Legend Biotech Corp - ADR Aktie

At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. asked a question during the session you will need to press star 1 1 on your telephone you would then hear an automated message advising your hand is raised withdraw your question, please press star 11 again. I would now like to turn the call over to Caroline Paul, Senior Director of Investor Relations. You may begin.

Good morning. This is Caroline Paul, Senior Director of Investor Relations at Legend Biotech. Thank you for joining us today to review our third quarter 2026 performance. Prior to this call, we issued a press release announcing our financial results, which can be found on the Legend Biotech Investor Relations website. Joining me on today's call are Ingrid Zhang, our Chief Executive Officer, Alan Bash, President of Carvykti, and Carlos Santos, Chief Financial Officer. Following the prepared remarks, we will open the call for Q&A. Yuhang Zhao, our interim head of R&D, will also join us for 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 herein.

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 an 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 income or loss and adjusted net income or loss per share enhances an investor's understanding of our financial performance. Our press release includes IFRS to non-IFRS reconciliations for these measures. With that, I will now turn the call over to Ingrid.

Thank you, Caroline, and good morning, everyone.

After reviewing our third quarter results, I'd like to share a few thoughts as this is my first earnings call as Legends CEO. Over the past several weeks, I have spent time with colleagues across the entire organization and engage with physicians and other stakeholders working to bring Carvykti to patients around the world. What has become clear to me is the strength of what Legend has built. Legend has demonstrated its ability to bring innovative cell therapy to market at meaningful scale through strong science, manufacturing excellence, and a deep focus on patients. This is incredibly difficult to accomplish and speaks to the foundation that exists that we can leverage for the rest of the pipeline. I've also been impressed by the quality of our people and the collaborative culture across the organization. Together, these strengths reinforce my confidence in Legend's future.

I joined Legend because I believe the opportunity ahead is significant. Carvykti continues to expand its impact for patients with multiple myeloma. Our pipeline provides an opportunity to extend our leadership in cell therapy for years to come. My priorities as CEO are clear. Number one, maximize Carvykti. Number two, advance our next generation pipeline. And number three, strengthen execution on all fronts to deliver sustained profitability. We enter this next chapter from a position of financial and commercial strength, with a differentiated asset that has extensive real-world results, an innovative platform, and the team focused on delivering for patients and external stakeholders.

With that, let me turn to our third quarter highlights. Slide seven, please. In the third quarter, Carvykti net trade sales increased approximately 36% year over year to 710 million. Growth was driven by continued adoption in the early line settings in the U.S. and new country launches, with net trade sales increasing 19% in the U.S. and 86% outside of the U.S. the U.S. on a year-over-year basis. We also continue to expand global patient access, reaching 373 active treatment sites globally. the quarter, we presented important long-term follow-up data from the CARTITUDE II cohort A study at the 2026 International Myeloma Society Annual Meeting, or IMS. These results further strengthen the growing body of evidence supporting the potential impact of Carvykti in earlier line multiple myeloma. We also received FDA clearance of our IND application for LB2501, an investigational in vivo CD19, CD20, dual targeting CAR-T therapy in relapsed or refractory B-cell malignancies, including B-cell non-Hodgkin lymphoma. This represents an important achievement step as we advance our next generation of cell therapy programs.

Slide eight, please. Turning to our IMS results. One of the most important data updates during the quarter came from a five year follow up analysis of CARTTITUDE2, cohort A in patients with relapsed or refractory multiple myeloma after one, two, three prior lines of therapy. The data demonstrated strong durability responses. Five years after single Carvykti infusion, half of the 20 patients from CARTITUDE 2, cohort A, remained alive and progression-free without further anti-myeloma treatment, compared with 33% in CARTITUDE 1. Five year overall survival was 69% compared with 51% respectively. Importantly, the safety profile remained consistent with the known profile of Carvykti, with no new CAR T-cell-related neurotoxicity reported during the extended follow-up period. Taken together, we believe these findings support the use of Carvykti in earlier line settings which may increase the likelihood of achieving durable treatment-free remission for patients living with multiple myeloma.

Earlier use of copy-to-tee was also reinforced by recent updates to NCCN guidelines, which Alan will explain in detail. As shown on the next slide, we continue to evaluate Carvykti in the CARTITUDE 5, CARTITUDE 6, and CARTITUDE 10 studies. These programs represent an important opportunity to evaluate Carvykti in frontline settings, including transplant-ineligible and transplant-eligible patients, and are central to our long-term strategy for that asset. Slide nine, please. Beyond Carvykti, we're advancing our in vivo CAR-T programs, along with additional programs across hematological malignancies and solid tumors. Slide 10, please. During the quarter, we achieved FDA clearance of IND for LB2501, representing an important step forward for our in vivo CAR-T platform. you might recall from our EHA presentation over the summer. Our NHL program, designed as a CD19, CD20, dual targeting therapy for relapsed or refractory B cell non-Hodgkin lymphoma. demonstrate compelling early data with a 100% ORR and 83% CR rate for six patients at dose level two. As you may have seen in the abstract for the upcoming American Society of Hematology Annual Meeting, We recently provided an update with 19 patients across three dose levels, compared to the 12 patients across two dose levels at EHA.

We are very pleased that LB2501 continues to demonstrate a favorable safety profile and encouraging efficacy. remarkable 100% ORR and 100% CR rates at dose level 2, with a median follow-up of nearly 5 months. We intend to share additional updates across dose levels at ASH. In terms of clinical development plans, the Phase Ia study for LB2501 is intended to confirm and further characterize dose selection in the U.S. clinical setting, based in part on insights from the ongoing IAT study in China. enabling the program to potentially transition quickly into Phase 1b. Phase 1B is planned to broaden the evaluation of LB2501 across multiple B-cell malignancies, including DLBCL, MCL, and CLL, as well as further inform patient selection. Following this, we intend to advance LB2501 into Phase II in appropriately selected patient populations to further characterize and confirm efficacy and safety. Regarding LB2505, our BCMA directed therapy for multiple myeloma, we do not have further updates to share at this time. remain focused on dosing patients as soon as possible. As a reminder, this program falls under the terms of our agreement with Janssen and Johnson pertaining to BCMA-directed CAR-T programs in multiple myeloma.

Overall, we are encouraged by the breadth of opportunities represented across our pipeline and remain focused on disciplined execution. Slide 11. Legend remains well positioned for long-term growth. Commercially, Carvykti remains leading CAR T therapy in multiple myeloma. by expanding global demand, early line adoption, and a growing body of long-term clinical evidence. Operationally, we ended the quarter with approximately 853 million in cash, cash equivalents, and time deposits, and remain focused on achieving company-wide profitability for full year 2026 on adjusted net income basis. Across our pipeline, we continue to advance our differentiated cell therapy programs, including our next-generation in vivo platform. Taken together, these strengths provide a solid foundation for sustainable long-term growth and value creation. With that, I will turn the call over to Alan Bash for a commercial update.

Thank you, Ingrid.

Carvicti continued to deliver solid global growth during the quarter. Net trade sales increased approximately 36 percent year-over-year to approximately $710 million, reflecting continued demand growth globally. In the United States, year-over-year growth was driven by ongoing adoption in earlier treatment settings and continued expansion of our authorized treatment network. Outside the U.S., growth was supported by launch execution across 20 markets worldwide and continued treatment site activation. Turning to the next slide, we want to provide an update on how we are accelerating growth through our earlier line momentum. Although we do not intend to break this out every quarter, we want to provide another update on the traction made in earlier line settings in the United States in recent months. This provides clear evidence that we are executing across our objectives.

