Legend Biotech Corp

NASDAQ:LEGN

Q4-2025 Earnings Call

[Operator]

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.

[Jessie Yeung, executive]

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.

[Ying Huang, executive]

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.

[Alan Bash, executive]

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.

[Carlos Santos, executive]

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]

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

[Terence Flynn, analyst]

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?

[Ying Huang, executive]

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.

[Operator]

Our next question comes from Jon Miller with Evercore.

[Jonathan Miller, analyst]

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?

[Alan Bash, executive]

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.

[Operator]

Our next question comes from Etzer Darout with Barclays.

[Unknown Analyst]

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?

[Alan Bash, executive]

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.

[Operator]

Our next question comes from Linhai Zhao with GS.

[Linhai Zhao, analyst]

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?

[Ying Huang, executive]

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.

[Alan Bash, executive]

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.

[Operator]

Our next question comes from Eric Schmidt with Cantor.

[Eric Schmidt, analyst]

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?

[Alan Bash, executive]

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.

[Ying Huang, executive]

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.

[Operator]

Our next question comes from Konstantinos Biliouris with Oppenheimer.

[Konstantinos Biliouris, analyst]

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?

[Ying Huang, executive]

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.

[Alan Bash, executive]

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.

[Operator]

Our next question comes from James Shin with DB.

[James Shin, analyst]

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?

[Ying Huang, executive]

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.

[Operator]

Our next question comes from Sean McCutcheon with Raymond James.

[Sean McCutcheon, analyst]

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?

[Ying Huang, executive]

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.

[Operator]

Our next question comes from Ash Verma with UBS.

[Unknown Analyst]

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?

[Alan Bash, executive]

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.

[Ying Huang, executive]

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.

[Operator]

Our next question comes from Leonid Timashev with RBC.

[Leonid Timashev, analyst]

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.

[Ying Huang, executive]

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.

[Operator]

Our next question comes from Yaron Werber with TD Cowen.

[Unknown Analyst]

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?

[Alan Bash, executive]

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.

[Ying Huang, executive]

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.

[Operator]

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

[Unknown Analyst]

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?

[Alan Bash, executive]

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.

[Operator]

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