Legend Biotech Corp (LEGN) Q3 2026 Earnings Call Transcript

Good morning, everyone. Welcome to Legend Biotech third quarter 2026 earnings call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask the question during the session, you will need to press star 1-1 on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star 1-1 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 Zong, our Chief Executive Officer, Alan Bash, President of Carvecti, and Carlos Santos, Chief Financial Officer. Following the prepared remarks, we will open the call for Q&A. Yuhang Chiu, 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 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 Ingrid.

Thank you, Caroline, and good morning, everyone. Before reviewing our third quarter results, I'd like to share a few thoughts as this is my first earnings call as LEGEND's CEO. Over the past several weeks, I have spent time with colleagues across the entire organization and engaged with physicians and other stakeholders working to bring COVID-19 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. We've also been impressed by the quality of our people and the collaborative culture across the organization. Together, these strengths reinforce my confidence in LEGEN's future. I joined LEGEN because I believe the opportunity ahead is significant. Calvictity continues to expand its impact for patients with multiple myeloma, while 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 Calvictity. 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 a team focused on delivering for patients and external stakeholders. With that, let me turn to our third quarter highlights. Slide 7, please. In the third quarter, COVID-19 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 the U.S. on a year-over-year basis. We also continue to expand global patient access. Reaching 373 activated treatment sites globally. During 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 COVID-19 in early-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 8, 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 cartitude 2, 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 cavity T infusion, half of the 20 patients from cartitude 2, cohort A, remained alive and progression-free without further antimyeloma treatment. Compared with 33% in cartitude 1, 5-year overall survival was 69%, compared with 51%, respectively. Importantly, the safety profile remained consistent with the known profile of carviditin, 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 carviditin in early-aligned settings. which may increase the likelihood of achieving durable treatment-free remission for patients living with multiple myeloma. Earlier use of cavity T was also reinforced by recent updates to NCCM guidelines, which Alan will explain in detail. As journal next slide, we continue to evaluate cavity T through the CARTITUDE-5, CARTITUDE-6, and CARTITUDE-10 studies. These programs represent an important opportunity to evaluate capidity in front-line settings, including transplant-ineligible and transplant-eligible patients, and essential to our long-term strategy for that asset. Slide 9, please. Beyond capidity, we're advancing our individual 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. As you might recall from our EHOP 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 2. 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 EHR. We are very pleased that LB2501 continues to demonstrate a favorable safety profile and encouraging efficacy, with remarkable 100% OR and 100% CR rates at dose level 2, with a median follow-up of nearly five months. We intend to share additional updates across the dose levels at ASH. In terms of clinical development plans, The Phase 1a study for LB2501 is intended to confirm and further characterize dose selections in the U.S. clinical setting, based in part on insights from the ongoing IIT 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 informed patient selection. Following this, we intend to advance LB2501 into Phase 2 in a properly selected patient population 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, but we remain focused on those in patients as soon as possible. As a reminder, this program falls under the terms of our agreement with Johnson & 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, IBV legend remains real position for long-term growth. Commercially, Tafix-T remains leading CAR-T therapy in multiple myeloma, supported by expanding global demand, early-aligned adoption, and a growing body of long-term clinical evidence. Operationally, we ended the quarter with approximately $853 million in cash, cash rate prevalence, and time deposits, and we remain focused on achieving company-wide profitability for full year 2026 on an 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% 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 wanted 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 Carvicti 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 first quarter of 2025. This trend reflects growing physician confidence in CARVIC-D'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 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 Carvicti 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 Carvicti, 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 perform much better than expected, improving to 58%, compared to our expectation in the lower 50% range. The improvement is primarily due to manufacturing efficiencies. While 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 decrease 16% year-over-year as the costs from the later-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 I 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 $0.14 per diluted share on a non-IFRS basis, compared with an adjusted net loss of $18.7 million or a loss of $0.05 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 CAR-VICT 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-wide 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 remain confident in the long-term outlook for the business.

Thank you, Carlos. The third quarter was marked by continued execution across all business. We expanded global access to COVID-19, presented important long-term COVID-19 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 not 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.

Yeah. Thank you. Compared to what we're presenting in EHA, the ASH abstract showed that 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 1, eight at dose level 2, five at dose level 3. Both the 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 ICANN, no non-ICANN neurotoxicities were reported. So the strong signal we 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 phone.

And, Terrence, this is Alan. Speaking to your question about the AnitaCell data, you know, we saw the abstract, and I think we remain very confident in the unique profile that Carvicti 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 neurotoxicities, and that has helped, I think, close this perceived gap based on what AnitaCell 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 one, 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.