As shown in teal on the far right, patients in the second and third lines represented 50% of Carvykti apheresis volume in the U.S. in the third quarter of 2026, which is a significant increase from the 41% in the first quarter of 2026 and 29% in the second quarter of 2026. in the first quarter of 2025. This trend reflects growing physician confidence in Carvicti's benefit-risk profile earlier in the disease course and our ability to reliably support that shift at scale. More broadly, we continue to see meaningful opportunities to expand market penetration as physician familiarity grows and as increasing numbers of eligible patients are referred earlier in their treatment journey, supported by the recent updates to the National Comprehensive Cancer Network guidelines. Turning to the recent updates. NCCN guideline updates from September. The guidelines state that all patients with myeloma should be referred to a T-cell therapy-capable center at the time of first relapse for consideration of available therapies, that when both BCMA CAR T and T-cell engagers are viable options, Current data suggests that CAR-T is preferred, given the established efficacy of TCEs following CAR-T cell therapy failure. And third, that prior BCMA-directed therapies should be minimized in patients planning to receive BCMA CAR-T cell therapy. We have been highlighting the updates in our recent discussions with physicians and other stakeholders involved in the development of clinical pathways and will continue to emphasize this new set of recommendations in the coming months.

In summary, we remain focused on operational execution, treatment center support and education, patient access, and ensuring that physicians and patients can benefit from Carvykti across the markets where it is available. With that, I will turn the call over to Carlos to walk through our financial performance.

Thank you, Alan. We have built a strong and scalable business model around Carvicti. Over the last several years, we have delivered revenue growth at a CAGR of 64% since 2023, while steadily improving operating efficiency across the organization. As revenue continues to scale, we are seeing increasing leverage throughout the business, reflected in improving operating margins and adjusted earnings performance. Importantly, we are making progress while we continue investing in our commercial execution, manufacturing network, and next-generation pipeline opportunities. While quarterly results may fluctuate, our focus remains on the long-term trajectory of the business. Based on the discipline with which we are managing our cost structure, we remain confident in our expectation of achieving company-wide profitability for the full year on an adjusted net income basis. Our financial performance this quarter reflects continued global demand for Carvykti.

This disciplined operating execution, and the benefits of increasing scale within the organization. Revenue growth continues to be the primary driver of financial performance, supported by ongoing expansion of Carvicti across geographies and treatment settings. Total revenue increased 32% year-over-year, driven by Carvicti demand and commercial expansion. We continue to manage our investment profile thoughtfully. We remain committed to advancing our pipeline and supporting long-term growth opportunities while maintaining a strong focus on operational efficiency. Moving down the income statement, gross margins performed much better than expected. improving to 58% compared to our expectation in the lower 50% range. The improvement is primarily due to manufacturing efficiencies.

Well, there is still likely to be some quarter-to-quarter variability in gross margin, we are revising our outlook for fourth-quarter gross margin on net product sales to be in the high 50% range for Q4. Research and development expense decreased 16% year over year. as the costs from the late stage BCMA frontline clinical studies roll off. This will be partially offset by increased spending on our in vivo assets as they move into phase one and later studies. Selling, general, and administrative expense decreased 20% and includes a 24 million one-time credit related to share-based compensation. Excluding this impact, SG&A would have increased by 8% year over year. Total operating expenses decreased 18% year over year, and similarly includes a 24 million one-time credit related to share-based compensation. Excluding this impact, operating expenses would have declined 6%.

As a result, excluding the impact of the one-time credit related to share-based compensation, operating margin improved to a positive 6% compared to a negative 16% in the third quarter of 2025. The result is a business that continues to demonstrate improving leverage as it grows. Although quarterly adjusted net income may vary from quarter to quarter over the near term, we are increasingly confident in the long-term durability of our profitability profile. Adjusted net income for Q3 was 55.6 million, representing 14 cents per diluted share on a non-IFRS basis. compared with an adjusted net loss of $18.7 million or a loss of 5 cents per diluted share in the same period last year. We view our balanced approach as critical to creating long-term shareholder value, investing where we see compelling opportunities while ensuring that revenue growth increasingly translates into earnings and cash generation over time. Our balance sheet remains an important strategic advantage. We ended the quarter with approximately 853 million in cash, cash equivalents, and time deposits, and no long-term debt, providing considerable flexibility to support both growth and innovation.

Our capital allocation priorities remain unchanged. We will continue investing in programs that have the potential to strengthen our leadership in cell therapy, including our in vivo CAR T platform. while remaining disciplined in how we deploy capital. Looking ahead, our expectations for the remainder of the year are centered on three key priorities. First, continuing to drive Carvykti growth globally as patient access expands and adoption continues to deepen. Second, advancing our pipeline and translating our innovation platform into future value-creating opportunities. And third, delivering on our goal of achieving company profitability in 2026 on an adjusted net income basis. Given the global growth we are seeing today, the expanding body of clinical evidence supporting earlier use of CARVICTI and the continued operational discipline across the organization, we believe we are on track to achieve company-wide profitability for the full year on an adjusted net income basis and we remain confident in the long-term outlook for the business.

Thank you, Carlos.

The third quarter was marked by continued execution across our business. We expanded global access to Carvicti, presented important long-term Carvicti data at IMS, and advanced our next-generation pipeline with FDA clearance of the LB2501 IND. We remain focused on executing our priorities and creating long-term value for patients and shareholders. Operator, we're now ready to begin the Q&A session. Thank you.

Ladies and gentlemen, as a reminder to ask the question, please press star 11 on your telephone, then wait for your name to be announced. To withdraw your question, please press star 11 again. Please stand by while we compile the Q&A roster. Our first question comes from the line of Terrence Flynn with Morgan Stanley. Your line is open.

Great. Thanks so much for taking the questions. I guess, obviously, Ash is coming up here. So, I just was wondering, on your 2501 program, if you can elaborate on how much more data we're going to see versus the abstract in terms of time of follow-up, and then any more details. on path to market here and then the other ash question is just there will be some updated data for a competitor BCMA CAR T when we see their data at ash what are you going to be most focused on thank you.

This is Alan. I'll answer the question about the competitor BCMA CAR T, but first let me turn it over to you, Hong, to speak to the 2501 data. Yes.

Thank you. Compared to what we're presenting in EHA, the ASH abstract showed an expanded patient experience. The sample size has increased from 12 to 19. As shown in the ASH abstract, as of June 28th, six patients were treated at dose level one, eight at dose level two, five at dose level three. OR and CR were 100% at dose level 2, and both the OR and CR were 60% at dose level 3. With a median follow-up of 4.8 months for all patients, no DLT, no ICANS, no non-ICANS neurotoxicity were reported. So the strong signal reported for DL2 at EHA has maintained and strengthened. So for the ASH presentation, we will have another data cut and the details will be available at the time of the conference.

And Terrence, this is Alan. Speaking to your question about the Anito-cel data, you know, we saw the abstract, and I think we remain very confident in the unique profile that Carvykti provides. We are the only BCMA CAR-T with five-year data, 15,000 patients treated, and we have demonstrated both in the later line setting and now in the early line setting based on the data that we presented at IMS, the potential for cure with CARVICTI based on a plateau of the curve and five-year long-term progression-free survival. We also note the fact that we have raised the efficacy bar in that fourth line setting based on a data set we presented at last year's ASH. which is that a 50-month PFS can be seen in our data sets across both CARTITUDE 1 and CARTITUDE 4. And on the safety front, I will note that I think we've made significant strides here in educating the community about the importance of bridging therapy to reduce tumor burden and reduce the risk of long-term or delayed neurodegenerative toxicities, and that has helped, I think, close this perceived gap based on what Anito-cel had previously shown. Finally, I'll just point out that I think it's important that as they do present their data, it's recognized that it's a limited data set. You know, you learn a lot about a therapy once you get into the real world. We treat more patients in a week than they've shown. in their entire program.

