Great. Welcome. Good morning, everyone. My name's Jess Fye. I'm a biotech analyst at J.P. Morgan, 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 hand. 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, J.P. Morgan, for inviting Legend to be participating in the J.P. Morgan 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 filing and also go to our company website. It's really a great pleasure for me to speak 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 standalone cell therapy company, and we're a pioneer in using immune cells to treat the toughest diseases. Legend Biotech is at the forefront of CAR-T therapy revolution with CARVYKTI, our one-time 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 CAR-T, utilizing our operating model that emphasizes 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.
Below this goal number 10,000, it is 10,000 lives being touched, 10,000 families, 10,000 patients' 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 combine 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 the 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 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% manufacturing success rate, and it's 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 four of our global supply sites.
While the United States remains a primary area of focus for us, we have been gradually expanding our presence globally, and we continue globalization expected this year. Our partnership with Johnson & Johnson is built to scale CARVYKTI to its potential of 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 number one 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 de-risks the global execution while also preserving innovation velocity as well as benefiting patients globally.
Here's 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 five-year remission survival in one-third patients after single infusion in a study called CARTITUDE-1, where patients had a median 6.5 prior lines of therapy of heavily pretreated patient population. Since ASCO, publications such as The New York Times and Forbes have highlighted CARVYKTI's survival and also unique curative potential, and a paper on this topic was published in the Journal of Clinical Oncology. It was ranked number one in readership. Our data maturity and also long-term follow-up create an advantage that is difficult for any later entry 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 three years or 35 months. In last month, at the annual ASH meeting, we presented data from 34 patients between CARTITUDE-2 and also CARTITUDE-4, where patients have been treated with triple class and also had three 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 III trial where we enrolled more than 400 patients with prior one to three prior lines of therapy, the median progression-free survival has not even been reached with a median follow-up of nearly three years.
So clearly, these data demonstrate that CARVYKTI is a category-leading therapy, and this data is category-defining and has transformed treatment of multiple 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, derived the best survival outcome compared to patients with two or three 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 bispecific 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. In fact, in patients enrolled in CARTITUDE-4, there's no case of delayed-onset parkinsonism in patients who responded to bridging therapy. This again emphasized the importance of effective bridging therapy. We're now able to meet the 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 targeted 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 algorithm 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 to date and also supports the hypothesis that with immune therapies 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 setting. And based on the data generated, we know that earlier treatment may deliver greater durability at lower lifetime cost. As we look to increase prescription of CARVYKTI in the community and also in the 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 setting. 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 one-third 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 further the growth because of CARVYKTI's unique delayed CRS profile at seven to eight days. Healthcare practitioners are able to utilize outpatient utilization administration to support the patient needs, as well as the existing hospital infrastructure. Today, outpatient use of CARVYKTI comprises 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 five-year treatment-free remission in one-third of heavily pretreated patients in a study called CARTITUDE-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 debulk the tumor burden 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 this slide, there's a paper published by Dr. Dhakal from Medical College of Wisconsin, drawing 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 Talvey, which is a GPRC5D bispecific antibody. Following that bridging therapy and CARVYKTI infusion, there were no cases of colitis or parkinsonism. In another paper that's presented at ASH, the lead author 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 cases 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 hot off the press. Last Friday, NCCN, the National Comprehensive Cancer Network, updated their treatment guidelines for multiple myeloma, and based on the data I just presented in the last slide, the panel now recommends Talvey 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 a cure.
CARVYKTI has proven data supporting its potential curative benefit, whereas no other CAR-T in myeloma has been able to substantiate this kind of long-term efficacy. There is also substantial evidence on how earlier treatment with CARVYKTI will derive better benefit in terms of both safety and also efficacy outcomes. Finally, CARVYKTI is a one-time treatment that offers flexibility in both inpatient and also outpatient settings, as well as lower lifetime cost saving, benefiting patients, healthcare practitioners, and payers. We're committed to building upon the most successful CAR-T launch to date as we continue to focus on 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 three 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 autologous CAR-T partnership with Novartis. And finally, we've also recently initiated phase 1 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 development 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 six months.
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 hold much promise for multiple indications by eliminating some of the manufacturing complexity while expanding reach. 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 only a handful of companies out there with an active phase one 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 red curve.
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 eight 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 one. 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 partnership. Moving to 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 true 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 equivalents, and how we have already generated operating cash in the third quarter for CARVYKTI. We continue to expect CARVYKTI's sales trajectory to be strong in 2026 with sequential quality 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 filing one to two U.S. INDs by the 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 answer 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 2026, can you expand on what your biggest goals are for the company this year?
Yeah, 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 in international launch.
Secondly, we'd like to continue to push forward in our pipeline. For example, we just presented for the first time in our presentation at ASH last month our gamma delta anti-CD19, anti- 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 2026. Those are top three priorities for the company.
Okay. 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?
You're kind of balancing how profitable you could be with how much you invest.
Yeah. So if you look at the first three quarters of last year, our R&D investment, in fact, was flattish compared to the same period of 2024. And that is because the maturing program for CARTITUDE . We're now seeing actually a lower investment in R&D for CAR-T program. So we're redeploying our capital from CARTITUDE, too program to now internal R&D effort with a focus on allogeneic 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.
