 10, months, there's a follow-up, which is needed also after we completed recruitment in October. So 9 to 10 months is probably a follow-up needed to see difference in treatment.

Okay. Interesting. So that could be something to look for later this year. When you think about earlier treatment lines with this product in particular, even when you look at like CARTITUDE-1 now out past 2 years, and Ying, you talked about the curves flat in there. Do you think it's possible to be talking about like actual cures and earlier treatment settings? I know it's a big word in cancer treatment. But I mean the data is pretty remarkable. Like how do you think about the impact it could have when you go even earlier?

So yes, of course, we would really like to secure in multiple myeloma, but in the last 10 or 15 years, right, in the field, multiple myeloma has always been deemed as incurable. So we're actually encouraged by that trend. And then one other anecdotal data point I want to point out here is that, Cory, if you look at the Phase I study, we conducted back in 2016. We enrolled a total of 74 patients. In fact, last November, we completed all the minimum 3-year follow-up for all the patients we could find from that Phase I trial. And we still have a very large portion of patients who remain in PFS. In fact, at the R&D Day in October last year, we did say this patient who has been now in PFS for more than 5 years. In fact, more than 5.5 years already by now. So can you say this patient has been functionally cured? Because he never received any follow-on treatment after that onetime treatment of cilta-cel. And yet, if you remember, he remains in complete response since then. And we do have a few examples like that in the Phase I. So that gives us the hope and that's why we believe cilta-cel could become the paradigm shift in treatment here in multiple myeloma. And then maybe, Lida, do you want to comment any further about how we think about that definition of functional cure and also what the other treatments we have done in the field compared to what we are seeing in cilta-cel?

Sure. Thanks. So yes, I guess, it's really, we hope, right? So the profile we see for cilta-cel is really exceptional. And I think not only in myeloma, in cancer care in general because as we reported in this later-line setting patients like [indiscernible] and later than that, like median PFS is still not reached. So it will be probably above years. So I think with a product like this, we, of course, have hoped like we can cure disease at the earlier stage. And that is reflected by our investment in Phase III trials in first front-line trial as well, which we have opened with Janssen.

Okay. We only have a few minutes left. I mean, I'd love to get beyond CAR-T. I guess as a segue to that, I'm just curious how much do you think the data for cilta-cel or CAR-T kind of validates Legend's platform and your approach to cell therapy overall?

Sure. So I think this is not just an extent of finding the fact that we're seeing a deep and durable responses in our trial for steel because our team spent 2 years actually screening and also optimizing those antibody fragments and then put them together in a stream design. So that's the same approach we are taking in our R&D programs, including our other allogeneic and also the solid tumor programs because we really pick [ pens ] in discovering and developing those antibody fragments. And we're really putting a lot of effort for those antibody binders here. So that's the approach we're taking. And we hope the same approach will bear fruition, right? For example, we do have a Phase I program in solid tumor in gastric cancer. And the initial data looks promising. And again, we believe the efficacy we're seeing in the clinic comes from the design of that binder. Also, I want to highlight that, Cory. We're putting into a clinic in the first half of this year for a trispecific program. So that's a CD19, CD20 and CD22 trispecific CAR-T. It's actually very difficult to design such a trispecific CAR-T. The reason is, once you have the second and the third antibody fragment in, every time that antibody binds with a target, it changes the confirmation of the other 2. That's why it's actually quite difficult in designing such a tries CAR-T. Yet our team actually put this into preclinical development. And so far in animal studies and everything else looks very promising. So we want to test that in human patients this year. So again, that's another example of the capability of Legends development in antibodies.

Okay. And we're down to under 1 minute. I want to get one question from the portal here. GPC3 CAR-Ts and GPC3 ADCs in the clinic have seen some modest activity in some cardiotox. Any comment on differentiation of your asset and expectation on efficacy and safety?

Sure. So I will answer that in 2 respects. First of all, of course, the fact that you do see some cardiovascular toxs. That means you have to be very cautious in designing the antibody, right, to make sure you have a therapeutic window and then to make sure you don't have any off-target bindings. So that comes out to a selection of the binder. That's one. And then secondly, I do think there's a very big difference between ADC or monoclonal antibodies and CAR-T because as you can see in the BCMA, right, the CAR-T is a direct killing effect compared to the monoclonal antibodies or [ vaccine ] antibodies. That's why we're seeing such a deep and durable response in the clinic because CAR-T works differently, right? It's not just binding with cancer. Instead, it's actually binding with the cancer and then, in fact, a direct killing of the cancer cells. So that's the difference between how the CAR T works versus how antibody or ADC works.

Okay. Perfect. Well, with that, we are out of time. Thank you guys very much. I appreciate you making the time for us as always.

Thank you so much.

Thank you, Cory.

Thanks.