And I also think that these are two different, very different studies. When you look at CARTITUDE 1, we had a very heavily pretreated population, six median prior lines versus what the IMAGINE study shows. So I think the differences will become evident now during the abstract and also over time.

Thank you. Please stand by for our next question. Our next question comes from the line of John Miller with Evercore. Your line is open.

I was struck by the progress that you've made in driving Carvykti use into the earlier earlier lines of therapy in the US. It seems like you're really accelerating that with the NCCN guideline, but it doesn't seem to be translating directly to sales growth in the U.S. So my question is with more patients in earlier lines and better outcomes and and a strong motion to get those patients on Carvykti as early as possible. When will this translate into resumption of U.S. growth for the franchise? And then just to follow up on that 2501 question, understanding that there's going to be a new cut, data cut at ASH, you know, should we be expecting evidence? evidence of dose responsiveness continuing as we increase in dose-to-dose level 3, or is dose level 2 going to be the best efficacy that we're going to see?.

John, to your question about where we're focused, again, as you saw in the data, we've been strategically focused on the early line setting, and that has translated into more of our business coming from the second and third line. And as you referenced, the fact that we're now reporting that 50% of our mix is coming from second and third line. So we are gaining share in second and third line, despite the continued and I would say strong uptake of the bispecifics in earlier lines based on the approval of Tecvayli earlier this year. So this is becoming an increasing competitive space, both in the early line setting and the late line setting. But we do believe that based on the fact that, A, we are starting to see that migration of business towards earlier lines, the NCCN guidelines, which we are now educating the community on around the concept of car teaming. T first and the fact that earlier is better when it comes to BCMA CAR T in terms of efficacy, safety, manufacturing, really selecting patients. We are very confident that we'll continue to gain share in the early lines and that will ultimately translate into continued growth for the product.

Thank you. Would you like to take the second question about what we can disclose at ASH?.

In terms of. In terms of DLL3, DLL2. DLL3, just DLL3 and DLL2.

What else? 2501. I'm sorry. So for ASH, right, as shown in the abstract, we have dose level two have eight patients. All eight of them have shown 100% response rate, overall response rate, and complete response rate. For dose level three, we have five patients and overall response rate and complete response rate are all 60%. Please stand by for our next question.

I'm sorry, did you have a response?.

Go ahead, operator.

Our next question comes from the line of Jessica Fye with JP Morgan, your line is open.

Hey, guys. Good morning. Thanks for taking my question. I was wondering if you could just give us your latest estimate for when we could expect top line results for CARTITUDE 5 and for CARTITUDE 6. And maybe just following up on that last question or maybe last question. comment, Alan, about the increasing competitiveness in earlier lines with Tecvayli. It does seem well understood that BCMA CAR T works better before and not after BCMA bispecifics. Why do you guys think it's competitive there? Thanks.

Sure. So in terms of timing for our cohort five and cohort six, you know, as we've said before, these are event driven. And fortunately for patients, I think outcomes continue to improve for patients in the newly diagnosed space. So we need to wait for the events to accrue. You know, we previously said that the soonest that we would see a readout for card 5 would be in 2027 but again I would just point to the fact that these are event driven and we need to wait for events to accrue and then And CART 6 would be beyond that. Again, this is a space where there's a demonstrated based on the literature a long PFS. I think we've also, as we've discussed before, continue to explore the concept, especially with CART 6, of the potential for leveraging MRD data in support of trying to get an early read that correlates very well with long-term survival, both PFS and OS. In terms of your question about the competitive landscape, I think what we acknowledge is the fact that physicians have a choice here and that it's important that we continue to educate physicians on the concept exactly as you said, that CAR-T before bispecifics is really a better choice for patients because of the fact that it allows both options to be used.

The NCCN guidelines were very clear on this point that the data suggests that CAR-T before bispecifics provides a better outcome versus the other way around where you potentially foreclose or forestall the option to ultimately get to BCMA CAR T. So, you know, I think we're acknowledging the fact that there are choices out there, but again, I think we're very, very pleased with the NCCN guidelines validating this concept that CAR T CAR-T first is the best way to go for patients. And so we're doing everything we can along with our partner to educate both the community referral physicians, as well as the treaters in the authorized treatment centers around this concept that it's really not about which product you choose. It's really about the sequence in which you offer them. Thank you.

Thank you. Please stand by for our next question. Our next question comes from the line of Leonid Timashev with RBC. Your line is open.

thanks for taking my question. I know we talked a lot about the commercial dynamics, but I was just wondering if you could maybe dive into them a little deeper, if we can get any kind of quantitative sense of what you're expecting for the 2027 trajectory, just balancing all the competitive headwinds. the bispecifics, the competitor CAR-Ts against where you're seeing the growth coming from and how you're thinking about the picture for 2027 across U.S. and ex-U.S. Thanks.

Thank you, Leo. This is Carlos. I'll take the question and maybe Alan, you can then complement. As you know, we don't provide guidance, but what I can share is that we're still expecting substantial year over year growth on a global basis. And as Alan mentioned earlier, in the earlier line setting, Carvykti continues to gain share and momentum despite the fact of the faster uptake of bispecifics. So for Q4, We believe that the sales consensus is at the higher end of the range of scenarios that we're actually seeing. And this is primarily driven by changes in launch dynamics outside of the U.S. And as I mentioned earlier, a slower earlier line share growth in the U.S. than we had. previously anticipated.

So that is for Q4. Now, regarding the trajectory for 2027, We do expect to see double digit growth year over year for Carvykti in 27. However, the current net trade sales consensus for 2027 would be at the higher end of the scenarios that we're currently anticipating. And again, this is in light of the launch delays in the OUS markets and we're seeing a slower earlier line share growth in the US than we had initially anticipated. Having said this, we remain really very confident in the long-term growth outlook for Carvicti.

I know, Alan, if you want to add some color to this. I'll add simply that when we go out and educate physicians about the concept of referring patients or using CAR T in their second and third line patients, it's a longer term selling cycle, right? It's more education. We have to do more work to make sure make sure that the broad spectrum of physicians understand this data, that patients understand this data, and that, you know, that will take a bit of a longer time for patients to get in, to be, you know, get their consultation, to be evaluated. And so this is what we're doing with the work throughout both teams across J&J and Legend are doing. And we now have the tools to do that, especially with the NCCN data, with the earlier is better data that we've shown with CART4, with the bridging data from CART4. So I think we have the tools to be able to tell this story and educate the community. And I will say, and I'll remind you that despite the increase increasing competitive nature of the space.

Only between 15 and 20% of patients in the second and third lines have been BCMA exposed, right? So that means that we still have up to 85%, between 80 and 85% of the patients in those early lines who have not been exposed. exposed to BCMA and that represents opportunity for us to continue to grow long-term and that's why we do believe that we will continue to grow this business and continue to achieve the potential of it which is a $5 billion plus potential.

Thank you. Our next question comes from the line of Edson Derouard with Barclays. Your line is open.