Okay. What do you think is most underappreciated or maybe misunderstood in the Legend story?
I think, first of all, maybe investors underappreciate the importance of this one-time 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 one-time 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, especially 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 the blood, right?
Beyond that, it's also a significant improvement in quality of life because with this one-time infusion following the one-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 three-year PFS, five-year survival in heavily pretreated patients. And we're also functionally curing one-third of those patients. We're looking forward to future updates for CARTITUDE-4.
So in second-line patients, we expect a higher proportion of patients will be able to enjoy that multi-year 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 standard of care. It's also written in the label in both U.S. by FDA and also in Europe by EMA. That is a 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?
Yeah, sure. As you can tell, in the last four 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 vein-to-vein and supply side is below 30 days. It's about four weeks, in fact. So we have done a lot of hard work. We're the trailblazer in CAR-T because, as you know, CAR-T 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 three years.
We and our partner 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. Question in the audience?
Yes, you pointed out that China is not included in the J&J transaction, but in 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 for 70% of the cost and also profit. And J&J will be responsible for 30%.
But because of the supply constraint and also the valuation and reimbursement pricing considerations, we have not launched CARVYKTI yet in China. So our research colleagues are working super hard on allogeneic 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 a lower cost and lower pricing will be likely the commercial path for CAR-T therapy in China. Thank you for that question.
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?
Yeah, so just 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 line 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 the end of this year should come from early line. 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?
Yeah, 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. It's about 5% in that market. So, believe it or not, today, the market in that second to fourth line remains dominated by older regimens such as doublet 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 negativity, 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 would 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? Yeah, I mean, I think these two are really correlated. As I mentioned, if you look at today, we have 141 treatment centers certified in the U.S., and about a third of those sites are hospitals and sites in the community setting. So these are regional community hospitals or completely clinics like Virginia Oncology Associates that do not even have beds, right? So that continues to be our focus.
Because of the unique profile of delayed CRS of about seven or eight days for CARVYKTI, in fact, more than half of the patients with CARVYKTI today already are receiving this treatment in an outpatient setting. Of course, if you think about those community patients, really, they would rather either commute to a site which is within driving distance rather than going to a tertiary center. This really hand in hand. That is why we're seeing actually more adoption in second line, more adoption in the community. For example, today, about 80% of all multiple myeloma patients in this country will be able to find a treatment center within 50 mi. Our goal is to increase that to maybe 100% within 30 mi, actually. Essentially, we're actually bringing this lifesaving therapy to the patients, to the community.
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?
Yeah, I mean, I'll continue to emphasize that in the treatment of oncology in general, efficacy is always, always the number one decision factor. 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. The difference is that in the community setting, the number one decision factor for patients and also physicians to choose a therapy for myeloma is survival, followed by PFS and their response rate.
While in the academic setting, PFS tends to be the number one 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 the 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 mature data shows a median survival of just over five years, and that is five years of additional life this patient can derive, and then in CARTITUDE-4, compared to the gold standard, the triplet, right, standard of care such as DPD, Darzalex, Pomalyst, and dexamethasone, again, we have shown a hazard ratio of 0.55, which means 45% risk reduction in death.
I think these data points are hard data points, and also they clearly convince the patients that this is a lifesaving therapy here, and that is our number one 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 four years. Today, we can stand here to say that we can satisfy all the demand, all the demand from patients who want CARVYKTI who are eligible, so there is no supply shortage anymore in that, and we have also the real-world use. No other therapies in CAR-T in myeloma have 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 advantages, 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?
Yeah, sure. So CARTITUDE-5 trial is an event-driven trial, which means we have to reach a pre-specified number of events before we can unblind the trial and conduct any analysis. So really, even though we completely enrolled 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 to maybe two years, so 2026, 2027.
I think we'll have a more reliable estimate once we get in 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 or two years, we'll have a readout. Now, in terms of what question 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 enroll 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 confidence. I'll 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 34-43 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 resort. And even in that case, we demonstrate nearly three years of PFS.
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 three years 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. Another important point is that, remember, if these patients are getting RVD for, let's say, two or three years in that setting, they're being continuously treated. Again, these drugs are immunosuppressive. You have neutropenia. You have infections. You have other untoward side effects. While this is a one-time treatment, right? Like I said, it is a really great improvement for quality of life for those patients. So they can enjoy a few years of treatment-free period. That's another advantage.
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.
Okay. And then kind of similar question, but for CARTITUDE-6 and 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?
Yeah, CARTITUDE-6 is really a very important trial. Like you said, this could be a paradigm shift because in the last 50 years, the gold standard of care for frontline has been bone marrow transplant.
Even though in a large phase III 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 six cycles or six months of DRVD quad therapy, so already they're getting the best possible therapy in consolidation, DRVD, and then we want to see again a one-time 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 negativity, 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 crude guess because right now, we're still just starting the follow-up period for those CAR-T 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 transplant.
Okay, great. We are out of time, so we'll stop there. Thank you. Thank you very much.