Hi, guys. Thanks for taking my question. I was struck by the progress that you've made in driving CARVIC-D use into the earlier lines of therapy in the U.S. 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 the other lines and better outcomes and a strong motion to get those patients on CARVC-D 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 data cut at ASH, should we be expecting 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 buy specifics in earlier lines based on the approval of TechDarra 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 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 next question about what we can disclose at ASH? In terms of?

In terms of DLL3, DLL2.

DLL3, DLL3, DLL2. 2501.

I'm sorry.

So for ASH, right, as shown in the abstract, we have dose level two, we have eight patients. All eight of them have shown 100% response rate, over response rate, and complete response rate. For dose level three, we have five patients, and the over 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 Fy with J.P. 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 comment, Alan, about the increasing competitiveness in earlier lines with Tecdera, it does seem well understood that BCMA CAR-T works better before and not after BCMA bispecifics, so why do you guys think it's competitive there? Thanks.

Sure. So in terms of timing for CAR-5 and CAR-6, 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 CART 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 CART 6 would be beyond that. Again, this is a space where there's a demonstrated based on the literature along 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 provide 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 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. Please stand by for our next question. Our next question comes from the line of Leonid Tomashev with RBC. Your line is open.

Hey, guys. 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 tees 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 compliment. 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, Carvicti 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 Carvicti in 2027. 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 U.S. than we had initially anticipated. Having said this, we remain really very confident in the long-term growth outlook for Carvicti.

No, Alan, if you want to add some color to this. I'll add simply that, you know, 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 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 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, you know, been 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 ETSA 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? Or 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 data set 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 Tenhoff with Piper Sandler. Your line is open.

Great. 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 I.O. candidate that you would anticipate developing in autoimmune disease? Thanks so much.

Yeah, 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 a legend, as a leading South Turkey 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 so very much.

Thank you. Please stand by for our next question. Our next question comes from the line of Lenhi Shao 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, more particularly given that in 3Q, we saw that U.S. cells 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 understand the more colors regarding the overall market demand for COVID-19 and also the quality timing, manufacturing, allocation, and to understand the U.S. 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 BCMA CAR T's? Thank you.

Yeah, I think we've addressed some of these points, but let me just add a couple of points here. Again, we 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 Carvicti, 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 early lines. And so we will continue to emphasize the value of CAR-T first, that earlier is better, and that, you know, 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, both, you know, we see not only from the approved buy specifics, but there are additional buy specifics coming onto the market. So, yes, this marketplace will continue to become increasingly competitive.

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 penetrating 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 be made out. And continued extension of our global footprint. And lastly, about bringing COVID-19 closer to patients. I think we do these 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 Javon Weber with TD Cohen. 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 U.S., do you need the green knot from J&J to actually do so, ProLine, with your agreement. Thank you.

Yeah, with regarding to the IIT, 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.

Can you 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's 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. Just thinking into the international growth a bit, I'm curious if you could 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 TechDara begins to expand internationally, what gives you confidence that ex-U.S. growth is going to remain a durable offset to any potential headwinds in the U.S.? Thank you.

Yeah, so as you saw from our disclosures, we are now in 20 markets worldwide. And the growth that you're seeing in the ex-U.S. 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 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 Amet on for Mitchell. Thanks for taking our question, and congrats on a strong quarter. So, two for me, one on CARVICTE and one on 2501. So, for CARVICTE, within the community, are you seeing the incremental patients coming from physicians making their first CARVICTE 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 and 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 the expanded CAR T cells were predominantly CD8 positive-effective memory cells with limited terminal differentiation and exhaustion-associated transcriptional signature in the samples that we analyzed. Thank you. In this study, of course, we'll continue with our translational analysis and keep a close eye on the phenotypes of the T cells that we observed.

Thank you.

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

Hi there. This is Natalie An-Farash. 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.

Yeah, your reference to the CAR-5 control arm, which is VRD, you know, 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. I think the important thing about CART-5 is that 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 CART-5 will be a meaningful data set versus an appropriate control arm.

Thank you. Our next question comes from the line of Jacob Orkowitz 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. I'm specifically seeing much higher responses in DL2, and we're curious if you anticipate a meaningful addition of activity at higher doses moving forward.

Yeah, 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. More patients in dose and with longer 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 showing no further questions in the queue. That concludes today's conference call. Thank you for your participation. You may now disconnect.