Great. Thanks for taking the question. A couple from me. I guess the first one, the second line, third line shift you're seeing, do you have expectations that maybe starting in the fourth quarter you can see incremental patients there versus primarily replacing later line volumes? maybe are those expectations maybe more for 2027 dynamic? That's one. And then maybe a point of clarification because I didn't hear the answer clearly, but will we see additional follow-up in the DL3 cohort dataset for 2501 at ASH? Thank you.

We are continuing to grow in the second line and third line. And so that's been ongoing and we'll continue to see that throughout the rest of this year and into early next year and beyond.

In terms of the DL3 and 2501, we will see additional updated data in ASH.

Thank you. Thank you. Our next question comes from the line of Edward Tenthoff with Piper Sandler. Your line is open.

Thank you very much for taking the question. I'm curious as we look forward with the IO candidate 2501, what are your plans to develop this in autoimmune disease beyond B-cell lymphoma. And is this the right candidate or is there potentially another IO candidate that you would anticipate developing in autoimmune disease? Thanks so much.

Yes, we are exploring all the options. We're very interested in autoimmune diseases using our in vivo platform and of course, 2501 is one of the candidates we're exploring.

Great. And what are the plans to advance it forward? Thank you. What are the plans to advance it forward?.

Well, as Legend, as a leading cell therapy company, right, we have our capabilities to doing IITs in China. So the first step we're going to do to explore anything would be to conduct IIT study to achieve early proof of concept.

Great. That makes a lot of sense. Thanks very much. Thank you. Please stand by for our next question.

Our next question comes from the line of Linhai Xiao with Goldman Sachs. Your line is open.

Thanks for taking my question. This is Linhai from Goldman. Just want to follow up on the second or third line dynamics. So more particularly, given that in 3Q, we saw that US sales going flat quarter over quarter, but we continue to see the continued shift in the pie chart where we see increasing patients in the earlier line versus the later line. So can you help us to understand the more colors regarding the overall market demand for Carvykti and also the quarterly timing, manufacturing allocation, and to understand the US growth momentum. And in addition to that, would you be concerned about the increasing earlier line TCE penetrations would make the patients ineligible for late line for TCE? for BCMA CAR T's. Thank you. Yes, I think we've addressed some of these points, but let me just make you know just add a couple of points here again.

continue to gain share and grow the business in the second and third line. And that's important because that really represents the best place for Carvykti, especially as we think about a late line entrance coming into the market. You know, the late line space is one where more patients, as you referenced, have been and will continue to be BCMA exposed. You have patients who are perhaps older, more frail, less willing to travel. And so it becomes, you know, I think the more favorable place for BCMA CAR T is in fact the place where we are indicated, which is in the middle. the early lines. And so we will continue to emphasize the value of CAR T first, that earlier is better, and that our best place is in second and third line, or as we also call it, at first relapse for patients. I think that really speaks to where we are strategically focused and where we believe we can continue to grow. this business.

And again, I think there will continue to be competition. We see not only from the approved bispecifics, but there are additional bispecifics coming onto the market. So yes, this marketplace will continue to become increasingly competitive. Yes, no, thank you, Alan. I would just add that.

you know, we at Legend are very confident, you know, ability to reach 5 billion plus peak potential, really driven by penetration into earlier lines. We talked a lot about second and third line. There's also the front line study, which of course we're waiting for the events to read out. Continue the extension of our global footprint. And lastly, about bringing Carvykti closer to patients. I think we do this well. We're very confident on the future of this franchise.

Thank you.

Thank you. Please stand by for our next question. Our next question comes from the line of Yvon Weber with TD Cowen. Your line is open.

Great, thanks so much. Maybe a quick question on 2505. Maybe can you give us a little bit of a sense, how fast can you start that study, that phase one in myeloma in China? And then secondly, to advance into an IND in the US, do you need the green light from J&J to actually do so, aligned with your agreement. Thank you.

Yes, with regard to the IAT, as we discussed previously, we are working to have the study started very soon. Regarding the IND, as a reminder, this LB2501 is subject to the collaboration agreement between Legend Biotech and Johnson & Johnson, and we will not be able to disclose more at this point.

when the time comes, we'll share more. comment whether J&J has officially opted in or that hasn't happened at this point. Thank you.

We're not going to say anything more at this point. When the time is right, we're going to share more.

Thank you. Our next question comes from the line of Costa Bularis with Opco. Your line is open.

Hi, thank you for taking our questions. This is Joe Thomas on for Costas. I'm just taking into the international growth that I'm curious if you give us some more color on if the growth reflected underlying demand at established centers or what mix was in new launches or new reimbursement agreements and looking forward as tech era begins to come into begins to expand internationally? What gives you confidence that ex-U.S. growth is going to remain a durable offset to any potential headwind in the U.S.? Thank you.

Yes, so as you saw from our disclosures, we are now in 20 markets worldwide. And the growth that you're seeing in the ex-US markets is really driven by both the combination of new markets launching, but also continued growth in markets such as Germany, Spain, and more recently, one of the big contributors, is Italy. So I think these markets are doing very well. We also see even some of the smaller European markets, Belgium, Denmark, Switzerland. These are all markets that are really starting to emerge as growth contributors in the full global picture. I think to your question about as bispecifics enter Europe, it's obviously going to be a dynamic we're going to watch, but we do believe that there are a couple of really favorable dynamics in Europe that support CAR T. One is the geography. Obviously it's easier for patients to get to some of the larger academic centers and get to the authorized treatment centers.

And those referral patterns and those patterns are pretty well established in many, especially the smaller markets around Europe. And the second point is that the single payer system really does provide this concept that the government is looking at the long term value of a one-time infusion. The one-time infusion is really cost effective, and that's a story that really helps, I think, improve all of our support for reimbursement and education and uptake across some of these key markets. So we do expect that the OUS contribution towards the global picture will continue to grow. and we do believe that that's going to be a significant driver of growth as we reach towards the 5 billion plus potential for this product.

Thank you. Our next question comes from the line of Mitchell Kapoor with HC Wainwright. Your line is open.

Hi, this is Amit on for Mitchell. Thank you for taking our question. Congrats on a strong quarter. So two for me, one on Carvykti and one on 2501. So for Carvykti, within the community, are you seeing the incremental patients coming from physicians making their first Carvykti referral or from existing referrers sending more eligible patients. And for 2501, so we've seen dose-dependent CAR T expansion. And so when you move into U.S. development, are there any particular T cell characteristics, baseline characteristics, or prior therapies that you're watching as predictors of T cell fitness and adequate expansion?.

Thank you. We're seeing both existing referrals as well as new physicians deciding to send their patients for consult and referral. And this has really been part of our educational effort to say, if you have a patient who's eligible, even before they are relapsed, to really start to think about plan out their treatment journey. And so part of that education is around sending patients for consult, sending patients ultimately for referral. And so we're seeing both the growth in the number of referrers and the number of patients that are being referred.

Okay, for 2501, from the IET study, what we have observed is that expanded CAR T cells were predominantly CD8 positive effector memory cells with limited terminal differentiation and exhaustion-associated transcriptional signature in the samples that we analyzed. In the IND study, of course, we'll continue with our translational analysis and keep a close eye on the phenotypes of the T cells that we observe. Thank you.

Please stand by for our next question. Our next question comes from the line of Natalie McArthur with UBS. Your line is open.

Hi there, this is Natalie on for Ash. Thanks for taking our question. We're just wondering how representative is the CARTITUDE 5 trial control arm of real world patients and current treatment patterns? And then how should we be thinking about efficacy benchmarks here as well? Thanks.

Yes, your reference to the CART5 control arm, which is VRD, we do see that this is an adequate control arm and an appropriate control arm, and obviously one we consulted with the FDA on. Having said that, I think you're probably alluding to the fact that more and more patients are getting quad therapy up front, DVRD. And so we will also plan to support and supplement that filing with data that shows a benefit from a DVRD population as well. You know, I think the important thing about Cartitude 5 is that there are, you know, about three quarters of the newly diagnosed patients are transplant ineligible or transplant. deferred. And so I think as transplant becomes less of an option that patients want to go through, we do believe that CART5 will be a meaningful data set versus an appropriate control arm.

Thank you. Our next question comes from the line of Jacob Horwitz with Raymond James. Your line is open.

Hi, guys. Thanks for the question. This is Jacob on for Sean McCutcheon. We're curious about whether you can speak to the driver of the thresholding effect that you're seeing from DL1 to DL2 with 2501, specifically seeing much higher responses in DL2. And we're curious if you anticipate a meaningful addition of activity at higher doses moving forward.

Yes, so look, we're still very early in the in vivo study and from what we can see, it seems there's a threshold in terms of response. That's why we see nothing in DL1 and we see 100% in DL2. And what we can find later on whether we can continue to see those response, we have to wait for additional patients in those and follow for longer for those. follow-up to get a better understanding on the relationship between dose, CAR T expansion, and response. Okay, great. Thanks.

Thank you. Ladies and gentlemen, I'm sure no further questions in the queue. concludes today's conference call. Thank you for your participation. You may now disconnect.

This live transcript is auto-generated without human intervention or review.

[Call has ended.]

This live transcript is auto-generated without human intervention or review.

Good day, everyone, and thank you for standing by. Welcome to Legend Biotech Second Quarter 2026 Earnings Call. [Operator Instructions] Please be advised that today's conference is being recorded.

Now it's my pleasure to hand the conference to Caroline Paul, Director of Investor Relations. Please go ahead.

Good morning. This is Caroline Paul, Director of Investor Relations at Legend Biotech. Thank you for joining our conference call today to review our second quarter 2026 performance. Prior to this call, we issued a press release announcing our financial results for the quarter, which can be found on the Legend Biotech Investor Relations website. Joining me on today's call are Alan Bash, the company's Interim Chief Executive Officer; 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 Interim Head of R&D, Yuhong Qiu, 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 equivalents. 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. Our press release includes IFRS to non-IFRS reconciliations for these measures.

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

Thank you, Caroline, and good morning, everyone. I want to start by briefly addressing the leadership transition announced last month. As you all know, Dr. Ying Huang stepped down as Chief Executive Officer and member of the Board, and the Board appointed me to serve as Interim Chief Executive Officer. On behalf of the Board and all our employees, I want to thank Ying for his leadership over many years and his many contributions to Legend Biotech. We want to be very clear. This is a leadership transition, not a strategy transition. Our priorities remain unchanged.

We remain focused on 3 main objectives: maximizing CARVYKTI, advancing our next-generation pipeline and strengthening our execution on all fronts. My commitment is to provide continuity, transparency and disciplined execution, working closely with Carlos, our senior R&D team, the Board and the broader leadership team to maintain momentum across the business. We are operating from a strong foundation with continued CARVYKTI momentum, meaningful progress across our in vivo CAR-T platform and as you are about to see from the Q2 results, the financial flexibility to continue investing in growth, innovation and long-term value creation. Notably, during the second quarter, we generated adjusted net income of $63 million, and we believe we will maintain adjusted net income profitability for the second half of 2026.

Now let's turn to our second quarter highlights. We had a strong second quarter at Legend as CARVYKTI continues to expand globally, maintaining its market leadership in CAR-T. Additionally, we recently presented compelling early efficacy and safety data from our in vivo CAR-T platform and plan to provide meaningful updates to these programs at future medical conferences. During the quarter, CARVYKTI delivered worldwide net trade sales of approximately $657 million, representing 50% year-over-year growth, driven by strong demand globally and increasing adoption in earlier lines of therapy. In the United States, sales increased 32% year-over-year, while ex U.S. sales grew 128% year-over-year.

Beyond commercial execution, we continue to advance our innovative next-generation cell therapy pipeline, particularly in our in vivo CAR-T platform, as highlighted by our participation at the ASCO Annual Meeting and the European Hematology Association Congress. We will turn to these updates in just a moment. Finally, we strengthened our balance sheet through the successful completion of a public equity offering, resulting in approximately $212 million of net proceeds and a cash position of approximately $965 million at the end of the second quarter.

Drilling deeper on CARVYKTI's second quarter performance, CARVYKTI global net trade sales increased 50% year-over-year to $657 million, delivering strong global sequential growth of 10% compared to the first quarter. In the United States, quarter-over-quarter growth of 9% was primarily driven by accelerating adoption in earlier lines of therapy. We continue to increase the usage in second and third lines, up from the 41% we discussed last quarter. We have also been expanding treatment access with more than 150 authorized treatment centers, of which approximately 40% are community hospitals.

Outside the United States, quarter-over-quarter growth of 13% was primarily driven by continued launch uptake across 19 markets and expansion of the activated treatment site network. We recently launched CARVYKTI in Ireland, further expanding availability to 348 global treatment sites, reflecting continued geographic expansion with our partner, J&J. Across geographies, we continue to see encouraging trends in both market penetration and earlier line utilization. These dynamics support our belief that CARVYKTI remains a durable growth opportunity.

Turning to our recent clinical data, we shared encouraging updates across both our solid tumor and multiple myeloma programs at ASCO this year. LB2102 is our DLL3 targeted CAR-T therapy being evaluated in small cell lung cancer and large cell neuroendocrine carcinoma. LB2102 demonstrated a manageable safety profile and encouraging clinical activity in a heavily pretreated patient population. Higher dose levels achieved an objective response rate of 28.6% and a disease control rate of 78.6% with durable responses observed. Solid tumors remain difficult to treat with limited therapeutic options. So this is an encouraging sign. 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.

We also reported additional CARTITUDE program data supporting the durable efficacy and consistent safety profile of CARVYKTI in multiple myeloma. These data included sustained progression-free and overall survival benefit across cytogenetic risk groups, along with a low incidence of immune effector cell-associated enterocolitis. Notably, in the CARTITUDE-4 subgroup analysis, patients who responded to bridging therapy demonstrated 30-month overall survival rates exceeding 85% with no cases of IEC-associated Parkinsonism. Taken together, these presentations further reinforce both the strength of the CARVYKTI clinical profile and the breadth of our innovation pipeline.

The most notable recent pipeline update was our Phase I LB2501 study with data presented at the European Hematology Association Congress in June. LB2501 is a CD19/CD20 dual-targeting in vivo CAR-T therapy for the treatment of relapsed/refractory non-Hodgkin's lymphoma. The new results were the first human data with our in vivo platform and from an ongoing dose escalation Phase I study. The data presented at EHA included 12 patients with 6 patients in each of the 2 dose cohorts as part of an investigator-initiated trial conducted in China.

We had compelling results at dose level 2, achieving a 100% objective response rate and an 83.3% complete response rate across the 6 patients with diffuse large B-cell lymphoma, mantle cell lymphoma and follicular lymphoma. We also observed impressive in vivo CAR T cell persistence in peripheral blood with cells detectable up to 116 days based on these early results. From a safety perspective, LB2501 was well tolerated with no dose-limiting toxicities, no serious adverse events and no deaths reported. We anticipate filing a U.S. IND for LB2501 by the end of the year to initiate a U.S.-based clinical program in NHL and plan to report additional data from the China study in due course. These results represent an important milestone for our entire in vivo CAR-T platform, which has broad applicability and includes other candidates with other targets in additional indications and supports our continued investment and development of candidates using our in vivo platform.

Beyond LB2501, we continue to advance a broad and diversified pipeline spanning autologous, allogeneic and in vivo cell therapies. As it relates to CARVYKTI, multiple frontline multiple myeloma studies remain ongoing, including CARTITUDE-5, CARTITUDE-6 as well as others, which could potentially expand our market opportunity into the first-line setting. Across our autologous portfolio, we continue to develop therapies targeting Claudin 18.2, DLL3, GPRC5D and dual target approaches for multiple myeloma. We are also advancing several off-the-shelf CAR-T programs ranging from allogeneic programs for autoimmune disease and B-cell malignancies as well as additional in vivo CAR-T candidates beyond LB2501, which I just described for its impressive first human data in a Phase I trial at EHA. Overall, we believe this portfolio reflects a balanced approach to innovation across the different modalities of CAR-T while leveraging our expertise in cell therapy, development and manufacturing.

Looking ahead, we believe Legend is well positioned for sustainable long-term growth. We continue to advance our pipeline and are working towards an IND submission for LB2501 by the end of the year. We ended the period with approximately $965 million in cash, cash equivalents and time deposits. And commercially, CARVYKTI remains a leading franchise in multiple myeloma and continues to demonstrate strong global momentum, expanding into new markets on a regular basis. We also continue to believe CARVYKTI has a peak annual sales potential exceeding $5 billion, and we are making meaningful steps to reach that goal. Supported by a durable commercial business, a deep pipeline and a focus on execution, we remain committed to achieving company-wide profitability in 2026.

And with that, I will turn over the call to Carlos.

Thank you, Alan. This quarter's financial results continue to demonstrate the operating leverage inherent in our business model. Revenue has scaled at a CAGR of 74% since the second quarter of 2023, supported by growing demand for CARVYKTI and continued commercial execution. At the same time, operating margins have improved significantly from negative 142% in the second quarter of 2023 to a positive 15% in the second quarter of 2026. This now marks a major milestone objective for Legend as the first quarter of company-wide profitability on both an IFRS and an adjusted basis. Going forward, we will continue to focus on adjusted net income as the metric for sustained profitability. While we remain focused on investing in the future growth of Legend, we are doing so with increasing discipline and operating efficiency.

Turning to our quarterly financial performance. Total revenue increased 52% year-over-year, driven by continued CARVYKTI demand and commercial expansion. Given the recent increases in international sales, we wanted to note that we are using Legend's foreign exchange rates for CARVYKTI collaboration revenue, which we also plan to use going forward. Each quarter, Legend receives the collaboration revenue through a profit split analysis in U.S. dollars as constant currency.

From an accounting perspective, the revenue is then converted to the appropriate functional currency using Legend's foreign exchange rates, which may differ from our partners. While we expect the differences each quarter to be small over the near term, we wanted to specifically call it out this quarter as international sales are becoming an increasing percentage of the overall revenue and in any given quarter, an increase in international revenue and/or a significant movement in foreign exchange rates between the euro and the U.S. dollar could result in additional divergence between the revenues reported by our collaboration partner and the revenue that Legend reports.

As we look at collaboration revenue growth for the remainder of the year, we wanted to offer some thoughts on quarterly progression in Q3 and Q4. As we have been consistently saying, we are pleased with the steady increasing rate of CARVYKTI penetration into the second to the fourth lines of treatment, which is our focus and has now grown to be over 70% of our volume. With the increasing penetration into earlier lines has also come increasing usage in the outpatient setting and with a higher percentage of outpatient volume contributing to the revenue mix comes a different set of gross margin dynamics. Additionally, we expect to see an increase in Q4 revenue from an extra selling week in this calendar year and greater international expansion compared to Q3. Despite these fluctuations, we remain confident in our adjusted net income profitability projections for both Q3 and Q4.

Moving down the income statement. Gross margin on net product sales grew 1% year-over-year improving to 58%, which was an improvement of 17% compared with 41% for the first quarter of 2026, which, as you may recall, was artificially low primarily due to onetime costs associated with manufacturing expansion, which we unwound in the second quarter, adding additional onetime favorability of a few percentage points to our Q2 gross margin. Going forward, gross margin on net product sales will be more reflective of volume as we continue to expect improvements over time by leveraging our investments in manufacturing to scale and increasing utilization across all nodes. However, it is important to realize that there is still likely to be quarter-to-quarter variability in gross margin, and we expect Q3 gross margin on net product sales to be in the lower 50% range with a rebound into the mid-50% range anticipated for Q4.

Total operating expenses increased only 7% year-over-year, reflecting our continued focus on disciplined investment and operating leverage. Research and development expenses decreased 2% year-over-year as the costs from the later-stage BCMA frontline clinical studies roll off. This will be partially offset by increased spending in our in vivo assets as they move into Phase I and later studies. Selling, general and administrative expenses increased 19%, primarily driven by investments supporting sustained leadership in BCMA CAR-T markets.

As a result, operating margin improved to a positive 15% compared with negative 9% in the second quarter of 2025. Regarding taxes, we had an income tax expense of $22.3 million during the second quarter compared to an income tax expense of approximately $600,000 for the same quarter last year. The year-over-year increase was primarily driven by an increase in taxable income across our U.S., Belgium and PRC entities. As we have now achieved company-wide profitability on a quarterly basis for the first time, I wanted to provide more detail on our tax rate and the effect of various tax jurisdictions as you develop your longer-term financial models.

We are in the process of negotiating a unilateral advanced pricing agreement with the Chinese tax authorities as part of our proactive tax governance strategy. Although a formal agreement has not yet been formally executed, we have now reflected the expected impact of the agreement as a component of income tax expense in our Q2 numbers. We expect to report income tax in each quarter that we are profitable. And although we are not yet at a point that we can provide more precise guidance, we anticipate a tax rate in the high 20% range over the next several quarters.

In addition, although quarterly adjusted net income may vary from quarter-to-quarter over the near term, primarily driven by some expected fluctuations in gross margins I mentioned earlier, we are increasingly confident in the long-term durability of our profitability profile. With adjusted net income of $650 million in Q2, we feel comfortable in maintaining our projection for adjusted net income profitability on an adjusted basis in 2026. On a non-IFRS basis, this represents $0.16 per diluted share compared with adjusted net income of $10 million or $0.03 per diluted share in the same period last year.

Turning to our balance sheet, which remains a significant strategic asset. As of June 30, 2026, we held approximately $965 million in cash, cash equivalents and time deposits and have no long-term debt. The equity offering in June contributed meaningfully to this strong cash position, allowing for additional flexibility to fund our pipeline programs and pay down our loan to Johnson & Johnson under the terms of our agreement. Our investment priorities have remained consistent, and our strategy has not changed. We remain committed to delivering sustainable profitability on adjusted net income while still advancing our in vivo CAR-T pipeline and making modest capital investments to support manufacturing capacity expansion.

Our key objectives include: first, continued quarter-over-quarter CARVYKTI growth through 2026 with a growing portion of our business coming from second to fourth-line patients. Second, adjusted net income profitability for the second half of 2026. Third, an IND submission for LB2501 in Q4 and lastly, presenting additional in vivo data at future medical conferences. We believe our strong financial position provides the flexibility needed to execute on all of these priorities. Let me end in the same way that Alan started this call. This is a period of leadership transition and not strategy transition. Our Q2 financial results support this. And you can expect that this leadership team will continue to deliver on the clear objectives that we just laid out and to provide transparency for the investment community as we move into the second half of 2026.

With that, I will turn the call back to the operator to open the line for questions.

[Operator Instructions] It comes from Eric Schmidth with Cantor.

Congrats on achieving the milestone of profitability. My question is on the in vivo CAR-T side and the BCMA program in particular. I think Alan mentioned you're working on a variety of different targets. So I assume that's still one of them. Can you provide for us kind of an update on your strategy with your partner, J&J and when we may hear something in addition on BCMA?

Thanks, Eric, for the question. Yes, previously, we had said that BCMA CAR-T programs were subject to the terms of Legend Biotech's collaboration agreement with J&J and previously, we cannot say more. We can now share an update that Legend will be conducting an investigator-initiated clinical study in China. Evaluating LB2505, which is an investigational BCMA-targeted in vivo CAR-T therapy for multiple myeloma. This program is subject to terms of Legend Biotech's collaboration agreement with J&J. So we're not able to share additional details at this time, but we do look forward to providing updates on LB2505 when appropriate.

[Operator Instructions] It comes from Terence Flynn with Morgan Stanley.

Great. This is Chris on for Terence. On LB2501, can you remind us of what the minimum duration of response you think is needed to be confident in the durability of a complete response? And is ASH a reasonable expectation for when you could release the updated Phase I data?

Yes. Previously, at the EHA conference, we had shared durability as long as 120 days. We would be targeting ultimately to be able to share data at the 6-month CR rate. And we will be able to provide updates at future medical conferences in terms of the 2501 program.

One moment for our next question that comes from John Miller with Evercore ISI.

This is [indiscernible] on for Jon. I wanted to touch on the recent announcement for the MonumenTAL-6 top line data where we saw a hazard ratio of 0.11. This seems like physicians are gradually getting comfortable with anticipating and managing the tox in the study. And there are also some commentary that on the GPRC5?

I'm sorry.

Hello? Yes, can you hear me?

Your line isn't coming in as clearly, if you could just repeat the question, please.

Yes. So I would like to ask a question on the recent announcement for the MonumenTAL-6 top line data. So it seems like physicians are gradually getting comfortable with managing and anticipating the tox in the study. And then there are also some commentary that the combo might be preferentially sequenced for later line usage. So I'd like to ask what kind of feedback have you been hearing from physicians on your end in terms of managing the tox and the sequencing that relative to CAR-T?

Yes. Thanks for the question. So yes, the MonumenTAL study was looking at the combination of TEC and TAL and as J&J has shared publicly, they intend for that combination to be primarily used in later lines, as you point out. I think more generally, as we've seen the bispecific data and indications emerge, we've been very focused on educating physicians and patients on the key points of differentiation of CARVYKTI relative to other options in myeloma, in particular, other BCMA options. Of course, one is that one and done, right, versus continuous therapy. That's a very important driver of patient preference, of quality of life and of the opportunity for a long-term treatment-free interval and a long-term remission.

The second thing that we've been really emphasizing relative to the landscape is that the data really suggests that earlier is better with CAR-T. You get better efficacy, better safety and improved manufacturing when you get CAR-T earlier and really where the conversation has gone is not really about CARVYKTI versus bispecific. It's really about the sequencing. And I think if you hear KOLs and the feedback we've been getting from KOLs, the storyline is really about the optimal sequencing and the data, both in the real world as well as additional studies or if you look at the biology, it really does point to the fact that patients will benefit if they can get to CAR-T first before other options in BCMA.

Our next question is from Leonid Timashev with RBC.

I just wanted to clarify some of the comments on the gross margins. Can you maybe just elaborate on why having more outpatients is going to change the gross margin dynamics? And then looking ahead, I think in the past, you've talked about aiming for large molecule like cost of goods. Is that still the plan here? Any sense of when you might achieve that with some of these CapEx -- modest CapEx spend plans?

Yes. Thanks for the question. All we would say at this point is that as outpatient grows and outpatient is starting to become approximately 60% of our overall mix. It does come with various dynamics, which could potentially impact gross margin. So that's all we're able to say at this point on that. But let me turn it to Carlos to your second question.

Yes. So Leonid, in terms of the path for gross margin, we are still expecting our cost of goods sold to decline over time. We have to get to a certain level of volume to keep up the consistency. But once all of our nodes are at a steady state, our gross margins will be in line with what we believe is industry standards of around 75%. And we actually have -- we see a clear path to 75% over time.

One moment for our next question that comes from Jessica Fye with JPMorgan.

I had 2 kind of on the financial side. First, can you just expand a little bit on the comments you made about how to think about the revenue cadence in 3Q and 4Q? And second, can you just recap the motivation behind the recent equity raise given that the company is still very committed to achieving profitability this year?

Let me start with talking about the raise. The follow-on was an opportunistic equity raise following the strong in vivo data that we presented at EHA. This additional capital really gives us greater flexibility to accelerate the development of LB2501 and our broader in vivo platform. This really allows us to be able to take our in vivo platform further in the development process, and this will provide us better BD optionality down the road. We continue to be confident in our profitability goals, and we will be in a stronger position to fund our R&D efforts following the loan repayment to J&J now that we have completed this raise.

And related to your first question, as we heard earlier in the call from Carlos, we are indicating a global growth on a sequential basis across the balance of the 2 quarters in the second half of 2026.

Our next question comes from Yaron Werber with TD Cowen.

Congrats on moving towards the IIT with in vivo in China. I have maybe just a 2-part question on the tax rate in China. That would be applied, it sounds like to the global profits from now on. Is that actually going to be a cash payment? Or is that an accounting tax rate? And then secondly, just to answer your answer to Jessica's question on the raise, and you said that the payment after the payment to J&J, can you just clarify, is that relating to historical CapEx and how big that is?

Sorry, Yaron, could you repeat your second question?

I think you mentioned that there was a -- I might have misunderstood a payment to J&J when you were talking about the financing. I just wanted to make sure, is there any historical sort of cell balance sheet cleanup that you need to do as part of CapEx? Or did you never actually borrow capital from J&J for building manufacturing facilities that's still outstanding?

Yes. So let me start there. So as part of our collaboration agreement, there was a loan of around $300 million and that accrued interest over time that became a current liability this year. So we have been paying down both principal and interest on that loan this year. And it's a combination of cash repayments to J&J as well as recoupment of profits from our collaboration. We expect to fully settle that liability this year. So with regards to the tax provision, we have reflected the expected impact of an agreement based on the information we have today as a component of our income tax expense in Q2. So this provision not only includes the China portion, but also profitability that's realized in other legal entities for Legend.

One moment for our next question that comes from Kostas Biliouris with Oppenheimer.

Maybe a couple of quick questions. One on the CEO search. We are wondering whether the Board is focused on a commercial operator for the CARVYKTI ramp or perhaps a platform CEO for the in vivo CAR-T development? And the second question is on the in vivo CAR-T development and commercialization. You already touched a little bit on the BCMA, but we are wondering how are you thinking about perhaps the lead program in NHL? Are you thinking to develop this by yourself? Or are you still looking for a partnership there? What is the latest status?

Thanks, Kostas. Yes. So as we previously announced, the Board has initiated a search and is conducting a thorough process for the full-time permanent CEO position. And I don't think the Board wants to put an artificial deadline on that process. They're also looking holistically and looking at various qualities that would provide for the best long-term leader given the stage of the growth of the company. So I don't think there's anything specific that they wanted to share at this point about that.

As it relates to your second question, as we mentioned on the call here, we are excited to say that we will be moving towards an IND with 2501 in the second half of 2026. And our intention is to be able to conduct that Phase I ourselves. We have the capabilities, and we obviously have the financial flexibility and the resources to do that. We continue to remain open to various options around partnership long term across the in vivo platform. We obviously made the announcement this morning with 2505 moving forward in multiple myeloma and BCMA, and we'll continue to assess all of our options to maximize the value, both in terms of maintaining economics, but also ensuring speed and scale to maximize the opportunity with in vivo.

One moment for our next question that comes from Etzer Darout with Barclays. Please proceed.

This is [indiscernible] on for Etzer. Real quick on the J&J partnership. How does that impact your in vivo development in immune disease? Will that change what you're able to pursue? And then maybe can you highlight any differences between your in vivo CAR-T platform and sales?

Sure. So yes, the announcement that we're making today is around BCMA CAR-T in multiple myeloma. That's the aspect of the program that is subject to the agreement with J&J. So at this point, now Legend will look and step back and assess our options for autoimmune disease. We remain very interested in autoimmune disease with multiple targets. We obviously have been looking at potentially BCMA, potentially CD19, CD20 and other targets in autoimmune, and we think in vivo can play a meaningful role there.

As it relates to the J&J deal that you mentioned with Sail, I'll remind you that Sail has a preclinical platform around circular mRNA and LNP. And so that's very different from our program, which is LV-based. And we've also already shown clinical data in a very meaningful market, which is non-Hodgkin's lymphoma. So I think these are 2 very different opportunities. And I think it speaks to the excitement across the industry in in vivo. Many large pharma companies are looking at multiple platforms, and we're very excited about the platform that we have to offer.

Our next question comes from Edward Tenthoff with Piper Sandler.

Thanks for the updates on the in vivo side and all the great progress with CARVYKTI. My question has to do with the rest of the pipeline, sort of the allogeneic approaches. It really sounds like the focus is in vivo going forward. So should we be expecting updates on either some of the other autologous CAR-Ts or some of the allogeneic CAR-Ts in the next year or so? Can you give us a sense for when to expect those updates?

Let me turn this over to you, Yuhong to answer your question.

So the in vivo platform and allogeneic platform each have a strength. We prioritize in vivo, but we still believe that allogeneic have a good place. We previously provided our G39D program in ASH last year, and we continue to provide additional updates in future conferences on that program.

It comes from Mitchell Kapoor with H.C. Wainwright.

This is Ahmed on for Mitchell. Congrats on the strong quarter. Just a couple of questions from us. One on how much of CARVYKTI's current 2L to 4L mix is in 2L and 3L versus fourth line? And how has that shifted Q-over-Q? And if any of these Sail launches in fourth line, what portion of CARVYKTI's current business would face direct overlap at launch? And the second one, I was wondering with Tyvek showing clinical proof of concept and LB2102 validating DLL3 CAR activity in small cell lung cancer, how are you thinking about extending the in vivo platform into solid tumors? And would DLL3 be the logical target? And would that fall within the Novartis agreement?

Let me answer your second question first and just say that we're looking across a range of potential solid tumor targets. A solid tumor obviously has its own unique characteristics, and I think there are challenges that we and other companies are continuing to try to solve with in vivo in solid tumors. So more to come on that one. We do think that the DLL3 auto CAR T data set was meaningful. And as you know, we have a partnership with Novartis where we will be having Novartis take the asset forward into full clinical development.

As it relates to your question about line of therapy, yes, you did hear us share a report -- an update today that our 2L through 4L now comprises 70% in fact, over 70% of our mix in the U.S. And that's exciting because that means that we are making significant progress in getting CARVYKTI to be used earlier in the treatment paradigm. And as you mentioned, where needle will be potentially indicated in later lines, depending, of course, on what label they do receive, our foothold in second through fourth line, I think, provides a meaningful opportunity for CARVYKTI going forward.

We -- last quarter, we did break down and share an insight that within the 2L and 3L specifically that, that represented 41% of the overall mix. And we did that because we wanted to share a point in time reference to the fact that we've made significant growth and significant progress in early lines, specifically 2L, 3L. And we said at the time, and we maintain today, we don't intend to provide that update on every single quarter. Really, it is an opportunity to share that we are growing in second and third line. It continues to be the fastest-growing part of our business, and we're excited with the fact that we do continue both from a clinical standpoint and a commercial execution standpoint to focus on the early line opportunities.

Our next question comes from Ash Verma with UBS.

Congrats on the progress here. So maybe just the first one, can you talk about the potential impact on CARVYKTI from J&J's growing body of clinical data, seen this MonumenTAL-6 data that for TECVAYLI/TALVEY showed a hazard ratio of 0.11 on PFS in second to fifth line patients. So just help us understand. I know you're growing a lot in second to third line, but just if competition catches up to that. And then secondly, I know you commented on the sequential global sales growth, but can you confirm that if it applies to the U.S. sales growth as well going into 3Q and 4Q?

Yes. At this point, and again, we are -- we stay very close to our partner, J&J here on this. So we wanted to just maintain the comment that we had previously, which is around global sequential growth quarter-on-quarter. But to answer your first question on the bispecifics, again, I pointed this out earlier, but I think it's important to emphasize that the bispecifics do have, I think, very compelling data, but they offer a very different value proposition for patients. And what we're focused on is the fact that -- and jointly with J&J, and J&J has reiterated the fact that CARVYKTI, even on their recent earnings call that CARVYKTI has the potential to be a $5 billion-plus peak sales asset, and we very much are in lockstep with them on that.

Both J&J and Legend are committed to the fact that CARVYKTI provides a very unique value proposition to patients, to physicians and to the market. One and done versus continuous therapy, the opportunity for a long-term remission and really meeting the definition of cure as defined by the IMWG guidelines, really, we have a potential for cure here based on the CARTITUDE-1 long-term 5-year data. We look forward to presenting updates in earlier lines over the next year or so, and we do believe that this one-and-done opportunity with long-term remissions and the potential for cure is what patients and physicians ultimately want.

And I would also add to your question, which is I mentioned earlier, there's really been a very robust conversation now at all the medical conferences and all the follow-on conferences about sequencing. And I think the real-world evidence that was presented at ASCO, whether it's the Germany registry or whether it's the Mountain West U.S. registry from TriNetX or whether it's other data sets, institution-specific real-world data suggests that when patients get CAR-T first, they have prolonged survival, they have better outcomes and you have less opportunity for antigen escape or antigen mutation. So you really have an opportunity to get CAR-T first, and that's really where the KOLs are on this topic.

We have a question from the line of Sean McCutcheon, Raymond James.

And speaking to earlier line, with the iberdomide PDUFA coming up in about a week on the MRD negativity results, how does this inform your calculus on potential for filing on MRD for CARTITUDE-6 and accelerating the time to market for CARVYKTI in the frontline transplant eligible population?

Let me ask you, Yuhong to comment about MRD as an endpoint.

As with the advancement of frontline therapies for multiple myeloma patients, the median PFS gets longer, longer, which is very good news for patients. But for the development of new therapies, some of those patients still relapse. So MRD become a necessary surrogate in order for those effective therapies to reach patients earlier. Although in the MRD ODAC, the correlation analysis does not include any of the CAR-T data set. We continue to work with FDA on the probability -- the possibility of MRD as a surrogate for registration purpose for the CAR-T therapy. So CAR-6 will continue on this effort.

Thank you. And as I see no further questions in the queue, I will conclude the Q&A session and conference for today. We want to thank everyone for participating, and you may now disconnect.

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.